                         TABLE OF CONTENTS

Abdominal aortic aneurysm ............................................22           */A-C,22/D-F,368/G-I,476/
Abdominal pain (Non Surgical) ........................................25           */J-L,629/M-O,678/P-R,838/
Abortion .............................................................28           */S-U,1052/V-Z,1215/
Abortion (Septic) ....................................................29
Abscess (Hepatic) ....................................................30
Abscess (Epidural) ...................................................32
Ace inhibitors .......................................................34
Ace inhibitors in myocardial infarction ..............................37
Acetaminophen toxicity ...............................................38
Acne .................................................................39
Acromegaly ...........................................................39
Adnexal masses .......................................................41
Adrenal insufficiency ................................................44
Adrenal Masses .......................................................46
Adult respiratory distress syndrome ..................................47
Aids and aspergillosis ...............................................51
Aids and the CNS .....................................................51
Aids and coccidioidomycosis ..........................................53
Aids and cryptococcal infections .....................................54
Aids and cryptosporidiosis ...........................................55
Aids and cytomegalovirus .............................................55
Aids and fever .......................................................57
Aids and the GI tract ................................................58
Aids and the GI tract ................................................61
Aids and histoplasmosis ..............................................63
Aids and isosporiasis ................................................64
Aids and kaposi's sarcoma ............................................64
Aids and the lung ....................................................65
Aids and mycobacterium avium intracellulare complex ..................70
Aids and pneumocystis carinii ........................................70
Aids and pneumonia ...................................................72
Aids and toxoplasmosis ...............................................75
Aids and tuberculosis ................................................76
Alcohol ..............................................................78
Alcoholic withdrawal .................................................80
Allergic bronchopulmonary aspergillosis ..............................80
Alopecia .............................................................82
Amebiasis ............................................................86
Amenorrhea ...........................................................89
Amenorrhea ...........................................................90
Aminophylline ........................................................92
Amiodarone ...........................................................93
Amphotericin B .......................................................96
Amylase ..............................................................99
Amyloidosis ..........................................................99
Amyotrophic lateral sclerosis ........................................104
Anaerobic infections of the lung .....................................105
Anemia ...............................................................108
Angina management without exacerbation of co-existing diseases .......108
Angina (Unstable) ....................................................110
Angioplasty (Percutaneous coronary) ..................................113
Anion gap ............................................................116
Ankylosing spondylitis ...............................................116
Anorexia .............................................................119
Antiarrhythmic agents (Classification) ...............................120
Antibiotics in renal failure .........................................122
Anticoagulant INR recommendations for various situations .............123
Anticoagulation ......................................................123
Anticoagulants and antiplatelet therapy in myocardial infarction .....126
Anticoagulation and prosthetic heart valves	..........................127
Anticoagulation and surgery ..........................................127
Anticoagulation (Prosthetic heart valves and noncardiac surgery) .....127
Antiphospholipid syndrome ............................................128
Antithrombin III deficiency ..........................................129
Aortic dissection ....................................................129
Aortic regurgitation .................................................135
Aortic regurgitation .................................................136
Aortic stenosis ......................................................136
Aortic stenosis ......................................................137
Aplastic anemia ......................................................138
Aquatic infections ...................................................141
Arrhythmias in acute myocardial infarction ...........................142
Arterial thrombosis ..................................................144
Ascites ..............................................................145
Aspergilloma .........................................................149
Aspergillosis (Invasive pulmonary) ...................................151
Aspirin toxicity .....................................................153
Ataxias ..............................................................154
Atrial fibrillation ..................................................157
Atrial fibrillation and embolism .....................................160
Atrial myxoma ........................................................162
Atrial septal defect .................................................163
Atrial septal defect .................................................166
Attention deficit hyperactivity disorder .............................166
Autoimmune hemolytic anemia ..........................................170
Automatic implantable cardiac defibrillators .........................173
Axillary thrombosis-effort thrombosis of the axillosubclavian vein ...175
Babesiosis ...........................................................176
Babesiosis ...........................................................178
Bacillary angiomatosis ...............................................178
Back pain ............................................................180
Back pain in children ................................................186
Bacterial vaginosis ..................................................187
Bartter's syndrome ...................................................187
Bell's palsy .........................................................188
Benign positional vertigo treatment ..................................189
Benign prostatic hyperplasia .........................................190
Beta blockers in cardiology ..........................................192
Beta blockers in myocardial infarction ...............................193
Blastomycosis ........................................................195
Bleeding disorders ...................................................197
Blood transufsion complications ......................................199
Boerhaave's syndrome .................................................202
Botulism .............................................................203
Bronchial asthma .....................................................206
Bronchiolitis ........................................................210
Brown recluse spider .................................................213
Bullous pemphigoid ...................................................214
Busulfan toxicity ....................................................216
Campylobacter ........................................................216
Cancer and cardiac emergencies .......................................218
Cancer of the colon ..................................................219
Cancer of the esophagus ..............................................220
Cancer of the head and neck ..........................................225
Cancer of the ovary ..................................................228
Cancer of the pancreas (Adenocarcinoma) ..............................235
Cancer of the prostate ...............................................241
Cancer of the stomach ................................................245
Cancer of the testis .................................................249
Cancer of the uterus .................................................253
Candida and AIDS .....................................................258
Candidiasis (Disseminated) ...........................................258
Captopril ............................................................261
Carbon monoxide poisoning ............................................261
Carcinoid syndrome (Symptoms) ........................................264
Carcinoma of unknown primary site ....................................265
Cardiac patients and non-cardiac surgery .............................267
Cardiac tamponade ....................................................270
Cardiac transplantation ..............................................271
Cardioembolic stroke (Treatment) .....................................273
Cardiogenic shock ....................................................274
Cardiogenic shock and acute myocardial infarction ....................276
Cardiomyopathy (Dilated) .............................................276
Cardiomyopathy (Dilated) .............................................278
Cardiomyopathy (Hypertrophic) ........................................280
Cardiomyopathy management ............................................284
Cardiopulmonary resuscitation ........................................287
Carotid artery disease ...............................................289
Carotid bruit (Innocent murmur) ......................................291
Carotidynia ..........................................................292
Cat scratch disease ..................................................293
Caustics and corrosives ..............................................294
Celiac disease .......................................................297
Central alimentation (TPN) ...........................................299
Central venous catheters .............................................300
Cerebellopontine angle tumors ........................................304
Cerebral abscess .....................................................305
Cerebrovascular disease ..............................................310
Cervical spine syndromes .............................................313
Chaga's disease ......................................................316
Chancroid ............................................................319
Chlamydia trachomatis (Urethral, cervical, rectal) ...................319
Cholera ..............................................................319
Cholestasis disease ..................................................321
Chronic obstructive pulmonary disease (Treatment) ....................324
Ciguatera fish poisoning .............................................326
Ciprofloxin ..........................................................328
Clostridium myonecrosis ..............................................330
Coagulase negative staphylococci (Staphylococcus epidermidis) ........332
Coarctation of the aorta .............................................333
Coarctation of the aorta .............................................334
Cocaine induced rhabdomyolysis .......................................334
Coccidioides immitis and AIDS ........................................336
Coccidioidomycosis ...................................................336
Coma (Common causes) .................................................338
Coma causes ..........................................................339
Common variable immunodeficiency .....................................339
Congestive heart failure .............................................340
Conjunctivitis .......................................................343
Creatinine clearance .................................................346
Crohn's disease ......................................................346
Croup ................................................................353
Cryoglobulinemia .....................................................353
Cryptococcus neoformans and AIDS .....................................356
Cryptosporidium and AIDS .............................................356
Cushing's syndrome ...................................................356
Cyanide poisoning ....................................................359
Cyclophosphamide toxicity ............................................362
Cystic fibrosis ......................................................363
Cytomegalovirus and AIDS .............................................368
Deep venous thrombosis (Causes) ......................................368
Delirium tremens treatment ...........................................368
Dementia .............................................................369
Depression and concurrent illness ....................................372
Dermatitis herpetiformis .............................................373
Diabetic diarrhea ....................................................375
Diabetic emergencies .................................................376
Diabetic gastroparesis ...............................................380
Diabetic infections ..................................................381
Diabetic neuropathy ..................................................382
Dialysis .............................................................383
Diarrhea (Chronic) ...................................................390
Diazoxide and hypertension ...........................................393
Digitalis intoxication ...............................................393
Digitalis toxicity ...................................................398
Discoid lupus erythematosus ..........................................400
Disseminated gonococcal infection ....................................402
Disseminated intravascular coagulation ...............................403
Drugs and lung disease ...............................................406
Drugs and systemic lupus erythematosus ...............................408
Dupuytren's contracture ..............................................409
Dyspareunia ..........................................................409
Dysphagia ............................................................410
Eaton-Lambert syndrome ...............................................414
Ebsteins's anomaly ...................................................415
Ectopic pregnancy ....................................................417
Ehrlichiosis .........................................................422
Ehrlichiosis .........................................................423
Emergency drugs ......................................................423
Enalapril and hypertension ...........................................428
Endocarditis .........................................................428
Endocarditis (Culture negative) ......................................429
Endocarditis prophylaxis .............................................432
Endometriosis ........................................................432
Endocrine disease and surgery ........................................435
Enterocytozoon bieneusi and AIDS .....................................436
Entrapment syndromes .................................................436
Enuresis (Nocturnal) .................................................441
Eosinophilia .........................................................444
Eosinophilic fasciitis ...............................................445
Eosinophilic gastroenteritis .........................................446
Eosinophilic granulomatous vasculitis ................................447
Epilepsy .............................................................448
Erectile dysfunction .................................................452
Erythema multiforme ..................................................456
Erythema nodosum .....................................................458
Esmolol and hypertension .............................................460
Esophageal variceal bleeding .........................................460
Exercise induced asthma ..............................................464
Facial pain (Treatment of atypical) ..................................465
Fascicular blocks ....................................................465
Fever clues ..........................................................467
Fever of unknown origin	..............................................468
Fever with relative bradycardia ......................................469
Fibrocystic disease of the breast ....................................469
Fluconazole ..........................................................471
Flucytosine ..........................................................472
Foot (Benign tumors) .................................................473
Fungal superinfections ...............................................476
Gait disturbances in the elderly .....................................476
Gastroesophageal reflux disease ......................................479
Gastrointestinal bleeding (Acute upper) ..............................483
Genital disease (Male) ...............................................488
Gentamicin and tobramycin dosing .....................................490
Giardiasis ...........................................................491
Glomerulonephritis (Focal glomerular sclerosis) ......................493
Glomerulonephritis (IgA) .............................................494
Glomerulonephritis (Membranous) ......................................495
Glomerulonephritis (Membranoproliferative) ...........................497
Glomerulonephritis (Minimal change) ..................................498
Glomerulonephritis (Post-Streptococcal) ..............................500
Gonorrhea (Urethral, cervical, rectal, uncomplicated) ................503
Gram negative bacteremia .............................................503
Guillain Barre syndrome ..............................................504
Gusto trial ..........................................................507
Gynecomastia .........................................................508
Hairy cell leukemia ..................................................510
Hantavirus pulmonary syndrome ........................................511
Headaches (Treatment) ................................................512
Hearing loss .........................................................516
Heart block ..........................................................516
Heart surgery follow up ..............................................518
Helicobacter pylori ..................................................520
Hematuria ............................................................521
Hemochromatosis ......................................................522
Hemolytic blood morphology by Wright's stain .........................524
Hemolytic-uremic syndrome ............................................524
Hemophilia A .........................................................527
Hemoptysis ...........................................................533
Henoch-Schonlein purpura .............................................534
Heparin ..............................................................537
Hepatitis (Chronic active autoimmune) ................................538
Hepatitis (Chronic persistent hepatitis) .............................542
Hepatitis (Autoimmune) ...............................................543
Hepatitis (Differential diagnosis by lab testing) ....................544
Hepatitis overview ...................................................544
Hepatitis B neonatal immunization ....................................550
Hepatitis B treatment ................................................552
Herpes simplex syndromes .............................................553
Herpes zoster and AIDS ...............................................557
Herpes zoster ........................................................557
Herpes zoster ........................................................560
Hirsutism ............................................................562
Histoplasma capsulatum and AIDS ......................................565
Histoplasmosis .......................................................565
Hoarseness causes ....................................................568
Hodgkin's disease ....................................................568
Hodgkin's disease and MOP-BAP ........................................569
Hodgkin's disease and MOPP ...........................................570
Hodgkin's disease and MOPP-ABV .......................................570
Hodgkin's disease and ABVD ...........................................570
Hodgkin's disease staging procedures .................................570
Human papillomavirus (External genital/perianal warts) ...............571
Hydralazine and hypertension .........................................571
Hypercalcemia ........................................................571
Hypercoagulable states ...............................................574
Hyperkalemia .........................................................578
Hyperpigmentation (Causes) ...........................................579
Hyperprolactinemia ...................................................579
Hypertension (Pediatric) .............................................584
Hypertension (Secondary) .............................................585
Hypertension (Treatment of secondary) ................................590
Hypertension and surgery .............................................593
Hypertensive crisis ..................................................593
Hypertensive cirsis and specific drug therapy ........................597
Hyperthyroidism (Treatment) ..........................................601
Hypomagnesemia .......................................................606
Hypothermia ..........................................................606
Hypothyroidism .......................................................610
Hypothyroidism and the heart .........................................615
Idiopathic hypertrophic subaortic stenosis ...........................616
Idiopathic pulmonary fibrosis ........................................616
Incontinence (Overflow) ..............................................618
Incontinence (Stress) ................................................618
Incontinence (Urge) ..................................................619
Incontinence (Urinary) ...............................................619
Incontinence (Urinary) ...............................................623
Infective endocarditis management ....................................623
Inflammatory bowel disdease (Extraintestinal manifestations) .........626
Intra-abdominal infections ...........................................626
Ischemic colitis .....................................................627
Isospora belli and AIDS ..............................................628
Itraconazole .........................................................628
Juvenile rheumatoid arthritis ........................................629
Kawasaki syndrome ....................................................632
Ketoconazole .........................................................635
Labetalol and hypertension ...........................................636
Lead poisoning .......................................................636
Legionnaires's disease ...............................................641
Legionnaires's disease ...............................................644
Leg pain (Radiating) .................................................644
Leptospirosis ........................................................646
Leukemia (Chronic lymphocytic) .......................................648
Leukemoid reactions ..................................................653
Leukocytoclastic vasculitis ..........................................654
Limping child ........................................................656
Lipidemic disorders ..................................................659
Lithium ..............................................................661
Livedo reticularis ...................................................664
Liver disease and surgery ............................................665
Liver failure (Acute) ................................................665
Liver function tests .................................................668
Lupus nephritis ......................................................670
Lyme disease .........................................................672
Lyme disease .........................................................675
Lymphoma (Central nervous system) ....................................676
Magnesium in cardiology ..............................................678
Malignant lymphoma and CHOP therapy ..................................680
Malignant lymphoma and C-MOPP therapy ................................681
Malignant lymphoma and CVP therapy ...................................681
Marfan's syndrome ....................................................681
Mediastinal masses ...................................................684
Megaloblastic anemias ................................................688
Melanoma .............................................................690
Meningitis ...........................................................693
Meningitis (Causes ...................................................694
Meningitis (Chronic) .................................................694
Meningitis (CSF profiles) ............................................698
Meningitis CSF tests .................................................699
Meningitis (Meningococcal) ...........................................700
Meningitis (Treatment) ...............................................702
Meningitis (Tuberculous) .............................................705
Meningitis (Viral) ...................................................709
Menopause ............................................................713
Menstrual disorders (Clues) ..........................................714
Meralgia paresthetica ................................................717
Mesenteric ischemia ..................................................717
Mesothelioma .........................................................720
Metamphetamine toxicity ..............................................720
Methanol and ethylene glycol poisoning ...............................720
Methicillin resistant staph aureus (MRSA) ............................721
Mitral regurgitation .................................................721
Mitral stenosis ......................................................726
Mitral valve prolapse ................................................732
Mitral valve prolapse ................................................732
Monoarticular arthritis ..............................................736
Monoclonal gammopathy ................................................744
Mucormycosis .........................................................746
Multiple myeloma .....................................................748
Multiple sclerosis ...................................................752
Multiple sclerosis ...................................................755
Murmurs and diagnostic maneuvers .....................................756
Mushroom poisoning ...................................................757
Myasthenia gravis ....................................................759
Mycobacterium avium and AIDS .........................................764
Myelodysplastic syndromes ............................................764
Myocardial infarction and drug therapy ...............................766
Myocardial infarction and myocardial enzymes .........................769
Myocardial infarction (An Overview) ..................................771
Myocardial infarction complications ..................................775
Myocardial infarction in the elderly .................................780
Myocardial perfusion imaging .........................................782
Myocardial perfusion imaging (Pharmacological stress) ................788
Neck masses ..........................................................791
Nephrotic syndrome ...................................................798
Neurofibromatosis ....................................................802
Neuroleptic malignant syndrome .......................................804
Neutropenia and fever ................................................808
Nicardipine and hypertension .........................................810
Nipple discharge .....................................................811
Nitroglycerin ........................................................811
Nitroglycerin IV .....................................................812
Nitroprusside and hypertension .......................................813
Nocardiosis ..........................................................813
Non-Hodgkin's lymphoma ...............................................816
Obsessive-compulsive disorder ........................................822
Oliguria (Sudden) ....................................................825
Orthostatic hypotension ..............................................828
Osmolar gap ..........................................................830
Osteonecrosis ........................................................830
Osteomyelitis ........................................................831
Osteoporosis .........................................................837
Paget's disease of the bone ..........................................838
Pancreatitis .........................................................842
Pancreatitis (Causes) ................................................850
Pancreatitis complications ...........................................851
Pap smear ............................................................852
Paraneoplastic syndromes .............................................853
Parasitic testing ....................................................857
Parkinson's disease ..................................................860
Parkinson's disease (Levodopa complications) .........................861
Parotitis ............................................................863
Paroxysmal supraventricular tachycardia ..............................864
Patent ductus arteriosus .............................................866
Patent ductus arteriosus .............................................867
Pelvic inflammatory disease ..........................................867
Pelvic inflammatory disease (Outpatient) .............................871
Pelvic pain ..........................................................871
Pemphigus vulgaris ...................................................871
Penile lesions .......................................................874
Pericarditis .........................................................875
Pericarditis (Constrictive) ..........................................877
Peripheral alimentation ..............................................880
Peripheral neuropathies ..............................................880
Peripheral vascular disease ..........................................891
Phenothiazine overdose ...............................................894
Pheochromocytoma .....................................................894
Pheochromocytoma .....................................................895
Phentolamine and hypertension ........................................899
Pituitary tumors .....................................................899
Pleural effusion .....................................................900
Pneumocystis carinii and AIDS ........................................904
Pneumonia (Atypical) .................................................905
Pneumonia in the elderly .............................................908
Poisoning ............................................................911
Polyarteritis nodosa .................................................914
Polyarthritis ........................................................917
Polyarthritis and fever ..............................................920
Polycythemia vera ....................................................920
Polycythemia vera and surgery ........................................923
Polymyalgia rheumatica ...............................................923
Polymyositis/Dermatomyositis .........................................925
Porphyria (Acute intermittent) .......................................928
Post coronary bypass ischemia ........................................931
Post PTCA care .......................................................932
Pregnancy and congenital heart disease ...............................934
Pregnancy and contraception (Newer methods) ..........................936
Pregnancy and drugs to be avoided ....................................939
Pregnancy and drugs that may be indicated ............................939
Pregnancy and heart disease ..........................................940
Pregnancy and the heart ..............................................942
Pregnancy and hematologic disorders ..................................952
Pregnancy and safe drugs .............................................958
Premenstrual syndrome (Treatment) ....................................958
Primary aldosteronism ................................................959
Primary biliary cirrhosis ............................................959
Primary sclerosing cholangitis .......................................962
Prinzmetal's angina ..................................................963
Progressive supranuclear palsy .......................................964
Propranolol and hypertension .........................................965
Prosthetic valve dysfunction .........................................966
Proteinuria ..........................................................968
Pruritus (Generalized) ...............................................969
Pseudomembranous colitis .............................................971
Pseudomonas aeruginosa ...............................................973
Pseudotumor cerebri ..................................................974
Psittacosis ..........................................................976
Psoriasis ............................................................976
Psoriatic arthritis ..................................................980
PTCA vs thrombolysis in myocardial infarction ........................983
Pulmonary embolism ...................................................984
Pulmonary flow murmur (Innocent) .....................................986
Pulmonary hypertension (Primary) .....................................986
Pulmonary regurgitation ..............................................989
Pulmonic stenosis ....................................................989
Pulmonary stenosis ...................................................991
Purpura (Palpable) ...................................................991
Rabies ...............................................................992
Radiation proctitis ..................................................995
Rash plus fever testing ..............................................996
Raynauds's syndrome ..................................................996
Reiter's syndrome ....................................................998
Renal calculi ........................................................1000	 
Renal failure (Acute) ................................................1008
Renal failure (Chronic) ..............................................1010
Renal failure (Reversible) ...........................................1014
Renal transplantation ................................................1015
Renovascular hypertension ............................................1020
Revascularization approaches .........................................1020
Reye's syndrome ......................................................1022
Rheumatic diseases and drug treatment ................................1025
Rheumatic fever ......................................................1030
Rheumatoid arthritis and the lung ....................................1035
Rheumatoid arthritis (Treatment) .....................................1038
Rheumatology lab testing .............................................1043
Right ventricular infarction .........................................1046
Right ventricular infarction treatment ...............................1047
Risk stratification in acute myocardial infarction ...................1047
Rocky mountain spotted fever .........................................1048
Rocky mountain spotted fever .........................................1051
Salicylate poisoning .................................................1052
Salmonella and AIDS ..................................................1055
Salmonellosis ........................................................1055
Sarcoidosis ..........................................................1059
Sarcoidosis heart disease ............................................1062
Scabies ..............................................................1064
Scombroid poisoning ..................................................1067
Sedimentation rate (Westergren) ......................................1068
Seizures .............................................................1069
Seizures (Treatment) .................................................1069
Selective IgA deficiency .............................................1072
Sepsis ...............................................................1073
Sexually transmitted diseases (Treatment) ............................1079
Shigellosis ..........................................................1081
Short bowel syndrome .................................................1082
Shy-Drager syndrome ..................................................1084
Sickle cell anemia ...................................................1085
Sick sinus syndrome	..................................................1090
Sideroblastic anemia .................................................1091
Signal averaged ECG ..................................................1094
Sinusitis (Fungal) ...................................................1096
Sjogren's syndrome ...................................................1098
Sleep apnea ..........................................................1101
Snake bites (Rattlesnake) ............................................1102
Solitary pulmonary nodule ............................................1104
Sotalol ..............................................................1107
Spinal cord compression ..............................................1110
Spontaneous bacterial peritonitis ....................................1112
Sporotrichosis .......................................................1115
Staphylococcus aureus bacteremia .....................................1117
Status epilepticus ...................................................1118
Stevens Johnson syndrome .............................................1119
Stroke (Causes) ......................................................1120
Stroke in the young ..................................................1121
Strongyloidiasis .....................................................1123
Subdural hematomas ...................................................1124
Superior vena cava obstruction .......................................1126
Sweet's syndrome .....................................................1127
Syncope ..............................................................1128
Syncope causes .......................................................1131
Syncope ..............................................................1131
Syncope (Neurocardiogenic) ...........................................1134
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) .....1134
Systemic lupus erythematosus .........................................1136
Systemic lupus erythematosus and the lung ............................1142
Systemic lupus erythematosus laboratory diagnosis ....................1144
Tachycardia scenarios ................................................1148
Tamoxifen and endometrial cancer .....................................1149
Temporal arteritis ...................................................1150
Tetanus ..............................................................1151
Tetralogy of Fallot ..................................................1153
Theophylline toxicity ................................................1156
Thrombocytopenia (Idiopathic) ........................................1160
Thromboembolism prophylaxis in surgery ...............................1162
Thrombolytic therapy .................................................1163
Thrombolytic therapy in myocardial infarction ........................1166
Thrombotic thrombocytopenic purpura	..................................1169
Thyroiditis (Hashimoto's) ............................................1170
Thyroididis (Silent) .................................................1171
Thyroiditis (Subacute) ...............................................1172
Thyroid nodule (Solitary) ............................................1174
Thyroid nodule .......................................................1177
Thyrotoxic crisis ....................................................1177
Tick borne relapsing fever ...........................................1178
Tilt table testing ...................................................1180
Tinnitus .............................................................1181
Torsade de pointes ...................................................1182
Tourette's syndrome ..................................................1183
Toxic epidermal necrolysis ...........................................1186
Toxic shock syndrome .................................................1187
Toxoplasma gondii and AIDS ...........................................1190
Transesophageal echocardiography .....................................1190
Transient hypogammaglobulinemia of infancy ...........................1194
Transient ischemic attacks ...........................................1195
Traveler's diarrhea ..................................................1196
Tremors ..............................................................1198
Tremor (Essential) ...................................................1198
Tricuspid regurgitation ..............................................1200
Tricyclic poisoning ..................................................1200
Trigeminal neuralgia (Treatment) .....................................1201
Trigger fingers ......................................................1202
Trimethaphan and hypertension ........................................1202
Tuberculosis (Drug resistant) ........................................1202
Tuberculosis (Isoniazid intolerance) .................................1203
Tuberculosis (Possible drug resistant infection) .....................1203
Tuberculosis (Rifampin intolerance) ..................................1203
Tuberculosis (Second line drugs) .....................................1203
Tuberculosis (Standard therapy) ......................................1203
Tuberculosis drugs ...................................................1204
Tumor lysis syndrome .................................................1205
Urticaria ............................................................1206
Uveitis ..............................................................1210
Vaginitis ............................................................1215
Vancomycin dosing ....................................................1218
Vasculitis (Overview) ................................................1219
Venous hum (Innocent murmur) .........................................1221
Venous thrombosis ....................................................1221
Ventilator weaning ...................................................1222
Ventricular septal defect ............................................1222
Ventricular septal defect ............................................1225
Ventricular tachycardia ..............................................1225
Ventricular tachycardia (Treatment) ..................................1226
Vertigo (Differential diagnosis) .....................................1229
Vibratory murmur (Innocent) ..........................................1230
Vincristine toxicity .................................................1230
Violent patients .....................................................1231
Vitamin B12 deficiency ...............................................1232
Visual loss (Transient and monocular) ................................1235
Von Willebrand's disease .............................................1236
Waldenstrom's macroglobulinemia ......................................1240
Warfarin .............................................................1241
Weakness .............................................................1243
Wegener's granulomatosis .............................................1246
Weight loss ..........................................................1249
Wilson's disease .....................................................1249
Wiskott-Aldrich syndrome .............................................1251
Wolff-Parkinson-White syndrome .......................................1252
Wolff-Parkinson-White syndrome .......................................1256
X-linked agammaglobulinemia ..........................................1257


                     -ABDOMINAL AORTIC ANEURYSM-
If a person has an abdominal aortic aneurysm and lives long enough rupture is
inevitable.  Studies with CT  and  ultrasonography have shown expansion rates
of about 0.4 cm per year.  However, large aneurysms expand  faster  than  the
smaller  ones.   With  aneurysms  less  than  4.0  cm in diameter the risk of
rupture is about 2 percent.  About 25-41% of aneurysms greater than 5 cm will
rupture within 5 years.  ABDOMINAL ULTRASONOGRAPHY: Abdominal ultrasonography
is  about  100%  sensitive,  but   depends  on  the  technician's  expertise.
Advantages  include  the  following:  no   contrast   material   is   needed,
longitudinal  and  transverse  sections  are available and reproducibility of
size is fairly good.  If the  patient  is  obese and there is inordinate gas,
this will preclude a good exam.  The exam does not give accurate data for the
surgeon, because it can't evaluate the proximal and distal aortic  extent  of
the  aneurysm.   The  visceral  vessels  are  not evaluated either.  However,
despite these, US  should  be  used  for  screening  detection and sequential
follow up.  COMPUTERIZED TOMOGRAPHY: CT is  very  specific  and  has  a  high
sensitivity  and  may  be  more  precise in estimating size than US.  CT also
gives data on the shape of  the  aneurysm  and relation of visceral and renal
vessels.  Arguments against using CT includes the  following:  radiation  and
contrast  has  to  be used, is more costly than US and is not as available as
US.  CT is  not  recommended  as  a  screen  or preoperative study.  MAGNETIC
RESONANCE IMAGING:  MRI  is  not  used  much  because  it  is  expensive,  is
contraindicated  in  patients  with  pacemakers  and those patients that have
clips, doesn't provide accurate associated occlusive arterial disease, and is
not widely available.  AORTOGRAPHY OR INTRA-ARTERIAL DIGITAL SUBTRACTION: The
use of these tests pre-operatively  is controversial.  Some surgeons use them
and some don't.  Mural  thrombosis  will  give  a  false  estimation  of  the
diameter of the aneurysm.  If supra-renal or juxta-renal aneurysm, mesenteric
stenosis,  associated  iliofemoral arterial occlusive disease, renal arterial
stenosis and hypertension  are  suspected,  then  aortography  should be done
pre-operatively.  Coronary artery disease is the main disease  that  must  be
corrected  prior  to repair of abdominal aortic aneurysm.  About 35% of EARLY
deaths  after  repair  of  the  aneurysm  can  be  attributed  to  myocardial
infarction and 39% of deaths  5  years  later  can  be due to coronary artery
disease.   In  patients  that  have  coronary  artery  clinically,   coronary
arteriography may or may not be done before myocardial revascularization.  If
patient  has  no symptoms of coronary artery disease then possibly stress ekg
tests with or without thallium, and echocardiography may be done to determine
status of heart.  If  the  patient  has  <  50%  of predicted FEV1, and vital
capacity, this may interdict aortic reconstruction.  Renal  artery  occlusive
disease  and  creatinine  elevations  above  3  mg/dl  must  be addressed and
corrected.   Absolute  contraindications  to  elective  aortic reconstruction
include intractable CHF and angina, myocardial infarction within the  last  6
months,  severe  renal  and  pulmonary  disease  with dyspnea at rest, stroke
patients that are severely impaired  and  a  life  expectancy of only about 2
years.  As a general consensus, all asymtomatic aneurysms > 5 cm should  have
surgery.  All ruptured and symptomatic abdominal aortic aneurysms should have
surgery.    Aneurysms   between   the  4-5  cm  size  is  controversial,  but
occasionally the rupture rate may  approach  6%  per  year in this group.  If
elective repair is indicated later for aneurysms between the  4-5  cm  range,
then  US  should be done every 6 months.  If for some reason aneurysms > 5 cm
do not come to surgery then these  should  be followed every 3 months via US.
Screening may be cost effective if one selects out those  patients  that  are
susceptible  to  aneurysm.   These would include patients between the ages of
55-80, hypertension, those  that  have  associated  aneurysms of popliteal or
femoral area, and families that have a  history  of  aneurysm.   The  overall
mortality is 90%.  About 50% who reach the hospital will survive.  First, one
must  make  the  diagnosis,  and  this  may not be clear.  Differential would
include diverticulitis, renal colic, and  GI hemorrhage.  Most textbooks give
the triad of hypotension, abdominal pulsatile  mass  and  back  pain  as  the
presentation.  Most aneurysm rupture into the left retroperitoneum.  However,
the pain can be in the back, buttocks or testicular area, and the pain can be
colicky.  Rupture can occur into the bowel, peritoneal cavity, and vena cava.
It  has been shown that resuscitating the patient with fluids and raising the
blood  pressure  before  definitive  surgery   can  result  in  loss  of  the
retroperitoneal tamponade.  Thus, these measures should be deferred until the
rupture is controlled.  Excision and prosthetic dacron graft  replacement  is
the  standard  approach.   Mortality  has  steadily  improved since the first
successful aortic resection was carried out  in Paris in 1951.  The mortality
has been reduced over the last 4 decades from about  20  to  4  percent,  but
these  figures are tempered with many variables as condition of patient, etc.
Early  complications  after  elective  surgery  include:  cardiac arrhythmia,
ischemia and CHF (15%), pulmonary  insufficiency  (8%),  renal  damage  (6%),
distal  thromboembolism  (3%),  bleeding  (4%),  wound  infection (2%).  Rare
complications  include  paraplegia,  stroke,   ischemic  colitis  and  sexual
dysfunction.  Late postoperative complications that usually occur  3-5  years
after  surgery  include  graft  occlusion,  infection,  and  aortic - enteric
fistulae.

                   -ABDOMINAL PAIN (Non Surgical)-
In this discussion some of the more uncommon non-surgical causes of abdominal
pain will be discussed.  PORPHYRIAS: The  porphyrias are a group of inherited
disorders that are caused by defects in porphyrin  biosynthesis.   There  are
several  types  of  porphyrias,  but  the  most  common is acute intermittent
hepatic   porphyria.    However,   all   of   the   hepatic   porphyrias  can
cause abdominal pain.  The abdominal pain  may  be precipitated by drugs  due
to  stimulation  of the hepatic P450 cytochrome system.  Common drugs include
barbiturates, chlorpropamide, glutethimide, griseofulvin, ethanol, estrogens,
meprobamate,  chloroquine,  chlordiazepoxide,  ergot  agents,  imipramine and
methyldopa.  Fever is usually absent, but can be present.   The  patient  may
also have psychosis, demyelinating neuropathies, inappropriate ADH secretion,
and  hypertension.  Diagnosis of acute intermittent hepatic porphyria is made
by the Watson-Schwartz urine test  for porphobilinogen.  The urobilinogen may
give a false positive test.  Treatment is avoidance  of  inciting  drugs  and
suportive  care.   IV hematin may be of some benefit.  VASCULITIS: Several of
the vasculitides  may  present  with  abdominal  pain.   The  most  common is
probably polyarteritis.  Other vasculitic diseases that may  cause  abdominal
pain   include  SLE,  Henoch-Schonlein  purpura,  Degos  disease,  intestinal
ischemia and dermatomyositis.  The  pain  may  be  in  the epigastric area or
periumbilical.  Fever may be present.  The clue in making the diagnosis rests
upon  other  clinical  evidence  of  multisystem  disease.    Tests   include
antinuclear  antibody  titer, rheumatoid factor, ESR, abdominal angiograpohy,
and biopsy of  skin  lesions.   FAMILIAL  MEDITERRANEAN FEVER: This inherited
disorder is common in those individuals originating  from  the  mediterranean
area.   It is characterized by recurrent attacks of abdominal pain with signs
of peritonitis.  Fever is usually  present  during  the attack, and there may
also be arthritis, pleurisy, and migratory erythematous skin leskons that are
not unlike that of erysipelas.  Rarely, there may be pericarditis and aseptic
meningitis.  Amyloidosis may develop in  patients  of  Turkish  or  Israelian
origin.   Since  there is no diagnostic test for this disorder, the diagnosis
is often tentative.  During an  episode,  the  WBC, ESR and fibrinogen may be
elevated.  An acute attack may be aborted by giving .6 mg  of  colchicine  PO
and  repeated  every  hour  x3,  then  every  2  hours  for  two  more doses.
Maintenance therapy with 1-2 mg/day  may  be of benefit in suppressing future
episodes.  SICKLE CELL DISEASE: Patients with sickle cell disease can present
with abdominal pain due to different causes.  Some patients  with  homozygous
sickle  cell disease can have abdominal pain on the basis of a vaso occlusive
event which may  involve  the  viscera  or  the  abdominal  wall.  Almost all
patients with sickle cell disease will have gallstones which sets them up for
acute cholecystitis  secondary  to  common  duct  obstruction  and  ascending
cholangitis.   The  diagnosis is made by a sickle cell prep and/or hemoglobin
electrophoresis.  Many patients will  have  fever  and an elevated WBC.  Most
patients will have chronic hemolysis, and some will have elevation of hepatic
function  tests.   INTESTINAL  PSEUDO-OBSTRUCTION:  This   disorder   usually
presents  as  recurrent  bouts  of  abdominal distention and obstipation with
colicky  abdominal  pain.   The  pain   pattern  can  simulate  a  mechanical
intestinal obstruction.  Causes may  be  due  to  several  diseases  such  as
myxedema,  diabetes  mellitus,  hyperparathyroidism,  pheochromocytoma,  SLE,
dermatomyositis,  polymyositis,  progressive  systemic sclerosis, Parkinson's
disease,  myotonic  dystrophy,  psychosis,  familial  autonomic  dysfunction,
amyloidosis,   Chagas'   disease,    sclerosing   mesenteritis,   jejunoileal
diverticulosis and jejunoileal bypass.  Otherwise, it may be due to a primary
disorder of  the  myenteric  plexus  or  the  smooth  muscle  of  the  bowel.
HEREDITARY  ANGIONEUROTIC  EDEMA:   Hereditary  angioneurotic  edema (HAE) is
inherited as an autosomal dominant  trait which causes angioneurotic edema of
the skin of the deeper parts of  the  dermis  and  the  subcutaneous  layers.
There  is no pruritis associated with HAE.  Often times, the patient presents
with abdominal pain which is  due  to  angioneurotic edema of the bowel wall.
The pain is described as a colicky pain and is  associated  with  nausea  and
vomiting,  but  physical  exam  of the abdomen is usually benign.  The WBC is
usually normal and fever is  absent  in  the  majority of cases.  The attacks
last about 24-72 hours.  Some patients may  also  have  edema  of  the  upper
airway  which  can  cause  sudden  airway obstruction requiring intubation or
cricothyrotomy.   Patients  lack  a  C1'  esterase  inhibitor  which prevents
activation of the complement system.  During the attack, serum levels  of  C2
and C4 are also low.  Diagnosis is made by assaying the C1' inhibitor protein
directly, or the C1' esterase inhibitor activity of the plasma.  Treatment is
with  anabolic  steroids  which  will  increase the synthesis of C1' esterase
acrtivity and reduce the frequency of  attacks.  Epinephrine is used to treat
the  upper  airway  obstruction.   NARCOTIC  WITHDRAWAL:  This  diagnosis  is
difficult to make because most addicts will not admit  to  taking  narcotics.
For  this  reason  the patient should be checked for mydriasis, piloerection,
rhinorrhea as  well  as  the  colicky  abdominal  pain,  nausea, vomiting and
diarrhea.  Beware of patients that request a specific  narcotic  that  really
works  for  them.   ADDISON'S  DISEASE: Many of these patients do not present
with  an  Addisonian  crisis,  but   present   with  a  subacute  or  chronic
presentation of abdominal pain, nausea, and vomiting.  Other clues  that  may
point  to Addison's disease include weight loss, anorexia, hyperpigmentation,
salt  craving  and  weakness.   Patients  may  have  orthostatic hypotension,
hyperkalemia, hyponatremia, hypoglycemia, azotemia and metabolkic  alkalosis.
Patients  suspected  of having Addions's disease should have a serum coritsol
level.  Treatment is  with  hydrocortisone,  saline and glucose.  PSYCHOGENIC
DISORDERS: Many of these patients are women  who  present  with  non-specific
abdominal  pain  from  many psychiatric disturbances.  Many of these patients
have  depression,   anxiety,   hypochondriasis,   conversion  reactions,  and
somatoform disorders.  CHRONIC LEAD INTOXICATION: These patients can  present
with  a painful abdominal crisis or the pain can be more insidious.  There is
usually abdominal tenderness and guarding, but no peritoneal findings.  OTHER
CAUSES: Other causes include  abdominal  tabes, abdominal epilepsy, abdominal
migraine,  abdominal  angina,  Meckel's   diverticulitis,   irritable   bowel
syndrome,  inflammatory  bowel disease, diverticulitis, massive intravascular
hemolysis, and black widow spider bite.

                            -ABORTION-
Must rule out ectopic pregnancy with vaginal  bleeding,  pelvic  pain  and  a
positive  pregnancy  test.  Get 3 tests: quantitative hCG, serum progesterone
and vaginal pelvic  sonogram.   A  serum  progesterone  higher  than 25 ng/ml
supports a good outcome and virtually rules out ectopic pregnancy.  No viable
pregnancies result when the progesterone is lower than 5  ng/ml.   The  serum
hCG  shoyuld  rise  steadily in early pregnancy and double every 48 hrs up to
the sixth or seventh week.   Vaginal  probe  US can detect cardiac activity 6
weeks after the last period.  Abdominal US doesnt visualize the  heart  until
7-8  weeks.  You should be able to see the site of pregnancy by vaginal probe
US when hCG has  reached  2000  mlU/ml.   Can  see  the  site of pregnancy by
abdominal US when hCG is 6,500 mlU/ml.

                         -ABORTION (SEPTIC)-
Any patient that  is  pregnant  or  is  suspect  for  septic  abortion with a
temperature > 38 C, tachycardia, vaginal bleeding, and peritonitis should  be
hospitilized  and  started  on antibiotic therapy. These patients may develop
bacteremia with  septic  shock  and  the  adult  respiratory  syndrome.  Many
patients present to their physician  late,  because  they  are  reluctant  to
reveal  that they have had an abortion.  The HCG beta subunit will usually be
positive as it takes 4-6 weeks for the HCG to become undetectable after there
has been complete uterine evacuation.   Illegal abortions with soap solutions
that contain phenol and  cresol  can  causes  renal  failure,  CNS  toxicity,
respiratory  distress,  cardiac  depression  and  uterine  necrosis.   If the
abortion  was  carried  out   with   rigid  insttruments,  perforation  is  a
consideration.   The  patient  should  be  examined  for  pus,  products   of
conception  and  lacerations  of  the  vagina and cervix, adnexal masses, and
x-ray of the abdomen to rule out free air and foreign objects.  The infection
is usually polymicrobial from the normal  flora of the endocervix and vagina,
anaerobes  from  perforation  of  the  uterus,  and  may   include   sexually
transmitted   organisms   such   as   Neisseria   gonorrhoeae  and  Chlamydia
trachomatis.  Clostridum perfringens is a possiblity if the abortion has been
illegal.  Cultures and Gram stain of the blood, urine, cervical os and tissue
obtained from  uterine  aspiration  should  be  performed.   For  mild septic
abortions, a trial  of  ofloxacin  +  clindamycin  or  metronidazole  can  be
attempted  as  an outpatient with very close observation.  Should the patient
fail to improve, the patient should be hospitilized and started on penicillin
5 million units IV q6h or ampicillin 2-3 grams IV every 6 hours + clindamycin
900 mg IV q8h + an  aminoglycoside  such as gentamicin or tobramycin (loading
dose of 2 mg/kg followed by 1.5 mg/kg q8h), contingent upon the renal  status
and the blood levels.  After the patient has been started on antibiotics, the
uterus  should  be  emptied.  This should be done without delay as failing to
evacuate the uterus can lead to mortality.  This is usually accomplished with
local  anesthesia  and   IV   sedation   using  vacuum  curettage.   Retained
midtrimester fetuses can be difficult, but  may  be  removed  with  curettage
which  is guided by ultrasound.  If this cannot be accomplished the 15 methyl
analogue of prostaglandin F2 alpha,  carboprost  tromethamine can be given as
250 ug every 2-3 hours IM.  This should  not  be  given  if  the  patient  is
asthmatic.   Furthermore,  the use of prostaglandin E2, or dinoprostone given
as a 20 mg vaginal suppositories should  not be given to patients with sepsis
because it can increase the temperature.  An alternate method  of  evacuation
is  oxytocin given as 50 units of oxytocin in 500 ml of D5W and normal saline
over a three hour period.  This is followed by a one hour observation period.
If there has been no fetal abortion,  100  units of oxytocin in 500 ml of D5W
is given for another 3 hour period.  The incremental increase of 50 units  of
oxytocin is continued every 3 hours until the fetus aborts or a total dose of
300  units  ooxytocin  has  been  given.   Should the patient have an uterine
perforation, bowel injury, clostridial  myometrits, pelvic abscess or uterine
evacuation is unsuccessful, laparotomy will  be  needed.   During  laparotomy
cultures should be obtained.  Septic shock should be managed with a Swan Ganz
catheter, arterial line and fluid therapy as needed.  Dopamine and dobutamine
may be needed to support the blood pressure.

                         -ABSCESS (Hepatic)-
In the USA the most common cause of hepatic abscesses is bacterial,  followed
by parasitic infection from Entamoeba histolytica.  Fungal abscesses are very
rare,  but  are  occasionally  due to Candida.  Candida hepatic abscesses may
follow chemotherapy  for  cancer.   The  most  common  bacterial  etiology is
secondary to disease of the bilary tract.  Other causes  include  suppurative
pylephlebitis  from  infection  starting  in  the  pelvis or elsewhere in the
peritoneal  cavity.  Pyogenic hepatic  abscesses  are more common in patients
with diabetes mellitus and previous heptatobiliary surgery.   Less  commonly,
hepatic  abscess  may  be  secondary  to  hepatic tumors that undergo central
necrosis and secondary bacterial infections of hydatid cysts, simple cysts or
ambebic cysts.  In the past ruptured  appendicitis was the most common cause.
Abscesses can be classified  as  solitary,  multiple  or  miliary.   Solitary
abscesses  are usually confined to the right lobe of the liver and suggest an
amebic etiology if there is  a  history  of  diarrhea  or recent travel to an
endemic area.  Multiple abscesses affect the right  and  left  lobe  equally.
Liver  abscesses  that  arise  from  the  biliary  tree are usually caused by
enteric gram negative aerobic bacilli and enterococci unless previous surgery
has been performed, in which  case, anaerobes are involved.  Hepatic pyogenic
abscesses secondary to pelvic  and  other  peritoneal  sources  are  commonly
polymicrobial  including  aerobic  and  anaerobic  species (Escherichia coli,
Bacteroides,  Streptococcus   faecalis,   and  Peptostreptococcus).   Hepatic
abscesses  secondary  to  hematogenous  dissemination  are  commonly  due  to
Staphylococcus aureus or a streptococcal species  as  Streptococcus  milleri.
Distant  septic foci that spread hematogenously would include pyelonephritis,
infective endocarditis  and  pneumonia.   CLINICAL:  Symptoms  include fever,
malaise,  fatigue,  weight  loss  and  anemia.   Only  about  50%  will  have
hepatomegaly, jaundice and right upper  quadrant  tenderness.   Jaundice  and
scleral  icterus  usually  indicate biliary obstruction such as a common duct
stone with cholangitis, or liver  failure.   In the elderly, fever of unknown
origin may be the only symptom.  History should include any previous  biliary
surgery,  or  diabetes.  About 90% of patients will have an elevated alkaline
phosphatase,   while   only   about   50%   will   have   elevated  aspartate
aminotransferase.  Leukocytosis occurs in 3/4 of patients  and  normochromic,
normocytic  anemia  in  50%.   The  WBC is usually > 16,000/uL with increased
immature  forms  and  PMNs.   However,  elderly  patients  may  present  with
neutropenia with a left shift.  The  chest  x-ray may reveal elevation of the
right  hemidiaphragm  with  right  basilar  infiltrates  and  right   pleural
effusion.   Blood  cultures  are  positive  in  approximately  50%  of cases.
Patients with endocarditis will usually have  a murmur.  CT of the abdomen is
the best test, for it can ascertain the size and number of abscesses and  can
direct  percutaneous  aspiration  and  drainage.   Ultrasound  is  useful  in
determining  whether  gall  bladder  calculi  and cholescystitis are present.
Indium labeled WBC scans or gallium  scans  can also be useful.  Amebic liver
abscesses  are  associated  with  a  95%  positive  ambebic  serology.    The
differential   diagnosis   includes   the  Fitz-Hugh-Curtis  syndrome,  acute
hepatitis,  acute  cholangitis  and  acute  cholecytitis.   Complications  of
hepatic abscess include rupture  of  the  abscess  into the periotneal cavity
producing acute peritonitis, hemobilia, secondary to rupture of  the  abscess
into  a  blood  vessel  and pseudoaneurysm.  TREATMENT: Treatment consists of
antibiotics and percutaneous  or  surgical  drainage.  The antibiotic therapy
may   consist   of   the   following:   Ampicillin-sulbactam   (Unasyn)    or
ticarcillin-clavulanate   (Timentin),   or   ampicillin  +  aminoglycoside  +
metronidazole, or imipenem-cilastatin (Primaxin).

                         -ABSCESS (Epidural)-
Epidural  abscess  (EA) usually presents with severe pain over the spine, and
tenderness to percussion.  This  may  be followed with radicular disturbances
such as bowel and bladder dysfunction,  abdominal  distension,  weakness  and
ultimately paralysis.  The diagnosis must be made swiftly as the average time
from  back pain to weakness is about 4 days.  The weakness typically advances
to paraplegia in 24 hours.  The patient  may have chills and sweats and boils
are found in about 15%.  Any patient  that  has  backache,  fever  and  spine
tenderness  should  be  suspected of epidural abscess.  The thoracic level is
the most common site of involvement  (50%), followed by the lumbar (35%), and
cervical (15%).  Chronic immunosuppressing diseases  such  as  chronic  renal
failure,   alcoholism,  diabetes  mellitus  and  IV  drug  abuse  are  common
underlying diseases that permit  epidural  abscesses to be established.  Most
cases are hematogenous (26-50%) to the epidural space or to a  vertebra  with
subsequent spread to the epidural space.  Clinical settings include bacterial
endocarditis,  urinary  tract  infections,  IV  drug abusers, skin infections
(most common), sinusitis, otitis  media,  pneumonia, and dental or pharyngeal
abscesses.  Direct extension to the epidrual space may  be  from  perinephric
abscesses,   psoas   abscess,   pharyngeal   abscesses,   mediastinitis,  and
penetrating wounds to the  abdomen  and  neck.   Post surgical procedures may
also lead to epidural  abscess.   These  include  lumbar  diskectomy,  lumbar
puncture  and  epidural  anesthesia.   The  most  common organism in epidrual
abscess is Staph aureus which  is  cultured  in greater than 50%.  The second
most  common  organisms  are  aerobic  and  anaerobic  streptococci.    Other
bacterial   that   have   been   incriminated  include  Serratia  marcescens,
enterobacter,  Pseudomonas   aeruginosa,   and   the  pneumococcus.   Chronic
infections  that  are  capable  of  causing  epidural  abscess  include   TB,
aspergillosis,  cryptococcosis,  brucellosis,  and Echinococcus.  LABORATORY:
The WBC is usually  elevated  in  the  acute  causes,  with an average WBC of
16,000.  In chronic causes such as TB, the WBC may be normal.  MRI imaging of
the spine is the procedure of choice with a  sensitivity  equal  to  that  of
myelograms  and  CT.  Furthermore MRI can differentiate other conditions such
as transverse myelitis or spinal  cord  infarction better than a myelogram or
CT.  An MRI can eliminate the necessity for a  lumbar  puncture.   TREATMENT:
The  patient must have surgical drainage of pus and debridment of granulation
tissue  followed  by  osseous  stabilization.   Most  epidural  abscesses are
posterior to the dura and can be approached with  an  extensive  laminectomy.
If  there  is  no  evidence of vertebral osteomyelitis, bony instability will
usually not develop	following  a  simple  laminectomy and antibiotic therapy.
Empiric antibiotic therapy includes a third generation cephalosporin such  as
cefotaxime + vancomycin to cover a methicillin resistant Staph aureus (MRSA),
until  MRSA can be ruled out.  Once MRSA is ruled out, Nafcillin can be used.
The ultmate antibiotic used  depends  on  the underlying cause.  For example,
gram-negative organisms are common in IV drug abusers.  The total duration of
antibiotic therapy usually is about 8 weeks (4 weeks of IV antibiotics and  4
weeks of oral therapy).

                           -ACE INHIBITORS-
Ace inhibitors are now being used for the treatment  of  hypertension,  heart
failure,  post  MI,  and  for diabetic nephropathy.  ACE inhibitors block the
converting enzyme that is responsible for  the conversion of angiotensin 1 to
the active angiotensin II, a vasoconstrictor.  ACE  inhibitors  also  possess
properties   that   will   increase   vasodilating  prostaglandins,  increase
bradykinin,  increase  endothelial   derived   nitric   oxide,  and  decrease
sympathetic activation.  HYPERTENSION: ACE inhibitors lower blood pressure by
decreasing systemic vascular resistance and decreasing left ventricular mass.
All of the present  ACE  inhibitors  have  similar  efficacy  and  safety  in
reducing  hypertension.   Monotherapy  with ACE inhibitors can  significantly
decrease blood pressure in greater than  50% of patients, but when a diuretic
is  added,  or  the  patient  is  sodium  restricted,  about  80-90%  can  be
controlled.  ACE inhibitores given by themselves may  be  less  effective  in
blacks  than  in whites.  HEART FAILURE: Congestive heart failure affects 3-4
million Americans with  400,000  new  cases/year.   Diastolic dhysfunction is
often overlooked as a cause of CHF.  Some cases of  CHF  are  placed  in  the
category  of  refractory  CHF.   Diastolic  dysfunction  can  be  detected by
identification  of  left  ventricular  filling  abnormalities,  most commonly
involving  impaired  ventricular  relaxation.   These  filling  defects   are
apparent  on echocardiography or radionuclide testing.  Diastolic dysfunction
can be treated by  lowering  the  heart  rate and decreasing left ventricular
hypertrophy with blood pressure  control,  and  the  use  of  an  angiotensin
converting  enzyme  inhibitor.   ACE inhibitors can be used as monotherapy in
patients  with  asymptomatic  left   ventricular  dysfunction  or  clinically
apparent heart failure.  Diuretics can be added if patients fail  to  improve
in  spite of optimal doses of ACE inhibitors.  Should this fail, then Digoxin
may be added.  ACE inhibitors can  reduce mortality in patients with moderate
and severe heart failure that is unrelated to an acute infarction.  This  has
been  demonstrated  in 3 separate multicenter trials that involved enalapril.
These included the Vasodilator  Heart  Failure  Trial (V-HeFT II), Studies of
Left Ventricular Dysfunction (SOLVD), and the Cooperative North  Scandinavian
Enalapril   Survival  Study  (CONSENSUS).   Patients  who  have  sustained  a
myocardial infarction, and have  a  moderate  or  severe decrease in the left
ventriuclar systolic function (ejection  fraction  less  than  35-40%),  will
benefit  from  ACE  inhibitors  by  slowing  or preventing the progression of
symptomatic  heart  failure.    Following   myocardial  infarction  there  is
ventricular dilatation and hypertrophy, activation of  the  renin-angiotensin
system,   increased   plasma  atrial  natiuretic  factor,  sodium  and  water
retention, increased  norepinephrine,  reduced beta-adrenergic responsiveness
of the myocardium, and peripheral  vasoconstriction.   Presently,  lisonopril
(Zestril, Prinvil) is given at 20 mg daily.  Quinapril (Accupril) is given at
20  mg BID, enalapril (Vasotec) is given at 10 mg BID and captopril (Capoten)
is given as 50 mg TID.  Two  major  trials have now addressed the efficacy of
ACE inhibitors  in  post  MI  patients.   In  the  Survival  and  Ventricular
Enlargement  (SAVE)  trial,  mortality was reduced to 19%, while in the Acute
infarction Ramipril Efficay (AIRE) trial  there  was a reduction of mortality
of 27%.  In the  SAVE  trial,  patients  with  a  left  ventricular  ejection
fraction  of  less  than  40%  were  started  on  captopril  within 3-16 days
following  a  myocardial  infarction.   The  long  term  results demonstrated
improved survival and reduced morbidity and mortality due  to  cardiovascular
events  in asymptomatic patietns.  When the study ended about 80% of patients
had reached a dose of  captopril  50 mg TID.  DIABETIC NEPHROPATHY: Captopril
has been shown to retard the progression of diabetic nephropathy (proteinuria
greater than 500 mg/day and serum creatinine less than 2.5 mg/dL) in  insulin
depenndent  diabetic  patients,  with  a 50% reduction in death, dialysis and
transplantation.  This effectiveness has been attributed to the production of
decreased intrarenal efferent arteriolar pressure.  Captopril is indicated in
patients with Type I diabetes  with  normal  blood pressure, and in those who
are hypertensive.  In patients with a  serum  creatinine  of  less  than  2.5
mg/dL,  the  dose  is 25 mg TID.  Patients with a creatinine greater than 2.5
will need a  dose  reduction  of  the  ACE  inhibitor.   ADVERSE EFFECTS: All
patients should be followed for changes in blood pressure, renal function and
serum potassium starting about 1 week after introducing ACE  inhibitors.   If
the  patient  develops  hypotension  or  renal  insufficncy, the fluid status
should be addressed.   The  initial  dose  of  an  ACE  inhibitor can cause a
significant  decrease  in  blood  pressure,  especially  if  the  patient  is
receiving a diuretic, or is on a  sodium  restricted  diet,  dialysis  or  is
hyponatremic.  If the patient is at risk for hypotension, the diuretic should
be  reduced  or  discontinued  prior to starting the ACE inhibitor.  Patients
using ACE inhibitors may  develop  hyperkalemia,  especially in patients with
renal dysfunction and the elderly.  All potassium sparing diuretics  such  as
triamterene,  spironolactone  and  amiloride  should be discontinued prior to
using ACE inhibitors.  If hypokalemia  persists following the introduction of
ACE inhibitors, the potassium sparing diuretics may be slowly and  cautiously
restarted.   ACE  inhibitors decrease renal perfusion, and this can lead to a
reversible elevation of the BUN and  creatinine.  If this becomes severe, the
dose of the ACE inhibitor and/or the diuretic can be reduced.  Patients  that
have  bilateral  renal artery stenosis, or stenosis in a solitary functioning
or transplanted kidney may develop  acute reversible renal	failure, and ACE
inhibitors should be used with caution in  these  patients.   Ace  inhibitors
should  not  be  used  in  pregnancy.   If  used  during the second and third
trimesters, ACE inhibitors can cause injury and even death in the fetus.  All
ACE inhibitors should be dicontinued  as  soon  as pegnancy is detected.  ACE
inhibitors cause a cough in as many as 15% of  patients.   This  may  develop
initially  or  after  some  months  of  therapy.   NSAIDs should be used with
caution in patients that  are  taking  ACE  inhibitors  as they can aggravate
renal insufficiency secondary to a reduction in vasodilating  prostaglandins,
and  can  also  interfere  with  the efficacy in lowering blood pressure.  In
these patients calcium channel or beta  blockers should be considered, if the
patient is taking ACE inhibitors.  Angioedema occurs in about .1-.2% and  may
be  life  threatening.  Other minor side effects include dizziness, headache,
and fatigue.  Captopril can cause taste changes (2-4%, and rashes (4-7%).

             -ACE INHIBITORS IN MYOCARDIAL INFARCTION-
There  have  been  several  studies  that suggest that angiotensin converting
enzyme inhibitors  when  used  in  post  myocardial  infarction patients with
severe left ventricular systolic dysfunction, can decrease mortality.  In the
GISSI-3 and ISIS-4 studies which used lisinopril  and  captopril,  there  was
early  reduction  of mortality when these agents were given to those who also
received  thrombolytic  therapy.   In  the  SAVE  (Survival  and  ventricular
enlargement) study  captopril  vs  placebo  was  given  from  3-16  days post
myocardial  infarction  to  patients  who  had  ejection  fractions  <   40%.
Captopril  was  given at 50 mg TID.  With this dose there was a 17% reduction
in the risk of re-infarction and  risk  for  death.  In the SOLVD (Studies of
left ventricular dysfunction) trial, enalapril given at a target dose  of  20
mg  per  day  vs  placebo  was  examined  in  those  patients  who had a left
ventricular ejection fraction <  35%.   There  were 7000 patients enrolled in
the study of which about 80% had known ischemic heart disease.  Most patients
had had at least one myocardial infarction in the past.  It  was  found  that
there was a 20% reduction in hospitilization risk for death, unstable angina,
and  fatal  and  non-fatal  myocardial  infarction.  The benefit for reducing
unstable angina and prevention of myocardial infarction was not evident until
the patients had recieved 6 months  of therapy.  This suggests that long term
ACE therapy is needed.  It is interesting that another study, the CONSENSUS 2
STUDY found no significant benefit after 6 months of therapy.  In this  study
6000  patients  were given either placebo or enalaprilat IV within one day of
the acute myocardial infarction, followed  by  oral enalapril or placebo.  In
some of these patients there was a suggestion of adverse  effects  attributed
to  enalapril.   Ace  inhibitors  have  considerable  merit in that they have
beneficial effects on left ventricular loading  and remodeling in the post MI
period coupled with the  possible  blockade  of  heart  failure  neurohormone
stimulation.

                     -ACETAMINOPHEN TOXICITY-
If  the patient is seen within 12 hrs of ingestion and is alert, ipecac 30 ml
with fluids is given.  Repeat in  15  minutes or gastric lavage.  Do not give
charcoal or cathartics.  LAB: acetaminophen level 4 hrs post ingestion, liver
tests, BUN, creatinine, glucose, PT.  THERAPY: Within  24  hrs  of  ingestion
give  Mucomyst  loading  dose  of 140 mg/kg PO, diluted 3:1 in juice, soda or
water, then maintenance of 70 mg/kg  PO  q4h  for 17 doses.  Beyond 24 hrs of
ingestion supportive therapy is indicated without mucomyst.  Avoid  diuresis,
sedatives and drugs that are metabolized in the liver.  Obtain daily labs for
at  least  4  days.   For a prolonged PT give vitamin K 10 mg IM.  Refractory
bleeding may require fresh frozen plasma.  The  toxic dose in adults is > 7.5
grams, with hepatic damage > 10 grams.  The  symptoms  are  malaise,  nausea,
vomiting and sweating.

                              -ACNE-
Retin-a cream .05%.  Apply once  daily  unless sensitive skin, then alternate
nights.  Wash face with a mild soap such as Purpose.   Gently  dry  face  and
wait  20  minutes.   Then  apply a pea size dose for the entire face avoiding
sensitive areas around the eyes, angles of the nose and corners of the mouth.
Discontinue any astringents or drying agents.  Apply moisturizer each morning
such as Lubriderm lotion or Moisturel lotion.  Use a sunscree of at least SPF
15 such as Sundown sunscreen.  Avoid excess exposure to the sun.

                             -ACROMEGALY-
Acromegaly  is  due  to  hypersecretion  of growth hormone (GH) and secondary
overproduction of insulin  like  growth  factor IGF-1 (Somatomedin-C).  About
99% of the cases of  acromegaly  are  caused  by  a  pituitray  GH  producing
adenomas.   Other  causes  are  ectopic  GH-producing tumors, hypothalamic or
pituitary GHRH producing  gangliocytomas,  pituitary GH producing carcinomas,
adenomas of the ectopic pharyngeal pituitary, and  autonomous  production  of
IGF-1.   The clinical presentation is dependent upon the age of onset.  Those
patients that have an onset  prior  to  puberty will present with accelerated
linear growth and pituitary gigantism.  After  puberty,  the  GH  will  cause
acromegaly.   The  patient  will  notice  growth  of the head, hands and feet
resulting in an increase  in  ring,  glove  and  shoe  size.  The patient may
complain  of  headaches  and  visual  field  defects  (typically   bitemporal
hemianopsia).   There  is  coarsening of facial features, increased sweating,
and  increased  frequency  of  skin   tags.   The  patient  may  complain  of
arthralgias, arthritis  and  carpal  tunnel  syndrome.   There  may  also  be
amenorrhea,  decreased libido, hypertension and glucose intolerance.  WORKUP:
Since growth hormone is pulsatile,  a  single  GH sample may not be elevated.
However, an elevated IGF-1 will confirm GH hypersecretion.  Therefore, if the
history and physical are suggestive of acromegaly, the first test to be  done
should  be  the  IGF-1.   If  this is normal, acromegaly is excluded.  If the
IGF-1 is borderline or  elevated  a  glucose  suppression test with GH levels
should be done.  This is done by giving the  patient  100  grams  of  glucose
orally.   GH levels are then measured at baseline, 1, and 2 hours.  Normally,
glucose will  suppress  GH  secretion.   However,  in  acromegaly,  the tumor
secretion is autonomous and does  not  suppress  the  GH.   The  hallmark  of
acromegaly is the nonsuppression of plasma GH below 2 ng/ml after the glucose
load.   If there is no suppression, the patient should then have a CT scan or
MRI of the pituitary.  If this  is  abnormal acromegaly is diagnosed.  If the
CT or MRI is normal, a growth hormone rleasing hormone (GHRH) tumor should be
ruled out, which most commonly arises from the lung or abdomen.  Diagnosis is
accomplished by ordering a CT of the chest and abdomen.   Another  test  that
can  be  done  to  help  confirm  the  diagnosis  of  acromegaly,  is the TRH
stimulation test.  This is performed by done by administratiion of TRH 200 ug
IV, and observing for an increase in GH which occurs in 80-90% of acromegalic
patients.  Hyperprolactinemia is  seen  in  30%  of patients with acromegaly.
Plasma GHRH levels are rarely needed to establish a case of  acromegaly  that
is due to excessive GHRH secretion.  TREATMENT: Transphenoidal surgery is the
treament  of  choice  for  most  patients.  Surgery results in improvement in
about 90% of patients.   In  patients  whose  GH  and  IGF-1 levels return to
normal, the recurrence rate is about 5%.   However,  in  patients  that  have
incomplete  tumor  removal, the recurrence rate can be greater than 50%.  The
patient should be examined 3 months postoperatively with measurement of IGF-1
levels and a glucose suppression test.  A TRH test may also be done if it was
abnormal prior to surgery.  Visual fields  should also be followed as well as
CT scanning and MRI studies.  Patients that have persistently elevated GH and
IGF-1 post surgery should be treated with radiation therapy to the pituitray.
However, patients with GH levels greater than 50 ng/ml are not likely  to  be
cured  by radiation by itself.  Because of the possibility of hypopituitarism
from radiation,  annual  testing  should  be  done.   Should  the  patient be
resistant to surgery and radiotherapy, bromocriptine may be used in doses  of
10-20 mg daily with meals.

                           -ADNEXAL MASSES-
DIFFERENTIAL  DIAGNOSIS:  The  differential  diagnosis  of  adnexal masses is
legion, but would include  the  following: Malignant ovarian neoplasm, benign
ovarian  neoplasm,  hydrosalpinx,  tubo-ovarian   neoplasm,   ectopic   tubal
pregnancy,   functional   ovarian   cyst,   hemorrhagic  cyst,  endometrioma,
leiomhyomas, para-tubal cyst and  endometriomas.   In general, malignancy can
be  suggested  by  assessing  such   factors   as   age   (premenopausal   vs
postmenopausal),  findings  on  examination such as cul-de-sac nodularity and
fixation, associated signs and  symptoms,  ultrasound characteristics such as
morphology, Doppler studies  and  ascites,  and  the  CA-125  level.   Eighty
percent  of  ovarian cancer occurs in women > 50 years of age.  The incidence
of malignancy in women between 40-49  is  35%, 50-59 years ofage (46%), 60-69
years (49%) and > 70 years old (29%).  ULTRASOUND TESTING: Bromley, et al has
proposed  a  scoring system based on the characteristics  of  ultrasound.  If
the score is < 4 the mass is likely to be benign: if > 4 malignancy should be
suspected.   A  clear  cyst < 3 cm on ultrasound is given a score of 1; clear
cyst > 3 cm gets a score of  2.  If the cyst has a slightly irregular wall on
one side a score of 3 is given.  If the cyst has uniform low level echoes  or
a  single  thin  septation,  the  score  is  4.  If  there is a solid ovarian
enlargement; cyst with irregular borders; non-specific ovarian mass the score
is 5-6.  Multiple septations and a  nodular  cystic mass registers a score of
7-9 (7=less nodular while a 9=more nodules and septations).   If  ascites  is
present  along with multiple septations and nodular cystic mass a score of 10
is given.  COLOR DOPPLER WITH  PULSED DOPPLER WAVEFORM ANALYSIS: In assessing
for malignancy the resistance index (RI) and the pulsatility index  (PI)  can
be  used.   If  there  is  found  to  be a low RI or low PI + a high score on
Ultrasound morphology, malignancy should be  suspected.  The combination of a
high RI or high PI and a low morphological score on US would tend to favor  a
benign  tumor.   The  problem  is that there is a significant overlap between
benign and  malignant  lesions  and  an  accurate  cutoff  between benign and
malignant tumors is difficult to establish.  The rationale  for  using  these
indices   is   that   intratumoral   blood  vessels  with  neovascularization
characteristically have low resistance  to  flow (high diastolic flow), while
non-malignant   tumors   and   normal   ovaries   usually   do    not    have
neovascularization  (low  diastolic  flow).   The  RI=systolic  peak  flow  -
diastolic  trough  flow/systolic  peak flow.  The PI=systolic peak flow - end
diastolic flow/mean flow velocity.  CA-125:  It  is estimated that the CA-125
is elevated in 80% of women that have epithelial ovarian  carcinoma,  but  is
elevated  in  <  50% of Stage I epithelial ovarian cancers and if elevated in
postmenopausal woman it is more  suggestive  of malignancy.  The normal value
is < 35.  The problem is that the CA-125 can be elevated in many  gynecologic
and  non-gynecologic  conditions  whether benign or malignant.  The following
illustrates  this  fact:  GYNECOLOGIC  CONDITIONS  ASSOCIATED  WITH  ELEVATED
CA-125: Endometriosis,  adenomyosis,  leiomyomas,  first trimester pregnancy,
benign   ovarian   cysts/tumors,    and    pelvic    inflammaotry    disease.
NON-GYNECOLOGIC   CONDITIONS:   Peritonitis,   pancreatitis,  renal  failure,
pericarditis, hepatic disease.  MALIGNANCIES ASSOCIATED WITH ELEVATED CA-125:
Gynecologic malignancies  include  epithelial  ovarian cancer, non-epithelial
ovarian  cancers,  endometrial,  cervical   and   fallopain   tube   cancers.
Non-gynecologic malignancies that will elevate the CA-125 include pancreatic,
hepatic, breast, lung and GI malignancies.  If there is a combination of high
CA-125  +  high  US  morphology  score  +  low RI or PI, malignancy should be
suspected.  If there is a  combination  of  a  low CA-125 + low US morphology
score + high RI or PI,  a  benign  tumor  should  be  suspected.   TREATMENT:
Laparoscopy  versus  laparotomy.   Laparoscopy  should  be  considered if the
patient is premenopausal  with  no  ascites  and  there  is low suspicion for
malignancy OR if the patient is postmenopausal with  a  unilateral  mass,  no
ascites,  normal  CA-125  and  there  is a simple cyst or cyst with few, thin
septations.  During laparoscopy there  should  be  inspection of the mass for
surface abnormalites, and inspection of the  pelvis  and  abdomen  for  tumor
implants.   Pelvic  washings,  frozen  section of mass and biopsies should be
carried out.   The  mass  can  be  removed  via  trocar  sites, via posterior
colpotomy or by enlargement of a midline trocar  incision.   Cyst  aspiration
for  fluid  cytology  is  controversial because cytology is often negative in
histologically malignant  tumors,  and  10-66%  are  read  as  benign but are
actually malignant.  Cyst leakage into the abdomen, if malignant, will change
the stage from IA or IB to IC (IA and IB do not always need chemotherapy,  IC
does).   However,  some recent studies show rupture has no significant effect
on prognosis or relapse.  If  laparotomy  is  chosen because of suspicion for
malignancy, staging should be done with frozen  section  for  histopathology,
washings,  omentectomy,  multiple biopsies of the pelvis, para-colic gutters,
diaphragms, adhesions, suspicious lesions,  right diaphragm scrapings, pelvic
and para aortic node sampling.  Total abdominal  hysterectomy  and  bilateral
salpingo-oophorectomy  should  be done (sometimes a conservation procedure is
done if the patient is young and desires fertility).

                      -ADRENAL INSUFFICIENCY-
Adrenal insufficiency (AI) can  be  a  medical  emergency  and the failure to
recognize it could have catastrophic consequences.  The incidence of  AI  may
be  rising  with AIDS and the increasing use of steroids.  CAUSES: The causes
can be divided into  two  categories:  primary adrenal disease and secondary.
PRIMARY  can  be  caused  by  the  following:  Granulomatous   disease   (TB,
Histoplasmosis  and  other  fungal  infections,  and sarcoidosis), Neoplastic
infiltration,    Amyloidosis,     Hemochromatosis,    Drugs    (ketoconazole,
mifepristone, anticoagulants), meningococcemia  with  Friderichsen-Waterhouse
syndrome,   adrenal  hemorrhage,  adrenoleukodystrophy  in  boys,  autoimmune
adrenalitis, and acquired  immunodeficiency syndrome.  SECONDARY hypothalamic
and or pituitary disorders  can  be  caused  by  pituitary  and  hypothalamic
tumors, lymphocytic hypophysitis, and withdrawal from glucocorticoid therapy.
Idiopathic autoimmune adrenalitis is the most common cause accounting for 80%
of  adrenocortical  insufficiency.   There  are  several  endocrine disorders
associated   with   this   disease:   (diabetes   mellitus,   thyrotoxicosis,
thyroiditis,  alopecia,  vitiligo,   myasthenia  gravis,  hypoparathyroidism,
pernicious anemia, ovarian failure, hypercalcemia,  chronic  moniliasis,  and
Schmidt's   syndrome).   Several  antibodies  are  often  found  as;  gastric
antibodies (20%), parathyroid antibodies  (20%), adrenal antibodies (60%) and
thyroid antibodies (40%).  Metastatic disease involves the adrenal glands  in
25%  of  oncologic  patients.   Ninety percent of the adrenal gland has to be
destroyed before a patient is  symptomatic.   Most cancer patients don't have
this amount of involvement.  AIDS can cause adrenocortical  insufficiency  by
infiltration   with   Mycobacterium   avium-intracellulare,  Cytomegalovirus,
Kaposi's  sarcoma,  and  Cryptococcus.    Ketoconazole  can  also  cause  AI.
CLINICAL DIAGNOSIS: Weakness and fatigue are the most frequent findings (94%)
followed by the following in  decreasing  frequency:  Skin  hyperpigmentation
manifested  as  tanning, freckles, vitiligo, blue-black discolorations of the
areolas and mucous membranes (91%),  Anorexia and weight loss (88%), Postural
hypotension  (81%),  Hyponatremia   (67%),   Nausea   and   vomiting   (66%),
Hyperkalemia  (55%),  Azotemia  (52%),  Diarrhea and abdominal pain (23%) and
hypoglycemia   (19%.    Dermal   hyperpigmentation   is   seen   in   primary
adrenocortical insufficency,  but  is  not  seen  in secondary insufficiency.
Look especially at the palmar creases and in scars where there  is  increased
pigmentation.   The  entire  body  can be affected but look especially at the
face,  neck,  upper  extremities,  scrotum,  penis,  axillary  areas  and the
periumbilical area.  Dilutional hyponatremia  is  more  common  in  secondary
insufficency  than  primary.   It is caused by increased arginine vasopressin
secretion and reduced free  water  elimination  by the kidneys.  Hyperkalemia
only  occurs  in  primary  adrenocortical  insufficiency   because   of   the
aldosterone deficiency.  LABORATORY: RAPID ACTH TEST- Give cosyntropin 250 ug
IV  and  measure plasma cortisol and aldosterone levels at baseline and after
30 min.  The normal response at 30 min  should be an increase of > 7 ug/dL of
cortisol and aldosterone OR double the baseline value OR an absolute value of
20 ug/dL of cortisol and aldosterone.  In primary AI  there  is  a  decreased
cortisol  and aldosterone level.  In secondary, there is a decreased cortisol
level and increased  aldosterone  level.   PLASMA  ACTH-  Measure the ACTH at
baseline before the rapid ACTH test is done.  The normal diurnal plasma  ACTH
level  is  0-70  pg/ml.   In  primary AI there is increased ACTH level and in
secondary AI there is decreased  ACTH  levels.   If you suspect acute adrenal
insufficiency, baseline levels of cortisol, aldosterone and  ACTH  should  be
done  along  with  routine  blood  chemistries.   Give  5% dextrose in normal
saline, about 2 liters in  the  first  6  hours.  Give dexamethasone, 4 mg IV
initially then 4 mg every 6 hours.  Next, for  diagnosis,  give  cosyntropin,
250  ug  IV  and determine the plasma cortisol after 30 minutes.  Investigate
the possible causes, get TB skin  test  and cultures and MRI of the adrenals.
TREATMENT: Give 20 to 30 mg of hydrocortisone daily, 2/3 in the early AM  and
the  remainder in the early afternoon.  If there is primary insufficency give
.05 to .3  mg  of  fludrocortisone  daily  to  maintain fluid and electrolyte
balance.  Before surgery and major  stress  give  hydrocortisone  100  mg  IV
followed  by  10 mg/hour during the procedure and postoperatively give 100 mg
of hydrocortisone every 8 hours until  the  patient is stable; then taper the
dose over 3-5 days.

                            -ADRENAL MASS-
Adrenal masses are occasionally found on routine CT of the abdomen, and it is
important to have a working plan when these are seen.  It is  estimated  that
they  are  seen  in up to 10% of abdominal CTs.  The autopsy rate for finding
incidental macroscopic adrenal nodules  ranges from 2-9%.  Several diagnostic
entities should immediately come to mind.  For example, is  the  history  and
physical    compatible    with    Cushing's   syndrome,   hyperaldosteronism,
pheochromocytoma,  or  adrenal  carcinoma  (either  primary  or  metastatic).
PHEOCHROMOCYTOMA is  rare,  but  when  present,  may  present  with sweating,
palpitations, chest pain, anxiety, pallor, nausea, weakness,  headaches,  and
paroxysmal  or sustained hypertension.  There may also be a family history of
multiple endocrine neoplasia (MEN) IIA or  IIB, and a good history may reveal
paradoxical responses to antihypertensive medications, or severe hypertensive
responses during anesthesia, surgery, and  pregnancy.   The  best  tests  for
pheochromocytoma  are the 24 hour urine metanephrines, vanillylmandelic acid,
and the  free  catecholamines  performed  by  liquid  chromatography.  If the
patient  is  hypertensive  at  the  time  of   the   urinary   determination,
pheochromocytoma is  essentially  ruled  out  by these tests.  If the patient
is not hypertensive at the  time  the  urinary tests are done, repeat testing
may need to be done.  It is also necessary to  eliminate  certain  drugs  and
foods  before the tests are done as they may interefere with the results.  If
the  patient  has  one  of   the   MEN   syndromes,  there  may  be  multiple
pheochromochytomas    present,     and     selective     venous     sampling,
meta-iodobenzylguanidine,   and   MRI   may   be   needed   to  localize  the
pheochromocytoma.  HYPERALDOSTERONISM: If the patient is hypertensive and has
hypokalemia,  an  aldosterone  secreting  tumor  should  be  ruled  out.  The
potassium should be obtained at a time when the patient is  on  a  normal  to
high  sodium diet and is not taking diuretics.  ADRENAL CARCINOMAS: These are
very  rare,  but  may  present  with  abdominal  pain  and  a  palpable mass.
Hypokalemia is also commonly seen.  There may be  signs  of  virilization  or
feminization  present.   Elevation of the 24 hour urinary 17-ketosteroids and
plasma  dehydroepiandrosterone  sulfate  (DHEA-S)  are  compatible  with  the
diagnosis.  Medical treatement  includes  metyrapone, aminoglugtethimide, and
mitotane.  CUSHING'S SYNDROME: These patients have truncal obesity,  proximal
muscle    weakness,    striae,    spontaneous   ecchymoses,   amenorrhea   or
oligomenorrhea, decreased libido,  impotence,  weight  gain and hypertension.
FOLLOW UP: For the patient that is essentially asymptomatic with  an  adrenal
mass  less  than  6  cm, a repeat CT scan should be done in 3 months.  If the
mass is increasing in size,  surgery  is  indicated.   If the adrenal mass is
stable, a repeat CT scan should be done at 6 and at 18  months.   Should  the
adrenal  mass  be  found  to  be  greater than 6 cm initially, then immediate
surgery is indicated.

                -ADULT RESPIRATORY DISTRESS SYNDROME-
Adult respiratory distress  syndrome  (ADRS)  is  characterized  by  dyspnea,
diffuse  bilateral  pulmonary  infiltrates, hypoxemia and stiff lungs that is
associated with several disorders.  Although  ARDS is associated with several
diseases, most patients will  demonstrate  similar  clinical  and  pathologic
features  independent  of  the cause.  Therapy is mainly supportive, although
occasionally specific therapy may be available.   Mortality may be as high as
50% if ARDS is not recognized and treated, and  cardiopulmonary  arrest  will
occur  in  90%  of patients.  If ARDS is accompanied by sepsis, the mortality
may reach 90%.  The largest cause  of  death in ARDS is nonpulmonary multiple
organ system failure, often with sepsis.  Of those patients who do respond to
therapy, there is usually little or no residual lung  dysfunction.   However,
patients  that  require  prolonged ventilatory support with an FIo2 > 50% are
prone to develop pulmonary fibrosis.   After  the initial lung insult, plasma
and blood leak into the interstitial and intra-alveolar spaces.  As a  result
atelectasis  ensues,  and  within a few days bronchoalveolar and interstitial
inflammation evolves with proliferation of interstitial and epithelial cells.
Following this, interstitial fibrosis occurs  within  2-3 weeks.  All of this
results  in  collapsed  terminal  respiratory  units,   decreased   pulmonary
complaince  and  increased intrapulmonary shunts and dead space.  In spite of
these changes the pulmonary  capillary  wedge pressure remains normal.  About
33% of cases of ARDS are secondary to sepsis syndrome.  CLINICAL: ARDS begins
suddenly with severe dyspnea that usually occurs 12-48  hours  following  the
pulmonary  insult.   Tachypnea  and  tachycardia are the first symptoms.  The
patient may be cyanotic  and  diaphoretic.   There is evidence of intercostal
and accessory breathing.  Auscultation may reveal high pitched  crackling  at
end  expiration,  wheezing, and rhonchi.  An arterial blood gas determination
at this time will show acute respiratory alkalosis, a very low PaO2, a normal
or low Paco2, and an  elevated  pH.   Chest x-ray will show diffuse bilateral
pulmonary infiltrates, not dissimilar to  pulmonary  edema  secondy  to  CHF,
except  that  the heart is of normal size.  These findings may lag behind the
clinical findings.  Air bronchograms occur in about 80% of cases and there is
usually no evidence  of  redistribution  (absence  of  upper lung zone venous
engorgement).  However, at this point a presumtive  diagnosis  can  be  given
because  of the normal cardiac size, failure to respond to oxygen therapy and
a normal capillary wedge pressure  in  a setting compatible for the diagnosis
of ARDS.  A low pulmonary arterial wedge pressure (PAWP) of less gthan 15  mm
Hg  is  typical  of  ARDS.  A high PAWP > 20 mm Hg is characteristic of heart
failure.  Pulmonary embolism should be ruled out, but diffuse pulmonary edema
is distinctly uncommon in PE.  Other considerations, particularly any patient
that is  immunocompromised,  would  include  Pneumocystis  carinii pneumonia.
Pleural effusion is usually absent in ARDS.  The overall lung  compliance  is
usually  less  than 50 ml/cm H2O with an increased shunt fraction (Qs/Qt) and
dead space ventilation Vd/Vt.  RISK FACTORS FOR DEVELOPMENT OF ARDS: ARDS may
be initiated by aspiration of gastric contents, bacterial or viral pneumonias
(Legionnaire's  disease,  pneumocystis,   mycoplasma,   miliary  TB),  fungal
pneumonia, prolonged shock, burns,  near  drowning,  cardiopulmonary  bypass,
massive blood transfusions, fat embolism, cardiopulmonary bypass, hemorrhagic
pancreatitis,   sepsis,   trauma,   disseminated  intravascular  coagulation,
thrombotic thrombocytopenic purpura,  head  injury, drugs (heroin, methadone,
barbiturates,   propoxhyphene,   Dextran    40,    paraldehyde,    narcotics,
ethchlorvynol,   hydrochlorothiazide,   ASA,   chlordiazepoxide,  colchicine,
phenylbutazone, Paraquat), toxic gas inhalation (chlorine, cadmium, phosgene,
sulfur  dioxide,  ammonia,  and  nitrogen  dioxide),  high  altitudes, oxygen
toxicity,    smoke    inhalation,	leukoagglutinin    reactions,    eclampsia,
carcinomatosis, and bowel  infarction.   COMPLICATIONS:  Since  patients  are
treated  with  positive  end expiratory pressure (PEEP) and positive pressure
ventilation (PPV), tension pneumothorax  can occur suddenly.  Pneumothorax is
also a complication that is usually suggested by tachycardia, hypotension and
a sudden increase in the peak inspiratory pressures required for ventilation.
Cardiac ouput may be decreased by PPV  and  PEEP,  due  to  decreased  venous
return.   Multiple  organ  sygtem failure is common in ARDS, especially renal
failure.  Gram  negative  lung  superinfections  (Proteus  spp., Pseudomonas,
Klebsiella)  may  occur.   TREATMENT:  ARDS  patients  must  continually   be
monitored   for  oxygen  toxicity,  superinfection,  barotrauma,  nutritional
deficiencies, decreased intravascular  volume  depletion,  renal failure, and
hypoxemia.  The patient may be dehydrated because of previous  diuretic  use,
underlying  sepsis,  or  because  of  PEEP  or  PPV.  Even in the presence of
alveolar edema, IV fluid  may  be  needed  to  improve  urine output, BP, and
peripheral perfusion.  Fluids should be monitored via a Swan  Ganz  catheter.
PAWPs  <  15 mm Hg would suggest a need for fluid replacement while PAWP > 18
mm Hg in conjunction  with  a  decreased  cardiac  output would suggest heart
fialure and a need for fluid restriction and inotropic support with  dopamine
or  dobutamine.   Crystalloid  solutions  should  be  used when intravascular
volume expansion  is  needed.   Packed  RBCs  can  be  given  to maintain the
hematocrit above 25% which will also sustain  a  reasonable  arterial  oxygen
content.   Cardiac output should be monitored with a thermodilution pulmonary
artery catheter as cardiac  ouput  falls with PEEP.  Hyperalimentation either
by parenteral or enteral means should be started.  Steroids are of no benefit
in ARDS.  Mechanical ventilation with endotracheal  intubation  and  assisted
ventilation  using  a volumn controllded mechanical ventilator will be needed
in most cases of  ARDS.   Patients  often  need  PEEP to increase mean airway
pressure and to rapidly lower the FIO2 from 1.0 to less than 0.6 in order  to
achieve a PaO2 of 60 mm Hg.  The peak pressure and respiratory rate has to be
monitored  to avoid both respiratory alkalosis and excessive airway pressures
greater than 50 cm H2O secondary  to nondistensible lungs.  A tidal volume of
10-15 ml/kg, FIO2 of 60% and  a  PEEP  of  5  cm  of  H2O  are  usually  used
initially.   In  some cases the PEEP may have to be increased to about 15 cm.
Remember that high PEEP can depress cardiac output in hypovolemic and even in
normovolemic patients.  If  airway  pressures  are  excessive, or if adequate
oxygenation cannot be achieved with a PEEP of less than 15 cm H2O, IRV,  with
pressure  control  may be used.  The prolonged inspiration will increase mean
airway pressure and increase oxygenation  by using terminal respiratory units
and preventing the collapse of unstable lung units.  An arterial PO2 of 60-70
mm Hg will give adequate Hb saturation and this level should be the  goal  of
PEEP.   A FIO2 > 50% for greater than 1-2 days can be toxic to the lungs.  It
is usually possible to reduce the FIO2 slowly to a level less than 50% within
a few hours.  For less severe cases a  CPAP mask may be used to deliver PEEP.
Intermittent mandatory venilation can also be used with an  initial  rate  of
10-12 ml/kg.

                     -AIDS AND ASPERGILLOSIS-
Aspergillosis is less common in AIDS patients.  A combination of  anti-fungal
agents  such  as amphotericin .5-1 mg/kg given IV daily and selective surgery
appears to have beneficial results  for most cases of invasive aspergillosis.
Total doses of 1.5-4 grams have been used.   Flucytosine  150  mg/kg/day  has
increased  response.  Itraconazole seems to be a good drug, and some patients
that have failed with amphotericin, have responded to itraconazole.  However,
itraconazole appears to produce variable serum levels from <1-25 ug/mL.

                        -AIDS AND THE CNS-
Patients  that  have HIV are prone to several opportunistic infections and to
the HIV  virus  itself.   By  far  the  most  common  lesions producing focal
neurologic deficits are  CNS  lymphoma  and  cerebral  toxoplasmosis.   Other
possibilities   include   bacterial  brain  abscesses,  tuberculomas,  fungal
abscesses and progressive multifocal leukoencephalopathy (PML).  CRYPTOCOCCAL
MENINGITIS:  Cryptococcal  meningitis  usually  presents  with  headache, and
fever.   Lab  should  include  a  serum   cryptococcal   antigen,   and   the
cerebrospinal  fluid  may show a low glucose and positive India ink stain and
cryptococcal antigen.  The cryptococcal  antigen  titers  are often very high
(greater than 1:1000).  However, CSF values may be deceivingly normal.  There
is usually a CSF pleocytosis of about 20 cells/ul, predominantly lymphocytes,
and elevated  protein.   Cultures  for  Cryptococcus  neoformans  is  usually
positive,  but may take several days.  Treatment is with Amphotericin B 0.5-1
mg/kg/d until the  patient  is  improved,  and  then  followed by suppressive
therapy with Fluconazole 200 mg PO  qd  OR  Itraconazole  200  mg  PO  qd  OR
Amphotericin  B,  1 mg/kg/wk IV.  MRI is more sensitive than CT for detecting
the punctate disseminated lesions of cerebral cryptococcosis.  TOXOPLASMOSIS:
Toxoplasmosis HIV patients with a  low  CD4+  cell count of less than 200/mm3
may present with a new headache, seizures or  focal  neurologic  signs.   MRI
should  be  done  as  it  is  more  sensitive  for small lesions than CT with
contrast.  Multiple discrete lesions that  have a ring shaped appearance with
contrast enhancement, and located  in  the  basal  ganglia  or  deep  in  the
cerebral  hemispheres,  is likely to be Toxoplasmosis.  A Toxoplasmosis titer
should be done  as  a  negative  titer  indicates  that Toxoplasmosis will be
present in < 5%.  Toxoplasmosis is usually due to reactivated infection.   If
titers  are  elevated  and  the patient has no symptoms, then no treatment is
needed.  Patients with typical brain  lesions are usually empirically treated
for at least 2 weeks to see if there is a favorable response.  If there is no
response to therapy within 2 weeks, or the patient develops  toxicities  from
the   therapy,   then  a  brain  biopsy  is  indicated.   Treatment  is  with
Pyrimethamine 100 mg/d PO + Folic acid  10  mg/d PO + Sulfadiazine 1 g PO qid
for 6-8 weeks, followed by suppressive therapy with Pyrimethamine 25-50  mg/d
+  Folinic  acid 10 mg/d + Sulfadiazine 2-4 g PO qd.  An alternative approach
would be to give Pyrimethamine 100 mg/d PO + Clindamycin 300-400 mg IV q6h or
600 mg PO q6h, followed by  suppressive therapy with Pyrimethamine 25-50 mg/d
+ Clindamycin 300 mg PO q6h.   If  there  is  cerebral  edema  and  increased
intracranial pressure add IV steroids.  Neutropenia is a major side effect of
Pyrimethamine.   Rash,  fever  and  renal stones can occur with Sulfadiazine.
Clindamycin may cause diarrhea, rash  and  fever.  CNS SYPHILIS: CNS Syphilis
is characterized by a positive VDRL in the  CSF.   MRI  of  neurosyphilis  is
characterized  as  patchy areas of enhancement in the basal ganglia or middle
cerebral artery territories.   Treatment  for  neurosyphilis  is with Aqueous
penicillin G 12-24 million U/d IV giving 2-4 million U IV q4h for 10-14 days,
followed by benzathine penicillin G 2.4 million U/wk IM for 3 weeks.  If  the
patient   is   allergic  to  penicillin,  desensitization  to  penicillin  is
recommended.  Rash and  fever  are  common  side  effects.  HIV DEMENTIA: HIV
Dementia presents early as  acute  aseptic  meningitis  and  then  later  the
patient  develops  cognitive  slowing  and  diffuse  cortical  atrophy on CT.
Treatment is with Zidovudine 200 mg PO 5-6 times per day.  MRI may show large
confluent patches  similar  to  CMV  lesions.   CYTOMEGALOVIRUS ENCEPHALITIS:
Cytomegalovirus Encephalitis is treated with Ganciclovir 5 mg/kg IV q 12h  or
Foscarnet  60 mg/kg IV q8h.  Side effects of Ganciclovir include neutropenia,
thrombocytopenia   and   anemia.    Side   effects   of   Foscarnet   include
nephrotoxicity, hypocalcemia and nausea.   The  MRI  may show large confluent
patches.  CNS LYMPHOMA: If a  single  lesion  on  MRI  is  seen  as  a  bulky
periventricular  lesion,  then  lymphoma  is  likely.  PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY: Progressive Multifocal  Leukoencephalopathy  is due to a
parvovirus and is characterized on the MRI as multiple discrete lesions  with
ill-defined  borders,  in  contrast  to  the  multiple  discrete  lesions  of
Toxoplasmosis  which  often  times have well defined borders.  PML is treated
with Cytarabine in some cases.  Bacterial meningitis is not more common among
HIV infected patients but can  occur.   Herpes virus infections due to herpes
can also occur.  MRI is more sensitive than CT  in  demonstrating  the  early
temporal lobe lesions of herpes simplex encephalitis.

                   -AIDS AND COCCIDIOIDOMYCOSIS-
Is uncommon in the immunocompromised patient,  except  for  the  southwestern
USA,  where  it  can occur with an incidence of about 27% in Tucson, Arizona.
Most patients have pulmonary lesions (26%), meningitis (12%), and knee joint,
skin, liver and inguinal nodes  in  14%.  Patients have positive coccidioidal
serology.  The CSF protein is elevated and the glucose decreased.  In endemic
areas, coccidiodomycosis may co-exist with PCP, and when there is no response
after  treating  PCP,  consider  coccidiodomycosis.   It  can  present   with
reticulonodular  infiltrates.   TREATMENT:  For meningitis, Amphotericin B is
used to a total of 1-3.6 grams of systemic therapy + a cumulative intrathecal
dose of 40-157 mg  for  3-137  months.   Systemic  amphotericin, only, is not
effective.  Survival has ranged from 51-100%, and seems to be correlated with
the total dose given.  Ketoconazole in a dose of 400 mg/d is as effective  as
800  mg  in  treating  patients with progressive pulmonary, skeletal and soft
tissue coccidioidomycosis.  Fluconazole is better tolerated than ketoconazole
and achieves higher penetration into the  CNS and is an excellent alternative
to amphotericin in a dose of 200-400 mg/day.  Some  consider  fluconazole  as
primary  therapy  for  C.  immitis.  Itraconazole using 100-600 mg/d has also
been effective.

                -AIDS AND CRYPTOCOCCAL INFECTIONS-
Cryptococcal  infections  account  for   the   highest  mortality  in  fungal
infections in patients with AIDS.  It occurs in 6-10% of all  AIDS  patients.
Ninety  percent  will  present  with  meningitis  secondary  to C neoformans.
Mortality is still about 50%  in  Cryptococcal meningitis with Amphotericin B
(.4-.6 mg/kg/d for at least 2 weeks or until CSF cultures are  negtative  for
C.  neoformans, with or without flucytosine 150 mg/kg/day in 4 divided doses.
However, in AIDS  patients  the  addition  of  flucytosine  has not decreased
mortality or shortened the duration of therapy.  Long term preventive therapy
consists of amphotericin .5-1.44 mg/kg/week,  which  will  prolong  survival.
Side  effects  of  amphotericin  consist  of  chills,  fever, nephrotoxicity,
headache, anemia, phlebitis,  seizures  and  edema.  Flucytosine side effects
include  neutropenia,   nausea,   vomiting,   enterocolitis   and   diarrhea.
FLUCONAZOLE  penetrates  the CSF extremely well achieving levels of 60-90% of
serum concentrations.  Fluconazole is given 200-400 mg/d.  The median time to
clinical improvements is about 2  weeks.  For chronic suppression fluconazole
is given at 200 mg/d and may be more effective than chronic suppression qwith
amphotericin B 1 mg/kg/week.  ITRACONAZOLE (Sporanox) has been  approved  for
blastomycosis  and  histoplasmosis  in  immunocompetent and immunocompromised
patients.  It doesn't penetrate the CNS well (<10%).  No adjustment in dosage
is needed for renal  dysfunction.   It  can potentiate cyclosporine, warfarin
and digoxin.  Patients given itraconazole 200 mg bid has shown a 65% response
rate in AIDS  related  cryptococcal  meningitis.   This  compares  well  with
amphotericin  B  or fluconazole.  SUMMARY: Initial therapy probably should be
with amphotericin B at  this  time.   Flucytosine  may  be added but patients
taking zidovudine may not be able to tolerate, because these  agents  produce
neutropenia.   Once CSF cultures turn negative fluconazole should be used for
chronic suppression, indefinitely.   Alternatively,  itraconazole may be used
for chronic prophylaxis.

                   -AIDS AND CRYPTOSPORIDIOSIS-
Cryptosporidiosis occurs in  10-15%  of  patients  in  the  USA  and causes a
profuse watery diarrhea that can approach 17 L/day.  It  is  associated  with
abominal  pain,  nausea,  vomiting,  fatigue and anorexia.  Diagnosis is made
observing oocysts  in  the  stool.   Currently,  there  is  no  specific drug
therapy.  Therefore, the  patient  is  treated  with  fluid  replacement  and
antidiarrhea  agents.   Paromomycin  500-750  mg  tid  for  10  days  may  be
effective.

                    -AIDS AND CYTOMEGALOVIRUS-
CMV is the most common virus causing life threatening infections in AIDS.  It
is  capable  of  causing retinitis, gastroenteritis, and pneumonitis, in that
order of frequency.  It  also  may  cause hepatitis, encephalitis, sclerosing
cholangitis,  papillary  stenosis,   adrenal   necrosis,   epididymitis   and
pancreatitis.   Diagnosis  is  made on clinical findings + positive cultures.
TREATMENT: Ganciclovir (Cytovene) will reduce the size of retinal lesions and
slow the progression of CMV retinitis.   It also is effective in CMV colitis,
gastritis, and esophagitis.  It is virustatic and not  virucidal  and  almost
all  patients  develop a recurrence when the drug is stopped, necessitating a
maintenance program.  Give ganciclovir 5  mg/kg q12h for 10-14 days, followed
by 5 mg/kg daily 5-7 days/week  IV.   Side  effects  of  ganciclovir  include
neutropenia,  psychosis, hepatitis, rash, nausea, anorexia, eosinophilia, and
pain or phlebitis at IV site.  Rarely, there may be thrombocytopenia.  All of
these are reversible  with  discontinuance  of  the  drug.   Patients who are
taking acyclovir for the treatment or prevention of other viral infections as
herpes simplex should have the acyclovir discontinued before  ganciclovir  is
initiated  because  the side effects may be amplified if on both drugs at the
same time.  Clinically, both drugs are not needed as ganciclovir has activity
against all of the viruses  inhibited  by acyclovir.  FOSCARNET (Foscavir) is
approved for treatment of CMV retinitis in AIDS.  Like ganciclovir, foscarnet
has poor bioavailabiltiy when given orally.  It is cleared  via  the  kidneys
and requires a dosage modification in renal dysfunction.  It also crosses the
blood  brain  barrier.   All  studies have shown foscarnet to be effective in
AIDS CMV pneumonitis, colitis,  esophagitis  and  retinitis.  Side effects of
foscarnet include nausea, fever, diarrhea, anemia, abnormal  renal  function,
acute  renal  failure,  increased  creatinine,  headache, vomiting, seizures,
hypocalcemia,   hypophosphatemia,   hypomagnesemia,   hyperphosphatemia,  and
hypokalemia.  A generalized cutaneous rash and penile ulcerations  have  also
been  noted.   Foscarnet is given IV at 60 mg/kg over a 1 hour period q8h for
14-21 days.  Alternatively,  90  mg/kg  q12h/d  may  be  given (this would be
advangtageous for home therapy).  Foscarnet comes as 250  and  500  mL  glass
bottles  of  24  mg/mL  of active drug.  Hydration with 1.5-2.5 L/d of normal
saline should also be given to minimize the nephrotoxic effects.  Maintenance
is 90-120 mg/kg/day given IV  over  a  2 hour period.  If retinitis progress,
reinduction may be started followed by another maintenance program.

                           -AIDS AND FEVER-
Many patients that are infected with HIV will present with fever, malaise and
nausea, without any other localizing  clues.   These patients will need blood
cultures, buffy coat cultures for CMV,  CD4  counts,  mycobacteria  cultures,
chest  x-rays  and a serum cryptococcal antigen.  It is important to know the
level of the CD4,  as  various  opportunistic infections develop at different
levels.  Patients with CD4  counts  >  500/mm3  are  at  increased  risk  for
sinusitis,   pharyngitis,   pneumonia,   herpes   simplex,   and  bacteremia.
Localizing features are  usually  present.   If  the  patient  is  an IV drug
abuser, blood cultures  and  echocardiograms  should  be  done  to  rule  out
endocarditis.   HIV  patients  with intermediate CD4 levels (200-500/mm3) are
prone to infections with Mycobacterium tuberculosis, Candida albicans, herpes
simplex, as well as those infections that occur in patients with CD4 counts >
500/mm3.   Patients  that  have  CD4   <   200/mm  should  be  evaluated  for
opportunistic  infections  such  Mycobacterium   tuberculosis,   Pneumocystis
carinii,  lymphoma,  cryptococcal  meningitis,  Mycobacterium  avium complex,
cytomegalovirus,  or  HIV  associated  therapy.   Most  patients  with  acute
sinusitis    and    bronchitis    can    be    treated    successfully   with
trimethoprim-sulfamethoxazole or amoxicillin.   Patients  that  have  chronic
sinusitis,  may  need  coverage  for  gram  negative  organisms,  Staph,  and
anaerobes.   If  a patient has an infiltrate that is localized to one lobe, a
bacterial  infection  should  be   suspected   which   may  be  treated  with
erythromycin 500 mg QID to cover Mycoplasma,  Legionella,  and  Streptococcus
pneumoniae.  If Hemophilus influenzae is isolated, the patient may be treated
with clarithromycin, trimethoprim-sulfamethoxazole, and ceftriaxone.  Any HIV
infected patient that has infiltrates in multiple lobes and hypoxic should be
hospitilized and treated with IV antibiotics.

                      -AIDS AND THE GI TRACT-
About  50%  of  HIV  positive  patients  will   have   involvement   of   the
gastrointestinal  tract.   The  main symptom is usually diarrhea and multiple
organisms may be present.  In  about  85%  of  cases a diagnosis can be made.
Pathogens can be found in 40-60% of patients  if  only  stool  specimens  are
examined.   If  endoscopy  is  added this increases to 70-85%.  The most most
common  organisms   found   are   Cryptosporidium,   CMV   and  Mycobacterium
avium-intracellulare.  Unfortunately, only a few of these  pathogens  can  be
treated  as  of this writing.  About 33% can be treated and another one third
can possibly be treated.  WORKUP:  There  should be 3 stool samples submitted
for examination of Clostridium difficile  toxin  and  parasites.   Upper  and
lower endoscopy may be needed to inspect the mucosal wall, biopsy of involved
sites  and  sampling  of  the  luminal  contents.  Electron microscopy may be
needed for adenovirus of the colon.   Tissue specimens should be stained with
hematoxylin-eosin for viral inclusion cells and protozoa.  Methenamine silver
or Giemsa stains are used for fungi and Fite's method for mycobacteria.   All
specimens  should be submitted for cultures for Salmonella, Shigella flexneri
and Campylobacter.  Acid-fast stains  of  the  stool should routinely be done
for cryptosporidium and isospora belli.  Duodenal tissue specimens should  be
obtained  for  mycobacteria  and  cytomegalovirus.   Electron examination for
Microsporidia may be needed.  PATHOGENS  AND PREFERRED SITES: COLON: Shigella
flexneri,  Cytomegalovirus,  Campylobacter  jejuni,  Histoplasma  capsulatum,
Cryptosporidium,  Mycobacterium  avium-intracellulare,  herpes  simplex   and
adenovirus.  SMALL INTESTINE: Microsporidia, Isospora belli, Cryptosporidium,
Salmonella,  Campylobacter  jejuni,  Mycobacterium  and avium-intracellulare.
ESOPHAGUS:  Candida  albicans,  Cytomegalovirus  and  Herpes  simplex  virus.
STOMACH:  Mycobacterium  avium-intracellulare  and  Cytomegalovirus.  BILIARY
DISEASE: Cryptosporidium and CMV may cause stenosis of the distal common bile
duct at the papilla.  This involvement produces severe nausea,  vomiting  and
right   upper   quadrant   pain.    Alkaline   phosphatase   elevations   are
disproportionately elevated as compared with the transaminases.  Diagnosis is
made  with  endoscopic  retrograde  cholangiopancreatography.  LIVER DISEASE:
Mycobacterial disease, CMV, hepatitis  B  virus  and lymphoma can cause liver
disease.  Percutaneous liver biopsy can be helpful but  blood  cultures  also
may  be  useful.   CLINICAL: CRYPTOSPORIDIUM commonly invades the small bowel
and produce dyspepsia, bloating, gas and large volume diarrhea.  The diarrhea
can be up to 10  Liters  per  day.   Multiple  stool specimens should be done
(3-5) and acid-fast stained.  Only symptomatic care  should  be  rendered  as
there  is  no  specific therapy.  MICROSPORIDIA: These pathogens are found in
the small bowel biopsy when examined with electron microscopy.  Spores in the
stool may be seen.  Microsporidia may account for about a quarter of cases of
unexplained diarrhea.  No specific  treatment  is available.  ISOSPORA BELLI:
These organisms can be found with acid fast stains of the  stool.   Treatment
is   with   pyrimethamine   or   sulfonamides.    SHIGELLA,   SALMONELLA  and
CAMPYLOBACTER: These patients present with abdominal pain, diarrhea which may
be bloody and fever.   Specialized  media  should  be used for Campylobacter.
Cultures should be done.  CMV: CMV  produces  hematochezia,  abdominal  pain,
ulcerations  and  low volume diarrhea.  If there is urgency and tenesmus this
may indicate involvement of  the  rectum.   CMV  produces a vasculitis of the
walls with subsequent ulceration of the esophagus and colon.   Tissue  biopsy
must  be  done  for  examination of typical viral inclusions.  Treatment with
ganciclovir and foscarnet have not been very effective.  Frequent recurrences
may occur.  HERPES SIMPLEX: Herpes  simplex typically involves the rectum but
may affect the colon and the esophagus.  The  patient  can  be  treated  with
acyclovir.   MYCOBACTERIUM  AVIUM-INTRACELLULARE  is  usually associated with
dissemination.  The patients may present with profound weight loss and are in
the advanced stages of HIV  infection.   They  have an affinity for the small
bowel but, may occur anywhere in the GI tract.  Tissue must be  obtained  for
diagnosis.  Cultures of the liver, lymph nodes and bone marrow also may yield
the  organism.   Because  of  the usual advanced stage, treatment often fails
with multiple drugs.  KAPOSI'S SARCOMA  AND  LYMPHOMA: Most of these patients
will present with bleeding and bowel  obstruction  but  diarrhea  can  occur.
TREATAMENT:  CANDIDA  ALBICANS  HERPES SIMPLEX and CMV: These 3 pathogens may
produce esophagitis.  Most of these  patients will have Candida albicans when
they present with odynophagia or dysphagia.  More than one  pathogen  may  be
found, however.  Treatment is with ketoconazole 200 mg per day or fluconazole
200  mg  initially  then  100 mg daily for 10-14 days.  Ketoconazole requires
acid for optimal  absorption  and  AIDS  patient  have  reduced acid amounts.
Therefore,  ketoconazole  may  be  ineffective  and  you  would  proceed   to
fluconazole.   If  the  patient  is  resistant to both of these then low dose
amphotericin B may be needed  at  0.3  mg/kg  IV qd.  Maintenance for candida
esophagitis is with ketoconazole 200 mg qd or fluconazole 50 mg qd.   If  the
patient  doesn't  respond  to  these  treatments  then  suspect CMV or herpes
simplex virus.   To  rule  these  out  do  endoscopy  and  examine the biopsy
specimen.  Inspection of the mucosa of the esophagus would reveal  the  white
plaques of candida as opposed to the ulcerations caused by Herpes simplex and
CMV.   Acyclovir  may  be  used  for  herpes simplex.  For mild mucocutaneous
involvement use acyclovir 200 mg po five times daily for 10 days.  For severe
mucocutaneous involvement use  IV  acyclovir  15  mg/kg/day  or Vidarabine 15
mg/kg/day  IV  or  Foscarnet  90  mg/kg/day  IV.   Maintenance  therapy  with
acyclovir 200 mg po tid may be needed.  CMV may respond  to  ganciclovir  and
foscarnet, but this is not uniform.  CRYPTOSPORIDIUM: Paromomycin 500 mg po q
6  hours.   ISOSPORA BELLI: Trimethoprim-sulfamethoxazole DS q 6 hours for 10
days,  then  maintenance  with   same   three  times  weekly.   MYCOBACTERIUM
AVIUM-INTRACELLULARE: Rifampin 600 mg po every day or rifabutin 300-450 mg po
daily plus ethambutol 15-25 mg/kg po daily plus  Clofazimine  100-300  mg  po
daily  plus  ciprofloxacin 750 mg po bid plus amikacin 7.5 mg/kg IV or IM qd.
(amikacin may or may not be  used).  SALMONELLA: Ciprofloxacin 750 po bid for
2-4 weeks or Trimethoprim 5-10 mg/kg/day plus sulfamethoxazole IV or po for 4
weeks or ampicillin 8-12 grams per day IV for 2 weeks followed by amoxicillin
500 mg po tid for 2 weeks.  Maintenance therapy would be amoxicillin  250  mg
po  bid  or ciprofloxacin 500 mg po qd or bid, or Trimethoprim 2.5 mg/kg plus
sulfamethoxazole po bid.  GIARDIA  LAMBLIA:  Metronidazole  250  mg tid for 5
days  or  quinacrine  100  mg  tid  for  5  days.    CLOSTRIDIUM   DIFFICILE:
Metronidazole  500  mg  tid  for 10 days or vancomycin 125 mg tid for 5 days.
CAMPYLOBACTER: Ciprofloxacin 500 mg bid for 7 days or erythromycin 500 mg qid
for 1 week.  SHIGELLA: Ciprofloxacin 500 mg  bid for 7 days or Bactrim DS bid
for 10-15 days.

                       -AIDS AND THE GI TRACT-
The differential diagnosis is as follows:  INFLAMMATORY  BOWEL  DISEASE-Check
for  anal  fistula,  extraintestinal findings as skin or joint abnormalities.
INTUSSUSCEPTION: can occur with with  AIDS as a complication of opportunistic
infection.  ADENOCARCINOMA: Check for anemia,  rt  sided  pain  and  fatigue.
There  is  no  increased  frequency  of adenocarcinoma in AIDS.  DIVERTICULI:
Diverticulosis   can   cause   GI   bleeding.    May   be   peritonitis  with
diverticulitis.  Check for mass.  APPENDICITIS: Starts with  epigastric  pain
and  then  localizes.  May be atypical with immunocompromise.  MYCOBACTERTIUM
AVIUM COMPLEX: Can cause diarrhea, but intestinal hemorrhage or peforation is
infrequent.  Systemic symptoms  as  fatigue,  lymphadenopathy may be present.
GI TUBERCULOSIS: Commonly presents with obstruction,  stricture  and  fistula
rather   than   hemorrhage   or   perforation.   SYSTEMIC  MYCOSIS:  Isolated
cryptococcal disease of the colon  in  the absence of meningeal, pulmonary or
skin  involvment  is  unusual.    Coccidioidomycosis   and   North   American
blastomycosis  of the GI tract is rare.  Esophageal candidiasis in common but
invasive candidiasis of  the  GI  tract  is  rare.  EXTRAPULMONARY P. CARINII
INFECTION: Has been reported  to  involve  liver,  spleen  and  lymph  nodes.
Colitis  and  GI  perforation  are rare.  NON-HODGKIN'S LYMPHOMAS: Are common
with advanced HIV infection and can cause hemorrhage or perforation.  Usually
there is  fever,  weight  loss,  splenomegaly  and  lympadenopathy.  KAPOSI'S
SARCOMA: GI Kaposi's occurs in  at  least  50%  of  patients  with  cutaneous
disease.   Usually  is  asymptomatic,  but rarely hemorrhage and perforation.
BACTERIAL  ENTERCOLITIS:   Shigella,   salmonella,  Yersinia  enterocolitica,
camphylobacter,  vibrio  species,   Escherichia   coli,   enteroinvasive   or
enterotoxigenic  E.  coli and Staph areus can cause severe enterocolitis with
hemorrhage.   Yersinia  enterocolitica  involves  the  small  intestine  more
commonly and usually presents with  obstruction rather than hemorrhage in the
adult.  Campylobacter can present as a colitis, but  typically  involves  the
upper GI tract and presents with bacteremia.  Shigella causes bloody diarrhea
and  is  among the most common enteric pathogens in AIDS and usually involves
the small intestine.   ENTAMOEBA  HISTOLYTICA:  causes  colitis and may occur
abruptly.  Has been rare in HIV despite a high frequency of  stool  carriage.
CRYPTOSPORIDIA,  iSOSPORA  BELLI,  MICROSPORIDIA:  are  common  with AIDS and
affect the small intestine mainly  with voluminous diarrhea and malabsorption
causing inanition.  TOXOPLASMA: is rarely a cause of colitis.  STRONGYLOIDES:
causes  eosinophilia.   GIARDIASIS:  usually  no   hemorrhage.    NECROTIZING
ENTEROCOLITIS:  occurs  in  neutropenic  cancer  patients.   Is also known as
typhlitis.  Sepsis is common and peritonitis may occur with perforation.  Can
occur in AIDS patients,  with  and  without  neutropenia and they are usually
receiving broad spectrum antibiotics.  PSEUDOMEMBRANOUS  COLITIS:  is  common
with  AIDS  because  of  the large number of antibiotics commonly taken.  Can
occur fulminantly  without  diarrhea,  with  signs  of  peritonitis.   May be
ascities  and  marked  thickening  of  the  colon.   Usually   involves   the
rectosigmoid  and  descending  colon.   COLONIC ISCHEMIA: Atrial fibrillation
causes embolization to superior mesenteric artery.  Ganciclovir and foscarnet
can cause arrhythmias.  Endocarditis  may  embolize.  Ischemic colitis can be
secondary to nonocclusive small vessel disease with diabetes.  Usually occurs
between the splenic flexure and the  sigmoid  colon.   Ischemic  colitis  can
occur   with  cytomegalovirus  vasculitis  in  AIDS  as  well  as  transplant
recipients.  CYTOMEGALOVIRUS COLITIS: Can  cause diarrhea intermittently.  It
may just be a commensal organism and histologic invasion is mandatory  for  a
diagnosis,  showing  the  typical  inclusion  bodies on biopsy.  There may be
enlargement of the  adrenal  gland  due  to  CMV  adrenalitis.  Foscarnet and
ganciclovir are used for treatment.  Foscarnet has  toxic  effects  including
renal  failure, hypocalcemia and seizures and must be given through a central
line.  Foscarnet is virustatic rather  than virucidal and rebounds may occur.
CMV is a common opportunsitic pathogen in late stage AIDS.  If CMV colitis is
untreated there is an indolent progressive course with  diarrhea  and  weight
loss,  although  there may be spontaneous remissions.  CMV is the most common
cause of both acute lower GI  hemorrhage  and bowel perforation in AIDS.  The
ileum and cecum are the most common sites.  CT will show marked thickening of
the bowel with pericolic and mesenteric inflammation.   Toxic  megacolon  may
develop.  CMV can also cause mild chronic pancreatitis.

                      -AIDS AND HISTOPLASMOSIS-
Any patient that presents with  a febrile illness, weight loss, hepatomegaly,
splenomegaly, skin and mucosal lesions, with or without respiratory  symptoms
should  be  suspect for histoplasmosis.  A silver stain should be done on the
buffy  coat  and/or  a  bone  marrow  biopsy  for  cultures  for  Histoplasma
capsulatum.  Also H. capsulatum antigen  should  be  sought for in the blood,
CSF and urine.  The incidence is more common in endemic areas.  Studies  have
shown  that  cure  is  not currently possible in AIDS patients, and long term
suppressive therapy is  needed.   Amphotericin  is  the  treatment of choice,
giving 50 mg/d or 1 mg/kg with a body weight < 50 kg for the first  2  weeks,
followed  by the same dose every other day until a total dose of 15 mg/kg has
been  given.   A  maintenance  dose  of  50  mg/week  is  given indefinitely.
Ketoconazole can also be used for chronic suppression, but is associated with
more relapses than amphotericin.  It  is  recommended  that  the  patient  be
monitored monthly for H. capsulatum polysacchardie antigen levels, and if the
level  reaches  or  is  >  2  U,  induction  therapy should be started again.
Results with  itraconazole  have  been  promising  using  it  as  primary and
maintenance therapy in patients with AIDS.

                       -AIDS AND ISOSPORIASIS-
It has a very low incidence in  the  USA  (.2%).   The  clinical  picture  is
indistinguishable  from cryptosporidiosis.  Diagnosis depends on isolation of
the oocyst in feces of infected patients.  Isosporiasis responds to treatment
with double strength sulfamethoxazole-trimethoprim which  is given qid for 10
days, followed by twice daily for 3 weeks.  This usually results in cure.

                     -AIDS AND KAPOSI'S SARCOMA-
It has been said that about 15-20% of homosexual men with  HIV  will  develop
Kaposi's  sarcoma.   It  is uncommon in women and children.  Kaposi's sarcoma
(KS) can affect the skin as  well as the viscera.  Cutaneous Kaposi's sarcoma
is the more frequent variety, causing the typical  palpable  purple,  nodular
skin  lesions.   They  tend  to  be  more  common  on  the  upper  and  lower
extremities,  anterior and posterior trunk and the face.  They usually do not
cause pain.  They usually begin as  solitary lesions, but may coalesce as the
disease advances.  Sometimes they have a central  pallor.   The  most  common
visceral  sites  of  involvement  include the GI tract, lung, liver and lymph
nodes.  Chest x-rays may  show  nodular densities, interstitial infiltration,
and pleural effusion.  Patients with KS of the lung usually  have  a  chronic
nonproductive  cough  and  dyspnea.   KS  of the GI tract may be asymptomatic
unless they enlarge to the point where  they can erode the mucosa and produce
bleeding, or obstruct the lumen.  If  there  is  just  mucosal  infiltration,
diarrhea  and  malabsorption  may occur.  Biopsy of the GI lesion is required
for diagnosis.  Pulmonary disease is  diagnosed by transbronchial, open lung,
or pleural biopsy.  Bronchoalveolar lavage has a low yield.  TREATMENT: Local
irradiation may be used to decrease the size of large cutaneous lesions.   If
the  lesions  are progressive and extensive, systemic interferon alpha can be
given using 10-20 million units per  day.   The response from this therapy is
contingent upon the CD4 status.  Those that have greater than  400  cells/mm3
will  respond  better  and  for  longer  durations.   In  general, the global
response rate is  about  40-60%.   Other  therapy  that  may  be used include
cytotoxic  drugs  such  as  adriamycin,  VP-16,  bleomycin,  vincristine  and
vinblastine.  These are usually used as single  drug  therapy  for  cutaneous
lesions.    For   visceral   disease   or  extensive  cutaneous  involvement,
combination chemotherapy can  be  employed.   Because of the myelosuppression
produced by the combination chemotherapy, patients usually  do  not  tolerate
concurrent zidovudine.

                         AIDS AND THE LUNG
Pneumocystis  carinii  (PCP)  was first described in 1910 and has always been
thought to be a protozoan until recent evidence indicates it may be a fungus.
PCP has three forms:  sporozoites,  trophozoites and cysts.  Trophozoites are
the most plentiful form in lung  tissue  and  bronchoalveolar  lavage  fluid.
Most children will have antibodies to PCP by the age of 4 and Pneumocystis is
probably  dormant  in  lungs  until  immunosuppression  occurs.  Pneumocystis
carinii in the past, before  AIDS,  was  rare and occurred mainly in patients
given immunotherapy for organ transplants and chemotherapy for cancer.   Now,
it  is  known  that  about  80%  of patients with AIDS will have at least one
episode  of  PCP  and  in  about  64%,  PCP  pneumonia  will  be  the initial
manifestation.   Opportunistic  pneumonia  is  the  most  common  respiratory
complication in AIDS especially when the CD4+ lymphocytes (T  helpers)  reach
200  per  cubic  millimeter and below.  Depletion of these lymphocytes occurs
both peripherally and locally  in  the  lungs.  The total lymphocytes usually
increase, but most of these are of the suppressor type.  Patients that have a
neutropenia don't appear to be at any further risk for  development  of  PCP.
CLINICAL:  The  clinical  onset  of  PCP pneumonia is characterized by fever,
dyspnea, cough and pulmonary infiltrates.  The presentation varies and may be
very subtle with symptoms developing  very  slowly  over weeks or months.  On
the other hand, the onset may be abrupt.  The fever can be low grade or high.
The cough is usually non-productive but can be a productive cough of  whitish
or  clear  sputum.   There  may be chest tightness, or sharp substernal pains
along with dyspnea,  tachypnea,  and  chills.   LABORATORY: The typical chest
x-ray consists of diffuse  bilateral  interstitial  or  alveolar  infiltrates
(48-86%)  or  both.   However,  chest  x-ray  findings may vary widely from a
normal chest x-ray (6-23%) to asymmetric or unilateral infiltrates, localized
homogeneous consolidation with air  bronchograms,  infiltrates located in the
periphery or upper lobe, nodular infiltrates, cavities,  pneumothoracies  and
cyst-like  lucencies  within  areas of alveolar infiltrates.  If patients are
receiving aerosolized pentamidine  for  prophylaxis, infiltrates localized to
the upper lung zones are seen.   Measurement  of  carbon  monoxide  diffusing
capacity  (DLCO)  by the single breath method is very sensitive for detecting
PCP in AIDS.  It is helpful if  the  chest x-ray and arterial blood gases are
normal, in which there will be a low DLCO if PCP is present.  Oximetry can be
used during exercise.  If exercise results in  a  decrease  of  3  percentage
points from resting oxygen saturation, the chances for PCP are high.  The LDH
is elevated but is non- specific.  LDH can be elevated in other diseases that
would  be  in  the  differential  as  TB, lymphoid interstitial pneumonia and
lymphoma.  Normal LDH may suggest  another  disease.   Gallium may be used if
the chest x-ray is normal, and the patient is unable to  exercise.   However,
the  specificity  is  low.   If the gallium uptake in the lung is equal to or
greater than the  uptake  in  the  liver  then  PCP  may  be present.  Sputum
induction with hypertonic saline inhalation or bronchoalveolar  lavage  (BAL)
obtained  by  fiberoptic  bronchoscopic  exam  is  used to obtain samples for
examination.  Sputum induction will yield a  diagnosis in 52-92%, and this is
recommended as the initial step for diagnosis.  The diagnostic sensitivity of
BAL is between 90 and 100%.  If the patient has  been  receiving  aerosolized
pentamidine  when  the  pneumonia  develops,  then the yield for both BAL and
induced sputum will decrease  considerably  (60-65%).  It is recommended that
transbronchial biopsy be added to BAL in these cases, as the sensitivity with
both of these procedures performed in pentamidine treated patients approaches
100%.   DIFFERENTIAL  DIAGNOSIS:  Differential   diagnosis   would   include:
BACTERIAL  PNEUMONIA  (The  most common are S. pneumoniae and H. influenzae).
FUNGAL  PNEUMONIA  (The   most   common   are  cryptococci,  histoplasma  and
coccidioides.  Disseminated disease is usually seen with these  3  organisms.
Cryptococcal infections can present as thoracic lymphadenopathy , parenchymal
or  pleural  involvement).   KAPOSI'S  SARCOMA (usually follows the cutaneous
involvement but not always.  Occurs  often with other visceral disease.  Lung
presentations  are  interstitial  disease,  pleural  effusions,  infiltrates,
nodules, lymphadenopathy and endobronchial involvement.  Gallium scan may  be
helpful   in  that  it  is  negative  in  Kaposi's  sarcoma).   TUBERCULOSIS,
MYCOBACTERIUM AVIUM INTRACELLULARE (occurs late  in  the disease of AIDS with
CD4+ counts below 100 per cubic millimeter.  Clarithromycin and  Azithromycin
may  be  effective.).   VIRAL  PNEUMONIAS (CMV is the most common but usually
isn't important  because  antiviral  therapy  against  it  doesn't  alter the
course), and  LYMPHOID  INTERSTITIAL  PNEUMONITIS  in  children.   TREATMENT:
Trimethoprim-sulfamethoxazole  (TMP-SMX)  and  Pentamidine  are  are  the two
principal    drugs    used     to     treat    PCP.     Trimethoprim-dapsone,
clindamycin-primaquine and atovaquone also have been used.  The success  rate
is  about  75%  with  TMP-SMX,  somewhat better than Pentamidine.  TMP-SMX is
preferred in patients with renal  failure,  and  patients in whom you suspect
other bacterial infections.  If the patient has an allergy to sulfa drugs, or
fluid restriction needs to be addressed, has an anemia,  thrombocytopenia  or
neutropenia, then Pentamidine may be preferred.  There is a high incidence of
adverse  reactions  to  TMP-SMX consisting of rash, elevated aminotransferase
levels, nausea and vomiting, CBC  depression,  and fever.  The rash and fever
can be treated with acetaminophen and  diphenhydramine  unless  the  rash  is
severe  and  then the TMP-SMX needs to be discontinued.  TMP-SMX treatment is
given with TMP, 20 mg/kg/day and SMX at 100 mg/kg/day in 3 or 4 divided doses
IV or orally for 21 days.  If  there is severe renal impairment (less than 30
mL/min creatinine clearance), reduce the TMP-SMX to 1/4 to 1/2 the usual dose
after the sixth dose of medication.  Pentamidine is given IV at 4 mg/kg in  a
single  daily  dose  for  3  weeks.   Watch  for hypoglycemia which can occur
anytime during the  treatment,  hepatic  and  nephrotoxicity, neutropenia and
hypotension.  When Dapsone  is  used  with  TMP  the  treatment  is  just  as
effective  as  TMP-SMX  in  mild  to  moderate initial episodes of PCP in HIV
patients and is better tolerated.   Give  Dapsone  100  mg orally in a single
daily dose  and  TMP  at  20  mg/kg/day  orally  q  8  hours.   Be  alert  to
methemoglobinemia,  rashes,  elevation of liver enzymes, nausea and vomiting.
The  incidence  of  side  effects  is  less  than  TMP-SMX.(50%  lower).  One
disadvantage of using TMP  and  dapsone  is  that  patients  will  have  more
opportunistic  infections  because  TMP-SMX  protects  against  H. influenza,
Streptococcus pneumoniae,  Nocardia,  and  possibly  Toxoplasma and Isospora.
Corticosteroids  can  decrease  the  incidence  of  respiratory  failure  and
increase survival.  Therefore, if the partial pressure of arterial oxygen  is
less  than  70  mm Hg or an alveolar-arterial gradient of more than 35 mm Hg,
steroids should be  started  as  early  as  possible,  preferably 72 hours of
diagnosis.   The  first  symptom  to  improve  with  effective  treatment  is
decreased cough.  The fever is reduced after a few days, but may take  up  to
one   week.    Improvement  in  chest  x-rays  may  take  a  month  or  more.
PROPHYLAXIS:  It  is  recommended  that   prophylaxis  start  when  the  CD4+
lymphocyte count drops to 200 or  less.   TMP-SMX  is  the  drug  of  choice.
Aerosolized  Pentamidine,  although  less  toxic,  can  be  used, but is less
effective and costs considerably more than  TMP- SMX.  Give 1 double strength
tablet containing 160 mg of TMP and 800 mg of SMX  once  daily.   If  adverse
effects   occur,  give  every  other  day.   If  this  isn't  tolerated  give
pentamidine, 300  mg  with  a  nebulizer  once  a  month.   Dilute  300 mg of
pentamidine in 6 mL of sterile water and deliver with an airflow  rate  of  6
L/min  from  a 50 psi compressed air source until the reservoir is empty.  If
the patient is in the supine position and breathes deeply there may be better
distribution of the drug to the  apices  of the lung.  Bronchospasm and cough
are side effects.  If this happens give an inhaled Beta2  agonist  and  start
the  pentamidine  10 minutes after the Beta2 agonist.  If the patient has TB,
inhaled pentamidine should not be  used because the pentamidine induced cough
may spread the TB.  Health care workers should always wear masks when  giving
the  treatment  and  the  pentamidine  should  be  given in negative pressure
ventilation  rooms  that  have   frequent   air   exchange  to  the  outside.
Pentamidine may be increasing the incidence of pneumothoracies.  If a patient
develops a pneumothorax while being treated with aerosolized pentamidine,  he
or  she  should  be  treated  for PCP, because almost invariably they will be
infected with Pneumocystis.  If a patient is unable to tolerate either of the
above drugs, then Dapsone alone at 100 mg daily, dapsone 100 mg/day + TMP 300
mg/day (in 3 divided  doses),  or  Pyrimethamine  25  mg + sulfadoxine 500 mg
every week can be given.

         -AIDS AND MYCOBACTERIUM AVIUM INTRACELLULARE COMPLEX-
MAC  is  the  most  common  non-tuberculous  mycobacterial  disease  in AIDS,
accounting for 97%.   Mycobacterium  kansasii  is  the  second  most  common,
accounting  for  < 2%.  Disseminated MAC should be suspected when the patient
develops  fever,  weight  loss,  and  debility.   Blood  cultures  are  often
positive.  Usually one or  more  opportunistic  infections are present at the
same time.  MAC is rarely seen when the CD4 is > .1 x 10 to the ninth power/L
and  is  usually  present  during  the  end  stages  of   AIDS.    TREATMENT:
Clarithromycin  500  mg  bid  plus 2 or more of the following: rifampin 600/d
mg/d, ethambutol 15 mg/kg/d,  ciprofloxacin  750  mg  bid, or clofazimine 100
mg/d.  Amikacin 7.5 mg/kg q12h IV may be added to this 3 drug regimen for the
first 2-3 weeks.  Rifabutin (Mycobutin) 300 mg/d used prophylactically,  will
delay  MAC  bacteremia  and reduce fever and fatigue.  It is recommended when
the CD4 drops to  .1  x  10  to  the  ninth  p;ower/L or less.  SIDE EFFECTS:
Clofazimine at the recommended dose of 100 mg/d	is well  tolerated,  but  can
cause  a  discoloration  of  the  skin  as  brownish  black  and  a red-brown
discoloration of the cornea,  conjunctiva  and  lacrimal  fluid.  It also may
cause anorexia, diarrhea, nausea and crystals in alveolar  macrophages.   The
macrolides  as clarithromycin cause mainly nausea and vomiting.  There may be
a drug interaction if patients are taking rifampin and a macrolide.

                   -AIDS AND PNEUMOCYSTIS CARINII-
PCP is the most common cause  of  pulmonary disease in AIDS and dissemination
is uncommon.  Many  drugs  have  been  used  to  treat  PCP  as  pentamidine,
sulfamethoxazole-trimethoprim,    dapsone,    clindamycin   and   primaquine,
trimetrexate  and  atovaquone.   Steroids  are   also  used  in  severe  PCP.
Prevention is with lower  doses  of  dapsone,  sulfamethoxazole-trimethoprim,
pyrimethamine-sulfadoxine         and         atovaquone.          TREATMENT:
SULFAMETHOXAZOLE-TRIMETHOPRIM  is given either orally or IV agt 20 mg/kg/d of
trimethoprim and is  as  effective  as  pentamidine,  with  response rates of
60-83% in AIDS patients.  Side effects are more common in pentamidine-treated
patients.    Side   effects    of    sulfamethoxazole-trimethoprim    include
thrombocytopenia,  leukopenia,  hyponatremia,  fever,  rash  and elevation of
liver funtion tests.  Blood  level  monitoring  should be helpful in reducing
the incidence of leukopenia.  Sulfamethoxazole should be kept below 100 ug/mL
and  the  trimethoprim  below  20  ug/mL.   Only   one   component   of   the
sulfamethoxazole-trimethoprim needs to be monitored.  The oral dose is almost
completely  absorbed  and therefore is preferred over the IV route.  Relapses
usually occur 4-6  months  after  being  treated.   In  patients  who fail to
respond to pentamidine, sulfamethoxazole-trimethoprim will  be  effective  in
about  90%  and  vice  versa.  PENTAMIDINE is given at 4 mg/kg/d IV or IM for
10-14 days.  Response rates  are  70-95%.   Side effects include neutropenia,
azotemia,  thrombocytopenia,  hypoglycemia  and  hypocalcemia.   Tachycardia,
nausea and  vomiting,  hypotension,  facial  flushing,  pruritus,  unpleasant
tastes,  syncope  and  hallucination  can occur in up to 75%.  Hypotension is
common and can be  helped  by  infusing  over  at  least 60 minutes.  Sterile
abcesses and skin necrosis occurs in about 7%, and pain with IM injections in
up to 18%.  Urticara can occur with IV administration.  Hypoglycemia is  more
common  in azotemic patients.  Pentamidine can also cause diabetes, which can
be controlled with low dose insulin.  DAPSONE  should not be used as a single
agent in the treatment of PCP.  Dapsone 100 mg/d + trimethoprim 20  mg/kg/day
has  been  effective.   However,  dapsone can cause rashes, nausea, vomiting,
decrease in  hematocrit,  neutropenia,  thrombocytopenia  and  elevated liver
function.  Patients should not  be  given  dapsone  with  glucose-6-phosphate
dehydrogenase  deficiency  because  of  possible  hemolytic anemia occurring.
CLINDAMYCIN-PRIMAQUINE combination results  have  been  variable with several
dosing schedules and should not be used as primary treatment for P.  carinii.
One  dosage  has  been  primaquine 30 mg daily + clindamycin 900 mg IV q6-8h.
Clindamycin may also be given orally at 450-600 mg every 6 hrs.  TRIMETREXATE
is less effective than  sulfamethoxazole-trimethoprim  for initial as well as
prevention.  It should only be used as an alternative.  ATOVAQUONE requires a
fatty meal for greater bioavailability.  The half life is 50 hours.  750  mg
tid  for 21 days has a response rate of 80%.  It should only be used in those
that are intolerant  to  sulfamethoxazole-trimethoprim.  PROPHYLAXIS: For HIV
patients who have not had PCP and have CD4 counts > .2  x  10  to  the  ninth
power/L, prophylaxis is not necessary unless there is a rapid decrease in the
CD4  or  have  symptoms  of  thrush  or unexplained fever.  Lymphocyte counts
should be done every 3-6  months.   All  patients who have recovered from PCP
should  receive  prophylaxis  with  sulfamethoxazole-trimethoprim,  1  double
strength tablet (160/800 mg) taken daily for life.  For  patients  unable  to
take  sulfamethoxazole-trimethoprim,  aerosolized pentamidine can be given at
300 mg once a month by a  small  particle aerosol generator, or via a patient
triggered ultrasonic nebulizer giving initially five 60  mg  doses  during  a
period  of  2  weeks,  followed  by  60  mg  every  2 weeks.  Before starting
aerosolized pentamidine,  patients  should  be  checked  for  tuberculosis by
history, chest x-ray and skin testing.  STEROIDS: Should be routinely used in
patients who have moderate to severe PCP who are over 13  years  of  age  and
have a PaO2 less tahn 70-80 mm Hg or an arterial alveolar oxygen greadient of
more  than  35 mm Hg.  Cryptococcus neoformans and Mycobacterium tuberculosis
and other lung infections should  be  ruled  out, because prednisone may mask
the symptoms.  Give prednisone 40 mg bid for 5 days, then 40 mg/d  from  days
6-10,  then  20  mg daily for the duration of PCP therapy.  IV therapy may be
given if unable to take prednisone orally.

                         -AIDS AND PNEUMONIA-
FOCAL PNEUMONIA: Patients that present  with focal pneumonia most likely have
a bacterial infection, especially if the CD4 is > 500/mm3.  The  differential
diagnosis   includes   the   following   organisms:   Hemophilus  influenzae,
Staphylococcus   aureus,   Streptococcus    pneumoniae,   Rhodococcus   equi,
Pseudomonas,  Klebsiella,  and  Legionella.   Atypical  Pneumocystis  carinii
pneumonia may  present  in  HIV  infected  patients  who  have  been  treated
prophylactically  with  aerosolized pentamidine.  Mycobacterium tuberculosis,
Mycobacterium avium, and Mycobacterium  kansasii  can  all present as a focal
pneumonia.  Fungal infections that may present focally include  Cryptococcus.
Tumors  such  as  lymphomas, Kaposi's sarcoma, and thromboembolic disease may
simulate a focal pneumonia.  Patients that present with a nonproductive cough
should suggest a pneumonia  caused  by  Mycoplasma, Legionella or an atypical
pneumocystis carinii pneumonia (PCP).  Patients  that  present  with  chills,
fever,  productive  sputa,  dyspnea and pleuritic chest pain should suggest a
bacterial  pneumonia.   Sputa  should  be  examined  by  Gram  stain.   If no
organisms are seen, this would suggest Mycoplasma, Legionella or  PCP.   Gram
postitive diplococci point to pneumococci.  Patient that present with chronic
lung  symptoms  should  be worked up for fungal infections with sputum fungal
cultures.  Any patient that lives  or  has traveled to endemic fungal regions
are at risk for fungal  infections.   These  regions  include  the  Southwest
(coccidioidomycosis),  and the Midwest and Southeastern USA (histoplasmosis).
Chest  x-rays  that  return  as  upper  lobe  infiltration  or  cavitation is
suggestive of atypical PCP in  patients  receiving  prophylactic  aerosolized
pentamidine,  or  Mycobacterium  tuberculosis.   Bacteremia  is common in HIV
patients.  Blood cultures should routinely be done in those patients that are
very  ill,  as  pneumococcal   bacteremia   is  common,  even  with  previous
pneumococcal vaccination.  Patients that present  with  a  dry  cough,  focal
infiltrate  on chest x-ray, lack of organisms on Gram stain should be treated
with  azithromycin,  clarithromycin  or   erythromycin  as  this  will  cover
Legionella,  Mycoplasma  and  pneumococcus.    DIFFUSE   PNEUMONIA:   Diffuse
pneumonia  in  patients  with CD4 counts < 200/mm3 most likely is PCP.  These
patients will present  with  shortness  of breath, nonproductive cough,weight
loss, fever and fatigue.   Other  organisms  to  be  ruled  out  include  CMV
(usually   only   colonizes   the   lung),  fungal  infections  (Histoplasma,
Cryptococcus   neoformans,   Mycobacerium   tuberculosis,   and  Coccidioides
immitis),   Mycobacterium   avium   complex,    microsporidiosis,    lymphoid
interstitial  pneumonia, lymphomas, and Kaposi' sarcoma.  Again, the level of
the CD4 is useful  in  identifying  which  organisms  are most likely.  CD4 >
200/mm3 usually excludes the opportunistic infections, and  the  more  likely
organism  would  be  Mycoplasma,  Legionella,  viral,  heart  failure or drug
reactions that are responsible for  the diffuse infiltrate.  CD4 counts below
200/mm3 usually means PCP if a diffuse interstitial  infiltrate  is  seen  on
chest  x-ray,  unless  the  patient  has  been receiving TMP-SMX preventative
therapy.  Ninety percent of  patients  with  PCP  will have an abnormal chest
x-ray.   About  10%  will  not  have  fever,  x-ray  findings   or   abnormal
oxygenation.  Patients that have thrush, hairy leukoplakia, diffuse perihilar
infiltrates,  sed rate > 50, and an LDH greater than 220 are at risk for PCP.
Obtain an LDH, as > 95% will  have an elevated LDH.  Induced sputum should be
obtained	for direct monoclonal immunofluorescent  antibodies.   This  will
positive  in  >  90%  of patients.  Any patient with CD4 counts < 200/mm3 may
also have diffuse fungal infiltrates.   These patients should have the sputum
and blood lysis-centrifugation cultures sent for fungal  culture  along  with
serum  cryptococal  antigen  tests.  Other appropriate fungal serology should
also be done.  If the diagnosis is still obscure, bronchoscopy should be done
with bronchoalveolar lavage and transbronchial biopsy.  Transbronchial biopsy
and bronchoalveolar lavage each  have  an  86% sensitivity for disclosing the
various organisms.   However,  when  they  are  both  done,  the  sensitivity
increases  to  98%.  Patients should be immediately started on TMP-SMX, since
the sensitivity is not affected by several days of therapy with TMP-SMX while
awaiting the results from  bronchoscopy.   Patients  that  have mild PCP with
minor hypoxia and early radiographic findings and a CD4 less than 200 can  be
treated  with  two  double  strength tablets TID or TMP-SMX 15 mg/kg PO daily
(trimethoprim component).  Patients that do not tolerate sulfa may be treated
with atovaquone 750 mg PO TID for  21 days.  Patients that do not tolerate IV
TMP-SMX at 15 mg/kg/day (divided into equal doses every 6  hours)  for  14-21
days  may  be  treated  with  pentamidine 3-4 mg/kg as a single dose per day,
given as a slow IV infusion  for  14-21  days.  Other drugs that may be given
orally include dapsone/trimethoprim (5 mg/kg PO q6h of TMP and 100  mg  daily
of  dapsone  for  21  days)  and  clindamycin/primaquine combination therapy.
Prednisone is given at 40 mg BID  for  5  days, then tapered over 21 days for
patients with moderate to severe PCP.  Prednisone therapy has been  shown  to
reduce  mortality  in  this  setting.  Mycobacterium avium complex is treated
with clarithromycin at  500  mg-1  gram  PO  BID  plus  three  or more of the
following drugs: Ciprofloxacin  (500  or  750  mg  PO  BID),  Ethambutol  (25
mg/kg/day  PO),  Clofazimine  (100  mg  PO  daily),  Rifabutin (300-600 mg PO
daily), or Amikacin (15 mg/kg/day  IV divided q8-12 hours.  Fungal infections
are  treated  with  amphotericin  B  using  up   to   .75-1   mg/kg/day   IV.
Cytomegalovirus  (CMV) infections are treated with ganciclovir at 5 mg/kg/day
IV given as a BID dose for 21 days.

                      -AIDS AND TOXOPLASMOSIS-
Toxoplasmosis is usually contracted by exposure to cat feces or by eating raw
or undercooked  meat.   In  the  USA  16-68%  of  adults  have  latent tissue
infection as discovered by serology.  From 3-40%  of  AIDS  patients  develop
toxoplasmic encephalitis.  AID's patient with a positive serology are at risk
for  developing  toxoplasmosis.   Toxoplasmosis can also cause pneumonia, and
occasionally, bone marrow, stomach,  heart  and liver involvment.  TREATMENT:
Pyrimethamine 200 mg loading dose, followed by 50-75 mg/d orally + 4-6  g  of
sulfadiazine/d  given  in  four  divided doses.  To prevent bone marrow toxic
effects  from  pyrimethamine,  folinic  acid  should  be  given  at  5  mg/d.
Zidovudine can  antagonize  the  therapeutic  benefit  of  pyrimethamine, and
should be discontinued while  pyrimethamine  is  being  given.   Response  is
within the first 2 weeks.  This combination is effective in between 40-70% of
patients.    Side   effects   include  rash,  fever,  nausea,  vomiting,  and
leukopenia.   About  40%  will  require   a  change  in  therapy  or  dosage.
Maintenance therapy must be given with pyrimethamine 25 mg/d  and  2  g/d  of
sulfadiazine,  both  given  2-3  times/week.   Patients  who  cannot tolerate
sulfadiazine, are given clindamycin 2400-4800  mg/d in 4 divided doses orally
or IV clindamycin 1200 mg every 6h.  Side effects include rash, diarrhea  and
granulocytopenia.    Alternative   drugs   that  may  be  beneficial  include
sulfamethoxazole-trimethoprim,   azithromycin,   clarithromycin,  spiramycin,
roxithromycin.  Some  patients  have  responed  to  atovaquone  750  mg  qid.
Interferon  gamma  may also be beneficial.  PROPHYLAXSIS: One double strength
sulfamethoxazole-trimethoprim twice weekly has been used with success.

                       -AIDS AND TUBERCULOSIS-
TB  has  been increasing by 3-6%/yr since 1984 due to AIDS.  The incidence of
extrapulmonary TB has increased by 20% since 1984, and occurs in 70% of AID's
patients.  TB may precede AIDS by months.   TB may affect the bone marrow, GI
tract, genitourinary tract, and CNS.  There is a high prevalence of TB in New
York and Miami.  HIV-related  TB  is  more  common  in  Haitians,  Hispanics,
Blacks,  and  those  who  use  IV  drugs.   TB becomes more common as the CD4
decreases, but may be seen at any  time.   If the CD4 is relatively high, the
presentation may be the same as that seen in non HIV patients; that is, upper
lobe disease, cavitation and a postivie PPD.   However,  in  immunosuppressed
patients,  the PPD is frequently negative and the patient presents atypically
with extrapulmonary  disease.   The  chest  x-ray  may  demonstrate a diffuse
interstitial  or  miliary  distribution,  lower   lobe   infiltrates,   hilar
adenopathy   or  pleural  effusion.   If  the  patient  presents  with  hilar
adenopathy,  the  differential  includes  Kaposi's  sarcoma,  fungal disease,
lymphoma and Mycobacgterium avium complex disease.  Norcardia, Legionell, and
Rhodococcus can simulate TB by presenting as cavitation.   Any  patient  that
presents  with  weight loss, cough and night sweats should be suspect.  A PPD
skin test may be considered  positive  in  HIV  patients if the induration is
only 2 mm or more at 48-72 hours.  If the CD4 is less than 200/mm3,  the  PPD
is  frequently  negative.   About  42%  of  HIV  related  TB  will have hilar
adenopathy, 29% pleural effusion, 25%  upper  lobe  disese, and 13% a miliary
distribution.  Only 6$ will demonstrate cavitation.  Sputums are positive  in
31-82%.   As many as 70% of patients will have evidence of extrapulmonary TB.
These consist of bacteremia, lymphadenitis, miliary disease, and CNS TB.  The
lymphadenitis is tender and  aspiration  biopsy  of  the nodes may yield AFB.
CNS disease (Tuberculous brain abscess and brain tuberculoma) may present  as
an  alteration  in  mental  status or be silent.  CT will show a hypodense or
ring enhancing mass.  Patients with  HIV  TB  CNS  disease will have a normal
chest x-ray in 70% of cases.  Tuberculous meningitis may present the same  as
non  HIV  patients with fever, meningeal signs, mental changes, and headache.
The CSF glucose can range from  0-48  mg/dL,  WBC from 0-1200.  AFB smears of
the CSF is only postitive in 22%, whereas the adenosine deaminase is positive
in 63%.  HIV patients with a positive PPD, or exposure to active  TB  in  the
face  of a normal chest-ray, negative sputum and symptoms, needs prophylactic
treatment with  INH  300  mg/day  for  1  year.   TREATMENT:  Is  the same as
immunocompetent patients except for the duration of treatment.  Isoniazid 300
mg/d, rifampin 600 mg/d (450 mg for those weighing < 50 kg), and pyrazinamide
20-30 mg/kg/day which is given for the first 2 months  only.   For  isoniazid
resistance,  include  ethambutol  25 mg/kg/day.  If resistant to isoniazid or
rifampin, ethambutol should  be  combined  with  the  remaining  agent for 18
months and pyrazinamide included for at least 12 months  and  possibly  18-24
months.   In  immunocompetent  patients,  therapy  is continued for 6 months.
Antituberculosis chemotherapy is well tolerated  in patients with AIDS taking
zidovudine without any increase in anemia  or  drug  interactions.   Patients
with a positive PPD should be treated with isoniazid 300 mg/d for at least 12
months.

                              -ALCOHOL-
SEIZURES: Withdrawal from acute  alcohol  intoxication  may  cause  seizures.
Most  occur  12-48  hrs  after  a  drinking binge, but may occur at any time.
Dilantin 1 gram IV over  30  minutes  with  continuous monitoring ECG and BP.
Renal and  liver  function  studies  should  be  obtained.   CT  of  head  is
considered.   Lumbar puncture should be seriously considered in patients with
sepsis  or  persistant  fever  in  whom  a  readily  evident  cause  for  the
temperature elevation cannot be  found.   DELIRIUM  TREMENS: This is the most
serious complication of alcohol withdrawal.  Usually starts a day or so after
drinking is stopped and may last for 1-2 days.   Characterized  by  agitated,
confusional state, tremulousness and autonomic hyperactivity.  Need hydration
and sedation.  WERNICKE'S ENCEPHALOPAHTY AND KORSAKOFF'S PSYCHOSIS: Wernickes
encephalopathy    usually   manifests   as   a   triad   of   encephalopathy,
ophthalmoplegia and  ataxia  due  to  thimanine  deficiency.  Neuropathologic
changes are seen in the tissues surrounding the 3rd and 4th ventricles,  most
prominently in the mamillary bodies and may be seen on MRI or CT.  Korsakoffs
psychosis  is a disabling memory disorder related to Wernickes encephalopathy
and may result from thiamine deficiency.   Patients should be given 100 mg of
thiamine  hydrochloride  (Betalin  S)  IV  daily  for  5  days.    CEREBELLAR
DEGENERATION:  is  seen  in  long  term  alcoholics.  Clinical manifestations
include gait ataxia  and  dysarthria.   Treatment  is supportive.  Abstention
from  alcohol  and  improvement  in  nutrition  have  reduced  the  rate   of
progression  and  in  some cases even reversed symptoms.  MARCHIAFAVA-BIGNAMI
DISEASE: is rare and may be acute, subacute or chronic in nature.  Clinically
it results in  dementia,  dysarthria,  spasticity  and  gait  apraxia and may
progress to coma.  Neuropathologic cause is necrosis of the  corpus  callosum
and  subadjacent  cortical white matter.  MRI may visualize.  CENTRAL PONTINE
MYELINOLYSIS:  There  may  be   an   aberrant  mental  state,  quadriparesis,
paraparesis, and  lower  cranial  nerve  dysfunction.   The  syndrome  occurs
following the rapid reversal of chronic and subacute hyponatremic states, and
may  result  from  conditions  other  than  alcoholics  such as chronic liver
disease, and burns.  In severe cases  it  may  result in a locked in syndrome
(complete  paralysis  except  for  the  eyes).   Neuroanatomically  there  is
demyelination of the base of the  pons.   Treatment  is  non-specific.   Slow
correction  of sodium dificiency by means of restriction of water consumption
or closely monitored administration  of  small  amounts of hyperteonic saline
solution should be carried out.  FETAL  ALCOHOL  SYNDROME:  Features  include
cranial-facial    dysmorphisms,   systemic   and   mental   retardation   and
developmental anomalies of several organ  systems.  Occurs in about .1-.3% of
live births in the USA and accounts for about 5% of congenital  abnomalities.
Partial  expressions  of  full  blown  clinical syndrome have been described.
PERIPHERAL NERVOUS SYSTEM EFFECTS:  They  may  correlate  with the extent and
length of alcohol use, and are  most  often  those  of  a  symmetric,  distal
polyneuropathy  involving sensory, motor, and autonomic nerves.  Paresthesia,
dysesthesia,   numbness   and   ataxia   are   common   as   are  symptomatic
mononeuropathies  resulting  from  local  trauma  or  compression  of  larger
peripheral nerves.  MYOPATHIES: affect about 50% of chronic alcohol  abusers.
May  occur  shortly after a drinking binge, manifested clinically by pain and
tnderness of an affected  muscle,  usually  a  proximal skeletal muscle.  Lab
reveals myoglobuinuria and an  elevation  of  serum  CPK-MM.   EMG  may  show
myopathy  and  muscle biopsies often demonstrate involvment of type I fibers.
Complications may include cardiac dysrhythmias, renal failure and electrolyte
abnormalities.  A chronic state  of  alcoholic mhyopathy, evidenced by muscle
cramping and atrophic changes particularly of the hip and shoulder girdles is
even more common.  Involvement of type II fibers  is  often  seen  on  muscle
biopsy in patients with chronic myopathy.

                       -ALCOHOLIC WITHDRAWAL-
Thiamine 100 mg IV  or  IM  prior  to  glucose  then  50  mg qid x 5-10 days.
Magnesium sulfate 50% soln 2 ml IM q12h x1 day then  once  daily  x  3  days.
Lorazepam  1-4  mg po or IV q4h OR Librium 25-100 mg po or IV q4-6h the first
day then reduce by 100 mg  each  following day.  Tenormin 50-100 mg daily for
tachycardia, increased BP and tremors.  Folic acid 1 mg po  daily.   Hydrate.
For seizures use valium, dilantin.

              -ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS-
Allergic  bronchopulmonary   aspergillosis   (ABPA)   is  a  hypersensitivity
pulmonary disorder that can complicate asthma, resulting in  transient  x-ray
infiltrates, often in the upper lobes, and central bronchiectasis.  CLINICAL:
All  patients  have asthma.  The asthma may be new or old.  Most patients are
young adults who are 20-40  years  of  age.   Most patients will have a cough
with mucopurulent sputum.  Some patients will expectorate sputum plugs, which
are actually casts of bronchi.  These have a brownish  discoloration  on  one
end  which is due to Aspergillus hyphae.  About 50% of the patients will have
hemoptysis  and  elevated   temperature   associated  with  the  radiographic
infiltrates.  A few  patients  will  complain  of  chest  pain  described  as
pleuritic  or  chest  wall  pain.   LABORATORY:  There  is  an array of x-ray
findings in ABPA.  These will be  discussed  in the order of their frequency.
INFILTRATES: The infiltrates may appear as nodular alveolar infiltrates up to
one cm in diameter and  have  either  an  ill  defined  or  distinct  margin.
CONSOLIDATION:  The  consolidation usually involves an entire segment or lobe
without air bronchograms and  is  due  to  an eosinophilic involvement of the
lung parenchyma.  Several other types of pneumonia  have  been  described  as
lymphocytic  interstitial  pneumonia,  desquamative  interstitial  pneumonia,
lipid  pneumonia  and  vasculitis.   All of these will rapidly disappear when
steroids are given.  TRAM  LINES:  Tram  lines  consist of two parallel lines
near the hila that extend outward toward the bronchi, and represent the width
of the normal bronchi.  PARALLEL line shadows are similar,  but  represent  a
dilated  bronchiectatic  bronchus.  Microscopically, the walls of the bronchi
are infiltrated  with  a  mixture  of  lymphocytes,  plasma,  eosinophils and
sometimes neutrophils.  There  may  or  not  be  granulomata.   There  is  no
Aspergillus  invasion  of the walls, but occasionally Aspergillus may be seen
in the lumen  of  the  bronchi.   With  steroid  treatment, the normal width,
inflamed bronchi will disappear, but the dilated bronchi  will  not,  because
these  represent  bronchiectasis.   BAND  (TOOTHPASTE) SHADOWS: These shadows
represent dilated bronchi that are  filled with inspissated mucous containing
Charcot-Leyden  crystals,  Curschmann's  spirals,  eosinophils,   mononuclear
cells,  and  fibrin.   If  the patient vigorously coughs these may disappear.
PERIHILAR SHADOWS:  These  shadows  may  simulate  hilar  adenopathy, but are
central bronchi filled with fluid and surrounded by infiltrates.   DIAGNOSIS:
ASTHMA:  All patients must have asthma, but the degree of asthma may be quite
variable, from  mild  to  severe.   Some  patients  will  have  a  history of
allergies and allergic rhinitis.  RADIOGRAPHIC INFILTRATES:  The  changes  on
x-ray will occur at some time during the course of ABPA, and may be absent at
diagnosis,  but  if  the  course  of  ABPA  is  followed  these  changes will
eventually be seen.  PERIPHERAL  EOSINOPHILIA:  This  finding  may not be too
specific, because peripheral eosinophilia may be present  in  asthma  without
ABPA.   However,  the eosinophilia usually ranges from 8-40% in ABPA.  If the
patient has been on steroids, the eosinophilia may not be present.  IMMEDIATE
SKIN SKIN  REACTIVITY  TO  ASPERGILLUS  ANTIGEN:  All  patients  will show an
immediate cutaneous reaction to Aspergillus fumigatus or  mixed  Aspergillus.
The prick test is usually done for testing.  ELEVATED TOTAL SERUM IgE: Normal
IgE  is  about  300  ng/ml.  However, in ABPA the IgE level may be as high as
40,000.  If the patient has been treated  with steroids, or the patient is in
remission, the IgE concentrations may not exceed 1000 ng/ml.  The IgE may  be
used  to  indicate exacerbations of the disease.  PRECIPITATING ANTIBODIES TO
ASPERGILLUS: This finding is  non-specific  because  about 10% of patient who
have asthma alone will have precipitating antibodies to  Aspergillus.   About
85%  of  patients with aspergillomas will also have precipitating antibodies.
Furthermore,  these  antibodies  may  be  suppressed  by  steroids.   CENTRAL
BRONCHIECTASIS: This finding  is  considered  diagnostic of ABPA.  TREATMENT:
Prednisone 0.5 mg/kg daily for 14 days, then give this dose on alternate days
for 3 months.  Following this, the dose should gradually be tapered, and then
discontinued.  The total serum IgE should then be measured every 2 months for
a year, as there may be exacerbations without clinical symptomatology.  Also,
chest x-rays should be obtained at 6 month  intervals.   These  measures  are
done  to  prevent progression of the lung disease to stage five, which is the
fibrotic stage  characterized  by  irreversible  obstructive  and restrictive
pulmonary abnormalities.

                             -ALOPECIA-
Alopecia may be classified in several ways.  One common way is by dividing it
into  nonscarring  and  scarring.   Non scarring alopeica may be secondary to
alopecia areata, toxic  alopecia,  trichotillomania  (hair  pulling) and male
pattern baldness.  Nonscarring alopecia can  occur  with  different  systemic
diseases  such  as  secondary  syphilis,  SLE,  pituitary  insufficiency  and
hyper/hypothyroidism.   Telogen  effluvium  is  another  cause  of  alopecia.
Telogen effluvium is a temporary hair loss that occurs in response to various
stressful  stimui.   There is a transitory increase in the number of hairs in
the resting (telogen)  phase  of  the  hair  growth cycle.  Telogen effluvium
usually occurs after a 2-4 month latent  period  from  the  inciting  factor.
About  150  hairs  will be lost per day compared to the usual 70-100 per day.
The prognosis is usually  good  and  it  diagnosed  by  the presence of large
numbers of hairs with white bulbs coming out by gentle removal of  the  hair.
Common  causes  include  physical  or  psychological stress, diffuse alopecia
areata, postpartum,  drugs  (anticoagulants,  clofibrate,  antithyroid drugs,
trimethadione, allopurinol, indomethacin, salicylates, levodopa,  gentamicin,
thallium,   prolonged   and  excessive  use  of  vitamin  A,  beta  blockers,
interferon, chemotherapeutic  agents,  retinoids,  and  oral contraceptives),
hypothyroidism, hyperthyroidism, hypopituitarism, high fever, surgery, shock,
crash dieting, iron and zinc deficiency and malnutrition.  ALOPECIA AREATA is
a sudden, nonscarring, noninflammatory, asymptomatic, circular loss  of  hair
most  commonly  on  the  scalp, but can occur on any hair bearing area of the
body.  Other areas that may be involved include the beard, brows, lashes, and
even the hairs in the nose.  The cause is usually idiopathic, but may be link
to an immunologic  process.   It  has  also  been  associated with pernicious
anemia,   vitiligo,   Addison's   disease,   and   Hashimoto's   thyroiditis.
Examination of the bald patch will reveal tiny hairs about 2-3 mm in  length.
These  are called exclamation hairs.  Alopecia areata is usually self limitng
with  regrowth  of  hair  in  about  80%  of  cases.   Alopecia  totalis  and
universalis  types  may  be  resistent.   The  most  effective  treatment for
localized involvement is with intralesional  corticosteroids.   Triamcinolone
acetonide  suspension  (10 mg/ml) is injected using a 30 gauge, .05 inch long
needle.  Aliquots of .1 ml are injected at 1-2 cm intervals, not exceeding 50
mg/month.  It is injected into  the  mid  to deep dermis and the subcutaneous
tissue should be avoided.  No more than 10 mg should be injected  per  office
visit  and  each  site  should not be injected more than once/month.  Topical
minoxidil (Rogaine)  may  be  effective  in  some  patients.   Potent topical
steroids may be of benefit, but should not be used  longer  than  about  6-12
weeks.   Super high potency topical steroids should not be used longer than 2
weeks.  If retreatment is needed, as rest period should intervene for several
weeks.  Anthralin 0.5%  ointment/cream  also  has  been  known to induce hair
gorwth.  Anthralin cream (.1, .25, .5, 1%) can be applied for 20 minutes  and
then  washed  off.  The duration and concentration depend on the response and
side  effects.   TRICHOTILLOMINIA   usually   appears   in  children  and  is
essentially a neurtoic compulsion to pull out one's hair.  The hairs  may  be
of  different  lengths  and  may  be  broken  off.  It is often confused with
alopecia areata.  It  is  difficult  to  diagnose,  but  scalp biopsy is very
useful in making the diagnosis.  Most cases  will  resolve  spontaneously  if
behavioral  modification  and  psychotherapy are employed.  HAIR TRACTION AND
CHEMICAL ALOPECIA: This may be a  common  cause  of alopeica in women who use
different tight hair styles such as braids, cornrowing, tight ponytails,  and
nightly  rollers  and  curlers.   This  type of hair loss is characterized by
noninflammaotry linear areas of hair  loss  at the periphery of the hairline,
along the part line, or scattered  throughout.   Hot  comb  alopeica  usually
occurs  at  the  peripheral hair line.  Treatment is avoidance of the various
hair styling and hair  straightening  procedures,  and utilization of natural
styling.  ANDROGENETIC ALOPECIA: Male pattern baldness usually begins as loss
of hair at the anterior part of the  hair  line.   There  may  be  associated
excessive  oiliness,  redness  and  scaling  in  this  area.   Treatment with
minoxidil (Rogaine) 2%, containing  20  mg/ml  of minoxidil has been helpful.
It is more effective in those less than 50 years of age, and those  who  have
had  alopecia  less  than  5  years with smaller areas of vertex involvement.
About 40% that have been treated BID  for one year have had moderate to dense
improvement of the vertex.  Female pattern alopecia is seen  fairly  commonly
in  women.   The  hair  loss  is  usually confined to the crown, parietal and
frontal  areas  and  complete   baldness   is   rare.   It  is  usually  seen
postmenopausally.   Androgenic  alopecia  may  also  be  seen  in  polycystic
ovaries, ovarian  hyperplasia,  adrenal  hyperplasia,  carcinoid,  and  drugs
(danazole, testosterone, anabolic steroids, progesterones, ACTH).  Androgenic
alopeica  in  women  can  be treated with minoxidil also.  Spironolactone has
also been used successfully, using a dose of 25-200 mg/day (is not listed for
use in the manufacturer's directive).   Birth control pills may be beneficial
in premenopausal patients and estrogen in postmenopausal patients.   SCARRING
ALOPECIA:  Cicatricial  or  scarring  alopecia  may  be  seen  in discoid LE,
granulomas such  as  sarcoidosis,  kerion,  bacterial  or  fungal infections,
factitial  ulcers,   TB,   syphilitic   gummas,   physical   trauma,   lichen
planopilaris,  severe  herpes  zoster,  scleroderma,  and ionizing radiation.
Biopsy may be  necessary  to  rule  out  cutaneous  lupus  from other causes.
Cultures for bacteria and fungi may be indicated.   Cicatricial  alopecia  is
irreversible  and  there  is no particular treatment.  DIAGNOSIS: Microscopic
examination of  plucked  hair  can  differentiate  some  forms of nonscarring
alopecia.  In the normal person about 80-90% of  hairs  are  in  the  angagen
(growing)  stage.   The  remaining 10-20% are in the resting (telogen) phase.
The plucked hair  should  consist  of  about  40-60  hairs.   These should be
counted to ascertain how many are in the anagen phase, and how  many  are  in
the  telogen  phase.  The anagen hairs can be recognized as they have sheaths
attached to the roots, whereas telogen  hairs have no sheaths, and have small
bulbs at the roots.  Patients that have postpartum and stress alopecias  will
have  an  increased  percentage of telogen hairs.  Alopecia areata hairs look
like exclamation points.  Alopecia due to antimitotic drugs and thallium will
show a normal percentage  of  telogen hairs.  Potassium hydroxide examination
and culture of the scale may be positive for tinea capitis.  Patients  should
have  thyroid  function testing, free testosterone and dehydroepiandrosterone
sulfate (in womenh with androgenic alopecia), serum ferritin, and VDRL.

                             -AMEBIASIS-
Amebiasis is caused by  a  protozoan,  Entamoeba histolytica which can infect
the intestine as well as the liver.  It is  usually  transmitted  by  fecally
contaminated food or water and by fecal-oral transmission.  The prevalence in
the USA is < 1% but probably greater in high risk groups as low socioeconomic
status,  migrant  labor  camps,  indian  reservations, male homosexuality and
institutional dwelling.  Water borne  outbreaks  have been reported with poor
plumbing.  Females are less affected  than  males.   The  disease  exists  in
essentially  two  intestinal  forms,  the  noninvasive and the invasive.  The
extraintestinal involvement is most common  in  the  liver and less common in
the lung, brain and skin.  CLINICAL: NONINVASIVE: E.  histolytica  exists  as
two  forms  in  the  large  bowel;  cysts  and  the motile trophozoites.  The
trophozoites encyst in the large  bowel.  Transmission usually occurs through
ingestion of cysts from fecally contaminated food or water.  Cysts can remain
viable for weeks to months, but the trophozoites are fragile  and  pass  from
the  bowel  and die.  In the noninvasive form the organisms live in the lumen
of the  large  intestine.   Without  diarrhea,  the  organisms usually encyst
before leaving  the  bowel.   There  may  be  no  symptoms  or  only  minimal
semiformed  stools  and abdominal cramps.  INVASIVE: The trophozoites usually
penetrate the large bowel in areas  of stasis as the cecum, appendix, sigmoid
colon and rectum.  The early lesions are small abscesses in the submucosa and
later ulcers form which are ragged  and  undermined.   In  mild  disease  the
lesions  are  focal  but  in  severe  disease,  there  may be confluence with
sloughing of mucosa, hemorrhage and edema.  Usually the muscularis layer acts
as a barrier, but sometimes the  ameba penetrate and cause perforation of the
bowel.  There may be abdominal cramps, flatulence, weight loss  and  fatigue.
There  are  periods  of  exacerbation and remission.  As the disease worsens,
dysenteric colitis or  severe  colitis  emerges  where  the  number of stools
increase and change from semi-formed to liquid.  Bowel movements  may  number
10-20  per  day  with  streaks  of  blood.   Pieces of necrotic tissue may be
passed.  The patients appears toxic and the  fever may rise to 104.9 F. There
can be vomiting, generalized abdominal tenderness and  liver  tenderness  and
enlargement.    If  the  disease  is  advanced  there  may  be  appendicitis,
peritonitis secondary to colon perforation, pericolonic abscess and fistulae.
If excessive granulation tissue  appears  in  response to the infection, then
there may be localized lesions  known  as  ameboma.   These  may  present  as
annular  constricting  lesions that are several centimeters in length and may
cause obstruction, or the masses may  project  into the bowel lumen which may
cause hemorrhage, pain and obstruction.   These  lesions  can  imitate  bowel
carcinoma,  tuberculosis,  lymphogranuloma  venereum,  and inflammatory bowel
disease.  HEPATIC AMEBIASIS: These patients  will  have fever, pain which may
be pleuritic, and an enlarged and  tender  liver.   There  may  be  sweating,
weight  loss, chills and anorexia.  There may be coughing and right lung base
findings, rales and x-ray changes.  LABORATORY: The WBC can reach high levels
of 20,000 or  higher.   There  may  be  slight  eosinophilia  but this is not
pronounced.  If there is tissue invasion the indirect  hemagglutination  test
may be positive.  Positive titers may persist for several years.  If patients
have  acute  amebic  dysentery or liver abscess then the tests is positive in
greater then 80%.  The test  is  positive  in  only about 10% of asymptomatic
carriers.  The indirect hemagglutination and ELISA  are  the  most  sensitive
tests.   Proper  stool examination is the most important aspect for diagnosis
and even with  good  specimens,  the  sensitivity  is  limited.  Three stools
should be collected at  every  other  day  intervals.   Specimens  should  be
collected in a clean container and there should be no contact with the toilet
bowl.   Trophozoites are fragile, lyse rapidly, and should be examined within
about 30 minutes, or the stool can be placed in 10% formalin for preservation
of cysts and polyvinyl alcohol for preservation of trophozoites.  If patients
have had recent antibiotics, antacids,  mineral oil, enemas, radiocontrast or
antacids, then the stool examination should be delayed for about 10  days  as
recovery  of  the  organisms  will be difficult.  Sigmoid exam should be done
without bowel preparation, and may  show  flask-like ulcers that measure 1 mm
to 2 cm covered with exudate.  This exudate should  be  pipetted  or  scraped
with  a metal curet for a wet mount in order to find the motile trophozoites.
Blood stained flecks of mucus  are  more  likely  to show the amebas.  Biopsy
specimens may show the trophozoites, and the biopsy specimen may  be  studied
by  immunofluorescence.   Formed stool should be examined for the cysts using
direct and concentrated stools exams.   Hepatic abscesses usually are oval or
round and localized to the upper right lobe of  the  liver.   Ultrasonography
may  show a hypoechoic center with diffuse echoes throughout the abscess.  CT
will  show  well  defined  round,   low  density  lesions  with  an  internal
inhomogeneous configuration.  Following contrast, the CT may show  hyperdense
halos  around  the abscess.  The serologic tests are usually positive and the
WBC  is  high.   Liver  function  tests,  surprisingly,  are  only  minimally
elevated.  The aspirate contains thick material that has a chocolate brown to
yellow color and contains  cytolyzed  tissue.   Cysts  are  not found and the
motile  amebas  tend  to  collect  around  the  periphery  of  the   abscess.
TREATMENT:  NONINVASIVE:  For noninvasive infection treat with iodoquinol 650
mg tid for 20 days.   INVASIVE:  For  ADULT invasive intestinal disease treat
with metronidazole 750 mg tid for 5-10 days followed by a 20  day  course  of
iodoquinol (diiodohydroxyquin) at 650 mg tid.  For CHILDREN use metronidazole
35-50  mg/kg/day  orally  in  3 divided doses, and iodoquinol 30-40 mg/kg/day
(maximum 2000 mg) in 3  divided  doses.  Alternative drugs for the iodoquinol
are paromomycin or diloxanide furoate.  These 3 drugs are only active against
the luminal trophozoites.  Paromomycin can be  given  for  7  days  at  25-30
mg/kg/day  in 3 divided doses for adults and children.  Diloxanide furoate is
given for 10 days at 500  mg  tid  for  adults  and 20 mg/kg/day in 3 divided
doses for children.  Emetine 1 mg/kg/day (maximum 60  mg)  OR  dehydroemetine
1-1.5  mg/kg/day  (maximum  90 mg) may be given IM for a maximum of 5 days in
order to treat invasive  intestinal  disease.   Extreme caution must be taken
when these are used,  for  the  drugs  are  toxic.   The  patient  should  be
monitored  by EKG and watched for tachycardia, and hypotension.  There may be
GI effects,  weakness  and  dermatoses.   The  drugs  are  contraindicated in
cardiac disease and pregnancy.  Emetine and dehydroemetine may also  be  used
in  the  treatment  of  hepatic  amebiasis,  but then should be combined with
chloroquine phosphate 1 gram (600  mg  base)/day  po  for 2 days, then 500 mg
(300 mg base)/day for 3 weeks for adults.  In  children  use  17  mg  (10  mg
base)/kg/day (maximum 300 mg base/day) for 3 weeks.  If E. histolytica can be
found  in  the bowel then iodoquinol may be added.  HEPATIC: Metronidazole is
given as 750 mg po tid  for  10  days  in  adults and 35-50 mg/kg/day po in 3
divided doses for 10 days for children.  Metronidazole is the drug of choice.
Side effects of metronidazole include nausea, vomiting and a  disulfiram-like
reaction  with  alcohol.   If  there is a favorable response to metronidazole
which usually takes place within 2-3  days  then  possibly a 2 week course of
chloroquine may be given to prevent late failures.  Alternatively, emetine or
dehydroemetine can be used as above.  A  luminal  amebicide,  as  iodoquinol,
should  be  given  in liver abscess depending on whether or not the organisms
are found in the stool.

                            -AMENORRHEA-
If  patient  has  secondary  amenorrhea,  first  rule  out  pregnancy  by   a
qualitative  HCG.   If  this  is  negative  give progesterone (Provera) 10 mg
bid	for 5 days.  If there is no  withdrawal  bleeding do FSH and LH.  The FSH
is elevated in primary ovarian failure as Turner's syndrome or menopause.   A
FSH:LH  ratio > 2.0 is seen in polycystic ovary syndrome.  A prolactin should
be done to rule out a  prolactin  secreting pituitary tumor or a hypothalamic
lesion.  Normal or low levels of serum LH and FSH are  seen  with  drug  use,
anorexia  nervosa,  jet  lag,  psychic  stress,  severe illness, pituitary or
hypothalamic disease or  uterine  problems  as  uterine synechiae (Asherman's
syndrome).  Do TSH to rule out hyper  or  hypothyroidism.   Electrolytes  are
done  to help rule out Addison's disease.  Cushing's syndrome should be ruled
out with a dexamethasone test.  Serum testosterone and other androgens may be
elevated in androgen  resistance  syndromes  and  in  hyperandrogen states as
congenital adrenal hyperplasia, polycystic ovary syndrome or  tumors  of  the
adrenal   or  ovary.   If  hirsutism  is  present  obtain  LH,  testosterone,
androstenedione,  dehydroepiandosterone  sulfate  and  17 hydroxyprogesterone
(congenital hyperplasia), serum estradiol, skull film with coned down view of
sella or CT.  Obtain history for dieting, stress, exercise, D&Cs,  postpartum
infection  or hemorrhage (Sheehans syndrome), obesity, weight gain/loss, head
injury, galactorrhea,  memnopause  symptoms,  headaches, visual disturbances,
thyroid symptoms, symtpoms of pregnancy, phenothiazines, alpha  methyl  dopa,
antidepressants, hormones, and family history of genetic abnormalities.

                            -AMENORRHEA-
Primary amenorrhea is defined as a lack of menses by the  age  of  18.   This
discussion  will  address secondary amenorrhea which can be defined as a lack
of  menses  for  at  least  3  months  in  a  previously  menstruating woman.
Amenorrhea following pregnancy and oral contraceptives may be more sustained,
often lasting for 6 months.  Secondary amenorrhea may  involve  abnormalities
in  the endometrium, ovaries, pituitary, hypothalamus, endocrine, chromosomes
and drug induced.  Pregnancy and  menopause  are  two common causes and these
should be excluded with a pregnancy test and FSH which  is  greater  than  40
mlU/ml.  Diabetes mellitus should be excluded also.  If the pregnancy test is
negative  then  obtain  a  TSH.   If  this  is elevated then the cause may be
hypothyroidism.  If the TSH is normal  obtain a prolactin level.  If there is
hyperprolactinemia get a MRI or CT of the head which may reveal  a  tumor  of
the  pituitary  which  can  be  treated  with  neurosurgery, bromocriptine or
radiation therapy.  PROGESTIN CHALLENGE  TEST:   If  the Prolactin is normal,
perform a progestin challenge test  which  is  done  by  giving  progesterone
(Provera  10  mg  po  daily  for  5  days  or  one  IM injection of 200 mg of
progesterone in oil.  If  bleeding  occurs  2-7  days  after the injection or
taking the last pill then anovulation is the problem.  With  bleeding,  there
is  sufficient  ovarian  production of estrogen to prime the endometrium, the
endometrium is intact, and there  is  a  patent outflow tract.  If withdrawal
bleeding occurs then rule  out  diseases  that  can  produce  anovulation  as
polycystic  disease of the ovaries, Cushing's disease and adrenal hyperplasia
or tumor and  ovarian  tumors.   Polycystic ovarian syndrome (Stein-Leventhal
syndrome) symptoms and signs would include obesity,  hirsutism,  infertility,
elevated  LH  and  decreased  FSH  with  enlarged  polycystic  ovaries.   The
estradiol  and  17 ketosteroids may also be elevated.  ESTROGEN AND PROGESTIN
CHALLENGE TEST: If there  is  no  withdrawal bleeding following the progestin
challenge give the patient estrogen as Premarin 1.25 mg po daily for 25 days.
Add progesterone as Provera 10 mg po daily from days 15-25.  If there  is  no
bleeding following this then there is a problem in the endometrium or outflow
tract.   Problems  with  the endometrium include Asherman's syndrome which is
due to curettage and  infection  from  tuberculosis,  etc.  Problems with the
outflow tract include imperforate hymen, cervical stenosis,  and  absence  of
the  uterus,  cervix or vagina.  On the other hand, bleeding means there is a
patent outflow tract and an endometrium that  is intact.  If this is the case
obtain a FSH.  If the FSH is high then there is ovarian failure that could be
on the basis of an autoimmune disease, Savage syndrome (insensitive ovaries),
menopause or, in younger patients, a chromosomal  problem,  and  the  patient
will  have  to  be  treated  with  hormonal replacement therapy.  Chromosomal
abnormalities include Turner's  syndrome  and testicular feminization.  Other
ovarian problems include ovarian radiation or chemotherapy, and  androgen  or
estrogen secreting ovarian tumors.  If the FSH is normal or low then obtain a
MRI  or  CT  of the head.  If this is normal, then the patient probably has a
hypothalamic problem producing the  amenorrhea  which  can  be due to stress,
weight gain or loss, exercise and anorexia nervosa.  If the Head MRI or CT is
abnormal there could be a pituitary tumor as a meningioma, craniopharyngioma,
empty sella syndrome, Sheehan's syndrome (post partum pituitary  infarction),
cerebral   aneurysm,   syphilitic   gummas,   and  granulomatous  disease  as
sarcoidosis.  If there is  hirsutism  present  on  examination of the patient
then  additional   laboratory   tests   would   include   LH,   testosterone,
androstenedione,  dehydroepiandrosterone  sulfate and 17 hydroxyprogesterone,
and serum estradiol.  Drugs such as phenothiazines, steroids, Danazol, GRH-RH
analogs, reserpine,  methyldopa,  tricyclic  antidepressants, MAO inhibitors,
thioxanthenes  can  cause  amenorrhea.   All  drugs  that   can   produce   a
hyperprolactinemia should also be checked.

                           -AMINOPHYLLINE-
For healthy adult nonsmokers give a loading dose of 6 mg/kg  IV  and  then  a
maintenance  of  .5  mg/kg/hr  based  on  ideal body weight.  Each 1 mg/kg of
aminophylline will increase the serum  theophylline  by about 1.7 ug/ml.  For
the elderly and patients with cor pulmonale give laoding  dose  of  6  mg/kg,
then  a  mainetenance of .3 mg/kg/hr.  For young adult smokers give a loading
dose of 6 mg/kg, then .8 mg/kg/hr.  For patients with heart failure and liver
disease give a loading dose of  6  mg/kg, then .1-.2 mg/kg/hr.  If patient is
already on theophylline and  patient  has  respiratory  distress,  and  serum
theophyllines  are not available, give 3 mg/kg of aminophylline IV which will
raise  the  theophylline  level   by   about  5  ug/ml.   AMINOPHYLLINE  DRUG
INTERACTIONS:  Increased  theophylline  levels:   cimetidine,   erythromycin,
propranolol,   allopurinol,   oral  contraceptives.   Decreased  theophylline
levels: phenytoin, phenobarbital, smoking.

                             -AMIODARONE-
Amiodarone is a benzofuran  derivative  that  blocks  the efflux of potassium
from  myocytes  and  prolongs   the   action   potential,   which   increases
repolarization  and the effective refractory period in atrial and ventricular
tissue.  Even though the QT interval  is  prolonged, torsades de pointes is a
rare complication of amiodarone, because the drug  increases  homogeneity  of
the action potential throughout the myocardium.  It slows the sinus node rate
and  recovery  time  and  prolongs  AV  node  conduction.   Amiodarone  is  a
noncompetitive  alpha  and  beta  antagonist  and  inhibits  the  release  of
neurotransmitter   from   presynaptic  adrenergic  neurons.   It  blocks  the
peripheral conversion of T4-triiodothyronine  (T3).   The  drug has very mild
negative inotropic action which is probably due to  a  decrease  of  systemic
vascular resistance.  This property allows its use in the treatment of lethal
arrhythmias  which often are associated with underlying severe LV dysfunction
with ejection fractions  less  than  30%.   About  50%  of  the  oral dose is
absorbed.  The bioavailability is 20-80% and the  plasma  levels  develop  in
6-12  hours.  Amiodarone is 95% bound to protein with widespread distribution
in almost all tissues, particularly  in  the liver, lungs and adipose tissue.
The concentration in the heart is about 20-40 times that found in the plasma.
It  is  metabolized  in  large  part  to  desethyl   amiodarone   which   has
pharmacologic  activity.  The major route of elimination is hepatic excretion
into  the  bile.   Renal   elimination   of  amiodarone  and  its  metabolite
desethylamiodarone is very small.  The half life  of  amiodarone  is  between
40-55 days.  The therapeutic serum level is 1.5-5 ug/ml.  The IV loading dose
is about 5 mg/kg (usually 300 mg) given over 2 hours with ECG monitoring.  In
an  emergency  it  may be given over 1/2 hour.  The patient should be watched
for hypotension.  The therapeutic effects when given IV are observed within a
few minutes.  To administer orally,  the  patient  is given a loading dose of
800-1600 mg/day for  1-3  weeks  or  longer  until  there  is  a  therapeutic
response.   Amiodarone  is  supplied  as 200 mg scored tablets.  It should be
given with meals such as 200  mg  TID.  With this dose the therapeutic effect
is observed in 1-4 days, but continues to increase with time.  When  adequate
arrhythmia  control  is  seen  or prominent side effects occur, decrease to a
maintenance dose of 400 mg/day.  This may be given as 200 mg BID for patients
with GI intolerance; otherwise,  it  may  be  given  as one dose.  MONITORING
should be carried out by obtaining baseline chest x-rays, pulmonary  function
testing  including  diffusion  capacity,  thyroid  function tests, potassium,
magnesium, and liver function tests.  Thyroid function testing should be done
every 3-6 months during therapy.   ECG  is needed for bradyarrhythmias and QT
prolongation.  Digoxin serum assay will have to be followed closely, and  the
dose   of  digoxin  should  be  halved.   If  oral  anticoagulants  are  used
concurrently, the dosage should  be  halved.   Holter monitoring is useful in
confirming arrhythmia  suppression,  torsade  de  pointes,  and  bradycardia.
Plasma  concentrations  can  be useful if the patient does not respond to the
drug, or there  is  unexpected  toxicity.   Amiodarone  is contraindicated in
those patients with second and third degree AV block, those with severe sinus
node dysfunction, and symptomatic bradyarrhythmias, except when  a  pacemaker
is  present.   It  also  is  contradindicated  in severe hepatic dysfunction,
porphyria, breast  feeding,  pregnancy,  and  iodine  sensitivity.   The drug
dosage may need to be decreased  or  discontinued  if  the  patient  develops
elevation  of  the  hepatic  enzymes  greater than 3 times normal, or 2 times
baseline  if  the  baseline   liver   enzymes  were  elevated,  hepatomegaly,
amiodarone  induced  interstitial/alveolar  pneumonitis,  proarrhythmia  with
paroxysmal ventricular tachycardia, CHF, hypothyroidism  or  hyperthyroidism.
INDICATIONS:  Amiodarone  is  indicated  in  lethal  ventricular arrhythmias,
sustained ventricular tachycardia, recovery from ventricular fibrillation, or
cardiac arrest.  The mortality in  survivors  of  cardiac arrest is about 66%
over a 5 year period.  Amiodarone may be useful in  this  group.   Amiodarone
prevents  the  recurrence  of  sustained spontaneous VT or VF (not associated
with acute MI) in up to  60%  of  patients.  Amiodarone is also indicated for
conversion of acute atrial fibrillation  to  sinus  rhythm,  particularly  in
patients with hypertrophic cardiomyopathy.  It may also be used in paroxysmal
atrial  fibrillation with rapid ventrciular rates that is refractory to other
therapies.  It is also indicated for the management of atrial fibrillation or
atrial flutter in patients with WPW  who  have rapid ventricular rates due to
anterograde conduction over the accessory pathway.  ADVERSE EFFECTS:  Adverse
effects are common with doses greater than 400 mg/day.  About 75% of patients
will  have  adverse effects and require discontinuation in 7-18% of patients.
GI complains are the most common with nausea and vomiting occurring in 10-33%
along with anorexia and constipation of 4-9%.  Neurologic complaints occur in
20-40% (tremor, ataxia and  peripheral  neuropathy).   Patients may also have
dermatologic complaints (15%), visual  disturbances  (4-9%),  photsensitivity
(10%),  CHF  (3%),  blue discoloration of the skin, pulmonary inflammation or
fibrosis  (5-15%),  and  abnormal  liver  function  tests  (4-9%).  Pulmonary
fibrosis may occur early or late  in  the  course  of  therapy  with  varying
dosages.  Patients develop a dry cough and dyspnea.  It may be rreversible if
detected early.  The patient should have serial chest x-rays every 3-6 months
to  detect  the interstitial changes.  Diagnosis may be enhanced by obtaining
abnormal decreases in diffusing  capacity  and gallium lung scans.  Prolonged
AV node conduction and asymptomatic  sinus  bradycardia  are  commonly  seen.
Exacerbation of ventricular arrhythmias may be seen, but is less ocommon than
swith  class  Ia  agents.  Amiodarone will lengthen PR, QRS and QT intervals.
Torasdes de pointes is rare.   Corneal  microdeposits usually develops in all
patients.  These depostis rarely interfere with vision,  although  some  will
notice halos around lights at night.  The occurrence is dose dependent and is
reversible   with   discontinuation   of   the   drug.    Hypothyroidism  and
hyperthyroidism  develop  in  a  minority  of  patients.   Amiodarone  blocks
peripheral conversion of T4-T3.  Therefore,  most  patients on this drug will
have mild elevations of T4, and decrease of T3.  The elevated T4 may make the
diagnosis of hyperthyroidism difficult, but if the free T3 is also  elevated,
the diagnosis of hyperthyroidism can be confirmed.  If the T3 and T4 are both
decreased, or the TSH is elevated, a diagnosis of hypothyroidism may be made.
Hepatitis  with  large  elevations  of  the  enzymes  occurs  rarely, but can
progress to cirrhosis.   Amiodarone  should  be  discontinued if transaminase
levels are greater  than  3  X  normal.   DRUG  INTERACTIONS:  Warfarin  will
increase  the  hypoprothrombin  effects,  digoxin  levels  will be increased,
flecainide levels will be  increased,  hydantoins will increase the hydantoin
levels  and  decrease  the  amiodarone  level,  theohylline   will   increase
theophylline  levels,  quinidine  will  increase  quinidine  levels, Class 1a
antiarrhythmic agents and erythromycin will  also prolong the QT interval and
may induce torsades de pointes.  Therefore, these drugs should not  be  given
concomitantly.  Use of verapamil and diltiazem with amiodarone can prouduce a
sinus arrest or AV block,  and  should  not be used together.  Sotalol should
not be used with amiodarone.  The beta blockers may be used with  amiodarone,
but  used  with  caution.   Tricyclics and phenothiazines, and moricizine can
induce torsades  de  pointes.   Diuretics  can  cause  hypokalemia  and cause
torsades de pointes.

                           -AMPHOTERICIN B-
Amphotericin B still has a place in treatment of fungal disease,  inspite  of
newer  agents  being  introduced.   It  is  the  drug  of  choice in invasive
pulmonary or extrapulmonary  Aspergillus.   The  total  dose for treatment in
Aspergillus is 30-40 mg/kg.  Flucytosine or rifampin  is  occasionally  given
with  the  amphotericin.  Most patients will need a total daily dose of 0.5-1
mg/kg.  Itraconazole is  an  alternative  antifungal  agent  that is given at
100-400  mg/day.   Patients  with  disseminated,  immunosuppressed,  or   CNS
Blastomycosis  can  also  be  treated  with amphotericin B. The total dose is
30-40 mg/kg.  Alternatively, itraconazole can be given orally.  Patients with
peritoneal dialysis who develop a  candidal  peritoneal infection can also be
treated with amphotericin B, either IV or topical.  For topical treatment add
2-4  ug/L  in  the  dialysate  fluid.   Sometimes  flucytosine  is  added  to
amphotericin.  It is given as 50-100 mg/L of dialysate fluid.  The peritoneal
catheter may have  to  be  removed  to  cure  the  infection.   For  IV  use,
amphotericin  B  is  given  to  a  total  dose of 3-10 mg/kg.  Alternatively,
fluconazole can be given  at  200-400  mg/day.   Candida bacteremia, which is
often  due  to  line  sepsis,  is  also  treated  with  amphotericin  B   IV.
Amphotericin  is  given  for a total dose of 3-10 mg/kg.  All lines should be
removed or replaced.  Candidal  endocarditis  is  treated with amphotericin B
+/- flucytosine.  The total dose required is 30-40 mg/kg of amphotericin  and
flucytosine  is  given at 150 mg/kg/day.  Surgery is usually always required.
Severe, progressive cavitary Coccidioides may  be treated with Amphotericin B
IV  using  a  total  dose  of  7-20  mg/kg.   Disseminated,  (non  meningeal)
Coccidioides is treated with amphotericin B IV  at  a  total  dose  of  30-40
mg/kg.   Coccidioides  meningitis  is treated with amphtoericin IV at a total
dose of 30-40 mg/kg  and  intrathecally,  .5-.7 mg 2 times/week.  Progressive
pulmonary cryptococcus is treated with amphotericin B IV for a total of 15-30
mg/kg +/- flucytosine.  Extrapulmonary (nonmeningeal) Cryptococcus is treated
with a total dose of 2-3 grams of amphotericin +/- flucytosine.  Disseminated
(including meningeal) Cryptococcus without AIDS is treated with  amphotericin
B  at  .3  mg/kg/day plus flucytosine 150 mg/kg/day for 6 weeks.  Crytococcal
meningitis in an AIDS patient is  treated with amphotericin B .5-.8 mg/kg/day
+/- flucytosine 100 mg/kg/day for a total of 15 mg/kg of amphotericin B  plus
a  negative  CSF  culture.   Alternatively,  the  patient may be treated with
amphotericin B .7 mg/kg/day for  10-14  days,  then fluconazole 400 mg/day PO
for 8-10 weeks, then maintenance of fluconazole 200 mg/day.   Fluconazole  is
given  only  if  the  mental  status  is  normal.   If  fluconazole fails for
maintenance, amphotericin B is given  at 1 mg/kg/week or itraconazole 200-400
mg/day.   Disseminated,  immunosuppressed   Histoplasma   is   treated   with
amphotericin  B  IV  for a total dose of 30-40 mg/kg.  For AIDS patients give
amphotericin at a dose  of  .5-1  grams, followed by maintenance itraconazole
orally at 400 mg/day or amphotericin B IV  1-1.5  mg/kg/week.   Pulmonary  or
extrapulmonary  phycomycetes  (Mucor,  Rhizopus  or  Absidia) is treated with
amphotericin B IV to a toal dose of  30-40 mg/kg, giving a daily dose of .5-1
mg/kg.    Rhinocerebral   involvement    requires    surgical    debridement.
Extracutaneous  Sporotrichosis) is treated with amphotericin B IV for a total
dose of 30-35 mg/kg at .5  mg/kg/day  OR itraconazole 100-200 mg po daily for
6-18 months.  ADMINISTRATION: The patient is usually given  a  test  dose  to
check for anaphylactic reactions prior to infusion.  This consists of 1 mg in
500  ml  of  5% dextrose and water given over 3-4 hours.  If the test dose is
tolerated the patient  is  infused  with  a  daily  dose  of  about 10 mg and
gradually increasing the dose until about 50 mg/day is given.  The exact dose
depends on the disease being treated.  In general, amphotericin can be  given
until  a  response  is seen with subsequent doses given on an every other day
basis.   Amphotericin  should  always  be  given  in  D5W  (not  electrolytic
solutions), and is  typically  given  over  4-6  hour  period.  SIDE EFFECTS:
Amphotericin is very toxic and there are numerous  side  effects.   Prior  to
administration  the  patient  should  be  evaluated for dehydration or sodium
depletion.  If found, the patient should receive  500 ml of 0.9% saline IV 30
minutes  prior  to  and  following  the  amphotericin  treatment,  until  the
condition is corrected.  Common complaints include  shaking  chills,  nausea,
vomiting,  fever, anorexia and headache.  Pretreatment with acetaminophen 650
mg po is commonly given.  Hydrocortisone  25  mg  given in the IV solution or
through the IV tubing will help relieve febrile  reactions.   Rigors  can  be
controlled  with  meperidine  25-50 mg IV.  Heparin 500 U IV may decrease the
phlebitis.  Heparin is not necessary  if  a  central line is being used.  The
patient should be monitored with serum  creatinine,  electrolytes,  magnesium
BUN  and  CBC  weekly during amphotericin therapy.  The serum creatinine will
increase in almost every patient being treated with amphotericin.  There is a
decrease of glomerlar filtration rate  GFR)  of  about 40% during the first 2
weeks, then stabilizes at 20-60% of normal.  If the creatinine rises  rapidly
the  infusions  should be interrupted for 2-5 days.  Otherwise, no adjustment
is given unless the creatinine reaches  2.5 mg/dl at which time the infusions
should be interrupted for a few days.  Improvement in renal function  usually
occurs  with  interruption  of therapy, but permanent impairment may occur if
the total cumulative dose is > 3 grams.   It is prudent to not give any other
neprhotoxic  antibiotics  or   chemotherapeutic   drugs   unless   absolutely
indicated.   Nephrocalcinosis  and  renal  tubular  acidosis  are  rare,  but
hypokalemia, hypomagnesemia, and normocytic, normochromic anemia are common.

                              -AMYLASE-
CAUSES OF HYPERAMYLASEMIA:  Pancreatitis,  parotitis,  pancreatic  carcinoma,
ruptured   ectopic   pregnancy,   biliary  disease,  intestinal  obstruction,
infarction  or  perforation,  peptic  ulcer  disease,  macroamylasemia, renal
insufficiency.

                            -AMYLOIDOSIS-
Amyloidosis  exists  as 3 major clinical forms causing organ dysfunction from
infiltration of tissues with insoluble  protein fibrils, or proteins that are
complexed  with  polysaccharides.   The  amyloid  consists  of  a   fibrillar
component, the P component (a normal plasma protein which is called amyloid P
protein),  and  glycosaminoglycans.   Diagnosis is made by examination of the
biopsy  specimen  stained  with  Congo  red  under  a  polarizing microscope.
Amyloid  shows  a  characteristic  green  birefringence.   The  prognosis  in
secondary amyloidosis depends  on  successful  treatment  of  the  underlying
disease.   Patients  with  multiple  myeloma  and  amyloidosis  have a dismal
prognosis.  All forms of  renal  amyloidosis  have  a  poor prognosis.  The 3
major forms of amyloidosis consist of the  primary,  secondary  and  familial
forms.   These  will subsequently be discussed.  PRIMARY AMYLOIDOSIS commonly
involves the  tongue,  heart,  skeletal  and  smooth  muscles, skin, thyroid,
nerves, and ligaments.   Primary  amyloidosis  is  characterized  by  protein
deposits  that  are  composed  of  immunoglobulin light chains (amyloid light
chains).  Primary amyloidosis can occur in conjunction with multiple myeloma,
Waldenstrom's macroglobulinemia, and  agammaglobulinemia.  Kappa light chains
are more common in amyloidosis associated with multiple myeloma, while lambda
light chains are more common in idiopathic amyloidosis.  When amyloidosis  is
associated  with multiple myeloma the prognosis is grave.  Amyloidosis occurs
in  about  5-15%  of  multiple  myeloma.   SECONDARY  AMYLOIDOSIS  is usually
associated with tuberculosis, rheumatoid arthritis, hypernephroma,  Hodgkin's
lymphoma  and leprosy.  However, is may also occur in ankylosing spondylitis,
tophaceous gout, inflammatory  bowel  disease, Behcet's syndrome, polymylagia
rheumatica, vasculitis, Sjogren's syndrome, melanoma, solid tumors of the GI,
GU and pulmonary systems, cystic fibrosis, diabetes mellitus, bronchiectasis,
drug abuse, and juvenile rheumatoid arthritis.  In the USA, the prevalence of
amyloidosis in rheumatoid arthritis is  less  than  1%.   Interestingly,  the
incidence  in  Europe exceeds 10%, and the most common mode of death is renal
failure.  The protein that is deposited in secondary amyloidosis is different
from that seen in primary or idiopathic amyloidosis.  Patients with secondary
amyloidosis have elevated serum levels of a protein that has been named serum
amyloid A (an acute phase reactant) that is a precursor to amyloid A protein.
Elevated levels of serum amyloid  A  may  also be seen in infections, chronic
inflammatory diseases, neoplastic  disorders,  and  even  in  normal  healthy
individuals.    FAMILIAL   (HEREDIATRY)   AMYLOIDOSIS  commonly  affects  the
peripehral nerves and viscera.  It is characterized by peripheral sensory and
motor neuropathies, autonomic  neuropathy,  cranial  neuropathies, renal, and
cardiovascular  amyloid  deposits.   The  inheritance  is  mostly   autosomal
dominant,  and  most  are  related to variants of transthyretin (prealbumin).
However, if amyloidosis is associated  with familial Mediterranean fever, the
inheritance is autosomal recessive and usually related to amyloid A  protein.
OTHER  FORMS  OF  AMYLOIDOSIS:  Amyloidosis  has  also  been  associated with
hemodialysis.  This usually occurs in long term hemodialysis and involves the
articular and periarticular areas.   Carpal  tunnel  syndrome is common.  The
protein deposits are beta2  microblobulin.   Membranes  that  are  made  from
cellulose and cuprophane cannot clear beta2 microglobulin.  This results in a
build  up  of  this  protein  in the serum.  Changing to a different membrane
helps in some cases, but doesn't  fully explain the etiology of the syndrome.
In some cases, carpal tunnel syndrome does not develop in patients with  high
levels  of  beta2 microglobulin.  Alzheimer's disease and Down's syndrome can
also be associated with  amyloid  deposits.  CLINICAL: Amyloidosis can affect
many organ systems, and in the  secondary  forms  cany  be  obscured  by  the
underlying  disease.   Amyloidosis  should  be considered in any patient with
unexplained  cardiomyopathy,   CHF,   carpal   tunnel   syndrome,  peripheral
neuropathy,  proteinuria,  hepatosplenomegaly  and   macroglossia.    Amyloid
arthropahty  is  characterized  by  a  chronic  symmetric  arthropathy of the
shoulders, fingers, wrists, and knees.   It is non-erosive with the exception
of the arthropathy that occurs in amyloidosis associated  with  hemodialysis.
It  may  mimic  rheumatoid  arthritis  in  patients  with  multiple  myeloma.
Examination  of the shoulder may reveal the shoulder pad sign which is a soft
tissue mass of the  shoulder  due  to  infiltration of the glenohumeral area.
Examination of the synovial fluid may reveal a few Congo red positive amyloid
fibrils and mononuclear cells.  Dermal involvement is more common in patients
with primary amyloidosis, and tends to affect the inguinal,  axillary,  upper
extremities  and  face.  Purpura may be seen or induced by pinching the skin,
and is due to  capillary  fragility.   Waxy,  indurated  papules may be seen.
Deposits of amyloid can lead to a  condition  that  is  not  unlike  that  of
scleroderma  or myxedema.  Biopsy of the dermis, and subcutaneous tissue will
reveal amyloid deposits.  Renal disease  is  common  to all forms and usually
starts as proteinuria.  Hematuria is not common.  Renal involvement is a very
common cause of death in patients with amyloidosis.  Hypertension  occurs  in
less  than  50% of patients with amyloidosis.  Nephrotic syndrome can develop
and lead to massive  proteinuria,  anasarca, and hypoproteinemia.  Renal vein
thrombosis is common.  Biopsy of the kidney will show amyloid  deposition  in
mesangial  and subendothelial regions of the glomerulus and arteriolar walls.
Neuropathy, another  manifestation  of  amyloidosis,  typically  is a sensory
polyneuropathy that involves  the  lower  extremities.   It  is  particularly
prevalent in hereditary amyoidosis, and also is seen in some cases of primary
or  myeloma  associated amyloidosis.  Carpal tunnel syndrome is seen in about
50% of patients.  Cranial neuropathies  may be seen in familial aamyloidosis.
Autonomic  neuropathic  involvement  can  lead   to   postural   hypotension,
incontinence,  impotence  and  sweating  disorders.   Cardiac amyloidosis can
present  as  cardiomegaly,  arrhythmia  or  intractable  heart  failure.   It
typically involves  the  myocardium,  but  can  involve  the  pericardium and
endocardium.  Patients may also develop  a  restrictive  cardiomyopathy  with
poor ventricular diastolic filling.  Coronary artery disease can also develop
due  to  amyloid deposits in the coronary arteries.  Atrial standstill may be
seen in some kinships.  EKG  findings  may include low voltage QRS complexes,
conduction  abnormalities  and   arrhythmias.    Echocardiograpy   may   show
refractile  changes  of  the  myocardium  that  are  described  as a granular
sparkling pattern.   Congestive  heart  failure  has  a  very poor prognosis.
Gastrointestinal  involvment  occurs  in  about  50%  of  cases  and   causes
esophageal,   small   and  large  bowel  motility  problems,  gastric  atony,
malabsorption, pseudo-obstruction, and  bleeding.   Patients  may complain of
diarrhea, dysphagia, hematochezia, or  melena.   Macroglossia  is  common  in
primary  and  myeloma  related  amyloidoses.   It  can  cause  dysphonia  and
difficulties with deglutition and breathing.  Hepatomegaly is found in 75% of
casess  of amyloidosis and is associated with elevation of the serum alkaline
pnhosphatase.  Portal hypertension and  elevation  of other liver enzymes are
unusual.  Splenomegaly may also  be  present  due  to  amyloid  infiltration.
Pulmonarhy  amyloidosis  is  seen  in  about  30%  of  pateints  with primary
amyloidosis.  Patients  with  secondary  amyloidosis  usually  are clinically
silent with lung lesions, even though lesions may be seen on  histopathologic
examination.   Patients can present with pulmonary nodules, hilar adenopathy,
tracheal-bronchial lesions, or diffuse alveolar infiltration.  Involvement of
the thyroid gland can result  in  a  firm symmetric nontender enlargerment of
the thyroid that clinically resembles  Hashimoto's  thyroiditis  or  Riedel's
struma.   DIAGNOSIS: Rectal biopsies are positive in about 80%, skin biopsies
50%, and abdominal fat  pad  biopsies  70%.   Other  sites  that may used for
biopsy include gingiva, nerve, kidney  and  liver.   All  tissues  should  be
stained  with  Congo  red and visulaized with a polarizing microscope for the
characteristic green birefringence of  amyloid.   About  90% of patients with
primary  amyloidosis  will  have   monoclonal   light   chains   on   protein
electrophoresis  of  the  serum  or urine.  Amyloid depostis can be localized
with injection of radiolabeled serum  amyloid  P protein.  TREATMENT: For the
most part, amyloidosis is progressive and has no cure.   Some  patients  with
primary  amyloidosis  may benefit from conbination therapy with melphalan and
prednisone.  Treatment of secondary amyloidosis  is aimed at treatment of the
underlying disease.  Chlorambucil has prolonged  survival  in  patients  with
juvenile   rheumatoid   arthritis   that   is  associated  with  amyloidosis.
Colchicine may be  useful  in  patients  that  have amyloidosis with familial
Mediterranean fever.   Digitalis  should  be  used  with  great  prudence  in
patients with amyloid cardiomyopathy as it can precipitate arrhythmias.

                   -AMYOTROPHIC LATERAL SCLEROSIS-
Amyotrophic lateral sclerosis  (ALS)  is  an idiopathic degenerative neuronal
disease that usually has its  onset  after  40  years  of  age.   It  has  an
incidence  of .8-1.2 per 100,000 and a prevalence of 4-6 per 100,000.  It may
be familial  in  8-10%  of  cases,  usually  following  an autosomal dominant
inheritance pattern,  but  occasionally  recessive.   Characteristically,  it
causes  no  sensory, autonomic or cognitive dysfunction, but is manifested by
mixed upper and  lower  motor  neuron  disease.   ALS typically presents with
weakness, atrophy and fasciculation in the hands with  spasticity,  cramping,
and hyperreflexia of the lower extremities.  The voluntary muscles of the eye
and urinary sphincter are spared.  There may be fasciculations and atrophy of
the  tongue.   Dysphagia and dysarthria are common, and caused by mixed upper
and lower motor neuron  disease.   Some  patients  (1-2%) may have a dementia
which can antedate the typical symptoms of ALS.  The main differential to  be
considered  is  cervical  spondylotic  myelopathy.   In  cervical spondylotic
meylopathy, or herniated cervical disc  syndrome,  there is neck and shoulder
pain, with sensory changes.  In ALS, the  EMG  will  show  fibrillations  and
positive  sharp  waves  in  advanced  disease,  which  may  be  absent early,
particularly if upper motor neuron  disease  is dominant.  Lower motor neuron
findings in the lower extremities and fibrillation potentials in  the  tongue
are  suggestive  of  ALS,  if  there  is no lumbar disease.  CSF findings are
usually normal with the exception  of  possibly  some slight elevation of the
the protein.  TREATMENT: There is  no  definitive  treatment  for  ALS.   The
spasticity  and  cramping  may  be treated with baclofen and diazepam.  Since
there is no treatment, the progression of the disease is relentless, and most
patients are dead within 5 years.  Aspiration may be the terminal event.

                  -ANAEROBIC INFECTIONS OF THE LUNG-
Anaerobic  infections of the lung can result from aspiration of oropharyngeal
contents into the lung in  patients  that  have altered mental states such as
alcoholism,  seizure,  anesthesia,  or  a  central nervous  system  disorder.
Patients may also develop anaerobic infections of  the  lung  in  those  with
endotracheal  tubes,  diseases  of  the  esophagus,  hematogenous spread from
distant sites  of  infection,  or  contiguous  spread  from subdiapharagmatic
abscess.  Many patients will aspirate during sleep,  but  defense  mechanisms
usually  prevent  infections.   Poor  oral  hygiene  predisposes to anaerobic
infections of  the  lung  because  of  the  high  concentrations of anaerobic
bacteria in oropharyngeal secretions.  Patients with pyorrhea and  gingivitis
may have up to 10 to the 12th power organisms/gram of tissue.  Alcoholics and
smokers are more susceptible because of suppression of respiratory epithelial
cilia  in  these  conditions.   Anaerobic  infections  of  the  lung produces
necrotizing  pneumonias,  lung  abscess  and  empyema.   Most  commonly,  the
infection is polymicrobial including Bacteroides melaninogenicus, Bacteroides
fragilis, Fusobacterium, and peptostreptococci.   Bacteroides fragilis is not
part of the oral flora, but nevertheless is  present  in  about  20%  of  the
infections.   In  about 40% of cases pneumococci and Staphyococcus aureus may
be   found.    Several   anaerobes   including   Bacteroides   fragilis,   B.
melaninogenicus, B. intermedius, B. ruminacolc, B gracilis and B. ureolyticus
are resistant to penicillin in about 25% of cases.  CLINICAL: The sequence of
development of anaerobic  infections  of  the  lungs  starts as an aspiration
pneumonitis which may be acute, subacute or chronic.  If  untreated,  it  can
progress  to  a  necrotizing  pneumonia  in the basilar segments of the lung,
followed by microabscesses which eventually coalesce to form a frank abscess.
The abscess can drain into the  airway  causing a foul smelling putrid sputum
or dissect into the pleural space setting up an empyema.  Empyemas  may  also
develop  from  bacteremia  secondary  to  pelvic  or  intestinal  infections.
Patients  may  have a chronic cough, fever, weight loss, putrid sputum, chest
pain,  night  sweats,  hisitory  of   aspiration  and  x-ray  evidence  of  a
necrotizing pulmonary infection.  Most cases of lung  abscess  have  a  fever
less  than 102 F. Patients with empyema often have fevers greater than 102 F.
Chills are uncommon.  Patients  that  develop  a subacute course may resemble
pulmonary TB or bronchogenic carcinoma.  The course may be indolent or acute.
The extent of the involvement of the lung is contingent upon the  volume  and
nature  of  the  aspirate.  Anaerobic infections are more common in the right
lung, and in those portions that  dependent, (posterior segments of the upper
lobes and the superior segments of the lower lobes when the aspiration occurs
in the supine position and  the  basilar  segments  of  the  lower  lobes  if
aspiration  occurs  in  the  upright  position).  Lung abscess takes from 1-3
weeks  to  develop  and  occurs  as  a  comlication  of  untreated  anaerobic
pneumonia.   These  patients  usually  present  with  a  subacute  or chronic
disease.  They have fever, cough, weight loss and anemia.  Putrid  sputum  is
found  in  about  50% of patients.  About 2/3 or the cases of empyema involve
the right pleural space.  The purulent  pleural fluid is usually loculated in
about 90% of cases, and most patients will have a putrid,  odiferous  sputum.
LABORATORY:   Sputa   analysis   is   unsuitable   for  culture,  because  of
oropharyngeal flora contamination.   Satisfactorhy  sources  for cultures and
Gram  stains  include  pleural   fluid,   transtracheal   aspirates,   blood,
transthoracic  pulmonary  aspirates  and  fiberoptic  aspirates collected via
protected brush technique.  However,  blood  cultures are rarely positive for
anaerobic organisms,  and  there  may  be  complications  from  transtracheal
aspirations,  including  hemorrhage  and  local  abscesses.   The  trachea is
sterile in about 80% of normal  individuals, while the remaining 20% may have
small quantities of anaerobes.  Thoracentesis  can  establish  the  diagnosis
because  of  the putrid odor that is present in almost all cases.  TREATMENT:
Since anaerobic  cultures  may  take  some  time  until  they becme positive,
treatment should be started based on the clinical situation.   Patients  that
present  outside  of the hospital in a community setting, with putrid sputum,
chest-x-rays cavities with an air fluid  level, are treated for lung abscess.
If the sputum is not putrid and  malordorous,  or  if  TB  or  neoplasms  are
considerations,  bronchoscopy  should  be  done  for  culture,  cytology  and
biopsies  of  endobronchial lesions.  Patients with mixed aerobic, anaerobic,
or anaerobic lung abscesses  should  improve  within  4-7 days.  If a patient
fails to improve after about 7-10 days, and is still febrile, a transthoracic
needle apsiration  may  be  necessary  to  secure  a  diagnosis.   Parenteral
antibiotic  treatment of anaerobic pulmonary infections should continue until
fever subsides and  stays  normal  for  several  days.   Following this, oral
antibiotics are given for about 6 weeks or until  the  chest  x-ray  resolves
completely.   Patients  with  lung  abscesses should be treated with postural
drainage and chest physical therapy.   If  patients with lung abscess fail to
undergo resolution, bronchoscopy should be done to ascertain why the drainage
is incomplete.  About  10-12%  of  patients  with  lungs  abscess  will  need
surgery.   Patients  with empyema will need a tube thoracostomy for drainage.
Patients that do not improve after one week of satisfactory thoracostomy tube
drainage will need either  insertion  of  multiple chest tubes, rib resection
for improved drainage, or pleurectomy.  ANTIBIOTIC  TREATMENT:  The  drug  of
choice  is  Clindamycin 600 mg IV q6h +/- an aminoglycoside or 3rd generation
cephalosporin.  Alternatively, Penicillin 2 million  U IV q4h may be started.
Uncomplicated pneumonias should be treated  for  7-14  days  with  parenteral
antibiotics.   Necrotizing pneumonias are usually treated for 14-21 days with
parenteral antibiotics.  Empyemas  are  treated  for  4 weeks with parenteral
antibiotics and lung abscess may require 6-12 weeks.  Parenteral  therapy  is
followed  by  oral penicillin V 500-750 mg QID, or penicillin + metronidazole
500 mg QID.  If Gram negative organisms such as Staph aureus or other aerobic
pathogens are cultured, therapy  is  dictated  by the sensitivity.  Anaerobic
empyemas secondary to  subdiaphragmatic  abscesses  will  need  coverage  for
Bacteroides fragilis and enteric gram negative bacilli, such as clindamycin +
aminoglycoside or third generation cephalosporin.

                              -ANEMIA-
MACROCYTIC  ANEMIA  WITH INCREASED RDW: Folate deficiency, B12 deficiency and
immune hemolytic anemia.   MACROCYTIC  ANEMIA  WITH  NORMAL RDW: Preleukemia,
aplastic anemia  and  alcoholism.   MICROCYTIC  ANEMIA  WITH  INCREASED  RDW:
Hemoglobin   H  disease,  S-beta  Thalassemia  and  iron  deficiency  anemia.
MICROCYTIC ANEMIA WITH NORMAL RDW:  Thalassemia  minor, and anemia of chronic
disease.  NORMAL MEAN CORPUSCULAR VOLUME WITH INCREASED RDW: Hemoglobinopathy
SS  or  SC,  sideroblastic  anemia,  myelofibrosis,  mixed  iron  and  folate
deficiency, early iron deficiency and folate  deficiency.   NORMAL  MCV  WITH
NORMAL  RDW:  Chronic liver disease, anemia of chronic disease, chemotherapy,
hemorrhage, chronic myelogenous  and  lymphnocytic  leukemia, aplastic anemia
hereditary spherocytosis.  CAUTION!!  False positive increased RDW can  occur
with  chronic  lymphocytic anemia if the absolute lymphocyte count > 150,000,
transfusion of normal cells into  a  patient with increased or decreased MCV,
fragmentation of RBC due  to  intravascular  hemolysis  and  cold  agglutinin
anemia.

  -ANGINA MANAGEMENT WITHOUT EXACERBATION OF CO-EXISTING DISEASES-
DIABETES MELLITUS: Diabetes increases  the  risk  of coronary artery disease.
Beta blockers are usually not used in insulin dependent diabetes  or  brittle
diabetics because they can mask hypoglycemia, worsen hypertriglyceridemia and
increase  glucose.   In  non  insulin dependent diabetes	beta blockers are
safer.  Beta blockers used in AMI  will improve morbidity and mortality, just
as they do in non diabetics.  In this case benefits may outweigh  the  risks.
PERIPHERAL  VASCULAR  DISEASE: Because beta blockers can aggravate peripheral
vascular disease they should  be  avoided  and  replaced with calcium channel
blockers which  possess  vasodilating  properties  and  in  addition  prevent
vasospasm.   ASTHMA AND COPD: Nitrates and calcium channel blockers should be
used in place of  beta  blockers  when treating angina.  However, oftentimes,
using low dose cardioselective B1 drugs as  atenolol  (Tenormin),  metoprolol
(Lopressor),  acebutalol (Sectral), or betaxolol (Kerlone) may be used if the
asthma or COPD  is  not  severe.   CONGESTIVE  HEART  FAILURE: CHF is usually
treated with digoxin, ace inhibitors and diuretics.  Nitroglycerin  is  given
for angina.  In some patients as the CHF resolves there is improvement in the
angina.  The combination of digoxin and diuretics could cause hypokalemia and
ventricular  arrhythmias  which  would  make the CHF worse.  Diuetics if used
should be used in low dosage as  the  use of ACE inhibitors will help resolve
the CHF.  If diuretics, ACE inhibitors, and potassium supplementation are all
used together, there is a chance of hyperkalemia,  as  ACE  inhibitors  spare
potassium  loss.  If angina cannot be controlled with nitroglycerin, a second
generation  dihydropryridine  calcium  antagonist  could  be  added  such  as
amlodipine  (Norvasc),  isradipine   (DynaCirc),   felodipine  (Plendil),  or
nicardipine (Cardene).  These agents are strong vasodilators of coronary  and
peripheral  vessels  and will not significantly slow the heart.  However, the
combination of ACE inhibitors and calcium blocker could cause hypotension, in
which case the dose  of  the  ACE  inhibitor  should  be lowered.  Do not use
verapamil (Isoptin, Calan), or diltiazem  (Cardizem)  in  CHF.   HYPERTROPHIC
CARDIOMYOPATHY:   Treatment   is  with  either  a  beta  blocker  or  calcium
antagonist.  If angina is  present,  it  is  usually relieved by these drugs.
Beta blockers  have  been  shown  to  reduce  sudden  death  in  hypertrophic
cardiomyopathy.   If  the patient is unable to tolerate beta blockers or they
are  ineffective  verapamil   may   be   used.    Calcium   blockers  of  the
dihydropyridine class should not be used as they do not reduce the heart rate
to facilitate filling.  Nitroglycerin should not be used for  angina  or  any
other  condition  in  hypertrophic  cardiomyopathy.  ARRHYTHMIAS: The primary
purpose in tachyarrhythmias is to  slow  the  rhythm and this can be achieved
with either diltiazem, verapamil, or a beta blocker.  The use of these  drugs
will  also  relieve  angina.   They  function  by  prolonging  AV conduction,
blocking reentrant pathways, and  slowing  the ventricular response in atrial
flutter and fibrillation.  Verapamil and diltiazem may both be  given  IV  in
the  acute  situation  in  order  to  control  the ventricular rate in atrial
flutter or fibrillation.  Inderal  may  be  added  if the ventricular rate is
insufficiently slowed.  Verapamil and diltiazem are both  contraindicated  in
Wolf-Parkinson-White  syndrome  because impulses are preferentially conducted
through the accessory pathway due  to  AV blockade by the calcium antagonist.
In paroxysmal supraventricular tachycardia, verapamil may be used in  a  dose
of 5-10 mg IV, followed by PO verapamil 80-120 TID or diltizaem 90 mg tid po.
Again,  drugs  in  the  dihydropyridine group should not be used because they
promote  tachycardia  and  could  exacerbate  angina.   These  drugs  include
nifedipine (Adalat, Procardia),  isradipine (DynaCirc), felodipine (Plendil),
and nicardipene (Cardene).  Amlodipine (Norvasc) has been approved for use in
angina but doesn't slow the heart.  Calcium antagonist  are  not  helpful  in
ventriular  arrhythmias.  For these arrhythmias, beta blockers may be used as
they will also ameliorate  concomitant  angina.  Hydralazine (Apresoline) and
minoxidil (Loniten), should not be used in patients with angina as  they  can
exacerbate  or  precipitate angina.  ACE inhitors are not directly helpful in
alleviating angina, but indirectly, by decreasing  the work of the heart, may
relieve angina.  Also when using nitrates for  angina,  tolerance  should  be
avoided by using intermittent PO, IV, ointment, and patch doses.

                         -ANGINA (Unstable)-
Unstable angina may be broadly defined as significant chest, left arm, jaw or
neck  pain  and  dyspnea  that  occurs  with rest or with minimal exercise or
mental stress.  The coronary lesion responsible for unstable angina is plaque
rupture with fissure formation  and  subsequent thrombus formation.  If there
is complete luminal thrombotic occlusion, myocardial infarction  will  ensue.
Partial  occlusion  may  produce  unstable  angina  or  non Q wave myocardial
infarction.  The thrombus may undergo spontaneous lysis with complete healing
or go on to organization  with  or without symptoms.  Alternatively, portions
of the thrombus may discharge with embolization.  The  status  of  collateral
circulation  will  play an important part as far as symptomatology.  Unstable
angina  is  treated   with   antithrombotic   and  antiplatelet  therapy,  IV
nitroglycerin and beta blockers.  These will all be  subsequently  discussed.
ASA:  ASA  should be given initially as 160 mg loading dose followed by 80 mg
daily.  This is used in  combination  with Heparin.  HEPARIN: Give IV heparin
as a loading dose of 100 U/kg bolus followed  by  an  infusion,  titrate  the
partial  thromboplastin  time  to 2-3 times control.  The continuous infusion
rate is 1000 U/hr or 15 U/kg.   The  heparin should be given for at least 3-4
days if the patient is stable, before  undergoing  coronary  angiography  and
PTCA.   This  interval  of  heparin  therapy  may  allow spontaneous lysis of
residual mural thrombus.   NITRATES:  IV  nitroglycerin  has several salutary
attributes that favor its use in unstable angina.  It has a short  half  life
and  therefore  is  safe and well tolerated.  The dose can be titrated and is
inexpensive.  It  will  reduce  preload  and  lower  left ventricular filling
pressures.  It also will increase coronary collateral blood flow  and  dilate
epicardial  coronary luminal diameters.  It also will reduce wall tension and
lower oxygen  requirements.   Potential  side  effects  of  nitroglycerin are
minimal and  can  be  averted  with  awareness  of  the  clinical  situation.
Hypotension  and  reflex tachycardia may occur which will increase myocardial
oxygen consumption with  subsequent  deterioration.  Therefore, nitroglycerin
should not be given if there is low systemic  blood  pressure.   In  patients
with  inferior  infarction,  right ventricular dysfunction can occur in which
nitroglycerin administration could compromise right ventricular function with
further  hypotension.    A   third   complication   that   may  develop  with
nitroglycerin administration is tolerance.  This can  be  overcome  partially
with  higher  doses  and  disrupting the continuous administration.  Start IV
nitroglycerin at  10  ug/min  and  titrate  up  to  between  50-200 ug/min as
tolerated  by  the  patient's  blood  pressure  and  heart  rate.    The   IV
nitroglycerin should be continued for a least 1-3 days.  This may be followed
with  heart  rate-lowering  calcium  channel  blockers  such  as diltiazem or
verapamil, or beta blockers.   BETA  BLOCKERS:  If  the patient has excessive
blood pressure or tachycardia either caused  by  nitroglycerin  or  increased
catecholamines  secondary  to  chest  pain,  beta  blocker  administration is
helpful.  IV metoprolol can be used giving 5 mg boluses every 5 minutes for a
total of 3 doses, followed by 50 mg po  qid for 2 days and then 50-100 mg bid
daily.  DECISIONS: If the patient stabilizes with the above  measures,  defer
coronary  angiography  and  continue  with  ASA and warfarin, and vasodilator
therapy.  Do a Thallium  perfusion  image.   If  the thallium scan determines
that the patient is at high risk, the patient should have immediate  coronary
angiography  with  possible  PTCA  or  CABG.   If the Thallium scan shows low
subsequent risk, continue the ASA  and  warfarin and discharge with follow up
observation.   If  the  patient  doesn't   stabilize   with   heparin,   ASA,
nitroglycerin,  and  beta  blockers,  these  should be continued and coronary
angiography done.  Depending on the  findings  of angiography the patient may
need  CABG  or  PTCA  and  possibly  supported  with   intra-aortic   balloon
counterpulsation.   CALCIUM CHANNEL BLOCKERS: Several multicenter trials have
shown that monotherapy with nifedipine is associated with high rates of death
and recurrent  MI  as  compared  with  placebo.   Tis dihydropyridine calcium
blocker can produce hypotension, and reflex tachycardia  and  should  not  be
given  as monotherapy or together with nitrates.  On the other hand verapamil
and diltiazem can reduce myocardial oxygen consumption, can be used with beta
blockers if there is no  LV  dysfunction and are cardioprotective in patients
following acute non-Q  wave  myocardial  infarction.   THROMBOLYTIC  THERAPY:
Several  small tirals have demonstrated that thrombolytic therapy yields only
minimal benefit, and for the most part will fail in preventing progression to
MI.  In the TIMI IIIB trial,  tissue  plasminogen activator was used in non-Q
wave infarction and unstable angina.  There was no effect on 6 week mortality
or nonfatal reinfarction.

                -ANGIOPLASTY (Percutaneous Coronary)-
Coronary  angioplasty  has  been used since 1977, when Gruntzig performed the
first percutaneous transluminal coronary  angioplasty  (PTCA).  Since then it
has been  used  in  patients  with  stable  angina,  unstable  angina,  acute
myocardial  infarction,  and  following  thrombolytic therapy.  Complications
rates are now  less  than  5%.   PTCA  has  a  success  rate  of about 90% in
producing a  luminal  diameter  that  is  no  less  than  50%  following  the
procedure.   In  the  10%  of  PTCAs  that  fail,  it is because the stenosis
suddenly closes following PTCA, or  the  stenosis  is too tight for the guide
wire or balloon to pass, or the stenosis simply cannot be dilated.   PTCA  is
less  successful  in  those  stenoses  that  are  calcified, long, angulated,
eccentric, associated with  intraluminal  thrombus  or  those  located at the
ostium of a branching area.  Multivessel angioplasty is  now  performed  with
great  success.   Additional advances in revascularization technology has now
included  other   methods   such   as   directional  atherectomy,  rotational
atherectomy, laser angioplasty and intracoronary stents.  However, even  with
these  advancements,  angioplasty still has 4 limitations such as restenosis,
acute closure, thrombosis  and  chronic  total occlusion.  RESTENOSIS usually
occurs within the first 6 months following the  initial  procedure  which  is
reflected  as recurrent, stable angina similar to the patients original pain.
If the patient fails to develop  restenosis  by 6 months, the likelihood that
it will occur within the next 3 years is less than 3%.  Greater than  80%  of
restenosis occurs within the first 3 months of angioplasty.  These restenoses
seldom  lead to myocardial infarction, arrhythmia, or unstable angina.  About
20% of restenoses are  silent.   Treadmill  exercise testing, with or without
thallium imaging, is usually successful in demonstrating the restenosis.  The
angiographic restenosis rate ranges from 33-50%, but the clinical  restenosis
rate  ranges from 20-25%.  The causes of coronary restenosis are a neointimal
hyperplasia composed of smooth  muscle  cells and fibroblasts, vessel recoil,
and thrombus formation.  The more the coronary artery is injured, the thicker
the  neointima  becomes.   Other  risk  factors  that  are  associated   with
restenosis  include  continued  smoking,  unstable angina, diabetes mellitus,
male sex, systemic  arterial  hypertension, hypercholesterolemia, vasospastic
angina, end stage renal disease, saphenous vein  grafts,  proximal  stenosis,
left anterior descending artery involvement, stenosis greater than 5-10 mm in
length,  chronically occluded arteries, use of undersized balloons, and small
residual lumens.  Angiographic risk  factors  for restenosis include thrombus
at the dilation site, tight initial stenosis,  chronic  total  occlusion  and
saphenous  vein  grafts.  Several pharmacologic agents have been used without
lasting benefit.   These  include  aspirin,  warfarin, heparin, dipyridamole,
calcium  channel  blockers,  ACE  inhibitors,  corticosteroids,  prostacyclin
analogs,  and  low  molecular  weight   heparin.    Lovastatin,   fish   oil,
triazolopyrimidine,  and  angiopeptin  may  have some benefit.  Restenosis is
usually treated with repeat PTCA which  is  more likely to be successful than
the first, and is less likely to  be  associated  with  acute  complications.
ACUTE  OR  ABRUPT  CLOSURE  is another complication of angioplasty.  The risk
factors for abrupt closure of the  coronary artery in patients undergong PTCA
include, unstable angina, multivessel coronary artery  disease,  female  sex,
eccentric  stenosis, calcified stenosis, stenosis located at or near a branch
or  bend  of  the   artery,   thrombus  formation  that  is  angiographically
demonstrable, stenosis greater than 10 mm or 2 luminal diameters  in  length,
severe  pre PTCA stenosis, diffusely diseased coronary artery, utilization of
oversized  balloons,  and extensive arterial dissection.  In most cases acute
closure is manifested  by  chest  pain  and  ECG  evidence for ischemia which
requires immediate repeat PTCA or bypass surgery.   Repeat  PTCA  is  usually
successful in about 50% of patients.  If this fails, a perfusion catheter may
be  used.  This catheter has proximal and distal balloon apertures, which can
establish perfusion to the distal  artery  for extended balloon inflations of
10-30 minutes.  In most cases, this  perfusion  catheter  is  effective.   If
unsuccessful, but there is good collateral circulation with a small amount of
jeopardized myocardium at risk, medical therapy may be elected.  If this does
not  obtain,  the  placement  of  an  intracoronary  stent may be considered.
However, this has a procedure rate infarction as high as 45%, even though the
blood flow may be restored  initially.   Furthermore, closure may occur later
in the following weeks in 10-15%.  If all of these  methods  fail,  emergency
surgery  will  be needed.  There is an increased risk of mortality associated
with emergency bypass surgery when  compared  to elective bypass surgery, but
those that do survive seem to have a good long term prognosis.  About  25-50%
of  patients  with  abrupt artery closure followed by successful surgery will
develop  a  Q  wave  myocardial  infarction.   PREPARATION  OF  PATIENTS  FOR
ANGIOPLASTY: Patients are given 325 mg of aspirin prior to and following PTCA
in order to  obviate  closure  of  the  dilated  artery.   If  the patient is
allergic to ASA, ticlopidine may be given, starting 5 days prior to PTCA.  In
order to diminish the incidence of coronary arterial thrombosis,  heparin  is
usually given 10,000-15,000 units IV during the procedure.  Nitroglycerin may
be  given  either intracoronary or sublingual, and a calcium channel blocking
agent may be given to decrease the ischemia that is produced during inflation
of the balloon.

                             -ANION GAP-
AG = Na-(Cl+HCO3).   Normal  AG=10-14  mEq/L.   An  anion  gap  > 14 suggests
metabolic acidosis, lab  error,  decreased  calcium,  increased  sulfate  and
phosphate,  administered  penicillin,  nitrates,  carbenicillin, unidentified
anions in uremic and hyperosmolar  states, methanol, salicylate poisoning and
ethylene glycol.  An anion gap < 10 suggests  hypoalbuminemia,  IgG  myeloma,
administered lithium, lab error or calcium increase.

                      -ANKYLOSING SPONDYLITIS-
Ankylosing spondylitis (AS)  is  a  disease  affecting  young  males  and  is
characterized   by  chronic  inflammatory  changes  of  the  axial  skeleton,
sacroiliac and peripheral joints.   New  osseous  formation tends to occur at
the attachment of ligaments and tendons to bones.  About  25  %  of  patients
will have peripheral joint involvement.  The incidence is about .5-5 per 1000
in white males.  Blacks and women do not have a high incidence.  The ratio of
male:female  is  about 3:1.  A patient is at risk if he has the HLA-27 marker
and there is  a  positive  family  history.   There  is  about  a 10% risk of
contracting AS for a HLA-B27 positive child of a parent  who  has  Ankylosing
spondylitis.   CLINICAL: There is usually an insidious onset of low back pain
that is initially  intermittent.   The  beginning  of  the disease is usually
between puberty and somewhere in the twenty year old range.   There  is  pain
and morning stiffness that improves with physical activity.  There is pain in
the  sacroiliac  areas  that may radiate down the posterior thighs.  The pain
may be partially eased with  a  bent  over position.  The patient may develop
anemia, fatigue, fever and weight loss.  As the disease  progresses  the  low
back  pain  tends  to ascend to the cervical area and there is restriction of
movement with the normal  lumbar  curve  becoming  flattened and the thoracic
curve becoming more pronounced.  Because of involvement of the costovertebral
joints, chest expansion also becomes limited.  In about 50% of cases there is
peripheral involvement mainly in the knees, hips and shoulders.  There may be
enthesopathic changes involving the insertions of the Achilles tendon and the
plantar fascia into the calcaneus.  EXTRAARTICULAR INVOLVEMENT: In about  33%
of  patients there are recurrent attacks of iritis that is usually unilateral
and needs to be monitored as it may develop into glaucoma.  The iritis may be
the sole symptom before the  full  syndrome  of AS evolves.  Lung involvement
may  produce  pulmonary  fibrosis  of  the  upper   lobes,   cavitation   and
bronchiectasis.  Aspergillus infection may intervene.  These findings tend to
occur  later  in  the  disease  of  AS.   Lung involvement of this nature may
simulate pulmonary tuberculosis.  Involvement of the heart can produce aortic
insufficiency  and  heart   block   after   several   years  into  ankylosing
spondylitis.  There may be aortic root dilatation in 20% of cases.  An aortic
regurgitant murmur develops in only about  2%.   Neurologic  involvement  can
develop  in  the  advanced  cases  with fractures and spinal cord compression
occurring in  an  osteoporotic  and  fused  cervical  spine.   A cauda equina
syndrome characterized by pain and sensory loss in the lower extremities  and
bladder/bowel malfunction can develop.  In this syndrome there may be urinary
incontinence,  impotence,  decreased anal and bladder sensation and decreased
or absent ankle reflexes.  Secondary renal  amyloidosis occurs in about 4% of
patients  and  a  minority  of  patients  may  develop  an  IgA  nephropathy.
DIFFERENTIAL  DIAGNOSIS:  Differential  diagnosis  would  include  rheumatoid
arthritis,   Reiter's   syndrome,   inflammatory   bowel   disease-associated
spondylitis,  diffuse  idiopathic   skeletal   hyperostosis   and   psoriatic
arthritis.   In  AS  there  is  rarely involvement of the small joints of the
hands and feet  as  in  rheumatoid  arthritis  and  the  rheumatoid factor is
negative in AS.  In diffuse idiopathic skeletal hyperostosis the  sacro-iliac
joints  are  not affected, the sedimentation rate is normal, and there is not
an increased incidence  of  HLA-B27.   This  disease  occurs typically in men
around the age of  50  or  greater.   Similarly,  there  may  be  ligamentous
calcification  affecting  the cervical and lower thoracic spine.  LABORATORY:
The incidence of HLA-B27 tissue antigen  is present in the general population
at about 5-8%.  In AS the incidence is 90%.  HLA-B27, however  may  be  found
with a greater frequency in Reiter's syndrome, inflammatory bowel disease and
psoriasis.   Patients  with  degenerative joint disease, rheumatoid arthritis
and gout do not  have  a  higher  incidence  than the normal population.  The
sedimentation rate is elevated in  about  85%  of  cases.   There  may  be  a
leukocytosis and anemia present, but the rheumatoid factor is negative in AS.
X-ray  of  the  sacro-iliac  joints  may  show  sclerosis and erosions of the
sacral-iliac joints.  Identical x-ray changes  of the sacral-iliac joints may
be  seen   in   Reiter's   syndrome,   psoriasis   and   inflammatory   bowel
disease-associated   arthritis.    There  is  apophyseal  joint  involvement,
calcification of the anterior  and  lateral spinal ligaments, ossification of
the annulus fibrosus, and squaring  and  demineralization  of  the  vertebral
bodies.   CT of the sacral-iliac joints may be needed early in the disease in
order to detect  early  changes.   To  detect  new  periosteal bone formation
x-rays of the ischial tuberosities, iliac crest and calcanei should be  done.
TREATMENT:  There  is  no cure and treatment is symptomatic with nonsteroidal
anti-inflammatory drugs such as indomethacin 50  mg tid or qid.  Side effects
of indomethacin include peptic ulcer, renal insufficiency,  headache,  nausea
and  vomiting,  depression  and  dizziness.   Other NSAID's such as naproxen,
sulindac, piroxicam, fenoprofen,	and  tolmetin  can  be  tried.  AS has an
unpredictable course and prognosis may be good if mobility  and  and  upright
posture can be maintained.  Flexion contractures of the hip and ankylosis may
contribute to the poor posture.  General measures that may be of help include
posture training and range of motion exercises along with breathing exercises
several  times  a  day.   Swimming, using a firm mattress and sleeping in the
prone or supine position without a pillow  may be of benefit.  If the patient
smokes, he should quit in order to help prevent obstructive  and  restrictive
lung disease.  Steroids or cytotoxic agents are not beneficial.  Steroids may
be  needed  for  the  acute  iritis  that  develops  along  with  mydriatics.
Occasionally  intra-articular  injections may help decrease severe peripheral
joint inflammation.  Enteric coated sulfasalazine  can be helpful starting at
a dose of 500 mg/day and then increasing by 500 mg/day at weekly intervals to
a one gram bid maintenance.

                              -ANOREXIA-
Anorexia  and  weight  loss are linked diagnostically.  Initially the patient
should have a CBC, chemistry panel, UA, ESR, thyroid funtion testing, fasting
plasma cortisol and ECG.  All  medications  that the patient is taking should
be  reviewed.   The  following  medications  may  be   implicated:   digoxin,
laxatives,   thiazides,   sedatives,  psychotropics,  appetite  suppressants,
narcotics, levodopa, and  antibiotics.   Endocrine  disorders should be ruled
out as a cause, such as diabetes, hyperparathyroidism, hypercalcemia, thyroid
disease, and adrenal insufficiency.  CNS disease  also  may  be  cause.   Any
patient  complaining of headaches, visual disturbance, papilledema or cranial
nerve involvment and anorexia should receive a  CT or MRI of the head to rule
out CNS tumors, particularly hypothalmalic tumors.  Gastrointestinal  disease
are  also  capable of causing anorexia and weight loss.  Malignancy of the GI
tract can cause weight loss (swallowing problems, gastric outlet obstruction,
esophageal obstruction or  motility  difficulties, biliary disease, abdominal
pain,  pancreatitis,  and  oral  pain).   Malabsorption  diseases   such   as
inflammatory  bowel disease, parasitic diseases, celiac sprue, and pancreatic
insufficiency should be ruled out.  Also consider peptic ulcer, hepatitis, GI
reflux  disease,  and  esopohageal   motility  disease.   Consider  obtaining
flexible sigmoidoscopy, upper GI with small bowel follow through,  and  stool
for  blood,  fat,  and parasites.  Psychological diseases to consider include
depression,  alcoholism,  drug  abuse,  psychosis,  anxiety,  bereavement and
dementia.  Anorexia and bulimia nervosa affect 1-4% of women and are  usually
diagnosed  in the second and third decades, but can occur in the thirties and
forties.  In these diseases there is a disturbed perception of body image, an
intense obsession with weight loss,  and  a fear of obesity.  Bulimia nervosa
have binge eating in association with self induced  vomiting,  cathartic  and
diuretic   abuse.    Other   medical   disease   for   consideration  include
cerebrovascular disease, abdominal ischemia, cardiopulmonary disease, chronic
infection and malignancy.

             -ANTIARRHYTHMIC AGENTS (Classification)-
CLASS  IA: Quinidine sulfate is given as 200-400 mg q6h PO.  Oral long acting
at 330-660 mg q8h.  The therapeutic  range  (TR) is 2.3-5 ug/ml and the major
route of excretion (MRE) is  hepatic.   Side  effects  are  QT  prolongation,
torsades  de pointes, conduction block, ventricular tachycardia, hypotension,
diarrhea,  thrombocytopenia,  vomiting,  and  enhanced  AV  nodal conduction.
Procainamide (Pronestyl) is given PO at 250-750 mg q4h.  Procan SR  is  given
500-1500  mg  q6-8h.   Give IV loading dose of 10-15 mg/kg at 25 mg/min, then
1-6 mg/min.  The TR is  4-10  ug/ml  and  MRE is renal.  Side effects include
lupus like syndrome (+ANA, arthralgias), agranulocytosis,  conduction  block,
and  polymorphic  ventricular  tachycardia.   Disopyramide (Norpace) is given
100-200 mg q6-8h PO or IV at 10-15 mg/min up to 3 mg/kg.  The TR is 2-5 ug/ml
and the  MRE  is  both  hepatic  and  renal.   Side  effects  include urinary
retention, constipation and CHF.  Moricizine (Ethomozine) is given at 150-300
mg q8-12h PO.  Side effects include new  or  exacerbated  arrhythmias,  heart
failure,  elevated  liver  enzymes and thrombocytopenia.  CLASS IB: Lidocaine
(Xylocaine) is given IV at 1-2  mg/kg  at 20-50 mg/min; then 1-4 mg/min.  The
TR is 1-5 ug/ml and the MRE is hepatic.  Side  effects  include  paresthesia,
dysarthria,  seizures,  and  drowsiness.  Mexiletine (Mexitil) is given PO at
200-400 mg q8h.  The TR  is  4-10  ug/ml.   The MRE is hepatic.  Side effects
include CHF, hypotension, tremor, dizziness, paresthesia, and nausea.   CLASS
IC:  Flecainide  (Tambocor)  is  given PO at 100-200 mg q12h.  The TR is .2-1
ug/ml.  The MRE  is  hepatic.   Side  effects  include CHF, conduction block,
arrhythmia  aggravation,  cardiac   arrest,   increased   pacing   threshold,
hypotension,   visual   disturbances,   paresthesia,  insomnia,  and  tremor.
Encainide (Enkaid) is given PO at  25-50  mg  q8h.  The MRE is hepatic.  Side
effects include VT, CHF, cardiac arrest, conduction  blocks,  and  aggravated
arrhythmias.   Propafenone (Rhythmol) is given PO at 150-300 mg q8h.  The MRE
is hepatic.  Side effects  include  conduction block, hypotension, headaches,
tremor, and nausea and vomiting.  CLASS II: Propranolol (Inderal) is given PO
at 10-100 mg q6h or IV at .1 mg/kg in divided 1 mg doses.  The TR is  .04-.1.
The MRE is hepatic.  Side effects include CHF, bronchospasm, SA and AV block,
bradycardia, Raynaud's phenomenon, hypotension, and hypoglycemia.  Metoprolol
(Lopressor)  is  given  PO at 50-200 mg BID or IV in acute MI as 5 mg q 2 min
x3, then 50 mg q6h PO x 48h, then  100  mg PO BID.  The TR is .5-.1.  The MRE
is hepatic.  Side effects are the same as propranolol.   Esmolol  (Brevibloc)
is  given  IV  at  500  ug/kg/min for 1 min, then 50 ug/kg/min for 4 min.  If
desired effect is not achieved in 5 min, repeat the loading dose and increase
to 50-200 ug/kg/min.  Excretion is  by  liver.  Acebutolol (Sectral) is given
PO at 200-600 mg BID.  The MRE is hepatic and renal.  CLASS  III:  Amiodarone
(Cordarone)  is  given  PO  loading  dose  of 800-1600 mg/day x 1-3 wks, then
600-800 mg/day x 2-4 wks, then  200-400  mg/day.  The TR is 1-2.5 ug/ml.  The
MRE is hepatic.  Side effects include hyper/hypothyroidism, corneal deposits,
hypotension, and skin photosensitivity.  Bretylium (Bretylol) is given IV  at
5-10 mg/kg at 1-2 mg/min, then .5-2 mg/min.  The TR is .5-1.5 ug/ml.  The MRE
is renal.  CLASS IV: Verapamil is given 80-120 mg q8h PO or .075-.15 mg/kg IV
over 1-2 min.  If unsuccessful, repeat IV in 10 min.  The TR is .1-.15 ug/ml.
The  MRE is hepatic.  Side effects include SA and AV block, hypotension, CHF,
constipation, and sinus bradycardia.  Diltiazem is given PO at 30-90 mg q6-8h
or IV at .25 mg/kg over 2 min.  Repeat  .35  mg/kg over 2 min IV in 15 min if
needed followed by infusion of 10-15  mg/hr.   Excretion  is  hepatic.   Side
effects  as verapamil.  OTHER: Adenosine (Adenocard) is given IV rapidly at 6
mg.  If unsuccessful give 12 mg  IV  in  1-2 min.  Side effects are flushing,
headache, nausea, dyspnea, chest pain,  dizziness,  AV  block,  palpitations,
tingling and apprehension.  All of these may be transient.

                   -ANTIBIOTICS IN RENAL FAILURE-
The  following  creatinine  clearance  format  sequence  will be used for the
following antibiotics: 50-80 * 50-10 * < 10: AMPICILLIN/SULBACTAM 1-2 G q6h *
1-2 G q6h * 1-2 G q12h.  AZLOCILLIN 2-4 G q4-6h * 1.5-2 G q8h * 1.5-3 G q12h.
AZTREONAM: 1-2 G q8-12h * 1-2  G  q12-18h  * 1-2 G q24h.  CARBENICILLIN 5-6 G
q4h * 2-3 G q6h * 2 G q12h (avoid).  CEFACLOR: 250 mg q8h *  usual  *  usual.
CEFAMANDOLE: .5-2 G q6h * 1-2 G q8h * .5-1 G q12h.  CEFAZOLIN: .5-1.5 G q8h *
.5-1  G  q8-12h * .25-.75 G q18-24h.  CEFONICID: 8-25 mg/kg q24h * 4-15 mg/kg
q24-48h * 3-15 mg/kg q3-5 days.  CEFOPERAZONE: 1-2 G q 6-12h * usual * usual.
CEFOTAXIME: 1-2 G q4-6h * 1-2 G q6-12h * 1-2 G q12h.  CEFOTETAN: 1-2 G q12h *
1-2 G q24h * 1-2 G q48h.  CEFOXITIN:  1-2  G  q8-12h * 1-2 G q12-24h * .5-1 G
q12-48h.   CEFTAZADIME:  1-2  G  q8-12h  *  1  G  q12-24h  *  .5  G  q24-48h.
CEFTIZOXIME: .5-1.5 G q8h * .25-1 G q12h * .25 G q24h.  CEFTRIAXONE:  .5-1  G
q12-24h * usual * usual.  CEFUROXIME: .75-1.5 G q8h * .75-1.5 G q 8-12h * .75
G  q24h.   CLINDAMYCIN:  300-900  mg  q 6-8h * usual * usual.  CIPROFLOXACIN:
.25-.75 G q12h * .25-.5 G q12h  *  .25-  .5 G q18h.  DOXYCYCLINE: 100 mg q12h
*usual * usual.  ERYTHROMYCIN: 1 G q6h * usual * usual.  ETHAMBUTOL: 15 mg/kg
q24h * 15 mg/kg q 24-36h * 15 mg/kg q48h.  FLUCYTOSINE: 37  mg/kg  q6h  *  37
mg/kg  q12-24h  *  not recommended.  GANCICLOVIR: 2.5 mg/kg bid * 2.5 mg qd *
1.5 mg qd.  GENTAMICIN:  loading  dose  of  2 mg/kg, then (1-1.5 mg/kg)/serum
creatinine   q8h.    (calculated   creatinine   clearance=(140-age)xkg/72   x
creatinine x (.85 if female).  IMIPENUM: .5 G q6-8h * .5  G  q8-12h  *  .5  G
q12h.   KETOCONAZOLE: 200-400 mg q12-24h * usual * usual.  METHICILLIN: 1-2 G
q6h * 1-2 G q8h *  1-2  G  q12h.   METRONIDAZOLE:  .5  G q6h * usual * usual.
MEZLOCILLIN: 3-4 G Q4-6h * 3 G q8h * 2 G q8h.   NAFCILLIN:  .5-2  G  q4-6h  *
usual  *  usual.  NORFLOXACIN: 400 mg bid * 400 mg qd * 400 mg qd.  OXACILLIN
.5-2 G q4-6h * usual * usual.  PENICILLIN G CRYST: 1-4 MU q4-6h * usual * 1/2
of usual.  PENTAMIDINE: 4  mg/kg  q24h  *  4  mg/kg  q24-36h  * 4 mg/kg q48h.
PIPERACILLIN: 3-4 G q4-6h * 3 G q8h * 3 G q12h.  RIFAMPIN: 600 mg/day * usual
* usual.  STREPTOMYCIN: 7.5 mg/kg q24h  *  7.5  mg/kg  q24-72h  *  7.5  mg/kg
q72-96h.    TICARCILLIN:   3   G   q   4h   *   2-3  G  q6-8h  *  2  G  q12h.
TICARCILLIN/CLAVULANATE:  3   G   q4h   *   2-3   G   q6-8h   *   2  G  q12h.
TRIMETHOPRIM/SULFAMETHOXAZOLE: 3-5 mg/kg q18h  *  3-5  mg/kg  q24h  *  avoid.
VANCOMYCIN: 1 G q 1-3 days * 1 G q3-7 days * 1 G q7-14d.

     -ANTICOAGULANT INR RECOMMENDATIONS FOR VARIOUS SITUATIONS-
Prophylaxis of venous thrombosis in high risk surgical procedures:  2-3  INR.
Treatment  of  pulmonary embolism: 2-3 INR.  Prevention of venous thrombosis:
2-3 INR.  Mechanical  prosthetic  heart  valves  at  high  risk: 2.5-3.5 INR:
Prevention  of  embolization  in  acute  myocardial  infarction:   2-3   INR.
Prevention  of  embolization  in  tissue  heart  valves:  2-3.  Prevention of
embolization in valvular heart disease:  2-3 INR.  Prevention of embolization
in atrial fibrillation: 2-3 INR.  Prevention of embolization in patients with
recurrent systemic embolism: 2-3 INR.

                          -ANTICOAGULATION-
RHEUMATIC MITRAL VALVE DISEASE: Patients with mitral rheumatic  stenosis  and
mitral  regurgitation  have  arterial  emboli  of  1.5-4.7%/pt/year.   If, in
addition, the patient has atrial  fibrillation,  there  is a 7 fold increase.
Warfarin is  given for patients with mitral  valve  disease  with  associated
chronic  or  paroxysmal  atrial  fibrillation  or  in those patients in sinus
rhythm with a left atrium of 5.5 cm or greater.  The international normalized
ratio (INR) is  kept  at  2-3  unless,  in  spite of optimal anticoagulation,
embolization continues.  In these cases dipyridamole may be added at a  daily
dose  of  225-400  mg/day.   CARDIOMYOPATHY:  Patients  that  have dilated or
hypertrophic  cardiomyopathies  can   develop   AF   when  associated  mitral
regurgitation and left  atrial  enlargement  develop.   Patients  with  these
cardiomyopathies  do  not  tolerate  AF well and will need to be electrically
converted under the  protection  of  heparin  if  DC  cardioversion is needed
immediately.  If  not  warfarin  can  be  started  about  3  weeks  prior  to
conversion.   The  INR  should be kept between 2-3 and the warfarin continued
for life after conversion.   Left  ventricular  thrombi  can occur in dilated
cardiomyopathies  also.    PREGNANCY   AND   ANTICOAGULATION:   Warfarin   is
teratogenic,   particularly   in   the   first  trimester  as  it  cause  CNS
abnormalities.  It  crosses  the  placental  barrier  and  later in pregnancy
hemorrhage can compromise the health of the fetus and the mother.  Once it is
known that the patient is pregnant the patient should be changed to  heparin.
Subcutaneous heparin is given in a dose of 12,000-15,000 U q12h.  The aPTT is
determined  about  6  hrs after injection and is kept between 1.5-2 times the
control.  The most significant side effect of heparin is thrombocytopenia and
occurs in about 10%  of  patients.   MECHANICAL PROSTHETIC VALVES: Mechanical
valve  prostheses  such  as  the   Starr-Edwards,   Bjork-Shiley,   and   the
Lilleheia-Kaster prostheses are associated with thromboembolism regardless of
whether   they  are  inserted  in  the  mitral  or  aortic  areas.   Warfarin
anticoagulation can reduce  this  from  23  episodes/100 patients/year to 2.5
episodes/100 patients/year.  The INR should be kept between  3-4.5  or  a  PT
ratio   of  1.5-2.0.   Should  recurrent  emboli  still  occur  with  optimal
warfarinization, the addition of  ASA  to  1  gram/day or dipyridamole at 400
mg/day  can  further  reduce  the   thromboembolic   events   to   1.8%/year.
BIOPROSTHETIC  VALVES:  Patients  with  biprosthetic  mitral  valves are more
likely  to  embolize  than  those  in  the  aortic  position.   The  risk  of
embolization after implantation is about 10%  for patients in sinus rhythm to
16% for those with AF over a 3 year period.  Warfarin is  usually  prescribed
for  6-12 weeks after implantation, whether in the mitral or aortic position.
ATRIAL FIBRILLATION: The incidence of  stroke  in patients 60-69 years of age
without AF is 9/1000 and 43/1000 with AF.  The  Boston  Area  Anticoagulation
Trial  for  AF  demonstrated that warfarin decreased the incidence of embolic
stroke from 3%/yr to .4%/year.   The  Copenhagen  (AFASAK) study also found a
64% decrease in strokes.  The INR is kept at 2-3  because  of  the  increased
hemorrhage  found  in  elderly  patients.   For  lone  AF  occurring in young
patients, anticoagulation therapy is not  needed.  Patients with AF secondary
to thyrotoxicosis occurs in about 30% of patients and about 33% of those with
AF will have cerebral embolization.  Therefore, warfarin is  indicated  early
in  thyrotoxicosis  until  a  euthryroid  and  sinus  state  can be achieved.
MYOCARDIAL INFARCTION: Patients with  large  anterior  AMI have a tendency to
develop LV thrombi with associated embolic stroke of  2-6%.   These  patients
are often heparinized followed by warfarin therapy for about 3 months keeping
the  INR  between  2-3  or  a  PTT  ratio of 1.3-1.5.  Anticoagulation is not
required beyond 3 months.   DC  CARDIOVERSION:  For elective cardioversion in
patients with AF, 2-3  weeks  of  warfarin  therapy  is  indicated  prior  to
conversion,  and  this  is  continued  for  about  4  weeks  after successful
cardioversion to sinus rhythm.   The  INR  is  kept at 2-3.  CEREBRAL EMBOLI:
Anticoagulation is not indicated for septic  emboli  secondary  to  infective
endocarditis.    Because   cerebral   embolization  can  be  associated  with
hemorrhage, warfarin is  usually  not  initiated  for  5-7  days  in order to
prevent further emboli which may occur at a rate  of  1%/day.   However,  the
time  interval  is  dictated  by  the size of the infarct and the presence of
hemorrhage that is seen  on  CT.   AORTIC  VALVE  DISEASE:  In the absence of
mitral valve disease and/or AF, anticoagulation is not indicated in  isolated
aortic valve disease as thromboemboli are uncommon.

           -ANTICOAGULANTS AND ANTIPLATELET THERAPY IN MI-
Several studies have shown the benefit  of  adding soluble ASA and IV heparin
to thrombolytic therapy in order  to  reduce  the  morbidity  and  mortality.
Soluble  ASA  in a dose of 160 mg + IV heparin in adequate doses for at least
48 hrs following thrombolytic therapy  should be instituted.  Heparin is also
useful in reducing the frequency of mural thrombus.  HEPARIN STUDIES: In  the
European  cooperative  study group there was randomization of 652 patients to
alteplase and ASA and to  either  placebo  or  IV heparin.  In those patients
receiving IV heparin only, there was an 83%  patent,  infarct-related  artery
seen  during  coronary  angiography  versus  only  75%  of patients receiving
placebo.  Left ventricular  thrombi  had  an  incidence  of  only 3.7% in the
heparin treated group versus 6.8% in  the  placebo  treated  group.   In  the
Heparin  Aspirin  Reinfarction  Trial  (HART)  study  there were 205 patients
randomized into those who received TPA  to either immediate IV heparin or low
dose oral ASA (80 mg/day).  A patent infarct- related artery was seen  at  18
hours  in  82%  of  those  who recevied IV heparin versus only 52% in the ASA
treated group.  In 16,000  patients  who  did not receive thrombolytic agents
the mortality rate was 13.1% in those who also did  not  get  heparin  versus
9.2%  in  3000  patients  that  did receive IV heparin.  In greater than 9000
patients who received thrombolytic therapy and IV heparin, mortality rate was
5.5% compared to 9.3% in  over  34000  patients  who did not recevie heparin.
ASPIRIN STUDIES: ASA therapy in AMI has been studied when used alone and with
thrombolytic therapy.  In the ISIS-II Study ASA +  Streptokinase  produced  a
lower  mortality rate than when streptokinase was given alone.  The 21-42 day
mortality was 8% in this study,  while in the GISSI Trial where streptokinase
was used without a clear protocol for ASA, the mortality was 10.7%.   In  the
Anglo-Scandinavian  Study  of  Early  Thrombosis  (ASSET)  of  2516  patients
thrombolytics  +  a  protocol  without pre-defined ASA regimen was associated
with a mortality rate of 7.2%.   In  the TIMI-IIB study of 3262 patients t-PA
was used with ASA and produced a mortality rate of only about 4.9%.   Soluble
ASA must be used initially, rather than enteric coated ASA.

            -ANTICOAGULATION AND PROSTHETIC HEART VALVES-
Warfarin should be  kept  between  2.5-3.5  INR  with  mechanical  prosthetic
valves.   INR  <  1.8 have a high risk of thromboembolic events and INR > 4.5
have an excessive risk of  bleeding.  Dipyridamole 375-400 mg/d plus warfarin
may have an additive effect without increased bleeding  risks.   Aspirin  100
mg/day + warfarin may have an additive effect without risk of major bleeding,
but  there  may be minor bleeding.  Patients with bioprosthetic valves in the
mitral position receive warfarin for the first 3 months at 2-3 INR.  Warfarin
therapy for aortic bioprosthetic valves for the first 3 months is optional if
the patient has sinus rhythym.   Patients with sinus rhythm and bioprosthetic
valves may receive long term therapy with aspirin 325 mg daily.

                    -ANTICOAGULATION AND SURGERY-
Discontinue  the  warfarin  2  days prior to surgery and start heparin at 1.5
control.  DC the heparin 4 hours prior to surgery.  DO PT and PTT.  If normal
do surgery.  Start warfarin again the nite  of surgery at 10 mg (takes 4 days
to get maximum anticoagulation).  Restart heparin 12-24 hrs post-op.

    -ANTICOAGULATION (Prosthetic heart valves and noncardiac surgery)-
Cataract surgery, teeth extractions and minor surgery can be done safely with
therapeutic levels of  anticoagulation.   Mitral  prosthetic  valves are more
thrombogenic than  aortic  prostheses,  regardless  of  the  type  of  valve.
Starr-Edward ball cage valves are more thrombogenic than standard disk valves
as  the St.  Jude.  The least thrombogenic are the bioprosthetic valves.  One
of 3 methods can be used  for regulation of coagulation: 1..as an outpatient,
discontinue warfarin to allow the PT to normalize  and  start  therapy  again
shortly  postoperatively.   2..reduce  warfarin as an outpatient and maintain
the patient in a  subtherapeutic  range during the procedure.  3..discontinue
warfarin therapy and instiute heparin in an inpatient  setting.   Heparin  is
discontinued  4  hours  before  surgery and started again with warfarin 12-24
hours after surgery.  This is used  in  major surgery in patients with mitral
valve prosthesis.  In most other cases, # 1 and 2 can used.

                     -ANTIPHOSPHOLIPID SYNDROME-
Clinical:  Venous  thrombosis  such  as  deep  venous  thrombosis,  pulmonary
thromboembolism, arterial  thrombosis  as  stroke,  myocardial infarction and
gangrene, Pregnancy loss and thrombocytopenia.  Less common  are  a  positive
Coombs  test,  livedo reticularis, heart valve sterile vegetations, migraine,
myelopathy, leg ulcers, chorea, and possibly avascular necrosis and pulmonary
hypertension.  TESTS include a  positive  anticardiolipin  test (IgG > 20 GPL
units, IgM > 20 MPL units) and a  positive  lupus  anticoagulant  test.   The
anticardiolipin  test  is  sometimes  positive  in  inflammatory,  malignant,
infectious or drug induced disorders or even in normal patients.  A diagnosis
is  more  likely  if  the IgG is positive at medium to high levels, and stays
positive for several weeks to months  and  years.  The IgM is more frequently
falsely positive than the IgG, although  rarely  only  the  IgM  is  positive
usually  at  high  titers.  The IgA should only be ordered if the IgG and IgM
are negative and there is  a  strong  potential  for the disease.  Serum (red
topped tube) is needed for the anticardiolipin test.  Plasma (blue top  tube)
is  needed  for  the  lupus anticoagulant.  The lupus anticoagulant cannot be
reliably performed if  the  patient  is  on  heparin  or oral anticoagulants.
TREATMENT  should  consist  of  stopping  smoking  and  oral   contraceptives
containing  estrogen.   Warfarin  +  1/2  of  an  adult  aspirin  is used for
treatment in those who have  had  a  stroke  keeping  the PT INR at 2.5-3 and
continue for as  long  as  the  anticardiolipin  is  positive.   If  patients
continue  to  have recurrent thrombosis despite warfarin or ASA therapy, high
dose prednisone and a monthly IV pulse of cyclophosphamide (500-750 mg/m2) is
given.  The prednisone is tapered  over  a few months, and then discontinued,
but the  cycloposphamide  is  continued.   When  the  antibody  is  negative,
decrease  the  cyclophosphamide  to  pulses  every  2,  then  3  months.  The
anticoagulant should  be  continued  during  immunosuppressive treatment.  In
order  to  prevent  pregnancy  loss,  the  patient  should  be  treated  with
subcutaneous heparin 5,000-10,000 units bid + one baby dose aspirin daily  if
there is a history of pregnancy loss.  About 50% of positive antiphospholipid
syndrome   patients  will  have  normal  pregnancies.   If  this  regimen  is
ineffective high dose IV gamma globulin of  0.4 gm/kg four days each month is
started as soon as pregnancy is detected.  If both heparin and gamma globulin
fail, prednisone 20-40 mg + a baby dose aspirin might be considered.

                    -ANTITHROMBIN III DEFICIENCY-
May  be  congenital  or acquired.  If congenital, there is a marked increased
risk of venous thrombotic  events  and  pulmonary  embolism.  Acquired may be
secondary to massive thrombosis, DIC,  heparin  therapy,  liver  Disease  and
protein  losing  disorders  of  the  kidney  and GI tract.  Therapy  includes
warfarin, ASA and dipyridamole.

                         -AORTIC DISSECTION-
Aortic dissection occurs when there is a tear  in  the  aortic  intima.   The
etiology  of  this  tear may be degenerative changes in the smooth muscle and
elastic tissue of the  media.   Sometimes  there  is associated cystic medial
necrosis.  Hypertension is the most common cause of medial degeneration,  and
about  66% of patients will have hypertension.  The peak age for hypertension
depends on the  etiology,  but  in  general  is  in  the  6th and 7th decade.
Patients  that  have  proximal  dissections  tend  to  be  somewhat  younger.
Approximately 60% of patients have intimal tears in  the  proximal  ascending
aorta.  Males predominate in a ratio of 3:1.  Marfan's syndrome as a cause of
aortic  dissection commonly presents in the 3rd and 4th decade.  Other causes
of aortic dissection include  Marfan's  and Ehlers-Danlos syndromes, Turner's
syndrome, relapsing polychondritis, coarctation of the aorta, bicuspid aortic
valves, patent ductus arteriosus, arteriosclerosis, trauma, and  injury  from
arterial catheterization and other vascular procedures such as cross clamping
injuries.   As the tear progresses the media is separated from the adventitia
with production of a false  channel  which  extends distally, and to a lesser
extent proximally.  The proximal dissection will produce incompetency of  the
aortic  valve.  Distal dissections may occlude vital tributaries of the aorta
with symptoms contingent upon  the  vessels  that  are compromised.  The most
common site of origination of the tear is within about 5  cm  of  the  aortic
valve,  and  in  the descending aorta near the ligamentum arteriosum and just
distal to the origin of the  left  subclavian artery.  Rupture may occur into
the pericardial cavity or left pleural space and produce mortality.   Without
treatment  90%  will be dead in 3 months.  If the patient is fortunate enough
to be  treated  60%  of  those  that  are  released  from  the hospital after
treatment  will  be  alive  5  years  later,  and   40%   10   years   later.
CLASSIFICATIONS  OF  DISSECTIONS:  Aortic dissections are considered acute if
they are less than 2  weeks  or  chronic  if  >  2 weeks.  There are two main
systems used for classification.  The Debakey system has been  in  place  for
many  years  and  reflects  the  site  of the intimal tear while the Stanford
University system does not address the site of the tear, but only involvement
of the ascending aorta.  In  the  Stanford  type  A tear, all ascending aorta
tears are addressed, and type B dissections address all  tears  that  do  not
involve the ascending aorta.  In the DeBakey classification there are 3 types
of  dissection.   Type  I starts in the proximal aorta and extends beyond the
brachiocephalic tributaries.  Type II  originates  at  the  same place but is
confined to the ascending aorta.   Type  III  originates  in  the  descending
thoracic  aorta  just  beyond  the  origin  of  the  left  subclavian artery.
CLINICAL: Patients  present  with  sudden  pain  that  has  been described as
ripping or tearing and is excruciating.  There is no crescendo tempo  to  the
pain.   The pain is maximal at the start.  If the dissection is proximal, the
pain tends to be  in  the  anterior  chest,  while  pain  in  the back in the
interscapular area suggests a distal dissection.  As the dissection  extends,
the  initial  pain  will  migrate  to another area.  This can be an important
diagnostic feature.   Other  symptoms  depend  on  the  tributaries  that are
occluded.  Some may develop myocardial infarction,  stroke,  or  paraparesis.
There  may  be  pain in an arm due to ischemia or there may be abdominal pain
secondary to mesenteric insufficiency  or  infarction.  Syncope may be caused
by rupture  into  the  pericardium  producing  tamponade.   Congestive  heart
failure  may develop secondary to severe aortic regurgitation.  If blood flow
is  interrupted  to  the  kidneys  there  is  renal  dysfunction  and further
elevation of the blood pressure due  to  excessive  renin  release  from  the
ischemic  kidney.   Physical  exam  may  reveal  the BP to be elevated with a
difference in BP between  the  arms.   There  may be jugular vein distention,
pericardial friction rub and pulsus paradoxus  suggesting  rupture  into  the
pericardium.   Other patients may present with hypotension, become clammy and
complain of  chest  pain  simulating  a  myocardial  infarction.  Hypotension
suggests rupture into the peritoneal cavity,  cardiac  tamponade  or  pleural
space.   Check  the  femoral  and brachial pulses as a decrease in these will
reflect a  distal  aortic  dissection.   About  16%  of  patients with distal
dissections will have diminished or absent pulses.  About 50%  with  proximal
dissections  will have diminished pulses.  Check the brachiocephalic branches
for  dissection  of  the  proximal  ascending  aorta.   Aortic  regurgitation
associated with proximal dissection occurs in  about 2/3 of cases.  This will
produce a diastolic murmur.  If the aortic regurgitation is severe,  as  well
as  acute,  the  murmur may be difficult to hear, and the patient may develop
congestive heart failure.  LABORATORY: The  patient may have an elevated LDH,
bilirubin and anemia secondary to hemolysis of the RBCs in the false lumen of
the aorta.  The BUN and creatinine may be elevated if there is compromise  of
the  renal  blood  flow  to  the kidneys.  If the dissection extends into the
coronary  arteries  there  may  be  EKG,  and  enzyme  changes  secondary  to
myocardial infarction.  The AST and CK  are  usually normal unless there is a
concomitant myocardial infarction.  A precise diagnosis must be  made  before
thrombolytic  therapy  is given for a myocardial infarction.  The chest x-ray
will demonstrate widening of the aorta in about 90% of cases.  There may also
be displacement of an aortic plaque of  5-10 mm or more.  If there is rupture
into the pericardium, the heart may be enlarged.  There may be a left pleural
effusion.  IMAGING PROCEDURES: TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE)  has  a
specificity  of  90%  or greater and a sensitivity of almost 100%.  It can be
done fairly  rapidly,  is  portable,  can  show  the  status  of the coronary
arteries and can demonstrate aortic regurgitation.  A  typical  exam  can  be
done in about 15 minutes.  At the present time with the new multiplane probe,
images  can  be  imaged in the transverse and longitudinal planes and various
in-between planes.  TEE can show  the  true  and false lumens and the intimal
flap as  well  as  the  branch  vessels  and  thrombi  in  the  false  lumen.
Pericardial  effusions  may  also  be  detected.   With  the  advent  of  the
multiplane  probe,  false  positive  intimal  flaps have been eliminated to a
large degree.  Transthoracic echocardiography  has  a sensitivity at the best
of about 85% and a 63-96% specificity.  It is best for detection of ascending
aorta	dissection.   MAGNETIC  RESONANCE  IMAGING  has  a  sensitivity   and
specificity  of  99%.   However,  it can not be used in an emergent situation
because  it  is  too  time  consuming.   It  also  is  not  available  at all
institutions and is very expensive.  Intravenous contrast is not needed which
is an asset if there is renal compromise or allergies.  The  true  and  false
lumens  are visualized.  The intimal flap is best seen when the blood flow is
rapid.  Secondary signs of aortic dissection  may  be seen as widening of the
aorta and thickening of  the  aortic  wall.   If  cine-MRI  is  used,  aortic
regurgitation  can be diagnosed with correlation paralleling Doppler studies.
However, utilizing cine-MRI will  extend  the  imaging  time by another 15-30
minutes so that the total time of imaging can  be  over  an  hour.   This  is
unacceptable in acute unstable aortic dissections.  Disadvantages include the
inability  to  visualize branch vessels and coronary arteries.  MRI cannot be
used in patients with mechanical  prosthetic valves, metal implants, surgical
clips or pacemakers.  COMPUTED TOMOGRAPHY has a sensitivity of about 90%  and
specificity  of  95%.   Most  institutions  now  have  CT  machines.   It can
demonstrate both the true  and  false  lumens  and flap.  False positives can
occur due to motion and streak artifacts, and false negatives may  occur  due
to  insufficient  contrast  in  the false lumen.  It is non-invasive but does
require intravenous contrast agents.   Branch  vessels and coronaries are not
visualized.  AORTOGRAPHY is mandatory if surgical  therapy  is  planned.   It
will  define the origin and extent of the dissection, the magnitude of aortic
regurgitation, and involvement of the branches  of the aorta and any coronary
occlusion.  It has a sensitivity of  90%  and  specificity  of  95%.   It  is
invasive,  requires  contrast and is somewhat time consuming.  TREATMENT: For
dissections of the proximal aorta,  surgery  is usually required while distal
aortic   dissections   are   treated   medically.    Patients   should   have
intra-arterial catheters inserted for blood pressure  monitoring.   Pulmonary
artery  catheters also are helpful, monitoring for pulmonary edema and volume
changes due to dissection and rupture.   The  goal in medical treatment is to
reduce the systemic blood pressure and the rate of  pressure  change  in  the
aorta  (dP/dT).   The systolic blood pressure should be reduced to around 120
mm Hg.  The combination of  sodium  nitroprusside and propranolol is a useful
combination.  Nitroprusside should not be used alone because it can  increase
the  dP/dT initially.  Nitroprusside is prepared by adding 50 mg in 250 ml of
5% D5W with a  starting  drip  rate  of  25ug/min  and  then titrating to the
desired BP level.  Propranolol may be given at .5-1 mg every 3-5 minutes to a
total of .15 mg/kg or until the pulse  slows  to  around  60  beats/min.   IV
labetalol  can  also  be  used  with  nitroprusside.   The  dose  is 10-20 mg
initially and then 20-40 mg every 15 minutes until the BP is controlled.  The
total dose should not be greater  than 300 mg.  Additional doses of labetalol
in the same range may be given prn every 4-8 hours.   Constant  infusions  of
labetalol  can  also  be  used  by giving the drug at 1-2 mg/min.  Other beta
blocker alternatives that can be  used  are esmolol, metoprolol and atenolol.
If patients are not candidates for beta blockers because of congestive  heart
failure,  bradycardia,  heart  block,  asthma  or  left  ventricular systolic
dysfunction, calcium channel blockers, and nifedipine may be used.  Verapamil
may be given at .05-.1  mg/kg  IV  and nifedipine 10-20 mg sublingually every
2-4 hours.  Trimethaphan camsylate may be used alone at a dose of 1-5  mg/min
IV.   It  is  initially  effective,  but  tachyphylaxis  may rapidly develop.
Furthermore, blurred vision, urinary  retention  and  ileus are side effects.
SURGERY is usually indicated in acute dissections  of  the  ascending  aorta.
Complications as stroke and myocardial are not absolute contraindications for
surgery.   Unless  there  is  dissection  into  branch  vessels  or impending
rupture,  dissections  of  the  aortic  arch  and  distal  aorta  are treated
medically.  The mortality associated with aortic  dissection  is  about  15%.
The  dissected  portion  of  the  aorta is excised with reconstitution of the
aorta with a synthetic graft.   If there is significant aortic regurgitation,
valve replacement should be done.  All patients, whether they  are  initially
treated  with surgery or by medical means, should be chronically treated with
a combination of beta blockers or  calcium antagonists plus an ACE inhibitor.
Hydralazine,   minoxidil   or   beta   blockers   that   possess    intrinsic
sympathomimetic  properties,  as  acebutolol or pindolol, should not be used.
All patients should be followed  for any recurrence of dissection, aneurysmal
development or progressive aortic valve insufficiency.

                       -AORTIC REGURGITATION-
CHRONIC AORTIC REGURGITATION (Medical Treatment): Patients with  mild  aortic
regurgitation need no restrictions in their activities.  Moderate AR patients
need  to  avoid  competitive  sports,  isometric  exercise and heavy physical
exertion.  All patients  will  need  antibiotic prophylaxis for endocarditis.
Those that have syphilitic AR need antibiotics to treat the syphilis.  If the
AR is due to Rheumatic  Fever,  antibiotic  prophylaxis  is  needed  for  the
rheumatic  fever.  Severe AR will need digitalis, diuretics and vasodilators.
Diuretics are needed if there is CHF.  Digitalis will increase contractility,
reduce end-diastolic  volume,  and  increase  the  ejection  fraction and the
cardiac output.  Calcium channel blockers such as nifedipine will  reduce  LV
end-diastolic volume and mass, increase LV ejection fraction and reduce blood
pressure.   Other vasodilators such as hydralazine and angiotensin converting
enzyme inhibitors will decrease the  severity of the regurgitation.  By using
these drugs in  asymptomatic  patients,  surgery  may  be  postponed.   VALVE
REPLACEMENT: When to replace the aortic valve is at the present time a matter
of   debate.   Surgery  should  be  done  before  there  is  irreversible  LV
dysfunction.  Systolic function is  probably  the  best indicator.  A reduced
ejection fraction by 2D echocardiography  and  radionuclide  ventriculography
are the best non-invasive tests for depressed systolic function.  Any patient
in  functional  Class  III or IV are candidates for surgery.  The patient may
benefit from aortic valve replacement even when the ejection fraction is 0.25
or less.  For functional Class  II  patients that have symptoms with ordinary
activity and have reduced ejection fraction at rest, valve replacement may be
indicated.  For patients in Class II with normal resting ejection  fractions,
some would recommend surgery.  For patient in Class I with a reduced ejection
fraction  at  rest, surgery again would be recommended by some.  For those in
Class I and a  normal  ejection  fraction,  surgery should be recommended for
those who have LV end-diastolic volume >150 ml/M2, LV internal  dimension  on
M-mode  echocardiogram  of  >  70 mm at end-diastole, > 50 mm at end systole,
and/or the LV ejection fraction shows a new persistent reduction to less than
0.54-0.60.

                       -AORTIC REGURGITATION-
May occur in Marfan's syndrome.  Bounding  pulses may be present.  The murmur
is an early blowing diastolic decrescendo murmur at or left  of  the  sternum
which  is  intensified  with sitting, leaning forward and holding the breath.
Thrill may be  present  as  well  as  a  secondary  midsystolic murmur due to
increased flow.

                          -AORTIC STENOSIS-
Most asymptomatic  patients  can  be  managed  with  conservative  care  with
interval  follow-up.   However, once symptoms develop the stenosis is usually
severe.  The average survival after development  of symptoms is 2-4 years and
many of these deaths are of  a  sudden  nature.   Antibiotic  prophylaxis  is
indicated  to  prevent  endocarditis.  AF should be reverted rapidly to sinus
rhythm.  Those that have  moderate  valve  stenosis  should avoid moderate to
severe physical exertion and competitive sports.  In young  patients  if  the
valve  is  pliable,  a palliative commissurotomy may be done, avoiding aortic
regurgitation.  Older patients and young patients with calcified rigid valves
will need valve replacement.   The  operative mortality for valve replacement
is about 3-5%.  Concomitant coronary  artery  disease  should  have  coronary
bypass  surgery  concurrently at time of valve surgery.  If there has been no
myocardial damage  prior  to  surgery,  LV  hypertrophy  will  regress toward
normal.  The 10 year survival is greater than 60%, while the 15 year survival
is > 45%.  CONGESTIVE HEART  FAILURE  AND  AORTIC  STENOSIS:  These  patients
should  be  treated  with  digitalis  and diuretics in preparation for aortic
valve  surgery.   If  they   do   not  optimally  respond,  catheter  balloon
valvulplasty  may  be  done  to  improve  the  patient  temporarily  until  a
definitive valve can be placed.  Valve replacement  in  a  patient  with  CHF
carries  a  10% mortality.  However, if it is successful, the 7 year survival
is 84%.  The LV function improves in all patients and becomes normal in about
66% of patients.  Also,  LV  hypertrophy  and  dilatation will regress toward
normal.  CATHETER  BALLOON  VALVULOPLASTY:  This  technique  should  only  be
recommended  in  those  who have only a short term life expectancy, as the 30
day mortality	is 14%, 1 year mortality,  35%, and the 3 year mortality 71%.
In most series, the complication rate has been high  and  the  success  rate,
which  is  determined  by  a  reduction  in  pressure gradient, has been only
moderate.   In   calcific   aortic   stenosis   following   catheter  balloon
valvuloplasty, the average increase in valve area is 0.3 cm2, with the  final
aortic  valve area averaging about 0.8 CM2.  Therefore, many continue to have
severe aortic stenosis.

                          -AORTIC STENOSIS-
The  ejection  murmur  is primarily at the URSB but will transmit to the neck
and LLSB, and associated with  a  thrill  and ejection click.  Is congenital.
The S2 split is usually narrower than in pulmonary stenosis.  Aortic stenosis
sometimes coexists with aortic regurgitation with a faint  diastolic  murmur,
producing the so called to-and-fro murmur.

                          -APLASTIC ANEMIA-
Aplastic  anemia  may  be  considered  as  a  group  of  disorders  that   is
characterized  by  a  peripheral  blood pancytopenia secondary to bone marrow
failure that may be from injury or  abnormal expression of the stem cell with
a resulting hypoplastic bone marrow.  Patients with acquired disease may have
either moderate to severe  disease.   Those  that  have  severe  disease  are
characterized  by  at  least 2 of the following: platelet count < 20,000/mm3,
reticulocytes count < 1%  after  correction  for the hematocirti, white blood
cell counts < 500/mm3 and a hypocellualr bone marrow.  Patients  with  severe
aplastic  anemia, if left untreated, have a median survival of about 3 months
and only 20% will survive for  1  year.   About 25% of patients with aplastic
anemia are under the age of 20 and over 1/3 are > 60 years old.  The acquired
aplastic anemias are estimated to occur in the pediatric population at  about
1  per million children per year with equal sex involvement.  Aplastic anemia
genetically occurs at a frequency of about 1/3 that of the acquired disorder.
The stem cells may be absent or  defective, or there may be abnormal hormonal
or cellular control of the stem cell, or there may be immune  suppression  of
hematopoiesis  or  abnormalites  in the marrow microenvironment.  In general,
the causes of  aplastic  anemia  may  include  rare  congenital forms such as
Fanconi's anemia, Scwachman-Diamond syndrome and dyskeratosis congenita,  all
which  occur  under  the  age  of 10 and have a male predominance.  Fanconi's
anemia is probably secondary to a  defect  in  DNA repair and is an autosomal
recessive disease with a frequency of  heterozygosity  of  1:600.   Fanconi's
anemia  is  extremely  rare  with only about 200 cases being reported.  It is
often associated at  birth  with  congenital  anomalies  such as cafe-au-lait
spots, hypoplastic, supernumerary or absent thumbs  with  or  without  radial
aplasia,  renal  malformations, strabismus, microcephaly, mental retardation,
deafness and hypogenitalism.  Other  causes  include idiopathic or autoimmune
aplastic anemia, SLE, Toxins (insectidcides, toluene, benzene),  chemotherapy
(busulfan,    cyclophosphamide),   antimetabolites   (cytosine   arabinoside,
mercaptopurine), antimitotic agents  (colchicine),  radiotherapy  and drugs (
phenylbutazone, sulfonamides,  carbamazepine,  chloramphenicol,  gold  salts,
phenytoin,   tolbutamide,   quinacrine),   pregnancy,   paroxysmal  nocturnal
hemoglobinuria and posthepatitis.  Chloramphenicol is associated with 2 forms
of bone marrow toxicity.  The most common is a reversible dose	and duration-
related suppression of the erythroid precursors, with occasional suppresssion
of the granulocytic and megakaryocytic  prcursors.   In  this case there is a
drop in the hematocrit, rise in the iron and decrease of  the  reticulocytes.
A  bone  marrow exam done at this point will reveal vacuoles in the cytoplasm
of the early  erythroid  and  granulocytic  precursors.   The  second form of
toxicity from chloramphenicol is due to an  idiosyncratic  reaction  with  an
incidence of 1:50,000 patients.  It is unrelated to the dose and duration and
is  capable  of  causing  a  fatal,  usually  irreversible  aplastic  anemia.
Aplastic  anemic  can  occur  following  non-A  non-B  (most  common), A or B
hepatitis.  It usually occurs  just  as  the hepatitis is resolving.  Viruses
also have been associated with aplastic anemia and would include Epstein-Barr
virus,  parvovirus,  rubella,  herpes,  and  cytomegalovirus.    DIFFERENTIAL
DIAGNOSIS  OF  PANCYTOPENIA:  Myelodysplasia,  acute  leukemia,  infiltrative
disease of the bone marrow (multiple myeloma, lymphoma, carcinoma, hairy cell
leukemia),  megaloblastic  anemia,  myelofibrosis,  hyperspenism,  infections
(AIDS,  TB,  brucellosis,  leishmaniasis),  and SLE.  CLINICAL: Patients will
complain of weakness and fatigue from the anemia.  The neutropenia will cause
bacterial infections and  the  thrombocytopenia  will  cause mucosal and skin
bleeding.  The patient will appear  pale  and  there  may  be  petechiae  and
purpura.   Hepatosplenomegaly,  lymphadenopathy  and  bone tenderness are not
present.  LABORATORY: Pancytopenia is eventually present, but early, only one
or two cell lines may be affected.  Reticulocytes are decreased.  Neutrophils
and plaltelets are reduced in  number  and  no abnormal or immature cells are
seen.  The MCV is usually normal, but occasionally may  be  increased.   Bone
marrow  exam  is  hypocellular, replaced with fat, with only small amounts of
normal hematopoietic progenitors.  Bone marrow aspirates may yield a dry tap.
No  abnormal  cells  are  seen.    The  RBC  are  normochromic  usually,  but
occasionally macrocytic.  TREATMENT: The treatment  of  choice  for  patients
under  the  age  of 40 who have HLA matched sibling is allogeneic bone marrow
transplantation with the best  results  in  those  patients  who have not had
prior blood tranfusions, which will increase the risk of graft rejection  due
to  sensitization to antigens present on hematopoietic progenitors.  For this
group of patients,  the  complete  response  rate  is  about  80%.  For older
adults, or those who  have  had  prior  blood  transfusions,  the  long  term
survival rates are between 40-70% Children with severe aplastic anemia who do
not  have  HLA  idential  siblings can be treated with allogeneic bone marrow
transplantation using  matched  but  unrelated  donors.   Candidates for bone
marrow  transplantation  should  not  receive  transfusions  for  anemia  and
thrombocytopenia if at all possible.  For patients > 40 or those without  HLA
compatible siblings, antithymocyte globulin (ATG) immunosuppression should be
given.   ATG  is  given over a 5-8 day period with antibiotic and transfusion
support.  The response is usually  partial,  but effective enough to increase
the blood counts in about 4-12 weeks.  About 40-50% will have a  complete  or
partial  response.   The  combination  of ATG + cyclosporine may be even more
effective than ATG given alone.  For patients with a predominat neutrophilia,
myeloid growth factos as G-CSF  (filgastrim)  or GM-CSF (sargramostim) can be
given, which will decrease  the  incidence  of  infections.   There  is  some
evidence   that   some   of   these   nontransplanted  patients  may  develop
myelodyplasia after many years.  Occasionally,  some patients will respond to
androgens such as oxymetholone 2-3 mg/kg PO daily.   Patients  with  aplastic
anemia  secondary  to  SLE  may  benefit  from  plasmapheresis  and high dose
prednisone.

                        -AQUATIC INFECTIONS-
ERISIPELOID: Also known as fish handlers disease because people who work with
sea food, oyster shuckers,  for  instance,  are often infected.  The organism
Erysipelothrix rhuslopathiae, a Gram + bacillus, enters the  skin  through  a
puncture wound or abrasion.  Within 1-7 days after injury, itching or painful
irritation may develop followed promptly by the appearance of a maculopapular
nonvesiculating,  sharply  defined,  raised purplish red zone surrounding the
wound.  Local swelling is usually present  and nearby joints may become stiff
and painful.  Centrifugal spread from the site of inoculation tends to  occur
at  a  rate  of  1-2  cm/day.   Specimens,  as biopsy, must be taken from the
advancing margin  of  the  wound.   Most  Erysipelothrix  infections are self
limited, resolving within 1-3 weeks and do not require  treatment.   In  some
cases  however,  the  infection  may recur or go on to cause systemic illness
such as septicemia,  endocarditis,  or  arthritis.   When it does, penicillin
2-20 million U/day is the drug of choice.  The duration can be as long  as  6
weeks.  MYCOBACTERIUM MARINUM: Many have pre-existing wounds, then exposed to
salt water.  Days to weeks after exposure they get a verrucous, granulomatous
lesion  a  few millimeters to a couple of centimeters in diameter.  These may
ulcerate and even migrate up  the extremity.  Although usually self limiting,
the lesion may take months  or  even  years  to  heal.   Sometimes  they  get
secondarily  infected.   Skin biopsy will isolate th mycobacterium.  Cultures
of Mycobacterium marinum  grow  best  at  32-33  C  instead of traditional 37
degrees C. Antibiotic treatment is reserved for deep,  soft  tissue  or  bone
infection.   Some are resistant to isoniazid, PAS and streptomycin.  Surgical
excision is another option.   VIBRIO  VULNIFICUS:  Most infections in the USA
occur along the Gulf and Atlantic coasts.  About 80-90% are  related  to  the
consumption  of  raw  oyster or other forms of uncooked seafood.  Most of the
infections occur in men who  are  over  the  age of 40.  Gastroenteritis with
nausea, vomiting, abdominal  cramps,  fever,  headache,  and  diarrhea,  that
sometimes  is  bloody.   A  local regional cellulitis may develop in patients
with primary wound infections  and  sometimes  it  progresses to myositis and
necrotizing  fasciitis.    Spontaneous   peritonitis   has   been   reported.
Septicemia,  which  often  occurs within 12-24 hrs after exposure is the most
feared complication.  Ninety percent  of  septicemia occurs between April and
October and affect people with  pre-existing  hepatic  dysfunction.   Seventy
five percent of patients with Vulnificus septicemia have some form of chronic
liver  disease.   The  mortality  is 60%.  To culture the organism requires a
special media as thiosulfate-citrate-bile-sucrose agar.  Treatment includes a
number of antibiotics as  tetracycline, Bactrim, gentamicin, chloramphenicol,
ciprofloxacin and  norfloxacin.   AEROMONAS  HYDROPHILA:  Similar  to  Vibrio
infections, but while Vibrio is found mainly in saltwater, Aeromonas is found
in  soil  and  fresh  water  streams  and  lakes.   Gastroenteritis is common
particulary during the summer months.   Wound  infections are next common and
causes  cellulits,  and  can  progress  rapidly  to   necrotizing   myositis.
Spontaneous  peritonitis  can  also  occur  with  Aeromonas,  and  pneumonia,
meningitis and endocarditis have all been reported.  Septicemia occurs usully
in immunocompromised people with greater than 50% mortality.  The antibiotics
used are the same as for Vibrio vulnificus infections.

            -ARRHYTHMIAS IN ACUTE MYOCARDIAL INFARCTION-
THIRD DEGREE HEART BLOCK: Third degree heart block is more common in inferior
MI and occurs in about 5% of patients.  If  it  occurs  in  anterior  MI  the
prognosis  is  worse,  and it is usually permanent and will require permanent
pacing.  It may take up to 2  weeks  to resolve in the absence of an inferior
MI.  SECOND DEGREE BLOCK: Second degree heart block is  divided  into  Mobitz
type I (Wenckebach) and Mobitz II block.  Mobitz type I is characterized by a
progressive  prolongation  of  the  PR interval followed by a non-conducted P
wave.  It occurs mostly in inferior MIs in up to 10% of patients.  It usually
requires no treatment, unless the  ventricular  rate  is slow enough to cause
symptoms.  It usually lasts about 2 days.  Mobitz type II usually occurs with
anterior MI, is less common than Mobitz I, is associated with a  high  degree
of cardiac necrosis and tends to progress to third degree heart block.  It is
characterized  by non-conducted P waves in the face of constant PR intervals.
Mobitz type II requires a  temporary  pacemaker.   If  it lasts longer than a
week a permanent pacemaker  may  be  indicated.   Narrow  QRS  complexes  are
usually  seen in Mobitz I, while wide QRS complexes may be seen in Mobitz II,
indicating an associated bundle  branch  block.   The  block  in Mobitz II is
infranodal.   VENTRICULAR  TACHYCARDIA:  Ventricular  tachycardia   that   is
sustained  in the presence of a normal BP is treated with IV lidocaine.  Give
a loading bolus	of 1 mg/kg IV.  A  repeat  of  0.5 mg/kg may be given up to a
total of 4 mg/kg followed by a constant infusion of 2-4 mg/min.  If lidocaine
is not effective, procainamide may be given at about 50-100 mg IV boluses q10
minutes up to a maximum of 1000 mg, followed by a constant  infusion  of  2-4
mg/min.  If this is unsuccessful, Bretylium may be used at 5-10 mg/kg IV over
a  5  minute  period, followed by an infusion of 1-2 mg/min.  (Add 2 grams to
500 ml of D5W and drip at 30 ml/hr).  Ventricular tachycardia in the presence
of hypotension should be  corrected with DC cardioversion.  SUPRAVENTRICULAR:
Most premature contractions are benign and do  not  require  treatment.   The
causes  are  multifactorial  such  as hypomagnesemia, hypoxemia, hypokalemia,
pericarditis, atrial ischemia or infarction,  LV dysfunction, or mitral valve
disease.  Paroxsysmal supraventricular tachycarida, if  prolonged  may  cause
hypotension  and  can  be treated with adenosine by giving a 6 mg IV	bolus.
If this is ineffective a 12  mg  bolus	may  be repeated.  This can cause a
transient AV block.  If there is no response to adenosine, verapamil 5 mg  IV
may  be given slowly.  Atrial flutter has an incidence of about 4% in AMI and
is treated by slowing the  rate  with  diltiazem, verapamil or beta blockers.
If these are not effective  and  the  patient  is  hemodynamically  unstable,
cardioversion  or  overdrive  pacing  may  be used.  SINUS BRADYCARDIA: Sinus
bradycardia is common with AMI.   It  is usually associated with inferior MI,
occurring in about 25% of patients.   If  there  is  associated  hypotension,
atropine may be given at 0.5 mg IV bolus and repeated every 5 minutes up to 2
mg.   If this is ineffective, temporary pacing may be required.  The cause of
sinus  bradycardia  is  usually  due  to  increased  vagal  tone  and/or beta
adrenergic blocking agents.  First degree AV block is innocuous and  requires
no  treatment.   It occurs in AMI in up to 14%.  VENTRICULAR FIBRILLATION: VF
occurs in about 8% of patients  that  survive to hospitilization.  It is more
common in very large Q wave infarctions.  Recent studies have  refuted  older
studies which stated that VF occurring within the first 24 hours did not lead
to  any  long  term  risks  in patients successfully resuscitated.  It is now
thought that VF occurring any  time during hospitilization is associated with
a poorer outcome.  VF occurring late in hospitilization is usually associated
with decreased LV systolic function and connotes a poor prognosis.  Early  VF
is  treated  by  cardioversion followed by lidocaine drip for about 36 hours.
VF that occurs late  in  hospitilization  should  have  a  work  up for a new
infarction, extension of  the  previous  infarction,  or  residual  ischemia.
SINUS  TACHYCARDIA:  ST  is  usually due to pain, anxiety, or hypovolemia and
occurs in about 25% of patients.   If the sinus tachycardia is prolonged beta
blockers should be given, if there is no severe LV dysfunction.

                        -ARTERIAL THROMBOSIS-
The differential diagnosis  of  unexplained  arterial  thrombosis  in a young
person less than 50 years is as follows:  Antiphospholipid  syndrome  (obtain
anticardiolipin and lupus anticoagulant), accelerated atherosclerosis (obtain
doppler  studies  and  angiography), nephrotic syndrome (serum albumin, 24 hr
urine protein, UA), cerebral vasculitis (cryoblobulins, complement, hepatitis
profile,    cerebral    angiography),     cerebral    emboli    from    heart
(echocardiography), antithrombin III deficienty (antithrombin III), Protein C
deficiency (Protein C), Protein  S  deficiency  (Protein  S),  homocystinuria
(serum  and  urine  homocystine),  Buerger's  disease  (history  of cigarette
smoking, arterial biopsy).

                              -ASCITES-
Ascites  is  an  accumulation  of  serous fluid within the peritoneal cavity.
Most cases are due to alcoholic liver disease, cirrhosis and are transudates.
Other  causes  include,  metastatic  peritoenal  cacinomatosis.  tuberculosis
peritonitis, congestive heart failure, constrictive pericarditis,  pancreatic
ascites, Budd-Chiari syndrome and veno occlusive disease, fungal peritonitis,
myxedema  ascites,  bile  ascites,  pseudomyxoma  peritonei, Meig's syndrome,
eosinophilic   gastroenteritis,   and   peritoneal   mesothelioma.    Several
interrelated  factors  lead  to  the  formation  of  ascites.   These include
hypoalbuminemia (decreased  hepatic  synthesis  causses  a  decrease  in  the
intravascular  oncotic  pressure  which  causes albumin leakage through lymph
into the peritoneal cavity  with  resulting increased intraperitoneal oncotic
pressure), portal  hypertension  with  increased  splanchnic  plasma  volume,
alterations  in  sodium  handling  by  the kidney, and increased formation of
hepatic and intestinal  lymph.   Complicatons  from  ascites include dyspnea,
reflux esophagitis, decreased cardiac  input,  ventral  hernia,  hydrothorax,
anorexia,  vomiting,  and increased risk for GI bleeding in those with portal
hypertension.   CIRRHOTIC  ASCITES:   Patients   with  cirrhosis  and  portal
hypertension have sodium retention by the kidney which leads to  an  increase
of  plasma volume.  This is reflected by low urinary sodium content as low as
10-20 mEq/day due  to  proximal  tubular  absorption.   Patients that develop
cirrhosis have a 2 year survival rate of about 40%.  The ascites accumulation
may be rather sudden or appear  insidiously  over  weeks  to  months.   Acute
accumulation  is  usually  due  to  some  disturbing factor such as infection
(systemic or intraperitoneal),  hepatotoxic medications, intravascular volume
depletion, hepatocellular carcinoma, acute thrombosis of the portal vein,  or
diverticulitis.  The cell count in cirrhotic ascites is usually less than 500
WBCs/ul  with less than 25% neutrophils (PMNs).  If the PMNs are greater than
250/ul bacterial  infection  from  perforation  of  a  viscus  or spontaneous
peritonitis should be suspected.   CLINICAL:  Patients  have  a  fluid  wave,
shifting  dullness,  bulging  flanks  and  may have an abdominal or umbilical
herniation, right  sided  pleural  effusion,  or  scrotal  and  penile edema.
LABORATORY: Patients that have less than 2 liters of ascites is difficult  to
detect,  but ultrasound is able to detect as little as 30 ml of ascities with
the patient in the right  lateral  decubitus  position.  CT is also sensitive
for small amounts of ascites, and can also evaluate the liver and spleen,  as
well  as  other  tumors.   Abdominal  x-rays may show separation of the bowel
loops, loss of the psoas shadow  and  a diffuse hazy appearance.  Once it has
been determined that the  patient  has  ascites,  a  diagnostic  paracentesis
should  be  done.   This  is  usually  done  in the midline on the linea alba
slightly below the umbilicus  or  the  left  lower  quadrant using a 21 gauge
needle or angiocatheter under sterile conditions.  A  Z-track  technique  for
needle  insertion will help avert ascitic fluid leakage.  It is done with the
head of the bed elevated and  the patient in the supine position.  Particular
care should be taken to avoid the urinary  bladder,  an  enlarged  spleen  or
liver,  external abdominal veins and surgical scars.  The patient should void
prior to the procedure, or have a catheter in the bladder.  Paracentesis is a
safe procedure with serious complications  reported  in less than 1% of cases
(hemorrhage,  bowel  perforation,  ascites  leakage).   To  ensure  a   safer
approach,  paracentesis  can  be done under ultrasonic guidance.  About 50 ml
should  be  obtained  to  detremine  the  white  and  blood  cell  count with
differential, total protein, albumin, triglycerides, culture for aerobes  and
anaerobes,  fungi  and  TB,  cytology  for  malignancy, gram stain, acid fast
stain, glucose,  and  amylase.   The  presence  of  blood  in  the ascites is
suggestive of TB, fungi or malignancy.  Ascites has  been  typically  divided
into transudates (protein concentration less than 2.5 grams/dl), and exudates
(protein  concentration  greater  than  2.4  grams/dl).   Alcoholic cirrhosis
ascites is usually due to a  transudate,  but about 20% of patients will have
proteins greater than  2.5  gm/dl.   Other  ascites  which  are  transudative
include   hepatic   vein   occlusion,  constrictive  epricarditis,  tricuspid
insufficiency, veno-occlusive disdease of  the  liver, portal vein occlusion,
inferior vena caval occlusion above the hepatic veins, and  acute  submassive
hepatic   necrosis.    Exudative  ascites  may  be  found  in  patients  with
tuberculosis  peritonitis,  pancreatic  ascites,  peritoneal  carcinomatosis,
myxedema,  nephrogenic  ascites,  eosinophilic  gastroenteritis,  and chylous
ascites.  Chylous ascites may be due to obstruction of the  lymphatics  by  a
malignant  process  or  rupture of the cisterna chyli.  It characteristically
has a  milky  appearance  with  high  triglycerides.  Tuberculous peritonitis
typically has a ascitic mononuclear leukocytosis.  Pancreatic ascites is  due
to a leaking pseudocyst or rupture of a pancreatic duct.  The ascitic amylase
is  high,  and and there is an increased number of neutrophils.  Eosinophilic
gastroenteritis will have increased  eosinophils  in the ascites.  Peritoneal
carcinomatosis has a high carcinoembryonic antigen (CEA), and a  high  lactic
dehydrogenase.  Another method for distinguishing transudates and exudates is
the  estimation  of  the  portal  pressure gradient.  This is essentially the
serum-ascites  albumin  difference  (S-A   gradient).   It  is  performed  by
obtaining  a  simultaneous  ascitic  albumin  and  serum  albumin,  and  then
subtracting the ascites albumin from the serum albumin.  If the S-A  gradient
is greater than 1.1 a transudate is present, whereas a S-A gradient less than
1.1  is  indicative of an exudate.  The S-A gradient is considered to be more
sensitive than the classic protein determination.  S-A gradients greater than
1.1 include cirrhosis, massive  liver  metastases, fulminant hepatic failure,
myxedema, right sided heart failure, Budd-Chiari syndrome, whereas a low  S-A
gradient  less  than  1.1  grams/dL  indicates  diseases  such as tuberculous
peritonitis, peritoneal carcinomatosis, nephrotic syndrome, and pancreatic or
biliary ascites.  TREATMENT: An assessment of the patient's medication should
be made.  All  hepatotoxic  drugs  should  be  avoided,  as  well as alcohol.
Nonsteroidal antiinflammatory drugs  (NSAIDs)  may  nullify  the  effects  of
diuretics  by  reducing  renal  blood flow, and glomerular infiltration rate.
Angiogtensin converting enzyme  (ACE)  inhibitors,  and  some calcium channel
blockers can reduce renal perfusion, decrease peripheral vascular  resistance
and  effective  vascular  volume.   Aminoglycosides  can cause renal failure.
Nutrition should be optimized.  Patients  with  a urinary sodium less than 10
meq/liter will be helped with dietary restriction of sodium (.5-1  gram/day),
and  restriction of fluids to less than 1 liter/day.  If the patient does not
respond to these simple  measures,  spironolactone  (Aldactone) is started at
100-200 mg/day given as a single dose.  Amiloride at 10 mg/day  may  be  used
instead  of  spironolactone.  Amiloride causes a more rapid diruesis and does
not cause gynecomastia.  If this does not produce a satisfactory diuresis and
the urinary  sodium  stays  below  10  meq/liter,  the  spironolactone may be
increaed to 600 mg/day.  Don't expect a rapid diuresis  from  spironolactone,
as it takes several days for a diuresis to occur.  The serum potassium should
be  monitored.  If diuresis with spironolactone is subotpimal, add furosemide
(Lasix), starting at 40 mg/day.   This  can  be escalated to 240 mg/day.  The
addition of hydrochlorothiazide may further  increase  diuresis.   Optimally,
the  diruesis  should  result  in  a  loss of 1 liter, or 1-2 pounds/day.  Be
careful with injudicious excessive diuresis,  as it may lead to hyponatremia,
azotemia, hepatorenal syndrome and encephalopathy.  For patients that do  not
respond   to   any   of  the  above  measures,  a  therapeutic  paracentesis,
peritoneovenous  shunt,  and  liver   transplantation  are  further  options.
Therapeutic paracentesis involves removal of about 4-6 liters/day  until  the
abdominal  ascites  is gone.  The paracentesis may be followed by IV infusion
of 40 grams of albumin, particularly  if renal function is marginal, or there
is no peripheral edema.  This is followed by maintenance diuretics and sodium
restriction to prevent further reaccumulation.  Peritoneovenous shunts should
only be considered in refractroy patients that have tried  combined  diuretic
therapy  and  large  volume  therapeutic paracentesis.  Patients that are not
candidates include those  with  heart  failure,  decompensated liver disease,
hepatic encephalopathy, peritonitis, sepsis, history  of  variceal  bleeding,
and malignancy.  Peritoneovenous shunts include the LeVeen and Denver shunts.
They remove ascitic fluid into the internal jugular vein via a one way valve.
Most  patients will also need diuretics at a low dose.  These peritoneovenous
shunts can improve renal blood flow, but there are serious complications that
may occur in more than  10%.   These include sepsis, mesenteric fibrosis with
bowel obstruction, disseminated  intravascualr  coagulation  (DIC),  ruptured
esophageal  varices,  and  congestive  heart failure.  Clotting of the shunts
occurs in  about  30%,  requiring  replacment.   There  is  a 10-15% surgical
mortality, and about 25% will die within one month.  Controlled studies  have
not  demonstrated  a  survival benefit in patients with these shunts.  If the
patient  is  a  candidate  for  orthotopic  liver  transplantation,  and  has
refractory ascites, the 12  month  survival  is  about 50-75%, whereas the 12
month survival of patients refractory to medical therapy is only 25%.

                           -ASPERGILLOMA-
Aspergilloma  is  a fungus ball that most frequently is composed of a ball of
matted Aspergillus mycelia floating in  a  cavity.  Other fungi have produced
balls, but fungus ball is almost synonymous with Aspergilloma.   The  patient
is usually a male around middle age, although there is a range of involvement
from  children  to  the elderly.  CLINICAL: Most patients will have a chronic
cough and purulent sputum (83%.  There is hemoptysis present in about 50-80%.
The bleeding can be disastrous  and  life threatening, but not always.  There
may  be  mild  streaking  of  the  sputum.   The  bleeding  site  is  usually
granulation tissue which is supplied  by  bronchial  and  systemic  arteries.
There  is  no  relation  between  the  rate  of growth of the fungus ball and
bleeding.  Minor bleeding doesn't  always  antedate  major bleeding, which is
defined as greater than 600 ml per 48  hours.   There  may  be  initial  life
threatening  hemorrhage  without  warning.   Many patients will have dyspnea,
usually due to the  underlying  disease.   If  the patient has a superimposed
bacterial infection there may be fever.  Weight loss may occur in  about  9%.
The  natural history of a fungus ball has shown that it may increase in size,
remain stable for many  years  or  even  regress.  The most common underlying
pulmonary disease is usually healed tuberculosis with a residual cavity which
serves as a nidus for the fungus ball.  In one study it was found that 11% of
patients with healed tuberculosis and a persistent cavity of 2.5 cm  or  more
had  an  aspergilloma.   Two  years  later  in  this study, the percentage of
aspergillomas had increased  to  17%.   Sarcoidosis, chronic obstructive lung
disease, abscess, and bronchiectasis are  other  diseases  that  are  fertile
ground  for the development of a fungus ball.  LABORATORY: X-rays will show a
solid, round mass located in a cavity.   The mass is separated from the walls
of the cavity by a crescent shaped air  space.   This  configuration  may  be
considered  diagnostic, but it may be simulated by a blood clot, tuberculoma,
bronchogenic cancer, hydatid disease  and  necrotic lung abscess.  The cavity
may be thin-walled with little surrounding diseased lung which  is  called  a
simple  aspergilloma.  On the other hand, there may be a complex aspergilloma
where  there  is  a  thick-walled  cavity  with  surrounding  diseased  lung.
Aspergillomas are usually freely suspended  in the cavity and decubitus films
will show a shift, which may help in clarifying the diagnosis.  Fungus  balls
are  very  common in the upper lobes and frequently can be bilateral.  Sputum
cultures for  Aspergillus  may  be  helpful.   In  one  series  there was 73%
positivity for Aspergillus.  The specificity, however,  is  poor  because  of
colonization.  Serum precipitins are present in about 85% of cases and may be
helpful,  but other diseases can have positive serum precipitins.  TREATMENT:
If the patient has life threatening hemoptysis  and the patient is not a good
candidate for surgical resection, bronchial  artery  embolization  should  be
done  which  has  a  success  rate  of about 85%.  Even though there are high
initial success rates there may be  recurrence  in about 15%.  The reason for
the incomplete eradication of bleeding is  that  the  granulation  tissue  is
supplied  by  multiple  arterial  sources  including  the bronchial arteries,
axillary and subclavian arteries.  Surgical resection of a lobe or segment is
the procedure of choice  if  there  is  reasonable pulmonary function and the
patient is capable  of  withstanding  this  type  of  intervention.   Medical
therapy may be used in many patients by treating any bacterial superinfection
with  antibiotics,  steroids  for  sarcoidosis  or  allergic bronchopulmonary
aspergillosis, and  bronchodilators  for  underlying  pulmonary disease.  For
mild bleeding, cough suppressants,  and  blood  transfusions  can  be  given.
Intracavitary  instillation  of  Amphotericin  B  has been successful in some
patients using 500 mg of Amphotericin.   Systemic Amphotericin B has not been
successful.

                 -ASPERGILLOSIS (Invasive Pulmonary)-
Invasive pulmonary aspergillosis usually invades the lung  in  about  90%  of
cases  and may be the only site in about 70%.  There are several predisposing
factors that lead  to  the  invasion,  including hematopoietic malignancy, as
acute lymphocytic and myelogenous leukemia  and  lymphoreticular  malignancy.
Patients   that  have  had  organ  transplantation,  especially  bone  marrow
transplants  during   periods   when   rejection   is   being   treated  with
immunosuppressive therapy.  Any patient that is being treated with  cytotoxic
agents,  corticosteroids and antimicrobials are subject to potential invasive
aspergillosis.  Granulocytopenia is especially fertile ground for invasion by
Aspergilla.  Aspergilla produce nodular lesions  that usually are less than 3
cm in diameter with smooth or ragged margins.  There is small artery invasion
by the fungi.  These lesions may be  multiple  and  confluent  with  necrotic
centers  with  a rim of hemorrhage.  Hemorrhagic infarctions present as large
pleural based, wedge shaped  lesions,  usually without cavitation.  There may
be major artery invasion with subsequent thrombosis.  CLINICAL: Most of these
patients present with an unremitting fever, and in the  right  circumstances,
such as granulocytopenia, immunosuppression, and underlying disease, invasive
aspergillosis should be suspected.  There may be pleuritic pain caused by the
hemorrhagic  infarctions  and  pulmonary  embolic  disease  may be simulated.
Aspergillus frequently colonizes  the  nasal  and  sinus cavities producing a
nasal ulcer or  epistaxis  and  sinusitis.   The  patient  may  develop  skin
lesions,  DIC,  and multiple organ failure with azotemia, acidosis, jaundice,
delirium, hypoxic and death.  CT may be helpful if one can find the halo sign
which consists of a lung  mass  or  nodule  surrounded  by  a zone or halo of
attenuation less than the center of the mass, but greater  than  air  in  the
surrounding  lung tissue.  This sign is not pathognomonic as it may appear in
patients with septic emboli due  to  aerobic bacteria.  The typical evolution
of a nodule is to cavitation in about 50%, or air crescents in 85%.  The  air
crescent  sign  appears later in the course than the CT halo sign.  There may
be a ball in the cavitation, but this  doesn't consist of a mass of hyphae as
in aspergillomas.  The ball is necrotic lung caused by arterial invasion  and
then  infarction.   Cultures of sputa are not reliable for diagnosis.  In the
first place, only 8-37% of  patients  with Aspergillus infection will culture
out the organism.  Even  if  it  cultured,  its  presence  may  just  signify
colonization  rather  than invasion.  Nasal cultures have been reported to be
somewhat helpful in  diagnosing  lung  invasion,  because of its co-existence
with invasive lung aspergillosis.  However, if the nasal culture is negative,
this doesn't mean that there is no lung aspergillus invasion.   Probably  the
two  best approaches for diagnosis are fiberoptic bronchoscopy and peripheral
percutaneous needle aspiration.  There  is  considerable debate as to whether
open lung  biopsy  is  appropriate  as  the  initial  diagnostic  measure  in
diagnosis.   Those  that  support  open  lung biopsy contend that an adequate
sample of tissue is  needed  for  histopathologic  exam, stains and cultures.
Those that oppose this view  state  that  there  are  sampling  errors,  with
erroneous diagnosis, and that even with a specific diagnosis there may not be
any  change  in therapy.  The reported survival rate has been estimated to be
from 0-35% and  the  survival  of  treated  patients  is  less than 30%.  The
diagnosis is only made in about 20-78% of cases.  TREATMENT:   When  invasive
aspergillosis  is  suspected  clinically, or is demonstrated on biopsy, there
should be immediate institution  of  Amphotericin  B  after a test dose.  The
total daily dose is 0.8 -1 mg/kg/day  IV  for  several  weeks  as  tolerated.
Thereafter, the dose is reduced to .6 mg/kg/d for a total dose of 2 grams.

                         -ASPIRIN TOXICITY-
LAB: Arterial blood gas, blood for ASA level (urine for ferric chloride  test
or  Ames Phenistix may be used if a rapid ASA is not available), electrolytes
(calculate the anion gap), BUN,  creatinine and PT.  GASTROINTESTINAL: Ipecac
or gastric lavage if within  12  hrs  of  ingestion.   If  bowel  sounds  are
present,  give  activated  charcoal  slurry  of  75-100  G  q4h  and sorbitol
catharsis.  ALKALINE DIURESIS: is used  to  maintain  a  urine pH > 7. In the
first hour hydrate with 500 ml in  the  adult  with  D5W  +  44  mEq  NAHCO3.
Thereafter,  IV hydration at 500 ml/hr of D5W with 30 mEq/liter of KCL and 22
mEq/liter NAHCO3.  Vary the rate  or  add  bicarbonate to tirate pH until the
ASA level is below 30 mg/dl.  Lasix 1 mg/kg IV may  be  needed  to  alleviate
fluid retention.  FOR SEVERE METABOLIC ACIDOSIS: give 1-2 mEq of NAHCO3 q 1-2
hrs to maintain arterial pH above 7.15 in addition to alkaline diuresis.  FOR
SEVERE CLINICAL TOXICITY, metabolic acidosis or ASA level above 100 mg/dl use
charcoal   hemoperfusion.    For  hyperthermia  use  external  cooling.   For
prolonged PT given vitamin K 10 mg IM.  Refractory bleeding may require fresh
frozen plasma.  For  persistent  (>24h)  ASA  level  elevation, obtain a flat
plate before and after contrast.  Concretion due to enteric  coated  ASA  may
dissolve with MAHCO3 150 mEq/liter; otherwise may require removal.

                              -ATAXIAS-
CEREBELLAR  ATAXIAS:  Cerebellar  ataxias  may  be  caused  by lesions of the
midline, or those  of  the  hemispheres.   Disorders  that affect the midline
produce  a  broadbased  stance,  lurching  gait,  small  stepped  gait,   and
occasional  falling.   The  patient has difficulty in standing on one foot or
with the feet  together.   There  may  be  truncal  tremor characterized by a
side-to-side motion.  The patient is unable to perform  tandem  walking,  and
there  may  be  different  forms of nystagmus.  Patients that have cerebellar
infarcts or masses may  produce  headaches  which  are  worse in the morning.
There may be nausea  and  vomiting.   There  may  be  vertigo  which  can  be
precipitated by changes in head position.  Hemispheric cerebellar involvement
produces  hypotonia  of  the ipsilateral extremitiy, and the patient tends to
fall to  that  side.   There  is  dysmetria  of  movement  with  overshoot or
undershoot of the target.  Intention tremor is common,  and  the  patient  is
unable  to  perform alternating movements.  There is a static tremor when the
hands are outstretched.  The  patient  is  unable  to  check movements at the
proper place.  Patients with bilateral cerebellar  disease  produce  symptoms
similar  to  that  seen  in  midline  or  vermal disease as well as bilateral
incoordination of limb movements.  The  midline cerebellum is the most common
site for primary brain tumors, such as cystic astrocytoma and medulloblastoma
in childhood.  Multiple sclerosis can produce demyelinating plaques  anywhere
in  the  cerebellar white matter.  Alcoholism can produce degeneration of the
vermis and the anterior cerebellum, producing gait ataxia.  The Arnold-Chiari
malformation (Type I is mostly  seen  in adolescence and adulthood, where the
cerebellar tonsils are displaced downward into the cervical  canal,  with  or
without  displacement  of  the medulla) and platybasia/basilar impression can
produce cerebellar manifestations.   Other  causes  of cerebellar dysfunction
include heavy metals (mercury, thallium,  lead),  phenytoin,  hypothyroidism,
Creutzfeldt-Jakob  disease,  and  head trauma.  The Dandy-Walker malformation
(posterior  fossa  cyst,   cerebellar   vermis  dysgenesis,  high  cerebellar
tentorium, enlarged posterior fossa, and  elevated  transverse  sinuses)  can
also  produce  cerebellar ataxia.  Alcoholic cerebellar cortical degeneration
produces characteristic  midline  features  such  as  a  broad  based stance,
inability to tandem  walk,  lurching,  staggering,  and  truncal  titubation.
CEREBELLAR  HEMORRHAGE  usually  occurs in long standing hypertension.  Other
causes   of   cerebellar   hemorrhage   include   anticoagulation,   vascular
malformation, and bleeding disorders.  These patients develop sudden onset of
occipital headache, vomiting, dizziness,  inabilty to stand, ipsilateral limb
ataxia, and often times coma.  There is impairment of congugate gaze  to  the
side of the lesion, and there may be an absent corneal reflex or facial palsy
on  the  side of the lesion.  If there is rupture into the subarachnoid space
there will be a xanthochromic spinal fluid and nuchal rigidity.  There may be
brain stem compression  and  cerebellar  tonsillar  herniation that can cause
death.  CEREBELLAR INFARCTION may  be  secondary  to  emobli  or  thrombosis.
About   33%   of   these  present  precipitously.   Patients  typically  have
hypertension, diabetes, cardiac disease and TIAs.  Symptoms include headache,
nausea, vomiting, vertigo, clumsiness of the  limbs, and inability to walk or
stand.  There is gaze paresis to to side of the lesion, nystagmus and  facial
palsy.  Cerebellar infarct extension via edema or infarction can compress the
brain  stem  leading  to  corticospinal dysfunction such as hyperreflexia and
extensor plantar  responses.   Some  will  develop  hydrocephalus  with coma.
NEOPLASMS:  Most  of  these  patients  will  have  papilledema  secondary  to
obstructive hydrocephalus, headache and gait difficulty.  If the  patient  is
over  the age of 40, about 1/3 will have metastases from the breast, lung, GI
tract, kidney or skin.  CEREBELLOPONTINE  ANGLE TUMORS can produce cerebellar
symptoms, such as sensorineural hearing loss,  tinnitus,  vertigo,  headache,
gait  ataxia,  ipsilateral  limb ataxia, fifth and seventh nerve involvement.
Giant aneurysms of the  vertebral  artery can simulate cerebellopontine angle
tumors.  Patients that have von Recklinghausen's neurofibromatosis  can  have
acoustic  neuromas  which  can  be  bilateral.  PARANEOPLASTIC: Carcinomatous
cerebellar degeneration can occur  as  a remote manifestation from carcinomas
of the lung, ovary and lymphomas.  In about 50% of cases, the  paraneoplastic
syndrome  will antedate the actual malignancy.  There is usually an insidious
onset of ataxia  of  limbs  and  gait,  diplopia, nystagmjus, dysarthria, and
vertigo.  CEREBELLAR ABSCESS: May be bloodborne or contiguous spread from  an
adjacent  area.   There  may  be  headache,  increased intracranial pressure,
brainstem compression, focal cerebellar  signs,  cranial nerve deficits of 6,
7, 8. SENSORY ATAXIA: These patients have difficulty in standing and  walking
because they are unaware of the position of their limbs due to lesions in the
afferent  fibers  in  peripheral  nerves,  dorsal roots, dorsal colums of the
spinal cord or medial lemnisci.  They have a broadbased gait just as in those
with cerebellar disease.  However,  unlike  cerebellar disease they can stand
with their feet together and eyes open, but when the  eyes  are  closed  they
will  sway  and  fall  (Romberg's  sign).   TABES  DORSALIS:  Tabes  dorsalis
(syphilitic posterior column lesions) causes a locomotor ataxia which results
in  pain,  ataxia, sensory changes and loss of tendon reflexes.  The onset is
insidious, with stabbing pain in the legs that recurs at irregular intervals.
Following this, unsteadiness of gait occurs that is worse in the dark.  There
may be hyperesthesia and paresthesias and a broadbased gait.  The patient may
lose  urinary   bladder   sensation   that   causes   urinary  retention  and
incontinence.  Argyll Robertson pupils are present and  there  may  be  optic
atrophy.   There is hypotonia, decreased or absent deep tendon reflexes, loss
of vibratory and  joint  position.   Romberg's  sign is positive.  HEREDITARY
ATAXIAS (Spinocerebellar ataxias):  Friedreich's  ataxia  is  a  spinal  cord
ataxia  (patholgogic  changes  in  the  corticospinal tracts, spinocerebellar
tracts and the posterior columns) which  usually presents between the ages of
6-16.  Initially the patient may have difficulty with running.   However,  in
well  established  cases there is a mixed sensory and cerebellar gait ataxia,
dysarthric  speech,  postive   Romberg   sign,  areflexia,  extensor  plantar
reflexes, ataxic arms, action and intention  tremors,  absent  vibratory  and
position  senses,  pes  cavus  and  cardiac  conduction abnormalities.  Other
spinocerebellar    hereditary    disorders    include    Refsum's    disease,
ataxia-telangiectasia, mitochondrial multi-system  disorder, Holmes and Marie
cerebellar  cortical  degenerations,  and   multiple   system   degenerations
(Shy-Drager,   Dejerine-Thomas,  Machado-Joseph,  and  Menzel).   LABORATORY:
Patients with gait  ataxia  should  have  tests for hypothyroidism, diabetes,
serologic  tests  for  syphilis  and  immunological  disease  (serum  protein
electrophoresis).  A CSF study for pleocytosis, VDRL and elevated protein may
be helpful.  There should be a thorough search for underlying malignancy that
may produce a paraneoplastic syndrome.

                        -ATRIAL FIBRILLATION-
There are several causes of paroxysmal or chronic AF and include mitral valve
disease, acute  and  chronic  coronary  disease, cardiomyopathy, hypertensive
cardiovascular disease, chronic  sinoatrial  disease,  hyperthyroidism  (1%),
pulmonary  embolism  (2.5%), alcohol, drugs as cocaine, caffeine, cholinergic
stimulation and cardiothoracic surgery.  The  prevalence  of  AF is 2% in the
general population and 5% in person >60  years  old.   May  use  IV  digoxin,
verapamil,  diltiazem  and  esmolol.   Digoxin  will slow the rate in about 2
hours.  Give 0.25 mg-.5 mg IV then 0.25  mg  IV q4h up to 1-2 mg in the first
24 hours, then maintain with 0.125-0.375 mg  po  qd.   Watch  for  AV  block,
ventricular  arrhythmias,  nausea,  anorexia & yellow vision.  Direct current
cardioversion should be done if  the  AF  is associated with CHF, hypotension
and persistent ischemia.  Diltiazem given as a bolus of 0.25 mg/kg IV over  2
min.  Repeat if necessary after 15 min as 0.35 mg/kg over 2 min.  This can be
followed  with  maintenance  of  5-15 mg/hr IV or 30-90 mg po qid.  Watch for
heart failure,  bradycardia  and  hypotension.   Don't  use in pre-excitation
syndromes or if mechanism of wide QRS is unknown.  Reduction  of  ventricular
response  will  occur  in  about  5  minutes  and  can last up to 10 hr after
infusion is stopped.  Verapamil can  be  used  but its effect is short.  Give
2.5-10 mg IV over 2 min then .005 mg/kg/min  or  5-10  mg  boluses  every  30
minutes or 80-160 mg tid.  Watch for bradycardia, hypotension, heart failure.
Should  not  be  used  in  pre-excitation  syndromes.  The digoxin level will
increase.  Esmolol could be used,  but  the  effect is extremely short.  Give
500 ug/kg IV over 1 minute, then 50 ug/kg IV for 4  min.   If  necessary  may
repeat  the loading dose and increase the maintenance dose by 25-50 ug/kg/min
q  10  min.   Watch  for  hypotension,  heart  failure,  bronchospasm,  local
irritation and use judiciously in renal failure.  For the acute situation use
DC cardioversion  or  IV  procainamide.   For  elective  cardioversion use IV
procainamide, quinidine, disopyramide, propafenone,  flecainide,  amiodarone,
or  sotalol.   Not  all  patients  need  to be restored to sinus rhythm.  One
reason is that about 50%  of  patients  restored  to sinus rhythm and treated
with Class 1A drugs, will revert to AF.  If the patient  has  had  AF  for  2
years  or  more then it is unlikely that they will maintain sinus rhythm.  If
left atrial enlargement is present, then  success is less likely.  If patient
has severe systolic or diastolic dysfunction, a  dilated  hypokinetic  heart,
severe  ventricular  hypertrophy,  then  they  need  the added atrial impetus
afforded by sinus rhythm.  Procainamide 10-15 mg/kg IV at 50 mg/min should be
given.  Observe for heart failure,  hypotension  and widening of the QRS.  Up
to 50% will convert with pharmacologic drugs.  Quinidine 200-400 mg  qid  may
be  tried.   Side  effects  include  proarrhythmia, increased digoxin levels,
nausea and diarrhea.  Disopyramide 100-300 mg bid is another alternative.  Be
aware  of  anticholinergic   effects,   proarrhythmia,   and  heart  failure.
Flecanide 50-100 mg bid may be used if no  contraindications.   Side  effects
are  heart  failure  and  proarrhythmia.   Propafenone  150-100 mg tid may be
effective and the side effects  are proarrhythmia and heart failure.  Sotalol
80-320  mg  bid  is  another  possibility.   Observe   for   heart   failure,
proarrhythmia  and bradycardia.  Propafenone and Sotalol have equal efficacy.
Amiodarone 100-400 mg qd may be used  but  this drug has many side effects as
bradycardia, hyper/hypo thyroidism, pulmonary and  hepatic  toxicity,  nausea
and  as  of this writing has NOT been approved for this indication.  However,
success rates of 60% have  been  reported  in patients that were in resistant
AF.  The longer the patient has had the AF the greater the energy required to
convert.  The smaller the left atria  (<4.0  cm)  and  the  more  coarse  the
fibrillatory  waves  (>2mm),  the less energy required.  Start at 100 Joules.
If unsuccessful increase to 200 J  after  a  Class I agent as procainamide or
quinidine has been  given.   This  will  result  in  restoration  of  75%  of
patients.   New  studies  have  shown  that  if  the  serum  digoxin level is
therapeutic, and not toxic, then no  need to withhold digoxin for 48-72 hours
as previously  done.   If  possible  give  warfarin  for  3  weeks  prior  to
conversion to avert embolization.  For acute protection give IV heparin if AF
is  greater  than  24  hours  duration  &  warfarin  for  3  weeks  prior  to
cardioversion.    For   chronic  protection  of  stroke,  anticoagulate  with
warfarin.  You can start warfarin at 5  mg  daily and check PT 4-6 days later
and monitor to keep the INR at 2.0-3.0.  If mechanical valves  are  in  place
then  keep INR at 2.5-3.5.  In pregnancy warfarin should not be used in first
trimester  and  preferably  not  during  the  entire  duration  of gestation.
Heparin is the preferred agent.   Warfarin  doesn't  cause  an  anticoagulant
effect in nursing infants.  There is some controversy for anticoagulation use
in  lone atrial fibrillation < 60 years of age and paroxysmal AF.  ASA 325 mg
daily will offer some  protection  if  unable  to anticoagulate with warfarin
because  of  bleeding  disorders,  active  peptic  ulcer,  alcoholism,   gait
disorders,  severe  renal or liver disease, previous hemorrhage, uncontrolled
hypertension  and  non-compliance.   If   patients   are  not  maintained  on
antiarrhythmic drugs, only about 15-30% will remain in sinus rhythm 6  months
after  cardioversion.   About  50-60% will stay in sinus rhythm for 1 year if
quinidine is used post-conversion.  Drugs in the  Class 1A, 1C, or III may be
used.  This situation  requires  a  special  approach  when  there  is  rapid
conduction  over  the accessory pathway which may lead to a fatal ventricular
arrhythmias.  Digoxin, verapamil or diltiazem should not be used because they
preferentially suppress conduction  over  the  AV  node,  and  thus may speed
conduction over the accessory pathway.  Procainamide IV is the drug of choice
as it slows conduction through the  accessory  pathway  and  will  frequently
reestablish  sinus rhythm.  If the patient is unstable, then DC cardioversion
is  in  order.   To  prevent  recurrences  of  AF,  quinidine,  procainamide,
disopyramide, flecainide and propafenone may be used, as these drugs suppress
antegrade travel over the  accessory  pathway  and  keep the patient in sinus
rhythm.   Also,  for  long  term  prevention  of  recurrences  radiofrequency
ablation of the accessory pathway by catheter is effective  in  over  90%  of
patients.  If this fails, then surgical interruption can be done.

                 -ATRIAL FIBRILLATION AND EMBOLISM-
It has been known for many years that patients with valvular disease  and  AF
have  an  increased  risk of embolism producing stroke.  It is now known that
any patient with non-valvular  AF,  particularly  those with previous stroke,
TIAs, hypertension, or other heart diseases  are  at  increased  risk.   Five
recent  clinical  trials  have demonstrated that warfarin can prevent stroke.
The average annual risk of stroke  or systemic embolism in those treated with
warfarin was about 2% as compared with 5% in controls.  This translates to  a
3%/yr  reduction  in the rate of stroke, or a risk reduction of approximately
60%.  The optimal INR  for  prevention  should  be  between 2-3 which was the
average target INR  in  the  studies.   The  studies  demonstrated  that  the
benefits of warfarin therapy outweigh the risks in those patients at low risk
of  hemorrhage.   However,  most of the patients enrolled in the studies were
less than 75 years  of  age.   In  patients  that were carefully selected and
monitored, the average increased risk of major bleeds with warfarin was  very
small at about 0.5%/yr.  The AFASAK study demonstrated no benefit by using 75
mg of ASA/day in protecting patients against embolic complications.  The SPAF
study,  however,  did  show  a  statistically  decrease in the annual risk of
stroke from 6.3% to 3.6%, for reduction  of  42%.  It was also shown that the
risk of major bleeding was similar in ASA and  placebo  treated  patients  or
about  1%/year.   Until  completion  of 3 studies that are ongoing as of this
writing, it  seems  preferable  to  use  warfarin  rather  than  ASA in those
patients that are not at high risk for bleeding, because of the magnitude  of
risk  reduction  with  warfarin  as  well  as  the  consistency	provided with
warfarin.  The TAATAF study, a Netherland trial, is randomizing 150 mg of ASA
to warfarin with target INRs  of  1.1-1.6,  and  warfarin with target INRs of
2.5-3.2.  In Europe there is another study that is comparing the efficacy  of
warfarin,  ASA  and  no therapy, in AF with recent stroke.  This study should
help clarify if there is increased risk of intracranial bleed with a previous
stroke.  At the present  time,  timing  of  anticoagulation in a patient with
recent stroke depends  on  the  size  and  appearance  of  hemorrhage  on  CT
scanning.

                           -ATRIAL MYXOMA-
Myxomas  are the most common cardiac tumors and account for 25% of all tumors
and cysts of the heart and  pericardium.   Myxomas have been reported in ages
from 3 to 83, but the mean age is 56 years.  Females are affected  in  a  3:1
ratio.   About  86 percent involve the left atrium and they are attached by a
stalk near the fossa ovalis.  They are typically 6-8 cm in size and histology
reveals   myxoma,   fibroblastic   and   endothelial   cells   in   an   acid
mucopolysaccharide matrix.  The right  atrium  is  the next most common site,
and rarely  the  ventricles.   They  are  very  friable  and  gelatinous  and
therefore  can embolize very easily after battering against the mitral valve.
They can contain  calcium;  especially  right  atrial myxomas.  They protrude
through the mitral valve during diastole.  If they become  entrapped  in  the
mitral  valve  they  can  cause  syncope.   Symptoms  can be more severe when
standing or during exercise, and  the  murmurs  can  come and go depending on
posture.  Myxomas can become infected and cause a bacteremia which would make
it difficult to distinguish from endocarditis, particularly if the attachment
could not be visualized by echocardiogram and it was thought the mass  was  a
vegetation  of  the  mitral  valve.  The presenting symptoms can mimic mitral
valve disease, primary pulmonary hypertension, connective tissue disease, CVA
& endocarditis.   Myxomas  can  simulate  polymyositis  and polyarteritis and
systemic amyloidosis.  About 7 percent have a family history  of  myxoma,  or
the  syndrome  myxoma,  which  can  include  primary  nodular  adrenocortical
hyperplasia,   myxomatous  mammary  fibroadenomas,  testicular  Sertoli  cell
tumors, pituitary  adenomas  with  excessive  growth  hormone production, and
pigmented cutaneous lesions.  Right atrial myxomas can embolize to the  lungs
and  so  can  left  atrial  myxomas  if there is a left to right shunt.  Left
atrial tumors embolize peripherally  and  can  be found in surgically removed
embolus.  Left atrial myxomas can cause CHF and hemoptysis (15%), murmurs  of
mitral  stenosis,  such  as  an increased first heart sound, diastolic murmur
(70%), tumor plop  (33%)  which  is  similar  to  the  opening snap of mitral
stenosis, and mitral insufficiency due to damage to the  mitral  leaflets  by
the myxoma, producing a systolic murmur (50%).  Syncope can occur.  About 25%
of  patients  have friction rubs.  Patients can have weight loss (25%), fever
(50%), arthralgias, fatigue,  sweating,  Raynaud's  phenomenon, clubbing, and
anemia, which can be hemolytic.  Hemoptysis occurs in 15 percent of patients.
There is elevation of the  ESR  (33%);  sometimes  very  high,  leukocytosis,
thrombocytopenia,  thrombocytosis,  and  erythrocytosis.   The EKG is usually
normal but occasionally there may be  p wave abnormalities.  Usually there is
sinus rhythm.  The chest x-ray is  usually  normal  as  is  the  heart  size.
Suspect  myxoma  if  the  heart  size  normal and there is CHF.  Right atrial
myxomas show calcification on fluoroscopy.  Transesophageal echocardiogram is
the method of  choice  for  diagnosis.   There  may be irregular echogenicity
secondary to cysts in the tumor.  Retrograde extension of the tumor into  the
pulmonary veins or invasion of ventricular or valvular tissue would suggest a
carcinoma.   CT  and  MRI  are also of value in diagnosing myxoma.  Embolized
tumor recovered for histologic examination can show the myxoma origin.  Blood
cultures are  negative.   Hyperglobulinemia  and  IgG  elevation  are common.
Treatment is surgical excision and the results are good with  excellent  long
term survival and low recurrence.

                       -ATRIAL SEPTAL DEFECT-
Atrial septal defect (ASD) is the second most common congenital defect and is
usually  asymptomatic  until  middle  age.   Early,  most  have cardiomegaly,
dilated pulmonary arteries  with  increased  vascularity  and an asymptomatic
murmur.  If the defect has not been closed by the fifth  decade,  almost  all
patients will be symptomatic with CHF, right ventricular failure, arrhthmias,
or paradoxical embolism.  Preferably, the defect should be closed between 2-5
years  of  age.   If  the  defect is closed before the onset of symptoms, the
natural  history  is  similar  to  those  patients  without  congenital heart
disease.  However,  there  is  an  increased  incidence  of  supraventricular
tachycardia,  atrial flutter and sinus node dysfunction in those ASD patients
that have been  repaired.   DIAGNOSIS:  There  is  a moderately loud systolic
ejection murmur that can be  heard  in  the  second  and  third  interspaces,
parasternally,   which  is  due  to  increased  pulmonary  artery  flow.   S2
demonstrates fixed splitting of the second heart sound and does not vary with
respiration.  In  ostium  secundum  defects,  right  axis  deviation or right
ventricular hypertrophy may be present.  Almost all cases of  ASD  will  have
either  incomplete  or complete right bundle branch block and a superior axis
deviation is seen in ostium  primum  defects.  In patients with sinus venosus
defects, the P axis is directed to the left of + 15  degrees.   Chest  x-rays
will show an enlarged right atrium and ventricle, small aortic knob and large
pulmonary  arteries, with increaseed pulmonary vascularity.  Echocardiography
can depict a large right atrium  and ventricle secondary to right ventricular
overload.  ECHO with saline bubble  contrast  +  doppler  flow  studies  will
detect  the  shunting  and  increased pulmonary flow.  MRI is also capable of
demonstrating the anatomy.  Radionuclide  flow  studies  are able to quantify
the left to  right  shunt.   Cardiac  catheterization  will  demonstrate  the
increase in oxygen saturation between the venae cavae and the right ventricle
which  is  due  to  the  admixture  of oxygenated blood from the left atrium,
measure pulmonary vascular resistance, and  quantify the shunt.  If right and
left ventricular contrast angiography is done, associated anomalous pulmonary
venous drainage or valvular abnormalites may be appreciated.  OSTEUM SECUNDUM
DEFECTS: The osteum secundum defects (OSD) or fossa ovalis defect is the most
common type of ASD.  Small defects almost always close before the end of  the
first  year.   Rarely,  do moderate or large defects close after the age of 1
spontaneously.  Surgical mortality is almost unknown in isolated secundum ASD
and all defects that have not closed should be repaired.  Increased pulmonary
resistance secondary to pulmonary hypertension  is rare in childhood or young
adults with secundum defects, but is more common in primum defects.  However,
after the age of  40,  cardiac  arrhythmias  as  atrial  fibrillation,  heart
failure,  and  pulmonary hypertension may occur in secundum defects.  Surgery
should not be  done  in  patients  with  pulmonary hypertension with reversed
right to left shunting because of the possible  development  of  acute  right
heart  failure.   Surgical  mortality is < 1 % in patients < 45 years of age,
have pulmonary artery pressures < 60  mm  Hg, and are not in cardiac failure.
Patients > 40 years of age, with pulmonary systolic pressure > 60 mm Hg,  and
in  cardiac  failure  have  a 5-10% mortality.  OSTIUM PRIMUM DEFECTS: Ostium
primum defects represent the  second  most  common  ASD.  They will not close
spontaneoulsy as some secundum defects do, and they are usually rather large.
Because these defects are AV septal defects, usually in  association  with  a
cleft   anterior   leaflet   of  the  mitral  valve,  there  will  be  mitral
regurgitation murmurs besides  the  fixed  S2.   As expected, surgical repair
tends to be more difficult than a secundum ASD, because of the need to repair
the mitral valve.  Patients with this defect tend to be more symptomatic at a
younger age than secundum ASD.  Post-operatively, in general, these  patients
do  fairly  well,  but there may be residual mitral regurgitation or stenosis
and a repeat operation may  be  needed  later,  either to repair the valve or
replace it.  Endocarditis prophylaxis  is  necessary  because  of  the  cleft
mitral valve.  SINUS VENOSUS DEFECTS: Sinus venosus defects may be frequently
associated with an anomalous connection of one or more of the pulmonary veins
which usually provide venous return to the right atrium or superior vena cava
from  the right lung.  These veins are close to the sinus venosus defect near
the junction of the superior vena  cava  and the right atrium, and because of
this, can be deflected into the left atrium when the ASD  is  closed.   There
frequently  is  scarring  and  stitches  near  the  sinus  node  which causes
post-operative chronic supraventricular arrhythmias.

                       -ATRIAL SEPTAL DEFECT-
Widely split, fixed S2, middiastolic murmur may be present,  ejection  murmur
at  ULSB, loud S1.  Common in fetal alcohol syndrome, congential lesion, left
chest may be enlarged.

              -ATTENTION DEFICIT HYPERACTIVITY DISORDER-
Attention deficit hyperactivity disorder (ADHD) may affect 2-9% of school age
children.   There  is a 3:1-8:1 higher incidence in males.  The most frequent
age of onset is below the  age  of  4,  but ADHD may not fully manifest until
school.  The etiology of ADHD is unknown,  but  probably  is  multifactorial.
There   has   been   an   increased  risk  in  Reye's  syndrome,  meningitis,
encephalitis, exposure to cocaine,  heroin  and  alcohol.  Many patients come
from deprived or  traumatic  backgrounds  that  can  result  in  anxiety  and
psychologic  trauma.  It has recently been shown that the disorder can extend
into adulthood.   Therefore,  the  disease  should  be  treated early.  These
patients demonstrate sustained motor activity, impulsivity,  distractibility,
and inattentiveness.  The child's behavior, in turn, can cause stress for the
parents.   The  diagnosis is usually established by comparing the behavior of
the afflicted child  with  that  of  other  children  of  the  same age.  The
diagnosis may first be entertained by school teachers.  Teachers may use  the
Conners, Children's behavior checklist and ADD-H comprehensive teacher rating
scales  to  render  an  objective  evaluation.   Following this the physician
should  obtain  a  complete  history  including  history  of  epilepsy, sleep
problems, and temper tantrums.  Laboratory tests may include tests for  lead,
iron  deficiency,  thyroid  and  chromosomal  abnormalities  and  EEGs.   The
diagnostic  criteria  for  ADHD consists of 8 or more of the following for at
least 6 months: Easy distraction,  inability  to  stay seated, can't wait for
his or her turn, is constantly squirming, constantly shifting from one  thing
to another without finishing the previous task, talks incessantly, can't play
quietly,  doesn't  listen,  loses  things,  doesn't follow through when given
instructions, can't complete work or  play, interrupts others' talk or games,
is reckless, and answers a question before the  question  is  finished.   The
patient  also must have the onset before the age of 7 and there must not be a
developmental disorder.  TREATMENT:  Treatment  of  ADHD  is a combination of
behavior management techniques and drugs.  Routines should be established  in
the  household  in an attempt to help the child accept order and consistency.
There should be  specific  times  for  TV,  homework,  chores, snacks, meals,
wake-up and sleep.  Rules for the household  must  be  established  that  are
consistently  carried  out  on a day-to-day basis.  The child must understand
what the consequences will be  if  the rules are broken.  Aggressive behavior
should not be tolerated such as pushing, hitting, biting, etc.  If the  child
violates  certain  rules,  he  or she should be told that the behavior is not
appropriate.  Moreover, the child should be told why that particular behavior
is inappropriate.  Immediately following  the  violation, the child should be
punished.  This may consist of sitting in a chair for  a  certain  length  of
time.   The  chair  should be in a quiet place that is away from distractions
such as TV, toys,  etc.   If  the  child  respects  the rules, they should be
praised for their observation of the rules.  However,  the  child  should  be
given  the  liberty to dissipate his or her energy such a running, walking or
bicycling in a safe environment.   Another  method for controlling the child,
is establishing a reward system.  The rewards may consist of extra  TV  time,
going  to  a  movie,  getting  a special dessert, going to a fast food store,
staying up  later,  or  almost  anything  that  doesn't  lead  to destructive
behavior.  The tasks that lead to the reward  may  consist  of  keeping  toys
together, putting clothes away, making the bed, taking out trash, setting the
table,  catching  the school bus on time, doing homework, hanging up jackets,
remembering  to  bring  homework  home,  waking  up  by  a  certain  time, or
practicing the piano.  Various tasks may accrue more points than others.   In
order  to  make  the  system  work,  it  is  helpful  to make a weekly chart.
Patients with ADHD should  not  be  placed  in  environments that would prove
difficult for patients, such as prolonged  shopping  trips,  extended  church
services,  attending  concerts,  etc.   In  order  to  increase  the  child's
attention  span,  a  certain  portion  of the day should be set aside for the
child and parent to interact in  a quiet environment.  During this time books
may be read aloud to the child and games can be played  which  will  increase
the  child's  attention.   As  the child responds favorably, praise should be
given in generous quantities.  Homework can be very distressing to the child,
parents and  teachers.   Homework  should  be  placed  within  the structured
framework of daily tasks.  It should be done in a quiet place that is free of
distractions, and should have time limits for work as well as breaks.  School
work may be enhanced by seating the child in the front  of  the  school  room
next  to  a  goal  oriented  child.  By seating the child in the front of the
room, distractions may be kept to a minimum.  In order to release some of his
energy, the child may  be  given  simple  tasks  such  as passing out papers,
erasing the blackboard, or other  constructive  tasks.   Children  with  ADHD
should  be  supervised  during recess, playground and cafeteria activities as
these activities can lead to  fights and physical disturbances.  MEDICATIONS:
About 80% of children will respond to psychostimulants  with  improvement  in
academic  achievement,  decreased  impulsivity,  increased attention span and
decreased adverse  behavioral  tendencies.   Medications  should  be  used in
conjunction with the above behavior methods.  Children that are of school age
are the best candidates for these psychostimulants, as children less  than  5
years  of  age are less likely to respond, and are more prone to adverse side
effects from  the  medications.   These  side  effects  can  range from sleep
disturbances to  irritability,  anorexia,  headache,  tics,  abdominal  pain,
dysphoria,  and  growth  delay.   Patients  that  have growth delay should be
removed from the drug  until  growth  has  "caught  up".   In the past, these
psychostimulants would be discontinued during school holidays, and  weekends.
This  is no longer recommended.  Drugs should not be started at the beginning
of the school year, as these periods  are  very stressful.  If the drug is to
be discontinued, to ascertain if it is still needed, this should  be  done  a
few  months  into  the school year.  METHYLPHENIDATE (Ritalin) is the drug of
choice and is usually started as 5  mg/day (.3 mg/kg/dose) and increased by 5
mg/week, until further clinical improvement or side effects occur.  The usual
dose per day is usually 5-25 mg divided into 2 doses.  This is usually  given
in  the AM and at noon.  DEXTROAMPHETAMINE SULFATE (Dexedrine) may be used if
Ritalin is not  helping  or  side  effects  have  developed from the Ritalin.
Dexedrine has a high potential for abuse and  is  not  the  drug  of  choice.
Dexedrine  comes as 5 mg tablets, elixir, and sustained release spansules (5,
10, 15 mg).  The tablet dose is .2-.4 mg/kg/dose.  If the spansules are used,
start at twice the  regular  tablet  dose,  and  give  in the AM.  The tablet
duration of effect is slightly longer than Ritalin.  PEMOLINE (Cylert)  works
just  as  well  as  the  above,  but has the potential for additional hepatic
toxicity.  Because of this, liver  function  testing is necessary in patients
taking pemoline.  The onset is slower  with  pemoline  and  the  duration  is
longer  than Ritalin or Dexedrine.  Therefore, Cylert can be given once a day
in the AM, starting with 37.5  mg  (usually 2.25 mg/kg/day) and increasing by
18.75 mg/day.  The usual effective range  is  between  37.5  and  75  mg/day.
CLONIDINE  (Catapres)  has  shown  to be effective in ADHD, with reduction in
impulsivity, hyperactivity, and inattention.  Indications for its use include
those  patients  that  are  only  partially  helped  with  Ritalin.   In this
situation both Ritalin and clonidine are given together.  It is also used  in
patients  that  develop tics with Ritalin or Dexedrine.  Clonidine is started
at .05 mg  (1/2  tablet)  given  at  HS.   It  is  then  increased  by .05 mg
increments at weekly intervals to a maximum of .3-.4 mg/day.  After the child
becomes acclimated to the HS dose, it is given as TID or QID.   Clonidine  is
supplied  as  .1  and  .2  mg  tablets and as a transdermal patch (.1-.3 mg).
Clonidine should not be  stopped  abruptly.  TRICYCLIC ANTIDEPRESSANTS: These
are usually used in adults or patients that are older than 13 years of age as
a third line treatment.  Imipramine (Tofranil,  Janimine)  is  given  as  1-4
mg/kg/day  (may  be  given  at  HS  or the daily dose can be divided into BID
doses).  Imipramine is  supplied  as  10,  25,  and  50 mg tablets.  Patients
should be monitored for cardiac problems while taking this drug.  Desipramine
(Norpramin) is given as 1-4 mg/kg/day (this may be given as an  HS  dose,  or
the  total  can be divided into two equal doses and given BID).  Despipramine
is supplied as 10, 25, and  50  mg tablets.  Again, cardiac monitoring should
be done.

                    -AUTOIMMUNE HEMOLYTIC ANEMIA-
Autoimmune   hemolytic   anemia   (AHA)   is   diagnosed   by   demonstrating
immunoglobulin  or  complement  on  the  patient's  red blood cells using the
direct antiglobulin test  (DAT)  (direct  Coombs'  test).  Macrophages in the
spleen and other parts of  the  reticuloendothelial  system  are  capable  of
detecting  the  Fc  portion  of  the  antibody.  This interaction between the
antibody coated RBC and the  splenic  marcrophages  causes the red blood cell
membrane to be removed.  This produces a spherocyte that is very vunerable to
destruction by the red pulp of the spleen because spherocytes have  decreased
deformability.  Likewise, if the RBC has C3b on the surface, Kupffer cells in
the  liver  will  also  participate  in  the  hemolytic  destruction  of  the
erythrocyte.   Immune  hemolysis  is  a secondary disease in about 2/3 of the
cases and idiopathic in the remainder.  The hemolysis is usually divided into
a warm reactive antibody (IgG  antibodies  that  bind most strongly at 37.5 C
and usually does not activate complement) AND a cold reactive  antibody  (IgM
antibodies  that  bind  most  strongly below body temperature with binding of
complement).  Warm reacting  antibodies  are  associated  with idiopathic and
secondary autoimmune hemolysis (secondary  to  lymphoproliferative  diseases,
collagen vascular diseases, carcinomas, and drugs).  Cold reacting antibodies
may  be idiopathic or secondary (lymphoprolierative diseases and infections).
COOMB'S TESTING: A positive anti-IgG  and  negative anticomplement is seen in
alpha methyldopa hemolytic anemias, lymphoproliferative disorders  and  other
cancers,  idiopathic  autoimmune  hemolysis,  delayed  hemolytic  transfusion
reactions  and  occasionally  in  patients  taking  penicillin.   A  negative
anti-IgG  and a positive anticomplement is seen in infections associated with
the  production  of  cold  agglutinins,  cold  agglutinin  disease, immediate
hemolytic  transfusion  reactions  secondary  to  ABO   incompatibility   and
lymphoproliferative  disorders or other forms of cancer.  A positive anti-IgG
and  a  positive  anticomplement  Coombs'  test  is  seen  in  immune complex
diseases, autoimmune diseases which produce circulating immune complexes  and
drug  related immune hemolysis.  LABORATORY: The patient will have a variable
degree of anemia, and spherocytes  and reticulocytosis may be present.  There
may be nucleated RBCs in the peripheral smear as well  as  elevation  of  the
indirect  bilirubin.   There  may  be  RBC polychromasia and elevation of the
plasma LDH.  Plasma hemoglobin, urine hemoglobin and urine hemosiderin can be
seen in cold antibody hemolytic  disease.   Erthrophagocytosis can be seen in
warm  antibody  hemolytic  anemia.    Haptoglobin   is   usually   decreased.
Examination  of  the  bone  marrow  is  not  usually  indicated but will show
erythroid hyperplasia.  The  direct  Coombs'  test  is  positive  for IgG and
possibly for complement.  The indirect Coombs' test can be positive (80%), if
there is a large amount of autoantibody that has saturated the binding  sites
of  the  RBCs.   Approximately  10%  of  patients with autoimmune spherocytic
hemolytic anemia will need to have a  micro  Coombs test in order to detect a
low burden of autoantibodies.  CLINICAL: Warm antibody  autoimmune  hemolytic
anemia  can  cause  the  patient  to present with dyspnea, decreased exercise
tolerance and other symptms of anemia.   Splenomegaly is present in aobut 33%
of patients.  Congestive heart failure sometimes develops  in  patients  that
develop  hemolytic  anemia  rapidly.   Physical  exam  may  reveal  signs  of
underlying disease that produce the hemolytic anemia such as lymphadenopathy,
petechiae,  hematuria, rash and fever.  TREATMENT: Prednisone is the mainstay
of treatment.  Prednisone is given at  1-2 mg/kg/day, usually starting with a
single dose of 60 mg/day and increasing the prednisone to 100 mg/day if there
has been no improvement after several  days.   A  response  is  usually  seen
between 10 days to 3 weeks and is heralded by a decrease of the reticulocytes
and  an  increase  in  the  hematocrit.   Prednisone  functions by decreasing
autoantibody  production  and  decreasing  the  expression  and  function  of
macrophage Fc  receptors.   After  a  response  is  noted,  the prednisone is
tapered over the following 3 months.  About 3/4 of  patients  that  have  the
idiopathic  form  will respond to large doses of prednisone, and about 1/4 of
these patients will have a sustained remission when the prednisone is tapered
completely to zero mg.  About 50%  will require maintenance therapy with 5-20
mg  of  prednisone/day.   The  remaining  25%  will  require  high  doses  of
prednisone to keep the hematocrit at  a  reasonable  level.   Splenectomy  is
indicated  in patients that do not respond to prednisone or those who require
large doses of prednisone.  About 50-60% of patients that undergo splenectomy
will have a good  initial  response  and  require  <  15 mg of predisone/day.
Complete remission secondary to splenectomy is not common and most  of  these
patients  must  be  supported  with  low  dose prednisone.  Only about 10% of
patients will be refractory to  steroids or splenectomy and require treatment
with   azathioprine,   cyclophosphamide   of    vinca    alkaloids.     These
immunosuppressive agents are cytotoxic and commonly cause marrow suppression.
For  this reason danazol is usually tried before the use of immunosuppressive
agents.  Danazol has been found to  be equally effective in patients with and
without their spleen.  Moreover, danazol works synergistically with  steroids
so  that the dose of steroids can be gradually reduced, and then discontinued
after which the  danazol  can  slowly  be  tapered.   It  is recommended that
danazol be continued for at least one year, since relapses are  common  after
withdrawal  of therapy within this time period.  Danazol is given in doses of
400-600 mg/day.  High dose IV immune  globulin (500 mg/kg daily for 1-4 days)
can be very efficacious in  decreasing  the  hemolysis.   Unfortunately,  the
benefit is short-lived and should only be used in emergency situations as the
drug  also  is  very  costly.  Also in life threatening hemolytic anemia, RBC
transfusion may be needed.  However, this poses more difficulties because the
lab  is  usually  unable  to   find   compatible  blood  since  the  patients
autoantibody reacts with the basic component of the Rh locus that  is  common
to  all  Rh phenotypes.  Only small amounts of washed RBCs should be given to
control the patients symptoms.   Plasmapheresis  is  useful for patients with
IgM induced hemolytic anemia.  It also may be useful in  some  patients  with
IgG immune hemolytic anemia.

            -AUTOMATIC IMPLANTABLE CARDIAC DEFIBRILLATORS-
Automatic  implantable cardiac defibrillators (AICD) are indicated in patients
with hemodynamically unstable ventricular  tachyarrhythmias that are unrelated
to electrolyte imbalance, drug toxicity, or acute myocardial infarction.  They
were introduced for clinical use in 1984, and since then have been shown to be
associated with low  recurrent  sudden  death  rates  in  patients  that  have
survived cardiac arrest attributed to VT or VF.  They are capable of detecting
ventricular  tahyarrhythmias  and  then  delivering a low energy shock that is
delivered either  through  epicardial  patch  electrodes  or  endocardial lead
electrodes within 30 seconds of the onset  of  the  arrhythmia.   Sensing  and
pacing  leads  can  be  epicardial or endocardial.  Endocardial electrodes are
inserted through the subclavian or cephalic veins into the right ventricle and
atrium.   Before  attaching  the  leads   to  a  thoracic  subcutaneous  pouch
generator, the system is tested to ascertain the amount of energy required  to
reproducibly  terminate  induced VF (defibrilaltion threshold).  After this is
determined, a safety  factor  of  about  10  Joules between the defibrillation
threshold and the ouput of the device is established.  Prior to discharge from
the hospital the device is tested again in the  electrophysiolgic  laboratory.
The longevity of the pulse generator is about 3-4 years.  The energey required
for  internal  defibrillation  is about 14-40 Joules compared with the 200-350
Jourles needed for external cardioversion.  These devices can be programmed to
sense tachycardias above a  predetermined  rate  and  deliver  a shock after a
predetermined period.  This can result in pseudo  shocks.   These  shocks  are
usually delivered during exercise or when there are no symptoms.  The shock is
delivered   in   response  to  supraventricular  arrhythmias  such  as  atrial
fibrillation with fast ventricular  responses,  recurrent  non sustained VT or
sinus tachycardia.  If these are frequent, the device can be reprogrammed,  or
cardiac  drugs can be added.  Other causes of false discharges occur with lead
fractures, or when muscle twitches are sensed.  During surgery, electrocautery
can  also  cause  false  discharges  from  the  device.   The  new  generation
defibrillators have antibradycardia pacing and algorithms for pace termination
of ventricular tachyarrhythmias.  For  example,  termination  of an episode of
ventricular tachycardia can be achieved by a burst  of  overdrive  ventricular
pacing.   If  this  fails  to  terminate  the  VT, a synchronized shock can be
delivered.  For ventricular  tachycardia  the  shock  is  synchronized, but is
asynchronous in ventricular fibrillation.  Shocks for ventricular  tachycardia
or  ventricular  fibrillation  depends  on  the rate and requires confirmation
before the discharge is delivered.  AICDs  are indicated if there has been one
or more documented episodes of hemodynamically  significant  VT  or  VF  in  a
patient  who  has not responded to any of the cardiac drugs, who has continued
inducibility at electrophysiologic testing,  who  has failed catheter ablation
or in those who have failed surgical correction.  AICD  is  not  indicated  in
recurrent   syncope  of  undetermined  cause  in  patients  without  inducible
tachycardias, or in those not due to hemodynamically significant VT or VF.  In
general, the perioperative mortality  for  endocardial  lead placement is much
less than epicardial leads.  The perioperative mortality for epicardial  leads
is  about  5.5%,  and the endocardial lead method is about .4%.  There also is
improved 1 year survival of  approximately  96% for endocardial leads compared
to about 85% for epicardial leads.

 -AXILLARY THROMBOSIS - EFFORT THROMBOSIS OF THE AXILLOSUBCLAVIAN VEIN-
This  is also known as the Paget Schroetter syndrome.  It usually affects the
young with a mean  of  23  years.   A  typical presentation would include the
sudden onset of a feeling of heaviness, with  noticeable  swelling  and  mild
cyanosis  of the affected extremity.  There is increased venous prominence in
the hand and forearm as  well  as  the  appearance of collateral veins at the
shoulder girdle.  Axillary pain or tenderness can be present.   All  patients
should  have  bilateral venography as contralateral involvement is about 65%.
Routine  hematologic  workup  includes  Protein  C  &  S,  Antithrombin  III,
anticardiolipin antibody, IgG and  IgM,  ANA  and  PTT.   Check to see if the
patient  is  on  contraception  therapy.   TREATMENT:  Venography  should  be
performed via the basilic vein.  A separate retrograde innominate or superior
vena caval injection from a transfemoral approach can be utilized in selected
cases to obtain better visualization of the central veins.  When  a  thrombus
is  seen  a  guide  wire is used to traverse the thrombus, and then a loading
dose of 250,000 IU Urokinase is infused  into  the clot over one hour at 4000
IU/min.  This can be continued for an additional hour, then changed  to  1000
IU/min  for up to 24 hours.  Following this, full heparinization is given and
Coumadin is started to obtain  a  1.5  to 2 times control.  Continue Coumadin
for 3 months.  The patient may need  transaxillary  first  rib  resection  or
resection of exostosis of the clavicular head.

                            -BABESIOSIS-
If you see a patient that is complaining of chills, fevers,  sweats,  fatigue
and  possibly dark urine during the summer months, always ask about travel to
the northeastern  sector  of  the  USA,  and  transfusions.  Transfusions can
transmit the organism.  Babesiosis usually follows a tick bite (the  northern
deer  tick,  Ixodes dammini), that harbors the Babesia microti organism.  The
patient may not even remember  the  tick  bite because the tick only measures
about 3 mm fully engorged and  usually  about  2  mm.   Human  babesiosis  is
endemic  in  the  northeastern  USA  especially  the  islands adjacent to the
southern New England  coast  as  Nantucket,  Martha's  Vineyard, Long Island,
Block  Island  and  Shelter  Island.   Southeastern  Connecticut,   Virginia,
Georgia,  Wisconsin,  Indiana, Maryland, and the West coast have all reported
the tick.  Babesia microti  infects  the  white  footed mouse, and the Ixodes
dammini tick lives on  the  white  tailed  deer.   Epidemiologic  studies  on
Nantucket  have  shown  that  about  60% of the white footed mice (Peromyscus
leucopus) are infected with B. microti.   The larval and nymphal stages of I.
dammini usually feed off the white footed mice and the adults feed  on  deer.
Following  infection,  Babesia  microti  invades  the  red  blood  cells  and
multiplies  by  binary  fission to produce four merozoites (the tetrad form),
which causes lysis of  the  cells  liberating  the merozoites to infect other
erythrocytes.  Thus, a chain reaction is set up producing a hemolytic  anemia
which  may be mild or severe depending on the immunocompetency of the patient
and whether the patient has a  functioning intact spleen.  If the patient has
been splenectomized or has asplenia it has been shown that  the  severity  of
the  disease  increases  dramatically.  Ordinarily, in the normal person, the
disease  is  self  limited  but  may  smoulder  for  months.   CLINICAL:  The
incubation usually ranges from 1 week to about 4 weeks after a tick bite, but
after a transfusion may be six to  nine  weeks.  If the patient has an intact
spleen, the symptoms may be  mild  and  gradual  with  malaise,  arthralgias,
nausea,   vomiting,   headache,  myalgias,  fatigue,  weakness,  chills,  and
drenching sweats.  This onset  is  not  unlike  several other illness such as
malaria.   Malaria  and  Babesiosis  can  both  cause  splenomegaly,  but  no
lymphadenopathy.  Another co-existent feature further  confuses  the  picture
even  more.   The  same  tick  Ixodes  dammini  can  carry the Lyme vector of
Borrelia  burgdorferi  and  both  of   these  diseases  are  endemic  in  the
northeastern USA.  So, the patient may present with symptomatology compatible
with Lyme disease as rash, cardiac and neurologic  symptoms.   In  fact,  the
first reported fatal case of Lyme disease occurred in a patient that harbored
babesiosis.  Ehrlichiosis, a rickettsia, that also occurs on the coast of New
England,  is  another tick born infection that is similar to the clinical and
laboratory findings of  bebesiosis.   In  this  disease  there  may be fever,
myalgias, thrombocytopenia, abnormal  liver  tests,  splenomegaly  and  rash.
Also,  you  would  have  to  rule out Rocky Mountain spotted fever and murine
typhus.    LABORATORY:   Babesiosis   produces   a   hemolytic   anemia  with
reticulocytosis, decreased haptoglobin and excess urobilinogen in the  urine.
Liver  enzymes  may  be elevated.  Thick and thin blood smears should be made
and examined, looking  for  the  intraerythrocytic  Babesia microti which may
appear  as  trophozoite  ring  forms  that  resemble  those   of   Plasmodium
falciparum,  but  the  pathognomonic  merozoite  tetrad  or  maltese cross is
diagnostic.  Other  forms  as  the  immature  piriform  bodies  can  be seen.
Parasitemia can reach as high as 80 to 90 percent in asplenic patients  which
may  require  exchange  transfusions.   In  general,  patients with an intact
spleen have a low grade parasitemia.   Babesiosis differs from malaria due to
P.falciparum  by  the  absence  of  hemozoin  (a  by-product  of   hemoglobin
digestion)  and  gametocytes  on  the  blood smears.  Thrombocytopenia may be
present.  Serologic testing with indirect  immunofluorescence for IgM and IgG
may be helpful, but there may be a low titer cross reactivity  with  malaria,
other  tick  borne  infections  and  other babesia species.  An enzyme-linked
immunosorbent assay  using  polyclonal  IgM  and  IgG  antiserum and antibody
capture assay are also available  for  diagnosis.   Inoculation  of  infected
human  blood  intraperitoneally  can  be  done for diagnosis, but is not used
much.  TREATMENT: In  patients  who  are  immunocompetent  and  have a normal
spleen there is spontaneous recovery from B. microti infection  and  possibly
no  treatment is needed.  If patients are asplenic, infected with B. bovis or
B. divergens, then those patients  will  need  to  be treated as the clinical
course is fulminant.  Clindamycin 300 mg IV or 600 mg po q 6 hours for  seven
days  +  quinine  650 mg orally q 6 hours for seven days has been successful.
Folic acid  1  mg  daily  may  be  needed  because  of  the hemolytic anemia.
Exchange transfusions may be needed.

                            -BABESIOSIS-
Babesiosis  can  occur  along  with  Lyme  disease, since Babesia microti and
Borrelia  burgdorferi  are  both   transmitted  by  Ixodes  scapularis.   The
incubation period is 1-6 weeks.  Symptoms include a flulike illness which can
be severe in splenectomized patients.  Examination of the  blood  smear  will
reveal ringlike sturctures in the red blood cells.  TREATMENT is with quinine
sulfate  (Quine,  Quinite,  Quinamm)  along  with  clindamycin  hydrochloride
(Cleocin).   The disease is potentially fatal.  Extremely ill patients can be
treated with exchange transfusion.

                      -BACILLARY ANGIOMATOSIS-
Bacillary angiomatosis is caused by Rochalimaea which are small gram negative
rods that are assigned to the  Rickettsiaceae, but may be reclassified to the
Bartonellaceae.  Rochalimaea species can also cause extracutaneous infection,
bacillary peliosis of the liver and spleen, Cat scratch fever, Trench  fever,
and  fever  and  bactermia.   Bacillary  angiomatosis  occurs  mainly in AIDS
patients, but can  occur  in  immunocompetent  patients  and organ transplant
recipients.  Exposure to cats is found in about  2/3  of  patients.   In  the
other  1/3 cat fleas or ticks may be instrumental in transmission.  CLINICAL:
Skin lesions are usually multiple,  may  be  tender, and are reddish vascular
papules or nodules.  There may also  be  fever,  chills,  headache,  malaise,
anorexia  and  weight loss.  HISTOLOGY: The diagnosis is made by skin biopsy,
showing  lobular  vascular  proliferations   composed  of  plump  epithelioid
endothelial cells.  Neutrophils are  scattered  throughout  the  lesion,  but
especially  around eosinophilic granular aggregates which are actually masses
of bacteria.  These can  be  see  by Warthin-Starry staining.  EXTRACUTANEOUS
FEATURES: There may be involvement of the GI,  respiratory,  cardiac,  liver,
spleen,  CNS  and  bone.   Bone infection is fairly common.  Patients present
with bone pain which may  be  underneath  a  skin lesion.  The lesions may be
seen on x-ray and bone scans.  Bone  disease  in  AIDS  is  rare.   Bacillary
peliosis   hepatis  presents  with  nausea,  vomiting  abdominal  distention,
diarrhea, fever, chills and  hepatosplenomegaly.  Pathological exam of biopsy
specimens show dilated capillaries or multiple blood filled cavernous spaces.
There  is  usually  elevation  of  liver  enzymes,  most  commonly,  alkaline
phosphatase and GTT.   Abdominal  imaging  will  show  hepatomegaly  with  or
without  splenomegaly.   Hypodense ring like lesions in the liver may be seen
with or without contrast  enhancement.   Liver  biopsy  is usually needed for
diagnosis.  The Rochalimaea bacteremic syndrome is characterized by  malaise,
fatigue,  weight  loss,  anorexia,  and  recurring fevers of gradually higher
elevations.  No focal  infectious  site  can  be  found.   The disease may be
present for months until a blood culture reveals  the  organism.   DIAGNOSIS:
Rochalimaaea henselae, elizabethae and quintana can be isolated from blood if
lysis-centrifugation blood cultures or Bactec blood culture systems are used.
R.  henselae  can  be isolated after direct plating of tissue from the spleen
and lymph nodes.   R.  henselae  and  quintana  have  been isolated from skin
lesions.  Indirect fluorescent  antibody  testing  for  R.  henselae  and  R.
quintana  can also be done.  There is presently an enzyme immunoassay for IgG
antibodies to  R.  henselae  which  is  5-10  times  more  sensitive than the
indirect fluorescent antibody test.  Blood cultures should be incubated for a
prolong period.   TREATMENT:  For  bacillary  peliosis  hepatis,  rochalimaea
bacteremic  syndrome,  and bacillary angiomatosis, erythromycin 500 mg qid is
the  drug  of  choice,  but   doxycycline   may  be  used  if  intolerant  of
erythromycin.  Bacillary angiomatosis should be treated in a timely  fashion,
because  of  the associated morbidity and mortality.  A response resembling a
Jarisch-Herxheimer   reaction   characterized    by   myalgias,   fever   and
constitutional symptoms may develop.  HIV  patients  should  be  treated  for
weeks  to  months  and  may  require  lifelong maintenance if relapses occur.
Immunocompetent patients are  treated  for  2-4 weeks.  Immunosuppressed, HIV
negative  patients  are  treated  for  1  month  or  until  immunosuppression
resolves, but may require longer periods.

                             -BACK PAIN-
Back pain is so common in the USA that it is very easy to miss more difficult
diagnoses than  the  usual  musculo-skeletal  sprain  or  strain.  You should
insert a whole new list of differential diagnoses into your thought processes
if the patient is over the age of 50.  History becomes very important in many
of the diseases that are capable of causing back pain.  When confronted  with
back  pain  you  should break down the causes into several categories such as
inflammatory, infectious, functional and  cancerous  etiologies.  It has been
estimated that back pain will affect 20% of the adult population at one  time
or  the  other.   Back pain in children is very unusual and if this complaint
develops in a  child  consider  malignancy  or  infectious causes.  CLINICAL:
Always ask the patient what medicines he is taking or  has  taken.   Steroids
can  cause  osteoporosis and avascular necrosis which can cause pain or these
conditions may develop into fractures  which  again  can cause back pain.  If
the  patient  has  been  taking  anticoagulants  as  heparin   or   warfarin,
retroperitoneal  bleeding  may occur and present as back pain.  Specifically,
inquire  into  trauma,  fever,  weight  loss  and  anemia.   Abdominal aortic
aneurysms occur in about 2% of the aging  population  over  the  age  of  50.
These  should  be  evaluated  by  palpation  of  the abdomen and CT if deemed
appropriate.   Usually  pancreatitis,   pyelonephritis,  kidney  stones,  and
penetrating peptic ulcer disease are easy  to  diagnose,  but  they  are  all
capable  of  causing  back pain.  Pelvic and rectal exams are helpful in some
cases in ruling out  pelvic  pathology  as  the  cause.   X-rays of the spine
should not routinely be done.   Rarely  are  they  helpful  except  when  you
suspect  infection,  malignancy,  trauma, or there is a neurological deficit.
If the patient is not  better  in  about  one  month, as a general rule, then
x-rays may be of some benefit.  CT or MRI should not  routinely  be  ordered,
either.   Indications for these would include neurologic deficiencies such as
paralysis, leg weakness, loss  of  bladder  and bowel function, suspicion for
abscess or epidural hematoma,  and  back-leg  pain  that  is  suspicious  for
malignancy  or  nerve  root  entrapment.   INFECTIOUS ETIOLOGIES: It has been
estimated  that   about   8-10   weeks   often   intervene  before  vertebral
osteomyelitis is diagnosed.  About 50% of these  patients  will  be  afebrile
when  they present to their physician.  Your arousal index should increase if
the patient is in any way immunosuppressed, is a child, is an IV drug abuser,
has pelvic inflammatory disease,  or  has  recently had back surgery.  Always
percuss the spine for tenderness to help elicit pain compatible with diskitis
or vertebral osteomyelitis.  Sedimentation rates should be done and  possible
bone  scans and CT if suspicious for an epidural abscess.  Epidural abscesses
may arise from vertebral osteomyelitis  or  by bacteremia from a remote site.
MALIGNANT ETIOLOGIES: Suspect multiple myeloma if the patient is over the age
of  50.   If  the  patient  is  anemic  order  serum  and   urinary   protein
electrophoresis  for M protein spikes.  Bone scans are not useful in multiple
myeloma and are usually normal.  X-rays of the spine may demonstrate lytic or
blastic changes in metastatic disease.  Keep in mind, however, that about 30%
of the bone must be  replaced  before  there  is visual evidence on x-ray for
metastasis.  Check the patient for weight loss, and previous history  of  any
cancer.  If the patient has had the back pain for more than a month, or fails
to  improve  and  is over the age of 50, order x-rays, CT and bone scans.  If
the patient has evidence of epidural compression, dexamethasone 100 mg should
be given  IV  and  followed  by  a  myelogram  to  assess  the  extent of the
compression.   Follow  with  chemotherapy  or  radiation  and  dexamethasone.
ENTRAPMENT ETIOLOGIES: As we age, the intervertebral disk degenerates and the
nucleus pulposus is capable of herniating.  If the patient  has  sharp,  well
localized  pain  in  the back associated with radiculopathy and paresthesiae,
suspect disk herniation.  The  radiation  in  disk herniation usually extends
below the knee.  Perform the straight leg raising test while the  patient  is
supine  and  sitting.   Functional  pain  is  often  found  when  the sitting
straight-leg raising  test  is  negative,  while  the  patient's attention is
diverted.  To be positive the patient must report pain down the leg,  not  in
the  back  on  straight  leg  raising.   The  test  is not perfect and may be
positive in between 60-90%.  The test  may be positive in other diseases than
disk herniation such as abscess, lateral stenosis and  tumor.   In  order  to
help incriminate disk herniation as the cause, perform a straight leg raising
test  in  the opposite leg.  This test is positive in over 90% if the patient
has a herniated disk.  Try  to  localize the herniation by physical findings.
Occasionally, EMG and nerve conduction studies may be needed.  For herniation
at the L5-S1 level there is impingement on the S1 nerve which  produces  pain
down the back of the leg, weakness of plantar flexion of the foot and sensory
loss  over  the back of the calf and lateral foot and decreased ankle reflex.
For herniation at the L4-5 level  there  is  impingement of the L5 nerve root
which will produce pain along the side of the leg, weakness  of  dorsiflexion
of  the  foot,  sensory  loss over the lateral lower leg and web of the great
toe.  No reflex changes occur.   For  herniation  at  the L3-4 level there is
impingement of the L4 nerve root which causes pain down the front of the leg,
weakness of extension of the leg at the knee, and sensory loss over the front
of the knee and a decreased knee  jerk.   Cauda  equina  syndrome  should  be
recognized  as  an  emergent condition.  In this condition there is usually a
very large protrusion  of  disk  material  compressing  the  caudal sac which
causes leg weakness, low back and leg pain associated with bowel and  bladder
dysfunction.   The  rectal  tone  should  be  checked with a digital exam and
perianal anesthesia is common.   The  patient  may have urinary incontinence.
Spinal stenosis is usually caused by  degenerative  changes  with  osteophyte
formation  and subsequent narrowing of the foramina and canal that impinge on
the nerve roots.  X-ray changes may support this diagnosis but doesn't give a
definitive diagnosis.  CT or  MRI  is  needed  for this.  Spinal stenosis can
simulate   peripheral   vascular   disease    with    the    production    of
pseudoclaudication.   Examine  the  peripheral  pulses to rule out peripheral
vascular disease.  The patient with  spinal  stenosis will have relief of the
pain by bending or stooping over, or sitting.  The pain is  not  relieved  by
standing  still after walking as is peripheral vascular disease.  The pain is
commonly felt in  the  buttocks,  thighs  or  calves  on  walking, running or
climbing stairs.  The patient may need decompression laminectomies to relieve
the condition.  INFLAMMATORY ETIOLOGIES: The patient should  be  checked  for
diseases  that cause inflammatory changes of the sacroiliac joint.  These are
usually seen in a younger age group  with males from 20-40 years of age being
affected.  Reiter's syndrome, ankylosing spondylitis, psoriatic arthritis and
inflammatory bowel disease may all  affect  the  sacroiliac  joint.   Inquire
about  any recent sexual exposure or gastrointestinal symptoms as diarrhea as
these frequently are precursors.   Ask  about urethritis, conjunctivitis, and
rashes that are seen with Reiter's syndrome.  Inquire about morning stiffness
and whether there is improvement of the back  pain  with  exercise  which  is
typical  of sacroiliitis.  Straight leg raising is normal.  X-rays may reveal
sclerosis, widening of the sacro-iliac  joint space and the squared vertebrae
that are seen in ankylosing spondylitis.  If there is bilateral, rather  than
unilateral  changes of the sacroiliac joint consider osteitis condensans ilii
which occurs in women  who  have  have  had multiple pregnancies.  Laboratory
tests  would  include  a  HLA-B27  antigen  to  help  rule   out   ankylosing
spondylitis.  Myofascial syndromes are quite common.  The piriformis syndrome
involves  the  piriformis  muscle  that arises from the middle portion of the
sacrum and inserts on  the  greater  trochanter.  Inflammation of this muscle
can simulate sciatica with pain in  the  sacro-iliac  area  and  the  gluteus
maximus  with  focal tenderness which is exacerbated by sitting.  This muscle
may become inflammed by falls in this area or by lifting heavy objects with a
wide based stance.  Test for this  entity  by having the patient sit with his
heels together and the knees widely separated.  As you try to close  the  gap
by squeezing the knees together, the patient will complain of intense pain in
the  involved  buttock  as he tries to resist the knee closing.  Steroids and
marcaine injections may help.   The  quadratus  syndrome  is suspected if the
patient states there is pain on lateral bending.  The quadratus lumborum is a
lateral flexor of the trunk  that  spreads  from  the  12th  rib  and  lumbar
transverse  processes  to  the  ilio-lumbar  ligament.  Palpation will reveal
tenderness at the  insertion  of  the  muscle  on  the  iliac crest.  Bending
forward or backward does not  cause  any  pain.   NSAIDs  and  local  steroid
injections  are  the treatments of choice.  Fibromyalgia is another condition
that is usually seen in young women that complain of fatigue, have depression
and disturbances of their sleeping pattern.  They have frequent headaches and
abdominal pain that  is  due  to  irritable  bowel  syndrome.  These patients
complain of AM stiffness, and frequent aches and  pains,  and  have  multiple
trigger  points  over  the  body  that  have  predilections for the trapezius
muscle, the  medial  aspect  of  the  elbows  and  knees, sternocleidomastoid
muscles, the second ribs and buttocks.  This condition is very  difficult  to
treat.   Amitriptyline and flexeril will help some.  Injection of the trigger
points with marcaine alone  or  combined  with steroid is helpful.  Posterior
facet joint inflammation will cause low back pain and  severe  tenderness  in
the  sacroiliac  joint  area with radiation to the buttocks area.  X-rays may
show sclerosis and degenerative  changes  of  the facet joints.  Treatment is
with NSAIDs, steroid injection of the  facet  joints  using  fluoroscopy  and
manipulation.   FUNCTIONAL  ETIOLOGIES:  Functional  back  pain  is common in
patients that are undergoing  litigation proceedings, patients being examined
for disability,  workmen's  compensation  claims,  in  those  who  have  been
involved  in  motor  vehicular  accidents and in drug addicts.  Depression is
another cause of functional back pain.  To test for functional back pain have
the patient seated and while his or her attention is diverted extend the leg.
If there is pathology the patient will  rear backwards with pain, in order to
relieve the stretch on the sciatic nerve.  Another test is axial loading that
is performed with the patient standing.  Application of a downward  force  on
the  head  is  perceived by the patient to cause pain, and will say that this
maneuver is painful when asked if  this causes pain.  In actuality, this test
applies no stress on ligaments or muscles and should be  painless.   A  third
test is performed also while standing.  Grab both of the wrists and hold them
close  to  the  patient's body, and then turn the body from side to side.  If
the patient complains of  pain  during  this  maneuver,  the patient is again
probably malingering.  Many of these functional patients are great actors and
will over react with  any  type  of  minimal  testing  or  maneuvers.   Light
touching  of  the skin will cause intense pain.  In summary, when examining a
patient for back pain  consider  the serious life-threatening conditions that
need immediate attention  and  use  the  laboratory  and  imaging  procedures
wisely.

                      -BACK PAIN IN CHILDREN-
Spondylolysis: is  due  to  a   fatigue   or  stress  fracture  of  the  pars
interarticularis.   Is  common  in  football  linemen,  weight  lifters   and
gymnasts.   It  is unilateral in only 20% of cases.  Eighty percent will have
tight hamstrings.  Is diagnosed on oblique x-rays.  Occasionally the x-ray is
normal and bone scan will be needed.  Treatment is NSAIDs, lumbar corset, and
activity restriction.  Can return to full activity in 3-6 months.  Surgery if
refractory.  SPONDYLOLISTHESIS: is an  anterior displacement of one vertebral
body on the body below.  The most common type is isthmic, which is  a  defect
or  elongation  of  the  pars  interarticularis.   A  spot lateral x-ray will
identify.  Surgery is used only in symptomatic patients or those with slips >
50%.  SCHEUERMANN'S disease: kyphosis of  the thoracic or thoracolumbar spine
can result from Scheuermann's disease.  Is first  seen  in  adolescents.   If
untreated it can lead to degenerative spondylosis in the adult.  There may be
compensatory hyperlordosis of the lumbar spine.  X-rays will show more than 5
degrees  of  wedging  of  at  least  3  adjacent vertebrae at the apex of the
deformity.   Schmorl's  nodes  (herniation   of  disc  material  through  the
vertebral end plates) are  present.   Can  be  successfully  treated  with  a
Milwaukee  brace if started before skeletal maturity and the kypnosis is < 70
degrees.  Lumbar  Scheuermann's  disease  (apprentice  kyposis) is associated
with strenous physical  activity.   Symptoms  usually  abate  within  several
months  with  restriction  of  heavy  activity  without  long  term sequelae.
TUMORS: hemangiomas which  cause  vertical  striation  of the vertebral body,
eosinopnilic granuloma, chordoma, Ewing's tumor, and metastases.  Tumors that
involve  the  posterior   elements   include   osteoblastoma,   osteosarcoma,
aneurysmal  bone  cyts, and osteoid osteoma may be difficult to see on x-ray.
Patients may present with  painful  kyphosis  with  atypical curves such as a
left thoracic curve.  Bone scans and CT may be  helpful.   Acute  lymphocytic
leukemia  usually  have  normal  x-rays,  and  MRI  and bone scan may also be
unremarkable.  INFECTION: infections may involve  the disc, vertebral body or
the sacroiliac joint.  TB may also cause Pott's disease.   Sacroiliac  septic
arthritis  is  diagnosed  with  bone  scan  or  MRI and aspiration.  Visceral
disease: pyelonephritis, hydronephrosis,  retroperitoneal abscess, retrocecal
appendix, inflammnatory bowel disease and pneumonia are common causes of back
pain.

                        -BACTERIAL VAGINOSIS-
Metronidazole  500 mg PO bid for 7 d. Alternatives: metronidazole 2 g PO once
or clindamycin phosphate 2% (Cleocin) 5  g  intravaginally at bedtime for 7 d
or metronidazole gel 0.75% (MetroGel-Vaginal) 5 g intravaginally bid for 5  d
or clindamycin HCL 300 mg PO bid for 7 days.

                         -BARTTER'S SYNDROME-
Bartter's syndrome (BS) usually presents in childhood, and the symptoms  that
exist  are  usually  secondary  to  hypokalemia, such as fatigue, generalized
weakness, muscle  cramps,  polyuria,  nocturia,  polydipsia and neuromuscular
irritability.  In children mental  retardation  and  growth  retardation  can
result  in  short stature.  These patients have normal blood pressure whether
Bartters occurs in children  or  adults.  Hypokalemia and metabolic alkalosis
are the main features of the disease.  The  potassium  typically  is  between
2.5-3.0  mEq/L.   The  hypokalemia  results  from  urinary potassium wasting.
Serum bicarbonates are usually between  32-36 mEq/L, while the arterial blood
gas will reveal a metabolic alkalosis with pH values of 7.5-7.55.  There also
is chloride wasting with spot urinary values for chloride typically exceeding
20 mEq/L.  Spot  potassium  urinary  values  are  usually  >  40.   Bartter's
patients  will  also  have elevated plasma renin activity, angiotensin II and
aldosterone.  Urinary excretion  of  prostaglandins  is increased.  There may
also be hypomagnesemia and hyperuricemia.  Sodium  wasting  is  also  present
which  results  in a chronic low plasma volume which keeps the blood pressure
in a normal range in spite  of  high renin and angiotensin.  Other conditions
can produce hyperaldosteronism  (such  as  primary  hyperaldosteronism),  but
Bartter's  patients  are distinguished by a normal blood pressure and lack of
edema that can occur in  secondary aldosteronism.  The differential diagnosis
includes vomiting, diarrhea, and laxative or  surreptitious  diuretic  abuse.
However,  if  a  spot urine for potassium is obtained it will usually be less
than 20  mEq/L  in  long  standing  GI  potassium  wasting  as from vomiting.
Chronic  diarrhea  usually  presents  with  metabolic  acidosis  rather  than
alkalosis, and can be excluded by the history and evidence of renal potassium
wasting.   Percutaneous  renal   biopsy   may   show   hyperplasia   of   the
juxtaglomerular cells.  However, hyperplasia of the juxtaglomerular cells can
occur  in  other  diseases  that  are associated with hyperreninemia, such as
Addison's disease, prolonged salt  restriction, chronic laxative, vomiting or
diuretic abuse.  TREATMENT: Basically the treatment is aimed at restoring the
serum potassium to normal levels which can be difficult.  Patients frequently
need 150-300 mEq daily to maintain the serum potassium.  Usually the  patient
will  need  spironolactone 150-300 mg daily, and even combining this with the
potassium supplements may not restore the  serum potassium to normal.  It may
be  necessary  to  use  amiloride  and   spironolactone   in   daily   doses.
Indomethacin  1-2  mg/kg/day  has  been  useful  in correcting excessive PGE2
urinary excretion.  Indomethacin  can  also  correct  the sodium and chloride
urinary wasting as well as increase the blood pressure.

                           -BELL'S PALSY-
Has a mean age of 40 in men and 44 in women.  Onset  is  acute  with  maximal
paralysis  in 48 hrs.  There may be mild pain, impairment of taste, inability
to close the eye with  tearing.   Hyperacusis  in the ipsilateral ear signals
paralysis of the stapedius muscle.  There is ipsilateral decreased or  absent
forehead  wrinkling,  flattening of the nasolabial fold and drooling.  Bell's
palsy is the most common cause  of unilateral facial weakness.  Small pontine
infarcts can also cause.  Facial paralysis occurs bilaterally  in  22-33%  of
Lyme  disease.  Herpes zoster can also cause.  TREATMENT consists of patching
the eye  to  prevent  keratitis.   Prescribe  artificial  tears as HypoTears,
Refresh and an ophthalmic lubricating ointment as Lacrilube, Refresh  PM  for
use   at   night.    Artificial   tears   can   be   used  2-4  times  daily.
Electromyography can be done if no  improvement  after 10 days.  If EMG shows
denervation, referral to  physical  therapy  for  electrical  stimulation  of
facial  muscle.   Prednisone (Deltasone, Orasone) 60 mg/d may be given during
the first 5 days then tapered during the  next 5 days, if the patient is seen
shortly after paralysis.

                -BENIGN POSITIONAL VERTIGO TREATMENT-
The  modified Epley maneuver: The patient sits in the middle of the treatment
table facing the end of the  table  with  the head turned toward the affected
ear.  The patient is then rapidly layed on her back while the  angle  of  the
head  is  maintained.   After  3  minutes in this position the head is slowly
maneuvered over the  course  of  1  minute  to  the  opposite side where this
position is maintained for 4 min.  The patient is then slowly returned to the
sitting position.  57% will obtain complete relief, 33% will improve and  10%
will not be improved.  THE SEMONT'Ss MANEUVER: The patient sits on the edge of
the  table  with the head turned 45 degrees away from the affected ear.  Move
the patient rapidly on her side  with  the affected ear down (vertigo usually
occurs).  After 4 minutes in this position rapidly swing the patient  to  the
opposite side while maintaining the head position (vertigo again occurs).  If
vertigo  doesnt  occur  after  one minute, rotate the head through a range of
motion  exercises to dislodge  any  debris  from  the  cupula.  Leave in this
position for 4 minutes, then slowly bring back to the sitting position.   70%
will  become asymptomatic, 20% will improve at least 70% and 10% will improve
less than 70%.  A soft  cervical  collar  should  be worn continuously for 48
hrs.  Then for the next 5 days they may lie down, but  not  on  the  affected
side.

                   -BENIGN PROSTATIC HYPERPLASIA-
This presentation will address the  medical  treatment of of BPH.  Presently,
within the United States there are two classes of drugs that are  used.   The
first is the 5 alpha-Reductase inhibitors and this includes only finasteride.
The second class of drugs are the alpha-Adrenergic antagonists and this class
consists  of  the  following drugs: prazosin (Minipress), terazosin (Hytrin),
and doxazosin (Cardura).  Terazosin  and  doxazosin  are both long acting and
given once a day.   Prazosin  must  be  given  given  several  times  a  day.
FINESTERIDE: Finasteride (Proscar) inhibits the conversion of testosterone to
the  very  potent  androgen dyhydrotestosterone and as a result the prostatic
size is  reduced  by  about  25%.   In  some  patients  this  will facilitate
micturition  by  decreasing  the  mechanical  obstruction  of  the  prostatic
urethra.  One advantage of using finasteride is that it  can  be  given  once
daily  and  the  side effects are minimal.  However, the monetary impact with
this drug would negate its usage.  It  is  estimated that a 1 month supply of
finasteride would cost about $61.00 with an annual expense of $732.00.   This
is  a  high  price  to  pay  for only a 3 ml/s increase in peak urinary flow.
Also, the alleviation of the symptoms may take 6-12 months to achieve maximal
benefit.  Furthermore, of  major  concern,  is  that finasteride consistently
reduces the prostatic specific antigen  (PSA)  by  about  50%.   This  is  of
concern  in  screening  and  following patients for prostatic cancer.  On the
basis of this, a new reference range of 0.0 to 2.0 ng/ml has been established
for patients taking 5 mg of finasteride daily rather than the usual normal of
0.0 to 4.0 ng/ml.  Also, the serum testosterone  with both 1 mg and 5 mg will
increased by about 10%.  How significant this will be remains to be answered.
By one year patients that were treated with 5 mg per day of  finasteride  had
only  a  14%  decrease  in  prostatic  volume.  Other side effects consist of
decreased libido (4.7) and decreased  ejaculate volume (4.4%).  There also is
a slightly higher incidence  of  impotence.   TERAZOSIN:  Terazosin  (Hytrin)
takes  only  2-3  weeks  to  realize  the  beneficial  effects.   It works by
decreasing the smooth muscle tone of  the bladder neck, prostatic capsule and
adenoma with resultant increase of flow through the prostatic urethra.  There
has been a 50% increase in peak urinary flow rates, a 46%  increase  in  mean
urinary  flow rate, a 67% decrease in obstructive symptoms and a 35% decrease
in irritative symptoms.  There is  no  change  in the PSA during treatment as
with the 5 alpha-reductase inhibitors.  Side effects are observed as follows:
dizziness (14%), headaches (10%), weakness (7%),  hypotension  (4%),impotence
(4%)  and  impotence (1%).  Treatment plan: days 1-3 give 1 mg hs., days 4-14
give 2 mg hs, days 15-21  give  5  mg  hs,  days  22-29 give 10 mg hs.  Check
frequently for orthostatic hypotension and other  side  effects.   The  final
dose  of terazosin for treatment of BPH is 5-10 mg/day, as less than 5 mg/day
is at placebo level.  Giving  the  dose  at  bedtime may decrease the cardiac
side effects.  DOXAZOSIN: Doxazosin (Cardura) will  decrease  the  irritative
symptoms decreased by 80%, and obstructive symptoms by 63%.  The peak urinary
flow rates increase by 25%.  Side effects are minimal with doxazosin, but can
include  syncope,  dizziness, somnolence, fatigue, edema, rhinitis, polyuria,
abnormal  vision,  orthostatic   hypertension,  sexual  dysfunction,  ataxia,
leukopenia, neutropenia and arrhythmia..  Treatment is  4  mg  per  day,  but
starting  low  and  building up to max of 16 mg per day would be prudent with
monitoring of blood pressure and side  effects.  Doxazosin is available as 1,
2, 4, and 8 mg tablets.  MONITORING FOR  PROSTATIC  CANCER  WITH  FINASTERIDE
USAGE:  RECOMMENDATIONS  FOR  MONITORING  FOR  PROSTATIC  CANCER  IN PATIENTS
RECEIVING FINASTERIDE Before a  patient  with  symptomatic  BPH is started on
finasteride, the prostatic gland should be examined digitally and a basal PSA
should be done.  If both of these are normal then the patient may be  started
on finasteride.  After 6 months of treatment, the PSA should be repeated.  If
the  PSA  has  not  decreased  by 50% then the patient should be examined for
cancer of the prostate.  The PSA  should  be  <  2.0 ng/ml.  If the PSA is in
this range then monitor the patient annually with digital exam and  PSA.   Be
aware  that  patients may not comply with taking the medication and this will
elevate the PSA.  If  compliance  is  an  issue  then  obtain serum DHT which
should  be  very  low  if  patient  is  taking  finasteride.    TRANSURETHRAL
RESECTION:  TURP  has  been  used  for  years  in the treatment of BPH.  Most
patients  will  be  benefited  but  the  surgical  procedure  can  have  some
morbidity.  About 20%  do  not  realize  an  improvement in voiding symptoms.
Complications of TURP are as follows: Transfusions (6.5-10.5%), Urinary tract
infection  (2.3-20%),   Impotence   (3.5-10.2%),   Epididymitis   (1.2-4.8%),
Incontinence (.4-3.3%) and Death of 0.2% in one series.

                    -BETA BLOCKERS IN CARDIOLOGY-
PARENTERAL BETA  BLOCKERS:  In  the  USA,  esmolol,  propranolol,  labetalol,
metoprolol,  and  atenolol  have all been approved for IV use.  Esmolol has a
very short half life and  has been approved for supraventricular arrhythmias.
Esmolol (Brevibloc) is given as 500 ug/kg over  a  one  minute  period  as  a
loading  dose  followed  by 50 ug/kg/min.  If ineffective reload the patient,
and increase the maintenance  dose  to 50-200 ug/kg/min.  Atenolol (Tenormin)
and metoprolol (Lopressor) have  been  approved  for  IV  use  in  acute  MI.
Atenolol  is  given  as 5-10 mg IV, then 50-100 mg po qd titrating to a heart
rate of <60 or a maximum of 200 mg/day po daily.  Metoprolol is given as 5 mg
IV every 2-5 min.  x 3 doses;  then  25  mg  po  q6h x 48 hrs, then 100 mg po
q12h.  Labetalol is approved for hypertension and is given as a 20  mg  bolus
(.25  mg/kg),  then  20-80  mg IV boluses every 10-15 minutes titrated to the
desired BP (maximum of 300  mg).   An  infusion  can  be given as .5-2 mg/min
(maximum 300 mg/day).  Propranolol is given as 1-10 mg loading dose,  then  3
mg/hr IV.  ARRHYTHMIAS: Beta blockers are frequently used in supraventricular
arrhythmias  and  exercise  induced  ventricular arrhythmias.  The CAST study
demonstrated that even near  complete  suppression  of ventricular ectopy did
not provide a successful outcome and recognition of  proarrhthmias  has  been
enhanced.   There  is now solid evidence in AMI for reduction in sudden death
when beta blockers are  used.   Acebutolol  and  propranolol are approved for
treatment of ventricular ectopy, but many of  the  beta  blockers  have  been
used.   Even  though  sotolol  is  a  class  III  agent, it has beta blocking
properties and is being used  for  life threatening arrhythmias.  OTHER USES:
Several small trials have indicated that  beta  blockers  have  a  beneficial
effect  in  dilated  cardiomyopathies.   About  20%  of  patients  with  this
condition  will be unable to tolerate beta blockers, but about 80-95% will be
able to tolerate if the initial doses are small.  Patients that have positive
tilt table testing for vasovagal symcope may benefit from beta blockers since
beta adrenergic stimulation is a predisposing factor for initiation of reflex
events  that  mediate  vaso-vagal  syncope.   Although  beta  blocker  reduce
mortality after MI,  data  regarding  patients  with  smaller  or  non Q wave
infarction have less or no survival benefit.  Beta  blockers  should  not  be
used  in  claudication, bronchospasm, sexual dysfunction or insulin dependent
diabetes.

              -BETA BLOCKERS IN MYOCARDIAL INFARCTION-
Thrombolytic  therapy is now considered the cornerstone of treatment for AMI,
and beta adrenergic blocking agents that do not have intrinsic sympthomimetic
or alpha blockade properties are now being  used early in the course of MI as
well  as  later.   They  function  by  reducing  myocardial  oxygen   demand,
decreasing  blood  pressure,  heart  rate  and  contractility.  Acutely, beta
blockers are given IV during  the  early  post infarction hours and have been
shown to decrease  mortality,  ventricular  arrhythmias,  infarct  size,  and
reduce  the  need for pain medications.  Metoprolol (Lopressor) is given at 5
mg IV q 2-5 minutes for 3 doses,  followed  by  25 mg po q6h for 2 days, then
100 mg po q12h.  Alternatively, atenolol (Tenormin) is given at  5-10  mg  IV
then 50-100 mg po qd, or propranolol	0.1 mg/kg IV divided into 3 doses q 5
min,  followed  in  one  hour  by 20-40 mg q6-8h (160-240 mg/day), or esmolol
(Brevibloc) 500 ug/kg  IV  over  one  minute,  then  50 ug/kg/min IV infusion
titrated to a heart rate of less than 60 (max  300  ug/kg/min).   There  have
been  several  randomized  large  scale clinical trials that have examined IV
beta blockers during the early hours of MI.  The first international study of
infarct survival (ISIS-1) has  been  the  largest  study.  In this study they
found that atenolol given IV within hours of the onset of symptoms  decreased
by  29% the risk for death in the first 24 hours.  This decrease in mortality
is probably due to the  prevention  of  arrhythmia and cardiac rupture in the
first 2 days.  Oral  administration  of  the  beta  blocker  does  not  allow
titration  in  the early hours.  Other studies with beta blockers given po at
about 2 weeks have shown to be effective by a 20% saving of life and decrease
of reinfarction.  Thus,  if  the  patient  is  not  a  candidate for early IV
therapy there still is an advantage for later blockade.  There  have  been  4
trials  as  of  this  writing, that have demonstrated the usefullness of beta
blockers given in conjunction  with  thrombolytic therapy.  Surprising, there
has not been an increase of hypotension.  The TIMI-2B study (Thrombolysis  in
Myocardial  Infarction) demonstrated that by giving metoprolol at the time of
thrombolytic therapy, there was a more beneficial response than by waiting by
the 6th post infarction day and giving the drug orally.

                           -BLASTOMYCOSIS-
Blastomycosis is caused by inhalation of spores of  Blastomyces  dermatitidis
into the lung and is then spread by lympho- hematogenous dissemination to the
lungs,  bone,  genitourinary  and skin.  Most patients with Blastomycosis are
young or middle  aged  men.   Adult  respiratory  distress  syndrome has been
reported in the elderly.  The fungus is airborne  in  rotten  wood  dust  and
prevalent in the great Lakes area and the Southeast with high rates in states
bordering  the  Mississippi  and  Ohio  Rivers.  The disease is rare in AID's
patients.    PULMONARY   BLASTOMYCOSIS:   Pulmonary   Blastomycosis   can  be
asymptomatic, acute or chronic.  The acute form may start abruptly or  slowly
and  may  be  asymptomatic  and  self  limited.  The patient may have fevers,
myalgias, arthralgias, chills, sweats,  cough  (which  may be dry and hacking
early, followed  by  a  productive  cough  later),  hemoptysis,  and  can  be
associated  with  erythema  nodosum.   Weight  loss  is  fairly  common.  The
incubation  period  is  60-90  days.    Chest   x-ray  may  show  upper  lobe
fibronodular infiltrates in 50% of cases and a mass lesion in 30%.  There may
be diffuse lung infiltrates, and  cavitation  occasionally  occurs.   Pleural
thickening,  pleural  effusions  (10%),  with  pleuritic chest pain and adult
respiratory  distress  syndrome   rarely   occur.   CUTANEOUS  BLASTOMYCOSIS:
Cutaneous blastomycosis may occur  with  or  without  pulmonary  disease  and
represents  the  most common extrapulmonary presentation.  The skin lesion is
typically a wart-like verrucous lesion  that  may  begin as a small papule or
pustule.  These may become crusted, and there may be  central  clearing  with
scar  formation.   There  also  may  be skin ulcers with raised borders and a
granulating base.   Painless  miliary  microabscesses  may  develop along the
borders of the lesions.  Dermatologic involvement occurs  in  40-80%  of  the
extrapulmonary  cases.   OSSEOUS BLASTOMYCOSIS: Osseous blastomycosis usually
affects the ribs, vertebrae and long bones (tibia and femur are common).  The
lesions are well  circumscribed  osteolytic  lesions.   There may be adjacent
paraspinous abscesses with vertebral involvement.  The skeletal  form  occurs
in   25-50%  of  extrapulmonary  cases.   GENTITOURINARY  BLASTOMYCOSIS:  The
prostate is most  frequently  involved  followed  by  the  epididymis and the
testes.  Prostate exam may reveal it to be tender  and  enlarged  along  with
perineal   discomfort,   and  the  epididymis  may  be  swollen  and  tender.
LABORATORY: Sputum cytology will often reveal the characteristic large single
budding thick walled yeast  forms.   Histopathologic  examination of the skin
lesions will reveal pseudoepitheliomatous hyperplasia.  Tissue and body fluid
should be cultured in Sabouraud's media and wet  mounts  should  be  done  to
demonstrate  the  yeast  form which appear as a broad based budding structure
with no capsule and  refractile  wall.   They  are  about 5-15 micrometers in
diameter.  Special Gomori methenamine silver stains may be done on tissue and
Periodic acid Schiff's stains will  color  the  wall  red.   If  there  is  a
question  of  diagnosis,  a  mucicarmine  stain  will  help  to differentiate
Cryptococcus (which has a capsule) from Blastomycosis dermatitidis (which has
no capsule).   For  the  disseminated  forms,  CT  or  MRI  may  be used with
involvement of the brain and spine.  Bone scan is helpful  for  detection  of
osseous  involvement.   Chest  x-ray  and  chest  CT  are  used for pulmonary
involvement.  TREATMENT: Acute Blastomycosis may not need any treatment as it
often times is  self-limited.   Amphotericin  B  is  associated with too many
adverse effects to be given routinely.  However, with the introduction of the
azole and imidazole drugs there is more of a tendency  to  treat  because  of
less  side  effects  with  these  newer  oral  drugs.   Unless the patient is
severely ill or has meningitis then  oral  therapy may be given for the acute
form and the chronic form.  Ketoconazole, fluconazole  and  itraconazole  are
the three drugs that can be used.  With the introduction of itraconazole this
drug  could be used instead of ketoconazole.  The dose of itraconazole is 200
mg  once  or  twice  a  day.   Itraconazole  does  not  inhibit  steroid  and
testosterone synthesis as  does  ketoconazole.   Side effects of itraconazole
consist of nausea, vomiting, hepatitis, hypertension, hypokalemia and  edema.
Treatment  should  be  given  for  6  months depending on the severity of the
disease.  Ketoconazole can be  used  for  the  milder  forms at 400-800 mg PO
daily for 6 months.  Amphotericin B is used  for  the  severe  forms,  giving
0.5-0.8  mg/kg IV over 4-6 hours daily for a total dose of 1.5 to 2 grams.  A
test dose of 1 mg in 200  ml  of  5%  in  water should be given IV over a 2-4
hours period.  The daily dose of Amphotericin B is increased by 10  mg  daily
until  there  is a maintenance dose of 0.5 to 0.8 mg /kg/day.  If the patient
develops fever with the  infusion  then treat with pre-infusion acetaminophen
and diphenhydramine.  If patient chills give merperidine.  The patient should
be  monitored  while  receiving  the  amphotericin  B  with  renal  function,
electrolytes (sodium, magnesium, potassium) and CBC twice  a  week.   If  the
creatinine  becomes  greater  than  1.6  mg/dl  then  change the Amphotericin
infusions to every  other  day.   The  patient  should  also be monitored for
development of hypotension and phlebitis.  Avoid all nephrotoxic drugs  while
receiving  amphotericin B. PROGNOSIS: If the patient is treated appropriately
there should be a cure rate of over 90%.  However, relapse does occur and may
be more frequent when ketoconazole is used as anti-fungal therapy.

                        -BLEEDING DISORDERS-
KEY  QUESTIONS  IN  HISTORY TAKING: 1....Have you ever had excessive bleeding
during surgery?  2....Have  you  ever  had  excessive  bleeding during dental
extractions?  3....Have you had excessive menstrual  bleeding?   4....Do  you
get spontaneous bruises or nose bleeds?  5....Do you have a family history of
bleeding  problems?  6....Have you had liver disease, renal disease, collagen
vascular disease,  cancer,  nutritional  deficiencies,  Cushing's  disease or
dysproteinemias?  7....Have you ever taken anticoagulant drugs?   Normal  PT,
PTT  and  bleeding  time  do  not  eliminate the possibility of a significant
bleeding disorder.   Von  Willebrand's  disease  is  the  disorder found most
commonly in combination with normal results on screening.  Diagnosis requires
von Willebrand's factor antigen assay and ristocetin cofactor assay.  In some
cases  electrophoretic  analyses  of  the  multimers,  that  constitute   Von
Willebrand's  factor  proteins,  is  also  needed.   Initial diagnosis of Von
Willebrand's disease in adulthood is  not uncommon, especially if the patient
has not undergone any surgical procedures in the past.  MILD Hemophilia A  or
B  may  also  present  in adulthood.  Mild cases may not adversely affect the
PTT.  In fact, a PTT may be normal even in some patients who have factor VIII
or IX levels as low as  20%  of  normal.   Less common conditions that may be
missed   when   screening   tests    are    normal    are    afibrinogenemia,
hypofibrinogenemia,  dysfibrinogenemia,  factor XIII deficiency and inherited
qualitative platelet defects.   ISOLATED  PTT ELEVATION: A....Poor collection
of venous  blood  with  some  clotting  present.   B....Lupus  anticoagulant.
(Mixing  the patients plasma with normal plasma doesn't correct the prolonged
PTT in patients  with  lupus  inhibitors.   Patients with lupus anticoagulant
usually do not experience bleeding complications, but one of the most  common
clinical  manifestations  is  thrombosis.   C....Factor  XII deficiency, high
molecular weight kininogen, or prekallikrein  can cause PTT prolongation, but
these patients do not have a significant hemostatic defect.   D....Hemophilia
A & B E....Von Willebrand's disease F....Acquired Factor VIII inhibition, and
circulating anticoagulants may cause significant bleeding problems.  ISOLATED
BLEEDING  TIME ELEVATION: A....Thrombocytopenia B....Von Willebrand's disease
C....Medications such as  alcohol,  antihistamines,  beta lactam antibiotics,
cardiovascular agents as calcium channel blockers, disopyridamole,  quinidine
and  NSAIDs.   D....Faulty  testing  technique.   ISOLATED  PT  PROLONGATION:
A....Deficiency  of  vitamin K-dependent factors (factors II, VII, IX, and X,
which result from poor nutrition,  therapy with warfarin or liver disorders).
B....Acquired coagulation factor inhibitors are seen rarely in patients  with
lymphoma or collagen vascular disease and can lead to prolongation of the PT.

                  -BLOOD TRANSFUSION COMPLICATIONS-
Blood transfusion complications  can  be  due  to  hemolytic  reactions,  non
hemolytic   reactions,   transfusion   reactions  associated  with  anti  IgA
antibodies,  delayed  hemolytic  transfusion  reactions,  febrile transfusion
reactions,  urticarial  transfusion  reactions,  circulatory  overload,   and
infectious  contamination  of  donor blood.  ACUTE HEMOLYTIC REACTIONS: These
are usually due to ABO  incompatibility.   These  may occur after infusion of
RBCs, white cells, platelets or fresh frozen  plasma.   In  most  cases,  the
donor  will  have  an  A  or  B  antigen on the RBCs.  Other hemolytic causes
include patient antibodies to donor Duffy,  Kidd, and Kell RBC antigens which
will cause a hemolytic anemia.  Females are more  at  risk  for  transfusions
reactions   since   they   become  sensitized  through  pregnancy  and  blood
transfusions secondary to  obstetrical  complications.   Age  also  is a risk
factor  because  older  patients  receive   more   transfusions.    Hemolytic
transfusion  reactions  include  pain at the site of infusion, fever, chills,
chest, back and abdominal  pain,  apprehension, nausea, flushing and dyspnea.
The patient may  develop  hypotension,  hemoglobinuria,  renal  failure,  and
bleeding  secondary  to DIC.  The severity of the reaction is proportional to
the amount of blood  the  patient  has  received.  Therefore, the transfusion
should be stopped immediately when suspected.  The patient  should  be  given
generous  amounts  of  IV  normal  saline  and  furosemide  to increase renal
cortical blood flow, keeping the urine output at 100 ml/hour.  If hypotension
does not respond to hydration, dopamine may  be started at a low dose of less
than 2ug/kg/min in an attempt to increase  renal  blood  flow.   The  use  of
heparin  for  DIC  is  controversial.   The  blood  bank  should  be notified
immediately.  Blood samples are  drawn  from  the  recipient and the serum is
checked for a pinkish or red color which would  indicate  hemoglobin,  and  a
direct  Coomb's  test.   DELAYED HEMOLYTIC REACTIONS: Usually occur about 5-7
days after transfusion, but  occasionally  may  be  seen  up to 3 weeks after
transfusion.  These are usually asymptomatic, but can be  quite  severe  with
the  symptoms resembling acute hemolytic reactions.  Most of these are due to
exposure to a previous antigen  from  pregnancy or transfusion.  The antibody
that is produced  is  usually  below  detectible  limits.   These  antibodies
include  anti-Fy,  anti-E,  anti-Jk,  anti-C, anti-D and anti-K.  No specific
treatment  is  usually  needed  for  delayed  hemolytic  disease.  URTICARIAL
REACTIONS: Occurs in about 2% of transfused  patients.   These  patients  are
treated by stopping the transfusion.  There is no evidence of acute hemolysis
and  the urticaria are due to a reaction to plasma proteins.  For prevention,
these patients are treated with antihistamines and washed RBCs.  ANAPHYLACTIC
IGA DEFICIENT REACTIONS:  These  produce  sudden  onset respiratory distress,
shock and urticaria.  They may also develop flushing, back pain, hypotension,
chest and abdominal pain, hives, and nausea.  They are rare and  are  usually
found  in  patients who are IgA deficient and have formed anti-IgA antibodies
during prior transfusion or pregnancy.  The anaphylaxis usually begins before
the patient has received 10 ml of  blood.  These patients are treated with IV
epinephrine .5 mg 1:10,000 every 5-10 minutes as needed, fluids, steroids and
dopamine if shock is present.  To prevent future episodes, autologous  blood,
washed RBCs or RBCs from an IgA deficient donor should be given.  TRANSFUSION
ASSOCIATED  ADULT  RESPIRATORY DISTRESS SYNDROME: This disorder is clinically
similar to fluid overload, but occurs  less commonly.  It causes dyspnea by 6
hours, hypotension, normal  pulmonary  capillary  wedge  pressure,  bilateral
pulmonary  infiltrates  and  fever.   The  patients  usually recovers rapidly
within 24-48 hours.  It is usually due  to an anti white cell antibody in the
donor blood of a multiparous female.  This antibody reacts with an antigen on
the patient's white cells with subsequent leukoagglutination and  obstruction
of  blood  flow.   There also is a release of toxic granulocyte products that
can cause capillary  vasoconstriction  producing increased pulmonary vascular
resistance.  Confirmation of this disorder requires a  search  of  the  donor
plasma  for  antigranulocyte  and/or  antilymphocyte antibodies which is time
consuming.   The  treatment  is  supportive,  with  many  patients  needing a
ventilator with positive end expiratory pressure,  furosemide  and  dopamine.
Some  patients  may  also  need  large  doses  of  methylprednisolone  sodium
succinate 30 mg/kg given once or twice.  Prevention is with leukocyte filters
and  washed  RBCs.  FLUID OVERLOAD: Fluid or circulatory overload can cause a
dry cough, tightness of the  chest  and  acute pulmonary edema.  It is fairly
common,  especially  in  infants  and  the   elderly.    Treatment   includes
pretreatment with furosemide and slowing the transfusion to about 1/2 unit of
packed RBCs given over 4 hours or about 100 ml/hour.  BACTERIAL CONTAMINATION
OF  THE DONOR BLOOD: This is a serious consequence of blood transfusions that
can have a high mortality with death occuring within 6-12 hours.  The patient
presents with fever,  chills,  dyspnea,  nausea, vomiting and hemoglobinuria.
Gram negative rods are  commonly  involved,  since  they  can  grow  at  cold
temperatures.   Yersinia  enterocolitica has been very common, but clinically
is rare.  It can be diagnosed  by  obtaining  a gram stain of the donor blood
obtained from the  blood  bag.   FEBRILE  REACTIONS:  Febrile  reactions  are
characterized  by  chills,  fever,  flushing,  tachycardia, and headache that
starts within one hour after transfusion begins, and may last for 8-10 hours.
It has a frequency of  about  1%  of  all transufions.  Febrile reactions are
usually due to antibodies  toward  donor  white  cells,  with  a  history  of
previous  transfusion or pregnancy.  The blood should be stopped immediately,
because acute hemolytic transfusions  reactions  can  also produce fever.  In
febrile reactions there is no hemolysis.   If  no  hemolysis  is  found,  the
treatment  is  supportive with antipyretics and use of leukocytic filters and
washed RBCs.   VIRAL  HEPATITIS:  NON-A,  NON-B  HEPATITIS:  Less  than 1% of
transfused patients will develop viral hepatitis with a risk of infection  of
0.1%/unit  transfused.   Non-A,  Non-B  is  the  most  common  cause  of post
transfusion hepatitis (90%).   The  duration  from exposure to seroconversion
varies between 6 weeks to 1 year.  Clinically, the patient has  elevation  of
liver enzymes and a positive hepatitis C antibody.  Other causes of hepatitis
must  be  ruled  out  as  alcoholic  hepatitis,  hepatitis  A,  B, and D, and
Epstein-Barr and CMV hepatitis.  Chronic  hepatitis secondary to non-A, non-B
hepatitis develops in 50%, cirrhosis (20%), and hepatocellular cancer in  5%.
If  a  patient has been accidently exposed to a blood transfusion with a test
suggestive of non-A, non-B hepatitis,  immune  serum globulin should be given
as some studies have suggested protection.  HEPATITIS B: Hepatitis  B  causes
about  10%  of  post-transfusion hepatitis.  The incubation period is about 3
months.  The sequelae are  similar  to  non-A, non-B hepatitis.  Treatment is
with hepatitis B immune globulin, 5 ml, + hepatitis B vaccine given IM in the
deltoid	at 0, 1, and 6 months.  CMV INFECTION:  This  infection  occurs  when
there  is  infusion  of  infected  white  cells (usually B lymphocytes).  The
primary risk  is  when  immunosuppressed  transplant  patients  and premature
neonates are infected.  The mortality in transplant patients is about 60-85%,
while neonates may have a mortality of 40% and a morbidity of  50%.   Because
of  this  high  morbitiy and mortality, all CMV negative transplant patients,
and all CMV negative premature neonates weighing less than 1250 grams, should
only be given CMV negative blood if needed.  The clinical symptoms consist of
hepatitis,  pneumonia,  hepatosplenomegaly   and  production  of  cytopenias.
Adults can develop colitis, esophagitis, gastritis, arthritis, retinitis  and
encephalitis.   OTHER TRANSFUSIONS COMPLICATIONS: Other rare post transfusion
complications include  malaria,  post-transfusion  purpura, Graft-versus-host
disease, leukemia (HTLV I) and paroxysmal nocturnal hemoglobinuria.

                        -BOERHAAVE'S SYNDROME-
Boerhaave's  syndrome  (BS)  is  due  to  a  spontaneous  perforation  of the
esophagus which usually occurs after  vomiting  in 75% of patients.  However,
it may also occur after any Valsalva maneuver such as  lifting,  laughing  or
during  childbirth.   It  also  has  been  associated with bulemia, alcoholic
binges and gluttony.  The  patients characteristically present with vomiting,
chest pain and subcutaneous emphysema.  They may report pain with swallowing.
Other causes  of  esophageal  perforations  include  iatrogenic  causes  from
endoscopy,  esophageal dilation, biopsy, intubation, blunt chest or abdominal
trauma,  convulsions,   defecation,   corrosive   injuries   (acid,  alkali),
carcinoma, and penetrating chest or abdominal trauma.  Chest x-ray  may  show
both  air  and fluid in the chest.  There may be evidence of Hamman's crunch.
In order to diagnose the  condition  a  gastrografin swallow of the esophagus
should be done.  If the  esophagram  is  negative,  endoscopy  may  be  done.
Thoaracentesis  may  reveal a high amylase, low pH of 2-3 and food particles.
Treatment shoulod be immediate as the mortality approaches 50% if the tear is
not repaired within 12 hours.  Antibiotics such as clindamycin, penicillin or
ticarcillin-clavulanate are  indicated.   If  pneumothroax  or  large pleural
effusions are present a tube  thoracostomy  should  be  placed.   Surgery  is
indicated for repair of the perforation.

                              -BOTULISM-
Botulism is a neurologic  disorder  that  is  caused by a neurotoxin produced
from Clostridium botulinum.  It is usually caused by  foods  that  have  been
improperly canned, or improperly prepared at home.  Home processed vegetables
and  fruits  are  particularly  at  risk.   Others  that have been implicated
include fish, condiments, milk,  beef,  poultry,  and pork.  Honey is another
source of food poisoning due to botulinum toxin.  Botulism may  also  present
as  infant  botulism or wound botulism.  Occasional cases of classic botulism
still occur in  the  USA,  usually  due  to  improper  home canning of foods.
Clostridium botulinum is an anaerobic gram positive rod that produces spores.
The elaborated toxin is a heat labile neurotoxin (botulin).  The spores of C.
botulinum are ubiquitous in the soil, and are not dangerous unless  thay  are
allowed  to germinate in an anaerobic environment with a pH greater than 4.6.
The spores may be destroyed by  pressure  cooking at temperatures of at least
250 F (120 C) for 30 minutes.  The toxin can be destroyed by boiling at 212 F
(100 C) for one minute, or by heating at 176 F (80 C)  for  20  minutes.   If
semi cooked foods are left out at ambient temperatures for at least 16 hours,
lethal amounts of botulin toxin can be produced.  The toxin is very powerful.
Approximately .05 ug of toxin, or a single taste of the toxin can prove to be
lethal.   C.  botulinum elaborates 8 different type of toxins.  Most cases of
human poisoning is due to type A, B,  and  E.  Type F is rare.  Types A and B
are the most potent.  Other types include types  Calpha,  Cbeta,  D,  and  G.
Clostridium  botulinum  type  A  toxin  is  more  commonly  found west of the
Mississippi, and toxin B is found  in  the  eastern USA.  Toxin E is found in
the Great Lakes region and in Alaska.  Type E toxin can occur at temperatures
as low as 37.4 F (3 C), and does not need strict anaerobic requirements.  The
toxins do their damage by blocking acethylcholine release at  the  peripheral
neuromuscular  and autonomic nerve junctions, by irreversible tissue binding.
FOODBORNE BOTULISM: The incubation  period  is  usually 18-36 hours following
ingestion, but can range from a few hours to 8 days.  The  onset  is  usually
sudden  with  early signs and symptoms of sore throat, dry mouth and GI upset
(nausea, vomiting, abdominal pain).   Following  this, diplopia, ptosis, loss
of pupillary light reflex and accommodation, pupillary  dilation,  dysphagia,
and  dysarthria  occur.   There  may be nasal speech and aspiration.  This is
followed by a descending paralysis and respiratory failure.  Maximal weakness
usually occurs 7-10 days after  the  onset  of  symptoms.  There is no fever,
mental obtundation or sensory changes and examination of the blood, urine and
CSF are usually normal.  The heart rate is normal or slow,  unless  there  is
infection present.  The deep tendon reflexes are usually normal, unless there
is  severe  weakness.  Constipation may be present.  The diagnosis depends on
the  identification  of  the  organism  or  toxin  in  the  patient  or food.
Specimens of feces, vomitus and serum shuld be examined.   An  enzyme  linked
immunosorbent assay (ELISA) test of the feces can identify the toxin in feces
within  24  hours,  or by isolation of botulism toxin by mouse neutralization
bioassay.  Specimens for toxin  analysis  should be refrigerated, but culture
samples for Clostridium botulinum should not.  C. botulinum can be  grown  on
selective  media  from samples of stool or foods.  High rate 40 Hz repetitive
nerve stimulation  will  demonstrate  incremental  responses  of the compound
action potentials in the motor nerves.  INFANT BOTULISM: Infants  at  highest
risk  include  those  aged  1  week  to 6 months who are breast fed and given
honey.  Infant botulism is  due  to  C.  botulinum  residing  in the GI which
produces the toxin.  The infants develop constipation, weak suck, pooled oral
secretions, difficulty in feeding, hyptonia, poor  gag  reflexes,  and  mild,
subtle  ocular palsies.  WOUND BOTULISM: Wound botulism is due to germination
of the organism in  infected  injection  sites,  which then produces toxin in
vivo.  It occurs chiefly in young adults who str  intravenous  drug  abusers.
It  may  also  be  seen in cocaine sniffers with germination of spores in the
nasal passages.  The  usual  incubation  period  is  4-14 days.  DIFFERENTIAL
DIAGNOSIS: includes Guillain-Barre  syndrome,  myasthenia  gravis,  poisoning
with   jimsonweed,   atropine,   belladonna,   and  curare,  tick  paralysis,
poliomyelitis,   stroke,   arsenic    intoxication,   rabies,   streptococcal
pharyngitis, and acute abdomen.  TREATMENT: If the patient is seen  within  a
few  hours  following exposure, vomiting should be induced with ipecac and/or
gastric lavage.  Enemas  may  help  eliminate  the unabsorbed toxin.  Classic
foodborne and wound botulism is treated with botulin  antitoxin  which  binds
the  circulating free toxin.  It is not capable of reversing previously fixed
neurologic manifestations.  Trivalent  antitoxin  (A,  B,  E) can be obtained
from the Centers for Disease Control (CDC), in Atlanta,  Georgia.   Trivalent
botulin  antitoxin contains 7500 IU of type A, 5500 IU of type B, and 8500 IU
of type E. The telephone number is 404-329-2888.  A polyvalent antitoxin that
contains A, B, C, D, E,  and  F  is  also available.  The antitoxin should be
given as soon as possible.  If it is given  later  than  about  3  days,  the
benefits  are  markedly decreased.  The patient is given 1-2 vials IV every 4
hours for 4-5 doses.  The  duration  of  the  therapy depends on the clinical
response.  It should not be given IM.  Prior to administration, a  skin  test
should  be  done,  and  the  patient  is  given diphenhydramine 1-2 mg/kg IV.
Epinephrine should be immediately available, because even if the skin test is
negative, anaphylaxis is  possible.   Trivalent  antitoxin is not recommended
for infant botulism.  Patients should be  monitored  frequently  with  serial
measurements  of  vital  capacity  as  respiratory  failure  can  occur  very
suddenly.   Wound botulism will need incision and debridement of all infected
tissue,  and  administration   of   penicillin  giving  300,000  units/kg/day
intravenously.  Other antibiotics that may be effective  include  clindamycin
30  mg/kg/day IV, and chloramphenicol 50 mg/kg/day IV.  Guanidine is given to
increase the release of acetylcholine at the nerve ending, which will improve
the ocular and limb paralysis.  The  dose is 15-50 mg/kg/day divided into 4-5
doses.   Guanidine  does  not  help  respiratory  paralysis.   Patients  with
respiratory paralysis will  need  intubation,  tracheostomy,  and  mechanical
ventilation  along  with  nasogastric  or  IV  feedings.   The mortality from
botulism is about 25%, and the duration  of  the disease can be from weeks to
months.

                         -BRONCHIAL ASTHMA-
Morbidity and mortality from bronchial asthma is increasing in  the  USA  and
world  wide,  and  is  thought  to  be  due  to  inadequate  treatment,  poor
compliance,  poor  insight  into the severity of the disease and inability of
some patients to achieve health  care.   In  this discussion, the severity of
bronchial asthma will be categorized as mild, moderate  or  severe,  and  the
accepted  therapy  within each category will be discussed.  For most patients
it is beneficial if the patient  can  purchase  a peak flow meter in order to
measure the peak expiratory flow rate (PEFR).  The PEFR  should  be  measured
during  the  attack  and after treatment.  In order to simplify the treatment
for the patient a color zone peak flow meter should be purchased.  This meter
then tells the patient  whether  the  status  is mild (Green light), moderate
(Yellow light), or severe (Red light).  This is useful for  telephone  calls.
The patient can report the color of the light to the physician over the phone
and  appropriate  therapy  can  then  be  given.  MILD BRONCHIAL ASTHMA: Mild
bronchial asthma is characterized  by  intermittent,  brief attacks of asthma
that occur up to 2 episodes per week.  The patient registers  a  green  light
and  the  PEFR  is  80-100%  of  the  predicted  value  and  the  patient  is
asymptomatic.   The  treatment  for  mild attacks is beta adrenergic agonists
delivered by MDI or  nebulization.   Exercise  induced asthma is treated with
with beta  adrenergic  agonists;  2  puffs  20  minutes  prior  to  exercise.
ALBUTEROL  (Proventil, Ventolin) MDI delivers 90 ug/inhalation.  Treatment is
2 inhalations prn.  If  using  nebulized  solution  the  dose  is 2.5 mg prn.
METAPROTERENOL (Alupent, Metaprel) MDI delivers .65 mg/inhalation.  Treatment
is 2-3 inhalations prn.  Nebulization treatment is .2-.3 ml of 5% solution in
2.5  ml  of  normal  saline.   TERBUTALINE  (Brethaire)   MDI   delivers   .2
mg/inhalation.   Treatment  is 2 inhalations prn.  BITOLTEROL (Tornalate) MDI
delivers  .37  mg/inhalation.   Treatment  is  2  inhalations  over  1-3 min,
followed by  a  third  inhalation  if  necessary.   PIRBUTEROL  (Maxair)  MDI
delivers  .2  ug/inhalation.   Treatment  is  2 inhalations prn.  The patient
should be instructed in the proper use of the MDI.  The head should be tilted
backwards slightly, and the patient  should  exhale.  The inhaler should be 3
inches from the mouth and the plunger pushed as the patient takes a deep slow
breath.  The breath should then be held for 10 seconds  and  exhaled  through
the  nose.  If the patient is unable to use good technique, spacers should be
used.  Oral beta agonists take too long to achieve the desired effect and are
best used  during  the  nocturnal  hours  for  patients  that  have nocturnal
attacks.  Anticholinergic agents such as Ipratropium isn't  as  effective  in
asthma as it is in chronic obstructive pulmonary disease.  MODERATE BRONCHIAL
ASTHMA:  Moderate bronchial asthma is characterized by several attacks weekly
with occasional nocturnal attacks.  The PEFR is 50-80% of the predicted value
or a yellow light.  Moderate  asthma  may represent an exacerbation of asthma
or the condition may be out of control.  Treatment of this  group  is  mainly
with corticosteroid aerosols.  Patients should gargle after each treatment to
help  prevent  oral  thrush.   About  15%  of  patients  will develop thrush.
BECLOMETHASONE  (Beclovent,   Vanceril)   MDI   delivers   42  ug/inhalation.
Treatment is 8 inhalations or 336 ug, then 2 inhalations bid after the asthma
has stabilized.  TRIAMCINOLONE (Azmacort)  MDI  delivers  100  ug/inhalation.
Treatment  is  8 inhalations or 800 ug, then reduce to 2 inhalations bid when
asthma is  stable.   FLUNISOLIDE  (Aerobid)  MDI  delivers 250 ug/inhalation.
Treatment is 4 inhalations or 1000 ug, then reduce to 2 inhalations bid  when
the  asthma  is  stable.   The aerosolized corticosteroids should be given in
conjunction with the beta adrenergic  agonists.   The  short term use of high
doses  of  the  aerosolized  corticosteroids  is  safe  and  doesn't,t  cause
significant adrenal suppression.  CROMOLYN (Intal) MDI is an  alternative  in
moderate  asthma, and delivers 800 ug/inhalation.  Treatment is 2 inhalations
qid.  A 4-6 week trial  of  this  drug  is  necessary to assess its efficacy.
NEDOCROMIL (Tilade)	has recently  been  approved  and  is  more  potent  than
cromolyn.   The  main  side  effect  of  these  latter  two  drugs  is cough.
SUSTAINED  THEOPHYLLINE  may  also  be   used   in  moderate  asthma  and  is
particularly useful in nocturnal asthma by giving a long acting  preparations
as  400-600  mg of theophylline at 5:00 PM nightly.  SEVERE BRONCHIAL ASTHMA:
Severe bronchial asthma  is  characterized  by  daily  symptoms with frequent
nocturnal disturbance of sleep.  The PEFR is less than 50% of  the  predicted
value  or  a  red  light.  The treatment in this group is with oral steroids.
The oral steroids are used  in  conjunction  with beta adrenergic agonist and
inhaled glucocorticoids.  PREDNISONE can be given at 40-60 mg every AM for up
to 2 weeks and then slowly taper the prednisone so that patient possibly  can
be   maintained  on  inhaled  steroids.   PEFR  should  be  monitored  daily.
METHYLPREDNISOLONE can be given IV at  250  mg  given over 30 minutes every 6
hours.  ENVIORNMENTAL CONTROL: The most common allergens causing  asthma  are
house  dust  mites, cockroaches, dander from pets, mold and airborne pollens.
Air conditioning is helpful in  reducing  airborne pollens and molds.  Indoor
molds have a high density in areas of the house that have high  humidity,  as
bathrooms,  basements and kitchens.  These areas should be cleaned frequently
and using a dehumidifier set  between  25-50%.  Patients should avoid outdoor
activity at noon and in the afternoon during pollen season.   Windows  should
be  kept  closed.  House dust mites like dampness, such as below ground level
and concrete floors.  These should be avoided.  Spraying agents to kill mites
may help.  If carpets are laid on concrete they should be replaced with tile.
Floors should be kept bare, bedrooms should not have carpeting or upholstered
furniture, closets should  be  well  ventilated  and  there should be minimal
furnishings.  Bedding should be aired daily if possible and frequently washed
in  hot   water.    Mattresses   and   pillows   should   be   covered   with
airtight-moisture   proof   casings.    Pillows   should  be  washed  weekly.
Cockroaches are a source of allergen  and  should be eliminated.  Cat and dog
allergens  play  an  instrumental  part  in  promoting   asthmatic   attacks.
Preferably,  dogs  and  cats should be prohibited and kept outside the house.
Cat allergen is worse  than  dog  allergen  and  tends to persist because the
allergen is difficult to remove by cleaning and stays  airborne  longer.   If
the family cannot be persuaded to eliminate pets, bathing the pets frequently
is  helpful.  Cigarette smoking should be eliminated and viral infections can
be reduced by washing the hands frequently.

                           -BRONCHIOLITIS-
Bronchiolitis is an inflammatory disorder  of the bronchioles that is usually
seen in children under the age of 2. The pathohistologic changes  consist  of
inflammatory  changes around the bronchioles with lymphocytes, destruction of
the bronchiolar epithelium and ciliary  lining,  plugging of the lumen of the
airways, and edema  of  the  bronchiolar  walls,  submucosa  and  adventitia.
Epidemics  usually  occur  between  October  and April.  The most susceptible
group is infants who are between 1 month and 2 years of age.  The attack rate
is very high in children  attending  day  care centers.  It is estimated that
about 95,000 children are hospitalized in the USA  with  RSV  infection,  and
that abaout 4500 die each year, although the prognosis is usually good.  Most
infants  will  recover fully from an attack of bronchilolitis, but may become
reinfected at a later date.  The highest incidence occurs in infants that are
2-6 months of age.  It  tends  to  be  more  severe  in neonates and in those
infants who are premature as well as those with underlying  congenital  heart
disease,  immunodeficiency or those with chronic lung disease.  It is usually
caused by  the  respiratory  syncytial  virus  (RSV),  but  can  be caused by
parainfluenza virus types 1 and 3, influenza virus types A and B,  adenovirus
types  3, 7, 21, and enterovirus.  RSV consists of a core of ribonucleic acid
(RNA) which is covered by  glycoprotein.   The immune response is dictated by
the surface projections of the glycoprotein.  Different strains have  varying
antigenicity  of  the  90  kd  or G protein.  CLINICAL: These infants usually
present initially with a nasal  discharge  and  low grade fever for about 1-3
days before the wheezing,  tachypnea  and  chest  retractions  appear.   Some
infants  will  present  with  apnea  and cyanosis and bradycardia if they are
under the age of 6, and  were  premature.  Ausculatation of the chest reveals
fine inspiratory crackles and a  prolonged  expiratory  phase.   Chest  x-ray
shows  signs  of  hyperinflation  with  flattened  diaphragms,  peribronchial
thickening  and  patchy  atelectasis.   There  is an incrased anteroposterior
thoracic diameter and prominent  retrosternal  space.  The WBC varies between
5000 and 24,000 cells/mm3 with a preponderance of polys.  A diagnosis usually
can be made by obtaining a rapid antigen detection test using ELISA or direct
fluorescent antibody staining.  The ELISA can quickly, within hours,  make  a
diagnosis  from  swabbing  the  nasopharyngeal  secretions.   However,  false
negative  results may be obtained in 5-20%.  DIFFERENTIAL DIAGNOSIS: The time
of the year is important  in  arriving  at  a diagnosis.  As stated, most RSV
bronchiolitis infections occur from October-April.  The progression  from  an
upper  respiratory  disease to wheezing, tachypnea and retractions in a child
from 2 months to 2 years is also important.  Asthma may present some problems
in the differential.   In  asthma  there  is  usually  a history of recurrent
wheezing, and allergy.  The presence of fine inspiratory  crackling  is  also
useful in differentiating bronchiolitis from asthma.  Cystic fibrosis usually
has  a history of recurrent wheezing, chronic diarrhea and recurrent bouts of
pneumonia.   Some  patients  with   congenital  heart  disease  will  wheeze,
particularly from large left to right shunts.  However, the  presence  of  an
enlarged  heart  is  against  a  diagnosis  of  bronchiolitis.  Patients with
bronchiolitis  obliterans  can  pesent   with  recurent  wheezing  and  chest
infections, and chronic cough.  Chest x-rays will show  obliteration  of  the
terminal  bronchiolar  lumens  and  dilation  of  the distal bronchioles, and
pulmonary angiography  will  reveal  narrowed  pulmonary  arteries.  Vascular
rings must be ruled out, as these children  may  present  with  wheezing  and
stridor.  The diagnosis is usually made by MRI and barium swallow.  Recurrent
aspiration  and  foreign  body  may  offer  additional  difficulty  with  the
diagnosis.   Inspiratory  and  expiratory  chest  films  are  helpful  for  a
diagnosis of foreign body.  TREATMENT: Patients with severe bronchiolitis are
very  ill  and hypoxemic.  The best predictor of severity is the SaO2.  Other
predictors include a respiratory rate greater than 70, younger than 3 months,
atelectasis, and those infants  that  were  premature  under 34 weeks.  These
infants may be placed in an oxygen tent.  High densities of mist  should  not
be  used  as they can worsen the bronchospasm.  Instead, the oxygen should be
humidified.  Oxygen may be administered  by  nasal cannula, face mask or tent
to keep the SaO2 greater thatn 95%.  Many of these infants are dehydrated and
should be treated with IV fluids slowly.  It usually is appropriate to  place
the  patient on antibiotics after cultures have been obtained.  Patients with
bronchiolitis often have hyperreactive  airways  and beta agonist therapy may
help  in  some  patients.   Aerosolized  beta  agonists  therapy   has   been
controversial,  but  it seems appropriate to try these agents.  Albuterol can
be given as .25 mL of .5%  albuterol  in  3 mL of normal saline via nebulizer
for 10-15 minutes every 1-3 hours as needed if the patient is under  the  age
of  1  year.   For  patients  greater  than  1  year  of age use .5 mL of .5%
albuterol solution in 3  mL  of  normal  saline.  Controlled studies have not
indicated any good data to support the  use  of  corticosteroids.   Ribavirin
(1-beta-D-ribofuranosyl-1,2,4  triazole-3-carboxamide)  aerosol  treatment is
known to decrease the severity, and shorten the course of the disease in some
patients.  It is a synthetic nucleoside that limits viral replication.  It is
most effective when initiated  early  in  the  course  of the disease.  It is
indicated in those patients  that  are  severely  ill  with  arterial  oxygen
tensions  of  less  than  65  mm  Hg.   or  oxygen  saturation less than 90%,
increasing arterial carbon  dioxide  tensions,  premature infants, those with
cystic fibrosis, bronchopulmonary dysplasia  or  any  chronic  lung  disease,
patients  being  treated  with chemotherapy, transplant recipients, and those
who are being mechanically ventilated.   Ribavirin  can be given in an oxygen
tent, mask, hood or through the ventilator tubing at a  concentration  of  20
mg/mL  delivered  by  a small particle generator.  It is usually given for 18
hours out of each  24  hour  interval.   The  maximum  effect is usually seen
within the first few days of therapy.  Patients should be monitored carefully
for respiratory failure and apnea.  Secondary  respirations  with  Hemophilus
influenzae,  Branhamella  catarrhalis,  Streptococcus  pneumoniae,  and other
viruses can occur.   Patients  who  have  had  bronchiolitis  are at risk for
subsequent bronchial hyoperreactivity and asthma.  The  incidence  of  asthma
has  been  shown  to  be  as  high  as 50% in those children who have had RSV
bronchiolitis as an infant.

                        -BROWN RECLUSE SPIDER-
The brown recluse spider (Loxosceles species)  is found mainly in the central
and southeastern part of the USA, such  as  Kansas,  Missouri,  Arkansas  and
Tennessee,  but  can  be  found  throughout  the USA.  The most common of the
Loxosceles family is Loxosceles  reclusa.   Of  the  13 species of Loxosceles
found in the United States, 5 are capable of  producing  ulcerative  lesions.
The  brown  recluse  spider prefers to live outdoors under woodpiles, debris,
and rocks, but can inhabit  the  household  in the basement, attic or storage
areas.  The spider is nocturnal and tends toward an introvert behavior.   The
envenomations  are common while sleeping, dressing or working in the house or
yard.  The spider measures 1-5 cm  from  leg  to leg.  There is violin shaped
brown to yellow marking on the dorsal cephalothorax.  There are  3  pairs  of
eyes  and the legs are long and slim.  CLINICAL: The initial envenomation may
only present as a mild, transient  irritation with a benign course.  However,
in some, a few hours later, a hemorrhagic bleb or blister  may  form  at  the
center,  followed  in  2-3  days by central necrosis and the development of a
black necrotic center.  A  bull's  eye  configuration occurs in some patients
immediately following the evenomation.  Over the following weeks, the  center
will  slough  leaving  an  ulcer that heals with gredat difficulty.  The most
severe lesions occur in fatty areas of  the body such as the thighs, buttocks
and abdomen.   Loxosceles  venom  contains  about  12-15  proteins  including
lipase,  phosphorylase,  sphingomyelinase, esterase, protease, hyaluronidase,
collagenase, and phospholipase.  These are capable of producing local as well
as systemic hemolysis,  complement  activation and intravascular coagulation.
Systemic effects may develop about 24-72 hours following the bite and include
chills, nausea, vomiting, myalgia,  arthralgia,  weakness,  fever  and  rash.
Actually, the development of a rash is often a good prognostic sign, as it is
commonly seen when a skin lesion suddenly improves and subsequently resolves.
However,  the  rash  may  be  missed.  It may be transient, faint, macular or
speckled, and commonly occurs  over  the  trunk  and  areas of flexure.  Some
patients will  develop  a  secondary  bacerial  infection,  lymphangitis  and
lymphadenopathy.   LABORATORY:  Patients  may  develop  anemia, leukocytosis,
thrombocytopenia, hemolysis and  disseminated intravascular coagulation.  The
hemolysis may lead  to  hemoglobinemia,  hemoglobinuria,  renal  failure  and
shock.  Patients may also develop liver injury, seizures, heart failure, coma
and  even death.  All patients with a brown recluse spider bite should have a
CBC and UA.  If  hemolysis  is  suspected,  plasma  and urine free hemoglobin
should be done, along with PT, PTT, fibrin degradation products,  fibrinogen,
liver  function  tests, electrolytes, BUN, and creatinine.  TREATMENT:General
measures include elevation  and  immobilization  of  the  affected area, cool
compresses, diphenhydramine, and tetanus  prophylaxis.   If  skin  ulceration
develop,   Dapsone   100   mg   every   12   hours  for  2  weeks  is  given.
Glucose-6-phosphate dehydrogenase deficiency  should  be  ruled  out prior to
starting  dapsone,  and  hematocrits  should  be  followed  after  initiating
Dapsone.  Patietns  that  develop  systemic  arachnidism  and  hemolysis  are
treated with methylpredisolone, 1-2 mg/kg every 6 hours IV, or prednisone 1-2
mg/kg/day  PO.   Surgical  excision  and  steroids are usually of no benefit.
Large ulcerations may need skin grafting.

                        -BULLOUS PEMPHIGOID-
CLINICAL: Bullous pemphigoid  is  a  benign  epidermal  disease affecting the
aged.  It is usually seen after the age of  60  and  is  characterized  by  a
chronic bullous eruption tending to affect the flexural areas.  Less than 25%
will  have  mucosal  involvement.   It  is  an  autoimmune disease because of
antibodies directed against  the  basement  membrane  of  the epidermis.  The
bullae are tense and tend to arise from normal  appearing  skin  usually,  or
occasionally  erythematous  skin.   The  bullae may be 2-10 cm in size.  They
usually contain clear fluid,  but  at  times  the  fluid may be blood tinged.
They appear on the extremities  initially  and  then  the  trunk.   They  are
pruritic,  as  opposed to pemphigus vulgaris.  Sometimes there is involvement
of the palms,  soles,  scalp  and  mucous  membranes.   The  number of intact
vesicles is greater than the number of erosions which is  opposite  from  the
findings  in  pemphigus  vulgaris.   Nikolski's  sign  is  absent  in bullous
pemphigoid.   Lesions  may  occur  in  the  mouth,  but  not  as  commonly as
pemphigus.   Other  mucosal  surfaces  tend  to   be   spared.    LABORATORY:
Circulating  autoantibodies  of IgG can be detected in the serum in about 70%
of cases  by  indirect  immunofluorescence,  and  90%  of  patients on direct
immunofluorescence of the epidermal basal cell layer.  Light microscopy  will
show  the  subepidermal blister with perilesional inflammation which contains
eosinophils.  TREATMENT: Treatment is  usually  started with prednisone which
is very effective in high doses	initially.  In  general,  dose  reduction  of
prednisone can be started much earlier than pemphigus and occasionally can be
discontinued.   Alternative  treatments consist of dapsone and sulfapyridine,
especially in mild cases.  Prednisone is  started  at 60-80 mg as a single AM
dose.  This is gradually tapered after several weeks to a  maintenance  level
of  20-40  mg/day.   From  this point there should be an attempt to switch to
every other day treatment.  Some  patients will respond to further reductions
of prednisone by about 5 mg decrements.  Relapse may  occur  and  it  may  be
necessary  to  increase  the  prednisone  or  add  steroid  sparing agents as
azathioprine, methotrexate or  cyclophosphamide.   Side  effects  from all of
these drugs must be monitored carefully.  Localized  bullous  pemphigoid  may
respond to high-potency topical steroids without using oral prednisone.

                         -BUSULFAN TOXICITY-
Busulfan is an alkylating agent that is used  in  the  treatment  of  chronic
myelogenous leukemia.  Hematologic complicatons include myelosuppression, and
agranulocytosis  which  can  progress to aplastic anemia.  Agranulocytosis is
rare, however.   Skin  changes  include  hyperpigmentation  which  usually is
reversible after therapy  is  discontinued.   Other  skin  side  effects  are
erythemia  multiforme,  urticaria,  erythema  nodosum,  dryness,  anhidrosis,
cheilosis,  porphyria cutanea tarda, and alopecia.  Patients may also develop
Busulfan  lung  (bronchopulmonary  dysplasia  with  fibrosis).   Should  this
happen, the busulfan  should  be  discontinued.  Reproductive changes include
amenorrhea, menopausal symptoms, ovarian suppression, azoospermia,  sterility
and  testicular  atrophy.  Patients can also develop a peculiar syndrome that
is not unlike  that  of  adrenal  insufficiency  which  consists of weakness,
anorexia, weight  loss,  fatigue,  nausea,  vomiting  and  hyperpigmentation.
Should  the  patient  develop  this  adrenal  insufficiency-like  syndrome or
busulfan lung, the drug should  be  discontinued  and started on an alternate
drugs such as melphalan.

                           -CAMPYLOBACTER- 
Campylobacter  infections are caused by small, microaerophilic motile curved,
or spiral gram negative bacilli  which  cause gastroenteritis in children and
adults.  The organism has a single flagellum at one or both poles.  There are
3 species, Campylobacter fetus, C. intestinalis and C. jejuni.  Campylobacter
jejuni reuires a selective medium and incubation at 42  C.  Growth  may  take
5-14  days  from  inoculation,  but  usually can be observed at 3 days if the
organisms are innoculated on  sheep  blood  and  chocolate agar in 5-10% CO2.
Campylobacter commonly colonizes  wild  and  domestic  animals,  particularly
poultry.   Dairy  cattle  are  considered  to  be a significant reservoir for
campylobacter, and there have  been  several  outbreaks of gastroenteritis in
individuals that have consumed  raw  milk.   Several  cases  have  also  been
associated  with  sick  puppies,  and  it  is  common  at  day  care centers.
Transmission is typically from  improperly  cooked poultry, contaminated food
and water, and fecal oral spread.  Campylobacter jejuni is a  frequent  cause
of  enteritis  in  humans,  whereas  Campylobacter  fetus  causes bacteremia,
endocarditis,  focal  abscesses,   and   meningitis   in  patients  that  are
immunocompromised, elderly or debilitated.  Campylobacter fetus has also been
implicated in abortion, stillbirth, and neonatal  infections.   Newborns  can
acquire  Campylobacter from their mothers at the time of delivery.  CLINICAL:
The incubation is  about  2-11  days,  which  is  followed  by an enterotoxin
induced watery diarrhea and vomiting which may be mild or severe.  The  onset
is usually sudden with headache, malaise, fever, abdominal cramps, nausea and
vomiting.  This is followed by diarrhea that may be water, mucoid, bloody, or
bile  stained.   Patients may have up to 20 stools per day.  Fortunately, the
disease is self limited after  about  2-7  days,  but  there is a fairly high
frequency of relapses (15-25%).   Complications  include  seizures,  erythema
nodosum,  reactive  arthritis,  cholescystitis  and urinary tract infections.
The organisms can be cultured  from  the  stools for 1-6 weeks if antibiotics
are not given.  LABORATORY: Darkfield or phase contrast microscopic  scrutiny
of a stool specimen will reveal darting bacilli.  These motile bacilli may be
confused  with  Vibrio  cholerae  and  Vibrio  parahaemolyticus.  Culture, as
mentioned, requires selective agar  and  incubation  temperatures of 42 C, 5%
CO2, and 5% oxygen.  The peripheral  WBCs  are  usually  elevated  with  band
forms.    DIFFERENTIAL   DIAGNOSIS:   Campylobacter   enteritis  may  imitate
salmonellosis,  shigellosis,  amebiasis,  viral  gastroenteritis,  ulcerative
colitis, Crohn's disease, appendicitis, intussusception, invasive Escherichia
coli and Yersinia  enterocolitica  enteritis.   TREATMENT:  Treatment is with
erythromycin at 30-50 mg/kg/day PO in 4 divided doses in children, or 250-500
mg QID in adults for 5-7 days.  Ciprofloxacin can also be used in adults at a
dose of 500  mg  BID  for  5-7  days.   Severe  systemic  infections  due  to
Campylobactger  fetus may be treated with gentamicin, kanamycin, ceftriaxone,
or  chloramphenicol.   Ceftriaxone  or   chloramphenicol  is  used  to  treat
associated meningitis, as they penetrate the blood brain barrier.

                   -CANCER AND CARDIAC EMERGENCIES-
PERICARDIAL   DISEASE:   Metastatic  pericardial  disease  is  fairly  common
occurring in about  1.5%-21%.   Primary  pericardial  tumors  are rare.  Most
patients will have carcinoma of the lung or  breast,  although  leukemia  and
lymphoma sometimes spread to the pericardium.  Other causes include radiation
induced,  drugs,  such as cyclophosphamide, cytarabine (Cytosar), and GM-CSF,
and infectious and  idiopahtic  pericarditis.   Symptoms of cardaic tamponade
include shortness of breath, edema, and ascites.  The blood pressure  may  be
normal  or  low  and  the  chest  x-ray  will show an increase in heart size.
Pulsus paradoxus, a decrease of  inspiratory  arterial systolic pressure of >
12 mm Hg, may be present, but also is seen in asthma, and chronic obstructive
pulmonary disease.  The  ECG  may  show  a  diminution  of  QRS  voltage  and
electrical  alternans.   The jugular veins may be distended.  Two dimensional
echocardiography  may  show  diastolic  collapse  of  the  right  atrium  and
ventricle with a reduced  diameter  change  of  the inferior vena cava during
respiration.  Pericardiocentesis with  echocardiographic  guidance  is  often
done  and  pericardial fluid is examined for bacterial, fungal, and acid-fast
cultures, and cytology.  Instillation of  sclerosing agents may be effective.
MYOCARDIAL  DISEASES:  Angthracyclines   and   cyclophosphamide   can   cause
myocarditis,  resulting  in  dyspnea, tachycardia, jugular venous distention,
S3, mitral and tricuspid regurgitation,  hepatomegaly and edema.  Chest x-ray
will show cardiomegaly and  pulmonary  edema.   Treatment  is  with  digoxin,
dobutamine  or  dopamine and afterlaod reducers.  ARRHYTHMIAS: Taxol has been
associated  with  bradycardia  and  AV  block.   Anthracyclines,  interferon,
5-fluorouracil,  interleukin-2,  ifosfamide,  etoposide  and  GM-CSF  have an
increased  incidence  of  supraventricular   and   ventricular   arrhythmias.
CORONARY  ARTERY DISEASE: Many patients that have concomitant coronary artery
disease and cancer will have  exacerbations  of their coronary artery disease
with various cancer treatment interventions.  Cancer chemotherapy  may  cause
bone  marrow  depression with anemia, which can cause angina.  Interferon and
interleukin-2  can  cause  a  high   output  state,  resulting  in  increased
myocardail oxygen demand.  Vinblastine, interleukin-2 and 5-fluorouracil have
been associated with angina and acute myocardial infarction.

                        -CANCER OF THE COLON-
Hepatic  arterial  infusion  is  expensive and does not result in substantial
palliation or improved survival.  Eighty  percent of patients with colorectal
cancer are potentially curable with surgery.  Stage I (Dukes'  stages  A  and
B-1, invasion to the muscularis propria without nodal involvment) gives a 90%
probability  of  cure.   Stage II (Dukes' stage B-2, invasion into or through
the serosa or  nonperitonealized  pericolic  tissue without nodal involvment)
gives a 75% chance for cure, while stage III (Dukes'stage  C,  metastasis  to
regional  lymph  nodes)  gives a 35% chance for cure.  Postoperative adjuvant
therapy for stage III with fluorouracil  + levamisole will reduce the risk of
recurrence by 41% and reduces the rate of death by  33%.   Stage  II  is  not
nearly  as  effective.   These two drugs are started simultaneously 3-5 weeks
following surgery.  Fluorourail  is  given  as  450  mg/m2 by rapid injection
daily for 5 days, then weekly for 48 weeks starting at 28  days.   Levamisole
is  given  at  50  mg  PO TID for 3 days every 2 weeks for 1 year.  Watch for
elevated alkaline phosphatase  and  less  often elevated aminotransferase and
bilirubin  which  occur  in  about  39%  and  sometimes  associated  with  an
increasing CEA and fatty liver depicted by CT or biopsy.   They  are  minimal
and reversible, and only of consequence because they raise a flag for hepatic
metastasis.   Neurotoxicity is seen in 4.5% as manifested by cerebellar signs
or   impaired   thinking.    MRI   may   show   changes   characteristic   of
leukoencephalopathy  which  usually  returns   to   normal  after  drugs  are
discontinued.

                      -CANCER OF THE ESOPHAGUS-
Cancer of the esophagus comprises  about  1%  of  all  cancers.   It  usually
develops  in  persons between the ages of 50-70 and the ratio of men to women
is about 5:1.  Cancer of the upper third of the esophagus occurs in 10-20% of
cases, middle third  (50%)  and  the  lower  third  (30-40%.  Esophageal skip
lesions can be seen up to 8 cm from the primary tumor because  of  submucosal
lymphatic   dissemination.    In  addition  there  is  a  1-3%  incidence  of
synchronous, and 4-9% of metachronous  associated primary malignancies of the
pharynx, larynx, lung  and  oral  cavity.   There  are  2  histologic  types;
squamous  cell  carcinoma  and  adenocarcinoma.  Squamous cell cancer is much
more common in blacks than whites regardless of sex.  About 90% of esophageal
cancer is squamous,  but  this  type  is  decreasing  in  the USA.  The three
subtypes of squamous cell cancer are infiltrative, polypoid, and  ulcerative.
About  50%  occur  in  the middle third of the esophagus and 25% occur in the
upper third and 25% in the  lower  third of the esophagus.  Adenocarcinoma is
more common in whites and is increasing in frequency.   Most  adenocarcinomas
develop  as  a  complication  of Barrett's metaplasia secondary to chronic GI
reflux.  Adenocarcinomas develop mostly  in  the  distal esophagus and may be
difficult to differentiate from stomach adenocarcinoma that has  invaded  the
gastroesophageal  junction.  Leiomhyocarcoma is the most common nonepithelial
esophageal cancer.  Other histologies  that  may  occur include non Hodgkin's
lymphoma which is increasing in  incidence  and  is  mostly  related  to  HIV
disease, Hodgkin's disease, salivary gland tumors (adenoid-cystic cylindromas
and   mucoepidermoid   carcinomas),   carcinoid   tumors,  primary  oat  cell
carcinomas, choriocarcinomas and metastiatic  cancer to the esophagus.  There
is an increased risk in those who consume alcohol, especially when it is home
brewed from maize or when it is used with tobacco smoking.  There is also  an
increased  risk  in  those  who  have  had  lye  esophagitis,  chronic peptic
esophagitis, short  esophagus,  Plummer-Vinson  syndrome (atrophic glossitis,
esophagitis, dysphagia and sideropenic anemia), Barrett's esophagus (columnar
epithelium in the lower esophagus), achalasia,  esophageal  webs,  epiphrenic
diverticula,  nitrosamine compounds, betel nuts, croton flaveus, bidi smoking
and opium consumption.  Bartenders,  construction  workers and waiters are at
higher risk probably because  of  exposure  to  tobacco  smoke  and  alcohol.
Native  Hawaiians,  alaskans  and  Puerto  Ricans  are more likely to develop
esophageal carcinoma than other groups  in  the USA.  CLINICAL: Most patients
will present with advanced cancer which is incurable.  It takes 3-4 years for
advanced cancer to develop from carcinoma in  situ.   First  there  is  local
growth,  which  procedes  to  lymmph node involvement and then dissemination.
Most patients  will  have  solid  food  dysphagia  (90%).   The  dysphagia is
sometimes associated with odynophagia.  Weight loss  is  common  and  erosion
into  the  bronchial  tree  can  result  in a tracheoesophageal fistula which
produces coughing, hemoptysis and  pneumonia.   Advanced  cases may result in
laryngeal involvement and hoarseness, edema (superior vena cava  obstruction)
and  dyspnea (phrenic nerve and diaphragmatic paralysis).  Metastatic disease
is suggestive when the patient  develops pleural effusions, Horner's syndrome
(miosis, ptosis and anhydrosis), cervical or supraclavicular adenopathy, bony
pain, heptomegaly and ascites.  Metastatic spread is most common to the liver
(32%), lung (21%), bone (1%), kidney (1%), pleura (1%)  and  CNS  (1%).   The
most  commonly  involved  draining  lymph  nodes  are  the celiac nodes.  The
incidence of celiac lymph  node  metastases  varies  depending on the inolved
segment of the esophagus.  In lower esophageal lesions, celiac inovlvement is
> 50%, middle third leions (44%), and upper third lesions  (10%).   Lymphatic
spread  is  to  cervical,  supraclavicular,  hilar, subcarinal, paratracheal,
paraesophageal, paraortic, gastric and  celiac  nodes.   The patient may also
develop paraneoplastic syndromes of  hypercalcemia,  inappropriate  ACTH  and
gonadotropin  secretion.   The  differential  diagnosis  includes  achalasia,
adenocarcinoma  of the gastric cardia with esophageal involvement, and peptic
stricture.    Others   included   in   the   differential   include  vascular
abnormalities (aberrant right  subclavian  artery  and  thoracic  aneurysms),
esophageal   webs,  infections  (TB,  syphilis,  pemphigus  and  acute  viral
laryngitis), neuromuscular disorders  (botulism  and  myasthenia gravis), and
poisonings (lead, alcohol and fluoride).  LABORATORY: There may be  elevation
of   the   aminotransferase  or  alkaline  phosphatase  in  hepatic  or  bony
metastases.  Hypoalbuminemia develops from malnutrition and anemia of chronic
disease or blood loss  may  be  present.   Barium  swallow can demonstarte an
intraluminal mass or the abrupt irregular strictures larger than 20  mm  that
are  associated with cancer, as opposed to benign strictures that are usually
smaller than 20  mm  with  gradually  tapering  ends.   Chest  x-ray may show
adenopathuy, a widened mediastinum, bony or  lung  metastasis,  or  signs  of
tracheosesophageal fistula such as pneumonia.  A chest CT is the best imaging
device  for  evaluating  the  extent  of  the primary tumor, mediastinal node
metastases and pulmonary metastases, and can predict resectability.  However,
about 10-20% of lesions that are thought  to be unresectable by CT because of
contiguous organ invasion are in fact resectable.   Esophagogastroscopy  with
biopsy  is  the  best  method for diagnosing esophageal cancer.  The biopsies
need to be deep as submucosal  invasion  may  be present.  In order to detect
this, rigid esophagoscopes are sometimes used instead of the flexible scopes.
Abdominal CT is used for metastatic  involvement  of  the  liver  and  celiac
nodes.   STAGING:  The  tumor  stage is characterized as follows: TX (primary
tumor cannot be assessed), T0  (no  primary tumor is present), T1s (carcinoma
in situ), T1 (tumor invades the lamina  propria  or  submucosa),   T2  (tumor
invades the muscularis propria), T3 (tumor invades the adventitia), T4 (tumor
invades  the  adjacent structures).  The lymph node stage is characterized as
follows: NX (regional lymph nodes  are  not  assessed), N0 (no regional nodal
involvement is present), N1 (Regional lymph  node  involvement  is  present).
Metastatic  stages  are  characterized  as  follows:  MX (presence of distant
metastases not assessed), M0 (no distant metastases are present), M1 (distant
metastases are  present).   The  histopathologic  grade  is  characterized as
follows:  GX  (grade  cannot  be  assessed),  G1  (well  differentiated),  G2
(moderately   well   differentiated),   G3   (poorly   differentiated),    G4
(undifferentiated).  Stage I involves a tumor that is < 5 cm of the esophagus
without  obstruction  or  nodal  involvement  and  corresponds to T1, N0, M0.
Stage II  includes  tumors  >  5  cm  and  nodal  involvement.   Stage  II is
subdivided into IIA corresponding to T2 or 3, N0, M0, stage IIB corresponding
to T1 or  2,  N1,  M0.   Stage  III  represents  extraesophageal  spread  and
corresponds  to T3, N1, M0, or T4 and any N, M0.  Stage IV represents distant
metastases and corresponds to any T  and  any N, M1.  Stage I tumors confined
to the mucosa and submucosa (7-10% of cases) has an 85-90% 5  year  survival.
The  five  year  survival  for  stage  II  is  34%  and for stage III is 15%.
TREATMENT: SURGERY: Only about 50%  are  candidates for surgery since most of
the cancers are well advanced.   However,  because  surgical  palliation  for
obstructive  symptoms  is successful in about 93%, resection may be advisable
even when the  likelihood  of  cure  is  cure.   Contraindications to surgery
include direct invasion of adjacent vital structures as the trachea, spine or
great vessels, widespread metastases with the expected survival is  6  weeks,
fixed  cervical  node  metastases with cervical lesions, and when the FEV1 is
less than 1.0, or  when  there  is  severe  cardiac  disease with an ejection
fraction < 40%.  Patients in whom curative en bloc  resections  are  possible
may  have  a  25-50% 3 year survival.  The surgical approaches may be divided
into the  Sweet  approach  (left  thoracoabdominal  incision), Lewis approach
(right thoracotomy/laparotomy), Belsey approach (right thoracotomy alone), or
the Turner approach (laparotomy and cervical  incision).   The  transthoracic
esophagectomy  is  the  traditional  procedure  for  removal  of  the  distal
esophagus  and  the  proximal  stomach.   SURGICAL RECONSTRUCTION: Continuity
after esophageal resection can  be  established by esophagogastrostomy, colon
interposition, jejunal interposition, and reversed gastric tubes.  For  those
patients  with  locally  advanced esophageal carcinoma who are not candidates
for resection,  palliation  of  the  obstruction  can  be  achieved by bypass
surgery, intraluminal intubation,  gastrostomy  and  cervical  esophagostomy,
esophageal dilation and laser therapy.  The neodymium yttrium-aluminum-garnet
(Nd-YAG)  laser can effect an increase of luminal diameters to as large as 16
mm after 3 laser  treatments  in  80%  of  patients.   This may last for 8-10
weeks.  RADIATION: Radiation therapy is used for  unresectable  lesions  less
than 5 cm in length without distant metastases or tracheoesophageal fistulae,
or  in  patients with resectable lesions who are not good surgical candidates
or who refuse surgery.  These patients are given 5000-7000 cGy delivered over
a period of 4-7  weeks.   Radiation  is  potentially curative, but good local
control or the tumor is achieved in only about 20-50% of  patients  and  they
rarely survive 5 years.  Adjuvant therapy can also be given in those patients
that  undergo surgery.  Postoperative radiation therapy may be given if gross
or microscopic tumor remains,  lymph  nodes  are  involved,  or the chance of
recurrence is thought to be high.   Preoperative  radiation  therapy  is  not
commonly  given  as  most studies show that there is no change in the overall
survival.  However, in spite  of  this  preoperative radiotherapy can improve
surgical resectability by decreasing bulky disease and improve curability  by
eradicating  microscopic  disease.   Radiation may also be given palliatively
for locally advanced (unresectable lesions  larger  than 5 cm) and metastatic
esophageal cancer.  Typically 4500-4800 cGy are given over 4-6 weeks.   About
75%  of  patients will have good short term symptomatic relief.  Side effects
include fistulae which can  develop  in 5-18%.  Other radiation complications
include radiation pneumonitis, fibrosis,  transverse  myelitis,  esophagitis,
esophageal  stricture and hemorrhage, pericarditis and pericardial tamponade.
CHEMOTHERAPY: Combination therapy  with  surgery,  chemotherapy and radiation
therapy affords the  best  hope  for  prolonged  survival.   Combinations  of
fluorouracil,  mitomycin-C, cisplatin and bleomycin with radiation therapy of
2000-6000  cGy  have  yielded   clinical   responses  of  71-100%.   Adjuvant
radiochemotherapy is used in the preoperative setting.  This may  consist  of
radiation  therapy  of  3000  cGy  over  3 weeks with fluorouracil and either
mitomycin-C or cisplatin.  Following this radiochemotherapy, 38-100% are able
to have surgery with  pathologic  complete  responses  in 17-55%.  The median
survival is 12-26 months.  PROGNOSIS: In general, the prognosis for  patients
with esophageal cancer is poor regardless of the stage.  Most of the patients
are dead by 6-12 months, with an overall 5 year survival of 6.2%.

                    -CANCER OF THE HEAD AND NECK-
Cancer  of the head and neck may present as lymph node metastasis to the neck
as a presenting sign in 25-50%  of  cases,  especially those who are 40 years
and older who have  a  history  of  alcohol  and  tobacco  abuse.   Submental
adenopathy  would  indicate a possible cancer of the anterior tongue, lips or
floor of the mouth.   Submaxillary  nodes (glossopalatine pillars, retromolar
trigone), Supraclavicular nodes (GI and GU tract, thyroid gland,  and  lung),
High  jugular  nodes  (base  of  tongue, tonsil, epipharynx, nasopharynx, and
larynx), Mid  jugular  nodes  (oropharynx,  epipharynx,  larynx  and  base of
tongue),  Low  jugular  nodes  (thyroid,  nasopharynx  and  epipharynx),  and
Posterior triangle nodes (nasopharynx).  Squamous cell cancers account for  >
50%   of   cancers   of   the  head  and  neck  presenting  as  neck  masses.
Adenocarcinomas present as  neck  masses  in  about  30-40%, usually from the
lung, breast and GI tract.  Cancer of the head and neck can involve the  oral
cavity,   nasopharynx,  oropharynx,  hypopharynx,  larynx,  salivary  glands,
paranasal sinuses or the ear.   Cancer  of  the  oral cavity can present as a
painful or non-painful nonhealing ulcer with or without bleeding.   Halitosis
may  be  present.  Premalignant lesions such as leukoplakia and erythroplakia
may be early warning  lesions.   Leukoplakia  can  present as whitish plaques
that show carcinoma in situ,  hyperplasia,  or  dysplasia.   Leukoplakia  may
evolve  into  malignancy  in  .15-6%  of  cases depending on the site, or may
spontaneously regress in  25%  of  cases.   Erythroplakia,  on the other hand
appears as red velvety  patchy  areas  which  may  show  carcinoma  in  situ,
dysplasia  or  invasive  carcinoma.   About 90% of these lesions will contain
carcinoma in situ  or  invasice  carcinoma.   Cancer  of  the nasopharynx may
present as nasal obstruction  with  posterior  drainage,  unilateral  hearing
loss, epistaxis, posterior cervical lymphadenopathy, unilateral serous otitis
media  and  cranial nerve V and VI involvement.  Cancer of the oropharynx can
present as a  chronic  sore  throat  with  intermittent bleeding that doesn't
resolve  with  antibiotics.   There  may  odynophagia,  dysphagia,   otalgia,
halitosis  and  trismus.   The  first  sign  may  be a neck mass representing
metastases from a tonsillar  or  base  of  the  tongue cancer.  Cancer of the
hypopharyngeal area may resemble those of laryngeal cancer.  Metastasis  from
the  hypopharynx  occurs  frequently  and  treatment  is  not  as  favorable.
Laryngeal carcinoma should be diagnosed early because of prolonged hoarseness
in  a  person  with  a  history of alcohol and smoking abuse.  Other symptoms
include, dysphagia,  odynophagia,  chronic  cough,  hemoptysis,  pain  in the
throat, and otalgia.  Dyspnea and stridor are late symptoms.  Cancer  of  the
nasal  cavity and paranasal sinuses are usually well advanced in about 70% of
cases because they  go  undiagnosed  posing  as  sinusitis.  Symptoms include
epistaxis, proptosis, and loosening of maxillary teeth.  Any patient that has
unilateral nasal obstruction and intermittent epistaxis that fails to resolve
should be investigated by rhinoscopy.  Cancer  of  the  ear  can  present  as
bleeding from the external auditory meatus, conductive hearing loss, pain and
otorrhea  as  early  symptoms.   Later,  there  may  be vertigo, facial nerve
paralysis, sensorineural deafness  and  external  otitis  that does not heal.
Salivary gland carcinoma may present as an increasing  painless  fixed  mass.
However,  most  salivary  tumors  are benign, especially those of the parotid
gland.  If there is  cranial  nerve  VII  involvement,  cancer of the parotid
gland is a possibility, and would  portend  a  poor  outcome.   CAUSES:  Poor
fitting   dentures,  periodontal  disease  and  poor  oral  hygiene  all  are
associated with cancer of the  oral cavity.  Occupational exposures to nickel
refining, leather and woodworking are risk  factors  for  nasopharyngeal  and
paranasal  sinus  cancer.  Tobacco and alcohol have the highest risk for head
and neck cancers  at  all  sites  except  for  the  salivary glands.  Chewing
tobacco is associated with cancer of the floor of the mouth.   Diets  low  in
riboflavin,  Vitamins A and C, and iron have also been associated with cancer
of the head and neck.  WORKUP:  Patients that have an identifiable lesion may
need CT or MRI of the head and neck, sinus films, chest x-ray, barium swallow
and liver and bone studies.   Laryngoscopy,  esophagoscopy  and  bronchoscopy
with  biopsy  may  also be needed.  The lungs typically are the first site of
distant metastasis from squamous cell  carcinoma  of the head and neck, which
then spreads to the liver, brain,  and  bone.   Chest  x-rays  are  necessary
because  it is well known that second primary tumors can occur at the time of
the initial presentation and  subsequently.   The  primary lesion is known as
the index tumor while the second  primary  malignany  is  either  synchronous
(diagnosed  within  1  month  of the index lesion) or metachronous (diagnosed
after the first month).   The  second  primary  cancer  usually occurs in the
upper aerodigestive tract and lungs.   The  incidence  of  a  second  primary
lesions  is  40-60% in patients who choose to continue to smoke compared with
6% in those who  quit  smoking.   Furthermore,  the  2 year survival has been
reported to be 27% following diagnosis of a second lesion.  Therefore, it  is
very  important  to  stress  to the patient the importance of terminating the
tobacco habit.  Triple panendoscopy is very  important in helping to rule out
the presence of simultaneous and  secondary  tumors.   The  complications  of
panendoscopy  occur  in  <  1%  of  cases  and  can  include  dental  injury,
pneumothorax, perforation, bleeding and airway compromise.  In those patients
that  present  with  cervical  adenopathy  without  any  primary identifiable
lesion, fine needle aspiration of  the  neck  mass is indicated.  It is safe,
accurate and cost effective and can identify the lesion as benign,  malignant
or  infectious.  Complications are rare and the fine needle approach does not
disrupt lymph node architecture  or  prevent  future histologic assessment in
excised nodes.  Fine needle aspiration does not seed the  needle  track  with
tumor  cells.   The  accuracy  of  diagnosing  lymphoma  or  undifferentiated
carcinoma  from  fine  needle aspiration is only about 50-60%, because of the
small specimen obtained.   If  there  is  a  suggestion  of lymphoma from the
aspirate, an excisional biopsy should be done to confirm  the  diagnosis  and
classify  the  lymphoma.   Approximately  10%  of  fine  needle aspirates are
nondiagnostic because of a suboptimal sample and the procedure may have to be
repeated.  Initial excisional biopsy should  be avoided because it can spread
the tumor.  If squamous cell carcinoma is obtained from  the  node  aspirate,
panendoscopy,  CT  and/or  MRI should be done for assessing the extent of the
primary site and lymph node  involvement,  along with additional studies as a
barium swallow, sinus x-rays, liver and bone studies.

                        -CANCER OF THE OVARY-
Epithelial adenocarcinoma of the ovary  is  a  leading  cause of death due to
gynecologic cancer with about 20,000 USA women diagnosed annually.  Most will
present with vague GI complaints as bloating and  most  patients  (75%)  will
present  with  stages III and IV.  Stage I is confined to the ovary, stage II
is confined to the pelvis and stage  III  is spread to the upper abdomen, and
stage IV  includes  spread  to  distant  sites.   Ovarian  epithelial  cancer
accounts for about 80% of ovarian cancer with the remaining consisting mostly
of  germ  cell  tumors.   In  the USA ovarian cancer accounts for 3.7% of all
malignancies in females  and  29%  of  female  genital tract tumors.  Ovarian
cancer is essentially a disease in the peri and post menopausal female,  with
a  peak of about 56/100,000 by the age of 70.  There is a greater risk of 1.5
time in caucasians versus blacks.   First  degree female relatives have a 40%
risk of developing ovarian tumors at an early age.  It  is  also  appreciated
that there is an increased risk of breast cancer in these patients.  Familial
ovarian  cancer  is  an autosomal dominant disease swith variable penetrance.
Patients with Peutz-Jeghers syndrome have  a 5% increased risk for developing
ovarian stromal tumors while  females  with  XY  gonadal  dysgenesis  have  a
predispostion  for  development  of  malignant  germ  cell tumors.  Increased
dietary fat may be  instrumental  as  an  etiology  for ovarian cancer.  Late
child bearing, nulliparity, delayed menopause, and infertility  all  increase
the  risk  of  ovarian  cancer.  Females with previous breast cancer have a 2
times increased  risk  for  developing  ovarian  cancer.   Talc  and asbestos
introduced into the peritoneal cavity also  may  develop  epithelial  ovarian
cancer.   Oral  contraceptives  will  reduce  the  risk  of ovarian cancer by
10-50%%.  CLINICAL:  Many  patients  will  have  no  symptoms  until advanced
disease is present or there is accidently found an adnexal mass.   There  may
be  vague  lower abdominal pain, vaginal bleeding, ascites, mass and pressure
sensations.   Patients  often  complain  of  bloating,  anoexia,  gas  pains,
dyspepsia and backache.  The pain is  usually  not severe.  If the disease is
advanced there may be inguinal lymphadenopathy, ascites, weight loss, pleural
effusion,  supraclavicular  adenopathy   and   increased   abdominal   girth.
Paraneoplastic   associations  include,  hypercalcemia,  inappropriate  ACTH,
hypoglycemia,  thombophlebitis  and  disseminated  intravascular coagulation.
CCB, alkalkine phosphatase, beta hCG, hepatic enzymes,  BUN,  creatinine  PT,
and  PTT  should  be  done.   The CA-125 antigen is found in more than 80% of
patients with non mucinous epithelial  ovarian carcinomas.  This test is used
to follow the progress of the tumor.  Pelvic ultrasound, chest x-ray  and  CT
of  the  abdomen  and  pelvis should also be obtained.  CT with both oral and
intravenous contrast can  assess  the  status  of  the liver, retroperitoneal
lymph  nodes,  peritoneal  disease  and  the  genitourinary   tract.    Alpha
fetoprotein  is  elevated in children and young females with endodermal sinus
tumors.  Carcinoembryonic antigen is elevated in both mucinous ovarian tumors
and colorectal cancer.  If  the  patient  presents  with upper GI symptoms an
upper GI series may be needed.  Likewise a barium  enema  is  needed  if  the
patient  presents  with  a  change  in  bowel  habits to exclude direct tumor
invasion into the colon.  In advanced cases, cystoscopy, proctosigmoidoscopy,
and esophagogastroduodenoscopy may  be  needed.   Fine  needle aspiration can
sample suspicious inguinal and  supraclavicular  lymph  nodes,  liver,  lung,
vagina  and  pelvic  masses.   Paracentesis should not be done for diagnostic
purposes because of seeding  along  the  needle  tract.  Thoracentesis may be
needed for staging in stage IV or for relief of dyspnea.   Uterine  curettage
may diagnose uterine metastases or a primary uterine cancer.  Mammography may
be useful as there is an increased incidence of breast cancer, or there could
be  metastases  to  the  pelvis  from a primary cancer of the breast.  MRI is
generally not used in preoperative evaluation or diagnosis of ovarian cancer.
HISTOLOGY: Malignant ovarian tumors are divided into the following histologic
types: SEROUS CYSTADENOCARCINOMA (about  50%  are  of this type and bilateral
primary tumors are found  in  30%  of  cases).   MUCINOUS  CYSTADENOCARCONOMA
(represents  about  10-15%.   About  50%  will  be  diagnosed before there is
extrapelvic extension and about 10%  occur bilaterally.  The histology may be
confused with colon carcinoma).  ENDOMETRIOID CYSTADENOCARCONOMA: (Occurs  in
10%.   10% are bilateral.  Concomitant endometrial cancer is present in about
20%, which is usually  well  differentiated.   About  30% are associated with
endometriosis.   CLEAR   CELL   CYSTADENOCARCINOMA:   (Is   associated   with
endometriosis  in  about  50%  of patients.  It is rare and rarely bilateral.
Paraendocrine diseases are associated commonly with this tumor.  These tumors
may have a worse prognosis than other epithelial cancers of a similar stage).
MALIGNANT BRENNER TUMORS: (represent  <  1%.   About  10% occur with mucinous
tumors or benign  teratomas  of  the  ovary).   MIXED  EPITHELIAL  CARCINOMAS
(Represent  10%.).   UNDIFFERENTIATED ADENOCARCINOMA: (Is very aggressive and
anaplastic).  METASTASIS: Most ovarian carcinomas  are metastatic at the time
of  diagnosis  (80%).   They  may  spread  by  direct  extension,  lymphatic,
intraperitoneal exfoliation and hematogenously.  Direct extension is  to  the
sigmoid  colon, uterus, cul-de-sac, sigmoid colon, small intestine, tubes and
pelvic peritoneum.  Lymphatic spread is  retroperitoneally to the para aortic
and  supraclavicular,  axillary  and  inguinal  nodes.   There  may  also  be
mediastinal node involvement.  Intraperitoenal implantation occurs  early  to
the  paracolic gutters, cul-de-sac, diaphragmatic surfaces, liver and splenic
capsules,  omentum,  and  intestinal  surfaces  and  associated  mesenteries.
Distant metastasis may  be  to  the  liver,  lung,  bone, CNS and peritoneum.
STAGING BY THE FIGO SYSTEM: STAGE  I=tumor  limited  to  the  ovaries,  Stage
Ia=growth  limited  to  one  ovary  without  tumor  on the external suface or
ruptured capsule and no  ascites  (T1a,  N0,  M0), Stage Ib=growth limited to
both ovaries without tumor on the external surface, or ruptured  capsule  and
no  ascites (T1b, N0, M0), Stage Ic=tumor either stage Ia or Ib, but there is
tumor on the surface  of  one  or  both  ovaries, ruptured capsule, malignant
ascites, or positive peritoneal washings  (T1c,  N0,  M0).   STAGE  II=growth
involving  one  or  both ovaries with pelvic extension, Stage IIa=metastases,
extension or both to the uterus  or  tubes (T2a, N0, M0), Stage IIb=extension
to other pelvic tissues (T2b, N0, M0), Stage IIc=tumor either  stage  IIa  or
Stage  IIb,  but  with  tumor on the surface of one or both ovaries, ruptured
capsule or capsules, malignant ascites  or positive peritoneal washings (T2c,
N0, M0).  STAGE III= tumor involving one  or  both  ovaries  with  peritoenal
implants  outside  the pelvis, positive retroperitoneal or inguinal nodes, or
all of these, Stage IIIa=tumor  is  grossly  limited  to the true pelvis with
negative nodes, but seeding  demonstrated  histologically  to  the  abdominal
peritoneal  surfaces  (T3a,  N0, M0), Stage IIIb=tumor of one or both ovareis
with histologically confirmed  abdominal  implants  no  larger  than  2 cm in
diameter and negative nodes (T3b,  N0,  M0),  Stage  IIIc=abdominal  implants
larger  than  2  cm  in  diameter and/or positive retroperitoneal or inguinal
nodes (T3c, N0 M0; T,  N1,  M0).   Metastases  to the liver capsule and tumor
limited to the true pelvis, but extension to the small bowel or  omentum  are
also  considered  Stage  III.   STAGE IV=growth involving one or both ovaries
with distant  metastases  (any  T,  any  N,  M1).   Metastases  to  the liver
parenchyma is Stage IV, and malignant  ascites  and  pleural  effusions  must
contain  histologically  confirmed  tumor  cells.   TREATMENT: STAGE I OR II:
Comprehensive staging is accomplished  by  obtaining  washings of the pelvis,
both paracolic gutters,  ascitic  fluid,  and  the  peritoneum  beneath  both
diaphragms.   All  adhesions  are biopsied, along with peritoneal biopsies of
the cul-de-sac, pelvic sidewalls, pericolic gutters, anterior abdominal wall,
and  intestinal  mesenteries,  if   there   is  no  macroscopic  evidence  of
involvement.  The entire peritoneum is visualized along with palpation of the
small and large colon.  All major organs should be visulaized  and  palpated.
Scrapings  or  biopsy  of the diaphragmatic surfaces should also be obtained.
Retroperitoneal exploration and  dissection  is  then  carried  out.  A total
abdominal hysterectomy and bilateral salpingo-oophorectomy  is  done  in  all
patients  except in women that desire future fertility with stage Ia, Grade I
lesions.  Cytoreduction of the tumor is usually fairly easily accomplished if
the disease is confined to the pelvis.   All adhesions should be lysed and an
infracolic omentectomy is done.  Patients  with  Stage  Ia  or  Ib,  grade  1
disease  will  not require any adjuvant treatment.  If there is more advanced
disease, adjuvant therapy will  be  needed such as postoperative chemotherapy
or irradiation.  Chemotherapy consists commonly of cisplatin 50-100 mg/m2  by
IV  infusion at 1 ml/min + cyclophosphamide 500-1000 mg/m2 by rapid infusion.
Both of these drugs are given on the  same day with 3-4 week cycles.  Stage I
cancers are treated with 3-6 cycles, while stage II tumors  are  treated  for
6-8 cycles.  Hydration is needed with 1 L of .45% saline before chemotherapy,
followed  by  2  liters over 10 hours after chemotherapy in order to keep the
urinary output at 100 ml/h  for  at  least  12 hours following the cisplatin.
Melphalan at .2 mg/kg/day for 5 days of every 28 days has been the therapy in
the past.  This therapy is given for 6-8 courses with a maximum of 12.  It is
an alternative which yields a 5 year survival as high as 78%.  There is a 10%
incidence of acute nonlymphocytic leukemia after  12  cycles,  and  therefore
should  not be used beyond 12 cycles.  RADIATION: Intraperitoneal 32P colloid
may be used as adjuvant  therapy  for  stage  I  and  Stage II tumors with no
residual gross disease.  The peritoneal cavity has to be  free  of  adhesions
for effective therapy.  P32 is given in 1-2 L of .9% saline using 15 mci as a
one  time  dose.   Whole abdominal irradiation has also been used as adjuvant
therapy.  The superior margin of  the  peritoneal  cavity is 1.5 cm above the
dome of the diaphragms and the lateral margins are 3 cm beyond the peritoneal
reflection.  The entire field is treated 5 days a  week  using  1.0-  1.2  Gy
fractions,  giving a total dose of 30 Gy with a maximum of 30 Gy to the liver
and 20 Gy to the kidneys.  The pelvic  area  is given a booster dose of 20 Gy
and the aortic nodes and diaphragm may receive an  extra  10-15  GY.   During
chemotherapy,  patients  should have monthly physical and pelvic examination,
CBC,  platelets,  and  differential  before  each  chemotherapy,  and halfway
between the  treatment  cycles.   BUN,  creatinine,  electrolytes  and  liver
function  should  be done at least once during each treatment cycle and serum
CA-125 is done  monthly.   During  radiation  therapy,  the patient should be
assessed for nausea and diarrhea.  Physical and pelvic examination should  be
done  monthly.  CBC, platelets, electrolytes, BUN, creatinine, liver function
tests and differential are done weekly.  A second look laparotomy can be done
in patients with stage II  who  have  received  chemotherapy.  It is not used
following primary treatment of Stage I lesions because it  will  rarely  give
positive  findings.   The follow-up after treatment consists of a history and
physical exam with pelvic exam and  serum  CA-125 levels every 3 months for 2
years.  Every 6 months,  chest  x-rays  and  possibly  CT  with  fine  needle
aspiration  of  any  masses  should  be done for 2 years.  A Pap smear of the
vaginal cuff should be carried  out  every  12  months  for 2 years.  After 2
years a pelvic exam, H&P, and serum CA-125 should be  done  every  6  months.
Chest  x-rays should be done as dictated by symptoms.  TREATMENT OF STAGE III
OR IV: Hysterectomy with  bilateral  oophorectomy and salpingectomy should be
done if possible.  Cytoreduction is carried out with an attempt to reduce any
residual tumor to less than 1.5 cm.  The  less  residual  disease  left,  the
better  the  prognosis.   If  the  cancer  occupies  the  pelvis  and en bloc
retroperitoneal dissection may  be  required,  removing  the ovaries, uterus,
pelvic peritoneum and  possibly  the  rectosigmoid  colon  as  one  specimen.
Omentectomy   must   be  done  for  advanced  disease,  using  an  infracolic
omentectomy if there is no gross  tumor  between the transverse colon and the
stomach or liver.   Otherwise  an  infragastric  omentectomy  is  done.   The
patient  may  need a transverse colectomy or splenectomy with the omentectomy
to  accomplish  the  cytoreduction.    The   liver  dome  and  the  diaphragm
mestastatic lesions should be resected to remove gross residual  tumor.   The
Cavatron Ultrasonic Surgical Aspirator and the argon beam coagulator are also
used  for  selective  destruction of tumor.  They are useful for debulking in
inaccessible places.   ADJUVANT  THERAPY:  Consists  of  either cisplatin and
cyclophosphamide as previously described or  alternatively,  6-8  courses  of
carboplatin  300 mg/m2, and cyclophosphamide 600 mg/m2.  Both drugs are given
on the same day by piggyback  infusion and repeated every 4 weeks.  Hydration
is carried out as above.  If the patient is unable  to  tolerate  combination
therapy,  melphalan  is given using .2 mg/kg daily for 5 days, repeated every
28 days if  the  white  cell  count  is  above  3000/uL  and  the platelets >
100,000/uL.  Whole body radiation can  be  given  if  there  is  no  residual
macroscopic  disease.   Complications  of radiation include myelosuppression,
nausea, and  diarrhea.   Radiation  enteritis  may  be  seen  up  to  2 years
following treatment which may require resection of a  large  portion  of  the
ingtestine.   Second  look laparotomy may be done as in early ovarian cancer.
About 30% of patients that show  no macroscopic evidence of disease will have
microscopic disease.  About 50-70% of patients with a  negative  second  look
laparotomy are free of disease at 5 years.  If macroscopic disease is present
on  second  look, the survival is about 12-18 months with aggressive therapy.
Paclitaxel (Taxol), derived from the bark of  the yew tree, has been shown to
obtain an objective response in about a third of previously treated patients.
It is given as 135 mg/m2 by IV infusion over 24 hours.  Complications include
peripheral neuropathy and neutropenia.  Anti-nausea meds are  not  needed  as
with  cisplatin.   PROGNOSIS:  	Patients  with  Stage I  disease who have had
comprehensive staging and adjuvant therapy have  a  5 year suvival as high as
90%.  Survival is even higher with Stage I. Stage II gives a 5 year  survival
of  about  50%.  Stage III survival at the present time is about 15-30%.  The
prognosis for stage IV is dismal at < 5% at 5 years.

              -CANCER OF THE PANCREAS (Adenocarcinoma)-
If  you have a jaundiced elderly male in your practice who has abdominal pain
and losing weight, consider pancreatic  carcinoma.   Even if the diagnosis is
made the outcome is dismal and has not changed  much  over  the  years.   The
reason  is  that  pancreatic  head  tumors are large with about 85% extending
beyond the pancreas at the time  of  diagnosis.   Tumors of the body and tail
are also diagnosed later, and tend to be larger than pancreatic head  tumors.
Local   extension   occurs   into   the  retroperitoneal  area  invading  the
peripancreatic fat, and  nerves  and  fixes  vessels.   With advanced disease
there is involvement of the duodenum, gallbladder,  liver,  peritoneum,  lung
and  stomach.   Tumors  in  the  tail of the pancreas will invade the splenic
vein,  spleen  and  the  left  adrenal  gland.   The  incidence  seems  to be
increasing in the USA from less than 5/100,000 in 1935  to  11-12/100,000  in
1985.   Mortality from pancreatic cancer is very high and ranks fourth in men
as the cause of  cancer  death  after  lung,  colon  and prostate.  In women,
mortality ranks fifth as the cause  of  cancer  death,  after  lung,  breast,
colon,  uterus and ovary.  Pancreatic carcinoma is only rarely seen below the
age of 40 with about 80% of  the  cancer occurring between the ages of 60-80.
The incidence seems to be higher in USA blacks and men.   Blacks  have  1.5-2
times  that  of  whites.   Blacks  in  Africa  do  not  share  this increased
incidence, suggesting there  is  an  environmental  factor that is operative.
About 60-80% of pancreatic adenocarcinoma occurs in the head of the pancreas.
If the tumor starts in the dorsal part  of  the  head  of  the  pancreas  the
intrapancreatic  portion  of the common bile duct will become obstructed with
production of jaundice.  If the  tumor  starts  in the central portion of the
pancreatic head behind the ampulla of Vater  or  the  uncinate  process,  the
symptoms  are  related  to  obstruction  of  the  main  pancreatic  duct with
pancreatic insufficiency.  CLINICAL:  Most  patients  will present will vague
upper abdominal pain that is constant, difficult to localize,  and  sometimes
radiating  to  the  back.   The pain may antedate jaundice by about 3 months.
Pain is the presenting symptom in  about 79%.  Jaundice is common in patients
that have carcinoma of the head of the pancreas.  However, with carcinoma  of
the  body  and  tail, jaundice is the first symptom in only 6-13% because the
common duct is not  involved  early,  but  there is hepatic metastasis and/or
porta hepatis lymphadenopathic compression.  Weight loss is  common  in  both
head,  body  and  tail  pancreatic  carcinoma.   The weight loss is usually a
composite of  causes  consisting  of  malabsorption  due  to  pancreatic duct
obstruction  and  reduced  caloric  intake.   Other  symptoms  would  include
anorexia, nausea, vomiting, pruritus, constipation, weakness and  depression.
Physical examination may reveal a palpable gall bladder in about 30% of cases
(Courvoisier's  law).   The  patient  may  have  hepatomegaly  and  jaundice.
Carcinoma  of the body and tail may produce ascites.  The patient may present
with migrating thrombophlebitis (Trousseau's sign).  LABORATORY: The alkaline
phosphatase may be elevated due  to  hepatic metastasis or obstruction of the
common duct.  The amylase and lipase are  not  useful  and  are  usually  not
elevated.   Diabetes  may  be present in up to 68% of pancreatic cancers.  CA
19-9: The carbohydrate antigen CA 19-9 is a tumor marker that may be elevated
in pancreatic carcinoma.  However, it is not tumor specific and should not be
used as a screening test.  This tumor marker has been positive in stomach and
colon malignancies.  If the patient  has  jaundice, abdominal pain and weight
loss it  may  be  of  some  value.   It  is  also  useful  in  post-operative
recurrences,  and  it  may  predict  resectability  and aid in post-operative
prognosis.  Pancreatitis, cirrhosis,  acute  cholangitis  and fulminant liver
failure may give false positive values for the CA 19-9.  The  sensitivity  of
the  test  is  associated  with the size of the tumor.  It has been estimated
that only about 4% of patients with a CA 19-9 level above 1000 U/ml will have
a  resectable  tumor.   If   the   patient   normalizes  the  CA  19-9  value
postoperatively, the mean length of  survival  is  about  19  months.   If  a
patient fails to normalize the CA 19-9 post-operatively, the mean survival is
only  about 7 months.  CARCINOEMBRYONIC ANTIGEN (CEA): Although the CEA tumor
marker is  positive  in  about  50-70%  of  pancreatic  carcinoma,  it is not
specific and can be seen in other gastrointestinal tumors.   False  positives
also   occur.   Currently,  its  main  utility  is  following  patients  with
colorectal  cancer.   CT:  The  sensitivity  and  specificity  for diagnosing
pancreatic cancer using CT has been 83% and greater than  90%,  respectively.
CT  also may be used to determine the resectability and staging of the tumor.
The criteria  used  for  non-resectability  are  encasement  of  the superior
mesenteric vein or artery, invasion of the duodenum or stomach,  invasion  of
peripancreatic fat, abnormal porta hepatis tissue, lymphadenopathy, and liver
metastasis.  CT is unable to detect small liver and peritoneal metastasis and
therefore  is limited in this regard.  MRI: MRI has recently been shown to be
better than CT in  detecting  small  tumors  of the pancreas.  Utilization of
contrast agents with MRI may even improve the  sensitivity  and  specificity.
US:  Ultrasound  is useful because it is inexpensive, but suffers because the
test is operator dependent, difficult in  obese and gaseous patients, and may
not visualize the pancreas in 13-38% of cases.  In  experienced  centers  the
sensitivity may approach 76% with a specificity of 90%.  However, in contrast
to  CT,  US  is  not helpful for staging and determination for resectability.
ANGIOGRAPHY: Angiography is  now  only  used  for assessing resectability and
staging pancreatic tumors.   CT  may  be  just  as  good  as  angiography  in
detecting  vascular  involvement,  but  in  some cases CT and angiography are
complementary.  Pre-operative angiography also may  be  of use to the surgeon
in   diagnosing   vascular   anomalies.     ERCP:    Endoscopic    retrograde
cholangiopancreatography   is   complimentary   to  CT  or  US  imaging.   In
experienced hands the sensitivity  and  specificity for diagnosing pancreatic
cancer using ERCP is over 90%.  Furthermore, it can  determine  if  there  is
invasion  into  the  duodenum.  Cytology studies may also be carried out from
the pancreatic  duct  secretions  which  may  help  with  the diagnosis.  One
drawback of ERCP is the risk of complications such as  perforation,  bleeding
and  pancreatitis.   ERCP  is of limited use in staging.  If tumor is seen in
the  duodenum  this  is  at  least  a  T2  stage.   PERCUTANEOUS  FINE NEEDLE
ASPIRATION BIOPSY: Fine  needle  aspiration  (FNA)  under  CT  or  ultrasound
guidance  is  controversial,  and  most medical institutions do not routinely
perform this test.   Sometimes,  however,  the differential diagnosis between
pancreatitis  and  cancer  is  difficult.   FNA,  by   obtaining   histologic
confirmation  of  cancer can aid in the selection of patients for surgery, or
conservative therapy for benign  or  non-resectable disease.  The sensitivity
for FNA has a wide range between 57 and  96%.   Specificity  approaches  100%
with  only  a  few  false positives obtained.  Complications from FNA include
possible  peritoneal  dissemination   and   seeding   of  the  needle  tract.
ENDOSCOPIC ULTRASONOGRAPHY (EUS): EUS is considered to be better than than CT
or US in detection of pancreatic tumor, especially small tumors less  than  2
cm.   EUS  cannot  make  the  distinction between pancreatitis and pancreatic
tumors, but there is excellent sensitivity  and specificity of over 90%.  EUS
may be of benefit in staging, by assessing whether there  is  lymph  node  or
vascular  involvement  of  the mesenteric and splenic veins.  The presence or
absence of enlarged lymph nodes  is  not critical for resectability.  EUS may
be better than US and CT for local staging of pancreatic cancers.   EUS  does
have  the  potential  for perforation, bleeding and infection.  DIAGNOSIS: If
you are suspicious for carcinoma of the pancreas, the first step in diagnosis
would be to obtain a CT of  the  abdomen  along with a Ca 19-9.  If these are
positive, staging procedures should be done for resectability  by  performing
EUS  and/or angiography.  If the patient is a candidate for resection surgery
by these methods a laparoscopic  exam  should  be  done to rule out any small
peritoneal  or  liver  metastases  that  may  have  been  missed  by  EUS  or
angiography.  Up to 40% of patients  will  have  metastasis  on  laparoscopic
exam,  but  negative  on CT and angiographic studies.  The metastatic lesions
are usually small and found on  the hepatic, omental and peritoneal surfaces.
If no metastatic lesions are found on laparoscopic  exam,  resection  of  the
tumor  should  be planned.  If by chance, metastasis or the tumor is found to
be unresectable during surgery,  a  surgical  bypass  of  the biliary tree or
gastrojejunostomy should be done.  If the CA 19-9  and  CT  are  both  normal
during  the  initial workup and there is still strong suspicion for carcinoma
of the pancreas, re-evaluation should  be  done  in about 2-3 months.  If the
tumor is found to be unresectable, endoscopic drainage of the biliary tree is
indicated.  TREATMENT: RESECTABLE SURGERY: The resectable rate for pancreatic
cancer is only about 15%.  The Whipple procedure (pancreaticoduodenectomy) is
the procedure of choice for carcinoma of  the  head  of  the  pancreas.   The
whipple procedure consists of resection of the head of the pancreas, proximal
duodenum,  bile  duct  and/or  gallbladder  and  gastric  antrum.  There is a
modification of the Whipple procedure  in  which  the pylorus and stomach are
preserved.  This helps obviate the dumping syndrome.  Continuity  of  the  GI
tract     is     re-established     with     a    choledochoenterostomy    or
cholecystoenterostomy,  a  gastrojejunostomy  and  a  pancreaticojejunostomy.
Pancreatic cancer has been found to be  multicentric in over 30% of cases and
some would elect for a total pancreatectomy, even though this procedure  does
not  decrease  surgical  mortality and morbidity or increase survival.  Total
pancreatectomy will produce pancreatic  insufficiency.  If the total pancreas
is  not  removed  a  pancreaticoenterostomy  will  be  done.   Post-operative
complications  consist  of  leaks  at  the  pancreaticoenteric   anastomosis,
gastroenteric  and bilioenteric fistulae and sepsis.  However, mortality from
the Whipple procedure has  improved  considerably  over the years.  Mortality
rates are now below 5%.   Mortality  rates  between  1960-1979  were  20-40%.
TREATMENT  OF BILIARY OBSTRUCTION: Endoscopic and percutaneous procedures are
now done to  decompress  the  biliary  tree.   With experienced operators the
success rate for endoscopic decompression is around 90% with a mortality rate
of about 1-2%.  Complications include stent occlusion  and  cholangitis,  but
this  can  be partially prevented by using large diameter stents, using metal
stents rather than  polyethylene  stents,  and  prophylactic stent exchanges.
For  INTERNAL   surgical   biliary   decompression,   a   choledochal-enteric
anastomosis  is  probably  superior  over  a cholecystojejunostomy because of
fewer  complications.   TREATMENT  OF  DUODENAL  OBSTRUCTION  Treatment  is a
gastrojejunostomy which can be done at  the  time  of  the  internal  biliary
decompression, or later, if it becomes necessary.  CHEMOTHERAPY: Results with
chemotherapy  are  poor.   The FAM regimen consisting of 5-FU, adriamycin and
mitomycin-C, has only  a  13-37%  response  rate.   Another  regimen, the SMF
regimen (streptozotocin, mitomycin-C and 5-FU) also has a poor response  rate
of  only  15-43%.  RADIATION THERAPY: Radiation may be given to control pain,
but radiotherapy itself doesn't prolong life.  Chemotherapy plus radiotherapy
will increase survival.

                       -CANCER OF THE PROSTATE-
The incidence of prostate cancer in men over the age of 50 varies from 14-46%
at autopsy.  It is the  most  common  malignancy  in  males and is the second
leading cause of cancer death.  The median  age  at  diagnosis  is  about  70
years.  Diets high in fat have been implicated as a cause.  There is a slight
increase  of 1.5 in blacks where the cancer tends to occur at an earlier age.
Most cancers of the prostate  are  adenocarcinoma.  They may be classified as
well differentiated, moderately well differentiated and poorly differentiated
by the Gleason prognostic classification system which assigns a grade between
0-5 to the primary and secondary differentiation patterns.  Grade I  is  well
differentiated  and  5  is poorly differentiated.  In general, the higher the
score the greater  the  possiblity  of  lymphatic involvement.  Most prostate
cancer will originate in the peripheral zone of the prostate (75%), with  25%
originating  in  the  central zone.  About 90% of metastases will involve the
bone, but can also occur in the lung, nodes and liver.  Metastases spreads by
direct extension involving the  seminal  vesicles  and pelvic side walls.  In
about 35% there will be obstruction of the bladder outlet or ureters.  Rectal
involvement is rare due to the resistant  Denonvillier's  fascia.   Lymphatic
spread  is  to  the  obturator and iliac lymph nodes.  The risk of lymph node
metastases based on the  Whitmore  and  Jewett  staging system is as follows:
A1=2%, A2=23%, B1=18%, B2=35% and  C=46%.   Hematogenous  spread  is  through
Batson's  venous  plexus  to  bones,  which  is  the  most  most common site,
producing osteoblastic lesions.  The  lung  is  involved  in about 49%, liver
35%, adrenal 17% and the kidney 10%.  The WHITMORE AND JEWETT STAGING SYSTEM:
Stage A=no palpable lesion, Stage A1=focal disease, Stage A2=diffuse disease,
Stage B=disease confined to the prostate.  Stage B1=a small  discrete  nodule
is  present,  Stage  B2=multiple nodules or a single large nodule is present,
Stage C=disease localized  to  the  periprostatic  area.  Stage C1=no seminal
vesicle involvement and the  tumor  weighs  no  more  than  70  grams,  Stage
C2=seminal  vesicles  are  involved  or  the tumor weighs more than 70 grams.
Stage  D=metastatic  disease.   Stage  D0=elevated  tumor  markers  alone are
present, Stage  D1=pelvic  lymph  node  metastases  or  urethral  obstruction
causing  hydronephrosis, Stage D2=metastases to bone, distant organs, distant
lymph nodes  and  soft  tissues,  Stage  D3=tumor  is  refractory  to hormone
therapy.   CLINICAL:  may  include  urinary  retention,   dysuria,   terminal
hematuria, dribbling, urgency, frequency with a palpable nodule being felt in
over  50%  of  patients  at  presentation.   Digital  rectal exam is the gold
standard for diagnosis,  even  though  only  about  10%  of nodules found are
sufficiently localized for cure.  The prostatic acid phosphatase will  detect
disease  that  has invaded the prostatic capsule and is abnormal in more than
80% of cases in  those  that  present  with  distant  metastases.  It is only
elevated in 4-10% of  those  cases  where  the  cancer  is  confined  to  the
prostate.   It should be done before the rectal exam, because elevated levels
may be found  for  1-2  days  following  manipulation  of  the prostate.  Non
prostatic causes of an elevation of the PAP include  osteoporosis,  Gaucher's
disease,   hyperparathyroidism,  hyperthyroidism,  erythropoietic  and  liver
diseases and osteogenic sarcoma.  The prostatic specific antigen (PSA) may be
elevated in benign hypertrophy, prostatitis  and  carcinoma.  It is useful in
following therapy.  Generally, it should be less than .2 ng/mL after  radical
prostatectomy and less than 4 ng/mL in normal males using a monoclonal assay.
Values  between  4-10 ng/mL can be due to benign enlargement or cancer, while
levels > 10 usually signify  cancer.   (Huge  benign prostates are capable of
elevating the PSA to > 10).  PSA should not  be  done  for  2-3  weeks  after
biopsy  of  the  prostate,  or  if  the  patient has prostatitis.  The normal
prostate on palpation measures about 3-4  cm  and has a rubbery feeling.  The
lateral margins should be sharp and distinct and the seminal vesicles  should
not be palpable.  About 30-50% of nodules are due to malignancy.  Transrectal
ultrasound (TRUS) usually appears as a hypoechoic area, but as many as 40% of
tumors  may  be  isoechoic.  TRUS can accurately depict capsular invasion and
seminal vesical  involvement  and  is  used  as  a  guide  for needle biopsy.
Prostatic biopsy is either done by fine  needle  aspiration  or  core  needle
biopsy.   Core  needle  biopsy is the gold standard in the USA, and is either
done  transrectallhy  or   transperineally.    The  transrectal  approach  is
associated with more  frequent  complications  as  septicemia,  bleeding  and
prostatitis,  but  is  slightly  more accurate than the transperineal biopsy.
Fine needle  aspiration  can  provide  a  diagnosis,  but well differentiated
cancers may be difficult to detect.  Other tests that may be  needed  include
IVP  for  urinary  obstruction,  technetium-99m  bone scan, chest x-ray, BUN,
creatinine, CBC, alkaline  phosphatase  and  liver transaminases.  TREATMENT:
Patients with Stage A1 can be managed with observation  and  periodic  rectal
exams  and  serum tumor markers.  Radical prostatectomhy and bilateral pelvic
lymphadenectomy is indicated for clinical Stages A2, B1, and B2 disease which
corresonds to TNM stages I and II.   In young patients it may be advisable to
perform a radical prostatectomy and  bilateral  pelvic  lymphadencectomy  for
Stage  A1.   Generally  speaking, radical prostatectomy is not indicatded for
Stage C or D  (Stages  III  and  IV).   The  retropubic approach is preferred
because potency can be preserved  and  simultaneous  lymph  node  biopsy  and
resection  can  be  done  without  a separate incision for lymph node biopsy,
which is necessary  if  the  perineal  approach  is  performed.  Initially, a
bilateral pelvic  lymphadenectomy  is  done  removing  nodes  medial  to  the
external  iliac  veins,  extending  to  the level of the obturator nodes.  If
microscopic tumor cells are seen at  this  time, the surgery is terminated at
this point.  If no malignant cells are identified in the lymph node specimens
a radical prostatectomy is done with removal  of  the  prostate  and  seminal
vesicles.   The Walsh nerve sparing retropubic approach is desirable becausse
urinary continence is preserved in >  98%,  blood loss is reduced and potency
is preserved > 60%.   RADIATION  THERAPY:  For  localized  carcinoma  of  the
prostate  in  stages  A  and  B  or  TNM  I  and II, external  beam radiation
consisting of 6000-7000 cGY given  over  6  weeks  can be used with a similar
survival to radical surgery.  Radiation therapy can also be used in Stages  C
and  D1  or TNM Stages III and IV.  ADJUVANT RADIATION THERAPY: Patients that
have  extracapsular  extension,  seminal  vesicle  involvement,  and positive
margins following prostatectomy can be given pelvic radiation.  External beam
radiation can also be given to  patients  that  have  a  rising  PSA  and  no
evidence of distant metastases following radical surgery.  Doses of 4500-6000
cGY are usually given which can give a 90% long term disease free survival in
patients  with  Stage  C.  Adjuvant  therapy  can also be used for local bone
metastases.  HORMONE THERAPY: is  used  in metastatic disease.  Early therapy
may prolong survival.  Most all patients will initially  respond  to  hormone
therapy,  but  the  disease  usually  progresses  after  2  years of therapy.
Luteinizing hormone-releasinjg  hormone  (LHRH)  agonists  such as leuprolide
(Lupron)  and   goserelin   (Zoladex)   will   suppress   gonadotropins   and
testosterone.   There  may be a flare reaction about one week after the start
of therapy due to a  transient  rise  in testosterone levels.  However, after
about 3 weeks the testosterone levels are suppressed to 2  ng/dL.   Flutamide
(Eulexin), a nonsteroidal antiandrogen, + LHRH agonists can increase the long
term  survival rate by as much as 25%.  Diethylstilbesterol (DES) is not used
much  any  more  because   of   side  effects  which  include  cardiovascular
complications,  thromboembolism  and   fluid   retention.    Orchiectomy   is
occasionally done, particularly in patients with cardiovascular or thrombotic
risk.   It  can  be  done under local anesthesia in patients with metastatic,
stage D. Chemotherapy  is  not  very  beneficial.   The  most frequently used
agents are cisplatin, cycloposphamide, doxorubicin and 5-FU.

                       -CANCER OF THE STOMACH-
For  some  reason,  the  incidence of carcinoma of the stomach is decreasing.
The decrease has been attributed to environmental factors.  It has been shown
that first generation migrants from areas  of  high incidence to areas of low
incidence have an intermediate risk.  Second  generation  migrants  have  the
same  risk  as  the general population.  In Japan the incidence is as high as
84/100,000.  Singapore, Iceland,  Costa  Rica,  and  Columbia  also have high
incidences.  It is interesting that in Hong Kong, the incidence is only about
5.8 cases/100,000.  Cancer of the stomach has decreased 73% since  1930  when
it was the most common cancer in the USA.  Gastric carcinoma currently causes
6 deaths/100,000 and 15,000 death/year.  Stomach cancer is most commonly seen
in  the  sixth  decade  and  is twice as frequent in men as women.  There is,
however, a steady increase of  stomach  cancer  of less than 1/100,000 at the
age of 35 to about 96/100,000 after the age of 85.   Blacks  have  a  3  fold
greater  risk  than  whites.   Nitrates  are  strongly  associated  with  the
development  of stomach malignancy.  Nitrates can be found in preserved foods
that are  salted,  pickled,  or  smoked.   The  nitrates  are  converted into
nitromsamimes which are powerful carcinogens.  Foods that are high in Vitamin
A and C can prevent  conversion  of  the  nitrates  to  nitrosamines  with  a
decreased  risk  for gastric carcinoma.  Patients that are exposed to nickel,
asbestos and rubber are  at  increased  risk.  The Peutz-Jeghers syndrome has
also been associated with an increased risk  of  stomach  cancer  if  gastric
hamartomas  are  present.   Pernicious  anemia and achlorhydria, and atrophic
gastritis also predispose to carcinoma f te stomach, but is lower now than in
the past.  Chronic gastric ulcers  should  be monitored, but the incidence of
malignancy is less than 3%.   Gastric  polys  larger  than  2  cm  should  be
removed,  but  benign  polyps  smaller  than  2  cm can be followed.  Partial
gastrectomy of 15 or more years  has  been  thought  to be linked to a higher
risk for adenocarcinoma of the stomach  in  the  gastric  remnant,  but  this
increased  risk  is  now  thought  to  be  lower than originally thought.  In
general, individuals of  low  socioeconomic  status  are  twice  as likely to
develop gastric carcinoma as those of higher socioeconomic status.  CLINICAL:
Symptoms are usually vague, and there are few signs and  symptoms  until  the
disease  has  advanced.   Patients  may  have  weight  loss,  abdominal pain,
anorexia, early satiety, change  of  bowel  habitis, and dysphagia.  Physical
may reveal jaundice, ascites, hepatic mass, Blumer's rectal shelf metastases,
metastases to the supraclavicular (Virchow's or Troisier's node in  the  left
suprclavicular area), axillary (Irish's node in the left anterior axilla) and
periumbilical  area  (Sister  Mary  Joseph  nodes).  Paraneoplastic syndromes
associated with carcinoma of  the stomach include migrating thrombophlebitis,
acanthosis nigricans, carcinoid syndrome,  dementia  and  cerebellar  ataxia,
inappropirate  ACTH  secretion, dermatomyositis, erythema gyratum repens, and
Eaton-Lambert syndrome.  Unfortunately  about  88%  of  patients will present
when the cancer has spread beyond  the  confines  of  the  stomach.   Distant
metastases occurs to the liver (45%), peritoneum (25%), lungs (20%), adrenals
(12%),  pancreas  (10%),  bone,  and  liver  (5%),  and  spleen and CNS (2%).
LABORATORY:  Patietns   should   have   CBC,   alkaline  posphatase,  hepatic
transaminases, nucleotidase, GGT, carcionoembryonic antigen (elevated  in  up
to  60%  in  advanced  cases,  but  is  nonspecific),  and  alpha fetoprotein
(elevated in 15-20% of patients).  CT  of the chest and abdomen are important
in evaluating for metastatic lesions.   Upper  GI  series  can  detect  gross
lesions.  Esophagogastroduodenoscopy with brush or needle biopsy will provide
a  diagnosis in greater than 90% of exophytic lesions and 50% of infiltrating
lesions.  Negative biopsies in a patient  with a strong clinical suspicion of
cancer should have  a  repeat  endoscopic  biopsy  or  surgical  exploration.
Gastric cancer may present as a polypoid, ulcerative, scirrhous, fungating or
infiltrative  lesion.   Ulcerative  lesions  occur  in 75%% of tumors.  These
tumors present  as  a  mass  with  a  central  necrotic ulceration.  Polypoid
lesions comprise about  10%  of  cancers.   They  are  associated  with  well
differentiated  noninvasive  tumors which carry a good prognosis.  Schirrhous
(linitis plastica) cancer comprise about  10%, and have a terrible prognosis.
Superficial cancers occur in about 5%.  Almost all cancers of the stomach are
adenocarcinomas    (95%).     Other    malignancies    include     lymphomas,
leiomyosarcomas, squamous cell, carcinoid and adenoacanthomas.  The prognosis
is  predicted  from  the  depth of penetration into the stomach wall.  Tumors
that have extended to or through the serosa have a 5 year survival of 20-40%.
The antrum of the stomach is involved in about 50%, the lesser curvature 22%,
body of  the  stomach  18%,  gastroesophageal  junction  7%,  and the greater
curvature 3%.  Patients with pernicious anemia and cancer of the stomach  may
have   a   22%  incidence  of  multicentric  disease.   STAGING  BY  THE  TNM
CLASSIFICATION: TUMOR  STAGE:  TX=Primary  tumor  cannot  be assessed.  T0=no
evidence of tumor.  Tis=Intraepithelial tumor with no invasion of the  lamina
propria  or  carcinoma  in  situ.   T1=Tumor  invading  the lamina propria or
submucosa.  T2=Tumor invading the  muscularis propria or subserosa.  T3=Tumor
penetrating the serosa, but doesn't  invade  adjacent  structures.   T4=Tumor
invading  adjacent  structures.   LYMPH  NODE  STAGE:  NX=cannot be assessed.
N0=no  regional  node  metastases  present.   N1=metastases  present  in  the
perigastric lymph nodes  within  3  cm  of  the  edge  of  the primary tumor.
N2=Metastases present in the perigastric lymph nodes more than 3 cm from  the
edge  of  the  primary  tumor,  or in the lymph nodes along the left gastric,
common hepatic, splenic, or celiac arteries.  Para aortic and retropancreatic
nodes are considered  distant  metastases.   METASTATIC STAGE: MX=presence of
distant metastases cannot be assessed.   M0=no  distant  metastases  present.
M1=distant metastases are present.  HISTOPATHOLOGIC GRADE: GX=grade cannot be
assessed.   G1=tumor  is  well  differentiated.   G2=tumor is moderately well
differentiated.    G3=tumor   is    poorly   differentiated.    G4=tumor   is
undifferentiated.  COMBINED STAGES: Stage 0=Tis, N0, M0.   Stage  1A=T1,  N0,
M0.   Stage 1B=T1, N1, M0 or T2, N0, M0.  Stage II=T1, N2, M0; T2, N1, M0; or
T3, N0, M0.  Stage  IIIA=T2,  N2,  M0;  T3,  N1,  M0;  or  T4, N0, M0.  Stage
IIIB=T3, N2, M0 or T4, N1, M0.  Stage IV=T4, N2, M0 or  any  T,  any  N,  M1.
HOERRING  STAGING  (Surgical  classification):  Stage  I=disease  limited  to
involvement  of  the  mucosa,  submucosa,  and  muscularis.  Stage II=disease
involving the serosa.  Stage III=contiguous spread.  HOERR METASTATIC STAGES:
Stage A=no metastases.   Stage  B=regional  node metastases.  Stage C=distant
metastases beyond regional nodal groups.  TREATMENT: The  prognosis  is  very
poor.   Surgery  offers  the only treatment for cure of adenocarcinoma of the
stomach.  For cancers  involving  the  distal  2/3  of  the stomach a radical
subtotal gastrectomy with a Billroth II reconstruction is  the  procedure  of
choice.  This includes removal of the node bearing areas along the lesser and
greater  curvatures,  and  the omentum.  Resection of adjacent tissue such as
the pancreas, transverse colon or portions of the liver may be required.  For
cancer  of  the  upper  1/3  of  the  stomach  involving  the esophagogastric
junction, a proximal gastrectomy and  resection  of  the  lower  2/3  of  the
esophagus  with  an  esophagogastrostomy  high  in  the chest will be needed.
Carcinomas in this area are  often  poorly  differentiated and of the diffuse
type, which carries a poor prognosis.  For patients  with  tumor  involvement
encompassing  most  of  the  stomach,  a  totol  gastrectomy  with  adjacdent
lymphadenectomy  may  be  needed.   Chemotherapy may be used for unresectable
disease,  or  as  an  adjunct  to  resection.   Combination  therapy  with  5
fluorouracil, (5-FU),  doxorubicin  (Adriamycin)  and  semustine (methy-CCNU)
produce slightly higher response rates than monotherapy.

                        -CANCER OF THE TESTIS-
Cancer of the testis is uncommon accounting for only 1%  of  all  cancers  in
males.   It  is  important  that  it  be  diagnosed  correctly for it has the
potential for cure even in the  face  of metastasis.  It is usually diagnosed
in young men between the ages of 20-35.  RISK FACTORS: Caucasians are at  4.4
times greater risk than blacks and there is an increased risk in first degree
relatives  of patients with cancer of the testis.  There is increased risk in
men with a history  of  cryptorchidism,  which  accounts for 10% of patients.
Patients with Kleinfelter's syndrome are also at  increased  risk.   Patients
that  have  a  history  of  testicular  cancer  are  at risk for developing a
secondary testicular  cancer.   CLINICAL:  The  patient  can  present  with a
painless mass in the testes, scrotal  pain  or  infertility.   Patients  with
advanced  disease  may  have  pulmonary  and  retroperitoneal metastases with
lymphedema of the lower extremities, chronic  back pain and weight loss.  The
differential diagnosis of a mass  in  the  testis  includes  hydrocele  (most
common),   spermatocele,   infections  such  as  orchitis  and  epididymitis,
tuberculosis, varicocele, benign tumors  such as epidermoid cyst, pseudotumor
of the testicular tunic, adenomatoid  tumor,  and  Sertoli  and  Leydig  cell
tumors.    The  patient  should  be  examined  for  unilateral  or  bilateral
gynecomastia, Virchow's  or  Troisier's  signal  node,  abdominal and hepatic
masses, and edema of the lower extremities.  The patient should have  a  CBC,
alkaline  phosphatase,  transaminases,  and  tumor  markers.   Tumor  markers
consist  of  elevated  serum  alpha-fetoprotein  (AFP),  beta human chorionic
gonadotropin (beta-hCG) which  are  elevated  in  about  85% of patients with
nonseminomatous germ cell tumors.  Alpha fetoprotein is a specific marker for
nonseminomatous germ cell tumor and is never elevated in pure seminoma.  Beta
hCG has the highest elevation in choriocarcinoma, but may be elevated in  67%
of  embryonal  cell  carcinomas  and  10% of pure seminomas.  Neuron specific
enolase  (NSE)  is  elevated  in  73%  of  patients  with  seminoma.  Lactate
dehydrogenase (LDH) elevation is a non specific  marker  for  cancer  of  the
testis.  Chest x-ray, and CT of the abdomen is very helpful in evaluating for
retroperitoneal  para  aortic and paracaval lymph nodes and liver metastases.
Chest CT should be used to  check  for metastasis to the lung.  Ultrasound of
the testis should be done in order  to  screen  for  various  masses  in  the
testis.   Bipedal  lymphangiogram  can  be occasionally helpful in evaluating
retroperitoneal and pelvic lymph node metastases.  The definitive	procedure
for diagnosis is  testicular  biopsy  employing  an  inguinal approach with a
subsequent  radical  orchiectomy  which  includes  removal  of  the   testis,
epididymis  and spermatic cord up to the level of the internal inguinal ring.
Radical orchiectomy specimens are used to  categorize the tumor into either a
seminoma or nonseminoma and help  stage  the  tumor  (T  stage).   HISTOLOGY:
Testicular  tumors are categorized into non-germ cell tumors and seminomatous
and non-seminomatous germ cell lesions.   Seminoma represents the most common
germ cell tumor, but often times there is a mixture of cell types.  Germ cell
tumors account for 96% of all testicular cancers.  Seminomas germ cell tumors
can  be  further  divided  into  the  classic  spermatocytic  and  anaplastic
seminonomas.  Nonseminomatous germ cell tumors include  embryonal  carcinoma,
yolk  sac  tumors, teratoma, teratocarcinoma, and choriocarcinomas.  Non-germ
cell tumors only account  for  about  4%  of  all testicular tumors and would
include the  Sertoli  and  Leydig  cell  tumors  and  mixed  gonadoblastomas.
Because of excessive androgen production, these tumors may produce phenotypic
changes.   Lymphoma  is  a non germ cell tumor which is common in males older
than 50.  METASTASIS:  Right  sided  germ  cell  tumors  will  spread via the
lymphatics to the interaorto-caval nodes, while left sided tumors will spread
to the para aortic lymph nodes.  Hematogenous spread is less common, but  may
spread to the lungs, liver, and CNS.  STAGING: Staging is accomplished by two
systems:  The  standard  system:  Stage  A=tumor limited to the testis, Stage
B1=microscopic metastases to  no  more  than  6  retroperitoneal lymph nodes,
Stage B2=microscopic metastases to more than 6 retroperitoneallymph nodes  or
gross  nodal  involvement,  Stage  C=metastases  above  the  diaphragm  or to
abdominal viscera.  The TNM system: TX=primary tumor cannot be assessed (used
if radical orchiectomy has not been  done), T0=histologic scar or no evidence
of primary tumor, TIS=intratubular tumor; preinvasive tumor, T1=tumor limited
to the testis, including rete testis, T2=tumor has invaded beyond the  tunica
albuginea  or  into  the epididymis, T3=tumor has invaded the spermatic cord,
T4=tumor  has  invaded  the  scrotum.   NX=regional  lymph  nodes  cannot  be
assessed, N0=no regional lymph node  metastases are present, N1=metastases to
a single lymph node that is no larger than 2 cm, in its  greatest  dimension.
N2=metastasis  to  a single node that is larger than 2 cm, but less than 5 cm
in its greatest dimension, or metastasees to multiple lymph nodes that are no
larger than 5 cm in their  greatest  dimension, N3=metastases to a lymph node
that is larger than 5 cm in its  greatest  diameter.   MX=distant  metastases
cannot   be  assessed,  M0=no  distant  metastases  are  present,  M1=distant
metastases are  present.   COMPARISON  OF  THE  2  STAGING  SYSTEMS:  Stage 0
(TIS,N0,M0), Stage 1 (T1-2, N0, M0), Stage II (T3-4, N0, M0), Stage III  (any
T,  N1,  M0),  Stage  IV (any T, N2-3, M0, any T, any N, M1).  TREATMENT: The
patient should  be  given  the  option  for  semen  cryopreservation prior to
orchiectomy, even though the patient may have  an  abnormal  semen  analysis.
Radical  orchiectomy  is indicated in all patients.  However, in patients who
refuse surgery, chest x-rays, testis  measurement and physical exam should be
done every 3 months, with ultrasound, CT and  serum  tumor  markers  every  6
months.   Patients  with  less  than  T3  or  M1  non  seminomatous germ cell
carcinomas with limted  local  or  regional  spread  is  treated with limited
retroperitoneal lymph node dissection.  If there  is  residual  tumor  and/or
elevated  levels  of  tumor markers after therapy, in spite of negative x-ray
studies, a complete retroperitoneal lymph  node  dissection is needed.  It is
estimated that about 20% will have residual disease after  chemotherapy,  40%
will  have fibrosis and 40% will have a mature teratoma (chemotherapy induced
differentiation of the original tumor).  About 30% with stage A cancer of the
testis will have nodal disease  after  normal preoperative studies.  In these
patients, retroperitoneal lymph node dissection  can  be  curative.   If  not
chemotherapy   may   be   indicated.   The  mortality  secondary  to  radical
orchiectomy approaches 0%,  while  the  mortality  from retroperitoneal lymph
node dissection is < 1%.   Complications  are  rare  after  orchiectomy,  but
complications  following  RPLND are more frequent, especially if chemotherapy
was given prior  to  surgery.   These  complications include ureteral injury,
lymphocele,  chylous  ascites,  infertility  and  small  bowel   obstruction.
Seminomatous  germ cell tumors are very radiosensitive and should be given to
the para aortic and  ipsilateral  pelvic  nodes  to  treat  the nearly 20% of
patients with clinical stage I and  stage  II,  who  will  have  occult  node
disease.   In  stage III and stage IV without metastasis above the diaphragm,
radiation therapy  to  the  infradiaphragmatic  para  aortic,  paracaval, and
ipsilateral pelvic nodes and contralateral  pelvic  nodes,  if  involved,  is
usually  recommended.   Radiation  above  the  diaphragm is usually not given
because it will hamper future  chemotherapy.   Radiation therapy is not given
to nonseminomatous germ  cell  tumors  because  they  are  not  sensitive  to
radiation.   Seminomatous germ cell tumors characterized as stages III and IV
without metastases above  the  diaphragm  are treated with infradiaphragmatic
para aortic, paracaval, ipsilateral pelvic node  and  contralateral  involved
pelvic  node  radiation.   Radiation  above  the  diaphragm  is not indicated
because it interferes with  future  chemotherapy, if needed.  Nonseminomatous
germ cell tumors are  not  treated  with  radiation  therapy.   CHEMOTHERAPY:
Combination  cisplatin  based therapy will result in > 90% response rates and
are usually given for 3-4  cycles.  Such combinations include: PVB=cisplatin,
vinblastine,  bleomycin  given   every   3   weeks,   VABVI=cyclophosphamide,
vinbastine,  actinomycin-D,  bleomycin,  and  cisplatin  are given in monthly
cycles, BEP=bleomycin, etoposide,  and  cisplatin  given  every  3 weeks, and
EP=ethoposide and cisplatin given every 3 weeks.  The 5  year  survival  rate
for  stage 0 is (100%), stages I and II (95-100%), stage III (91%), and stage
IV (80%).  Patients should be followed  every  3  months for 2 years, every 6
months for an additional 3 years, then yearly.   CBC,  alkaline  phosphatase,
transaminases,  beta-hCG, AFP, LDH, chest x-ray, CT of the chest, abdomen and
pelvis, and contralateral  testis  ultrasound  should  be  done as indicated.
SUMMARY OF TREATMENT BASED ON STAGES	 FOR  SEMINOMA:  T1-T4,  N0=radiation
therapy  to  the  retroperitoneum,  T1-T4,  N1-N2=radiation  therapy  to  the
retroperitoneum,  T1-T4,  N3=chemotherapy  with  radiation therapy as needed,
Distant   metastasis=chemotherapy.    Stage    I=radiation   therapy,   stage
II=radiation therapy, Stage III=chemotherapy, stage IV=chemotherapy.  SUMMARY
OF TREATMENT BASED ON STAGES  FOR  NON-SEMINOMAS:  T1-T4,  N0=observation  or
Retroperitoneal  lymph  node  dissection (RPLND), T1-T4, N1-N2= RPLND with or
without chemotherapy,  T1-T4,  N3=chemotherapy  with  adjuvant RPLND, distant
metastases=chemotherapy with resection of residual tumor as necessary.  Stage
I=observation?, stage  II=chemotherapy,  stage  III=chemotherapy,  and  stage
IV=chemotherapy.

                        -CANCER OF THE UTERUS-
Cancer of the uterus represents  the  fourth  most  common  malignancy  after
breast,  colorectal  and  lung  in  females,  and the most common gynecologic
cancer.  Most patients will present  in  the early stages.  RISK FACTORS: The
median age of cancer of the uterus is 58 years of age and is mostly a disease
of psotmenopausal females.  Only about 2-5% of cases will  occur  before  the
age  of  40.   Obesity  will  increase the risk by 3-10 times and there is an
association  with  the  total  fat  intake  world  wide.   The  incidence  of
endometrial cancer will be  reduced  by  50%  in those that smoke, apparently
because of the antiestrogenic effects of nicotine.  Unopposed  estrogen  also
will  increase  the  risk  of  endometrial  cancer  by  6-8  times.  Low dose
progesterone containing oral  contraceptives  will  reduce  the risk by about
50%.  Hypothyroidism, diabetes, hypertension, arthritis and tall stature have
all been associated with an increase risk of uterine  cancer.   It  has  also
been  shown  that  patients  having  previous pelvic irradiation, such as for
carcinoma of the cervix, are  at  increased risk for both uterine endometrial
adenocarcinoma  and  uterine  sarcoma.   There  is  a  higher  incidence   of
endometrial  cancer  in  those women with a history of cancers of the breast,
colorectum and ovaries, and cancer of  the  uterus tends to occur in the high
socioeconomic groups.  Nulliparity and late menopause also will increase  the
risk.   CLINICAL:  About  90% will present with vaginal bleeding while only a
small  minority  will  present  with  pelvic  pain,  uterine  enlargement and
purulent vaginal discharge.  Approximately 50% will show abnormal endometrial
cells on the Pap smear.  If the disease is advanced there may be weight loss,
ascites,  jaundice,  pleural  effusion,   hydronephrosis,   bone   pain   and
supraclavicular   or   inguinal   adenopathy.   Some  patients  will  develop
paraneoplastic  syndromes   such   as   hypercalcemia,  thrombophlebitis  and
inappropriate ACTH secretion.  Palpation and visual inspection of the  vagina
and cervix should be carried out with bimanual examination.  Pap smear should
be  done.  The most common sites of metastatic disease are the adnexa and the
pelvic and para aortic lymph nodes.   The patient should have a CBC, alkaline
phosphatase,  transaminases,  BUN,  creatinine,  UA,  beta  human   chorionic
gonadotropin,  PT, PTT, CA-125, chest x-ray, endometrial biopsy, endocervical
curettage,and  uterine   sounding.    Depending   on   the   extent   of  the
disease,	IVP, barium enema, Technettium 99m bone scan, MRI and CT  may  be
needed.  CT can evaluate the extent of the cancer, such as involvement of the
rectum, bladder, uterine adnexa, retroperitoneal pelvic and para aortic lymph
nodes  and  ureters.  If the endometrial biopsy is inconclusive, a fractional
D&C should be done under regional or general aneshtesia.  Hysteroscopy may be
useful for guided endometrial biopsies.   Fine  needle aspiration may be used
for sampling of supraclavicular, inguinal, and retroperitoneal nodes as  well
as  vaginal, pelvic, liver and lung masses.  METASTASES: Cancer of the uterus
can spread by  direct  extension,  lymphatics,  hematogenous or transtubally.
Direct extension may extend to the cervix, ovaries, fallopian tubes,  vagina,
bladder,   ureter,   and  rectum.   Peritoneal  involvement  may  occur  from
transtubal  spread.   Lymphatic  spread  is   to  the  pelvic,  para  aortic,
supraclavicular nodes, parametrial and  vaginal  area.   Stage  I  (Grade  I)
neoplasms  with  only  superficial  myometrial  invasion  only  have  a  0-5%
incidence of pelvic and para aortic lymph node spread.  However, those tumors
with  higher  grades  and  deeper  myometrial  involvement will have a 10-40%
incidence.  Metastatic  spread  to  the  liver,  lung,  CNS  and  bone has an
incidence of only 3%.  Cervical extension occurs in 15% and pelvic  extension
in  about  7%.  Myometrial invasion is best determined following hysterectomy
with either frozen or permanent  sections.  Endocervical curettage may have a
false positive  rate  of  50%  and  a  false  negative  rate  of  about  10%.
HISTOLOGY:  Most cancers of the uterus will arise in the fundus and more than
95% are adenocarcinoma which are given a grade  of 1, 2 or 3 depending on the
degree of glandular proliferation.  Uterine sarcoma only represents 3% of all
uterine  malignancies  and  includes  leiomyocarcomas,  endometrial   stromal
sarcomsas  and  mixed  mesodermal  tumors.   Endometrial  hyperplasia  may be
designated as cystic hyperplasia  with  no malignant potential or adenomatous
hyperplasia with or without atypia.  If there is severe  atypia  there  is  a
tendency  for  malignant  progression  in about 25%.  STAGING: Currently, the
best staging can be accomplished  by  using the surgical FIGO staging system.
The tumor stage is  as  follows:  Stage  IA=tumor  that  is  limited  to  the
endometrium.   Stage  IB=tumor that invades less than half of the myometrium.
Stage  IC=tumor  that  invades  more  than  half  of  the  myometrium.  Stage
IIA=tumor involving the endocervical glands only.  Stage  IIB=tumor  invading
the  cervical stroma.  Stage IIIA= tumor invading the serosa of the adnexa or
positive  peritoneal   cytology.    Stage   IIIB=vaginal  metastases.   Stage
IIIC=metastases to the pelvic or para aortic  lymph  nodes  or  both.   Stage
IVA=tumor  invading  the  bladder or bowel mucosa or both.  Stage IVB=distant
metastases  including  intra-abdominal  or  inguinal  lymph  nodes  or  both.
GRADING: Grade 1=well differentiated,  grade 2=moderately differentiated, and
grade 3=poorly differentiated.  TREATMENT: The treatment  of  cancer  of  the
uterus  in the absence of metastatic or systemic disease is a total abdominal
hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO).  Contraindications to
surgery include direct extension to the pelvic sidewall, a fixed pelvic tumor
mass and metastatic disease in a very sick patient.  The surgical approach is
usually performed through a low midline abdominal incision.  Patients in poor
health or grossly obese  may  need  a transvaginal hysterectomy and bilateral
salpingo-oophorectomy.  Once inside the peritoneal cavity cytologicl washings
are obtained from the pericolic  gutters,  subdiaphragmatic  spaces  and  the
pelvic  cul-de-sac.  If ascites is present, cytology is obtained.  The liver,
diaphragm,  omentum,  intestines  and  retroperitoneal  lymph  nodes  are all
palpated.  The distal ends of the fallopian tubes  are  tied  or  clipped  to
prevent spread of any endometrial cancer cells.  Pelvic and para aortic lymph
nodes  are  sampled  for  metastatic  disease.  The hysterectomy performed is
extrafascial and the removed uterus  is  then  examined in the operating suit
for cervical involvment, and to determine the depth of the myometrial  cancer
invasion.  If the cervix is involved, either a radical hysterectomy with BSO,
and  pelvic  and  para  aortic lymphadectomy with irradiation OR whole pelvic
irradiation followed by one intracavitary  implant  which is then followed by
total hysterectomy and bilateral salpingo-oophorectomy can be done.   If  the
cervix  is  of  normal  size and grossly normal, an extrafascial TAH/BSO with
complete  surgical  staging  followed  by  postoperative  irradiation  can be
carried out.  Stage  III  disease  is  treated  with  a  TAH/BSO  with  tumor
debulking.   If  there  is  extrapelvic  disease, extended field irradiation,
chemotherapy or hormone therapy may  be  needed.   Patients with Stage IV are
treated with hormones or chemotherapy, and reserving  pelvic  irradiation  or
hysterectomy   for  palliative  control.   RADIATION:  External  beam  pelvic
irradiation is delivered via multiple  fields, giving 180 cGy daily fractions
over 5-6 weeks for a total of 5000  cGy.   Intracavitary  radiation  is  used
before hysterectomy using radium 226 or cesium 137 delivering 6000 cGY to the
uterus  and 4000 cGy to the vagina over 48-72 hours.  Vaginal vault radiation
is given post-operatively  to  patients  with  superficial  invasion, Grade 2
lesions, or to those patients who  are  unable  to  tolerate  more  extensive
therapy.   The  total  surface  vault dose is 5500-6000 cGy.  Intraperitoneal
phosphorus 32 can  be  used  to  prevent  recurrences  in  patients that have
positive  peritoneal  cytology,  but  no  distant  metastases.   Preoperative
radiation therapy may be indicated in Stage 1 disease, using a single  radium
implant before hysterectomy in order to reduce the incidence of recurrence in
the vaginal cuff and pelvic lymph nodes, or in Stage 2 disease using external
beam  pelvic radiation and intracavitary radium 226 or cesium 137 followed in
6  weeks  by  extrafascial  radical  hysterectomy  or  in  advanced  disasee.
Postoperative radiation is  used  in  patients  to  reduce  the risk of local
recurrence in patients that  are  at  high  risk,  such  as  deep  myometrial
invasion,  high  grade  tumors,  large  volume tumors and pelvic, adnexal and
cervical extension.  Chemotherapy is used  in locally advanced and metastatic
uterine cancer.  Doxorubicin is the most effective drug with  response  rates
of   30-40%.    High   dose  cisplatin  may  have  the  same  response  rate.
Fluorouracil and  cyclophosphamide  have  a  response  rate  of  only 10-20%.
Combination therapy offers no improvement  over  doxorubicin  and  cisplatin.
Approximately  a  third  of  patients  with advanced or recurrent endometrial
cancer will  respond  to  progestin  therapy.   These  patients  usually have
hormone receptors with well differentiated cancers.  The median  survival  in
responders  is  24  months,  but only 6 months in non-responders.  Progestins
used  include  medroxyprogesterone   acetate  (Provera),  hydroxyprogesterone
caproate (Delalutin), and megestrol acetate (Megace).  Tamoxifen can be  used
for  palliation  in  far advanced cases.  The overall 5 year survival for all
stages is 67%.  With FIGO  staging,  the  following  5 year survival has been
established: Stage I, 75%, Stage II, 58%, Stage III, 30%, and Stage IV,  10%.
Patients should be followed every 3 months for 2 years, every 6 months for an
additional  3  years  and  then  yearly  searching  for  pelvic  and  distant
recurrence.   Cervical and vaginal Paps smears should be done along with CBC,
alkaline phosphatase, transaminases,  BUN,  creatinine,  UA, and chest x-ray.
CT should be used if metastasis is suspected.

                         -CANDIDA AND AIDS-
Oral  thrush:  Nystatin  solution  or  tablets  500,000-1,000,000  U  PO  3-5
times/day or Clotrimazole troches 10 mg PO 5 times/day or Ketoconazole 200 mg
PO qd or Fluconazole 50-100  mg  PO qd.  Esophagitis: Ketoconazole 200-400 mg
qd or Fluconazole 100-400 mg PO or IV qd or Amphotericin B .3  mg/kg  IV  qd.
Maintenance therapy: Ketoconazole 200 mg qd or Fluconazole 50 mg qd.

                     -CANDIDIASIS (Disseminated)-
Disseminated candidiasis refers to established organ or tissue infection with
Candida species resulting  from  hematogenous  dissemination.  There are more
than 100 species of Candida, but only  a  few  are  of  clinical  importance.
Candida  albicans respresents the majority of isolates (50-70%).  Others less
frequently involved include	C.  tropicalis,  C. parapsilosis, and C. glabrata
(Torulopsis  glabrata).   Candida   lusitaniae   and   Candida   krusei   are
infrequently isolated (0-2%), but are important to know because C. lusitaniae
is resistant to amphotericin B and C. krusei is resistant to fluconazole.  In
general,  candidal  overgorwth  is promoted by broad-spectrum antibacterials,
corticosteroid and immunosuppressive therapy.  Patients with HIV and diabetes
mellitus are also  susceptible  to  candidiasis.   The  msot common organs of
involvdement in blood borne dissemination are the  eyes,  skin,  kidneys  and
reticuloendothelial  system.   Typical  settings for disseminated candidiasis
include the intensive  care  unit,  those  with  multiple indwelling devices,
those on mechanical ventilation, and surgical patients.  Neutropenic patients
with intravenous catheter related candidemia can develop a  fulminating  deep
yeast infection.  The diagnosis may be difficult.  The only clinical symptoms
may  be  fever,  or  clinical  deterioration  with a sepsis like syndrome and
septic shock.  If disseminated candidiasis  is  suspected, the eyes, skin and
kidneys should be investigated.  Retinal lesions may  appear  as  whitish  or
grayish  circumscribed  cotton  ball  lesions.   Retinal  lesions are rare in
neutropenic patients, and  only  occur  in  10%  of non-neutropenic patients.
Skin lesions may appear as purpuric or nodular lesions that measure from .5-1
cm in diameter.  Skin lesions are seen in about 13% of cases.   Candida  seen
in  the  urine  is  suggestive  of  candidemia.   About  60% of patients with
disseminated  candidiasis   will   have   candiduria.    The  development  of
endocarditis with candidemia is  more  common  in  patients  with  prosthetic
valves.   Candida species is a significant cause of endocarditis in the first
2  months  following  valve  replacement.   If  candidemia  is  suspected, an
echocardiogram should be done to ascertain if vegetations are  on  the  heart
valves.   Valve  infection  with  candida  is rarely eradicated without valve
replacement.   Positive   blood   cultures   for   candida   rarely  parallel
dissemination.   About  50-80%  of  patients  with  dissemination  will  have
negative blood cultures.  TREATMENT: The treatment  for  acute  and  subacute
disseminated  candidiasis  is amphotericin B IV.  Alternatively, fluconazsole
or itaconazole  have  been  used  for  subacute  dissemination.   For chronic
disseminated candidiasis fluconazole given  IV  or  PO  may  be  the  primary
treatment  with  amphotericin  B  and itraconazole being secondary drugs.  No
standardized doses for  amphotericin  have  been established for disseminated
candida.  However, it is common practice to given a minimum total dose of 500
mg in uncomplicated cases up to 1.5 grams if the  patient  has  intravascular
catheters,  prosthetic  devices  that  cannot  be  removed,  endophthalmitis,
hepatosplenic  involvement and endocarditis.  After a test dose of 1 mg in 20
ml of D5W given over 20 minutes,  the dose is increased to .5-.6 mg/kg daily,
giving the  infusion  over  a  3-4  hour.   5-Flucytosine  can  be  added  to
amphotericin  B, if amphotericin B inadequately controls the infection, or in
those patients that have  hepatic/splenic candidiasis, or endophthalmitis. It
is given as 75-100 mg/kg/day in four divided doses with adjustments for renal
insufficiency, which is common when used with amphotericin  B.  Side  effects
are  enterocolitis  and  bone  marrow toxicity.  Try to keep the serum levels
below 100 ug/ml  to  reduce  the  side  effects.   A  recent report has shown
comparable efficacy for fluconazole and amphotericin B  when  used  to  treat
candidemia  in  non-neutropenic  patients,  the  majority  of  which  had  C.
albicans.   These  patients  received  fluconazole  at  400  mg/d or  .5-.6
mg/kg/day of amphotericin B. High dose fluconazole at 10 mg/kg/day have a 83%
response  rate  as  compared  with  a  60%  response rate when treated with 5
mg/kg/day with comparable side effects.   Side  effects  of  fluconazole  include  headache, rash,
nausea, vomiting, asymptomatic elevations of liver enzymes in  1-7%,  with  a
rare  case  of hepatitis.  Fluconazole will elevate serum levels of warfarin,
cyclosporine, carbamazepine,  phenytoin,  and  sulfonylureas.   Rifampin will
decrease serum levels of fluconazole.  Therefore, monitoring of serum  levels
is recommended.  All patients with central lines should have these removed or
changed.

                             -CAPTOPRIL-
(Capoten) can be used in treating  diabetic nephropathy in patients with type
I insulin dependent diabetes mellitus and  retinopathy.   It  is  capable  of
reducing  the  risk  of development of serious outcomes such as death or need
for dialysis or transplant  by  51%.   Capoten  also  has  been used to treat
hypertension since 1981 and heart failure since 1982.  It was  also  approved
in 1993 for post myocardial infarction left ventricular damage.

                     -CARBON MONOXIDE POISONING-
Carbon  monoxide  is  a  colorless,  odorless  gas  that  is  produced by the
combustion an any type of  carbon  containing  material.   It may be found in
automobile exhaust, coal and gas heaters, and as a toxin in smoke  inhalation
patients  from  fires.   As  many  as  40% of smoke inhalation victims die of
carbon monoxide poisoning.   The  most  common  sources  for exposure include
automobile exhausts, faulty space heaters  and  furnaces,  fires,  improperly
vented  wood  stoves  and fireplaces, and engines used without ventilation in
enclosed spaces.  Cigarette  smokers  are  constantly  exposed  to CO and can
reach a COHb level as high as 10% in chronic smokers.  The severity of carbon
monoxide (CO) varies depending on the ambient CO  concentration,  the  minute
ventilation  of  the individual, the health status of the individual, and the
duration  of  exposure.   Equilibrium   is   reached  much  more  rapidly  in
individuals  who  engage  in  vigorous  physical  activity.   Patients   with
underlying  heart  and  lung disease cannot tolerate hypoxia produced by even
small  or  moderate  CO  levcels.   Infants  are  even  more  at  risk  to CO
poisioning, because fetal hemoglobin has a very high  affinity  for  CO.   CO
poisoning  occurs  as  a  metabolic  breakdown product of methylene chloride.
Fumes  from  paint  strippers  that  contain  methylene  chloride  which  are
metabolized  to  CO.   CO  is  rapidly  absorbed  through  the  lungs  and is
eliminated by  the  lungs.   It  produces  toxicity  by  hypoxemia,  cellular
asphyxia  and ischemia.  It combines with hemoglobin with an affinity that is
about 250 times that of oxygen.   Therefore,  even at low levels of CO, there
can be excessive saturation of hemoglobin binding sites, severely limitng the
blood's oxygen carrying capacity.  As  little  as  0.1%  CO  (1000  ppm)  can
produce  potentially  fatal  50%  saturation  of  hemoglobin  at equilibrium.
Exosure at workplaces is  restricted  to  50  ppm  as  an eight hour average.
Levels approaching 1500 ppm are considered dangerous to life.  CO binding  to
hemoglobin  changes  the  shape  of the oxygen hemoglobin dissociation curve,
which causes a left  shift,  resulting  in further decreases of intracellular
oxygen concentrations.  Decreased cardiac  output  occurs,  probably  due  to
intracellular  binding  of  CO  with  myoglobin, causing decreased output and
hypotension.  CO may also  bind  to  intracellular cytochromes, which negates
oxygen utilization.  The consequent tissue hypoxia results  in  ischemic  and
cellular   damage,   a   conversion   to  anaerobic  metabolism,  a  reactive
hyperglycemia secondary to liver  glycogen  breakdown, and a severe metabolic
acidosis.  CO poisoning accounts  for  almost  50%  of  all  fatal  poisoning
occurring  yearly  in  the  USA.  CLINICAL: The symptoms depend on the carbon
monoxide hemoglobin levels.  Individuals with 0-10% usually have no symptoms.
Levels of 10-20%  will  cause  complaints  of  headache, tightness across the
forehead, dilation of cutaneous vessels,  dyspnea  with  minor  exertion  and
angina in coronary artery patients.  Patients with levels between 20-30% have
throbbing  headaches,  dyspnea, nausea, and dizziness.  Levels between 30-40%
have vomiting, very  severe  headaches,  and  poor judgement.  Levels between
40-50% have syncope, confusion, tachycardia, and tachypnea.   Levels  between
50-60%  have  seizures,  syncope  and  coma.  Levels between 60-70 present in
coma, hypotension, arrhythmias  or  death.   Levels  greater than 70% usually
leads to respiratory failure and death.  The diagnosis cannot be made  unless
you  suspect  exposure.   If  the  patient  is found in a car with the engine
running, your suspicion should  be  heightened,  just  as in finding multiple
victims in a common room.  Cans of paint strippers and solvents that  contain
methylene  chloride  found with the victim in a poorly ventilated room should
also arouse your suspicion.   Carbon  monoxide  may  commonly be diagnosed as
influenza with headache, nausea and  vomiting.   Most  textbooks  stress  the
cherry  red  coloration  of  the  skin, but in reality this is very rare, and
cannot be relied upon  for  diagnosis.   Sometimes retinal hemorrhages may be
seen.  Arterial blood gases usually show a metabolic  acidosis,  due  to  the
tissue  hypoxia  and  ischemia.   The  arterial  PO2 and the calculated oxgen
saturation is typically normal because  dissolved  oxygen in the serum is not
affected by CO.  Pulse oximetry  oxygen  saturation  usually  remains  normal
despite  severe  CO  poisoning.  The diagnosis is confirmed by the laboratory
measurement of COHB levels in the  blood.   High COHb levels greater than 20%
indicate a dangerous exposure.   Patients  that  seemingly  recover  from  CO
poisoning   may   not   recover   fully.    CO   poisoning   can  produces  a
neuropsychiatric syndrome days to weeks following recovery consisting of dull
mentation,  behavioral  changes,  loss   of  memory,  cognitive  changes  and
garrulousness.   Complications  include  blindness,  deafness,  parkinsonism,
seizures, incontinence,  cortical  blindness,  aphasia,  apraxia,  psychosis,
cogwheel   rigidity,   rhabdomylolysis,   myoglobinuria  and  renal  failure.
DIFFERENTIAL DIAGNOSIS should include  head trauma, hypoglycemia, meningitis,
alcohol and drug intoxication.  Cyanide, hydrogen  sulfide  and  other  toxic
gases  should  also  be considered in the differential.  TREATMENT: Treatment
begins with the administration of  100%  oxygen provided with a tight fitting
mask or a non-rebreather mask with oxygen reservoir, or  by  an  endotracheal
tube  at  a flow of 10 liters/min.  Hypotension is treated with 1-2 liters of
crystalloid solution.  Low potassium is frequently seen and should be treated
in order  to  avert  cardiac  arrhythmias.   Patients  with  mild to moderate
metabolic acidosis (pH 7.2-7.3) should not be treated  because  the  acidosis
can  facilitate oxygen deliver to the tissues by moving the oxygen hemoglobin
dissociation curve to the  right.   Administration  of  100% oxygen will also
shorten the CO half life from 5 hours in room air  to  40-80  minutes.   With
hyperbaric  oxygen  at 2-3 atmospheres, the arterial pO2 is raised as high as
2000 mm Hg and the COHb half life  can be further reduced to 23 minutes.  The
indications for hyperbaric oxygen include any one who has lost  consciousness
due to CO exposure or a symptomatic patient with a COHb level extrapolated to
25% at the time of the initial exposure.  Children with COHb levels of 20% or
higher  at the time of exposure can be candidates.  Pregnant patients exposed
to COHb levels as low as 20% are also candidates.  If patients are treated by
hyperbaric oxygen, urgency is the  key.   Patients that were treated within 6
hours had a 13.5% mortality, while 30.1% died if treated later than 6 hours.

                   -CARCINOID SYNDROME (Symptoms)-
SYMPTOMS:  The  spectrum of symptoms usually don't appear until the tumor has
metastasized to the liver.   The  tumor  usually  originates in the GI tract.
Other sites of origin do not require liver metastases for development of  the
carcinoid  syndrome.  Other sites include ovary, lung or pericardium.  Of all
patients with carcinoid tumors,  only  about  20%  will develop the carcinoid
syndrome.  The diagnosis is solidified by demonstrating an  elevated  urinary
excretion  of  5-hydroxyindoleacetic acid which is a metabolite of serotonin.
False positive urinary  5-HIAA  may  result  from eating bananas, pineapples,
walnuts, and can also occur in Whipple's disease and celiac  disease.   False
negative  results  occur  from  phenothiazine  ingestion.   Symptoms  include
flushing  over  the  face  and  neck  which  can  be precipitated by alcohol,
physical activity, ingestion  of  food,  and  strong emotions.  Palpitations,
hypotension and abdominal symptoms may be present along  with  the  flushing.
The  GI  symptoms  include  abdominal  cramps, diarrhea, nausea, vomiting and
borborygmi.   There  may  be   wheezing,  cough  or  dysphagia,  arthropathy,
telangiectasia, fibrosis of the pulmonary or tricuspid valves.  Pellagra like
skin lesions and and increased incidence of peptic ulcer may be seen.

                 -CARCINOMA OF UNKNOWN PRIMARY SITE-
Occasionally you will encounter a patient, that after all of  the  laboratory
workup, and a complete history and physical, there will be no obvious primary
site  for cancer.  The physical examination should involve a good testicular,
pelvic, breast, rectal, lymph node  and skin exam.  The histo-pathologic exam
is very important in leading one to a  correct  primary  site,  so  that  the
patient  may  be treated with the appropriate medication.  There should be an
adequate  specimen  that  may  be   subjected  to  electron  microscopy,  and
histochemical and  immunohistochemical  staining.   The  specimen  should  be
divided  into  three  parts: One part is put in formalin for routine studies.
The second portion should be  frozen  without  fixation, and this is used for
immunohistochemical  studies.   The   last   part   should   be   placed   in
glutaraldehyde  for electron microscopy.  If the pathologist's report returns
as a poorly  differentiated  or  poorly  differentiated adenocarcinoma, which
occurs in about 35% of patients, it is incumbent on the physician  to  obtain
further  work-up  as  about  30-70%  of  this group will have a non-Hodgkin's
lymphoma.  Base line studies would include beta-hCG, alpha-fetoprotein, serum
prostatic specific antigen, acid phosphatase and CT of chest, abdomen, pelvis
and  mammography.   Immunoperoxidase  staining  should  be  done  against the
leukocyte  common  antigen  (for  lymphoma),  cytokeratin  (for   carcinoma),
prostate  specific  antigen  (for  prostate  carcinoma),  thyroblobulin  (for
follicular  thyroid carcinoma), S-100 protein, HMB-45 antigen, vimentin, (for
melanoma), chorionic gonadotropin,  alpha-fetoprotein (for germ-cell tumors),
neuron  specific  enolase,  chromogranin  (for   neuroendocrine   carcinoma),
calcitonin  (for medullary thyroid carcinoma), desmin (for rhabdomyosarcoma),
and factor VIII antigen (for angiosarcoma).   Any person that is less than 50
years of age, who has a poorly differentiated carcinoma involving the midline
structures of the mediastinum and retroperitoneum, with or without  bilateral
pulmonary nodules, should be classified as the extra gonadal germ cell cancer
syndrome.  These patients will respond to a cisplatin based chemotherapy that
is  used  in  testicular  cancer  as  VIP (VP-16, ifosfamide, cisplatin) OR a
combination of  bleomycin,  etoposide,  and  cisplatin.   Symptoms  and signs
should dictate which testing will be most suitable.  If a patient  has  chest
symptoms  and  x-ray  mediastinal  involvement,  then fiberoptic bronchoscopy
should be done.  If a  patient  has  an adenocarcinoma involving the axillary
lymph nodes then they should receive mammography and measurement of  estrogen
and  progesterone  receptors.   Modified  radical mastectomy could be done in
these patients as 40-70%  of  patients  will  harbor  an occult tumor that is
usually less than 2 cm in diameter.  In general, the prognosis  equates  with
that  of a stage II breast cancer.  Adjuvant therapy may also be carried out.
Male patients that have osteoblastic  metastasis should have a serum prostate
specific  antigen  and  immunoperoxidase  PSA  done.   Any  woman  that   has
peritoneal  metastasis should have cytoreduction by exploratory laparotomy as
many will have carcinoma of the ovaries.  Squamous cell carcinoma is found in
70% of patients from lymph nodes located high in the neck or midneck.  Biopsy
of these  nodes  is  controversial  because  of  presumed  increase  of local
reoccurrence, wound necrosis and metastasis.  Fine needle aspiration  may  be
used as a substitute.  The most common carcinomas in this group would include
tonsil,  base  of tongue, nasopharynx and hypopharynx.  These patients should
be examined with pan-endoscopy and biopsy and  MRI of the neck.  If a primary
site cannot be determined after this, the patient should be  treated  anyway,
because  those that have upper and mid-cervical involvement, and subsequently
have neck dissection followed  by  radiotherapy,  have  a  5 year survival of
30-50%.  Even unknown low-cervical nodes without a primary should be treated,
but the results are not as good.  If there is involvement of the  lower  neck
and  supraclavicular  areas,  then  cancer  of  the  lung would be suspected.
Fiberoptic bronchoscopy  should  be  done.   Occasionally metastatic squamous
carcinoma will metastasize to the inguinal areas.   If  after  an  exhaustive
search  for  this subset of patients, no primary site can be determined, they
should be  treated  with  inguinal  lymph  node  dissection  with  or without
radiation because long term survival has been shown.  Usually, however, lymph
node involvement  in  the  inguinal  area  would  dictate  an  anoscopic  and
colposcopic  exam.   Many patients with carcinoma of the penis, vagina, anus,
vulva and cervix can  be  cured.   Occasionally,  one finds only one solitary
lymph node in the axillary, cervical or inguinal lymph nodes, and no  primary
site  can  be found.  These patients should probably be treated, although the
response and long term results are poor.There has been some response in 20-40
percent with a  6-8  week  trial  of  combination  therapy with fluorouracil,
doxorubicin, mitomycin and cisplatin combinations.  If there is  a  response,
then  continue  therapy  for  4-6 months.  Some poorly differentiated cancers
will present as  neuroendocrine  tumors  that  can  be  diagnosed by electron
microscopy.  These tumors are aggressive and should be treated,  as  many  of
these  will  be  sensitive  to Cisplatin regimes as cisplatin, etoposide, and
bleomycin.

              -CARDIAC PATIENTS AND NON-CARDIAC SURGERY-
PREPARATION:  Patients  that are at high risk for coronary artery disease and
are scheduled for  major  surgery  should  have pre-operative thallium stress
testing.  If  unable  to  exercise,  dipyridamole,  adenosine  or  dobutamine
thallium  imaging  should  be  done,  especially  those  that have peripheral
vascular disease or aortic  aneurysm.   Patients  scheduled for major surgery
should be monitored with Swan-Ganz catherterization  in  patients  with  left
ventricular dysfunction, significant aortic or mitral valve disease, prior MI
and  angina,  cardiomyopathies, and pulmonary complications of heart disease.
The Coronary  Artery  Surgery  Study  (CASS)  showed  that  CABG  surgery can
decrease  the  mortality  in  patients  considered  for  noncardiac  surgery.
Patients with unstable  angina  will  probably  need  coronary  arteriography
followed  by  angioplasty,  CABG, and medical treatment.  Patients that are 3
months post acute MI have  an  incidence  of reinfarction of 5.7% while those
4-6 months, 2.3%.  At any rate, all  elective  surgery  should  be  postponed
until  at  least  6  months  post MI.  Beta blockers should not be terminated
abruptly  prior  to  surgery  because  of  the  possibility  of  MI,  angina,
hypertension, and arrhythmias.  They  should  be  continued  up to the day of
surgery  and  continued  postoperatively.    If   unable   to   take   orally
postoperatively,  IV  propranolol  may  be given at a dose of 1 mg q2h, or by
infusion of .01-.05 mg/min.  Alternatively,  esmolol (Brevibloc) can be given
as a 500 ug/kg loading dose, followed by  100-200  ug/kg/min  infusion.   MIs
usually  occur  around  the  third  day  postoperatively  due to tachycardia,
hypoxia, hypotension, and decreased cardiac output.  All nitrates and calcium
blockers  should  be  continued  to  the  day  of  surgery.   ASA  should  be
discontinued one week prior to surgery  and  NSAIDs may be discontinued a few
days prior to surger.  Patients with cor pulmonarle do poorly  in  noncardiac
surgery  and  should  be  treated  maximally  with bronchodilators, aerosols,
antibiotics and should terminate their  smoking.  Arterial blood gases should
be used frequently.  Likewise, cyanotic  congenital  heart  disease  patients
tolerate  surgery  poorly,  and  only emergency surgery should be considered.
Patients who have had a patent  ductus  ligated or divided, or those who have
had an atrial septal secundum defect repaired with sutures without  patch  do
not  require  antibiotic  prophylaxis  past 6 months post surgery.  All other
congenital heart  disease  lesions  should  have  antibiotic  prophylaxis for
endocarditis.  VALVULAR HEART DISEASE: If a patient is a poor  candidate  for
surgery  and  has aortic or mitral valvular stenosis, balloon angioplasty may
be done.  Otherwise, patients should have correction of the stenosis prior to
noncardiac surgery, if the stenosis is significant.  Patients with NYHA Class
I or II valvular heart disease  will  tolerate  surgery better than III or IV
who have more complications with a worse prognosis.   Patients  that  develop
atrial  fibrillation,  sinus  tachycardia  and  fluid  overload  are prone to
develop pulmonary edema  in  patients  with  stenotic lesions.  Patients with
aortic and mitral regurgitation usually do well  if  LV  dysfunction  is  not
severe.   Prophylactic  antibiotics  should  be given for valvular lesions or
prosthetic valves prior to noncardiac surgery  as well as those patients with
mitral valve  prolapse  and  associated  regurgitation  or  thickened  valve.
Patients  with  aortic  prostheses  have a lower incidence of thromboembolism
that do mitral valve prostheses,  and  a  bioprosthesis has a lower incidence
tha a mechanical prosthesis.  Dental extractions have been done with  the  PT
1.5  x  control.   The  warfarin should be discontinued about 3 days prior to
surgery and the PT  should  be  allowed  to  return  to  within 20% of normal
followed by an IV heparin drip.  Prior to surgery protamine can  be  used  to
reverse  the  effects.   Following surgery heparin and warfarin are restarted
and when the PT  is  therapeutic,  the  heparin  is  DC'd.  High embolic risk
patients are those with a mitral prosthesis and chronic atrial  fibrillation,
previous  emboli, and patients with multiple prosthetic valves.  ARRHYTHMIAS:
Patients with chronic atrial  fibrillation  should have their rate controlled
with digoxin.  It is not necessary to convert the AF.  Patients that have  LV
dysfunction  and  ischemic  heart  disease  have complex VPBs, such as pairs,
runs, multifocal origin, more than 5/min  and  R  on T phenomonen, and can be
controlled with lidocaine during surgery.  Supraventricular tachycardias  can
be  controlled  with  adenosine,  beta  blockers,  diltiazem  and  verapamil.
Patients   with   bifascicular  block  do  not  need  prophylactic  temporary
pacemakers.  Electrocautery used  in  surgery  can inhibit demand pacemakers,
and should be kept away from the pacemaker.  The pacemaker could be converted
to a fixed mode for  protection.   Should  the  patient  need  defibrillation
during surgery and has a pacemaker, the axis of defibrillation should be kept
perpendicular  to the axis of the pacing wire.  Perioperative hypertension is
controlled with nitroprusside, labetalol, or esmolol.

                         -CARDIAC TAMPONADE-
Cardiac tamponade occurs when ventricular  and atrial filling are compromised
by increased intrapericardial volume and pressure, with subsequent  decreased
cardiac  output  and hypotension.  Pericardial effusions may be due to fungal
infections, TB,  malignancy,  trauma,  thyroid  disease, autoimmune idseases,
acute and chronic renal failure,  aortic  dissections,  endocarditis  and  in
post-cardiac surgery.  Echocardiography can ascertain if there is pericardial
effusion  and/or  tamponade.   Tamponade  criteria  include right ventricular
diastolic or  right  atrial  systolic  collapse,  swinging heart, respiratory
variation in the left and right ventricular chamber sizes  and  right  atrial
indentation.   Confirmation of these findings may be necessary by inserting a
balloon flow directed pulmonary  artery catheter and determining equalization
of  right  atrial,  left  atrial  and  ventricular  end-diastolic  pressures.
Ancillary bedside findings  of  a  pulsus  paradoxus  (augmented  respiratory
variation  in  the  pulse  pressure  of  greater  than  10 mm Hg), along with
distended neck veins,  dyspnea,  orthopnea, tachycardia, tachypnea, decreased
heart sounds and hypotension are usually present.   Electrical  alternans  on
ECG, and water bottle cardiomegaly may also be present.  TREATMENT: The first
line  of  treatment  is  fluid loading and dopamine in order to stabilize the
patient until pericardiocentesis can  be  accomplished which is essential for
treatment  and   diagnosis.    Under   echocardiographic,   fluoroscopic   or
electrocardiographic   guidance,   an  intrapericardial  catheter  should  be
introduced using the Seldinger method.  Having  a  tube in place for at least
24 hours will allow drainage of  large  effusions,  and  provide  access  for
instillation  of  chemotherapeutic,  sclerosing or anti-infective agents.  In
patients that  have  malignant  effusions  from  lung  cancer, breast cancer,
melanoma,  leukemia,  lymphoma  or  Hodgkin's  disease,  sclerotherapy   with
bleomycin,  tetracycline  or  fluorouracil  may  decrease  the  recurrence of
tamponade.  If the  patient  has  a  life  expectancy  of  >  6 months or the
effusion  cannot  be  controlled  with  sclerosis,  pericardiectomy  may   be
indicated.   Open  surgical  drainage  has the advantage of a generous biopsy
sample, lysis of adhesions for loculated  fluid and less danger of laceration
of a coronary  artery  or  muscle.   Hemodialysis  patients  are  treated  by
increasing  the frequency of dialysis or pericardiocentesis and triamcinolone
instillation.

                      -CARDIAC TRANSPLANTATION-
ACUTE  CELL  MEDIATED  REJECTION:  Current cardiac rejection prophylaxis uses
triple  therapy  consisting  of  cyclosporine,  azathioprine  and prednisone.
Cyclosporine is given BID using target trough levels in the first 3 months of
300 ng/ml, 250 ng/ml from 3-6 months, 200 ng/ml at 6-12  months  followed  by
150 ng/ml for maintenance therapy.  Azathioprine is given at 2-3 mg/kg if the
WBC  is  >  3000/mm3.   Prednisone  is  given  at  1  mg/kg/day tapered to .2
mg/kg/day by 6 months, .15 mg/kg at 1 year and .15 mg/kg after 2 years.  Some
protocols are tapering  steroids  so  that  by  6  months  they are no longer
employed.  Endomyocardial biopsy is currently the best method  for  detecting
rejection.   No other test has approached the sensitivity or predictive value
of  endomyocardial   biopsy.    Rejection   is   usually  clinically  silent.
Increasing heart size or decreasing ECG voltages are suggestive of rejection,
but  the  rejection  may  be  advanced  when  these  findings  appear.   Most
rejections are treated with bolus steroid therapy using Solu-medrol  500-1000
mg  given daily for 3 days, followed by repeat biopsy.  If rejection is mild,
prednisone may be used  at  .5  mg/kg/day  tapering to .10-.15 mg/kg/day.  If
this fails antilymphocyte globulins are used.  POST TRANSPLANT INFECTION: CMV
is the  most  common  post-transplant  infection  occurring  usually  from  a
ppositive  CMV  donor.   Some  centers  use  ganciclovir  prophylaxis for CMV
negative recipients who receive a  CMV  positive donor.  Most late infections
(later than  30  days)  involve  Pneumocystis,  fungi,  and  cytomegalovirus.
Prophylaxis for these include Mycelex and Nystatin for fungal prophylaxis and
Trimethoprim-sulfamethoxazole  prophylaxis for Pneumocystis.  POST TRANSPLANT
CORONARY DISEASE:  Coronary  disease  may  present  as myocardial infarction,
sudden death, CHF, or arrhythmia.  The abnormal coronary arteries present  as
diffuse narrowing, tapering and pruning.  Intravascular ultrasound may emerge
as  the  best  test  for  some  of  these  subtle progressive changes.  These
abnormal vessels cannot be bypassed or treated with angioplasty, and the only
recourse is re-transplantation.  POST TRANSPLANT MALIGNANCY: Azathioprine may
cause  cutaneous  malignancies.    Cyclosporine  induced  lymphoproliferative
tumors  may  occur  at  12-18  months  after  transplantation.   In  general,
post-transplant malignancy  occurs  at  2%/year.   AMIODARONE  COMPLICATIONS:
Amiodarone  that  has  been used before transplant can create post-transplant
ARDS pulmonary  capillary  leak  after  cardiopulmonary  bypass which usually
lasts for about 4 days requiring long periods of assisted ventilation.  Other
complications include  rhythm  irregularities  which  require  atrial  or  AV
sequential  pacing  for a variable period of time.  About 5% will not develop
an appropriate  rhythm,  necessitating  a  permanent  pacemaker.  Patients on
pre-transplantation amiodarone may not regain an acceptible rhythm  for  some
time.    Patients   may  also  have  right  ventricular  dysfunction  due  to
donor/recipient  size  mismatch,  pre-existing  pulmonary  hypertension,  and
myocardial preservation  which  can  be  treated  with  fluid administration.
DONOR HEARTS: Donor hearts are rejected if there is severe occlusive coronary
disease, clinical evidence of  structural  heart  disease,  prior  myocardial
infarction,  HIV  positive,  intractable  ventricular arrhythmias, death from
carbon  monoxide   poisoning,   or   inadequate   oxygenation  on  mechanical
ventilation.  Following brain death, all potential donors  must  be  screened
for  HIV  and hepatitis status, ABO blood type and body size.  The best donor
is < 35 years  old.   CONTRAINDICATIONS FOR TRANSPLANT: Contraindications for
cardiac transplantation include severe peripheral cerebrovascular obstructive
disease, irreversible liver, lung  and  renal  dysfunction.   The  creatinine
cannot  be  >  2  mg/dl  or  the  creatinine  clearance  <  50 ml/min.  Other
contrtaindications include  active  infection,  coexisting  neoplasm, insulin
dependent diabetes  with  end  organ  damage,  acute  pulmonary  embolism  or
infarction,   active   peptic   ulcer   disease,   active  diverticulosis  or
diverticulitis, myocardial  infiltrative  and  inflammatory  diseases, severe
obesity, psychosocial instability or substance abuse, severe osteoporosis and
pulmonary hypertensin with irreversible pulmonary  vascular  resistance  >  6
Wood  units  or  3  Wood  units after treatment with vasodilators.  SCREENING
TESTS FOR TRANSPLANT:  Serology  for  HIV,  CMV, Toxoplasmosis, varicella and
rubella titers, EB viral capsid  IgG,  IgM  antibodies,  herpes  virus,  Lyme
titers,  Histoplasmosis  and coccidioidomycosis complement fixing antibodies,
VDRL, urine viral cultures  for  CMV  and  adenovirus,  throat swab for viral
cultures for adenovirus, herpes simplex virus and CMV, skin  tests  for  PPD,
histoplasmosis,  coccidioidomycosis,  mumps, dermatophytin, HLA typing, blood
typing and antibody screen.

                 -CARDIOEMBOLIC STROKE (Treatment)-
A CT of the head should be done  48  hours  after  the  onset  of  stroke  to
document  the  absence of spontaneous hemorrhage, in nonhypertensive patients
with small to moderate  sized  embolic  strokes.   If  no hemorrhage is seen,
start heparin followed by warfarin to prolong the PT to an INR  of  2-3.   If
the  stroke is considered to be large from embolization, therapy is postponed
for 7-14 days.

                         -CARDIOGENIC SHOCK-
HYPOVOLEMIA: If  a  patient  with  acute  myocardial  infarction demonstrates
hypotension without rales, or jugular  distention,  consideration  should  be
given  to  hypovolemia.   If  the pulmonary capillary wedge pressure measures
less than 12-18 mm Hg, a trial of an intravenous fluid bolus should be given.
RIGHT VENTRICULAR INFARCTION:  Another  cause  of  hypotension is acute right
ventricular infarction.  It has been estimated that  about  33%  of  patients
with  inferior  infarcts have right ventricular dysfunction.  These patients,
again, have no dyspnea  or  other  indications  for left ventricular failure.
They do have jugular venous distention and elevated ST segments in the  right
precordial  ECG leads.  Pulmonary filling pressures are elevated in the right
ventricular chambers while the left sided filling pressures are normal or low
with low cardiac output.  The  treatment again is expanding the intravascular
compartment with saline up to 15-20 mm Hg as measured by the  central  venous
pressure.    VENTRICULAR  SEPTAL  DEFECT:  Acute  ventricular  septal  defect
secondary to acute myocardial infarction  should  be  ruled out as a cause of
hypotension.  In VSD there is a holosystolic murmur along  the  left  sternal
border  which  usually  appears  1-7 days following the acute MI.  It is seen
more frequently with anterior MI, but  the  prognosis is worse when it occurs
with inferior infarctions.  It can be diagnosed by echocardiography.   If  it
is not surgically repaired, the mortality usually approaches around 90%.  The
patient  may  be temporarily supported with an intraaortic balloon pump until
the surgical repair can  be  effected.   PAPILLARY MUSCLE RUPTURE: Rupture of
the papillary muscle will cause acute mitral regurgitation which will produce
a holosystolic apical murmur with radiation to the  left  axilla.   Papillary
muscle  rupture  can be diagnosed with echocardiography.  The rupture usually
occurs on days 1-7  post  acute  myocardial  infarction,  and is treated with
mitral valve surgery  using  adjunctive  intraaortic  balloon  pump  support.
RUPTURE  OF  THE  LEFT VENTRICULAR FREE WALL: This usually occurs on days 1-7
following AMI.  Rupture of the  left  free  wall  is  rare and is more common
following late thrombolytic therapy, and after the first MI.  If time allows,
surgical  repair  is  the  treatment.   LEFT  VENTRICULAR   ANEURYSMS:   Left
ventricular  aneurysms  usually occur after AMI.  True aneurysms will develop
in up to 15%  of  patients.   These  are  associated with mural thrombosis in
about 35-50%.  If the  dyskinetic  area  is  large  enough,  hypotension  can
develop.    If   the   patient  develops  embolic  episodes  with  refractory
arrhythmias and hypotension,  resection  may  be indicated.  TRUE CARDIOGENIC
SHOCK: If no other cause can be found for the shock, true  cardiogenic  shock
may  be  present.   It  is  characterized by left ventricular wedge pressures
greater than 18 mm Hg, cardiac  index  < 1.8, and persistent hypotension.  It
has an incidence of about 7-10% of all myocardial infarctions and  is  caused
by large infarcts involving 40% or more of the left ventricle.  The mortality
is  extremely  high  at  about  85-95%%  unless  coronary  perfusion  can  be
established  via  PTCA.  The patient is stabilized initially with intraaortic
balloon pump in order to  decrease  the afterload, improve cardiac output and
increase coronary blood  flow.   This  is  followed  by  PTCA.   Thrombolytic
reperfusion  is  not  effective.   If the patient is not a candidate for PTCA
then CABG should  be  considered.   Supplemental  support  can be rendered by
administering dopamine at 5-15 ug/kg/min IV (400  mg  in  250  ml  D5W,  1600
ug/ml),  and titrating to a cardiac index greater than 2 and a cardiac output
greater than 4, and systolic  p;ressure  greater than 90; AND/OR Dobutamine 5
ug/kg/min IV, max 15 ug/kg/min (500 mg in 250 ml D5W, 2 ug/ml), and titrating
to CI >2 and CO >4 and systolic >90 AND/OR amrinone 0.75 mg/kg given  over  3
min  (may  repeat once after 30 minutes), followed by 5-10 ug/kg/min with the
maximum  dose  being  10   ug/kg/min.   Nitroprusside  is  a  venous-arterial
vasodilator and is started at an initial dose of  0.1-0.2  ug/kg/min  IV  and
increased  by increaments of 5 ug/min up to a maximum of 10 ug/kg/min.  It is
prepared by adding 50 mg of nitroprusside  in 250 or 500 ml of normal saline.
Nitroprusside can be used with dopamine and/or  dobutamine  to  maintain  the
cardiac  index  between  2-4.   Nitroprusside  can cause a coronary steal and
nitroglycerin  may  be  a  better   vasodilator.   Most  patients  with  true
cardiogenic shock cannot  be  treated  solely  by  pharmacologic  means,  but
require angioplasty.

         -CARDIOGENIC SHOCK AND ACUTE MYOCARDIAL INFARCTION-
Conservative  therapy is associated with a mortality rate of 80%.  Aggressive
intervention with angioplasty or bypass grafting with or without thrombolysis
can increase survival to 53-100%.   Coronary  angiography  is the only way to
determine the extent of coronary artery disease  and  if  the  patient  is  a
candidate  for  PTCA  or  CABG.   Shock  may  also  occur from rupture of the
ventricular wall or papillary muscle.  Thrombolytic agents are less effective
in patients with cardiogenic shock.   Patients  with severe 3 vessel coronary
artery disease may be candidates for urgent bypass grafting.

                     -CARDIOMYOPATHY (Dilated)-
Dilated cardiomyopathies may be  caused  by  a heterogenous group of diseases
that all produce left ventricular dilation and decreased  systolic  function.
The  dysfunction is usually global, but there may be some areas that are more
severely affected than others.  The  right  ventricle becomes more dilated as
the  disease  evolves  and  dilates  variably,  depending   on   the   cause.
Compensatory  hypertrophy of the ventricles may occur.  The most common cases
of a dilated cardiomyopathy in  the  USA  is coronary artery disease.  Triple
artery disease can produce a global hypokinesis, while MI tends to produce  a
segmental hypokinesis.  Other causes in the USA are viruses such as echovirus
and  coxsackie  virus group B, which can cause a myocarditis.  Some of the so
called idiopathic dilated  cardiomyopathies  may  be  due to viral infection.
Autoimmune cases may be due to connenctive tissue disease such  as  SLE,  and
peripartum  cardiomyopathy.   This cardiomyopathy usually develops just prior
to or within 3 months  post  delivery.  Alcoholic cardiomyopathy is caused by
ethanol  and  acetaldehyde,  both  of  which  are  cardiotoxins.    Alcoholic
cardiomyopathy  may be reversible if alcohol is interdicted.  Doxorubicin, an
anticancer drug, is also  capable  of  causing a cardiomyopathy.  Other cases
include  sarcoidosis,  hemochromatosis,   lymphoma,   leukemia,   acromegaly,
diabetes,  hyperthyroidism,  hypertension,  valvular  heart disease, Chagas's
disease,  drug  reactions  secondary  to  methyldopa,  sulfonamides,  uremia,
phenothiazines, radiation, cobalt,  thiamine  deficiency  and genetic causes.
DIAGNOSIS: Most patients will develop symptoms of heart failure  insidiously.
There  may  be  dyspnea,  fatigue,  orthopnea,  cough, leg edema, or ascites.
Physical exam may  reveal  a  sustained  apical  impulse,  moderate to severe
cardiomegaly, S3, S4 sounds, mitral and tricuspid regurgitation murmurs.  ECG
may demonstrate atrial and ventricular enlargement, sinus tachycardia, bundle
branch block, ST-T changes, conduction abnormalities, and ventricular ectopy.
Cardiac catheterization will show LV dilation and dysfunction, high diastolic
pressures, and low cardiac output.  Chest x-ray shows an enlarged  heart  and
possibly  pulmonary  congestion.   The echocardiogram shows dilated cavities,
reduced ejection fraction,  decreased  fractional  shortening, and mitral and
tricuspid regurgitation.  Myocardial biopsy should be carried out which might
reveal a specific diagnosis of sarcoidosis, amyloidosis,  hemochromatosis  or
an  infection.  Many causes of cardiomyopathy produce histologic changes that
are indistinguishable.  TREATMENT:  Vasodilators  are  used to manage dilated
cardiomyopathies.  They are capable of reducing both preload and  after  load
which  will  result  in  decreased  ventricular volume, reduced wall tension,
decreased oxygen demand  and  an  increase  in  cardiac  output.  Some of the
vasodilators that could be used include oral and sublingual nitrates, IV  and
oral  hydralazine, IV nitroprusside, oral prazosin and ACE inhibitors such as
enalapril and captopril.  Hydralazine is used in a dosage of 25-100 mg TID or
QID.  If  used  long  term,  however,  a  lupus  like  syndrome  may develop.
Prazosin is an alpha adrenergic blocking agent that will dilate  arterial  as
well  as  venous beds.  The initial dose is 1 mg at HS to prevent symptoms of
hypotension that occurs with the first dose.  It is usually given PO in a BID
dose, not  to  exceed  10  mg  BID.   Double  blind  cooperative sutdies have
demonstrated long term survival when using enalapril or a hydralazine/nitrate
combination.  When  enalapril  was  added  to  patients  taking  digoxin  and
diuretics   there   was   improved  survival  compared  with  placebo.   This
improvement was seen in Class II as  well as Class III and IV.  Enalapril has
proved to be superior to hydralazine/isosorbide dinitrate combination as  far
as  improved  survival  and  furthermore, is better tolerated with fewer side
effects than the combination.   When  compared  to  placebo, prazosin was not
associated with improved survival.  The long term use of  beta  blockers  has
been  reported  to decrease heart size and benefit heart failure in about 50%
of patients.  Long term  oral  anticoagulation  should be considered in those
with chronic atrial fibrillation, intracardiac clots, prolonged bed rest  and
those with systemic or pulmonary thromoembolism.  Alcohol should be curtailed
in  all  patients  with  alcoholic cardiomyopathy as abstinence may result in
recovery.  Doxorubicin therapy should  not  be  given  in  doses > 500 mg/m2.
Cardiac transplantation may be indicated in  young  patients  without  severe
pulmonary  hypertension or other organ involvement.  The 1 year survival rate
is greater than 80%.

                     -CARDIOMYOPATHY (Dilated)-
Dilated cardiomyopathy was formerly known as congestive cardiomyopathy and is
characterized by poor systolic function.  The  onset may occur at any age and
afflicts men more often than women.The course is usually one  of  progressive
deterioration  with 75% dying within five years of onset of the symptoms.  In
those over age 55 most die  within  two years of symptom onset.  Symptoms and
signs usually develop gradually and include  dyspnea,  orthopnea,  paroxysmal
nocturnal dyspnea, fatigue and in 25-50% of cases, chest pain.  There also is
an  increased  incidence of pulmonary emboli.  Physical exam reveals moderate
to severe cardiomegaly, S3  or  S4  gallop,  and  a systolic murmur caused by
mitral regurgitation, jugular  venous  distention  and  hepatic  engorgement.
There  may  be, in severe cases, pulsus alternans and a narrow pulse pressure
secondary to decreased  stroke  volume.   CHEST  X-RAY:Cardiac enlargement is
seen in the majority of cases and there are increased  vascular  markings  in
the  upper lobes indicating elevated pulmonary venous pressure.  There may be
diffuse densities in the hilar areas  and pleural effusions and curly B lines
indicating  engorged  pulmonary  lymphatics.   EKG:  EKG   may   show   sinus
tachycardia,  atrial  and  or  ventricular  dysrhythmias,  non-specific  ST-T
abnormalities,  intraventricular  conduction defects, left ventricular strain
pattern, left and  right  atrial  enlargement  and in ischemic cardiomyopathy
evidence of previous myocardial  infarctions.   MUGA:  MUGA  studies  usually
reveal  a  reduced  left  ventricular  ejection  fraction  of  less than 40%.
ANGIOGRAPHY: Angiography reveals a  diffuse hypokinetic left ventricle, often
with mitral regurgitation.  Cardiac catheterization  may  help  differentiate
between   ischemic   and  other  types  of  cardiomyopathies.   It  can  show
intracavitary  pressures,  cardiac  output,  left  ventricular  function  and
coronary anatomy.   Also,  one  can  obtain  pulmonary  artery  pressures and
pulmonary vascular  resistance.   ECHOCARDIOGRAM:  Echocardiography  shows  4
chamber  cardiac  dilatation,  normal  left  ventricular  wall thickness with
global hypokinesis and abnormal diastolic  mitral valve motion.  OTHER LAB:If
patient is being considered for cardiac transplantation then CT of the  chest
and  abdomen,  24  hour creatinine clearance, serologies for Toxoplasma, HIV,
Cytomegalic inclusion virus and Epstein-Barr virus, hepatitis A,B,C serology,
liver and renal  function  and  dental  x-rays.   Endocardial biopsies may be
indicated.  CAUSES: Toxins: such as alcohol, daunomycin, cobalt in  beer  and
arsenic.   Neurological  causes:  would  include  Refsum's  disease, myotonic
muscular dystrophy, limb girdle  muscular  dystrophy and Friedreich's ataxia.
Collagen   vascular   causes:   SLE,   polyarteritis   nodosa,    endocardial
fibroelastosis  (occasionally  seen  in children due to a treatable inherited
carnitine   deficiency.    Other   causes:   would   include  thyrotoxicosis,
pheochromocytoma,  homocystinuria,   hypophosphatemia,   beriberi,   diabetes
mellitus,  peripartum, idiopathic (50% of which 20% are familial if relatives
are tested) and ischemic.  Infectious  causes:  especially coxsackie B in the
USA, meningoocccal,  diphtheria,  mycoplasma,  influenza,  echovirus,  yellow
fever,  mumps,  polio,  rubella,  Chaga's  disease,  toxoplasmosis  and other
parasites, and HIV.  TREATMENT:  Digoxin, furosemide, potassium chloride, ACE
inhibitors, as captopril and enalapril,  Isosorbide  dinitrate,  Hydralazine,
continuous IV infusion of dobutamine, and cardiac transplantation which has a
75% 5 year survival.  Digoxin has several drug interactions with antibiotics,
quinidine,  verapamil,  cholestyramine and amiodarone.  If the cardiomyopathy
is due to alcohol then  abstinence  may  halt the progression or even reverse
the progression of alcoholic cardiomyopathy.  Anticoagulation is  recommended
for  all  patients even in the absence of atrial fibrillation or a history of
thromboembolic events.  Warfarin is preferred  with  maintenance of the PT at
1.3- 1.5 times the control.  Antiarrhythmic agents should  be  utilized  only
for  symptomatic  or  serious dysrhythmias, since most of these have negative
inotropic properties that will worsen the CHF and even induce proarrhythmias.
Salt  restriction  and  attention  to  electrolytes  and  magnesium  are also
important.

                   -CARDIOMYOPATHY (Hypertrophic)-
Hypertrophic cardiomyopathy (HCM) was originally applied to those cases  with
hypertrophy  that  was asymmetric, involving the septum, that would sometimes
cause  LV  outflow  obstruction  and   was   given  the  name  of  idiopathic
hypertrophic subaortic stenosis.  Now there is a  tendency  to  classify  all
idiopathic  hypertrophy,  whether  disproportionate  or  not  as hypertrophic
cardiomyopathy.  About 50 % are  genetic with autosomal dominant inheritance.
Asymmetric hypertrophy is the usual presentation involving the  whole  septum
or  less  commonly,  the  apex  or  mid  portion.   Histologically,  there is
myocardial cellular  disarray  which  is  distinctive  for  the genetic form.
PHYSIOLOGY:  There  is  usually  hyperdynamic  systolic  contraction  with  a
tendency to produce late  systolic  LV  cavity  obliteration,  with  ejection
complete  after  2/3  of systole followed by an isometric period.  Because of
the asymmetric septal hypertrophy coupled  with  LV cavity obliteration, a LV
outlet obstructive gradient may be created due to appostion of  the  anterior
mitral  valve  leaflet against the hypertrophied septum which then produces a
late systolic Venturi  effect.   Any  maneuver  that  decreases  LV volume or
shortens diastolic filling, decreases preload or diastolic filling, decreases
preload or enhances contractility  will  aggravate  the  gradient.   Examples
include amyl nitrate, straining phase of Valsalva's maneuver, standing from a
squatting to standing position, diuretics, digitalis and dehydration.  All of
these will increase the obstructive component.  On the other hand, squatting,
the  late  phase  of the Valsalva maneuver, isometric excercies, and negative
ionotropic agents may improve  the  outflow  gradient.   CLINICAL: The 3 most
common symptoms are dyspena, syncope  and  chest  pain.   These  usually  are
present  in  early  adulthood and become progressive, albeit slowly.  Many of
these symptoms are noticed during exercise.   The chest pain may be difficult
to differentiate from typical angina.  Syncope may be orthostatic or  induced
by  exercise  and  may be secondary to arrhythmias, LV outflow obstruction or
the incapability of increasing  stroke  volume during exercise.  Sudden death
is fairly common with this disorder, affecting  asymptomatic  young  patients
and   probably   induced   by  ventricular  arrhythmias  as  well  as  atrial
fibrillation which all can  cause  decreased diastolic filling and subsequent
LV  outflow  obstruction.   Physical  exam  will  reveal  a  rapidly   rising
bisferiens  carotid  pulse, a prominent a wave on the jugular venous pulse, a
loud S4, a triple apical  impulse  due  to the prominent atrial filling wave,
and a loud systolic ejection murmur along the left  sternal  edge,  a  longer
apical  systolic  murmur,  both  which will increase with Valsalva strain, or
upright position.  Atrial  fibrillation  may  be  due to chronically elevated
left atrial pressures.  Ventricular arrhythmias may also be present.  The ECG
may reveal deep, abnormal Q waves that are present  in  30-50%  of  patients.
These  Q  waves are known as pseudoinfarction waves and are not indicative of
MI.  LV hypertrophy is present  and  there  may  be a short PR interval.  The
echocardiogram  is   diagnostic   revealing   asymmetric   left   ventricular
hypertrophy  (usually  increased septal thickness) with a septal/LV posterior
wall thickness ration > 1.3-1.5/1.0  Systolic anterior motion of the anterior
leaflet of the mitral valve helps define the outflow obstruction.  SAM begins
after completion of early ejection and terminates in end-systole  before  the
S2.   As  a  result  of  the dynamic mid-systolic obstruction to outflow, the
aortic cusps may demonstrate premature  closure with late systolic reopening.
Diastolic movement of the mitral valve is impaired, resulting in a flat E  to
F  slope.   Doppler  can  document mitral regurgitation, and quantitation and
localization of outflow obstruction.   Early velocity as ventricular ejection
begins is about 1.5 meters/sec, compatible with  the  rapid  early  ejection.
Later,  the  Doppler  velocity  will progressively increase to peak in mid to
late systole and  then  return  to  baseline  at  the  end of ejection.  This
pattern is in contrast to a fixed obstruction  as  aortic  valvular  stenosis
where  there  is a smooth contour of increasing velocity, even as it peaks in
midsystole.  The left ventricular cavity  is  normal  to small and there is a
hyper-contractile LV with delayed relaxation and filling of the LV.   Cardiac
catheterization  doesn't  add  much  to  echo  and  Doppler exam.  TREATMENT:
Medical  treatment  should  aim  at  improving  the  hemodynamics,  relieving
symptoms and treating arrhythmias.   Relief  of  symptoms  may be obtained by
using either verapamil or diltiazem, OR beta blockers.   Patients  that  have
outflow  tract  gradients  are  treated with beta blockers or disopyramide as
they may decrease the obstruction.   Ventricular arrhythmias are treated with
procainamide, disopyramide, quinidine and  amiodarone.   Atrial  fibrillation
must be treated aggressively as its presence signifies a potential for sudden
death.   It is treated either with digitalis, a beta blocker and/or a calcium
angagonist to slow the ventricular rate.  Using a Type I antiarrhythmic or DC
electrical  cardioversion  is   indicated   for   conversion  of  the  atrial
fibrillation if feasible.  Surgery is indicated in those  patients  who  have
failed  medical  therapy  and  are  symptomatic  with  a  resting  LV outflow
gradient.  Patients that are placed  on calcium channel blocking drugs should
be monitored closely as some will worsen with  heart  failure,  while  others
will   develop  hypotension,  deterioration  and  even  death.   Disopyramide
(Norpace) has negative inotropic properties and will not cause LV dysfunction
as some calcium channel  blockers.   Those  patients  using beta blockers may
have symptomatic improvement that lasts for years, although the dose may have
to be increased from time to time.  Rarely, a daily dose of propranolol > 480
mg may be necessary.  Unfortunately, beta blockers have  not  been  shown  to
decrease  the  incidence of sudden death or ventricular arrhythmias.  Certain
drugs are  contraindicated  in  hypertrophic  cardiomyopathy.   These include
diuretics, nitrates and digitalis.  Digoxin, however, hs been used to control
atrial fibrillation.  Ventricular tachycardia has been demonstrated in HCM in
about 30% of patients that are monitored for 72 hours  with  ECG  monitoring.
If  the  ventricular  arrhythmias are refractory to class I drugs, amiodarone
has been shown  to  suppress  atrial  and  ventricular arrhythmias and sudden
death.  Prophylactic  therapy  for  bacterial  endocarditis  is  recommended.
Anticoagulation  should  be  instituted with intermittent or sustained atrial
fibrillation to  prevent  thromboembolism.   PROGNOSIS:  The annual mortality
rate is about 4% per year.  Many deaths occur  suddenly  in  young  patients.
Family  members  of  patients  with  hypertrophic  cardiomyopathy  should  be
examined for this cardiac disease, as many of these will be asymptomatic with
the  potential  for sudden death.  Identifying those patients at high risk of
sudden death is still an ongoing investigation.

                     -CARDIOMYOPATHY MANAGEMENT-
DILATED CARDIOMYOPATHY: Dilated cardiomyopathy was formerly called congestive
cardiomyopathy and is characterized by poor SYSTOLIC function.  The cause  is
often  unknown  although  it  can  be caused by chronic ingestion of alcohol,
systemic hypertension,  infection,  tobacco  use,  endocrine  disorders, poor
nutrition and familial disorders.  There is LV dilatation  with  low  cardiac
output  and/or  clinical  pump failure.  The walls do not enlarge.  The onset
may occur at any age and afflicts  men  more often than women.  The course is
usually one of progressive deterioration with 75% dying within five years  of
onset  of  symptoms.   In  those  over  age  55, most die within two years of
symptom  onset.   SYMPTOMS:  Symptoms  develop  gradually.   Common  symptoms
include dyspnea, orthopnea,  paroxysmal  nocturnal  dyspnea,  fatigue, and in
25-50% chest pain.  Also,  there  is  an  increased  incidence  of  pulmonary
emboli.   PHYSICAL:There is moderate to severe cardiomegaly, S3 or S4 gallop,
and  a  systolic  murmur  caused  by  mitral  regurgitation.   Jugular venous
distention and hepatic engorgement may be present.  In severe cases, there is
pulsus alternans.  A narrow pulse pressure is present secondary to  decreased
stroke  volume.   LABORATORY:  CHEST  X-RAY....There  is cardiac enlargement,
pulmonary   venous   hypertension   and   occasionally   pleural   effusions.
EKG....sinus   tachycardia,    atrial    and/or   ventricular   dysrhythmias,
non-specific ST-T abnormalities and intraventricular conduction  defects  may
be present.  MUGA....This study usually reveals a reduced left ventricular EF
of  less  than  40%.   ANGIOGRAPHY....There  is  a  diffuse  hypokinetic left
ventricle often with  mitral  regurgitation.   ECHO....There  is a dilated LV
cavity, normal LV wall thickness, decreased  LV  contractility  and  abnormal
diastolic  mitral  valve  motion.   TREATMENT:  Treatment  consists  of  salt
restriction,  diuretics,  digitalis  and vasodilators.  Antiarrhythmic agents
should be utilized only for  symptomatic  or serious dysrhythmias, since most
are negative inotropes and worsen CHF.  Anticoagulation  is  recommended  for
all  patients  even  in  the  absence of atrial fibrillation, or a history of
thromboembolic events.  Warfarin is preferred  and you should maintain the PT
at 1.3 - 1.5 times control.   Alcoholics  must  refrain  from  alcohol  since
cessation  of  alcohol  can  halt  progression  or  reverse  the  progress of
alcoholic related cardiomyopathy.  Cardiac transplantation may be considered,
but unfortunately, most  elderly  patients  are not candidates.  HYPERTROPHIC
CARDIOMHYOPATHY: Hypertrophic cardiomyopathy was previously  referred  to  as
obstructive  cardiomyopathy  and  IHSS.   It  is  characterized  by  impaired
DIASTOLIC  function.  Although it is considered a disease of young adults, it
is becoming more frequent  in  older  persons.   The etiology is unknown, but
there may be a familial  tendency  that  appears  to  be  transmitted  as  an
autosomal  dominant with a link to the HLA system.  Eventually the LV becomes
a rigid non compliant  chamber,  although  the  cavity remains normal size in
diastole, but is reduced in systole.  The ventricle fills  slowly,  resulting
in   an  elevated  left  ventricular  end-diastolic  pressure.   Hypertrophic
cardiomyopathy may present  with  or  without  outflow  obstruction, but when
obstruction is present it is often due to an asymmetric hypertrophied septum.
SYMPTOMS:The most common complaint is dyspnea while 75%  complain  of  angina
pectoris.    Other  symptoms  include  a  dry  hacking  cough,  palpitations,
tachycardia, anorexia, edema and syncope,  or near syncope, particularly with
the assumption of a standing position.  Syncope indicates  a  poor  prognosis
since   it   relates   to   a  significant  amount  of  outflow  obstruction.
PHYSICAL:There is mild  to  moderate  cardiomegaly,  with  an apical systolic
thrill and heave associated with a brisk carotid upstroke.  S3 or  S4  gallop
is  often  present  as  is  a  harsh crescendo-decrescendo systolic murmur of
mitral regurgitation that increases with production of the Valsalva maneuver.
Jugular venous distension, hepatomegaly, edema and ascites may also be noted.
LABORATORY:CHEST X-RAY....There may  be  evidence  of  CHF with cardiomegaly.
EKG....There is LVH and non specific  ST-T  changes,  abnormal  Q  waves  and
atrial  or  ventricular  dysrhythmias.   When  present,  atrial  fibrillation
suggests  a  poor prognosis since cardiac output is decreased.  ECHO....There
is a normal or decreased  LV  cavity,  increased LV wall thickness, normal or
increased LV contractility and asymmetrical septal hypertrophy with a  narrow
outflow   tract.    MUGA....This   test   is   recommended  since  it  allows
visualization of the  size  and  orientation  of the interventricular septum.
TREATMENT:Treatment consists of avoidance of exercise, digoxin, nitrates  and
beta  adrenergic  stimulators since all increase myocardial contractility and
outflow obstruction.   Diuretics,  which  decrease  venous  return and reduce
diastolic filling, should be used sparingly if at all.  Beta blockers are the
mainstay of treatment.  They  prevent  an  increase  in  outflow  obstruction
accompanying  exercise.   Patients  often require large doses usually greater
than 320 mg  of  Inderal  a  day,  a  dose  that  frequently produces adverse
reactions in elderly patients.  Calcium channel antagonists enhance diastolic
filling.  Unfortunately, they may also worsen symptoms of  CHF  and  must  be
used  with  caution.  Surgical intervention which involves myotomy/myomectomy
of the septum reduces outflow obstruction.   Patients over the age of 65 have
a similar success rate when compared to younger patients, so age  should  not
be considered a deterrent to surgical therapy.  Sudden death occurs during or
immediately after physical exertion.

                   -CARDIOPULMONARY RESUSCITATION-
Cardiopulmonary  resuscitation  starts   with   the   ABCs:  Airway  control,
Breathing,  and  Circulation.   Airway  control  is  best   accomplished   by
endotracheal   intubation  which  will  allow  access  for  drug  therapy  as
epinephrine, lidocaine, atropine and naloxone  if IV access is not available.
The dose of these drugs is usaully about 2-2.5 times the IV dose.   Prior  to
this  mouth  to  mouth  and  bag  valve  mask  may  be  used.  Circulation is
accomplished by external chest  compression in a compression:relaxation ratio
of 1:1 and a compression rate of 80-100/minute.  Adults should have  a  depth
compression  of  about  2-2.5  inches.   External chest compression will only
restore about 25% of normal circulation.  Open cardiac massage provides about
50% of the normal  circulation.   This  method  may be used when conventional
methods are not successful.  Venous access  includes  the  acquisition  of  a
suitable  peripheral vein.  Even the femoral vein may be used.  Central lines
can be established after the patient  has been intubated by using an internal
or subclavian approach.  The interanl jugular approach is  preferred  because
the  subclavian  approach  has  a  higher  risk for pneumothorax.  As soon as
ventricular fibrillation  or  ventricular  tachycardia  has  been identified,
defibrillation should be carried out starting at 200 Joules and repeating  at
300  and  360  Joules  if  the  defibrillation  is unsuccessful.  Ventricular
fibrillation must be carried out early if optimal results are to be expected.
If ventricular fibrillation  or  venntricular  tachycardia persists after the
first 3 shocks, CPR should be continued, and the patient given epinephrine  1
mg  IV  push  every  3-5  minutes.  If this fails, the dose of epinephrine is
escalated to 3 and 5 mg IV  push every 3-5 minutes.  Epinephrine is effective
in ventricular fibrillation, electromechanical dissociation and asystole, due
to its vasoconstrictive effects, inotropic and chronotropic effects.  It  can
convert  fine  ventricular  fibrillation  to  coarse ventricular fibrillation
which  enhances  the   effectivness   of  defibrillation.   Epinephrine  also
increases cerebral and coronary flow.  Successive shocks  are  applied  after
each  dose of epinephrine.  If ventricular fibrillation persists after all of
this, Lidocaine is given at 75 mg or  1.5 mg/kg IV bolus and repeated with 50
mg every 10 min x 3, followed by an infusion of  2  mg/min.   Following  this
defibrillation  is again tried.  If unsuccessful, Bretylium 500 mg or 5 mg/kg
is given IV and repeated with 10  mg/kg  every 5 minutes x 2, and followed by
another shock.  Bretylium works synergistically with lidocaine.  It may cause
hypotension.  If still unsuccessful Procainamide 100  mg  is  given  every  5
minutes  up  to  1  gram and followed by an infusion at 2 mg/min, and this is
followed  by  another  shock.    If  epinephrine,  lidocaine,  bretylium  and
procainamide  are  all  ineffective,  magnesium  sulfate,  propranolol,   and
amiodarone may all be tried.  ASYSTOLE: Treatment for asystole may be treated
with  transcutaneous  pacing, epinephrine 1 mg IV push and repeated every 3-5
minutes, followed by atropine 1 mg IV  and repeated every 3-5 minutes up to a
total of 0.04 mg/kg.   Hypokalemia,  hyperkalemia,  hypoxia,  acidosis,  drug
overdose  and hypothermia should all be corrected.  Dopamine is used to raise
the blood pressure and is given at 10-40 ug/kg/min IV.  Sodium bicarbonate is
no longer given as first line drug  therapy.  It is given, guided by arterial
pH determinations, at  1  mEq/kg,  followed  by  0.5  mEq/kg  at  10  minutes
intervals.   Calcium is no longer used as it may cause reperfusion injury and
CNS dysfunction.  It may  be  considered  in those patients receiving calcium
channel blockers and suspected hyperkalemia or hypokalemia.  The dose is  10%
calcium chloride 5 ml every 10 minutes x 4. Magnesium is used at 1-2 grams IV
bolus  over  a  2 minutes period and repeated in 5-10 minutes, followed by an
infusion  of  2-20  mg/min.   It   is  indicated  in  refractory  ventricular
fibrillation or Torsade  de  pointes.   Pacemaker  therapy  is  indicated  in
asystole,  and  hemodynamic significant bradycardia < 50 that is unresponsive
to atropine (1-2 mg  IV),  or  isoproterenol  (2-10  ug/min), second or third
degree heart blocks, and recurrent or unstable rhythmns that  are  refractory
to  drugs.  It is not indicated after prolonged CPR (must be done immediately
to be  effective),  electromechanical  dissociation  with  heart  rates > 50.
ELECTROMECHANICAL DISSOCIATION: Prognosis is poor  unless  some  identifiable
factor  is  active.   Correctable  causes  should  be  sought as hypovolemia,
cardiac  tamponade,   shock,   acidosis,   pulmonary  embolus,  pneumothorax,
pulmonary edema and hypoxia.  Epinephrine may be  used  in  combination  with
dopamine  infusions  to  maintain blood pressure.  If patient is hypovolemic,
volume challenges should be given.   If patient is acidotic give bicarbonate.
Patients  with  myocardial  or  aortic  rupture  have   a   poor   prognosis.
TERMINATION  OF  CPR:  Most  cases  of  CPR  can be terminated if there is no
response to organized cardiac activity  after  10-15 minutes of advanced life
support.  Survival is unlikely if CPR extends beyond  30  minutes.   Patients
that   present   with   drug  intoxication,  electrocution,  hypothermia  and
refractory ventricular fibrillation may be candidates for extended CPR.

                       -CAROTID ARTERY DISEASE-
Carotid artery disease is extremely prevalent in the population, and accounts
for about 30% of  strokes.   It  may  be  asymptomatic and detected only upon
routine examination, or it may present as a transient ischemic attack  (TIA).
Several  studies have now been done to serve as guidelines for the prevention
and treatment of carotid artery  stenosis.  ASYMPTOMATIC CARTOID STENOSIS may
be discovered on routine physical examination by  auscultation  of  a  bruit.
Carotid stenosis is also an indicator for more global atherosclerotic disease
involving the coronary arteries and peripheral vascular disease.  It has been
estimated  that  about 25-70% of patients with cerebrovascular disease but no
cardiac symptoms will have  abnormal  ECGs  and myocardial perfusion studies.
Thallium imaging should be considered in all patients prior to endarterectomy
in order to assess the degree of myocardium at risk.  The risk for stroke  in
asymptomatic  patients  has  been addressed in several studies.  A study that
was carried out at  the  stroke  research  Unit  at Sunnybrook Health Science
Centre in Toronto followed 500 patients with Doppler proved stenosis for  one
year.   After  one  year,  stroke  was  observed at 5% in a group with severe
stenosis of 75-100%.  A later study  by  the  same group that was carried out
for up to 95 months, found that the annual stroke rate was 3.3%  in  a  group
with  severe  stenosis,  and  only  1.3%  in patients with a lesser degree of
stenosis.  At  the  present  time  there  is  no  indication  for  surgery in
asymptomatic  carotid  stenosis.   The  Veterans  Affairs  Cooperative  study
substantiated this position.  In this study 444 male veterans with a mean age
of 64.5 years with asymptomatic, angiographically proved stenosis of over 50%
were randomly assigned to carotid endarterectomy plus aspirin or  to  aspirin
only.   After  4  years of study, there was no difference in the incidence of
stroke.  Furthermore, the incidence of  death  was  found  to be 41.2% in the
surgical group, and 44.2% in the medical group.   This  is  a  high  rate  of
mortality,  but  has  been  attributed  to  the  coexistence of cornonary and
peripheral vascular  disease.   Patients  with  asymptomatic carotid stenosis
should be treated by risk factor modification, with consideration for the use
of antiplatelet agents.  SYMPTOMATIC LOW GRADE STENOSIS: This  population  is
defined  as  carotid  stenosis consisting of plaques or stenosis up to 29% on
Doppler interrogation.   Studies  from  the  European  Carotid  Surgery Trial
(ECST) has found no benefit from carotid  endarterectomy  in  this  group  of
patients.   Therefore,  it  is recommended that risk factor modification, and
antiplatelet therapy be instituted.   SYMPTOMATIC MODERATE STENOSIS: Moderate
stenosis is  defined  as  stenosis  from  30-69%  as  determined  by  Doppler
examination.   Optimally,  since  this stage of disease is controversial, the
patient should be referred to  a  participating  center in the North American
Symptomatic Carotid Endarterectomy Trial (NASCET) for further  study.   These
patients  should  be  considered for arterial carotid angiograpy.  IV digital
subtraction angiography should  not  be  used.   The  benefits of angiography
include assessment of the  collateral  circulation  and  significant  disease
above  the  carotid  artery  which  could  preclude  surgical  ingtervention.
Patients  that  are  considered  at  risk because of coexisting heart disease
should  be  treated  with  antiplatelet  agents  and  risk  factor reduction.
Patients that have symptomatic moderate stenosis and ulcerated plaque are  at
risk for increased stroke, and carotid endarterectomy should be considered on
each  individual  case.   SYMPTOMATIC  SEVERE HIGH GRADE STENOSIS: High grade
stenosis is defined as  70-90%  stenosis  of  the  carotid artery via Doppler
examination.  Thanks to the North American Symptomatic Carotid Endarterectomy
Trial (NASCET) and the European Carotid Surgery Trial (ECST) studies, it  can
now  be  said that carotid endarterectomy is the treatment of choice for this
group.  Complications of  endarterectomy  include  hematoma, false aneurysms,
infection, stroke and death.  In the NASCET study patients with  moderate  or
severe  stenosis  were  randomly selected for surgery and aspirin, or aspirin
alone.  The  study  was  terminated  early  because  the  cumulative  risk of
ipsilateral stroke over 2 years was found to be 26% in the medical group  and
9%  in  the  surgical  group.   These findings were substantiated by the ECST
study, which had similar results.  This  may  change in the future as balloon
angioplasty studies become available.   All  patients  should  have  arterial
angiography  prior  to  the  surgery.   Some of the patients that have 98-99%
stenosis by Doppler will be found to  have total carotid occlusion which is a
contraindication for endarterectomy.  The patient should  first  be  assessed
for  surgical risk.  In the NASCET study, it was found that the perioperative
disabling stroke and death rate  was  5.8%.  All patients should be continued
on aspirin following endarterectomy.

                  -CAROTID BRUIT (Innocent murmur)-
This may be present at any  age.   The murmur disappears on supination.  Is a
systolic murmur near the clavicles or over the  carotids.   It  is  soft  and
there may be a faint thrill.

                            -CAROTIDYNIA-
Carotidynia characteristically presents with unilateral pain in the neck that
may radiate to the face, ear or malar region.  The pain may be mild to severe
and may be  made  worse  by  yawning,  swallowing,  sneezing, coughing, or by
turning the head to the opposite side with the head elevated.  The  pain  may
be  throbbing  or  dull  and may vary in intensity from day to day.  Physical
examinination will reveal tenderness of  the  carotid bulb and prominence and
throbbing of the carotid pulse.  It may be confused with  acute  pharyngitis,
dental  disease,  lymphadenitis,  peritonsillar  abscess, submandibular gland
disease, atypical facial  pain,  myositis, sinustitis, thyroiditis, neuralgia
and  tumors  of  the  larynx,  tongue,  or  salivary  glands.   The  pain  of
thyroiditis and tracheitis are more centrally located.  Facial  pain  may  be
caused  by  Eagle's  syndrome  (facial  pain  caused  by an elongated styloid
process).  However this pain typically  can  be reproduced by finger pressure
at the the base of the tongue.  Carotidynia can be caused  by  migraine,  and
viral  infections,  giant  cell  arteritis,  carotid artery aneurysm, carotid
artery occlusion and carotid artery dissection.  One of the most common cause
is due to migraine.  Many of  these patients will have a migraine personality
such as compulsiveness, conscientious and sensitive.  The  pain  in  migraine
carotidynia  usually  will  respond  to  typical migraine medications such as
tricyclic antidepressants,  beta  blockers,  calcium  blockers, ergonovine or
methysergide.   The  other  common  cause  of  carotidynia  is  secondary  to
pharyngitis, viral upper respiratory infections or infected aphthous  ulcers.
These   cases   are  treated  symptomatically  with  heat,  reassurance,  and
antiinflammatory agents.   Reasurance  is  very  important because unilateral
neck pain may last for some time and can cause a great deal of  distress  and
anxiety  in the patient.  Since carotidynia may be associated with giant cell
or temporal arteritis, a sedimentation  rate  should  be done in all patients
regardless of age.  Steroid therapy is  the  treatment  of  choice.   Carotid
artery dissection typically presents with an abrupt onset of cervical, facial
or  head  pain  followed  in  hours  or  days  by ischemic symptoms, Horner's
syndrome, amaurosis  fugax  and  pulsatile  tinnitus.   Tests  should include
carotid duplex ultrasound, MRI and carotid arteriography.  Carotid dissection
can lead to stroke in children and young adults.   Treatment  is  IV  heparin
acutely  followed  by  warfarin  for 6 months.  Surgery may be needed in some
cases.  Carotid  artery  aneurysm  may  also  present  with carotidynia.  The
aneurysm can occur anywhere along the common or internal carotid arteries.  A
pulsatile mass may or may not be present.  Trauma  and  arteriosclerosis  are
the  most  frequent  causes, but other causes include cystic medial necrosis,
pyogenic infections, previous  carotid  artery  surgery, syphilis, congential
defects, ionizing  radiation  and  Marfan's  syndrome.   These  patients  may
develop  neurological complications as amaurosis fugax, syncope, stroke, TIAs
and coma.  Rupture of the aneurysms is rare.  Arteriography is the diagnostic
method  of  choice  and  treatment  is  surgical  resection.   Carotid artery
occlusion  may  also   develop   from   subintimal   hemorrhages   underneath
atheromatous plaques and lead to carotidynia.

                        -CAT SCRATCH DISEASE-
CLINICAL: Cat scratch disease is an  infection  caused  by  Afipia  felis,  a
flagellated gram negative organism, that occurs world wide, usually affecting
children  and  young  adults  that  have been in contact with a cat.  The cat
often times is a kitten and  appears  healthy.  The disease has been reported
in AIDs, also.  It is characterized by the development of a cutaneous  lesion
that  is  erythematous,  may  be  crusty  with a scabbed ulcer or a papule or
rarely a pustule, measuring about  2-6  mm,  and occurs about 3-10 days after
the bite.  These lesions will occur in about 60-90% of the cases.   Following
the  lesion,  about  1-3 weeks later, fever (usually less than 50%), headache
(13%) and malaise (29%) may  develop  and  the regional nodes enlarge.  These
nodes may be tender or non  tender.   They  may  be  axillary,  epitrochlear,
cervical, submandibular or inguinal.There may be overlying skin inflammation.
Suppuration  occasionally  occurs  with  fistula  formation,  but  the pus is
sterile.  The lymphadenopathy and skin lesion usually disappear spontaneously
within 2-5 months without  any  special  treatment.   Rarely, the patient may
develop  a  conjunctivitis  with  palpable  preauricular  nodes   (Parinaud's
oculoglandular  syndrome)  (6%),  Cat scratch encephalopathy (2%), osteolytic
lesions, mesenteric adenitis, erythema  nodosum, and thrombocytopenia.  AID's
patients  have  developed  a  disseminated  form  that  resembles   bacillary
angiomatosis.   Bacillary  angiomatosis  is  caused  by  a  rickettsial  like
organism  which  is  treated  with  erythromycin  or  tetracycline  which are
ineffective in cat scratch  disease.   LABORATORY: Microscopic examination of
the node shows hyperplasia, granuloma, microabscess and suppurative necrosis.
The organism can be seen with the  silver  stain  of  Warthin-Starry  or  the
Brown-Hopps  tissue  gram  stain.  The organisms are seen in the walls of the
blood vessels.  The ESR is elevated  and  eosinophils may be increased with a
leukocytosis.  The CSF  protein  is  increased  with  occasional  mononuclear
cells.   The  skin  test is not readily available.  TREATMENT: Treatment with
antibiotics has not been  good.   However,  there  may  be some response with
ciprofloxacin  500  mg  bid  for  14  days.   In  vitro  studies  have  shown
susceptibility to cefotaxime, cefoxitin,  mezlocillin  and  IV  gentamicin  5
mg/kg/day has been used in the disseminated disease.

                      -CAUSTICS AND CORROSIVES-
Corrosive agents include acids that  produce  a coagulation type necrosis and
eschar which limits the amount of damage.  Alkalies, on the other hand, cause
a liquefactive necrosis which tends to penetrate into the deep  tissues  with
extensive  damage.   Many  agents can cause  corrosive injury.  These include
hydrochloric acid such as muriatic  acid, swimming pool cleaners, toilet bowl
cleaners, sulfuric acid ( toilet bowl and commercial drain cleaners,  battery
acid), drain pipe cleaners, paint removers, lithium, ammonium, lye, ammonium,
calcium hydroxides, bleach (sodium hypochlorite), potassium permanganate, and
button  batteries.   Exposure  to these occur as inhalations, ingestions, and
dermal or ocular exposures.  The most  common cause in toddlers is accidental
ingestion  of  household  cleansers  that  contain  caustic  agents.    These
cleansers  can  contain alkaline corrosives such as phosphoric acid (in floor
cleaners), sodium hydroxide (in oven  cleansers), and hydrofluoric acid (rust
and  concrete  cleaners).   Button  batteries  can  contain  up  to  50%   of
concentrated  potassium  hydroxide,  and  if  swallowed,  leak  out and cause
ulcerations in the esophagus or  GI  tract.  Clinitest tablets contain sodium
carbonate, copper sulfate,  sodium  hydroxide,  and  citric  acid  which  can
produce  erosions  of  the  esophagus  if  swallowed.   ACID  INGESTION: Acid
ingestion  causes  pain  in  the  buccal,  pharyngeal,  and  epigastric area,
dysphagia, nausea, vomiting, hematemesis, stridor and shock.  Perforation  of
the  GI  tract is uncommon.  The late complications of acid ingestion include
pyloric  and  esophageal   stenosis.    ALKALI   INGESTION:  Alkalis  produce
liquefaction necrosis of the oral and esophageal mucosa.  Alkali exposure  to
the  skin,  eye  and lung by inhalation may also cause problems.  The natural
history of a caustic injury starts with  the  acute phase which lasts up to 3
days with drooling, dysphagia, pain and anorexia.  This is  followed  by  the
intermediate  phase  which consists of a slow resolution of the oral symptoms
over the  next  2-3  weeks.   The  late  phase  is  characterized  by chronic
dysphagia and abnormal esophageal motility with stricture  formation  of  the
esophagus.   Patients  may  also  develop  esophageal ulcers and perforation,
pericarditis, mediastinitis, chemical  gastritis  of the stomach, perforation
of the stomach with peritonitis, arterial rupture and bleeding, and laryngeal
obstruction.  Examination of the oral  mucosa  may  show  redness  and  white
burns,  swelling  of the lips and tongue.  Patients that complain of stridor,
dysphagia, and abdominal pain indicate  more extensive damage.  However, even
those  patients  that  do  not  complain  may  have  esophageal  lesions  via
endoscopic examination.  Patients with inhalation of a caustic  gas  such  as
hydrogen  chloride  or  chlorine  may comnplain of chest tightness, wheezing,
dizziness, coughing and dyspnea  which  can subsequently progress to chemical
pneumonitis and pulmonary edema.  Exposure of the eyes leads to lid swelling,
tearing and loss of vision.   TREATMENT:  ACIDS:  The  use  of  dilution  and
neutralization  is  controversial.   Dilution  of strong acids with water can
cause exothermic reactions resulting in  further necrosis.  Some would pass a
nasogastric tube in acid ingestions  and  aspirate  the  stomach  completely,
followed  by  large  volumes of cold milk.  If a weak acid has been ingested,
cold milk or  water  may  be  administered  for  dilution.   Emesis should be
avoided in  all  patients.   ALKALI:  Emesis  is  contraindicated  in  alkali
ingestions.   Nasogastric  tube  and  lavage  is  also  contraindicated as is
charcoal.  Dilution with  cold  milk  is  indicated.  Esophagoscopy should be
done within 12-24 hours to assess for esophageal injury.  Patients  that  are
found    to   have   esophageal   ulcerations,   white   plaques,   erosions,
circumferential erosions, and sloughing will probably need a gastrostomy with
subsequent serial dilatations by bougienage.  Steroids are controversial, and
probably do not prevent fibrosis  and stricture.  Patients with erosions will
need IV antibiotics.  Upright chest and abdominal x-rays  may  be  needed  to
determine  if  any  mediastinal  air or  abdominal  air  is  present.  Button
battery ingestion usually causes  no  problem  unless  they  fail to pass the
esophagus or lodge in a  Meckel's  diverticulum.   The  battery  should  pass
within  48-72 hours.  If any new symptoms develop, such as abdominal pain and
vomiting, complications should be  suspected.   Contamination  of the eye and
skin with caustics requires copious irrigation  with  normal  saline  for  at
least 30 minutes.

                          -CELIAC DISEASE-
Celiac disease, also known as gluten enteropathy, is a malabsorptive  disease
caused  by  an  intestinal sensitivity to the polypeptide gliadin fraction of
gluten.  The gliadin fraction of gluten  is  found  in wheat and rye and to a
lesser extent in barley and oats.  Gliadin acts as an antigen combining  with
antibodies  to  form  an  immune  complex  in  the jejunal mucosa that causes
aggregation of lymphocytes which are  capable of inciting mucosal damage with
proliferation of crypt cells and loss of villi.   Most  of  the  cases  occur
during  the  second  year  of  life,  the  age  at  onset and the severity is
variable.  A family history  may  be  elicited  with  10% of the first degree
relatives affected.  There is a higher incidence of the disease in Canada and
Europe than in the USA and the disease is uncommon in blacks and Asians.  The
prevalence of the disease in southwest Ireland is about 1:300.  The incidence
in the USA is about 50-75 in 100,000.  CLINICAL: The characteristic  symptoms
are  usually  seen  in  infancy after the child starts eating food containing
gluten.  There is defective  absorption  of fat, protein, carbohydrates, iron
and water.  There also is malabsorption of Vitamins A, D, and K. Osteomalacia
may develop.  About 33% of patients with  gluten  enteropathy  have  symptoms
that  begin  in  early childhood.  There may be a period where the disease is
inactive, or clinically not  detected,  and  then reappearance in later life.
There is a fraction of patients that will not respond to a gluten free  diet.
There  is failure to thrive, abdominal pain and bloating, with large, greasy,
frothy, bulky stools that are pale and malodorous.  There may be constipation
and  vomiting.    Iron   deficiency   anemia   will   develop,   and  if  the
hypoproteinemia is severe there will  be  edema.   The  typical  child  shows
wasting  of  the  buttocks  and  limbs  with a pot belly.  Patients that have
dermatitis herpetiformis have associated celiac sprue which may or may not be
symptomatic.  In adults there is no single typical presentation.  The patient
may develop weight loss,  anemia,  bone pain, edema, paresthesiae, dermatitis
herpetiformis, and may or may not have  diarrhea,  abdominal  distention  and
pain.   Diagnosis  is  confirmed by biopsy, demonstrating the flattened villi
and improvement of the biopsy  and  clinical  symptoms on a gluten free diet.
This is not an entirely benign disease, as there may be mortality  associated
with  the  development  of  lymphoreticular  disease as intestinal lymphomas.
LABORATORY:  There  is  a   positive   anti-gliadin  IgA  and  IgG,  positive
anti-reticulum and anti-endomycial antibodies.  The 72 hour fecal  fat  shows
greater  than  7% fat malabsorption.  There is a decrease of calcium, sodium,
potassium, cholesterol,  vitamins  A,  C,  B12,  folic  acid,  iron and total
protein.  There may be elevation of the alkaline phosphatase and prolongation
of the prothrombin time.  The anemia is hypochromic and  microcytic.   Biopsy
of  the small bowel will show flattened villi, hyperplasia and lengthening of
crypts, infiltration of plasma cells  and  lymphocytes in the lamina propria.
C3 and C4 may be low in untreated patients.   The  serum  IgA  is  normal  or
increased  and in about 50%, the IgM is reduced.  A 3 day collection of stool
will usually reveal fecal fat  levels  greater than 4.5 g/d.  Normally, there
is about 5-10% of excretion of ingested fats.  In  celiac  disease  there  is
excretion  in  excess of 15% of the daily fat intake.  Absorption of D-Xylose
is also impaired  with  blood  levels  less  than  20  mg/dL 60 minutes after
ingestion.  Small bowel  studies  will  reveal  segmentation,  and  clumping.
DIFFERENTIAL  DIAGNOSIS:  Other  diseases  of malabsorption must be ruled out
such as regional enteritis, intestinal tuberculosis, tropical sprue, acquired
immune  deficiency   syndrome,   giardiasis,   eosinophilic  gastroenteritis,
pancreatic insufficiency, hypogammaglobulinemia, lymphoma,  nodular  lymphoid
hyperplasia,  and  amyloidosis.   TREATMENT:  A  strict  gluten  diet must be
followed.   Even  slight  indiscretions  may  cause  an  exacerbation  of the
disease.  Consultations with a dietician is crucial to exclude hidden  gluten
that  may  be  found  in sauces, ice creams, hot dogs, commercial soups, etc.
The patient should be given supplementary vitamins, minerals and iron.  Folic
acid  and  calcium   gluconate   may   be   needed   along  with  vitamin  D2
(ergo-calciferol).  Vitamin K may  be  needed  if  the  prothrombin  time  is
abnormal.   The  diet  should be high in calories and protein and low in fat.
Some patients will not respond to a  gluten free diet.  However, be sure that
the patient is not ingesting gluten that is unknown to the patient.  In  this
case  prednisone  may  be  given in a dose of 10-20 mg bid which will usually
improve the disease.

                    -CENTRAL ALIMENTATION (TPN)-
TPN is used when there are increased metabolic demands as in  burns,  sepsis,
trauma,  chronic  bowel  obstruction  as  in Crohn's, radiation enteritis and
fistulae.    Complications   include   electrolyte,   vitamin   and   glucose
alterations, liver dysfunction  and  fluid  overload.   Vitals should be done
every 6 hours.  Daily weights should be done as > 1.5 kg/week  suggest  fluid
and  salt  retention.  I&O and urine glucose is done every 6 hrs.  If patient
develops a temperature >100.4 F  or  38  degrees C., blood cultures should be
done.  If the source of the temperature cannot be identified within  24  hrs,
the  TPN catheter should be changed over a new guidewire and the catheter tip
cultured, and if positive the site is  changed.  Urine glucoses that are 4 +,
mandate a serum glucose.  Sudden hyperglycemia can indicate incipient sepsis.
Glycosuria is normal during the first 24-48 hrs of TPN as  insulin  secretion
increases.   Sustained  elevated  glucoses  and diabetics will need exogenous
insulin.  Five to 10 units of regular  insulin  can be added to each liter ot
TPN.   Baseline  CBC,  electrolytes,  chemistries  including   Mg,   PT   and
triglycerides  should  be  done.   If  the  patient  is  malnourished,  order
nutritional assessment tests as transferrin, transthyretin, nitrogen balance,
vitamins  and  retinol  binding protein.  Do not given lipid emulsions if the
baseline triglycerides  are  >500  mg/dl.   Lipid  clearance  or triglyceride
levels  6-8  hrs  after  the  first  lipid  emulsion  should  be  done.   The
triglyceride level should return to preinfusion levels within  4  hours.   If
the  level  stays  elevated  change  to  10%  emulsion  and/or  order smaller
subsequent amounts of  the  20%  lipid  emulsion  and follow the triglyceride
level.  IV tubing and central cather dressing should be changed according  to
hospital  protocol.   Chemistires and electrolytes should be done daily until
stabilization and then order glucose and electrolytes every other day and CBS
and chemistries weekly.  TPN is given as 500 ml D50W + 500 ml amino acids (7%
or 8.5%) over the first 24 hrs.  One  liter is given during the first 24 hrs.
The volume is increased as tolerated by one liter/day until the  protein  and
caloric needs are accomplished, which is usually 2-3 liters/day (2000 ml/day;
660 Cal/L;675 mOsm/L).  Fat emulsion 20% is given as Intralipid 500 ml over 8
hrs during each 24 hr period (1000 Cal; 165 mOsm).  Specify the desired final
TPN   content  of  calcium,  electrolytes,  Mg,  phopsphorous  and  vitamins.
B-complex MVI 2.5 ml/day,  ascorbic  acid  250  mg/day, folic acid .5 mg/day,
zinc 4 mg/day should be added to one of the daily  bottles.   Trace  elements
are given if the TPN is prolonged beyond 3 weeks.  The standard final content
in  mEq/L  of each TPN liter is usually sodium 40, potassium 40, chloride 35,
calcium 4.6, phosphorous 12, magnesium  8.1.   Lab values for these should be
done in order to modify these additive.  Special preparations  are  available
for liver and heart failure, and nondialyzed renal disease.

                      -CENTRAL VENOUS CATHETERS-
There are 4 major types of central venous catheters (CVC) in use.  The first,
a polyurethane catheter, is a short  term  CVC that is inserted directly into
the subclavian vein with the distal tip just proximal to  the  right  atrium.
The second type is a long term central venous silastic catheter which has its
proximal  portion  tunneled  subcutaneously  before  exiting  the skin on the
anterior chest wall.  The usual  entry  site  is the jugular vein.  These are
used for long term continuous therapy.  There is a  slight  increase  in  the
infection  rates.   Examples  of  this  type  include  the  Hickman, Broviac,
Groshong, and Quinton catheters.   The  third  type  is  a long term silastic
catheter that  has  a  subcutaneous  titanium  reservoir  which  is  tunneled
subcutaneously  in  the  anterior  chest  wall.   The entry site includes the
cephalic,  jugular  or  subclavian  veins.   These  are  used  for  long term
intermittent therapy.  They are popular because of the reduced  incidence  of
infection,  cosmetic appearance, and they may be used for extended durations.
These catheters include  the  Port-A-Cath,  Mediport,  and Infus-A-port.  The
fourth type is the peripheral silastic (PICC) catheter that uses a basilic or
cephalic vein for entry.  These are used for intermediate term or  continuous
therapy.   Advantages  include  low  risk  of  placment  in  thrombocytopenic
patients,  and  ease of placement.  The disadvantages are that infections and
sterile  phlebitis  are  common.   The  Hickman  type  catheter  can  be used
immediately after placement following verification of  its  position  in  the
superior vena cava or right atrium.  The Port-a-Cath cannot used immediately,
but  can  be  used  after 24 hours or more.  The skin overlying the reservoir
should be cleaned  with  10%  povidone-iodine  solution  using serile gloves.
Hickman type catheters may have 1  or  2  ports  which  can  be  accessed  by
releasing  the  Luer-Lock  between  the skin exit site and the administration
site.  The Luer-Lock prevents air  embolization  or leakage of blood from the
catheter.  Following the use of the catheter, heparinized saline (5 ml of 100
units/mL) is injected into the catheter and the Luer Lok is closed.   Hickman
type catheters should be irrigated twice a week with heparinized saline (5 mL
100  units/mL)  twice  weekly.   The Groshong catheter is flushed only once a
week.  COMPLICATIONS  OF  CENTRAL  VENOUS  CATHETERS:  GENERAL: Pneumothorax,
hemothorax, hydrothorax, arteriovenous fistulas, cardiac tamponade,  catheter
embolism,  pulmonary embolism, arrhythmias, catheter migration, extravasation
of sclerosing agents, right  atrial  and  ventricular thrombi, perforation of
the heart and great vessels.   EXIT  SITE  INFECTIONS  are  the  most  common
infections.   Staphylococcus aureus and Staphylococcus epidermidis constitute
the usual offending  organisms.   There  may  be  fever, chIlls, tachycardia,
tenderness, erythema, induration and pus at the  site.   Gram  stains,  local
cultures  and  blood cultures should be done if indicated.  Treatment is with
IV vancomycin which can be  given  through the catheter.  The catheter seldom
needs to be removed to eradiacte exit site infections.  If the patient  fails
to  improve  after  about  3  days  of therapy, the catheter must be removed.
TUNNEL INFECTIONS are signaled  by  tenderness,  redness and induration along
the tunneled catheter.  Most infections again are caused by Staph aureus  and
epidermidis.   Treatment  is  with vancomycin given through the catheter.  To
broaden the coverage, ceftazidime can  be  added.  About 33% of patients will
have their tunnel infections cured without removing the catheter.   If  there
is  no improvement after 72 hours, the catheter is removed.  CATHETER RELATED
SEPSIS usually  presents  with  fever,  chills,  tachycardia, hypotension and
leukocytosis.   Always   check   for   bacteremic   complications   such   as
endocarditis, psoas abscess or septic pulmonary emboli.  Patients should have
blood  cultures  from a peripheral vein along with chest x-rays, UA and blood
chemistries.  About 50% of catheter  infections  are  due to Staph aureus and
Staph   epidermidis.    Other   organisms   include   candida,   pseudomonas,
corynebacterium, klebsiella, enterococci and non  enterococcal  streptococci.
Recommended  therapy  is  with vancomycin and ceftazidime OR piperacillin (or
other antipseudomonal penicillin) plus  gentamicin (or other aminoglycosides)
given through the catheter for 2-3 days.  If the  patient  fails  to  improve
after  2-3  days the catheter must be removed.  OBSTRUCTION OF CENTRAL VENOUS
CATHETERS is usually due  to  thrombosis  or  fibrin  sheath formation at the
distal tip of  the  catheter.   Other  causes  include  dislodgement  due  to
coughing,  straining and compression of the catheter between the clavicle and
the first rib.  It presents  as  difficulty  in injecting or withdrawing from
the catheter.  Fibrin sheath formation  has  a  characteristic  presentation.
Fluids   can  be  infused  easily,  but  blood  withdrawal  is  difficult  or
impossible.  Venous thrombosis is more  common in patients that are receiving
chemotherapy for solid tumors such as adenocarcinoma of the  lung.   Patients
that   have   swelling  of  the  ipsilateral  arm  suggests  subclavian  vein
thrombosis.  Patients with  neck  swelling,  chest  wall  vein prominence and
dyspnea should be evaluated for thrombosis of  the  superior  vena  cava.   A
superior  vena  cavagram  should  be  done  to  rule  out  malignancy  versus
thrombosis.  The gold standard for diagnosing venous thrombosis is venography
using a peripheral vein.  The catheter should not be used.  Color flow duplex
doppler  may  also be used for diagnosis.  Patients that have difficulty with
infusion of fluids,  pain  or  signs  of  extravasation  without arm swelling
should have a catheter venogram using a water  soluble  contrast  agent.   If
there  is  difficulty  in aspirating blood, but infusion of fluids is normal,
consider kinking or fracture of the  catheter.   A chest x-ray should be done
to confirm a correct position of the  catheter.   Various  maneuvers  may  be
attempted  to  alleviate  the  kinks.   Put  the patient in the Trendelenburg
position, raise the ipsilateral  arm  above  the  head and infuse crystalloid
fluids.  Treatment for venous thrombosis, confirmed by a  venogram,  is  with
urokinase,  streptokinase, or recombinant tissue plasminogen activator (TPA),
if there are no  contraindications.   Give  5000  units of urokinase into the
catheter and let it remain for 20 minutes.  If not successful  on  the  first
attempt, repeat attempts may be carried out.  If still unsuccessful, give 500
units/kg/hr.   This may be increased to 2000 units/kg/hr.  Alternatively, the
patient may be given streptokinase 50,000  units  as a one time dose.  TPA is
given as 48 mg in the first hour followed by 32 mg over the next 2 hours.  If
all  these  measures  fail,   the   catheter   must   be   removed.    SEPTIC
THROMBOPHLEBITIS  is  another  complication  of central venous catheters.  It
usually  presents  with  systemic  infection  symptomatology  such  as fever,
tachycardia, leukocytosis, plus signs of central venous obstruction  such  as
arm, or neck swelling and prominence of the chest wall veins.  These patients
will  need venography.  CT may reveal air bubbles in the thrombus of patients
with septic thrombophebitis.  Treatment is  removal of the catheter, possible
debridement, antibiotics and  heparin.   About  33%  of  patients  will  have
pulmonary   emboli.   EXTRAVASATION:  Central  venous  access  catheters  are
commonly  placed   for   chemotherapeutic   administration.    Many   of  the
chemotherapeutic agents can cause necrosis  if  extravasated.   Those  agents
that  can  produce  necrosis include dactinomycin, doxorubicin, daunorubicin,
mechlorethamine, vinblastine, vincristine, and  mitomycin.  Those agents that
do  not  cause  local  necrosis  include  cisplatin,  bleomycin,  cytarabine,
cyclophosphamide, L-asparaginase, methotrexate, thioptepa, and  fluorouracil.
Treatment  for vinblastine and vincristine extravasation include injection of
hyaluronidase subcutaneously or intradermally  into  the  leading edge of the
extravasation,  and  warm  compresses  for  2  days.    For   mechlorethamine
extravasation  inject  isotonic  sodium thiosulfate subcutaneously around the
involved area, and  apply  cold  compresses  for  48 hours.  For doxorubicin,
daunorubicin and mitomycin extravasation apply dimethylsulfoxide (DSMO)  over
the  involved  area  (air dry and leave uncovered), and apply cold compresses
for 2 days.  All infusions  should  be  terminated for extravasation, and the
extremity should be elevated.

                   -CEREBELLOPONTINE ANGLE TUMORS-
Most cerebellopontine angle lesions are caused by acoustic neuromas (80-90%).
Meningiomas  account for 5-10%, and epidermoids such as cholesteatoma account
for 5-7%.  Acoustic  neurormas  usually  present  with progressive unilateral
hearing loss, tinnitus, and unsteadiness.  Late in the disease there  may  be
facial  nerve involvement.  Tumors that are > 3 cm may cause trigeminal nerve
involvement with changes in  the  corneal  reflex.  Calcified meningiomas may
present with the  same  findings  as  acoustic  neuromas,  but  facial  nerve
involvement  may be seen earlier, and hearing loss is usually a late finding.
Other  causes  of  cerebellopontine  angle  lesions  include  arachnoid cyst,
aneurysm, metastases, trigeminal neuromas and neurinomas of the 9, 10, 11, 12
cranial nerves, dolichobasilar ectasia, and spread of  (pituitrary  adenomas,
craniophayngiomas,  brain stem or cerebellar gliomas, glomus jugulare tumors,
choroid plexus  papilloma  from  the  4th  ventricle  through  the foramen of
Luschka, chordomas and tumors of the skull base, and primary  tumors  of  the
temporal bone such as carcinomas and sarcomas).

                         -CEREBRAL ABSCESS-
Brain abscess can be caused  by  a  contiguous focus of infection from otitis
media, calvarial osteomyelitis, dental infection, or sinusitis,  hematogenous
dissemination  from  a distant area such as cardiac valves, lung, skin, bone,
abdomen    and    pelvis,    or    head    trauma    and   post-neurosurgery.
Hematogenous-caused brain abscesses tend to be multiple and multiloculated as
opposed to the contiguous-spread brain abscesses which tend to  be  solitary.
The  average  age  of  brain  abscesses is 30-40 years of age, but ultimately
depends on the cause.  About  25%  of  brain abscesses occur in children that
are less than 15 years of age.  There has been  considerable  improvement  in
the  mortality  rate  over  the  last few years due to advances in CT and MRI
scanning resulting in earlier diagnosis  and treatment.  At the present time,
the mortality rate is about 5-10% which is  considerably  improved  over  the
previous  mortality rate of 40-60% About 60-70% of brain abscesses are caused
by aerobic, microaerophilic and anaerobic streptococci which normally live in
the oral cavity, female  genital  tract  and appendix.  Staphylococcus aureus
accounts for about 10-15% cases  of  brain  abscess,  especially  those  that
originate  from  bacterial endocarditis and head trauma.  Bacteroides species
can be isolated in about  20-40%  of  cases.  Patients that have otitis media
cause brain absecesses that harbor Proteus species,  Klebsiella,  Pseudomonas
species  and  Escherichia  coli.   Fungi  can  also  cause  brain  abscess in
immunocompromised  patients.   Patients  that  have  neutropenia  may develop
Aspergillus,  Candida  and   Rhizopus   cerebral   abscesses.    Cryptococcus
neoformans  may  cause  brain  abcesses,  but  more likely cause meningtitis.
Mycobacterium  tuberculosis  can  cause  tuberculomas.   Actinomyces  species
causes  brain  abscess  from   odontogenic   and  pulmonary  foci.   Listeria
monocytogenes   and   Nocardia   asteroides   cause   brain   abscesses    in
immunocompromised  patients.  AIDS patients can cause Toxoplasma gondii brain
lesions.  Other  causes  of  brain  abscess  are  cysticercosis and Entamoeba
histolytica.  CLINICAL: Brain abscesses occur  between  the  ages  of  30-40,
whereas  cerebral  tumors  and  cerebral metastasis occur between the ages of
55-60.  Patients present with headache,  fever  and focal changes mainly, but
there may also be seizures and mental changes.  Seizures occur in  about  25%
of  patients.   Fever  only occurs in 50% of patients and in elderly patients
fever is characteristically absent.   About  20%  of  brain abscesses have no
source of infection.  Most cerebral  abscesses  occur  superficially  in  the
frontal  and  parietal  lobes and about 75% are solitary.  Toxoplasma gondii,
however, tends to occur in the basal ganglia.  Frontal lobe abscesses usually
arise from the sinuses and temporal  lobe or cerebellar abscesses from otitis
infections.  Blood cultures are only positive in about 10-20 % of cases.  The
WBC and sed rate may be elevated.  Lumbar puncture is not  usually  indicated
and may be contraindicated.  The spinal fluid analysis usually is not helpful
unless there is a concomitant meningitis.  CT scans of the sinuses, ears, and
mastoids  should  be  obtained.   Dental history and x-rays should be carried
out.  CT of the head  will  show  changes  from  focal cerebritis to a mature
capsule formation.  This evolution usually  takes  about  2  weeks.   In  the
cerebritis  stage  the  CT will show a non-enhancing focal low density lesion
and the MRI will show  a  hypointense lesion.  Ring enhancing usually doesn't
occur until about 3 days and at this stage there may be no clinical symptoms.
Most patients will present with a ring enhancing mass.  Air may  be  seen  in
the  mass,  which  helps  in  diagnosing  the  lesion  as  an  abscess.   The
surrounding  edema  of  abscesses  tends to be less than that seen with brain
tumors.  The abscess may  rupture  into  the ventricles and satellite lesions
may be seen.  Steroid administration can decrease the  temperature  and  also
reduce  the  size of the mass and surrounding edema.  DIFFERENTIAL DIAGNOSIS:
Brain abscess is usually diagnosed by  CT  or MRI.  Ring enhancing masses are
typically seen.  However, ring enhancing masses may also be seen  in  tumors,
cerebral   infarction,   radiation  necrosis,  acute  demyelinating  disease,
granulomas and resolving cerebral  hematomas.   Neoplasms are the most common
cause of  ring  enhancing  masses  and  are  caused  mainly  by  gliomas  and
metastasis.   The  average age for presentation for these two are 55-60 years
of age.  Brain tumor produces  headache,  seizures, mental changes, and focal
weakness.  The headache is  usually  relieved  early  by  analgesics  and  is
usually  more  severe  in the morning hours.  About 33% of brain tumors cause
seizures.  If the tumor  is  located  in  the  posterior fossa or the patient
develops hydrocephalus, gait ataxia may be present.  Lesions  that  occur  in
the  frontal, temporal or occipital lobes may be silent.  Frontal lobe tumors
may produce inattention, apathy and  abulia.  Temporal lobes tumors can cause
olfactory hallucinations and personality alterations.  Occipital lobe  tumors
may produce visual field defects that are silent as far as patient awareness.
The  onset  of  brain  tumors  is usually subacute unless there is hemorrhage
within the tumor  which  then  can  present  as  a  stroke.  Brain metastasis
usually originate from  cancers  of  the  lung,  breast,  or  melanomas,  but
prostate,  ovarian  carcinomas and even sarcomas may metastasize to the brain
occasionally.  Lymphomas may metastasize to  the  brain, but account for only
1% of brain tumors.  About 25% will of lymphoma patients will  have  multiple
lymphomatous  brain  lesions.  Malignant gliomas are multifocal in only about
5% of cases.  Clinically significant  hemorrhage into the tumor occurs mainly
in metastatic lesions from melanomas, choriocarcinomas,  renal  cell  cancers
and  bronchogenic cancers.  Calcification in brain tumors is mainly seen with
oligodendrogliomas.  Gliomas  characteristically  spread  through  the corpus
callosum to the opposite  hemisphere.   BASICS  OF  ANTIBIOTIC  THERAPY:  The
organisms that are cultured from various sites of origin for cerebral abscess
is  well known, and therapy may be started empirically before stereotactic CT
guided aspiration of the abscess  is  carried  out.   Those sites that have a
high rate of isolation of streptococci  are  treated  with  penicillin  G  or
cefotaxime  of  ceftriaxone.  Penicillin G is also useful for Actinomyces and
Fusobacterium anaerobic species.  However,  it  is  not active active against
Bacteroides fragilis which occurs in about 20-40% of  brain  abscesses.   For
Bacteroides  fragilis metronidazole should be used if possible because it has
several favorable attributes over  alternative  anaerobic antibiotics such as
chloromycetin   and   clindamycin.    Metronidazole   achieves   very    high
concentrations  within  the abscess, is bactericidal, and its influx into the
abscess is  not  affected  by  concomitant  steroid  therapy.  Staphylococcus
aureus is common after cranial trauma and following neurosurgery.   Nafcillin
should  be used in these cases unless the patient has a methicillin resistant
Staph aureus or  is  allergic  to  penicillin.   If  the  latter  is the case
vancomycin should be used.  For patients that  have  a  high  likley-hood  of
infection  with  the Enterobacteriaceae such as otitis patients, treatment is
with a third generation  cephalosporin or trimethoprim-sulfamethoxazole.  For
Pseudomonas aeruginosa, ceftazidime is the drug of choice.  If  a  Norcardial
cerebral   abscess  is  suspected  sulfonamides  either  given  alone  or  in
combination with trimethoprim is  a  good initial choice.  EMPIRICAL THERAPY:
SINUSITIS: If the patient has CT findings consistent with  sinusitis  of  the
frontal, ethmoid or sphenoid sinuses the patient most likely is infected with
Bacteroides  species,  Enterobacteriaceae, Streptococci, Haemophiulus species
or Staphylococcus aureus.  The patient  may  be  started on vancomycin 1 gram
every 12 hours + metronidazole 30 mg/kg/day given every 6 hours + ceftriaxone
2 grams IV every 12 hours.  DENTAL INFECTION:  Dental  infection  is  usually
caused  by  streptococci,  Bacteroides species and Fusobacterium.  These will
respond to Penicillin giving 4 million units IV every 4 hours + Metronidazole
30 mg/kg/day given every  6  hours.   OTITIS MEDIA AND MASTOIDITIS: Bacterial
isolates recovered usually consist  of  anaerobic  or  aerobic  streptococci,
Enterobacteriaceae and Bacteroides species.  These will respond to penicillin
4  million  units IV every 4 hours + metronidazole 30 mg/kg/day given every 6
hours + ceftriaxone 2 grams IV every  12 hours or Cefotaxime 2 grams IV every
4 hours.  LUNG ABSCESS, BRONCHIECTASIS, or EMPYEMA: Organisms  obtained  from
these  sites  include Bacteroides species, streptococci, Nocardia asteroides,
Actinomyces and Fusobacterium.   Treatment  consists  of penicillin 4 million
units IV every 4 hours + metronidazole 30  mg/kg/day  given  as  equal  doses
every  6  hours  +  Trimethoprim-sulfamethoxazole 10 mg/kg/day (trimethoprim)
given every 12 hours.   BACTERIAL  ENDOCARDITIS: Common organisms isolated in
bacterial  endocarditis  include  streptococci  and  Staphylococcus   aureus.
Empirical  treatment  would  consist of vancomycin 1 gram IV every 12 hours +
gentamicin 3-5 mg/kg/day given every  8  hours IV.  CONGENITAL HEART DISEASE:
Haemophilus speicies and streptococci are common bacterial organisms cultured
out in congenital heart disease.  If congenital heart disease is suspected as
the cause of brain abscess begin therapy with penicillin 4 million  units  IV
every  4  hours  +  ceftriaxone  2 grams IV every 12 hours or Cefotaxime 8-12
grams/day given every 4-6  hours.   POST  NEUROSURGERY OR PENETRATING CRANIAL
INJURIES: Common infectious agents in this situation  include  Staphylococcus
aureus,  streptococci,  Clostridium and enterobacteriaceae.  Treatment before
cultures have been obtained is  with  vancomycin  1  gram IV every 12 hours +
ceftriaxone 2 grams IV every 12 hours or Cefotaxime 2 grams IV every 4  hours
IV.   Patients  may  be  treated with surgery plus antibiotics or antibiotics
only.  Patients that  are  treated  with  antibiotics  alone include multiple
abscesses, cerebral abscess plus meningitis or ependymitis, abscesses smaller
than 3 cm, cerebritis  that  resolves  with  antibiotics,  deep  inaccessible
locations  of  the  abscess,  and  patients  that  are at high risk for brain
surgery.  If the patient has  not  had  surgical excision of the abscess, but
has been treated soley with antibiotics, the patient should  be  treated  for
about 4-6 weeks with IV therapy.  Following the IV therapy, oral therapy with
an appropriate agent may be continued for another 2-6 months.  If the patient
has  had  surgical  extirpation  of  the abscess, treatment with high dose IV
antibiotics are given for  about  3-4  weeks.   Of  course, if the patient is
immunocompromised, antibiotic treatment must be prolonged and in case of  HIV
infection  must,  in  many  cases,  be  put on maintenance therapy.  In AIDS,
Toxoplasmosis is the most common cause of multiple enhancing brain lesions as
seen on CT or MRI.   Treatment  of Toxoplasmosis is with pyrimethamine 25-100
mg/day orally given once a day + sulfadiazine 4-6  grams/day  given  every  6
hours orally.

                      -CEREBROVASCULAR DISEASE-
ETIOLOGY:  TRANSIENT  ISCHEMIC  ATTACKS  (TIA)  may  originate from ulcerated
plaques in the extracranial  portion  of  the  carotid artery, vegetations on
heart valves, atrial fibrillation, valvular prostheses, mechanical kinking of
vessels during rotation of the head, and  transient  hypotension.   Transient
ischemic attacks in the carotid system manifest by amaurosis fugax (transient
monocular blindness on the side of the lesion), contralateral hemiparesis and
sensory  deficit,  and aphasia if the dominant hemispehre is involved without
loss of consciousness.  Many  patients  with  carotid  stenosis will not have
bruits and false positive bruits over  the  carotid  may  be  heard  in  10%.
Transient   ischemic   attacks  in  the  vertebrobasilar  system  consist  of
unilateral or  bilateral  visual  field  defects  (posterior  cerebral artery
insufficency),  vertigo,  ataxia,  diplopia,   dysarthria,   hemiparesis   or
hemisensory loss, and rarely drop attacks.  Transient ischemic attacks in the
subclavian   steal   syndrome   consist   of  symptoms  from  vertebrobasilar
insufficiency and claudication  of  an  exercised  arm  due  to subclavian or
innominate  artery  occlusion  with  reversal  of  flow  in  the  ipsilateral
vertebral artery.  Transient global amnesia may  be  due  to  vertebrobasilar
insufficiency  and  is manifested as an abrupt memory loss and confusion.  It
tends to be more common in  men.  CEREBRAL THROMOBOSIS may be associated with
diabetes, syphilis, TB, polyarteritis nodosa, temporal arteritis, SLE, trauma
to the  head or neck,  shock,  surgical  anesthesia,  vigorous  treatment  of
chronic  hypertension, myocardial infarction, heart block, polycythemia vera,
DIC, sickle cell anemia,  thrombocytopenic purpura, epsilon aminocaproic acid
and oral contraceptives.  Obstruction of the middle cerebral artery  consists
of  contralateral  hemiplegia,  homonymous  hemianopsia,  hemianesthesia, and
expressive and receptive  aphasia  if  the  dominant  hemisphere is involved.
There is more involvement of the face and arm than the leg.   Obstruction  of
the  anterior cerebral artery usually affects the contralateral leg more than
the face and arm.  There  often  is grasping and suckling present.  Occlusion
of the posterior cerebral  artery  will  show  homonymous  hemianoptic  field
defects, and disturbance in reading, visual learning, recognition and spatial
orientation  if  the  dominant  hemispehre is involved.  Brainstem infarction
presents as ipsilateral  cranial  nerve  palsy  and contralateral hemiplegia.
Midbrain infarction may present as Weber's syndrome  (ipsilateral  oculomotor
paresis  and  contralateral hemiparesis) or Nothnagel's syndrome (ipsilateral
oculomotor palsy, paralysis of gaze, and ipsilateral ataxia of gait.  Pontine
infarction may present as the Millard-Gubler syndrome (ipsilateral facial and
abducens palsy, contralateral hemiplegia and  loss of position and vibration)
or Foville's syndrome (the same symptoms as in Milard-Gubler syndrome + palsy
of gaze to the side of the lesion.  Occlusion  of  the  vertebral  artery  or
posterior   inferior   cerebellar   artery  causes  the  Wallenberg  syndrome
(ipsilateral decreased pain sensation of the face, ipsilateral paresis of the
palate  and  vocal  cord  (dysphonia  and  dysphagia),  ipsilateral  Horner's
syndrome, ipsilateral  ataxia  of  the  extremities,  contralateral  pain and
temperature loss in the limbs and  trunk,  nystagmus,  nausea  and  vomiting.
Lacunar infarction results from occlusion of the deep penetrating branches of
the  large  cerebral  arteries.   It  can  cause  localized infarction of the
internal  capsule  or  pons  resulting  in  pure  motor  hemiplegia,  pontine
infarction  (dysarthria/clumsy  hand  syndrome),  thalamic  infarction  (pure
sensory  stroke  involving  the  face,  arms  and  legs,  capsular infarction
(ipsilateral ataxia and spastic weakness).  CEREBRAL EMBOLISM  can  originate
from  the  heart  from mitral stenosis and/or atrial fibrilaltion, prosthetic
heart valves,  mitral  valve  prolapse,  bacterial  and nonbacterial marantic
thrombotic endocarditis associated with cancer, cardiac  myomas,  ulcerations
or   plaques  of  the  extracranial  carotid  arteries,  and  mural  thrombus
associated with myocardial infarction.   INTRACRANIAL BRAIN HEMORRHAGE may be
secondary to arterivenous malformations, hypertension, deep seated aneurysms,
anticoagulant therapy, leukemia, hemophilia, DIC, sepsis with vasculitis, and
liver  failure.   Cerebellar  hemorrhage  may  present  as  sudden  headache,
vomiting, ipsilateral ataxia, lower motor neuron facial palsy, and gaze palsy
to the side of the lesion.  There  may  be  abnormal  pupillary  and  corneal
reflexes,  transtentorial  herniation, high CSF pressure, and disturbances in
the sensorium.  SUBARACHNOID HEMORRHAGE is  mainly due to ruptured congenital
aneurysms.  Other causes include bleeding disorders,  anticoagulant  therapy,
hemorrhage  from  a  tumor  or arteriovenous malformation, and trauma.  These
patients may  present  with  stupor,  hemiparesis,  decerebrate rigidity, and
coma.  The greatest risk of rebleeding is seen during the first 2 weeks after
the original bleed.  Suspect a subarachnoid hemorhage  if  there  is  sudden,
terrible  headache,  nuchal  rigidity,  confusion,  oculomotor nerve paresis,
focal neurologic deficit, bruit over the skull (AV malformation), bloody CSF,
and subhyaloid  retinal  hemorrhages.   TONIC  DEVIATION  OF  THE EYES: Tonic
deviation of the eyes may be a clue to the  type  and  site  of  involvement.
Tonic  deviation  to  the  involved side of the brain indicates a capsular or
putamen hemorrhage.   Tonic  deviation  of  the  eyes  to  the  opposite side
suggests a cerebellar hemorrrhage or pontine lesion.  Paralysis of  conjugate
gaze  associated with pinpoint light reactive pupils and flaccid quadriplegia
suggets  a  pontine  lesion.   Tonic  deviation  of  the  eyes  downward with
unreactive pupils, and paresis of conjugate upward gaze suggests a lesion  of
the pretectum or a thalamic hemorrhage.

                     -CERVICAL SPINE SYNDROMES-
Most patients that you will see,  will  present with a non radiculopathy or a
cervical  radiculopathy.   Both  of  these   conditions   will   respond   to
conservative measures.  How these respond will depend on many factors such as
co-existing   cervical   findings,   age,  litigation  and  basic  underlying
personality of the patient.   As  one  ages,  degenerative changes take place
that may be the cause of the radiculopathy or just be incidental when seen on
investigative studies.  As one ages, the gelatinous nucleus of the disk dries
out and the annulus loses  its  elasticity  and  the  facet  joints  take  on
osteoarthritic  changes.   The  uncovertebral joints of Luschka produce spurs
that can squeeze out the nerve  roots.   CLINICAL: When a patient presents to
you, your  first  task  is  to  determine  whether  the  pain  is  due  to  a
radiculopathy,  non-radicular neck pain, a cervical spondylotic myelopathy or
instability.  This can  be  done  immediately  by  just  putting together the
patients symptoms.  If there is neck pain that radiates to the arm  or  hand,
then this may be a radiculopathy caused by nerve root compression from a bone
spur  or  herniated  disk.   If  there  is only neck pain, this may just be a
muscle spasm or disk degeneration  and represent a non-radicular pattern.  If
the patient reports numbness, loss of bowel or bladder control, this may be a
cervical  spondylotic  myelopathy  due  to  cervical  stenosis.   Also,   the
situation   in   which   the   symptoms  occur  should  also  be  taken  into
consideration.  If this  is  a  motor  vehicular  accident,  then fracture or
dislocation may be present.  Open mouth views for C1  and  C2  visualization,
full  lateral  cervical  spine  including  C7, and oblique views to check for
fracture of the posterior processes should be done.  If the patient has signs
of infection, as fever, then  sepsis  with spinal abscess is a consideration.
If there is any history of carcinoma, such as breast, kidney,  lung,  thyroid
or  prostate,  metastasis  to cervical spine is always a possibility.  In any
patient around 50 years  of  age,  multiple  myeloma  also must be ruled out.
CERVICAL RADICULOPATHIES: Cervical radiculopathies  represent  about  10%  of
cervical  spine  disease.   If  the  patient is under the age of 45, then the
radiculopathy may be due to herniation  of the soft nuclear material from the
disk and resolution is usual with conservative measures.  If the  patient  is
over  45  years  of age then osteophytes and calcification of the annulus may
compromise the nerve roots.  The pain  in  this group usually never goes away
completely, and there will  be  exacerbations  and  remissions.   An  MRI  is
probably  the  procedure  of choice to identify the structure of the cervical
spine.   However,  the  specific  nerve  root  that  is  involved  cannot  be
ascertained with certainty.  CT with  intrathecal contrast is usually used if
the MRI doesn't show the pathology.  Myelography also is used  to  confirm  a
diagnosis  of  radiculopathy,  and  also  to  rule  out  infection  or tumor.
Myelography is less sensitive than  MRI  or CT with intrathecal contrast, and
can miss central soft disk  lesions.   Patients  also  have  pain  with  this
procedure,  and there can be false positives with myelography.  Most cervical
spine radiculopathies involve C6  and  C7.   If  there  is a C6 radiculopathy
there will be pain in the lateral arm, radial forearm, thumb and index finger
associated with weakness in the biceps,  wrist  and  thumb  extensors  and  a
diminished  biceps reflex.  If there is a C7 radiculopathy the pain is in the
posterior arm, radial forearm and the  index and long fingers.  There will be
triceps and finger extensor weakness and the triceps  reflex  is  diminished.
C8 radiculopathies are fairly rare, but when present are usually more severe.
There  is  pain in the medial forearm, ulnar palm and the 4th and 5th digits.
There  is  weakness  of   the   intrinsic   muscles   of  the  hand.   In  C5
radiculopathies there is shoulder and lateral arm pain and  weakness  of  the
deltoid  and  biceps  muscles  that  is  very  severe.  TREATMENT OF CERVICAL
RADICULOPATHIES: Most cervical disk  herniations  involving  C6 and C7 can be
managed conservatively.  C5 radiculopathies  may  be  so  severe  that  early
surgery  must  be  done  to  save  the  motor  function.  Surgery consists of
anterior diskectomy and  interbody  fusion  or laminectomy-foraminotomy.  The
results or these two procedures are comparable.  That is, if there is  a  one
level  procedure,  the  results for pain relief is 93 % and 85% for a 2 level
procedure.  However, like  all  other  injuries  that  may be associated with
workers compensation and or  litigation,  the  results  are  poor  until  the
litigation  is  settled.   Also,  any  person that is dysfunctional with many
somatic complaints and depression, will not respond optimally.  Alcoholic and
drug  abuse  is  another  subset   of  patients  that  do  poorly.   CERVICAL
SPONDYLOTIC MYELOPATHIES: Patients may be older men with  several  levels  of
cord  compression  seen  at  C3-4,  C4-5  and C5-6.  There is lower extremity
weakness, poor balance, difficulty  with  gait  and  paresthesia in the upper
extremities.  Ultimately, the patient may lose bladder  and  rectal  control.
The  cause  is  usually  due  to  multiple degenerative bone spurs at several
levels.  Men are affected  more  commonly  than  females,  and the patient is
usually over the age of 55.  Large central  disk  ruptures,  spinal  cord  or
epidural   tumors,   multiple   sclerosis,  diabetic  polyradiculopathy,  and
arteriovenous malformation all must be ruled out prior to surgery, which will
be needed for stabilization.  TREATMENT OF CERVICAL SPONDYLOTIC MYELOPATHIES:
The anterior approach  with  anterior  diskectomy  with  or without interbody
fusion is usually done if there are 1-2 sites of  involvement.   If  multiple
levels must be addressed, then laminectomy with wide decompression is usually
a  better  approach.   The  latter  may result in instability of the cervical
spine because  of  the  multiple  wide  laminectomies.   If  the  patient has
cervical kyphosis, then the posterior approach is contraindicated because the
site of cord compression is usually anterior.  Patients must be told that the
surgery is done to prevent further cord compromise and that stabilization  of
the  spine  will  not undo previous cord damage.  INSTABILITY OF THE CERVICAL
SPINE: Instability due to rheumatoid arthritis and trauma are major causes of
instability.  If there is subluxation  greater than 4mm, then the probability
of cord compression increases, and if there is any disturbance of upper motor
function surgery may be indicated.   Surgery  usually  comprises  fusion  and
internal fixation to stabilize the spine and prevent cord compression.

                          -CHAGA'S DISEASE-
Chaga's  disease,  also  known  as  American  Trypanosomiasis  is a protozoan
disease of humans and mammals  that  is  caused  by Trypanosoma cruzi.  It is
endemic in Mexico and Central America.  It is estimated 16-18 million  people
have  chronic  T. cruzi infection, and that 50,000 people expire from Chaga's
disease each  year.   About  20,000  new  cases  of  T  cruzi  in  Brazil are
transfusion associated.  Immigrants to the USA that  are  infected  with  the
parasite  are troublesome, as some of these will donate blood in the USA.  No
assay for detection has been licensed by  the FDA for use in blood banks, and
screening is not done.  Transplantation  of  body  organs  by  immigrants  is
another  problem in the USA.  Due to the large number of immigrants coming to
the USA, the disease is now appearing  in the South and Southwestern USA.  It
is transmitted by several species of triatomine bugs that become infected  by
ingesting   blood   from   infected  animals  and  humans  that  contain  the
trypanosomes.  These organisms then  multiply  in  the digestive tract of the
bug with production of infectious feces.  These bugs  (reduviid  bugs),  then
contaminate the conjunctiva, mucosal surfaces or skin bites with their feces.
The  infected organisms then spread hematogenously.  In about 2-5% of infants
born to infected women, the parasties  can  pass from the mother to the fetus
causing abortion or congenital Chagas's disease.  The parasite occurs  in  an
acute,  latent  and chronic stage.  Children are mainly affected in the acute
stage    producing    prolonged    fever,    tachycardia,    lymphadenopathy,
hepatosplenomegaly and myocarditis.   The  chronic  stage is characterized by
cardiac   failure   and   cardiac   arrhythmias,   dysphagia,   constipation,
megaesophagus and megacolon.  CLINICAL: The acute stage is  characterized  by
edema  of  the  eye (Romana's sign) or a furuncle-like lesion associated with
local lymphadenopathy (Chagoma).  These  local  manifestations are due to the
bite of the  bug.   The  patient  then  develops  headache,  fever,  malaise,
generalized  lymphadenopathy,  hepatomegaly  and  splenomegaly.   Muscle  may
become  parasitized  leading  to  myocarditis, and biventricular failure, The
parasite also  attacks  the  central  nervous  system,  usually  in children,
producing meningoencephalitis which can be fatal.  The acute illness  usually
lasts  about 4-6 weeks and then evolves into the latent stage.  Most patients
will remain in the latent  phase  which  can  last from 10-30 years.  In this
phase, the patient is usually asymptomatic,  but  some  may  have  low  grade
parasitemia  producing  subtle signs of GI and cardiac disease.  About 10-30%
will enter the chronic  phase  after  the  latent  phase.  In this phase, the
heart  is  chiefly  affected,  producing  biventricular  enlargement,   mural
thrombi,  apical aneurysms, and thinning of the ventricular walls.  There can
be right bundle branch block, left  anterior fascicular block, or complete AV
block due to widespread lymphocytic infiltration, interstitial  fibrosis  and
myocardial atrophy.  Sudden cardiac arrest can occur in young patients due to
ventricular  fibrillation.   Some  patients  will  develop megaesophagus, and
megacolon producing  dysphagia,  regurgitation,  aspiration and constipation.
These  latter  symptoms  are  common  in  Argentina,   Chile,   and   Brazil.
LABORATORY: Serological tests are usually enigmatic, because of their lack of
specificity.   False  positive  tests  are  typical  with  serum samples from
patients  with  leishmaniasis,  syphilis,   malaria,  and  collagen  vascular
diseases.    These   tests   consist   of   complement   fixation,   indirect
immunofluorescence and  hemagglutination,  and  enzyme  linked  immunosorbent
assays.    The  diagnosis  is  made  by  detection  of  the  parasites.   The
circulating forms of T. cruzi can  frequently  be seen on microscopic exam of
anticoagulated blood or buffy coat, and thick stained blood smears.   If  the
patient  is  immunosuppressed,  the  parasites  may  be seen in the CSF, bone
marrow and pericardial fluid.  A  definitive  diagnosis can be made in almost
all acute cases, and up to 40%  of  chronic  cases.   The  diagnosis  in  the
chronic stage can only be made by culture or xenodiagnosis.  Xenodiagnosis is
made  by  having  non-infected  bugs  of  the local major vector, feed on the
patient  and  then  examining  their  intestinal  contents  for trypanosomes.
Patients in the acute and the chronic stages should have blood cultures using
Nicolle-Novy-MacNeal medium, and then inoculated into laboratory mice or rats
3-10 days old.  TREATMENT:  The  treaatment  of  acute  and  chronic  Chaga's
disease is very difficult, due to the toxicity and the ineffectiveness of the
drugs.   Cure  is  usually  possible  in  the  acute phase, but not so in the
chronic stage.  Nifurtimox is given at  8-10 mg/kg/day in three divided doses
for 50-150 days.  Side  effects  include  weight  loss,  tremors,  peripheral
neuropathy,  hallucinations,  convulsions, and anorexia.  Benznidazole is the
drug of choice,  but  is  not  available  in  the  USA.   It  is given at 5-7
mg/kg/day for 30-120 days with  side  effects  similar  to  nifurtimox.   The
cardiomyopathy  is treated with diuretics.  Digoxin is poorly tolerated.  The
arrhythmias  can  be  treated  with  lidocaine,  procainamide,  quinidine and
amiodarone.  Patients should be watched for  proarrhythmias.   Patients  with
end  stage  heart  disease  may have cardiac transplantation.  However, after
cardiac transplantation many of these will  have reactivation of the T. cruzi
infection in the heart ,despite prophylactic preoperative treatment.

                             -CHANCROID-
Azithromycin 1 g PO once or ceftriaxone 250 mg IM once or  erythromycin  base
500 mg PO qid for 7 d. Alternatives: Amoxicillin 500 mg/potassium clavulanate
125 mg (Augmentin) PO tid for 7 d or ciprofloxacin 500 mg bid for 3 d.

         -CHLAMYDIA TRACHOMATIS (Urethral, cervical, rectal)-
Doxycycline 100 mg PO bid  for  7  d  or azithromycin(Zithromax) 1 g PO once.
Alternatives: Erythromycin 500 mg PO aid for 7 d or ofloxacin (Floxin) 300 mg
PO bid for 7 d or sulfisoxazole (Gantrisin) 500 mg PO qid for 10 d.

                              -CHOLERA-
Cholera,  caused by Vibrio cholerae, is an acute infection of the small bowel
characterized by a secretory  profuse  watery  diarrhea.  Vibrio cholerae are
ingested and colonize in the small intestine produceing an explosive onset of
rice like watery  diarrhea.   Vomiting  can  precede  the  diarrhea.   Vibrio
cholerae  serogroup 01 is a motile curved, short motile aerobic gram negative
rod with a single flagellum.  The  name  is derived from "vibrio" because the
organisms show vibration in wet preparations.  The cause of the diarrhea is a
protein  enterotoxin  synthesized  by  Vibrio  cholera.   The  organism  also
produces a neuraminidase and mucinase that hydrolyzes intestinal mucus.   The
toxins  activate  adenosine triphosphate (ATP) to form 3' 5' cyclic adenosine
monophosphate (cAMP)  which  stimulates  the  intestinal secretory mechanism,
mobilizing liquid and electrolytes from the  extracxellular  space  into  the
intestinal  lumen.   Vibrio  depends  on gastric acid, and patients that have
decresed amounts of acid or achlorhydria  are  more at risk.  The diarrhea is
massive with up to 15 liters being produced per day.  Individuals  living  in
endemic  areas gradually acquire immunity.  Cholera is spread by ingestion of
seafoods, water and other foods  that  have been contaminated by excrement of
individuals that are symptomatic or those who  have  asymptomatic  infection.
Cholea  occurs  in epidemics where there is crowding, poor sanitation, famine
and during wars.  In endemic  areas,  outbreaks usually occur during the warm
months affecting chiefly children, but epidemics can occur during any  season
affecting  all  ages.   Cholera  was almost unknown in the USA prior to 1991,
when epidemic cholera broke out  in  the Western Hemisphere, starting with an
outbreak in the coastal cities of Peru.  The organism was  biotyped  El  Tor,
which  is  found  to  be  endemic  in  Southeast Asia and in several areas in
Africa.  It has now spread to involve Mexico, South and Central America and a
few cases have been imported to  the  USA.  In 1991 frozen coconut milk which
was imported from Thailand produced  an  outbreak  of  cholera  in  Maryland.
Cholera  is especially common in Bangladesh, India and other regions of Asia.
Some cases have been transported into  Japan  and Australia which have led to
localized outbreaks.  CLINICAL: Cholera has an incubation period of 1-3 days.
Following this there may be a mild or fulminant form.  The onset  is  usually
sudden  producing  diarrhea and vomiting.  Stools often have a frequency of 1
liter/hour.   This  leads  to  loss  of  water  and  electrolytes,  metabolic
acidosis,   weakness,   muscle    cramps,   hypovolemia,   hemoconcentration,
hypotension, oliguria and anuria.  The stools are liquid, gray,  and  without
odor,  blood  or pus.  If left untreated there is circulatory collapse, renal
tubular necrosis and death  with  a  mortality  of  greater than 50%.  If the
patient is promptly treated with fluid and  electrolytes,  the  mortality  is
less  than  1%.   Most patients will be free of disease in about 2 weeks, but
some become chronic biliary carriers.   LABORATORY: Rectal swabs are cultured
which will reveal Vibrio cholerae.  Agglutination by specific  antiserum  can
identify  the  organism  as  serogroup  01.   TREATMENT: Patients with severe
disease are treated  with  IV  lactated  Ringer's  solution  or .9% IV sodium
chloride, delivered at 1-2  mL/kg/min  until  the  patient  is  normotensive.
Usually  a  total of 100 mL/kg will be needed in severe cases.  Potassium can
be  supplied  by  adding  10-15  mEq/L  to  the  IVs.   Vasopressors  are not
indicated.  Patients with mild to moderate infections  may  be  treated  with
oral  solutions giving 75 mL/kg over a 4 hour period.  The oral solution that
is used by the WHO uses a solution composed of 20 grams of glucose, 3.5 grams
of sodium chloride, 2.9 grams of  trisodium citrate dihydrate or 2.5 grams of
sodium bicarbonate, and 1.5 grams of potassium chloride added to one liter of
drinking water.  After the patient has been rehydrated  with  this  solution,
liberal amounts of the solution should be given dictated by the diarrheal and
vomitus  losses.   In areas where this may not be available, oral replacement
can be achieved by adding 1 teaspoon  of  table salt and 4 teaspoons of sugar
added to one liter of water.  Adults are treated with tetracycline 500 mg  PO
every  6  hours for 3 days.  Doxycycline can also be given as a single 300 mg
dose, which is almost  as  effective as tetracycline.  Tetracycline resistant
cases can be treated with Furazolidone at 100  mg  PO  q6h  for  3  days,  or
trimethoprim/sulfamethoxazole  (TMP/SMX) 5/25 mg/kg BID for 3 days.  Children
less than 8 years of age can be treated with Furazolidone at 5 mg/kg/day in 4
equally divided doses for  3  days,  or  TMP/SMX  5/25  mg/kg BID for 3 days.
Tetracycline can be used in children less than 8 years of  age,  but  with  a
small  risk  of  teeth discoloration.  If tetracycline is used in children it
can be given as 30-50 mg/kg/day in 4 divided doses for 2-3 days.  Antibiotics
are effective in reducing stool volumes  by  about 50%, and can eliminate the
diarrhea within 48 hours.

                        -CHOLESTASIS DISEASE-
DEFINITION  OF  CHOLESTATIC  JAUNDICE:  Elevated  alkaline  phosphatase  with
pruritus and possibly, but not always jaundice.  CAUSES OF ACUTE CHOLESTASIS:
1....Alcoholic hepatitis 2....Amyloidosis 3....Benign recurrent  intrahepatic
cholestasis  4....Cholestasis of pregnancy 5....Drug use..Augmentin, Anabolic
steroids,   Diabenese,   Contraceptive   steroids,   Danazol,   Erythromycin,
injectable gold compounds,  interleukin-2, Megace, Phenothiazine derivatives,
Bactrim 6....Hodgkins disease 7....Postoperative cholestasis 8....Sarcoidosis
9....Sepsis  10...Sickle  cell   anemia   11...Total   parenteral   nutrition
12...Toxic  shock syndrome 13...Viral hepatitis (especially type A) CAUSES OF
CHRONIC CHOLESTASIS: 1....Drug  use..Thorazine,  Diabenese, Floxapen, Haldol,
Imipramine, Dilantin, Orinase, Bactrim 2....Idiopathic  adulthood  ductopenia
3....Primary    biliary   cirrhosis   4....Primary   sclerosing   cholangitis
5....Sarcoidosis POSTOPERATIVE JAUNDICE:  In benign postoperative cholestasis
the  jaundice  typically  appears  2-10   days   after   surgery.    Although
aminotransferase  levels are not significantly elevated, jaundice may be deep
and the  serum  bilirubin  level  may  reach  as  high  as  40.  Patients are
otherwise healthy, and jaundice usually resolves by the  third  postoperative
week.   The  absence of stigmata of chronic liver disease and the presence of
nondilated bile ducts on  ultrasound  support  the diagnosis.  These patients
are often in ICU and the causes are  multifactorial.   The  pigment  load  of
multiple  blood  transfusions,  renal  insufficiency with decreased bilirubin
clearance, resorption of extravasated  blood,  hypoxemia and hypotension, use
of drugs and anesthetic agents and concurrent infection may  all  contribute.
SEPSIS:  These  patients  may become deeply jaundiced.  However, the liver is
actually normal, and the source of sepsis may be far removed from the biliary
tree.  It is also called "septic jaundice".  Typically, patients present with
overwhelming, usually gram  negative  sepsis.  Hyperbilirubinemia, usually of
conjugated bilirubin, may be profound and the serum bilirubin  may  reach  30
mg/dl.   Serum  aminotransferase  and  alkaline  phosphatase  may be slightly
elevated.  You must differentiate  from  septic cholangitis (liver is usually
tender), whereas  urosepsis,  pyelonephritis  or  pneumonia  suggests  septic
jaundice.      If    there    is    doubt,    get    endoscopic    retrograde
cholangiopancreatography.   HODGKIN'S   DISEASE:   Most   commonly  lymphomas
infiltrate the portal  tracts.   The  alkaline  phosphatase  is  raised,  but
jaundice  is  mild.  Fever is common.  Liver biopsy, laparoscopically guided,
may  increase  yield  as  there  is  patchy  distribution  of  involvement in
Hodgkins.  Occasionally a large lymph node will obstruct the  porta  hepatis.
CT  is  helpful  in  making this diagnosis.  DRUG USE: Bland cholestasis is a
reaction  caused  by  contraceptive  steroids.   Liver  biopsy  shows  little
inflammation.   Exudative  cholestatic  hepatis  can  result  from  drugs  as
erythromycin and thorazine.  Drug  induced  cholestasis  is usually mild, but
jaundice may be prolonged, occasionally launching a search  for  extrahepatic
obstruction.   The  associated abdominal pain, increased alkaline phosphatase
level and weight loss can strongly  suggest pancreatic neoplasm.  ERCP may be
done unnecessarily.  In general, an alkaline phosphatase elevated more than 2
times normal is a cause for concern, as is  progressive  elevation.   PRIMARY
BILIARY  CIRRHOSIS:  Primary  biliary  cirrhosis  affects middle aged females
predominantly,  but  all  ages  and   occasionally  men  as  well.   Alkaline
phosphatase is  elevated.   PBC  accompanies  hypothyroidism  and  autoimmune
thyroiditis.   Pruritus  is  present,  and the patient may have osteoporosis,
rheumatoid  and  psoriatic  arthritis,  Sjogren's  and  sicca  syndromes, and
Scleroderma.  There is an association between PBC and breast cancer.  95%  of
patients  have elevation of the mitochondrial antibodies.  Liver biopsy helps
stage the disease.  Cholestyramine  in  doses  up  to 16 grams/day can afford
symptomatic relief.  Despite profound cholestasis in these patients, jaundice
is rare.  If it occurs it is a  signal  of  impending  liver  failure.   Once
persistent  jaundice  evolves,  liver  transplantation  should be considered.
PRIMARY  SCLEROSING  CHOLANGITIS:  Primary   sclerosing  cholangitis  can  be
diagnosed  with  ERCP.   PSC  today  ranks  as  a  major  cause  of   chronic
cholestasis,  especially  among young men with underlying ulcerative colitis.
Some are asymptomatic.  More  typically  though,  these patientS present with
pruritus and sometimes abdominal pain and fever.   If  the  constricted  bile
ducts  close off, obstructive jaundice may develop.  SARCOIDOSIS: Sarcoidosis
can  be  diagnosed  by  liver  biopsy.   Even  then  the  finding  of hepatic
granulomas can sometimes create more questions than answers.   The  condition
is  often asymptomatic, but marked fatigue may be present.  Pruritus is not a
dominant feature.   Jaundice  is  not  common  but  can  occur.  Treatment of
hepatic sarcoidosis is not mandatory.  In symptomatic patients a brief course
of steroids may be efficacious.

         -CHRONIC OBSTRUCTIVE PULMONARY DISEASE (Treatment)-
The mainstay of treatment  for  COPD  is  with  bronchodilators.  It has been
reported that ipratroprium and nebulized atropine provide a greater degree of
bronchodilation than usual doses of Beta  agonists.   However,  when  maximal
doses  of beta agonists are given, the degree of bronchodilation may be about
equal.  At any rate,  both  are  effective  for  acute exacerbations of COPD.
Neither will potentiate the action of the other.  Ipratropium  (Atrovent)  is
better  used  on a regular basis than a PRN basis as it has a slower onset of
action and longer duration of action.   It  will reduce the volume of sputum,
but will not change its viscosity.  The convential dose  of  Ipratropium  has
been  two  puffs  four  times  a day.  Because ipratropium is well trolerated
without appreciable side  effects,  giving  3-6  puffs  QID  will enhance its
bronchodilating properties.  Beta agonist  and  ipratropium  should  both  be
given  with  a MDI and spacer.  Beta agonist are typically given as 2-6 puffs
every 3-6 hours.  However,  as  the  number  of  puffs is increased, the side
effects will increase.  A number of beta agonists are  available  as  metered
dose   inhalers   (MDI).    These   include   isoproterenol,  metaproterenol,
isoetharine,   terbutaline,    albuterol,    pirbuterol,    and   bitolterol.
Theophylline has its most beneficial effects when  given  at  bedtime.   When
given  in  this fashion it can reduce nocturnal decreases in FEV1 and morning
symptoms.  Theophylline preparations have  little bronchodilating effect over
that of inhaled medications, but can  improve  respiratory  muscle  function,
mucociliary   clearance,   increase   collateral   ventilation,  and  central
respiratory drive.  Long acting  theophylline  preparations are used in doses
of 300-900 mg/day aiming at a serum level of 8-12 ug/ml.  They are the  third
line  of  therapy  after  ipratropium  and  beta  agonists.   Steroids may be
beneficial  in  a  certain  percentage  of  patients  with  COPD,  but  it is
impossible to predict who will be helped.  Steroids are given as a last  step
in  those who are being treated maximally with the above medications, but are
not improving.  Intermittent daily steroid  therapy should be given as needed
in those who do respond, such as prednisone 40 mg/day for 14 days.  Long term
treatment should only be  used  in  those  patients  who  have  a  documented
improvement in airflow or exercise performance.  Giving steroids on alternate
days  or  via inhalation has not been shown to be helpful.  Reduction of risk
factors is also important in patients  with COPD.  These risk factors consist
of continuation of cigarette smoking, occupational exposures  to  particulate
dusts,  air  pollution, IV drug abuse and talcosis.  Cessation of smoking can
slow the rate of decline of the FEV1 in smokers so that it approaches that of
the non smoker.  This  can  be  accomplished with nicotine patches, clonidine
patches and nicotine gum.  Prevention of hypoxemia by oxygen therapy is  also
important.   The  goal of therapy is to keep oxygen saturation > 90%.  Marked
hypoxemia may occur  during  exercise  or  nocturnally,  even  in the face of
normal day time oxygen saturations.  By giving oxygen therapy nocturnally one
can decrease nocturnal arrhythmias and improve daytime performance.  Portable
oxygen devices are now available as reservoirs and  demand  delivery  devices
that  will  prolong  the  supply.  Transtracheal devices are used in patients
that require  high  oxygen  requirements.   The  recommended  indications for
supplemental oxygen in COPD is as folllows: PaO2 < 55 mm Hg or SaO2 < 89%  at
rest  or  PaO2  < 55 mm Hg or SaO2 < 89% with exercise, or PaO2 < 55 mm Hg or
SaO2 < 89% during sleep, polycythemia and a PaO2 of 56-59 mm Hg or SaO2 < 90%
at any time, or evidence  of  pulmonary hypertension or cor pulmonale, mental
or psychological impairment.  Medicare indications  for  supplemental  oxygen
therapy  that is reimbursable are PaO2 <55 mm Hg or SaO2 < 88%, PaO2 56-59 mm
Hg or SaO2 < 89% if there is evidence of cor pulmonale (polycythemia, CHF, or
P pulmonale).  Treatment  of  pulmonary  hypertension  and  Cor Pulmonale are
difficult.  Oxygen is the main therapy.  Digoxin is not used unless there  is
concomitant  left  sided  heart  failure.   Vasodilators  are  not  useful of
pulmonary hypertension.  Theophylline will improve right ventricular function
and exercise performance and has shown some pulmonary vasodilating properties
and  positive  cardiac   inotropic   effects.    Patients   that  have  acute
exacerbations may be improved with terbutaline as they may decrease pulmonary
pressures and resistance.  Phlebotomy is used for polycythemia to  lower  the
hematocrit to 50%.

                     -CIGUATERA FISH POISONING-
Many patients with Ciguatera fish poisoning that seek medical attention  from
symptoms of gastroenteritis are missed.  A patient that presents with nausea,
vomiting,  diarrhea,  diaphoresis  and  numbness  and  tingling, particularly
around the mouth,  may  be  mis-diagnosed  as  hyperventilation syndrome plus
viral gastroenteritis.  Key points to differentiate Ciguatera fish  poisoning
from  the  garden  variety  gastroenteritis  are:  Ciguatera  fish  poisoning
produces  a  phenomenon  known  as  sensory  reversal  dysesthesia, whereby a
patient perceives cold objects as warm  and vice versa.  The second key point
is that alcohol will produce a return of the symptoms or a worsening  of  the
symptoms.   The  third  point  is that Ciguatera fish poisoning will last for
about 1-2 weeks and  about  50%  of  patients  will  still have symptoms at 2
months.    The   neurologic   symptoms   persist   much   longer   than   the
gastrointestinal symptoms.  Ciguatera poisoning is contracted by eating  fish
that  harbor the single cell toxic producing parasite, Ganbierdiscus toxicus.
There are more than 400 fish species  that live around coral reefs and harbor
the parasite.  Ganbierdiscus toxicus attaches itself  to  marine  algae,  and
small  fish  will  eat  the algae.  Larger fish will eat the smaller fish and
thus a poisoning  chain  is  set  up.   In  particular, grouper, red snapper,
amberjack, barracuda, sturgeon fish, jack tuna, sea bass, moray eels and king
mackerel are the common fish involved with this infestation.  The larger  the
fish,  the  larger  the concentration of the poisonous toxin, and the greater
the magnitude of the symptoms.  Fish  under  5 pounds are relatively safer to
eat than those over 25 pounds.  Ciguatoxin cannot be deactivated by  cooking,
freezing,  drying,  smoking,  marinating,  salting,  or pickling, and gastric
enzymes and  acids  will  not  inactivate  it.   The  toxin  is tasteless and
odorless.  The toxin doesn't cause any ill affects in the fish,  even  though
there  are  high  concentration  in the viscera such as the gonads and liver.
Florida and Hawaii are common states  that  have a higher incidence, but with
modern transportation any state can be affected.  Ciguatera fish poisoning is
endemic in tropical regions as the Caribbean and  the  Indo-Pacific  islands.
CLINICAL:  Approximately  2-24  hours  after  ingesting  the  affected fish,
nausea, vomiting, watery diarrhea, abdominal cramps, myalgias and diaphoresis
will begin.  The abdominal  symptoms  usually  last  about  3 days but can be
longer.   Eighty  percent  of  patients  will  develop  paresthesias  of  the
extremities, numbness and tingling around the mouth and hot and cold reversal
as mentioned above.  The patient may also have dizziness,  ataxia,  pruritus,
facial  pain,  rash,  tremors,  nuchal  rigidity, and rarely audio and visual
perturbations,  confusion  and   coma.    TREATMENT:   Treatment  is  mainly
supportive with IV fluids and electrolyte replacement.  The pruritus  may  be
managed  with  terfenadine  60 mg bid.  Amitriptyline, 25 mg bid may help the
pruritus and the dysesthesias.  Mannitol 20%, 1 gram/kg given over 30 minutes
may help in the severe cases.   The  patient  should be told to avoid alcohol
and further fish ingestion.

                            -CIPROFLOXIN-
Ciprofloxin has an excellent sprectrum  of  activity,  but  suffers  in  some
coverage.   It was introduced in the USA in 1987 as the first oral antibiotic
that had activity  against  Pseudomonas  aeruginosa.   Ciprofloxacin has only
modest activity against S. pneumoniae and anaerobes.  For this reason  it  is
not  the  drug  of  choice  for  community  acquired  pneumonia or aspiration
pneumonias.   Otherwise,  it  has  excellent  activity  against  other common
respiratory pathogens  seen  in  community  acquired  pneumonia  such  as  H.
influenze,  chlamydia,  M. catarrhalis, and legionella.  It has cure rates of
greater than 80% in nursing home, hospital and community acquired pneumonias.
For hospital pneumonias, IV  ciprofloxacin has comparable therapeutic effects
to  broad  spectrum  beta  lactams,  including  ceftazidime,  for  sepsis  in
neutropenic patients, hospital acquired pneumonia or gram negative  bacillary
infections.   In  addition,  it  is  active against N. gonorrhoeae (including
penicillin resistant strains),  M.  tuberculosis,  Legionella pneumophila and
Brucella.  Excellent concentrations are achieved in most body fluids.  It has
excellent activity against S. aureus, including methicillin  resistant  Staph
aureus (MRSA).  The dosage is 500-750 mg BID or 200-400 mg IV q 12 hours.  In
general, it is well tolerated and toxicity is uncommon.  The most common side
effects  are  GI  symptoms  (3-6%).  CNS effects such as dizziness, headache,
sleep disturbances occur in 1-2%.   Rash  has been reported with an incidence
of .5-2%.  It has a relative  contraindication  in  pregnancy  because  fetal
deaths  and  skeletal  abnormalities  have  been  noted  in animals in utero.
Likewise, it should not be used in  individuals under the age of 18.  Reduced
doses should be used with  creatinine  clearances  less  than  20  mL/min  or
hepatic  dysfunction.   It  may  produce  seizures  in  patients  with CNS or
convulsive disorders.  Hydration  should  be  maintained,  and alkaline urine
should  be  avoided  to  prevent  cyrstalluria.   Ciprofloxacin  can  elevate
theophylline plasma levels and is potentiated by probenecid.   Phenytoin  and
oral  anticoagulant  levels  should  be  monitored  while  on  ciprofloxacin.
Concomitant  use  of  antacids,  iron,  zinc  and  oral  sucralfate should be
avoided.  The injudicious  use  of  ciprofloxacin  can  lead to antimicrobial
resistance.  Data from  Europe  has  shown  that  there  is  increasing  drug
resistant  strains  of  Pseudomonas  aeruginosa  and  S.  aureus  due  to its
overzealous use.  The  emergence  of  resistance  seems  to  be high in those
infections where there are many organisms present such as  osteomyelitis  and
cystic fibrosis.  CLINICAL USE: Ciprofloxacin has been used with good success
in  complicated  and  uncomplicated  urinary  tract  infections,  and chronic
prostatitis.  The cure rates are less in infections due to enterococci and in
complicated infections.  Ciprofloxacin  can  also  be  used  for treatment of
infectious diarrhea, but recurrence of Salmonella and resistance to C. jejuni
have been reported.  It also is used as a prophylactic measure in  traveler's
diarrhea.   Ciprofloxacin can eradicate the S. typhi carrier state.  The oral
biovailability is excellent and  can  be  used  for nursing home acquired, or
hospital acquired pneumonias,  if  S.  pneumoniae  has  been  excluded.   For
patients  that are unable to tolerate beta lactams or with organisms that are
resistant to beta lactams, IV ciprofloxacin  400  mg q 12 hours combined with
an aminoglycoside is an effective alternate.  If ciprofloxacin is used alone,
there may be rapid emergence of resistance.  Therefore, it  is  important  to
combine ciprofloxacin with an aminoglycoside when treating serious nosocomial
pneumonias,  sepsis  in  neutropenic  patients, and P. aeruginosa infections.
Ciprofloxacin should not  be  used  as  the  first  line  empiric therapy for
nosocomial  pneumonia,  because   beta   lactams   are   usually   effective.
Ciprofloxacin  can  also  be  used  in  malignant  external  otitis due to P.
aeurginosa, aerobic gram negative  bone  and  joint  infections, and skin and
soft tissue infections that are not due to streptococcal cellulitis.  It also
has activity against M. avium  intracellulare  and  multiple  drug  resistant
tuberculosis,  and uncomplicated gonococcal urethritis or cervicitis.  It may
also be used as an alternative agent for the prophylaxis of meningococci.

                      -CLOSTRIDIUM MYONECROSIS-
Clostridium  myonecrosis  can  be  divided  into  two  categories.  The FIRST
CATEGORY is related to the traumatic contamination of tissue with clostridium
spores.   This  type  of   myonecrosis   is  secondary  to  septic  abortion,
penetrating wounds, open fractures, and colon and biliary  surgery.   In  one
series,  compound  fractures,  gastrointestinal trauma and criminal abortions
accounted for 50% of  cases  of Clostridial myonecrosis.  Surgical procedures
accounted for 34% and 16 percent were probably  spontaneous.   The  traumatic
category  is  usually  caused by Clostridium perfringens.  The disease course
can be extremely swift, culminating in  death if intervention does not ensue.
Other organisms that  are  capable  of  producing  aggressive  infection  are
Streptococcus  pneumoniae,  Strep  pyogenes,  and  Neisseria.   Less frequent
causes are gram negative enteric  bacilli  and Staphylococcus aureus.  If the
patient is asplenic, Capnocytophaga canimorsus can also  cause  an  explosive
infection.   Organisms  that  can  cause  gas  production include Clostridia,
facultative  gram  negative  enteric  bacilli,  beta  hemolytic streptococci,
Staphylococcal aureus and several  anaerobic  organisms.   Gas  formation  is
common  in diabetic patients.  The SECOND CATEGORY of Clostridial myonecrosis
is that which arises spontaneously  or  atraumatically.  It is usually caused
by Clostridium septicum, but Clostridium perfringens  may  be  the  causative
agent.   Clostridium  septicum is more aerotolerant than C. perfringens which
allows it to survive better  than  C.  perfringens.  The inoculum required to
initiate an infection  is  usually  lower  with  C.  septicum.   There  is  a
significant  association of this organism with cancer of the gastrointestinal
tract or a hematologic malignancy, diabetes mellitus and acyclic neutropenia.
Most of the hematologic  malignancies  are  not occult, but readily apparent.
The cancer of the GI tract is usually  localized  in  the  distal  ileum  and
cecum.  Necrosis of the tumor is an important factor needed for Clostridia to
initiate   an   infection.    Chemotherapeutic  agents  and  neutropenia  are
additional factors that may  be  operative  in causing mucosal ulceration and
neutropenia which then sets the stage for  the  myonecrosis.   The  increased
incidence  in  diabetic  patients  may  be explained by accompanying vascular
disease, which  triggers  devitalization  and  necrosis.   Carriage rates for
Clostridium septicum in the feces is only 2 percent of human beings, but  the
appendix  carrier  rate  is  much  higher, ranging from 10-63 percent.  It is
interesting to note that one other organism, Strep bovis, has been associated
with carcinomas  of  the  colon.   This  usually  occurs  in  the  setting of
bacterial  endocarditis.   The  death  rate   for   spontaneous   clostridial
myonecrosis  is  higher  than  for  other clostridial infections.  Clostridia
species are ubiquitous.  They can be  found  in the feces, vagina and skin of
humans and are widespread in the soil.The most common organism in human feces
is C. ramosum and then C. perfringens.  They are obligate anaerobes, but some
species such as C. septicum, C. histolyticum, C. tertium  and  C.  perfringes
are  aerotolerant and can live for years as spores.  Clostridia can grow with
amazing speed with the generation  time  of  C.  perfringes as short as eight
minutes.  Clostridium perfringes, C. septicum and C. novyi can produce toxins
and proteolytic enzymes which  can  cause  local  and  systemic  injury,  and
because  of  this  are  the  most  virulent.  Clostridium histolyticum and C.
bifermentans cause more of a bland infection as they produce only proteolytic
enzymes.  CLINICAL: The onset  is  sudden  with hypotension, tachycardia, and
fever.  Terminally there is stupor,  delirium,  prostration  and  coma.   The
wound  is  swollen  with  surrounding  skin  that  is  pale.  There is a foul
smelling brown, blood tinged discharge.  Later, there is formation of reddish
bullae.  Gas may be  felt  in  the  tissues.   Hemolysis  and jaundice may be
present and later,  acute  renal  failure  and  DIC  may  develop.   A  rapid
diagnosis  can  be made by the gram stain which will yield gram positive rods
with a paucity of neutrophils.  Anaerobic culture will confirm the diagnosis.
X-rays  may  show  the  gas.    TREATMENT:  The  patient  should  be  treated
aggressively  with  volume  replacement,  early   surgical   debridement   of
devitalized tissue until healthy, bleeding tissue is seen.  Fasciotomy may be
required  and  surgical  reinspection  is  often  done in 24 hours.  The best
combination of antibiotics is not  known.   A reasonable approach would be to
start with  IV  penicillin  G  12  million  units  in  divided  doses  daily,
Gentamicin or Tobramycin 1.5 mg/kg every 8 hours and Clindamycin 600 mg every
6  hours.  Serum levels of aminoglycosides must be followed to avert toxicity
and ensure that  the  Gentamicin  is  effective.   Hyperbaric oxygen might be
beneficial in gas gangrene.   Oxygen  is  bactericidal  on  most  species  of
clostridia  and  is  required  for killing by neutrophils.  (a tissue partial
pressure of oxygen of 30 mm Hg is needed for normal function of neutrophils).
The partial pressure in tissues can  be  lower than this in infected tissues.
If a partial pressure of 250 mm Hg can be achieved, then there is  inhibition
of alpha toxin which is elaborated by Clostridium perfringens.  There is data
from  uncontrolled  case  series  that  have shown a reduction in the rate of
spread, mortality and  edema  when  hyperbaric  oxygen  was incorporated into
therapy with antibiotics and surgery.

       -COAGULASE NEGATIVE STAPHYLOCOCCI (Staph epidermidis)-
Is a common  cause  of  osteomyelitis,  usually  after  joint arthroplasty or
prosthetic implants, prosthetic  valve  endocarditis,  wound  infection,  and
meningitis post neurosurgical procedures.  Peritonitis can occur with chronic
ambulatory  peritoneal  dialysis  and  bacteremia  occurs  with intravascular
devices.  TREATMENT: removal of  foreign  body.  If methicillin resistance is
present, treat with vancomycin.  Prosthetic  valve  endocarditis  is  treated
with vancomycin + rifampin for 6 weeks and gentamicin  for at least the first
2  weeks.   Ciprofloxacin  is active against most strains, but solo treatment
causes rapid emergence of resistance.  Ciprofloxacin + rifampin is useful.

                     -COARCTATION OF THE AORTA-
Coarctation of the aorta is a  localized constriction of the aortic arch just
distal to the origin of the left subclavian artery.  In about  a  quarter  of
the  cases, it is associated with a bicuspid aortic valve.  It can be divided
into symptomatology related to  the  neonatal  period OR children and adults.
Infants with aortic coarctation may have sudden onset of  heart  failure  and
metabolic  acidosis  as  the  ductus  closes  and  there  is decreased distal
perfusion.  These infants may require an infusion of prostaglandin (PG) E1 at
a dose of .05-.1 ug/kg/min  to  reestablish patency of the ductus arteriosus.
With patency of the ductus there is improvement of  renal  blood  flow  which
will  allow  time  for  surgical  correction.   Oter  cardiac  defects may be
associated with neonatal coarctation  such  as  VSD.   There is a decrease of
lower extremity pulses and a differential of blood pressure between the right
arm and the  legs.   Chest  x-ray  with  VSD  may  show  increased  pulmonary
vascularity, while the ECG shows right ventricular hypergtrophy. There may or
may  not  be  a  murmur.   Adults and children usually have no symptoms until
hypertension produces left  ventricular  failure  or cerebral hemorrhage from
associated  cerebral  aneurysms.   There  is  upper  extremity  hypertension,
diminished femoral pulsations and a cardiac murmur.  The murmur is  heard  in
the  back medial or below the left scapula, left axillary area or in the left
infraclavicular area.   It  is  a  murmur  that  peaks  late  in  systole and
continues into diastole.  There may be a  continuous  murmur  head  over  the
chest  due  to  arterial  colalterals.   There  also may be murmurs of aortic
stenosis and regurgitation,  and  ventricular  septal  defect  if  there is a
bicuspid aortic valve and VSD present.  There also may be a systolic ejection
click.  ECG can show left or right ventricular  hypetrophy  or  both.   Chest
x-ray  may show post-stenotic dilation of the descending aorta.  Rib notching
is often seen after the age of  5, due to colaterals that develop extensively
from branches of the internal  mammary,  subclavian,  axillary  and  superior
intercostals.    Diagnosis   is   primarily   made  via  catheterization  and
aortography, measuring the  gradient  across  the  lesion.   Doppler also can
estimate the degree of obstruction.  Most patients, without intervention will
die by the age  of  45  from  rupture  of  the  aorta,  cerebral  hemorrhage,
infective  endarteritis,  aortic  dissection,  or hypertensive complications.
Surgical  mortality  of  resection  is  1-4%.   Balloon  angioplasty  may  be
effective also, but has the potential for aortic tears.

                     -COARCTATION OF THE AORTA-
The arm pulses are stronger  and  earlier  than  leg pulses and heaving apical
impulse may be present.  Causes  an  innocent  sounding  grade  2-3  ejection
murmur  heard in the left interscapular area.  A suprasternal thrill might be
palpable.  May be an associated bicuspid valve that causes an early diastolic
murmur. Ejection click may also be present.

                   -COCAINE INDUCED RHABDOMYOLYSIS-
Cocaine has been responsible for several misfortunes such as coronary  artery
spasm,   ventricular   arrhythmias,   acute   myocardial   infarction,  acute
cardiomyopathy,  hyperthyroidism,  hepatic   necrosis,  stroke,  subarachnoid
hemmorhage,  cerebral  vasculitis  and   sudden   death.    Cocaine   induced
rhabdomyolysis can be caused by every form of cocaine use.  It can eventually
lead  to acute renal failure and electrolyte alterations secondary to massive
muscle breakdown, which leads to the release of the intracellular contents of
the myocyte  into  the  circulation.   CLINICAL:  Patients characteristically
present with delirium and agitation.  Nausea and vomiting may be present  and
occasionally  there  will  be  flank  pain.   Only about 50% will complain of
myalgias and muscle weakness  is  noted  even less frequently.  Some patients
have been  erroneously  diagnosed  with  polyarteritis  nodosa  or  infective
endocarditis,  because  they  develop fever and rash that suggests a systemic
vascultis.  Early in the course of the disease, the serum creatine kinase and
serum myoglobin are elevated.  The initial  creatine kinase levels may be low
initially, but will peak after several  days.   Metabolic  acidosis  with  an
increased  anion gap, decreased serum bicarbonate concentration, elevated BUN
and  serum  creatinine  are  present.   Hyperkalemia,  hyperphosphatemia  and
hypocalcemia are common.  Later,  in  the  course there may be hypercalcemia.
The ALT and AST are elevated secondary to release from damaged  muscle.   The
patient's  urine  is  dark  due  to  the  presence of ferroprotein myoglobin.
However, in about 18% of cases,  even in the face of clinical rhabdomyolysis,
there will be  a  negative  orthotoluidine  test  for  blood  in  the  urine.
Therefore,  the  diagnosis  cannot  be  excluded  just  because  the urine is
negative for heme or RBCs are present.   The bilirubin may be elevated due to
the breakdown of myoglobin, or to  liver  disease  secondary  to  concomitant
alcohol   abuse   or  other  toxic  substances.   Disseminated  intravascular
coagulopathy can develop in severe  cases.   The patient should be questioned
about use of other drugs because rhabdomyolysis has been  caused  by  heroin,
amphetamine,  alcohol,  and  phencyclidine.   TREATMENT:  If  the patient has
concomitant  seizures,  hyperthermia,  hypotension,  hypoxemia  or  excessive
exertion, these should be treated.   The  primary  treatment goal is to avert
any kidney insult by establishing diruesis.  Many patients will be dehydrated
and  correction  of  hypovolemia  should  be  corrected  before  diuresis  is
attempted.  Rehydration will improve renal blood flow and decrease the  toxic
effects  of myoglobin.  Saline should be used for hydration.  Some would  use
mannitol.  The urine  output should  be  kept  at  about  250 ml/hour with an
osmotic diuretic if needed, after volume has been replaced.   If  the  pH  is
low,  bicarbonate  may  be given to keep the pH above 6. When the pH rises to
about 7.45 acetazolamide can be  given  to prevent alkalosis.  Loop diuretics
are controversial.  Dialysis may be needed.

                  -COCCIDIOIDES IMMITIS AND AIDS-
Amphotericin  B  .6  mg/kg  IV  qd.   Maintenance  therapy:  Amphotericin B 1
mg/kg/wk.

                        -COCCIDIOIDOMYCOSIS-
Coccidioidomycosis  is  caused   by   inhalation   of  the  arthroconidia  of
Coccidioides immitis, a mold that is endemic in the soil in the  southwestern
USA,  Mexico  and  in  Central  and  South America and affects men aged 25-55
frequently.  Suspect this disease in any  one that lives or visits this area.
Most natives that live in this endemic area  acquire  the  disease  in  their
youth.    Dark   skinned   persons   such  as  Filipinos,  African-Americans,
immunocompromised hosts, pregnant women  and  diabetics are at increased risk
in acquiring this disease.  It has principally two forms.  The first involves
the lungs and the second is progressive or disseminated.  THE PULMONARY FORM:
The Pulmonary form is usually minor, subclinical and self-limiting  in  about
60%.   In 40% there may be symptoms varying from a flu-like presentation with
fever, chills pleuritic  pain  and  predominantly  dry  cough.   There may be
swelling of the knees and ankles, conjunctivitis  and  erythema  nodosum  may
appear  2-20  days after onset of symptoms.  Pleural effusions may develop in
10% of cases with chest  pain,  sore throat and hemoptysis.  Leukocytosis and
eosinophilia may be present.  Chest x-ray findings include small thin  walled
cavities, large cavities and infiltrates that may be diffuse or nodular.  THE
DISSEMINATED  FORM:  In  this  form  the pulmonary findings become worse with
mediastinal and hilar lymph node  enlargement  and lung abscesses may rupture
into the pleural space with empyema.  There may be a miliary dissemination to
the lungs, bones, viscera, genitourinary tract, skin, pericardium, myocardium
and meninges.  The dissemination may  occur  weeks,  months  or  occasionally
years  after  the  primary infection.  There is loss of weight, anorexia, low
grade fever and malaise.  Of all  of the complications meningitis is the most
dreaded, because  it  is  extremely  difficult  to  eradicate.   Coccidioidal
meningitis  is  chronic  with  headache  and confusion being common.  The CSF
shows increased protein, decreased glucose and lymphocytosis which is similar
to Tuberculosis.  Antibodies in the  spinal  fluid  are  found in over 90% of
cases and are pathognomonic.  LABJORATORY: Cultures usually  appear  after  a
few  days  growth  as  a white mycelial growth.  Laboratory workers should be
extremely careful, as simply removing the top off a Petri dish containing the
highly contagious C.  immitis  arthroconidia,  may  induce  an infection.  In
coccidioidal meningitis, culture growth is very  infrequent  (30%),  and  the
diagnosis  is usually made by serologic tests.  The tissue form of C. immitis
is a  very  large  thick  walled,  nonbudding  spherule  (sporangia).  If the
spherule containing multiple endospores is visualized in tissue the diagnosis
of coccidioidomycosis is secure.  The characteristic spherules of C.  immitis
are  found  in  sputum,  pleural fluid, CSF, pus from abscesses, exudate from
skin  lesions,  gastric  washings,  biopsy  specimens  and  on  culture.  The
coccidioidin skin test which is a delayed cutaneous hypersensitivity reaction
to coccidioidin or spherulin usually appears 10 to 21  days  after  infection
and  remains  positive  for  years.  In the disseminated progressive form the
skin test is negative.  A persistently rising complement fixation titer > 1:8
is very suspicious for  dissemination.   Complement fixation antibodies (IgG)
rise at  1-3  months.   However,  if  there  is  meningitis  without  further
dissemination  then  the  complement  fixation  titer may be low.  There is a
false negative rate  of  up  to  30%  in  HIV related coccidioidomycosis.  If
patients have very mild symptoms they may never develop a positive  serology.
Blood  cultures  may  be  positive  in  about  30%  of  cases  of the acutely
disseminated forms.  Serology precipitin antibodies (IgM) rise within 2 weeks
and disappear after  2  months;  TREATMENT:  For  mild  pulmonary symptoms no
treatment  is  necessary.   For  progressive  pulmonary   or   extrapulmonary
dissemination,  Amphotericin B IV can be used.  Therapy should be given for a
total of 2.5-3 grams and if meningitis is present this may have to be treated
for life with Amphotericin B.  Intrathecal  Amphotericin B is generally given
on a weekly basis until the disease comes under  control,  then  monthly  for
several years.  If meningitis is not treated the mortality is 100%.  However,
with  the  advent  of Fluconazole and Itraconazole results are being obtained
that are similar to Amphotericin, obviating the need for intrathecal therapy.
If disease is limited to the  chest  Ketoconazole  200-800 mg daily 1 hour AC
breakfast can be used for 6 months.  If the patient develops  giant  infected
or ruptured cavities then surgery may be needed.  The progressive form can be
fatal in 55-60% of cases.

                       -COMA (Common Causes)-
INFECTION: Meningitis,  subdural  empyema,  encephalitis,  and brain abscess.
TUMORS: Primary tumors  with  gliomas  being  the  most  common.   Metastatic
disease most commonly from breasts, lungs, GI, and kidney.  VASCULAR DISEASE:
Subdural   hematoma,   epidural   hematoma,   subarachnoid   hemorrhage   and
intracerebral   hemorrhage.    DRUGS   AND  TOXINS:  Heavy  metals,  alcohol,
salicylates,  barbiturates,   opiates,   tranquilizers,   sedatives.   FLUID,
ELECTROLYTE AND ACID BASE DISORDERS: All  are  capable  of  causing  coma  if
severe.    HYPOXIA:  Anemia,  hypo  and  hypertension,  respiratory  failure,
decreased cardiac output.  ENDOCRINE  DISEASE:  Hypo and hyperglycemia.  Hypo
and hyperthyroidism, hypo and hyperadrenalism, hypo and  hyperparathyroidism,
hypo  and  hyperpituitarism.   OTHER:  Uremia,  heat  stroke and hypothermia,
Vitamin deficiences as  thiamine  which  can cause Wernicke's encephalopathy,
seizures, concussion, status epilepticus.

                            -COMA CAUSES-
INFECTION: Sepsis, encephalitis, meningitis,  abscess,  granulomatous,  viral
encephalitis.    TRAUMA:  concussion,  contusion,  laceration,  subdural  and
epidural   hematoma.    NEOPLASTIC:    metastatic    and   primary.    TOXIC:
antidepressants,    ethanol,    tranquilizers,    barbiturates,    narcotics,
anticonvulsants,  anticholinergics,  cimetidine,  bromides,  cyanide,  carbon
monoxide,  cyanide,  heavy  metals,  digoxin,   lithium,   methemoglobinemia,
phenothiazines,  organophosphates,  salicylates,  radiation.  SYSTEMIC: renal
failure, hypoventilation,  hepatic  frailure.   HYPOPERFUSION  AND HYPOXEMIA:
respiratory failure, status epilepticus, post cardiac arrest, severe  anemia,
aortic   stenosis,   altitude   edema,   arrhythmias,   DIC,   carotid  sinus
hypersensitivity,   fat   and   post   bypass   emboli,   pulmonary   emboli,
hyperventilation,  hypertensive   encephalopathy,   hyperviscosity,  malaria,
hypovolemia,  malaria,  syncope,  SBE,  vasculitis  and  autoimmune  disease.
METABOLIC: increased or decreased glucose, calcium and  sodium,  hyperosmolar
state,  severe  acidosis and alkalosis, Addison's or Cushings syndrome, hyper
and hypothermia,  carcinomatosis,  hypopituitarism,  increased  and decreased
magnesium,  decreased  phosphorous,  superior  vena  cava   syndrome,   acute
porphyria,  toxic  shock syndrome, increased and decreased thyroid, thiamine,
niacin, B6 and B12 deficiency.

                  -COMMON VARIABLE IMMUNODEFICIENCY-
Common variable immunodeficiency (acquired  agammaglobulinemia,  CVID)  is  a
heterogeneous  group  characterized  by  hypogammaglobulinemia affecting both
females and males starting in the  second  and third decades.  IgG levels are
usually less than 500 mg/100 ml, and the IgA and IgM levels are usually  less
than  50  mg/100  ml.   The  presence  of  normal  numbers  of  B  cells will
distinguish CVID from X-linked  agammaglobulinemia.   Plasma cells are rarely
seen in the spleen, bone marrow or lymph nodes in CVID, but can  be  seen  in
the lamina propria of the intestines.  Cellular immunity is usually intact in
CVID,  but  may be defective in some patients.  Eventually many patients will
develop T cell  abnormalities.   About  50%  will  have cutaneous anergy, and
about 25% will have a  severe  reduction  or  missing  immunoglobulin-bearing
lymphocytes.   Symptoms  rarely  occur  before  the  age of 6. It presents as
recurrent  bronchitis,  sinusitis,  and   pneumonia  that  can  develop  into
bronchiectasis.   About  60%  of  patients  develop  a  sprue  like  syndrome
manifested  by  diarrhea,  steatorrhea,  malabsorption,  and  protein  losing
enteropathy.  Sometimes, there is jejunal villous atrophy, intestinal nodular
lymphoid hyperplasia and bacterial overgrowth of the bowel.  At other  times,
the  intestinal  biopsy  is  normal.   Giardia lamblia infections are common,
which  respond  to   metronidazole   (Flagyl).    Many   patients  also  have
non-caseating granulomas of the spleen, liver, lungs and skin.  There may  be
associated  hematologic  disorders such as hemolytic anemia, anemia secondary
to vitamin B12  and  folate  malabsorption,  leukpenia, thrombocytopenia, and
pernicious  anemia.   Some   patients   have   developed   amyloidosis,   and
hemolytic-uremic   syndrome.    There  also  is  an  increased  incidence  of
malignancy  (usually  lymphoreticular).   Autoimmune  abnormalities,  such as
thyroiditis, Addison's disease and rheumatoid arthritis, are common.   Adults
often  develop gastric atrophy with achlorhydria.  Males occasionally develop
ataxia and  optic  atrophy  that  can  develop  into  fatal  encephalitis.  A
dermatomyositis like syndrome occasionally develops with peripheral  cyanosis
and myopathy. TREATMENT: Treatment is with immunoglobulin and antibiotics.

                      -CONGESTIVE HEART FAILURE-
CAUSES: Coronary artery disease is a major  cause  of  CHF  and  can  produce
systolic,  or  diastolic  dysfunction  or  both.  Systolic dysfunction can be
secondary to previous  MIs  with  scar  and  hibernating myocardial tissue or
decreased cardiac output  secondary  to  mitral  regurgitation.   Dilated  or
congestive  cardiomyopathies  may be caused by viral myocarditis and alcohol,
and   infiltrative   disease    such    as   sarcoidosis,   amyloidosis   and
hemochromatosis, cardiotoxins and drug toxicity.   Systemic  hypertension  is
also  an important cause.  Valvular causes include mitral and aortic stenosis
and  regurgitation.   Diastolic   dysfunction   is  present  in  hypertrophic
cardiomyopathies and  should  be  differentiated  from  systolic  dysfunction
causes.   LABORATORY: A CBC should be done to rule out anemia or polycythemia
as a cause of high output failure.  Electrolytes should be determined as well
as renal function  tests  and  thyroid  function  studies.  If amyloidosis is
suspect, rectal, gingival or skin biopsies are useful.  Iron  studies  should
be  done if hemochromatosis is being entertained.  Myocardial biopsies may be
needed for myocarditis.  An ECG is  indicated  to  help rule out acute or old
MI, arrhythmias, left ventricular hyertrophy, low voltage  and  pericarditis.
A  chest  x-ray may reveal pulmonary venous hypertension, interstitial edema,
Kerley B lines, cardiomegaly,  and  pleural  effusions.  An echocardiogram is
very informative.  It will allow detection of pericardial  effusion,  shunts,
valvular  abnormalities,  segmental or global wall motions, chamber size, and
wall thickness.  A radionuclide gated  blood  pool scintigram can measure the
left ventricular ejection fraction.  TREATMENT: Digitalis is still useful  in
patients  with  a dilated left ventricle and reduced stroke volume, depressed
ejection fraction and  S3  gallop.   Digoxin  is  also  indicated when atrial
fibrillation complicates CHF.  The dose  is  modified  dependent  upon  renal
function,   and   is   contraindicated   in   patients   with  sinoatrial  or
atrioventricular   nodal   disease    because   of   resulting   bradycardia.
Cholestyramine, broad spectrum oral antibiotics,  antacid  and  kaolin-pectin
combinations  may  decrease  absorption  of  digoxin.   Verapamil, quinidine,
propafenone and  amiodarone  will  increase  digoxin levels.  Hypomagnesemia,
hypokalemia,  and  hypercalcemia   will   enhance   the   digitalis   effect.
ANGIOTENSIN  CONVERTING  ENZYME  (ACE)  inhibitors  are now becoming standard
therapy in CHF.  Captopril, enalapril,  lisinopril and quinipril are approved
at the present time.  ACE inhibitors will reduce LV and right atrial  filling
pressures  and  increase  cardiac  output.   They also cause vasodilation and
inhibition of increased neurohormonal  activity.   These agents are effective
over long time follow-up.  They also are important in correcting hyponatremia
and diuretic induced hypokalemia which can lead to arrhythmias.  Two studies,
the SOLVD (Studies On Left Ventricular Dysfunction) and  SAVE  (Survival  and
Ventricular  Enlargement)  trials  demonstrated that they can delay the onset
and progression of heart failure in patients with symptomatic LV dysfunction.
Survival rates are also improved  by  ACE inhibitor therapy.  Hypotension may
supervene in some patients, particularly  those  with  hypovolemia,  prerenal
azotemia,  and  patients  with  hyponatremia.  Diuretics should be reduced or
withheld initially when  ACE  inhibitors  are  initially  given in low doses.
Captopril is useful initially because of its short duration of action.  It is
usually started at 6.25-12.5 mg TID.  Chronic captopril therapy is  typically
50 mg TID and enalapril 15-20 mg daily.  NITRATES: Nitroprusside is useful in
acute  CHF  as  it  is an arteriolar and venous dilator, which will result in
increased cardiac output as well as  reduced LV filling pressures.  It may be
combined with dopamine or dobutamine in acute decompensation.   Nitroglycerin
ointment  1-4  inches  q6h, isosorbide dinitrate 20-80 mg PO every 6-8 hours,
and sublingual nitroglycerin may be beneficial also.  Chronic nitrate therapy
leads to tolerance and can be  prevented by intermittent therapy, allowing an
8-12 hour nitrate free interval.  DIURETICS:  Diuretics  are  usually  always
needed  in  moderate  to  severe heart failure.  Thiazides become ineffective
when the glomerular filtration rate < 30 ml/min, at which time loop diuretics
should be used.  Loop diuretics  as  furosemide 20-320 mg daily or bumetanide
1-8 mg daily given as a single or divided dose are  usually  used  in  severe
heart  failure.   Refractory  cases  may  respond  to  metolazone plus a loop
diuretic.   BETA  BLOCKERS:   Certain   subsets   of  patients  with  dilated
cardiomyopathy that have gallop rhythms, tachycardia, and elevated  capillary
wedge  pressures may respond to beta blockers, which should always be started
at low doses.

                           -CONJUNCTIVITIS-
Conjunctivitis can be divided  into  bacterial,  viral and allergic.  Most of
these are painless with only  a  sensation  of  minor  irritation,  with  the
exception  of  herpes  simplex  virus.  Most cases of conjunctivitis are self
limiting, except for Neisseria gonorrhoeae or herpes simplex.  A more serious
problem usually exists  if  there  is  evidence  of photophobia, visual loss,
ocular pain, corneal  ulceration,  decreased  ocular  motility,  exophthamos,
perilimbal  flush  of iritis and the localized inflammation of scleritis.  If
the patient complains of pain,  glaucoma,  keratitis and corneal ulcer should
be ruled out.  If there are  pupillary  abnormalities,  consider  iritis  and
glaucoma.   If  there  is  reduction  or visual loss, consider corneal ulcer,
uveitis, and glaucoma.  Photophobia should bring to mind uveitis or a corneal
ulcer.  Any patient that has a perilimbal flush should be studied for iritis,
keratitis, and corneal ulcer.  If  the  patient  has  a white spot on the eye
consider a corneal ulcer.  If there are vesicular eruptions  consider  herpes
simplex  virus  or  herpes  zoster  infection,  and  if  there is a dendritic
configuration, herpex simplex virus  is  possible.   Always be aware that the
inflammation may be due to a foreign object that is not elicited on  history.
BACTERIAL  CONJUNCTIVITIS:  Bacterial conjunctivitis produces an exudate that
is mucoid or mucopurulent that  causes  the  eyelids to stick together in the
morning.  Bacteria that are commonly involved include Haemophilus  aegyptius,
Streptococcus  pneumonaie,  Haemophilus influenzae and Staphylococcus aureus.
Culturing the conjunctiva with a swab may aid in the diagnosis.  Treatment is
with Polytrim (trimethoprim sulfate/polymyxin  B sulfate ophthalmic solution,
Bleph-10, Sodium  Sulamyd,  AK-Sulf	(sodium  sulfacetamide  10%  ophthalmic
solution  or  ointment),  and Polysporin (polymyxin B sulfate/zinc bacitracin
ophthalmic ointment).  If  the  patient  has  a complicated infection Ciloxan
(ciprofloxacin) and Chibroxin (norfloxacin) can be used.  Although  Genoptic,
Garamycin,  and  Gentafair  (gentamicin  sulfate) is useful, the spectrum for
gram positive organisms is limited,  and  there is an increased potential for
allergic reactions.  Gentamicin should not be used for longer than 7-10 days.
VIRAL CONJUNCTIVITS: Viral conjunctivits produces a serous exudate  that  can
have  a  mild  purulent  component.   Always  check the preauricular area for
adenopathy as this  is  a  clue  for  viral involvement.  Viral conjunctivits
tends to be bilateral, especially if due  to  adenoviruses,  as  it  is  very
contagious.  Adenovirus is spread by direct contact, contact with fomites and
droplet   dispersion.    Herpes   simplex   virus  is  typically  unilateral.
Adenovirus is the most common organism, which can present as acute follicular
conjunctivitis,      acute      pharyngoconjunctivitis,      and     epidemic
keratoconjunctivitis.  In acute follicular conjunctivitis, examine the  lower
lid  cul-de-sac  for enlarged lymphatic follicles.  The upper lid may also be
involved.  The patient may  also  have  rhinitis and preauricualr adenopathy.
The  pharynx  is  usually  not  involved.    In   contrast,   patients   with
pharyngoconjunctivitis have a sore throat, fever, preauricualr adenopathy and
red   watery   eyes.   There  may  be  submandibular  adenopathy,  indicating
involvement of the oropharynx.  The most serious adenovirus infection is that
of epidemic keratoconjunctivitis which  may  be  caused by several serotypes.
The most common are serotypes 3, 7, and 8. These  serotypes  produce  an  eye
that  is  intensely  injected  with  a  more  copious discharge.  It can also
produce punctate keratitis, pseudomembranes, subepithelial opacities, corneal
scars and decreased  vision.   This  conjunctivitis  starts  out usually as a
unilateral involvement that rapidly involves the other eye, and may last  for
2   weeks   or  more.   There  is  no  definitive  treatment  for  adenovirus
conjunctivitis.   Patients  are   usually   given   broad  sprectrum  topical
antibiotics  for  the  posssiblity  of  bacterial  superinfection.   HERPETIC
CONJUNCTIVITIS: The first episode of herpetic  conjunctivitis  (Primary  HSV)
usually  produces an associated blepharitis.  Look for ulcerations on the lid
margins.  The cornea  may  show  a  dendritic  pattern (branching).  Herpetic
conjuctivitis is common in children up to the age of 10.  Patients  may  also
have  a  herpetic  keratoconjuctivitis  characterized by a preauricular node,
painful  foreign  body  sensation,  decreased  vision,  watery  discharge and
follicle formation.  Treatment is with Viroptic (trifluridine  1%  ophthalmic
solution),  Vira-A  (vidarabine  3% ophthalmic ontment), and Dendrid, Herplex
(idoxuridine).   Trifluridine  is  considered  the  most  effective  drug for
herpetic simplex  virus.   Corticosteroids  should  be  avoided.   CHLAMYDIAL
CONJUNCTIVITIS:  Chlamydial  conjunctivitis is more common in sexually active
individuals and newborns,  and  is  caused  by Chlamydia trachomatis (usually
serotypes  D  through  K).   Chlamydial  conjunctivits  can  simulate   viral
conjunctivitis  as it also produces preauricular adenopathy, follicles on the
lower and upper eyelids,  and  a  serous  discharge.   However, it is usually
unilateral  and  can  cause  superior  vascularization  of  the  cornea,  and
peripheral epithelial opacities.  Patients may also have urethritis.  It  can
be  diagnosed  by  culture or immunofluorescent antibody tests.  Treatment is
with tetracycline 500 mg QID for  21  days  or  doxycycline 100 mg BID for 21
days.  For patients unable to  tolerate  these,  erythromycin  may  be  used.
ALLERGIC  CONJUNCTIVITIS:  These  patients  may  have  a history of asthma or
atopic disease.  The discharge is typically a clear watery discharge that has
tenacious strands of mucous (ropy  mucous).   Some of these patients (usually
young  males),   develop   the   conjunctivitis   in   the   spring   (vernal
conjunctivitis).   Vernal  conjuctivitis is assocated with itching, and giant
papillae on the upper  eyelid.   Some  patients  have limbal involvement with
small white dots seen at the junction of the cornea and the sclera.  Patients
may have swelling of the eyelids and lacrimation.  Some patients who are soft
lens wearers will develop  giant  papillary  conjunctivitis.   This  produces
giant papillae on the upper tarsal conjunctiva, erythema, itching, and mucous
discharge.  Treatment for mild giant papillary conjunctivitis associated with
soft  lens  includes discontinuance of lens wear.  Some of these symptoms are
due to poorly  fitting  lenses.   Enzymatic  cleaning  of  the lenses at more
frequent intervals  may  also  help.   If  unable  to  resolve  the  problem,
switching  to  rigid  gas  permeable  lenses  may help.  In general, systemic
antihistamines such as  terfenadine  (Seldane)  and astemizole (Hismanal) are
used.  The itching can be improved with ketorolac tromethamine .5% ophthalmic
solution  (Acular),  1  drop  QID,  or  naphazoline  HCL/pheniramine  maleate
(AK-Con-A, Opcon-A, Naphcon-A).  Cromolyn sodium 4% given 6 times/day is also
useful.

                       -CREATININE CLEARANCE-
Calculated   creatinine   clearance=(140-age)  x  (ideal  body  weight)/serum
creatinine x72 (x 0.85 if female).

                          -CROHN'S DISEASE-
Crohn's disease is an inflammatory  condition  that may be caused by genetic,
immunologic or infectious causes, but at  the  present  time  is  essentially
idiopathic.   About  17%  of  patients  with  Crohn's disease will have first
degree relatives that have the disease.  There also is an increased incidence
in monozygotic twins and siblings.  The disease seems to be more prevalent in
Jews and men.  It is estimated  that  Jewish  men have an incidence six times
that of the general population.   It  has  been  postulated  that  infectious
agents,  such  as  mycobacteria, RNA viruses, or cell-wall defective bacteria
may be the cause.  Crohns's disease is characterized by a subacute onset with
diarrhea, fever, lower right  quadrant  pain,  tenderness and mass.  In about
33% there is involvement exclusively of the small bowel,  most  commonly  the
terminal ileum, but the inflammation can occur anywhere from the mouth to the
anus.  In about 50% of cases, there is small bowel and colon involvement, and
in  about  15-20%  the  colon  is  the only site of involvement.  The disease
usually  occurs  in   young   individuals   with  chronic  exacerbations  and
remissions.  The peak incidence occurs between 12-30 years with  a  secondary
peak  arising  at  50 years of age.  Since the disease process is transmural,
complications  may  be  frequent.   There  is  pronounced  thickening  of the
submucosa, nonspecific granuloma formation, mucosal ulcerations and  lymphoid
hyperplasia.   There  may  be linear or deep serpiginous mucosal ulcerations,
with cobblestoning alternating  with  normal  mucosa.   Focal granulomata are
found in about 50% of biopsy specimens.  It is common for there to be matting
and enlargement of mesenteric lymph nodes.  Complications include strictures,
fistulae and abscess formation.  CLINICAL: The most  common  presentation  in
Crohn's  disease  is  fever, which is usually low grade, non-bloody diarrhea,
weight loss, pain, tenderness, and possible mass in the lower right quadrant.
The pain may be steady  or  cramping.   There may be flatulence, anorexia and
malaise present.  Patients may notice that milk and  milk  products  increase
their  symptomatology.   Patients  are  often misdiagnosed as irritable bowel
syndrome, which can also have  remissions  and exacerbations.  If the patient
develops intestinal obstruction,  postprandial  cramping,  and  bloating  may
occur.   Intestinal obstruction may be the presenting symptom in about 25% of
cases.  Intestinal obstruction usually  develops  later  in the course of the
disease as fibrosis sets up.  However, acute inflammation and  spasm  of  the
bowel  can  occur early with intestinal obstruction.  In approximately 33% of
patients that have involvement of  either  the large or small bowel, perianal
disease will develop.  If this happens, the patient will complain of pain and
tenderness with  and  without  defecation  as  anal  fissures,  fistulae  and
abscesses   develop   in   this   area.   Since  the  disease  is  transmural
fistulization can occur.  If a fistula  develops  from the colon to the small
bowel, there may be bacterial  overgrowth  with  diarrhea,  malnutrition  and
weight  loss.   Fistulae  to  the  mesentery  can  cause  retroperitoenal  or
intra-abdominal  abscesses  with  production  of  chills, fever and abdominal
masses.  However,  most  mesenteric  fistulae  are  asymptomatic.  Also, most
enteroenteric fistulae are asymptomatic  and  require  no  specific  therapy.
Fistulas  may  also  occur  to  the  bladder,  vagina, skin, or previous scar
formation.  Extraintestinal  manifestations  consist  of  hepatic and biliary
disease, kidney disease, arthritis, anemia, dermatologic problems and  ocular
disease.  There may be pericholangitis, fatty liver, hepatitis, cirrhosis and
sclerosing   cholangitis.    Gall   stone  prevalence  is  increased  due  to
malabsorption  of  bile  salts  from  the  terminal  ileum.   A  non-specific
hepatitis with elevation of liver enzymes is  found in up to 70% of patients.
There is an increase in calcium  oxalate  stones  due  to  increased  oxalate
absorption  as  well  as  an  increase in uric acid stones which is due to an
increased cell turnover.  Episcleritis or uveitis  can  occur in up to 10% of
patients.  Erythema nodosum and pyoderma gangrenosum may be seen.  Ankylosing
spondylitis has an incidence of from 2-10%, and peripheral arthritis  can  be
seen in about 10% of patients.  There is an increased incidence of colorectal
or small bowel cancer in Crohn's disease, but the incidence is less than that
of  ulcerative colitis.  Hemorrhage is very unusual in Crohn's disease, which
is in contrast to ulcerative  colitis.  LABORATORY: Anemia in Crohn's disease
may be mutifactorial.  The anemia may be due to chronic inflammatory changes,
iron deficiency secondary to mucosal blood  loss,  nutritional  due  to  poor
intake,  vitamin  B12  malabsorption due to small bowel resection or terminal
ieum  inflammation.   Leukocytosis  may   be  due  to  inflammation,  abscess
formation or steroid use.  Albumen is usually low due to poor dietary  intake
of   protein,   protein   losing   enteropathy,  malabsorption,  and  chronic
inflammation.  The  sedimentation  rate  is  usually  elevated.   An upper GI
series and small bowel study may reveal strictures, fistuale and ulcerations.
Colonoscopy will reveal several types of ulcerations of the  mucosa  such  as
linear,  aphthous  or stellate which have a segmental involvement alternating
with normal mucosa.  Strictures may also  be visualized on endoscoppy as well
as barium enema  and  small  bowel  study.   If  biopsy  reveals  granulomas,
Crohns's  disease  is suggested.  However, granulomas are only found in about
25-50% of specimens.  In about 10% of cases it is impossible to differentiate
Crohn's disease  from  ulcerative  colitis.   DIFFERENTIAL DIAGNOSIS: Several
diseases that may locate in the terminal ileum will need to be differentiated
from Crohn's disease.  These include, lymphomas  and  mycobacteria.   If  the
patient  has  HIV disease, Mycobacterium avium intracellulare will have to be
distinguished.  Yersinia  enterocolitica  infection,  radiation enteritis and
appendicitis may also present as Crohn's  disease.   The  differentiation  of
Crohn's  in  the  colon	include  ischemic  colitis, Entamoeba histolytica,
Chlamydia,   tuberculosis   and   diverticulitis   with   abscess  formation.
TREATMENT: PREDNISONE: Prednisone still is the treatment of choice for  ACUTE
Crohn's  disease.  Up to 90% of mild to moderate Crohn's disease will respond
to prednisone.  The dose is usually 40-60 mg/d given for about 2-3 weeks with
tapering  at  5 mg/week  until the patient  reaches 20 mg/day.  At that point
the tapering is at 2.5 mg/wk or every other week  until  the  patient  flares
again.  Some patient can't be weaned completely off steroids and will have to
be  maintained at 2.5-10 mg/day.  Prednisone plus sulfasalazine has been used
together and may give a  better  initial  result.  The usual complications of
steroids  are  seen,  such  as   aseptic   necrosis,   cataracts,   diabetes,
hypertension,   growth   retardation   in  children,  psychosis,  and  sodium
retention.  Rapidly metabolized corticosteroids are in clinical trial in this
country.  They will  probably  be  available  in  oral, suppository and enema
preparations.  They presumably have  less  affect  on  the  pituitary-adrenal
axis,  resulting  in  fewer  side  effects.   Budesonide  is one of these now
undergoing clinical trials.   Others  include fluticasone and beclomethazone.
SULFASALAZINE: Sulfasalazine (Azulfidine or Azulfidine EN-tabs) is a congener
of sulfapyridine and mesalamine and has been in use for  over  50  years  for
inflammatory  bowel  disease.   It  is not effective for disease of the small
intestine, but is  useful  for  ACUTE  mild  to  moderate Crohn's colitis and
ileocolits.  It is probably not effective for chronic maintenance therapy  in
Crohn's  disease.   The  dose  is usually 2-4 grams daily.  Side effects will
limit  its  usefulness,  however.   Headache  and  nausea  are  dose related.
Hypersensitivity reactions include  pancreatitis,  arthritis,  pleuritis  and
rash.   There  is also reversible suppression of male fertility.  The patient
may also develop  leukopenia,  agranulocytosis,  folate deficiency, hemolytic
anemia, exacerbation of colitis, hepatitis, pneumonitis  and  a  lupus-  like
syndrome.   To  avoid  the folate deficiency, folic acid 1 mg/d can be added.
TOPICAL MESALAMINE: Mesalamine  (Rowasa)  enemas  have  been  shown  to be as
effective as sulfasalazine or  steroids  in  treating  Crohn's  proctitis  or
proctosigmoiditis.   The  dose  is 60 ml (4 grams) given as a retention enema
daily for about 3-6 weeks, or  a  suppository  can be used bid for 3-6 weeks.
By using these topical agents you can avoid the side affects of sulfasalazine
or steroids.  Mesalamine can also be used when the patient becomes refractory
to sulfasalazine.  ORAL MESALAMINES: Oral mesalamines are useful in those who
cannot tolerate sulfa drugs.  These include Asacol which  is  active  in  the
terminal  ileum  and  colon;  Claversal which is active in the midjejunum and
ileum, and Pentasa which is active in the duodenum, jejunum, ileum and colon.
Some of these have been  approved  for  ulcerative colitis, but have not been
approved as of this writing for Crohn's disease.  Asacol comes in  a  400  mg
delayed  release  tablet.   The  dose is 800 mg tid for 6 weeks in ulcerative
colitis.  Pentasa comes as a 250  mg controlled release capsule.  The dose is
1 gram QID for up to 8 weeks in ulcerative colitis.   Side  effects  of  oral
mesalamines  include  a reversible and dose dependent secretory diarrhea that
can affect about 15% of  patients.   Also, pancreatitis and pericarditis have
occurred.  Dipentum (olsalazine) may be used in Crohn's colitis  as  well  as
ulcerative  colitis.   The  dose  is 500 mg BID with food.  This drug is also
capable  of  causing  a   troublesome  secretory  diarrhea,  rash,  headache,
depression, fatigue, exacerbation of colitis, and hair loss.   METRONIDAZOLE:
Metronidazole,  oral  quinolone  antibiotics  or  both  may  be  effective in
treatment of perineal Crohn's disease.  They are useful in patients that have
abscess or fistula formation and  intestinal perforation.  Some patients with
Crohn's colitis will respond to metronidazole when sulfasalazine has  failed.
The  dose  is 10-20 mg/kg/day.  Peripheral neuritis is a side effect that may
be seen in 50% or more of  patients.   The neuritis may last for months after
the  medication  has  been  terminated.   Starting  with  smaller  doses   of
metronidazole  may  help  alleviate  the  side  effects.  IMMUNOSUPPRESSIVES:
Although azathioprine and 6-mercaptopurine have  not been approved for use in
Crohn's disease, they may be useful in refractory cases of Crohn's.   Closing
of  fistulae  has  been reported.  This class of drugs is usually tried after
all other measures have failed.   The  starting dose of azathioprine (Imuran)
and 6-mercaptopurine (Purinethol) is 50-75 mg/day.  Therapeutic response  may
be  delayed  for  greater  than  3 months in about 68% of patients.  However,
about 67% improve.  Effective  doses  of  these  drugs  should keep the white
blood count to between  4,000  and  5,000.   If  the  patient  responds  with
remission,   90-95%   will   stay   in   remission  if  the  azathiorpine  or
6-mercaptopurine is continued.   These  two  drugs  may  also spare the large
doses of steroids that are needed to help maintain remission.   Side  effects
of  these  drugs  include  pancreatitis  in  the  early  stages  of  its use,
hepatitis, leukopenia and allergic reactions.  All of these side effects tend
to be less than 10%.  Apparently, there has been no reports of neoplasia when
used  in  patients  with  inflammatory  bowel  disease.   Lymphoproliferative
diseases such as lymphoma  have  been  reported  in transplant patients using
these drugs.  Patients should not receive azathioprine  in  conjunction  with
allopurinol   because   allopurinol   will   block  azathioprine  metabolism.
METHOTREXATE and CYCLOSPORINE: Methotrexate  and  cyclosporine have also been
used in inflammatory bowel disease with success, but have not  been  approved
for  use  as  of  this  writing.   TOTAL PARENTERAL NUTRITION: TPN is used in
patients that are malnourished with  fistulae, in preparation of patients for
surgery, in patients with active disease and  in  those  who  are  unable  to
tolerate  enteral feedings.  TPN plus bowel rest may also decrease the use of
steroids.  It  is  more  effective  in  Crohn's  disease  than  in ulcerative
colitis.    SYMPTOMATIC   TREATMENT:   Some    patients    cannot    tolerate
lactose-containing  foods, and in those with lactose intolerance, Lactaid may
be of benefit.  Patients  that  are  hypoproteinemic may benefit with protein
supplements such as Sustacal HC, and Ensure Plus.  It is recommended that  at
least  100  grams  of  protein  intake  be  used  per day.  If the patient is
bothered with diarrhea, free elemental  diets such as Travasorb-HN, Precision
High Nitrogen and Criticare may be useful as they require minimal  digestion.
Enteral  therapy with an elemental diet such as Vivonex given for 4 weeks has
been shown to be as  effective  as  steroid  therapy in creating a remission.
However, when the elemental diet is discontinued, and the patient returns  to
a  normal  diet,  there  may  be  relapse.   Diarrhea  may be controlled with
diphenoxylate + atropine (Lomotil) in a  dosage  of 1-2 tablets every 6 hours
or lopermaide (Imodium) using the same dosage.  These  drugs  should  not  be
used  in  SEVERE  Crohn's  disease as they may lead to toxic megacolon.  High
fiber supplements, such  as  Citrucel,  Hydrocil,  ad  Metamucil, may also be
useful in controlling excessive stool.  Abdominal cramping may be  controlled
with  antispasmodics  such as Bentyl, Levsin and Donnatal.  Again, this class
of drugs can induce  toxic  megacolon.   If  the  patient has had small bowel
resections of less than 100 cm, diarrhea may be troublesome.   These  can  be
helped  by  adding  cholestyramine  (Questran)  or  colestipol (Colestid) and
placing the patient on a  low  fat  diet of 40-60 grams/day.  Steatorrhea can
cause hyperoxaluria and calcium or vitamin D malabsorption.  If  the  patient
has  hyperoxaluria,  food  high  in  oxalate  such as rhubarb, cola, tea, and
grapefruit should be avoided.   Calcium  carbonate or calcium gluconate given
at a dose of 1.5 grams/day  and  vitamin  D  given  at  a  dosage  of  50,000
units/week  will  help prevent osteomalacia and osteoporosis, and the calcium
will also bind oxalate  in  the  bowel  which  will decrease urinary oxalate.
SURGERY: Surgery is usually reserved for complications  of  Crohn's  disease,
such  as obstruction, hemorrhage, internal fistulae, abscesses and intestinal
perforations.  In order to preserve bowel, stricturoplasty may	be indicated.
Extensive resection of small bowel may  lead to the short bowel syndrome with
malabsorption of vitamin B12, hyperoxaluria, osteomalacia, macrocytic anemia,
and  steatorrhea.   Removal  of  diseased  tissue  does  not  prevent  future
occurrences.

                               -CROUP-
Occurrence peaks in  the  late  fall  and  early winter.  Racemic Epinephrine
delivered by nebulization alone at a concentration of .25-5 ml of 2.25%  drug
diluted  to  a total volume of 3 ml isotonic saline.  Relief is transient and
obstructive symptoms  often  return  within  2  hrs.   The  patient should be
observed for 3-4 hours post-treatment as an out  patient.   Dexamethasone  .6
mg/kg may be given as a one time dose within the first 24 hours.

                         -CRYOGLOBULINEMIA-
CLINICAL: Any  patient  presenting  with  purpura,  arthralgias  and weakness
should bring to mind cryoglobulinemia.  The most common complaint is  purpura
and  usually  involves  the  lower  extremities,  but can extend to the lower
abdomen and buttocks.  Several  triggering  events have been noted, including
medications as penicillin, salicylates, pulmonary infections and cold.  There
may be recurrent purpura that lasts for about 2 weeks and there may  be  some
itching  or  burning  associated with the purpura.  Ulcerations, particularly
around the malleolar area, and necrosis  of  the ears, fingers, toes and nose
can occur.  There  also  may  be  minor  episodes  of  Raynaud's  phenomenon.
Arthralgias  occur in about 72% of cases and involve the knees, ankles, hands
and elbows  in  a  symmetric  and  migratory  fashion.   Frank arthritis will
develop in a few.  RENAL disease develops in about  55%  of  cases  of  mixed
cryoglobulinemia.     Hypertension    and   edema   are   common   with   the
glomerulonephritis of CG.  Usually, renal disease is a late manifestation and
presents as a subacute  disease,  or  can  be rapidly progressive.  (Systemic
diseases associated with rapidly progressive glomerulonephritis would include
poststreptococcal  glomerulonephritis,   infective   endocarditis,   visceral
sepsis, Hepatitis B infection, SLE, Goodpasture's syndrome, Henoch- Schonlein
purpura,    Necrotizing    vasculitis,    polyarteritis   nodosa,   Wegener's
granulomatosis  and  Cryoglobulinemia).    Renal   biopsies  show  a  diffuse
proliferative glomerulonephritis or a focal  involvement.   Immunofluorescent
studies  usually  reveal granular deposition of immunoglobulins which are the
same as the serum cryoglobulins,  such  as monoclonal IgM and polyclonal IgG.
Complement may also be present.  Eosinophilic hyaline material may be seen in
glomerular capillaries.   Electron  studies  may  show  fibrillar  glomerular
deposits   in  the  subendothelial  region,  and  also  occasionally  in  the
intramembranous  and  intraluminal  regions.   These  fibrillar  deposits are
considered to be a unique finding associated with cryoglobulinemia  and  when
seen  can solidify the diagnosis.  LIVER disease is found in about 70% and is
sometimes  associated  with  hepatitis   B  infection.   Several  cases  have
demonstrated hepatitis B antigen and hepatitis B surface  antibodies.   Other
cases  are  asymptomatic.   The  histology  may  range from mild triaditis to
chronic  active  hepatitis  and  cirrhosis.   LUNG  disease  is  not commonly
present, but occasionally there will be  hemoptysis  and  pleural  effusions.
There   may   be  interstitial  lung  involvement  and  cardiac  involvement.
LABORATORY: There  are  3  types  of  cryoglobulins.   Type  I are monoclonal
immunoglobulins and account for about 1/4 of the  cryoglobulins.   These  are
frequently present in amounts often greater than 5 mg per milliliter.  Type I
cryoglobulins   are   associated  with  multiple  myeloma  and  Waldenstrom's
macroglobulinemia.  IgM is the most  frequent  type of immunoglobulin in Type
I. Type II Cryoglobulins account for  about  1/4  of  the  cryoglobulins  and
consist  of  a  monoclonal  immunoglobulin  which  is  usually  IgM and has a
rheumatoid factor or anti-IgG activity mixed  with at least one other type of
polyclonal immunoglobulin which is usually IgG.   This  combination  accounts
for  the  most  common  Type  II  cryoglobulins.   Type  II cryoglobulins are
associated  with  chronic  lymphocytic  leukemia  and  lymphocytic lymphomas,
Sjogren's syndrome,  rheumatoid  arthritis,  essential  cryoglobulinemia  and
autoimmune  hemolytic anemia.  Type III cryoglobulins account for 50% and are
composed entirely of polyclonal  immunoglobulins.  The IgM-IgG combination is
the  most  frequent,  and  sometimes  is  in  combination   with   complement
components.  Type III have less than 1 mg per milliliter in 80% of the cases.
Type  III  is  occasionally  associated  with  chronic  lymphocytic leukemia,
lymphocytic lymphomas, idiopathic thrombocytopenic purpura, hemolytic anemia,
Sjogren's  syndrome,  polyarteritis  nodosa,  rheumatoid  arthritis,  SLE and
infections.  The infections are Viral  infections:  (as  Epstein-Barr  virus,
cytomegalovirus,   and   hepatitis  B),  Bacterial:  (endocarditis,  leprosy,
lymphogranuloma),  Fungal:  (coccidioidomycosis),  Parasitic: (toxoplasmosis,
schistosomiasis and malaria).  About 30% of  patients  with  cryoglobulinemia
will have no association with other diseases and the cryoglobulins are of the
mixed  variety.   This is called essential mixed cryoglobulinemia, and occurs
mostly in women around 50 years  of  age.  These patients will have recurrent
palpable purpura of the lower extremities for many years which may result  in
hyperpigmentation.   Ulcers  may be present, and if these ulcers are biopsied
they show  vasculitis.   Other  lab  findings  in  mixed cryoglobulinemia are
rheumatoid factor activity, which is usually present, and in 45% percent, the
titers are greater than 1:640.  Immunoglobulins are elevated in  60%.   Serum
complement  levels are decreased.  About 80% have a decrease in CH50.  C3 and
C4 are usually decreased with  a  striking  depression  of C4 in some series.
Anemia and increased sedimentation rate are present in about 70%.   Transient
Coombs'  positive anemia and speckled antinuclear antibodies are seen in some
patients.  TREATMENT:  Treatment  is  with  Prednisone,  Cytotoxic  drugs and
plasmapheresis.

                 -CRYPTOCOCCUS NEOFORMANS AND AIDS-
Amphotericin  B,  .6  mg/kg/day  IV  or  Amphotericin  B  .3  mg/kg/day  IV +
flucytosine 100-150 mg/kg/day PO in 4 divided doses or Fluconazole 400 mg  PO
qd.  Maintenance therapy: Amphotericin B 1 mg/kg IV weekly or Fluconazole 200
mg PO qd.

                    -CRYPTOSPORIDIUM AND AIDS-
Paromomycin 500 mg PO q6h.

                        -CUSHING'S SYNDROME-
When dealing with this topic, one must make the distinction between Cushing's
SYNDROME  and  Cushing's  DISEASE.   Cushing's  disease refers to a pituitary
tumor producing excessive ACTH, where as  Cushing's Syndrome may be caused by
a pituitary tumor (such as a  basophilic  adenoma  or  chromophobe  adenoma),
adrenocortical tumor (such as adrenal cortical adenomas and carcinomas) or an
ectopic ACTH producing tumor (such as a small cell carcinoma of the lung or a
bronchial carcinoid).  Cushing's syndrome may be fairly easy to diagnose, but
Cushing's  disease  may  be very difficult to distinguish from adrenocortical
tumors and ectopic ACTH producing tumors.   At first thought, you might think
this differentiation is very simple.  Just order a MRI- gandolinium  enhanced
scan  of  the  pituitary,  and  a  CT  or  MRI of the abdomen to evaluate the
adrenals, and if a tumor  is  seen,  then  we have found the cause.  However,
this is not the case, because it has been shown by autopsy that about 1/3  of
patients  with  no  known  endocrine  syndromes during life have unsuspected,
non-functional pituitary  tumors,  and  5-10%  have  unrecognized  benign non
functional adrenal tumors.  With this in mind, a reasonable approach will  be
discussed  in  the  following discussion of Cushing's syndrome.  CLINICAL: In
80% of cases of pituitary Cushing's disease, the adenoma is small enough that
no visual field defect or abnormality on  routine x rays of the sella turcica
will be seen.  There is a female predominance over males in a ratio  of  4:1.
Weakness  occurs  in about 90%, thin skin (84%), obesity which is centripetal
with  truncal  obesity  (79%),  moonface,  buffalo  hump  and supraclavicular
fullness (51%, easy bruising and hypertension (77%), hirsutism  (67%),  edema
and  osteoporosis  (48%),  menstrual disorders and hirsutism (67&), impotence
and striae (53%, psychiatric symptoms  (31-70%) and proximal myopathy.  Other
findings that have been reported include: acne,  pathologic  fractures,  poor
wound  healing,  galactorrhea,  renal  stones  and  exophthalmos.  Laboratory
findings include:  leukocytosis  with  a  relative  lymphopenia, occasionally
polycythemia and hypercalcemia, hyperglycemia, and hypokalemic alkalosis seen
with ectopic ACTH secretion.  Ectopic ACTH producing tumors may  include  the
following:  small  cell  carcinoma of the lung (this is the most common cause
occurring in only about  2%),  islet  cell  tumor  of the pancreas, bronchial
carcinoid adenoma, hypernephroma, craniopharyngioma, neuroblastoma, seminoma,
pheochromocytoma, medullary thyroid carcinoma, and carcinoma  of  the  ovary,
prostate,  parotid,  breast, colon and esophagus.  These tumors often present
with  marked  hypokalemic   alkalosis,   weakness   and  muscle  wasting  and
hyperpigmentation due to production of Beta melanin  stimulating  hormone  by
the  tumor.   Adrenal  carcinomas  are rare, but adrenal adenomas account for
approximately 10%  of  cases  of  Cushing's  syndrome.   Adrenal adenomas and
carcinomas often  present  with  virilization.   Adrenal  carcinoma  patients
usually  survive  for  only  2-4  years, whereas adrenal adenomas have a good
prognosis.  These tumors are found  more  frequently  on  the left and can be
bilateral.   TESTIMG  IM  CUSHING'S   SYNDROME:   A   screening   test,   the
Dexamethasone test should be done by giving 1 mg of dexamethasone po at 11 to
12  PM  with  measurement  of  the  plasma  cortisol  at 7-8 AM the following
morning.  If the patient is normal,  there  will be a plasma cortisol of less
than 5 ug/dL.  Most patients  with  non  pituitary  Cushing's  syndrome  will
continue  to  secrete cortisol.  By far, the most reliable test for Cushing's
syndrome is the 24 hour urinary free cortisol measurement.  Most all patients
with Cushing's SYNDROME will have an elevated value above 100 ug.  The normal
value is < 90 ug or  less.   If  the  assay is done with high pressure liquid
chromatography, the upper limit  of  normal  is  50  ug.   To  distinguish  a
pituitary  abnormality from the other 2 forms of Cushing's syndrome, the oral
dexamethasone suppression test is done.  In the low dose test, if 0.5 mg q 6h
for 2 days is given to  normal  subjects  there will be an inhibition of ACTH
with urinary free cortisol decreasing to < 10 ng/24 hours on the second  day.
If  the  patient  has  Cushing's  Disease,  there is a relative resistance to
suppression and the urinary free cortisol  will not decrease.  If the dose of
dexamethasone is increased to 2 mg every 6 hours for 2 days there will  be  a
50%  reduction  in  free  urinary  cortisol.   If  the patient has an adrenal
adenoma or ectopic ACTH tumor  there  will  be  no change in the free urinary
cortisol.  To differentiate between an adrenal tumor  and  the  ectopic  ACTH
syndrome,  the  plasma  ACTH  concentration should be done.  The ACTH will be
markedly elevated if the patient has an ectopic ACTH producing tumor, usually
greater then 200 pg/mL, and too low  to measure if there is an adrenal tumor.
Patients with Cushing's disease usually have a moderately elevated ACTH level
between 75 to 200 pg/mL.  The CRH test is another test that may  be  used  to
differentiate  between  adrenal tumors and ACTH secreting tumors.  TREATMENT:
If the pituitary is the problem,  then transsphenoidal surgery should be done
to excise the tumor.  The surgery is successful in about  70%  and  the  best
results  are  obtained with microadenomas < 1 cm in diameter.  If no tumor is
found then pituitary  irradiation  is  done  delivering 4000-5000 rads.  With
irradiation the response time may require several  months.   If  the  patient
does  not  respond  to  transphenoidal  surgery or irradiation then bilateral
adrenalectomy may  be  done.   Following  this  procedure,  Nelson's syndrome
occurs in 5-10%, whereby there is growth of the pituitary gland with a  large
increase  in  ACTH  and B melanocyte stimulating hormone which will result in
hyperpigmentation.     Hypophysectomy    may    be    ultimately    required.
Adrenocortical tumors are removed surgically.   If the patient has an ectopic
ACTH secreting tumor, again, surgery may be needed.  However, many  of  these
tumors   are   metastatic   and  surgery  cannot  be  done.   Metyrapone  and
aminoglutethimide, ketoconazole and RU  -  486  have  all been tried.  If the
patient has  a  pancreatic  islet  cell  tumor,  octreotide,  a  long  acting
somatostatin analog, may be tried.

                         -CYANIDE POISONING-
Cyanide is a very toxic chemical  that  is  rapidly  absorbed  by  ingestion,
inhalation  or  skin absorption.  Adult ingestions as little as 200 mg of the
sodium or potassium salts  can  cause  death.   Its presence is ubiquitous in
commercial laboratories, industry, homes, and research labs.  It  is  present
in many forms.  The gaseous form, hydrogen cyanide, is an ingredient of smoke
from  fires.   Hydrogen  cyanide  is  also  a  combustion by product of wool,
burning plastics and other  synthetic  products.   Hydrogen cyanide gas has a
ceiling limit in workplaces of 10 ppm.  Exposure to levels as low as  150-200
ppm  can  cause  death.  Fifty ppm is considered a threat to life.  Aliphatic
nitriles such as acrylonitrile  and  propionitrile  are used in plastics, and
are eventually metabolized to cyanide.  Cyanide is also present as  amygdalin
and  other  cyanide  generating  glycosides  in  apricot  pits,  and cassava.
Acetonitrile, present in some nail glue  removers, is an important source for
intoxication, particularly in pediatric patients.  Cyanide is  released  from
nitroprusside  on  exposure to light.  Acute cyanide poisoning as a result of
nitropursside infusion is rare when normal infusion concentrates and infusion
rates are used.  Hydrogen cyanide  is  used as fumigants and acrylonitrile is
used in the production of synthetic rubber.  Cyanide also  can  be  found  in
some  furniture  and silver polishes, and some fertilizers contain cyanamide.
Cyanide interrupts  cellular  function  by  inhibitng  cytochrome oxidase and
preventing  the  cell's  ability  to  use  oxygen.   CLINICAL:  Symptoms  are
immediate in most  cases,  except  after  ingestion  of  nitriles  and  plant
cyanogenic  glycosides,  in which the symptoms may be delayed from minutes to
hours.  The patient may or may  not  have the classic odor of bitter almonds.
This may be appreciated from the breath or vomitus.  Patients typically  have
headaches,  arrhythmias,  pulmonary edema, nausea, dizziness, abdominal pain,
confusion, syncope,  seizures,  shock,  coma  and  death.   The venous oxygen
saturation may be elevated to greater than 90% in severe toxicity because  of
a  lack of tissue uptake of arterial oxygen.  This translates to a bright red
color of venous  blood.   LABORATORY:  Laborotory  testing  is  usually of no
benefit due to the rapid effects of cyanide.   However,  whole  blood  levels
greater  than  .5-1  mg/L  are deemed toxic.  Levels as high as 1 mg/L may be
reached if there is rapid infusion of nitroprusside.  Smokers can have levels
as high  as  0.1  mg/L.   Patients  routinely  should  have determinations of
glucose, serum lactate,  mixed  venous  oxygen  satsuration,  arterial  blood
gases,  and carboxyhemoglobin if there has been smoke inhalation.  TREATMENT:
The patient shold be  given  100%  oxygen.   Mouth  to mouth resuscitation is
contraindicated.  The Lilly cyanide antidote kit  contains  amyl  and  sodium
nitrites    which    produce    methemoglobinemia   and   thiosulfate.    The
methemoglobinemia  binds  to   free   cyanide,   while  thiosulfate  promotes
conversion of cyanide to  thiocyanate  which  is  less  toxic  than  cyanide.
Specifically,  the Lilly kit contains ampules of sodium nitrite (300 mg in 10
mL vials), ampules of sodium  thiosulfate  (12.5  grams  in 50 mL vials), and
amyl nitrite (.3 mL) for inhalation.  The following are the ADULT doses: Amyl
nitrite should be inhaled for 30 seconds every minute until the  patient  has
received  sodium  nitrite.  A  new  ampule  should  be  used every 3 minutes.
Administration of 100% oxygen is  given between inhalations of amhyl nitrite.
The amyl nitrite in the kits should be changed annually.  Sodium  nitrite  is
given  IV  at  300  mg  (10  ml  of 3% solution over a 20 minute period.  The
methemoglobin concentration should be monitored, so that nitrite can be given
to obtain a methemoglobin of 25%.   It  is important that a firm diagnosis is
at hand before the sodium nitrite is given, because of its ability to produce
methemoglobinemia which can be lethal if given for a misdiagnosis,  if  adult
doses  are  given  to  a  pediatric patient, or if given to a carbon monoxide
patient.   Do  not  give  methylene  blue  for  methemoglobinemia  in cyanide
poisoning.  The dose of sodium nitrite for a child is  6  mg/kg.   The  adult
dose  for  sodium thiosulfate is 12.5 grams IV given over a 20 minute period.
Sodium thiosulfate is fairly benign  and  can  be given when the diagnosis is
tenuous.  The dosage of sodium nitrite and sodium thiosulfate in children  is
based  upon  the hemoglobin level as follows: For a hemoghlobin of 14 gm give
sodium nitrite 3%, not to exceed  10  mL,  as .39 mL/kg (11.6 mg/kg).  Sodium
thiosulfate , not to exceed 12.5 grams,  is  given  at  1.95  mL/kg.   For  a
hemoglobin  of  12  grams,  give sodium nitrite 3%, not to exceed 10 mL, 0.33
mL/kg (10 mg/kg).  Sodium thiosulfate, not  to exceed 12.5 grams, is given at
1.65 mL/kg.  For a hemoglobin of 10 grams, give sodium  nitrite  3%,  not  to
exceed 10 mL, 0.27 mL/kg (8.7 mg/kg).  Sodium thiosulfate, not to exceed 12.5
grams,  is  given  at  1.35  mL/kg.   For a hemoglobin of 8 grams give sodium
nitrite 3%,  not  to  exceed  10  mL,  at  0.22  mL/kg  (6.6  mg/kg).  Sodium
thiosulfate, not to exceed 12.5 grams, is given at 1.1  mL/kg.   If  patients
improve,  but  then  subsequently  deteriorate,  sodium  nitrite  and  sodium
thiosulfate can be repeated at 50% of the original dose, both given over a 20
minute period.

                     -CYCLOPHOSPHAMIDE TOXICITY-
A major side effect  of  cyclophosphamide  is  hemorrhagic cystitis caused by
metabolic products.  The risk of  developing  hemorrhagic  cystitis  is  dose
related.   Ifosfamide,  an  analogue  of  cyclophosphamide,  can  also  cause
hemorrhagic  cystitis.   If ifosfamide or cyclophosphamide is used along with
mesna, a neutralizing agent,  bladder  toxicity  can be averted.  Hemorrhagic
cystitis occurs more frequently in those  that  have  a  concentrated  urine.
Early  symptoms  of  bladder  toxicity  include frequency and dysuria without
bacteriuria.  About 20% of patients  will develop these symptoms.  Should the
patient develop microscopic hematuria.  the patient should be  hydrated,  the
cyclophosphamide   discontinued,  and  given  phenazopyridine.   With  severe
cystitis, there may  be  gross  hematuria  and  widespread involvement of the
bladder.   These  patients  should  be  observed  for  obstruction.   Bladder
fibrosis and renal insufficiency can also  develop.   SIADH  is  possible  in
patients that are taking doses > 50 mg/kg.  Hematologic complications include
leukopenia,  anemia  and  thrombocytopenia.   Hepatic  side  effects  include
elevated  alkaline  phosphatase,  bilirubin and aminotransferases.  Pulmonary
complications  include  intersitital  fibrosis  with  prolonged  high  doses.
Cutaneous side effects  include  alopecia,  oral ulcerations, stomatitis, and
darkening  of  the  fingernails  and  skin.    Cyclophosphamide   can   cause
azoospermia and amenorrhea.

                          -CYSTIC FIBROSIS-
Cystic Fibrosis (CF) is a leading cause  of death in early adulthood, and has
an incidence of 1:2000 Caucasian births.  The incidence in  blacks  is  about
1:17,000,  while  the  incidence  in  Orientals is 1:90,000.  The lung is the
major  organ  affected,  although   the   gastrointestinal,  liver  and  male
reproductive systems can be  involved.   The  disorder  is  inherited  in  an
autosomal  recessive manner.  The chief metabolic abnormality is an elevation
of the sodium and chloride content in sweat, but not necessarily in the tears
or saliva.  Chronic  salt  depletion  can  occur,  particularly in the summer
because of salt loss by sweating or with gastroenteritis.  Some patents  have
reported  that  their  children  taste  salty.   The  increase  in sodium and
chloride is caused by a  decrease  in  sodium reabsorption in the sweat duct.
Almost all patients  will  develop  obstructive  lung  disease  with  chronic
infection.   The  cystic  fibrosis  gene  has been located on the long arm of
chromosome 7 near the centromere.   The  most frequent mutation is a deletion
of a phenylalanine residue in the 508 position of the protein which is  found
in  70%  of  patients.   About  85%  of  patients  with  CF  will have severe
pancreatic disease.  Those  that  are  homozygous  for  the delta 508 genetic
abnormalty almost always have pancreatic abnormalties and malabsorption.  The
pancreatic manifestations are characterized by impaired secretion  of  water,
electrolytes  and bicarbonate causing protein hyperconcentration.  There is a
resulting deficiency in trypsin and lipolytic enzymes leading to steatorrhea,
and malabsortpion.  This, combined  with  the  pulmonary impairment, leads to
mucoviscidosis.  The lung lesion can be present at birth, but in  most  cases
infants  present  with  elevated sweat chloride and meconium ileus and normal
lungs.  The lesions  in  the  lungs  start  as  hypertrophy  of the bronchial
glands followed by plugging of the small peripheral airways, which  leads  to
chronic  infection, bronchiectasis, pulmonary hypertension, cyanosis, and cor
pulmonale.  Extensive collateral  circulation  through the bronchial arteries
develops that can lead to bleeding from these vessels.  The initial infection
in the lungs is caused by Staphylococcus  aureus,  but  this  soon  leads  to
mucoid  strains  of  Pseudomonas  aeruginosa,  which  is  very  difficult  to
eradicate  from the lungs.  Other Pseudomonas species such as P. cepacia, may
emerge, which have a tendency  to  cause  severe  disease in females with CF.
Concurrent viral infections  such  as  parainfluenza  viruses,  adenoviruses,
influenza  A  and B, and respiratory syncytial viruses may be instrumental in
causing exacerbations.  Allergic  bronchopulmonry  spergillosis may also lead
to acute pulmonary deterioration.  This can be diagnosed by sputum and  blood
eosinophilia and type I and tye III immune responses to Aspergilus fumigatus.
CLINICAL:  The disease can present in the neonatal period with meconium ileus
prolonged jaundice, or failure to  gain  weight.  The meconium ileus can lead
to intestinal obstruction which causes abdominal distention.  A  Gastrografin
colon  study may reveal the presence of meconium througnhout the large colon.
Edema may be present due to protein deficiencies.  Fat malabsorption leads to
bulky  stools.   Rectal   prolapse   is   common.   Any  recurrent  pneumonia
(especially due to P. aeruginosa) or persistent lung infiltrate at  any  age,
should  raise the possibility of CF.  These patients may present with chronic
episodic wheezing and  coughing  that  may  simulate  asthma.  As the disease
advances, there is widespread tissue destruction with bronchiectasis.   About
25%  of  patients  less than 10 years of age will have hypogammaglobulinemia.
Older children can develop  cirrhosis  with  portal  hypertension as the only
manifestation of CF, with the exception of the elevated  sweat  electrolytes.
Any  patient  with  nasal  polyps  should be tested for sweat electrolytes as
nasal polys can develop in children  and adolescents with CF.  These patients
have frequent episodes of sinusitis.  Males almost always have aspermia which
is due to obliteration of the vas deferens.  About 1%  of  patients  with  CF
will  develop diabetes mellitus and this increases as the child ages.  By the
age of 18, about 15% will have diabetes.  However, vascular complications and
ketoacidosis are  rare,  although  some  may  develop  proliferative diabetic
retinopathy.  The standard confirmation  test  for  CF  is  the  quantitative
pilocarpine   iontophoresis   sweat   test.   The  Gibson-Cooke  quantitative
technique is the acceptable  method.   A  sweat chloride concentratin greater
than 60 mEq/L is  diagnostic.   INDICATIONS  FOR  A  SWEAT  TEST:  Intestinal
obstruction  in  the  newborn,  failure  to  thrive  in infancy or childhood,
infants and children with steatorrhea  or  chronic diarrhea, infants who pass
the initial meconium late, infants with rectal  prolapse,  infants  who  have
radiologic   signs   of   atelectasis   and   hyperaeration,   infants   with
hypoprothrombinemia,  all  of  the siblings of patients with CF, children and
adults with nasal polyposis, children  and  adolescents with cirrhosis of the
liver  and  portal  hypertension,  all  patients   that   are   suspect   for
disaccharidase  intolerance or celiac disease, infants and children who taste
salty,   patients   with   recurrent   pneumonia,   bronchiectasis,   chronic
atelectasis, chronic  cough,  asthma,  those  with  staphylococcal pneumonia,
infants with clubbing of the digits and who have been diagnosed with  asthma,
infants  with  hypoproteinemia,  and  infants  with unexplained hyponatremia.
About 65% of cases of CF are diagnosed  within the first year of life, 90% by
the age of 5. Hyperinflation of the lungs is the first  radiographic  finding
in  infants,  progressing  to  bronchiectasis  and  nodular  densities.  Lung
changes typically occur in the right upper lobes with involvement of the lung
bases last.  The chest x-ray  may  also show bronchial wall thickening, hilar
adenopathy,  flat  diaphragms,  segmental  atelectasis,  enlarged   pulmonary
arteries,  and right ventricular hypertrophy.  TREATMENT OF PULMONARY DISEASE
IN CF: Antibiotic therapy  should  empirically be started against Pseudomonas
with addition of others if needed.  Antibiotics  for  P.  aeruginosa  may  be
given  IV  as follows.  Ceftazidime 35-50 mg/kg q8h, or tobramycin/gentamicin
2.5-6 mg/kg q8h, or  amikacin  5-10  mg/kg q8h, or carbenicillin, ticarcillin
50-100 mg/kg q6h, or piperacillin 50-100 mg/kg q6h,  mezlocillin,  azlocillin
50-100  mg/kg  q6h,  or imipenem/cilastatin 12-25 mg/kg q6h, or ciprofloxacin
15-30 mg/kg q8h.  For Staph  aureus,  nafcillin  may  be given IV at 25 mg/kg
q6h, or clindamycin 5 mg/kg q6h IV.  Oral antibiotics  against  Staph  aureus
include   dicloxicillin   10-30   mg/kg   q6h,   cefaclor  10-20  mg/kg  q8h,
amoxicillin/clavulanate 10-15 mg/kg  q8h,  and  erythromycin 15-25 mg/kg q6h.
Antibiotics that may  be  given  IV  against  Hemophilus  influenzae  include
cefotaxime 25-40 mg/kg q6h, and cefuroxime 25-40 mg/kg q6h.  Oral antibiotics
against   H.   influenzae   include  trimethoprim/sulfamethoxazole  10  mg/kg
(trimethoprim) q12h, amoxicillin 15-30 mg/kg q8h, and amoxicillin/clavulanate
10-15 mg/kg q8h.   Aerosolized  antibiotics  may  be  useful in home therapy.
Aerosolized gentamicin, and tobramycin are given at 40-80 mg/dose in  2ml  of
saline  q6-12h,  carbenicillin,  ticarcillin  500-1000 mg/dose in 2 ml saline
q6-12 hours, and ceftazidime 500-1000  mg/dose  in 2 ml saline q8h.  Patients
may also benefit from chest physical therapy  and  human  recombinant  DNase.
Recombinant  Dornase  alfa (Pulmozyme) is not recommended in children under 5
years.  Over 5 years the dose is  2.5 mg daily via nebulization.  This may be
increased to 2.5 mg BID.  Side effects include laryngitis, pharyngitis, rash,
conjunctivitis and chest pain.  It is supplided as 2.5 ml  amps.   HEMOPTYSIS
can occur up to 70% of patients with cystic fibrosis, usually precipitated by
sustained lung infections, which leads to erosion of the bronchial walls into
the collaterals.  Hemoptysis less than 20 mL will usually stop spontaneously.
Chest  physical therapy should not be done during hemoptysis.  Vitamin K 5-10
mg should be given SQ  for persistent bleeding.  Bronchoscopy frequently does
not find the point of bleeding.  For massive bleeding, vasopressin  20  units
IV  given  over  15  minutes  followed  by 0.2 units/min has been successful.
Artery embolization also has been  successful, but recanalization occurs with
further bleeding.  PNEUMOTHORAX: About 19% of patients over  the  age  of  14
will  have  a pneumothorax at some time.  Patients with a new pneumothorax of
10-15%  with  dyspnea  may   be   watched   in   the  hospital.   For  larger
pneumothoraces tube thoracostomy is used  with  chemical  sclerosing  agents,
because  of  the  high incidence of continued air leak and recurrence.  NASAL
POLYPS AND SINUSITIS: Nasal polyps are  seen  in 10-25% of children and up to
50% in adults.  These CF patients may present with chronic  sinusitis,  nasal
congestion  and rhinitis as the only manifestation of CF.  These patients are
treated with antibiotics  and  nasal  steroids.   Surgery  usually results in
recurrence.  RIGHT VENTRICULAR FAILURE:  These  patients  will  present  with
edema,  jugular  venous  distention,  dyspnea,  enlarged  tender liver, and a
tricuspid regurgitant murmur.  The heart is increased in size with large main
pulmonary arteries.  The ECG  and  echocardiogram will show right ventricular
hypertrophy.  These patients are treated with furosemide 1 mg/kg  po  or  IV.
Digoxin is not effective.  The patient should be given supplemental oxygen to
mainatain  the  Pao2  at  around  60  mm  Hg.   TREATMENT OF GI DISASE IN CF:
PANCREATIC   INSUFFICIENCY:    Pancreatic    exocrine    insuffiency   causes
malabsorption of protein, fat, and carbohydrates.   Patients  have  bloating,
bulky  and  greasy  stools,  poor  wiehgt  gain,  delayed maturation, lack of
subcutaneous fat  and  muscle,  and  poor  weight  gain.   These patients are
treated with intestinal enzyme replacement therapy using tablets, capsules or
microspheres.  Enzyme replacement therapy can be monitored by measuring fecal
fat.  INTESTINAL OBSTRUCTION: Neonatal  patients  with  meconium  ileus  will
present with abdominal distention, lack of passage of meconium, and vomiting.
Perforation  and  peritonitis  can  intervene.  About 10% of newborns with CF
will have meconium ileus  (obstruction  of  the  distal ileum with dehydrated
meconium).  About  15-25%  of  older  patients  may  present  with  recurrent
episodes of intestinal obstruction, manifested by colicy right lower quadrant
abdominal  pain, distention, constipation and vomiting.  There may be a right
lower quadrant  mass.   Diatrizoate  meglumine  (Gastrografin)  enemas can be
diagnostic as well as therapeutic.  Gastrografin  enemas  can  sdifferentiate
intussusception  from  meconium  ileus  eqivalent (seen in older children and
adults).  Abdominal radiographs  may  shows  air  fluid levels, dilated bowel
loops, ground glass appearing material in the the lower  central  abdomen  or
the  RLQ.   Patients should be hydrated and treated with nasogastric suction.
N-acetylcysteine (20% solution) 30 ml  diluted  in  120  ml of water given by
nasogastric tube and by rectal enema has been effective.  Patients  may  also
be helped with stool softners.

                    -CYTOMEGALOVIRUS AND AIDS-
Retinitis:  Foscarnet  60  mg/kg  IV  q8h  or  Ganciclovir  5  mg/kg IV q12h.
Maintenance therapy: Foscarnet  90  mg/kg/day  IV  infusion  or Ganciclovir 5
mg/kg/day IV or 6 mg/kg IV 6 days/wk.

                  -DEEP VENOUS THROMBOSIS (Causes)-
ACQUIRED:   estrogens,   inflammatory  bowel  disease,  oral  contraceptives,
carcinoma of the pancreas, lung  and GI, acute hemolysis, nephrotic syndrome,
malignant   hyperthermia   with   tissue   necrosis,   lupus   anticoagulant,
polycythemia   vera,   paroxysmal   nocturnal   hemoglobinuria,    pregnancy,
thrombocytosis.   INHERITED:  Antithrombin  III  deficiency,  Protein C and S
deficiency,   dysfibrinogenemias.    VENOUS   STASIS:   atrial  fibrillation,
prolonged   immobility,   anasarca,   CHF,    cardiomyopathy,    constrictive
pericarditis,  obesity,  COPD,  myocardial infarction, stroke, post-operative
settings, especially for abdominal,  pelvic,  lower extremities, prostate and
spleen, volume depletion as in  diabetic  ketoacidosis,  hyperosmolar  state,
venous  insufficiency of the legs and the elderly.  VESSEL DAMAGE: history of
previous thromboembolism, trauma to lower  extremity as in hip fracture, post
operative states, recent childbirth, and vasculitis as in Behcet's syndrome.

                    -DELIRIUM TREMENS TREATMENT-
Check  blood  coagulation,  CBC, ECG, renal, liver function and electrolytes.
CT is done if localizing signs, seizures, persistent and prolonged depression
in level of consciousness.   Cervical  spine radiographs, and lumbar puncture
if persistently febrile and CT is normal.  IV fluids  of  Dextrose  2.5%  and
.45%   saline   at  a  rate  of  150  ml/hr  and  add  potassium  as  needed.
Multivitamins and thiamine 100 mg IV  daily  x5.   Valium 10 mg IV q30 min as
needed.  Paraldehyde 8-12 ml in orange juice as needed  if  patient  able  to
take  oral  meds.   Phenobarbital  or  Amytal  60-120 mg IM or IV q3-4 hrs as
needed.  Librium, thorazine, atarax or  compazine may be used.  Labetalol may
be infused to control the blood pressure.

                             -DEMENTIA-
Dementia  may  be  defined  as  an  impairment of intellectual function.  The
differential  diagnosis  is   wide,   but   Alzheimer's  dementia  (DAT)  and
multi-infarct dementia (MID) account for about 85% of cases  of  dementia  in
those  patients  over  the  age of 65.  There is no specific test for DAT and
thus other causes must be  ruled  out.   There  is an increasing incidence of
dementia as one ages.  ALZHEIMER'S DISEASE DEMENTIA: About 15%  of  DAT  will
have  a  family  history  of  the  disease.   It is inherited as an autosomal
dominant disease.  Most cases, however  are non-familial.  DAT usually starts
insidiously, but is always progressive with ultimate total disability.  Death
usually comes in about 15 years or sooner from infection or complications  of
the  disease.  In about 50% of patients there may be motor and extrapyramidal
abnormalities.  Depression is  very  common.   Patients  are unaware of their
problems.  There is  inattention,  difficulty  with  abstract  reasoning  and
orientation.   There  is  sparing of the visual system, the corticospinal and
the corticosensory systems.  CT of  the  head  may show atrophy of the medial
and anterior  temporal  lobes.   The  MRI  also  will  show  atrophy  with  a
periventricular  halo  on  the  T2  weighted  studies.   If positron emission
tomographic scans are available they will  show a decrease of cerebral oxygen
and glucose metabolism, particularly in  the  parietal  and  temporal  lobes.
MULTI-INFARCT  DEMENTIA:  Multi-infarct dementia is less common than DAT, but
can easily be differentiated from  DAT.   MID is caused by multiple bilateral
cerebrovascular occlusions as a result of either emboli or  primary  arterial
occlusive  disease.   MID  is  usually  caused by small lacunar infarcts with
lipohyalinosis.  Progression is usually predictable  as each new infarct will
worsen the clinical condition.  The patient may  have  a  very  slow  thought
process,  irritability,  apathy  and  inertia.   MID  is  closely  related to
hypertension, diabetes mellitus, hyperlipidemia, smoking and cardiac disease.
It becomes more common after  the  age  of  60-70  and is more common in men.
Depression is common and suicide may be entertained.  The patient may develop
pseudobulbar  palsy,  hemiplegia,  extrapyramidal   symptoms   and   abnormal
inappropriate  laughing  and  crying.   CT of the head typically demonstrates
hypodensities in the periventricular  white  matter or the subcortical areas.
MRI will also show these white matter lesions.  DRUG DEMENTIA: Several  drugs
may  cause  a pseudodementia.  The following medications in particular should
send  up  a  red   flag   in   the   elderly:  Beta  blockers,  barbiturates,
benzodiazepines,  tricyclic  antidepressants,   anticholinergics,   steroids,
cimetidine,  MAO  inhibitors,  reserpine,  anticholinergics,  and  digitalis.
Occasionally  methyldopa,  clonidine,  phenytoin,  baclofen, NSAIDs, and oral
hypoglycemic agents will  cause  a  dementia.   NORMAL PRESSURE HYDROCEPHALUS
DEMENTIA:  Normal   pressure   hydrocephalus   (NPH)   is   a   communicating
hydrocephalus.    One   should   try  to  elicit  a  history  of  meningitis,
encephalitis, subarachnoid hemorrhage or repeated  head trauma as a cause for
the dementia.  A small minority of patients will have tumors of the  midbrain
causing the NPH.  The patient may present with a spastic ataxic gait, urinary
incontinence  and  positive Babinski.  The gait is usually described as slow,
ataxic, shuffling and wide  based.   Isotope  cisternography may be useful in
diagnosis.  The CT will show an enlargement of the ventricular  system.   MRI
may  show  the  CSF  void  sign  which  is  a decreased image of the cerebral
aqueduct due to increased  CSF  flow.   Periventricular  thinning may also be
present.  Insertion of a ventriculoatrial shunt may  alleviate  some  of  the
symptoms,  but  usually  is not totally effective.  Also, it is impossible to
predict which patients  will  improve  with  the  shunt.  AIDS DEMENTIA: Aids
dementia usually is a late finding in HIV infection.  The patient  will  have
slowing  of motor function and thinking, apathy, difficulty in concentrating,
ataxia and extensor plantar responses.   Zidovudine may improve the dementia.
DEPRESSION  DEMENTIA:  A  helpful  clue  in  diagnosing  dementia  caused  by
depression is that the patient will often complain of memory loss, whereas in
other dementias the patient will not complain of memory  loss.   Even  though
depressed  patients  respond  to  questions  slowly,  the answers are usually
accurate.  Current events are  usually  not  lost in depressive dementia, and
these patients also have their best behavior at night time.  In addition, the
appetite is poor, there is disturbance of sleep, and constipation.  METABOLIC
DEMENTIA: Hypothyroidism and hyperthyroidism can sometimes be  confused  with
dementias.   However  high  sensitive TSH blood tests can be used to rule out
these two causes.  Hyponatremia and hypercalcemia can also lead to a demented
state.  SUBDURAL  DEMENTIA:  In  alcoholic  and  elderly  patients a subdural
hematoma should be suspected of causing a dementia.   Most  patients  do  not
remember  the  trauma that caused the hematoma.  INFECTIOUS DEMENTIA: Chronic
meningitis from fungal and tuberculosis infections can cause dementias.  Also
neurosyphilis, HIV and viral infections as Creutzfeldt-Jakob disease may lead
to dementias.  Creutzfeldt-Jakob  is  characterized  by a rapidly progressing
dementia,  myoclonus,  rigidity  and  behavioral  changes.   The  EEG   shows
triphasic  waves.   There is no	treatment for Creutzfeldt-Jakob  disease  and
it  usually  is   fatal   in   1-2   years.   LCOHOLIC  DEMENTIA:  Wernicke's
encephalopathy and Korsakoff's syndrome may  cause  dementia.   Even  chronic
alcoholism  itself may lead to cerebral atrophy and dementia.  B12 AND FOLATE
DEFICIENT  DEMENTIA:  In  particular,  Vitamin  B12  deficiency  can  cause a
dementia.  The dementia may occur early prior to the  typical  blood  changes
and  peripheral  neuropathy  that  accompany B12 deficiency.  LABORATORY: The
following lab tests should  be  done  if  deemed appropriate: B12 and Folate,
FTA, CT or MRI of the head, heavy metal and toxicologic analysis, EEG, Lumbar
puncture, thyroid tests, Cortisol, hepatic tests, electrolytes, HIV,  isotope
cisternography, VDRL, calcium, ceruloplasmin, magnesium and ANA.

                 -DEPRESSION AND CONCURRENT ILLNESS-
Drugs of choice  for  depression  with  concurrent  diseases  are as follows:
OBSESSIVE COMPULSIVE DISORDER:  sertraline,  fluoxetine,  paroxetine  (SSRI),
clomipramine.   OBESITY: bupropion, fluoxetine.  Avoid doxepin, trimipramine,
amutriptyline.  PANIC: desipramine,  imipramine,  phenelzine,  low dose SSRI,
alprazolam.   Avoid  bupropion,  trazodone,  buspirone.   BIPOLAR   DISORDER:
carbamazepine,   valproic,  lithium,  bupropion,  MAOI.   Avoid  TCAs  alone.
ANERGIC   BIPOLAR   DEPRESSION:    bupropion,   tranylcypromine.    INSOMNIA:
Amitriptyline, trazodone, doxepin.  Avoid SSRI alone,  bupropion.   ANOREXIA:
fluoxetine,  TCA.   BULIMIA:  imipramine,  phenelzine, SSRI high dose.  Avoid
bupropion.  PSYCHOTIC  FEATURES:  TCA  and  neuroleptic,  ect, or amoxapine?.
Avoid TCA alone.  SEASONALITY: MAOI/lithium, bright articficial light.  Avoid
dark workplaces.   VENTRICULAR  DYSRRHYTHMIA:  SSRI,  imipramine,  bupropion.
Avoid  trazodone.   HYPERTENSION: captopril, MAOI, trazodone.  Avoid aldomet,
clonidine,  reserpine,   propranolol.    OVERDOSE   RISK:   SSRI,  trazadone,
bupropion, Eskalith CR.   Avoid  TCA,  amoxapine,  lithium  cargbonate,  TCA,
maprotiline.    SEIZURE   DISORDER:   carbamazepine,  valproic  acid.   Avoid
bupropion, maprotiline, TCAs?.   COCAINE  ABUSE: desipramine.  ALCOHOL ABUSE:
Lithium, buspirone.  Avoid  benzodiazepines.   CHRONIC  PAIN,  FIBRTOMYALGIA,
IRRITABLE   BOWEL  SYNDROME,  ULCER:  amitriptyline,  trimipramine,  doxepin.
MIGRAINE: amitriptyline.  Avoid trazodone.

                     -DERMATITIS HERPETIFORMIS-
CLINICAL: Dermatitis herpetiformis (DH) is a chronic  eruption  characterized
by  intense  pruritic  vesicular,  papular  and urticarial involvement of the
extensor surfaces of the  forearms,  elbows, knees, buttocks, sacrum, occiput
and upper back.  About 33%  of  patients  will  have  vesicular  and  papular
involvement  of  the  face  and  neck.   The  itching is extremely severe and
chronic scratching will  often  obscure  the  vesicles.   The vesicles may be
grouped.  If the lesions are early or incomplete they may resemble urticaria.
The lesions will heal without scarring, but scratching may cause a  secondary
infection.   Males have a slight predominance over females in a ratio of 2:1.
The disease has its onset usually in  the  second or third decade of life and
is life long, but sometimes with aging it becomes  less  severe.   Dermatitis
herpetiformis  is associated with a gluten sensitive enteropathy in about 90%
of cases.  However, these patients  almost always are asymptomatic.  A strict
gluten free diet can be effective in clearing or improving the  skin  lesions
within  a  few  months.   Maximal  results  do  not occur for 1.5 to 2 years.
However, patients find it difficult to  adhere to a gluten free diet, because
it is so unappetizing, and the diet must be permanent to maintain control  of
the  eruption.   Any  type of diet indiscretion will cause an exacerbation of
the disease.  Biopsy  of  small  bowel  will  reveal  villous atrophy and IgA
deposition beneath the mucosa.  There  also  is  an  increased  incidence  of
thyroid  disease  and  a  small  increased risk for small bowel lymphoma.  By
maintaining  a  gluten  free  diet  the  risk  of  lymphoma  may  be reduced.
HISTOPATHOLOGY: Biopsy examination reveals subepidermal vesicles.  There  may
be  collections  of eosinophils within the vesicle.  Granular deposits of IgA
are found at the dermal-epidermal  separation  in about 90% of patients.  The
IgA is  deposited  in  the  dermal  papillae  which  is  directly  below  the
epidermis.   There  may  be  dermal-epidermal  microabscesses.   In  order to
confirm the diagnosis, immunofluorescent  examination  of  a biopsy should be
done from a non-lesional area of skin over the buttocks.   This  will  reveal
the  granular  deposition  of  IgA  and  C3  in  the  dermal papillae in most
patients.  Antiendomysial antibodies are found in most cases of DH, and these
are very sensitive  and  specific.   TREATMENT:  Treatment consists of either
dapsone or sulfapyridine.  Dapsone is much more effective.   Prior  to  using
this  drug the patient must be tested for a glucose-6-phosphate dehydrogenase
deficiency.  It is  usually  started  at  50  mg  po  bid  or tid.  Relief is
dramatic.  The itching is relieved  within  1-3  days  and  can  serve  as  a
diagnostic  procedure.   If  after  2  weeks  the eruption is controlled, the
dapsone may be reduced to 25-50 mg  daily or every other day therapy.  On the
other hand, if the eruption is not controlled on 50 mg bid the  dose  may  be
increased to 200-300 mg daily in divided doses at 2 week intervals.  Patients
should  be  monitored  while  on  dapsone  with  a CBC, and liver enzymes.  A
hemolytic anemia may develop and the patient may develop cholestatic jaundice
or a mononucleosis-like syndrome.  The  methemoglobin level should be checked
if cyanosis or lethargy develop.  Methemoglobin up to 15% may develop, but is
considered a normal response with dapsone.  Lethargy and headache  may  be  a
problem,  but  usually  improves with time.  Peripheral motor neuropathy is a
potential side effect of dapsone.  It  is usually reversible when the drug is
withdrawn.  Non-steroidal anti-inflammatory drugs should be avoided  as  they
may  activate  the  eruptions.   Sulfapyridine  may be used if the patient is
unable to tolerate or does  not  respond  to  dapsone.  The initial dose is 2
grams divided into 4 doses.  If the patient fails to respond to  this  amount
the  sulfapyridine  may  be  increased  to  4  grams daily.  Side effects are
nausea, renal stones,  hemolysis  and  lethargy.   Fluids should be increased
while on sulfapyridine.  Patients receiving either dapsone  or  sulfapyridine
should  have  weekly CBC for 1 month then q 2-3 weeks for 2 months and then q
3-4 months thereafter.

                         -DIABETIC DIARRHEA-
Diabetic diarrhea usually occurs in patients with long  standing  history  of
insulin  dependent  diabetes  mellitus.   Peripheral  neuropathy  is  usually
present  along with autonomic neuropathy (orthostatic hypotension, impotence,
retrograde ejaculation, urinary bladder  dysfunction, anhidrosis and abnormal
pupillary responses).  There may also be nausea and  vomiting,  fullness  and
impaired  gastric  emptying.   The  diarrhea  is  very  often  nocturnal  and
associated  with  anal  incontinence,  and  can  be  very  severe  along with
tenesmus.  Males  are  slightly  more  affected  than  females.   The overall
prevalence varies between 8-22%.  CAUSES: Diabetic diarrhea may have multiple
causes as the following: Bacterial overgrowth in the small  bowel  (there  is
greater  than  10  to  the  fifth colony forming units/ml of bacterial in the
small bowel aspirate), abnormal  colonic  motility (abnormal GI manometry and
transit studies),  exocrine  pancreatic  dysfunction,  anorectal  dysfunction
(abnormal  rectal  sensation  on  anorectal  manometry  and decreased resting
pressure.   About  20%   of   long   standing   diabetics   will  have  fecal
incontinence), alterations in intestinal secretion,  associated  sprue  (flat
biopsy  of  the  small  bowel), bile acid malabsorption (increased stool bile
acids), ingestion  of  sorbitol,  lactose  intolerance  (abnormal  results of
lactose hydrogen breath test)  and  sorbital  ingestion.   OTHER  CAUSES:  Of
course,  other  causes may occur in diabetic patients and should be ruled out
with analysis of stool for  blood, leukocytes, ova and parasites, clostridium
difficile, cultures and mucosal biopsies with sigmoidoscopy  or  colonoscopic
exam  to rule out inflammatory bowel disease, HIV, carcinomas and polyps etc.
TREATMENT: For patients that one can find no cause, treat with loperamide and
diphenoxylate which can decrease diarrhea  associated with a rapid intestinal
transit.  For patients that have intestinal motility or  secretory  disorder,
clonidine  may help by giving 0.1 to 0.6 mg bid.  Be aware that clonidine may
decrease gastric emptying and  may  cause orthostatic hypotension.  Bacterial
overgrowth can be treated with tetracycline,  quinolones,  metronidazole  and
cephalosporins  for  14  days  each  month, rotating these so that resistance
doesn't develop.  A gluten free diet is given for celiac disease, and lactose
free diet for lactose intolerance.   Bile  acid malabsorption is treated with
cholestyramine in a dose of 4 to 12 g/day, or aluminum hydroxide.  Octreotide
acetate, a long acting somatostatin analogue may be given subcutaneously,  50
to  75  ug  bid  and  can be given with the insulin.  Be aware, however, that
octreotide can inhibit  exocrine  pancreatic  secretion.   Patients that have
pancreatic insufficiency can be given pancreatic replacement enzymes.

                       -DIABETIC EMERGENCIES-
DIABETIC  KETOACIDOSIS:  Diabetic  ketoacidosis is usually easy to recognize.
The  patient  will  present   with  polyuria,  polydipsia,  hyperventilation,
decreased level of consciousness, and weight loss.  In addition  the  patient
may  have  abdominal  pain with vomiting.  If the patient is unconscious, the
differential  would  include  hypoglycemia,  diabetic  ketoacidosis  (DKA) or
diabetic hyperosmolar state.  If an emergent state is present and  a  glucose
will  not  be  available  for some time, blood work should be drawn including
blood glucose and ketones, and then  treated for hypoglycemia with IV glucose
.5 grams/kg (maximum of 25 grams).  If  the  patient  is  hypoglycemic,  this
amount will reverse the obtunded state and if the patient has DKA, the amount
of  glucose  given  will  not  harm the patient.  In DKA the serum glucose is
greater than 250 mg/dL and the pH is less than 7.3.  The serum bicarbonate is
less than 15  mEq/L  and  the  patient  has  a  ketonuria.  Serum ketones are
positive at 1:2 dilution.  The osmolality is variable and can  be  calculated
by  using the following formula: 2[Na + K+ (mEq/L] + glucose (mg/dL)/18.  The
patient  should  be  evaluated  to  establish  a  reason  for  the  DKA.  The
triggering mechanism is either an absolute deficiency of  insulin  or  actual
resistance to insulin.  The main effect of insulin in preventing ketoacidosis
is  to  inhibit adipose breakdown and thus prevent formation of ketones.  All
patients  that  have  DKA  are  volume  depleted  because  the  hyperglycemia
increases glomerular filtration of glucose, and because of this, the kidney's
ability to absorb glucose is  exceeded.   As  a result the hyperosmolar urine
pulls free water off into the urine producing dehydration.  Ketones  such  as
beta  hydroxybutyrate, acetoacetate and acetone are produced in the liver and
then released into the circulation producing acidosis.  The acidosis in turn,
causes a shift  of  potassium  from  the  intracellular  to the extracellular
compartment which is then excreted into the urine producing hypokalemia.   In
a  70  kg  patient  with DKA, the water deficit is about 7 Liters, the sodium
400-500 mEq, with smaller amounts of magnesium and phosphorus deficits.  When
the patient presents  with  DKA  a  history  should  be  obtained in order to
ascertain the cause of the DKA.  Viral or bacterial infections and myocardial
infarction may have precipitated  the  ketoacidosis.   The  preceding  events
should be reviewed.  Some patients may have missed their insulin, and because
of  nausea and vomiting and abdominal pain have decreased their fluid intake.
Physical exam should focus on the  degree  of  dehydration and a search for a
precipitating infection such as appendicitis,  pelvic  inflammatory  disease,
dental  abscess, pneumonia, etc.  Laboratory tests would include electrolytes
such as  calcium  phosphorus,  magnesium,  sodium,  potassium, chloride, BUN,
creatinine, arterial blood  gases,  glucose,  ketones,  osmolality,  amylase,
lipase  and  EKG plus CK if myocardial infarction is a serious consideration.
Be aware that the  amylase  in  DKA  may  be  elevated initially, but usually
returns to normal in 2-3 days.  Also, there may be a pseudo- elevation of the
creatinine secondary to the acetoacetate, and this should be  repeated  in  a
few days also.  TREATMENT: Treatment consists of 4 challenges.  Fluids should
be  given  to  correct  dehydration,  electrolytes  are  given to correct the
deficits,  insulin  is  given   to   reverse   the   ketotic  state  and  the
hyperglycemia, and all  precipitating  causes  should  be  corrected.   FLUID
THERAPY:  During the first 2 hours normal saline should be given at 400 mL/hr
if the patient has a mild depletion  of 5% body weight.  If there is moderate
depletion affecting 10% of the body weight, 700 mL/hr should  be  given.   In
severe  depletion  affecting 15% of the body weight, 1000 mL/hr is given.  If
the pH is less than 7 give 44  mEq of sodium bicarbonate per liter to correct
the acidosis.  After about 4 hours the normal saline can be changed to  0.45%
saline  with  the  drip  rate  cut in half, if the patient is hemodynamically
stable.  The urine output should be monitored keeping the output greater than
30-60 mL/h.  In elderly  patients  and  those susceptible to congestive heart
failure, the above fluid infusion should be modified.   ELECTROLYTE  THERAPY:
If  urine  output  is  adequate,  the plasma potassium less than 4 mEq/L, and
there are no EKG signs of hyperkalemia,  KCL  should be added giving KCL at a
rate of 10-40 mEq/hr.  Potassium phosphate may be used in place of KCL if the
phosphorus is lower than .5 mg/dL.  KCL is not routinely added to the first 2
liters of IV fluid, because the potassium early is usually  normal  or  high,
and  the  urinary  output  has  not  been established.  However, later in the
course of treatment the potassium level  will drop due to the insulin induced
intracellular  shift  of  potassium,  correction  of  the   dehydration   and
correction  of  the  metabolic acidosis.  The patient should be followed with
continuous EKG monitoring in  order  to  detect  any arrhythmias secondary to
hypokalemia.   If  potasssium   phosphate   is   used,   hypomagnesemia   and
hypocalcemia  may develop.  When the blood glucose reaches about 250 mg/dL, a
change from the 1/2 normal saline to D5 and .45% saline is started with 20-40
mEq KCL or  K  phosphate  added.   INSULIN  THERAPY:  Regular insulin such as
Humulin R insulin should be initially given as a loading dose of .2  U/kg  or
about  10-20  units  IV bolus.  Then a continuous infusion of regular insulin
should be started by adding 50 U in 250 ml of .9% saline and giving .1 U/kg/h
or about 5-10 U/hr (25-75 ml/hr).   Before starting the infusion flush the IV
tubing with 20 ml of insulin solution  before  starting  the  infusion.   The
continuous  insulin drip should be adjusted so the glucose decreases by about
100 mg/dl or less per hour.  If  the serum glucose has not dropped by greater
than 10% after 2 hours of the insulin drip, double the  infusion  rate  every
hour  until a drop in the glucose occurs.  When the glucose reaches about 250
mg/dl, decrease the insulin to  about  2-4  U/hr.  When the ketones and anion
gap have normalized change to a subcutaneous sliding  scale  and  discontinue
the  insulin  drip about 2 hours after the subcutaneous dose.  If ketones and
anion gap are still abnormal and the  glucose is less than 100 mg/dl while on
insulin, change to 10%  glucose  at  50-100  ml/h.   If  the  patient  has  a
refractory hyperglycemia and the insulin requirement is greater than 100 U/h,
hydrocortisone  should  be  given  IV every 4 hours.  COMPLICATIONS: Cerebral
edema is a complication of DKA.  Be  aware if the patient has an inordinately
high initial sodium level.  This may indicate that  the  patient  has  severe
hyperosmolarity.   Most  patients after 10 hours of DKA will have some degree
of brain swelling, particularly  in  children  and younger patients.  In most
cases, this is clinically silent.  However, significant clinical symptoms can
occur during the first 24 hours such as headache, disorientation, and further
decreasing levels of alertness.  Following  these  warning  signs,  seizures,
vomiting,  bradycardia,  hypertension and difficult respirations may develop.
In the advanced stages of cerebral edema due to DKA brain stem herniation may
occur with dilatation and fixation  of the pupils, coma and cardiorespiratory
arrest.   Treatment  of  cerebral  edema  is  treated   by   intubation   and
hyperventilation.   Steroids as dexamethasone, and mannitol may be given.  IV
mannitol is given at .5 to 1 gram/kg with a maximum of 50 grams.  MONITORING:
The patient should have fingerstick  glucoses  done  every 1 hour for about 6
hours.  These may then be be reduced to  every  3-6  hours  if  the  expected
improvement  is  occurring.   SMA  and ketones should be done every 4-6 hours
until the ketones and the anion gap have improved.  Cardiac enzymes should be
done every 8  hours  x  four,  along  with  EKG monitoring.  Amylase, lipase,
phosphate, magnesium, calcium, CBC, arterial blood gases,  blood,  urine  and
sputum  cultures, UA, urine protein, and serum pregnancy tests should also be
done.   NONKETOTOIC  HYPEROSMOLAR   SYNDROME:   The  management  of  diabetic
hyperosmolar state does not differ that much from  DKA.   Aggressive  insulin
therapy  as  in DKA is less of an issue.  The main thrust in treatment of the
diabetic hyperosmolar state is  fluid  management.  The elevated glucose will
normalize to a large extent with only minimal insulin therapy.  In Nonketotic
hyperosmolar syndrome the serum glucose is greater than 600 mg/dL.  The pH is
greater than 7.3 and the serum bicarbonate is greater than 20  mEq/L.   Serum
ketones  are  negative at 1:2 dilution and the osmolality is greater than 320
mOsm/kg.  Many of these  patients  present  in  a comatose state.  TREATMENT:
FLUIDS: The patient is given 1-6 liters of normal  saline  over  a  1-7  hour
period.  Following this .45% saline is given at a rate of 200-500 ml/hr.  The
urine  output  should  be  kept  at  greater  than  60 ml/h.  Electrolyes are
replaced as in DKA and a change  to  D5 in .45% saline when the blood glucose
is about 250 mg/dL.  INSULIN: A  loading  dose  of  regular  insulin  is  not
necessary  and  the amount of insulin given is reduced in treating nonketotic
diabetic hyperosmolar syndrome.  Add 50 U of regular insulin to 250 ml of .9%
saline and deliver 3-5 U/h (15-25 ml/hr).  The IV tube should be flushed with
20 ml of the insulin solution prior to the constant infusion.

                      -DIABETIC GASTROPARESIS-
Symptoms  include  vomiting,  nausea  or early satiety.  The patient may have
diabetic retinopathy, peripheral  neuropathy  or orthostatic hypotension.  In
an elderly patient rule out pancreatic carcinoma.  A diagnosis  is  suggested
if  a  non  contrast  radiograph  of the abdomen shows residual matter in the
stomach after an overnight  fast,  if  a  barium contrast study shows gastric
dilatation,  poor  or  absent  peristalsis,  bezoar  formation  or  prolonged
retention of barium in the stomach, or if esophagogastroduodenoscopy  reveals
food  particles  after  an  overnight  fast.   The  most  accurate  test is a
radionuclide gastric emptying scan.   TREATMENT  is with bethanechol (Duvoid,
Urecholine) 10 mg PO qid, or metoclopramide syrup (Reglan) 10 mg PO  QID,  AC
and  HS,  or cisapride (Propulsid) 10-20 mg PO QID AC and HS, or erythromycin
suspension (EryPed, Ilosone) 200 mg  PO  QID,  or domperidone 10-20 mg PO tid
(currently investigational).

                        -DIABETIC INFECTIONS-
MUCORMYCOSIS:  Amphotericin  B.  Give a test dose of 1 mg.  If OK, then 15 mg
given over a 2-4 hr period  that  same day.  Subsequent doses  are  increased
by 5 mg/day up to 1 mg/kg/day is reached.  Give total  of  3-4  grams.   Some
patients  tolerate  QOD  using  1.5  mg/kg/day.  Side effects of amphotericin
include chills, fever, nausea,  vomiting controlled with ASA, antihistamines,
antiemetics and small doses of steroids.  Febrile reactions can be controlled
with Demerol.  Lab: electrolytes,  CBC,  paltelets,  calcium,  magnesium  and
creatinine   and   UA.    IF  creatinine  rises  to  3-3.5,  discontinue  the
amphotericin until the creatinine is normal.  Then, resume, using 1/2 dose of
the previous dose.  Diagnosis is made with biopsy.  The extent of the disease
is determined with CT or MRI.   The  necrotic tissue and bone must be removed
and sinuses and focal abscesses drained.  MALIGNANT INVASIVE EXTERNAL OTITIS:
Ticarcillin + gentamicin and ceftazadime or aztreonam.  It is  almost  always
caused  by  Pseudomonas  aeruginosa.  CT will show the extent of involvement.
Surgical debridement is  needed.   EMPHYSEMATOUS CHOLECYSTITIS: The infection
is polymicrobial with clostridium spp.  and  gram  negative  bacteria  as  E.
coli,  Klebsiella,  etc.   It has a virulent course with gas in or around the
gallbladder.  There is a predominance in men with a high rate of gall bladder
gangrene and perforation.  The  mortality  rate  is 15-25%.  Serial abdominal
x-rays should be done for 4 days to detect gas.   Cholecystectomy  should  be
done  within  48  hours  of diagnosis.  EMPHYSEMATOUS PYELONEPHRITIS: Is life
threatening.  The diagnosis made by showing gas mottling of the kidney on KUB
or on CT.  The gas  tends  to  go  to the subcutaneous tissue.  Oftentimes, a
nephrectomy is required and drainage along with antibiotics for  2  weeks  or
more.    RENAL  PAPILLARY  NECROSIS:  Characterized  by  flank  pain,  fever,
microscopic or macroscopic hematuria  and  pyruria.   About 15% develop renal
failure.  Retrograde pyelography  shows  ureteric  obstruction.   Antibiotics
should  be  given.   PERINEPHRIC ABSCESS: The patient appears to have typical
pyelonephritis, but  the antibiotic response  is  poor.  US or CT will reveal
the  diagnosis.   Surgical  drainage  plus  antibiotics   will   be   needed.
Percutaneous drainage may be used.

                        -DIABETIC NEUROPATHY-
Distal symmetric sensory polyneuropathy (burning feet with pins and needles):
Treat with amitriptyline or desipramine 25-75 mg at HS.  DIABETIC  AMYOTROPHY
(diabetic  femoral neuropathy, proximal motor neuropathy) is characterized by
progressive leg weakness and knifelike  back  and thigh pains.  Difficulty in
arising from a chair and climbing stairs,  and  weight  loss.   The  creatine
kinase  is  normal.   Do  MRI of back to rule out lymphoma, or central lumbar
disk herniation.  EMG and nerve conduction studies should be done.  The blood
glucose may be normal or  only  slightly elevated.  Treatment is high protein
diet and increase of calories.  Switch to insulin may also help.  Improvement
in 6 months to 2 years is typical.  DIABETIC  OPTHALMOPLEGIA:  eye  pain  and
double  vision.   Usually  3rd  nerve paresis and occurs suddenly, reaching a
maximum in 3 hours and  then  improves  over  several weeks.  There is ptosis
with limitation of medial and upward movement and mild limitation of downward
movement.  Pupils are normal sized and react equally to light.  MRI is normal
as is magnetic resonance angiography, which can help rule out an aneurysm  of
the  internal  carotid  or  posterior communicating artery..  The eye pain is
deep and stabbing and needs analgesics  for  about 1 week.  Eye patch is used
for double vision.  Recovery is usually complete.  The differential diagnosis
includes syphilis, giant cell arteritis and cancer at the base of the  brain.
DIABETIC  CARPAL  TUNNEL  SYNDROME:  pain  worse at night awaking the patient
causing patient to dangle or  shake  the hand.  Cervical radiculopathy (which
rarely causes pain  at  night)  can  mimic  carpal  tunnel  syndrome  as  can
arthritis  and  pronator  syndrome  with  entrapment  of  median nerve in the
proximal forearm.  A positive  Tinel's  just  distal to the antecubital fossa
may be a clue.  Nocturnal pain in the pronator  syndrome  is  not  prominent.
Treat with nighttime splints.  If there is thenar atrophy and EMG evidence of
axonal injury, surgery is indicated.

                              -DIALYSIS-
There are 3 major types of dialysis;  intermittent  hemodialysis,  peritoneal
dialysis  and  continuous arteriovenous hemofiltration.  The type of dialysis
depends on several factors  such  as  respiratory compromise, bleeding risks,
previous abdominal surgery, fluid overload,  vascular  access  problems,  and
hypercatabolism.   In  general,  hemodialysis  is  used  in patients that are
hemodynamically stable  in  whom  solute  removal  is  the principal concern.
Peritoneal dialysis is used when heparin associated  bleeding,  and  lack  of
vascular  access  is  a  concern.  Continuous arteriovenous hemofiltration is
used in  patients  that  need  fluid  removal  from  massive  fluid overload.
INDICATIONS: Dialysis is usually started  when  the  BUN  irreversibly  rises
above 100 mg/dL.  In patients that have an elevated BUN secondary to prerenal
aztoemia  or obstruction, the BUN may be permitted to rise to about 150 mg/dL
for short periods of  time  until  the  etiology  is reversed.  Patients that
manifest the uremic syndrome (pericarditis, encephalopathy,  uremic  platelet
dysfunction,   somnolence,  convulsions,  myoclonus,  asterixis,  and  muscle
twitching  are  candidates  for  dialysis.   Patients  with  hyperkalemia are
candidates for hemodialysis because  the  rate  of  removal  is  rapid.   The
clearance  rates  are  100-200  mL/min.   Peritoneal dialysis and continusous
arteriovenous hemofiltration have potassium clearance rates of only around 20
mL/min.  Uremic acidosis is  best  managed  with  hemodialysis, but the rapid
removal of acid can pecipitate a disequilibrium syndrome.  The dialysis  bath
should  contain  at  least  2  mmol/L  of potassium because correction of the
acidosis is associated with hypokalemia.  Calcium (2.5 mea/L) is usually also
added to the dialysate bath because  correction of the hypocalcemia can cause
vomiting, nausea, hypertension and muscle cramping.  In  the  hemodynamically
stable  patient,  intermittent  hemodialysis  can  provide  the fastest fluid
removal by removing  1-2  L  of  fluid/hour  by ultrafiltration.  Peritooneal
dialysis can remove 2-3 L/d.  If too much fluid  is  removed  (>5-10  L/day),
hypernatremia  may  supervene, since peritoneal dialysis luid is hyponatremic
as compared with plasma.  Patients that  have massive fluid overload are best
treated with continuous arteriovenous hemofiltration, since the ultrafiltrate
is iso-osmotic.  HEMODIALYSIS: Most patients  with  oliguria  or  anuria  are
treated  by  intermittent  hemodialysis using 4 hours treatments, three times
per week, removing 2000-3000 ml of fluid during each session.  This will keep
the patient euvolemic.  If patients  have some remaining renal viability, the
weekly treatments may be reduced, especially if the  patient  does  not  have
oliguria.   The standard dialysate solution used for hemodialysis consists of
sodium  140  mEq/liter,  potassium   2  mEq/liter,  chloride  102  mEq/liter,
bicarbonate  35  mEq/liter  or  acetate  35  mEq/liter  and  calcium  2.5-3.5
mEq/liter.  This dialysate is prepared with purified water.  The  water  must
be   softened   to  remove  minerals,  and  deionized,  in  order  to  remove
electrolytes.   Treatment  with  reverse  osmosis  will  remove  aluminum and
electrolytes.  The water  is  then  filtered  by  an  ultrafilter  to  remove
endotoxins   and  bacteria.   Disadavantages  for  intermittent  hemodialysis
include the need for large bore hemoaccess, and the need for anticoagulation.
The rate of removal of solute depends on  the blood flow rate and the type of
dialyzer, but most can remove urea at around 150-200 mL/min with  blood  flow
rates  of  200-300 mL/min.  In general, a 4 hour dialysis will lower the urea
levels by about 50%.  Most  dialyzers  are  also capable of producing between
1-3 L of ultrafiltrate, depending on the patient's cardiac status.   Vascular
access for hemodialysis is accomplished either by a sugically placed Scribner
shunt,  or  percutaneous  cannulation  of the subclavian or femoral vein with
double lumen catheters.  Shunts consist  of two types; Arteriovenous fistulae
and arteriovenous grafts.  Arteriovenous fistulae are created  surgically  by
anastomosis  of  an  artery and vein (most frequently using the radial artery
and the cephalic vein).  It  is  usually  created  in the nondominant arm and
requires 4-6 weeks for maturation  to  take  affect.   Maturity  consists  of
thickening  of  the  venous  wall  so  that dialysis needles can be inserted.
Arteriovenous grafts are  created  when  the  patients vessels are unsuitable
because of arteriosclerosis.  Polytetrafluoroethylene grafts  (PTFE,  Gortex)
and  bovine  heterografts are the most commonly used foreign material to form
an anastomosis between an artery  and  a vein.  The femoral vein percutaneous
double lumen catheter is the most  frequently  used  for  rapid  access.   In
general,  the  catheter  can  only  be  left  in  place  for  about 3-5 days.
Complications  of  the  femoral   approach  include  pulmonary  embolism  and
retroperitoneal hemorrhage, thrombophlebitis, arteriovenous fistulae, sepsis,
hematomas and infection.  The subclavian  vein  approach  allows  the  double
lumen  catheter  to  remain in place for longer periods of time, and provides
the  patient  with  mobility   as   contrasted  with  the  femoral  approach.
Complications  include  pericardial  tamponade,   hemothorax,   sepsis,   air
embolism,  thrombophlebitis, cardiac arrhythmias, pneumothorax and subclavian
venous stenosis.  The efficiency of  hemodialysis depends on blood flow rates
of 200-300 mL/min.  The use of double lumen  catheters  may  result  in  very
inefficient  dialysis.  Anticoagulation is needed for hemodialysis and can be
a serious disadvantage.  In order  to  reduce hemorrhage, low dose heparin is
used at 10-20 units/kg/hour.  In order to avoid anticoagulation,  high  blood
flows  and  frequent  saline  flushes  of  the  filter, using 200 mL every 20
minutes,  has  been  successful.   COMPLICATIONS  OF  HEMODIALYSIS: Digitalis
toxicity may be seen if the potassium is  rapidly  lowered.   Most  dialysate
baths  routinely  contain 2 mmol/L of potassium.  By increasing the potassium
in the dialysate bath  to  3.5  mmol/L,  digitalis toxicity can be decreased.
Cardiac arrhythmias can be induced  by  magnesium  and  calcium  alterations,
pericarditis,   myocardial   infarction,   hypoxia,   acetate   toxicity  and
misdirections in subclavian catheterizations.   Heparin induced hemorrhage is
another  complication  that  is  managed   with   protamine   administration.
Protamine,  1  mg,  is given for every 100 units of heparin administered.  No
more than 15 mg of  protamine  should  be given over 5 minurtes.  Hypotension
during hemodialysis can be caused by large  amounts  of  fluid  removal,  and
acetate  intolerance.   This  can  be  averted  by  using  bicarbonate  based
dialysates.   The  "first  use  syndrome"  (incompatibility of cuprophane and
cellulose based membranes) can  lead  to respiratory distress and hypotension
via activation  of  complement.   Increasing  fluids  does  not  improve  the
hypotension.   The  syndrome  is treated with IV aminopylline or cubcutaneous
epinephrine.  Infections in patients with  grafts  occur  in up to 20%.  This
can be a potentially serious  situation.   Most  are  due  to  staphylococci.
Infection  is  less  common  in  fistulae  than  in  artificial  grafts.  The
infection can  lead  to  loss  of  the  access,  bacteremia,  and metastiatic
infection.  Patients can present  with  fever  only,  or  local  redness  and
tenderness.    Blood   cultures  should  be  drawn  from  a  nonaccess  site.
Vancomycin is commonly used giving single  dose vancomycin, 1 gram IV.  Since
vancomycin is highly protein bound, it will remain in the blood for 5-7 days.
If gram negative organisms are found, a single dose of gentamicin, 1.7  mg/kg
is  given IV.  Gentamicin is mildly hemodialyzable and requires an additional
dose at the end of the  subsequent  hemodialyses.  Most of these patients can
be treated as outpatients.  Clotted vascular access sites can occur when  the
patient  is  hypovolemic  or  hypotensive.  This usually occurs following the
dialysis treatment.  Patients may  also  occlude  by sleeping on the affected
side.  Management of the clotted vascular access sight consists of  hydration
and  the utilization of urokinase 2,500-5,000 IU infused locally, followed by
arteriography.  Bleeding sometimes  occurs  from  the  dialysis puncture site
after the procedure.  This is related  to  qualitative  platelet  defects  of
uremia,   systemic   heparinization  or  transient  thrombocytopenia  due  to
dialysis.   External  hemorrhage  can  usually  be  controlled  by  pressure.
Pseudoaneurysms and  aneurysms  sometimes  develop  from  the  many punctures
needed  for  dialysis.   Pseudoaneurysm  represents  a  pulsatile   mass   of
extravascular  blood that can dissect extravascularly and cause a loss of the
fistula.  Sometimes a vascular  steal  syndrome  develops  at the access site
with ischemia of the hand distal to the vascular access.  This  occurs  as  a
result  of  blood  being shunted through the vascular access.  It occurs most
frequently in patients with atherosclerosis  and diabetes.  In this condition
the extremity becomes  cool,  cyanotic  and  painful.   It  is  corrected  by
surgical revision or ligation.  A dialysis disequilibrium syndrome is another
complication.  This consists of nausea, vomiting, muscle twitching, seizures,
coma,  lethargy  and headache usually occuring during dialysis or immediately
following dialysis.  It is  caused  by  osmotic  shifts resulting in cerebral
edema in patients that are treated aggressively, and  in  those  with  severe
uremia.   In  order  to  prevent this, the dialysis time is shortened and low
blood flow rates are utilized.   Dialysis dementia usually occurs in patients
that have been on dialysis for many years.  It is due  to  aluminum  toxicity
from  aluminum-containing  phosphate  binders and from water high in aluminum
content used for the dialysis.   Symptoms  include personality changes with a
stuttering speech, seizures, myoclonus  and  progressive  dementia  that  can
ultimately   lead   to   death.   Dialysis  induced  amyloidosis  is  another
complication that occurs in  patients  that  have  been  on dialysis for 5-10
years.  The amyloid deposits are due to beta2-microglobulin, which is  poorly
cleared  by  dialysis.   Peritoneal  dialysis  may  clear beta2-microblobulin
better  than  hemodialysis.   It  can  cause  a  carpel  tunnel  syndrome and
arthropathy that commonly involves the large joints, such  as  the  hips  and
shoulders.   X-rays  usually  reveal  lytic  lesions.   PERITONEAL  DIALYSIS:
Peritoneal  dialysis  is useful in patients who have not had recent abdominal
surgery or who have  inadequate  hemoaccess.  Anticoagulation is not required
in  peritoneal   dialysis.    Indications   include   those   patients   with
cardiovascular  instability,  patients  with  contraindications  to  systemic
heparinization,  patients who must travel long distance for hemodialysis, and
patients who have  no  vascular  access.  Contraindications include abdominal
hernias,   ostomies,   recent   abdominal   surgery,   and   pleuroperitoneal
communications.  Complications include peritonitis, large amounts of  protein
loss,   hydrothorax,   respiratory  embarrassment,  glucose  and  electrolyte
abnormalites.  Chronic ambulatory  peritoneal  dialysis  (CAPD)  uses 2 liter
exhanges every 4-6 hours, three times per  day,  using  1.5%  dextrose.   The
fourth  exchange  is  done  at  night  for  8  hours  using  4.25%  dextrose.
Continuous  cyclic peritoneal dialysis (CCPD) is used in patients that prefer
the freedom of no exchanges during  the  day.  An automatic cycler is used to
obtain 4-6 two liter exchanges during 8-10 hours nocturnally.   The  final  2
hour  exchange  remains throughout the day until the following cycle the next
night.  Access to the peritoneal cavity is by two methods.  The safest method
employs a plaible silastic catheter  (Tenckhoff).  This allows the patient to
be ambulatory.  The other method uses  a  stiff  teflon  catheter  for  rapid
access.   In  the latter case, the patient is bedridden and drainage problems
are frequent.   Other  complications  include  bowel perforation, hemorrhage,
infection, and leakage around  the  catheter.   COMPLICATIONS  OF  PERITONEAL
DIALYSIS:  It  has been estimated that about 60% will have peritonitis during
the first year.  It should be suspected in patients that have abdominal pain,
cloudy fluid, and a peritoneal dialysis cell  count > 100 WBCs/mm3 with > 50%
neutrophils.  Most  cases  (60-75%)  of  peritonitis  are	caused  by  gram
positive Staph epidermidis and Staph aureus.  The remaining 25% are caused by
gram negative organisms.  Staph epidermidis and Staph aureus are treated with
intraperitoneal  vancomycin  1  gram  (per 2 liter) every 5 days for 3 doses.
Alternatively  Staph  epidermidis   may   be   treated  with  intraperitoneal
cefazolin.  The initial dose is  1  gram  (per  2  liter),  followed  by  500
mg/exchange  (2  liter)  for  14 days.  Pseudomonas aeruginosa peritonitis is
treated  with   gentamicin   70-100   mg   as   a   loading   dose  given  x1
intraperitoneally (per 2 liters), followed by 15 mg/exchange (per 2 liters) x
14 days.  Escherichia coli infections are  treated  with  ampicillin  loading
dose  of  500  mg  given  intraperitoneally  (per  2 liters), followed by 100
mg/exchange (per 2 liters) for  14 days.  Fungal peritonitis usually requires
removal of the catheter and termination of peritoneal  dialysis.   Exit  site
infections  usually  present  as  local  inflammation,  purulent drainage and
crusting.   Treatment  includes   frequent   cleansing   of   the  area  with
povidine-iodine or peroxide  and  antibiotics.   The  antibiotics  are  given
orally  and  usually  consist of cephalexin or trimethoprim-sulfamethoxazole.
The purulent  drainage  should  be  cultured.   Tunnel  infections  should be
suspected if exit site infections fail to clear with antibiotics, or when the
patient develops several episodes of peritonitis with the same  organism,  in
spite   of  adequate  antibiotic  therapy.   Ultrasound  may  be  helpful  in
diagnosis.  Therapy cponsists of unroofing  of the tunnel for drainage.  Most
of the problems occurring in peritoneal dialysis are mechanical  and  consist
of  poor  fluid  drainage  due  to  kinking,  catheter  migration, partial or
complete  blockage  of  the  catheter  by  omentum  or  by  fibrinous debris.
Frequently these patients are obese with large omentums.  Dialysate fluid may
migrate through the tunnel and leak out of the exit site.  Changing positions
and checking the tube for kinks should be tried.  Contrast  catheter  studies
may  be  done  to  ascertain  the  site  of obstruction.  Manipulation of the
intraperitoneal catheter  by  a  sterile  trochar,  infusion  of thrombolytic
agents may all be tried.  Intraperitoneal administration of heparin (500-1000
units  per  2  liter  bag  can  decrease  the  formation  of  fibrin  debris.
Occasionally giving the patient an enema will relieve the mechanical problem.
If unsuccessful, the Tenckhoff catheter will have to be  replaced.   Patients
will  occasionally  complain  of  abdominal  pain,  and pain in the shoulders
secondary to diaphragmatic irritation.   These  may  be due to the hypertonic
and ascitic fluid.  These will usually improve after the patient has been  on
dialysis   for   several   weeks   to   a  month.   CONTINUOUS  ARTERIOVENOUS
HEMOFILTRATION: This has utility in patients that are oliguric or anuric, and
are  receiving   high   volume   hyperalimentation.    Arterial   access  and
anticogulation are needed.  The Scribner shunt, and the combined  cannulation
of  the  femoral artery and vein are the two most used methods.  The Scribner
shunt is the safest.

                        -DIARRHEA (Chronic)-
The causes of chronic or recurrent diarrhea are legion.  The following should
be considered: DRUGS: colchicine, lactulose antacids, antibiotics, quinidine,
antihypertenisve agents, caffeine, digitalis, laxatives, sorbitol.  PROTOZOA:
Giardia  lamblia,  Entamoeba  histolyica,   Cryptosporidiosis   INFLAMMATORY:
Ulcerative  colitis,  Crohn's  disease,  Ischemic  colitis,  pseudomembranous
colitis TUMORS: Villous adenoma, carcinoid syndrome, islet cell tumors, bowel
carcinoma, medullary carcinoma of the thyroid MALABSORPTION: sprue, bile salt
malabsorption,  intestinal  lymphoma,  Whipple's disease, Lactase deficiency,
pancreatic    insufficiency,     disaccharidase    deficiencies,    alph-beta
lipoporteinemia.   FUNCTIONAL:  Irritable  bowel  syndrome,   diverticulosis.
POSTSURGICAL:  postgastrectomy  dumping  syndrome,  blind  loops, short bowel
syndrome,  enteroenteric   fistulas,   parasympathetic  denervation.   OTHER:
diabetes mellitus,  heavy  metal  intoxication,  cirrhosis,  hyperthyroidism,
Addison's  disease,  Pellagra,  amyloidosis,  cirrhosis.   The  cause  of the
diarrhea may be  surmised  by  association  with  other  symptoms as follows:
MARKED WEIGHT LOSS: malabsorption, inflammatory bowel disease, thyrotoxicosis
and  cancer.   ARTHRITIS:  Crohn's  disease,  ulcerative  colitis,  Whipple's
diseas, Yersinia  infection.   NEUROPATHY:  diabetic  diarrhea,  amyloidosis.
EOSINOPHILIA:     eosinophilic     gastorenteritis,     parasitic    disease.
LYMPHADENOPATHY:   Whipple's   disease,   lymphoma.    POSTURAL  HYPOTENSION:
Addison's disease, idiopathic  orthostatic  hypotension,  diabetic  diarrhea.
FLUSHING:    malignant   carcinoid   syndrome.    PROTEINURIA:   amyloidosis.
HYPERPIGMENTATION:  celiac  disease,  Whipple's  disease,  Addison's disease,
eosinophilic gastorenteritis, pancreatic cholera.  The HISTORY  can  be  very
important  in  pin-pointing  the  cause.   Check  for  constipation and fecal
impaction.  Small bowel disease is  suggested by large, loose bowel movements
+ periumbilical or right lower quadrant pain  or  when  the  diarrhea  starts
after  a  meal  or  ingestion  of  certain  foods.   Rectosigmoid  disease is
suggested by frequent passage  of  small  loose  stools  + crampy, left lower
quadrant abdominal pain or tenesmus.  Diarrhea that occurs after a meal  also
may  be  due  to  dumping  syndrome,  fistula, osmotic or malabsorption.  Fat
malabsorbtion causes foul, bulky, and greasy stools.  Fever and bloody stools
suggest invasive infection, inflammaotry  bowel  disease or neoplasm.  Flatus
and  frothy  stools  suggests  poorly  absorbed  carbohydrates.   Alternating
constipation and diarrhea with  mucous  supports  irritable  bowel  syndrome.
Recent travel should cause suspcion for giardiasis and amebiasis.  Antibiotic
therapy  can  cause pseudomembranous colitis.  Sexual and AIDs history should
be elicited  as  there  may  be  polymicrobial  enteritis  in  AIDs patients.
LABORATORY:  CBC,  amylase,  liver  funtion  tests,  PT,  glucose,   calcium,
eosinophils,  serum  carotene  and  B12  for  malabsorption.  Stool assay for
Clostridium difficile toxin,  ova  and  parasites, culture, stool leukocytes,
Sudan III fat stain.  If the Sudan stain is positive, then obtain a  72  hour
quantitative stool fat determination.  Normally, stool fat should not be > 6%
of  daily  fat intake.  Stool fat > 6 grams/day while on a test diet of 100 g
of fat/24 hours  suggest  fat  malabsorption.   There  may  be false positive
results for stool trophozoites from enemas, antibiotics,  barium  kaolin  and
bismuth.   Several stool samples may be needed and the stool should be fresh.
Trophozoites require a fresh sample.  Less fresh samples can be used for ova.
Indirect hemagglutination assay for  amebic  disease  is usually > 1:128.  It
takes 2-4 weeks for the seroconversion to occur.  It is  85%  sensitive  with
intestinal  disease  and  95%  sensitive with extraintestinal disease.  Small
bowel   aspiration   and   biopsy   may   be   needed   for   giardiasis  and
cryptosporidiosis.  Laxative abusers can be suspected by checking  the  stool
for  phenolphthalein  after alkalinization of the stool.  A D-Xylose test can
be done for detection of small bowel disease.  Fecal fluid analysis should be
done for pH nad Osmolality  and  solute  gap.  In osmotic diarrhea the solute
gap is > 100.  In secretory  diarrhea  the  solute  gap  is  <  50.   Osmotic
diarrhea  can  be  caused  by  lactase  deficiency which is common in blacks,
Orientals, Eskimos, and people from the Middle East.  The pH of ths tool is <
6 and blood sugar increases <	20  mg/100 mL after lactose ingestion.  There
is an abnormal H2 breath test and jejunal  biopsy  results  are  normal  with
decreased  disaccharidase  levels.   Secretory  diarrhea produces the WHDA or
Verner-Morrison  syndrome  (pancreatic  cholera)   which  produces  a  watery
diarrhea, hypokalemia and achlorhydria.  The diarreha is massive with 5 L/day
typical.  There may be other multiple endocrine adenomatosis tumors producing
hyperglycemia and hypercalcemia.  It is associated with a non beta islet cell
tumor of the pancreas.  Vasoactive intestinal  peptide  is  the  most  common
cause,  but  also  may be mediated by prostaglandin, secretin and calcitonin.
Hormone levels should be  done  along  with  pancreatic scan and angiography.
Carcinoid tumors also produce  a  secretory  diarrhea  along  with  abdominal
cramping,  nausea,  vomiting  and  flushing.   Hepatic metastasis is present.
Diagnosis is made by  elevated  urinary  levels of 5-hydroxyindoleacetic acid
(5-HIAA) and liver  biopsy.   Laxative  abuse  also  can  cause  a  secretory
diarrhea.   Approximately 15-30% of the elderly take laxatives and usually do
not admit to taking laxatives.  Proctoscopy will show melanosis coli.  Barium
enema will show a dilated hypomotile colon with absent haustra.

                    -DIAZOXIDE AND HYPERTENSION-
(Hyperstat).  50-100 mg IV bolus,  repeated  or  15-30 mg/min by IV infusion.
Side effects: hypotension, flushing, nausea, tachycardia, chest pain.

                      -DIGITALIS INTOXICATION-
Digitalis has a  narrow  therapeutic  index  and  toxicity  is fairly common,
developing in about 20% of patients.   In  the  USA  digoxin  is  the  common
preparation  that  is  used  for  treating  congestive  heart failure, atrial
fibrillation/flutter and  supraventricular  tachycardia.   Cardiac glycosides
act by inhibiting the sodium-potassium adenosine triphosphatase membrane pump
in the myocardial cells.  In toxicity, this usually leads to an  increase  of
intracellular  calcium  and  sodium  and  the  loss  of  potassium.  In acute
overdoses of digitalis there is  frequently hyperkalemia.  Digitalis causes a
decrease in the refractory period of both atrial and ventricular heart cells.
There  is  lowering  of  the  resting  membrane  potential   which   promotes
excitability.   Phase  4  of  the  action potential is usually increased with
increased automaticity.  Vagal tone is  increased and there is a prolongation
of phase 3 of the action potential  in  the  AV  node  and  the  His-Purkinje
system.   Digitalis  increases  the inotropy of myocardial cells.  Changes in
the EKG with therapeutic  doses  of  digitalis  include  shortening of the QT
interval and prolongation of the PR interval.  Digitalis effect is  indicated
by a downsloping and scooping of the ST segments.  Digitalis, typically, will
slow  the  ventricular rate of atrial fibrillation.  The daily maintenance of
digitalis varies, ranging from about .0005  mg/kg in premature infants to .75
mg in adults with a mean average dose of .25 mg in adults.  Approximately 80%
of the oral tablets of digoxin will be absorbed with a bioavailability of the
capsules approaching 95%.  The drug is eliminated via the kidneys with a half
life of about 1.5 days.  After acute overdose, blood  levels  done  before  8
hours  do  not  accurately  reflect  the  tissue  concentrations of the drug.
Normal  serum  digoxin  levels  are  .5  ng  to  2  ng/mL  as  determined  by
radioimmunoassay.  This is only  a  rough  guide  as  some patients are toxic
within this range while others have no toxicity even though the upper  limits
of  2  ng/mL are exceeded.  CLINICAL: Digitalis poisoning may be divided into
chronic and acute overdoses.  The  chronic variety is usually non-intentional
and seen in older patients, while the acute toxicities may be intentional and
massive.  The acute overdoses are usually associated with hyperkalemia  while
the  chronic  toxicities  are associated with hypokalemia.  If the patient is
fairly healthy, acute overdoses of  less  than  5  mg of digoxin will usually
cause no severe toxicity.  However, doses of 10 mg are associated with  fatal
outcomes.  There are several predisposing factors that will lead to toxicity,
and must be recognized, so that dosage adjustments can be made.  Hypokalemia,
hypomagnesemia,  and  hypercalcemia  all  can  lead to toxicity.  If there is
significant renal insufficiency  there  is  an  accumulation  of the drug, as
digoxin is eliminated by the kidneys.  In  general,  the  elderly  population
requires  less  digitalis.   Any  patient  that is hypoxic and has myocardial
ischemia is particularly  susceptible  to digitalis toxicity.  Hypothyroidism
can predispose to digitalis toxicity.  Drugs that  will  increase  the  serum
level  of  digoxin  include  quinidine,  verapamil,  amiodarone, propafenone,
spironolactone, diphenoxylate  and  propantheline  bromide.   Drugs that will
decrease digitalis  levels  include  sulfasalazine,  neomycin,  antacids  and
cholestyramine.   Any  patient  that  takes  beta  blocker  concurrently with
digitalis  should  be  monitored   closely   to  prevent  excessive  AV  node
depression.  Diuretics will cause hypokalemia and  hypomagnesemia,  which  in
turn   leads   to   increased  toxicity.   Amphotericin  B  will  also  cause
hypokalemia.  Clinical symptoms  commonly  associated with digitalis toxicity
include fatigue, weakness, nausea,  anorexia  and  visual  aberrations.   The
classic  visual  changes  of  yellow green color is common, but there is also
red, brown, blue and  white  color  visual alterations.  Some patients report
photopsia, photophobia, snowy vision and even decreased  visual  acuity.   In
descending  order  of  frequency, abdominal pain, dizziness, abnormal dreams,
headaches, diarrhea and vomiting can  also  occur.  Any patient who is taking
digitalis and has any of the above constitutional symptoms with various types
of cardiac arrhythmias should be investigated for digitalis toxicity.  A host
of various arrhythmias can occur in digitalis toxicity.  The most common  are
ventricular  premature contractions.  It has been said that paroxysmal atrial
tachycardia with  block  is  pathognomonic  of  digoxin toxicity.  Junctional
tachycardias, ventricular tachycardia, especially  bidirectional  ventricular
tachycardia,  may  be  seen.   Ventricular  tachycardia  in  association with
digoxin toxicity may have a mortality  as  high as 50%.  This may deteriorate
into ventricular fibrillation.  Any patient who  develops  regularization  of
the ventricular response to atrial fibrillation with junctional escape beats,
secondary   to   AV   block,  should  be  suspected  of  digitalis  toxicity.
Bradyarrhythmias may also occur in  digitalis  poisoning.  There may be sinus
bradycardia, sinus exit  blocks  or  1st,  2nd  and  3rd  degree  AV  blocks.
Evaluation of digitalis toxicity includes an accurate history for other drugs
that  may  be  causing  an interaction.  Cardiac monitoring, determination of
electrolytes, creatinine and a  serum  digoxin  level  should be ordered.  If
there has been an acute overdose, the serum digoxin should be drawn at  least
8  hours  post-ingestion.  TREATMENT: Gastrointestinal decontamination should
be carried out with repeated doses  of activated charcoal.  Ipecac should not
be used.  If the patient demonstrates bradyarrhythmias, 0.5 mg of atropine IV
may be tried, but if the bradyarrhythmia is hemodynamically  significant,  it
may  be  necessary  to insert a pacemaker.  Ventricular tachydysrhythmias may
respond to  either  lidocaine  or  phenytoin.   Phenytoin  has  a theoretical
advantage over lidocaine in that it is able to enhance  AV  node  conduction,
but clinically there is essentially no difference in the efficacy.  Phenytoin
is  given at 25 mg/min until the arrhythmia is abolished or 15 mg/kg has been
administered.  Lidocaine  is  given  as  a  1  mg/kg  bolus.   If effective a
continuous drip of 2-4 mg/min may be  started.   Magnesium  sulfate  is  also
effective  even if the serum magnesium level is normal.  This can be given as
a 2-3 gram dose IV over 1  minute, followed by a continuous 4-5 hour infusion
at 2 grams/hour.  Electrical  cardioversion  of  ventricular  tachycardia  is
dangerous   in   digitalis  toxicity,  because  it  can  produce  ventricular
fibrillation.  However, if it is used,  the  patient should be first be given
phenytoin 200 mg IV, and then converted at low energies of 5-10 watt-seconds.
Isoproterenol is  contraindicated  in  the  treatment  of  digitalis  induced
bradycardia,  because  it  may  produce  more  arrhythmias.  Type IA drugs as
quinidine and procainamide should not be  given as they have the potential of
depressing conduction in the AV node, sinoatrial node  and  the  His-Purkinje
system.   Bretylium  also  should  not  be  given as it can cause ventricular
fibrillation and exacerbate ventricular  arrhythmias.  Although beta blockers
may decrease the digitalis induced automaticity, it also will potentiate  the
digitalis-induced  toxic  effects  on  the sinoatrial and AV node.  Likewise,
verapamil should not be  used  as  it  has  an  adverse drug interaction with
digitalis,  increasing  the  serum  levels  of  digoxin,  and  also   further
depressing  AV  node  conduction.   Hyperkalemia  above 6 mEq/liter should be
treated with IV 10% glucose, IV sodium bicarbonate, IV insulin and Kayexalate
retention enema,  25%  in  sorbitol  25%.   Hyperkalemia  is  very serious in
digitalis poisoning, and a pacemaker may be needed along with hemodialysis if
the hyperkalemia proves to  be  refractory  to  conservative  measures.   For
severe cases of digitalis toxicity with hyperkalemia and cardiac instability,
digoxin  immune  Fab  should  be  given.   Indications for the use of digoxin
immune Fab (Digibind) include ingestion of more  than 10 mg in adults or more
than 4 mg in children, steady state serum digitalis  levels  greater  than  5
ng/mL  in  children or 6 ng/mL in adults, serum potassium greater than 6 mE/L
in children or 5.5  mEq/L  in  adults,  progressive symtomatology in spite of
conventional therapy, and any  potentially  life  threatening  conduction  or
arrhythmic  situation.  Each vial of Digibind contains 40 mg of Fab fragments
and this will neutralize .6 mg of  digoxin or digitoxin.  The number of vials
needed if the ingested dose is known is calculated by multiplying 1.7  x  the
ingested  dose  in  mg.   If  the steady state serum digoxin concentration is
known the number  of  vials  needed  is  calculated  by multiplying the serum
digoxin in ng/mL x body weight in kg x  .0093.   If  neither  the  amount  of
digoxin ingested or the serum digoxin level is known, 5-10 vials in adults is
an  appropriate  amount  to use.  Hyperkalemia is quickly reversed by the Fab
fragments,  and  bradyarrhythmias  will  usually   resolve  in  1  hour,  and
tachyarrhythmias are  corrected  within  a  few  hours.   Side  effects  from
Digibind have been few even though the IgG antibodies are derived from sheep.
The  incidence  of acute hypersensitivity or delayed serum sickness reactions
have been minimal after initial  doses.   Remember that digoxin levels should
be drawn at least 8 hours post ingestion, and that after using Fab  fragments
the  serum  digoxin  level  by  radioimmunoassay  will  rise  as  the drug is
extracted from tissue for  binding.   False  positive elevations of the serum
digoxin  level  may  be  seen  in  newborns,  patients  that  have   abnormal
immunoglobulin  levels,  and  chronic renal failure, because of an endogenous
digoxin-like  substance  that  cross  reacts  with  most  common  immunoassay
antibodies.  Eventually, after administration  of  the Digibind, there may be
worsening of the conditions for which

                        -DIGITALIS TOXICITY-
Digitalis intoxication can occur whether from a single acute overdose or as a
consequence of chronic accidental ingestion.   Digoxin  is  secreted  by  the
kidneys  and  attention  should be directed toward kidney function, potassium
and magnesium levels.  The  patient  may  develop nausea, vomiting, anorexia,
confusion, amblyopia, and diarrhea as well as various arrhythmias.  Excessive
digitalis can produce prolonged PR intervals, Wenckebach rhythm, and complete
heart block due to its effect on the AV node.  Digitalis also  increases  the
automaticity   of   Purkinje  fibers  with  increased  reentry  resulting  in
ventricular tachycardia, ventricular  fibrillation  or coupled extrasystoles.
Bidirectional ventricular tachycardia is diagnostic  of  digitalis  toxicity.
Nonparoxysmal  junctional tachycardia due to enhanced junctional automaticity
can also  be  seen.   Predisposing  factors  for  digitalis  toxicity include
cardiomyopathies, ischemia, conduction  abnormalities,  hypoxemia,  diuretic,
verapamil, beta blockers, quinidine, amiodarone, hypomagnesemia, hypokalemia,
hypernatremia,  hypercalcemia  and  renal  insufficiency.   Some patients can
develop digitalis toxicity even  if  digoxin  blood  levels are within normal
limits with the above predisposing factors prevailing.  TREATMENT:  Treatment
starts with discontinuing the cardiac glycoside and replacing serum potassium
unless  there is renal insufficiency, AV block, serum potassium > 5 mEq/L, PR
interval > .26 sec or there has been a huge overdose of digitalis.  Potassium
chloride 80 mEq is added to 1 L  of D5W and given at 6 mL/min.  Hyperkalemia,
on the other hand, can be treated with polystyrene sulfonate 15 G  in  20-100
mL  of  syrup PO 1-4 times daily OR 30-50 G in 100 mL of water by rectum q6h.
Dialysis and digitlais antibodies  are  also useful in treating hyperkalemia.
Bradydysrhythmias may be treated with atropine at .5 mg IV and repeated at  5
minute  intervals as needed up to a dose of 2 mg.  If atropine is ineffective
temporary pacing  may  be  started.   Treatment  of  tachydysrhythmias may be
treated with IV magnesium 2 grams given over 20-30 minutes if  there  are  no
contraindications such as renal insufficiency.  If there is no improvement of
the   ventricular  arrhythmias  with  potassium  and  magnesium  replacement,
lidocaine may be given as a  50-100  mg  IV  bolus, and repeated in 5 minutes
until a favorable response is achieved, or a total of 300 mg of lidocaine has
been given.  If the arrhythmias  is  controlled,  a  continuous  infusion  of
lidocaine given at 2-4 mg/min should be started.  Phenytoin is also useful in
treating ventricular arrhythmias given as 100 mg q 5 minutes up to a total of
1000  mg.   Isoproterenol is contraindicated in digitalis toxicity because it
may cause or exacerbate  ventricular arrhythmias.  Likewise, cardioversion in
patients with digitalis toxicity can cause refractory ventricular  tachycaria
and  fibrillation  or  even asystole.  Cardioversion is only safe in patients
with normal digitalis levels and no evidence of toxicity.  The administration
of specific antibody  fragments  to  digoxin  (digoxin  immune fab, Digibind)
should be used when there are life  threatening  dysrhythmias  that  are  not
responding  to  the  above  thyerapeutic  measures,  in those patients with a
serium potassium > 5 meq/L, in adult  patients who have ingested more than 10
mg of digoxin or 4 mg in children, and in  those  patients  who  have  steady
state  digoxin level > 10 ng/mL.  Each vial of digoxin immune Fab contains 40
mg of antibody which will bind .6  mg of digoxin or digitoxin.  If the amount
of ingestion is unknown or the digoxin level is not available, and  there  is
an  indication  for Digibind, 20 vials (800 mg) should be given.  This amount
is successful in about  70%  of  cases  in treating the dysrhythmia.  Digoxin
specific antibodies have a high affinity  for  digoxin.   Not  only  do  they
circulate  in  the  intravascular  space,  but  they  also  diffuse  into the
extracellular space where they bind free digoxin.  The complex formed is then
excreted via the kidneys.  Due  to  the gradient formed intracellular digoxin
will diffuse into the extracellular spaces and be bound.  Calculation of  the
number  of vials of Digibind to be used can be found by multiplying 1.5 x the
ingested dose in mg,  OR  by  multiplying  the  serum  digoxin (ng/mL) x body
weight (kg) x 10 to  the  minus  2.  A  third  method  first  determines  the
calculation  of  the body load of digoxin either based on the amount ingested
or based on the  serum  level  which  is  measured 6-8 hours after injestion.
Based on the amount ingested: multiply the amount ingested in mg x .8 to  get
the  body  load  of  digoxin.   Based on the serum levels: multiply the serum
concentration (ng/ml) x 5.6  x  body  weight  (kg)/1000.   As  a last step to
ascertain the number of vials needed, divide the body load of digoxin  in  mg
as calculated above by .6 mg/vial.

                    -DISCOID LUPUS ERYTHEMATOSUS-
CLINICAL: Discoid lupus  erythematosus  (DLE)  is  a  chronic  disorder  that
primarily  affects  the  skin  with  sharply marginated, dull red macules and
plaques  that  have  adherent  scales,  erythema,  telangiectasia, follicular
plugging and atrophy.  When the scales are removed there  is  a  carpet  tack
appearance  of  the  skin.   The  lesions  are  rarely  pruritic,  and  mouth
ulcerations  will  occur  in  about  15%.   Older lesions undergo atrophy and
appear as smooth  white  or  hyperpigmented  scars  with telangiectasia.  The
predominant age group affected is 20-40.   Females  are  affected  more  than
males  in  a  ratio of 3:1 in localized DLE, and 9:1 in generalized DLE.  The
typical lesions are seen on the  malar  areas,  lower lip, ears and bridge of
nose in localized DLE.  Alopecia may develop with scalp lesions present.   In
generalized DLE the lesions can be found on the thorax and upper extremities.
The disease is chronic and may persist or recur for years.  Sun exposure will
worsen the disease.  DLE is a scarring disease and as it undergoes healing it
may  leave  depigmented, depressed, scars that are disfiguring.  In less than
5% of patients there may  progression into systemic lupus erythematosus.  The
localized disease of the face may also convert to a more widespread cutaneous
disorder involving the upper portion of the trunk and the  extensor  surfaces
of  the extremities.  However, unlike SLE there are no renal complications or
systemic vascular involvement.  LABORATORY:  Every patient that presents with
cutaneous  signs  needs  to  have  a  workup  to  rule  out  systemic   lupus
erythematosus.   Biopsy  should be done from the active margin of the lesion.
Biopsy will not differentiate  DLE  from  SLE,  but  will help separate other
diseases  involved  in  the  differential.   ANA,  double  stranded  DNA  and
complement should all be done.  If these are positive,  then  SLE  should  be
considered.  About 20% of patients that have DLE will have a positive ANA and
about  20%  will  have  positive  tests  for  single  stranded  DNA  (ssDNA).
Antibodies  against  double  stranded  DNA  are almost never positive in DLE.
Occasionally in DLE there  may  be  a  positive  Ro/SSA in patients that have
marked photosensitivity, but a negative ANA.  Patients with DLE  may  have  a
slight  leukopenia.   Immunofluoroscopic  examination  of  the  biopsy may be
needed for confirmation of  the  diagnosis,  but  may  be falsely positive in
sun-exposed areas.  Typically, there  would  be  basement  membrane  antibody
present.  DIFFERENTIAL DIAGNOSIS: The differential would include polymorphous
light  eruptions,  drug  eruptions,  seborrheic  dermatitis,  rosacea, plaque
psoriasis, sarcoidosis, and actinic  keratoses.  Rosacea usually has pustules
and there is no atrophy.  Polymorphous light eruptions are not  atrophic  and
will  usually vanish when sunlight is avoided.  Seborrheic dermatitis lesions
are not atrophic and involve  the  nasolabial area.  Lymphoma and sarcoidosis
may cause some difficulty that will be sorted out after biopsy.  If there  is
scarring  of  the  scalp  and  the  concha  of  the ear this will help in the
diagnosis of DLE.  In  lupus  vulgaris  there are nodulations and ulcerations
that are not seen in DLE.  TREATMENT: Patients should avoid sunlight and  use
sunscreens.   Most  of the lesions of DLE can be controlled with high potency
topical  steroids  or   intralesional   steroids.    Drugs   that  can  cause
photosensitive reactions such as piroxicam and thiazides should  be  avoided.
Topical   steroids   such  as  clobetasol  propionate  (Temovate)  cream,  or
halobetasol propionate (Ultravate) may  be  applied  at bedtime.  The effects
may be enhanced by  covering  with  saran  wrap.   Intralesional  therapy  is
accomplished with triamcinolone acetonide suspension using 2.5-10 mg/mL.  The
lesions  may  be  injected  at  monthly  intervals.  Atrophy may develop as a
result.  Excessive use should be  avoided.  Antimalarials should only be used
after local therapy has  been  unsuccessful  and  the  diagnosis  of  DLE  is
definite.   Antimalarials  are  effective  in about 60% of cases.  Flares may
occur if antimalarials are  given for psoriasis.  Ophthalmologic examinations
should be done prior to treatment and every 6 months.  Baseline G6PD  levels,
creatinine,  and  hepatic  enzymes must be done prior to initiating treatment
with antimalarials.  Hydroxychloroquine sulfate is given at 200-400 mg orally
and daily for several weeks.  The  drug  should  be  given at least a 3 month
trial before terminating.  Quinacrine has not caused any eye damage,  but  it
does  discolor  the skin yellow.  The dose is 100 mg daily.  Dapsone is given
at 50 mg/day po.  Isotretinoin has been  used at 80 mg/day.  but will produce
teratogenicity in pregnant women.  Before using this drug  a  pregnancy  test
must  be  done,  along with informed consent and the patient must be using an
efficacious contraceptive.

                 -DISSEMINATED GONOCOCCAL INFECTION-
Ceftriaxone 1 g IM or IV q24h daily until improvement, followed by cefuroxime
axetil 500 mg bid  PO  or  amoxicillin  500  mg  with  clavulanic acid tid to
complete 7 days of therapy or Ceftizoxime 1 g IV q8h daily until improvement,
followed by cefuroxime 500 mg bid or amoxicillin 500 mg with clavulanic  acid
tid  to  complete  7  days  of therapy or Spectinomycin 2 g IM bid for 3 days
(treatment  of   choice   for   disseminated   infections   caused   by  PPNG
(penicillinase producing N. gonorrhoeae).

              -DISSEMINATED INTRAVASCULAR COAGULATION-
Disseminated intravascular  coagulation  (DIC)  is  predominantly  a bleeding
disease that is caused by some underlying severe disease.  However, in  about
8%  of  patients,  thromboembolic  complications  may occur such as pulmonary
emboli, acute arterial occlusions,  necrotic  skin lesions, stroke, ischemia,
and myocardial infarctions.  Also, thrombosis is more common than bleeding in
CHRONIC dissemianted intravascular coagulopathy.  In classic DIC bleeding may
occur into the skin, GI tract, GU tract, mucous membranes and  the  CNS.   It
typically  produces bleeding or ecchymoses at venipuncture sites.  Histologic
findings include  fibrin  thrombi,  large  and  small  vessel thrombosis with
frequent involvement of the lungs, kidney, liver, GI mucosa, adrenal  glands,
brain  and  pituitary  gland.  This involvement may present as renal failure,
adult respiratory distress syndrome,  neurologic  dysfunction and the classic
skin lesions that  are  described  as  lesions  with  a  hemorrhagic-necrotic
centers  with an	erythematous periphery.  DIC is a dynamic process and may be
severe with decompensation,  compensation  or  over compensation depending on
the fibrinogen level.  It also may be acute or chronic  in  nature.   DIC  is
initiated by activation of the coagulation pathway by several mechanisms such
as  contact  factors  (vessel  wall  damage  by Rocky mountain spotted fever,
sepsis), release of tissue  thromboplastin  (tissue  injury secondary to dead
fetus,  abruptio  palcenta,  cancers,  brain  injury),  shock,  stasis,   and
reticulendothelial  damage (Kassabach-Merritt syndrome), and antigen antibody
interactions (mismatched  blood  transfusions,  purpura  fulminans).   All of
these can result in accelerated utililization  of  the  coagulation  factors.
Infections  that are capable of causing DIC include bacteria (Staphylococcus,
streptococcus,    pneumococcus),    fungi    (histoplasmosis,   aspergillus),
rickettsia, viruses and protozoa.  Endotoxin from gram negative organisms  is
a  common  inciting  cause.   Gram  negative  sepsis is more common than gram
positive sepsis as  a  cause  for  DIC.   Several  obstetric problems such as
premature separation of the palcenta, septic and induced abortion, postpartum
hypertensive renal fialure, placenta previa and retained dead fetus  are  all
capable   of   causing  DIC  by  releasing  tissue  thromboplastin  into  the
circulation which in turn  can  activate  the coagulation process and consume
clotting  factors.   Carcinoma  of  the  lung,  stomach,  breast,   lymphoma,
pancreas,  and prostate are the most common malignancies that cause DIC.  The
patient  may  present  with  the  Trousseau  syndrome  which  is  a migrating
thrombophlebitis of the arterial and the venous systems.  Acute promyelocytic
leukemia, acute  renal  failure  associated  with  cardiogenic  shock,  liver
disease,  hemangiomas,  aortic aneurysms, angiography, burns, crush injuries,
acidosis and alkalosis, gunshot  wounds,  mucinous adenocarcinomas and severe
hemolytic transfusion reactions are other causes  of  DIC.   Excess  thrombin
activity  seems  to be the underlying pathophysiologic basis for DIC.  Excess
thrombin  will  cleave  fibrinogen  to  fibrin  monomer,  stimulate  platelet
aggregation, activate factors V  and  VIII  and release plasminogen activator
which  will  generate  plasmin.   The  plasmin  then  cleaves  fibrin,  which
generates fibrin  degradation  products  and  this  then  further  inactivate
factors  V  and  VIII.  Thrombocytopenia occurs in 90% of patients, increased
prothrombin  time  in  90%  of  patients  and  hypofibrinogenemia  in  70% of
patients.  Hypofibrinogenemia is the most  important  diagnostic  feature  in
differentiating  between  other  causes  of  bleeding.  The only other causes
producing  hypofibrinogenemia  are   severe   liver  disease  and  congenital
hypofibrinogenemia.  However, in some cases of DIC, the  fibrinogen  will  be
normal  in  DIC,  but  if  a baseline fibrinogen is available, the fibrinogen
might  have   been   initially   elevated   secondary   to  malignancies  and
inflammation.  Eventually however, the fibrinogen should drop.   Classically,
in  severe  DIC  the plasma fibrinogen is reduced to between 10-50 mg/100 ml.
The PTT may or may not be prolonged.  In some cases the peripheral smear will
reveal microangiopathic changes of  the  RBCs  (25%).   Also, the presence of
toxic granulations and Dohle bodies or spur cells of  liver  failure  may  be
present which would lend support to the etiology of the underlying illness of
DIC.  Routine assays for fibrin degradation products (FDP) do not distinguish
between fragments of fibrinogen and fibrin.  The D-dimer may be more specific
for  DIC  while  the  FDP  is more sensitive.  Antithrombin III levels can be
severely depleted.  Factors V and  VIII  are regularly decreased, but factors
VII and X are normal in DIC.  If the  patient  has  subacute  DIC,  the  only
hematologic   abnormalites   may  be  thrombocytopenia  and  elevated  fibrin
degradation products.  Fibrinogen levels are  usually  normal and the PTT can
also be normal.  DIFFERENTIAL DIAGNOSIS: Excessive bleeding  can  be  due  to
several  other  causes besides DIC.  Liver disease can prolong the PT and the
PTT, but the fibrinogen levels are  usually normal in mild liver disease, and
the platelets are usually normal or only mildly depressed.  Factor V  may  be
decreased in liver disease, but factor VIII is normal.  Factors VII and X are
decreased in liver disease.  Severe liver disease can deplete the fibrinogen.
Thrombotic  thrombocytopenic purpura can produce a microangiopathic hemolytic
anemia, but  fibrinogen  and  other  coagulation  factors  should  be normal.
Vitamin K deficiency does not affect the fibrinogen or platelets  and  should
be  corrected  by  vitamin  K  therapy.  Other conditions to rule out include
transfusions of large amounts of  stored whole blood, bleeding following open
heart surgery, snake bites, and acquired inhibitors directed against specific
coagulation factors.  TREATMENT: The most important goal in treating  DIC  is
to  treat  the  underlying illness causing the DIC.  If the patient has a low
fibrinogen, low platelet count and low  levels of clotting factor, and is not
bleeding or does not require surgery, no treatment is needed.  Howver, if the
patient is bleeding or requires  surgery,  treatment  is  with  fresh  frozen
plasma,  cryoprecipitate  and platelets.  Platelet transfusion should be used
to  maintain  the  platelets  >  50,000/uL.   Fibrinogen  is  replaced  using
cryoprecipitate  with  an  end  point   of   of   150  mg/dL.   One  unit  of
cryoprecipitate will raise the fibrinogen by 6-8 mg/dL.   Therefore,  it  the
fibrinogen  is about 50, 15 units of cryoprecipitate would raise the level to
150 mg/dL.  Coagulation factor  can  be  corrected using fresh frozen plasma.
Heparin is sometimes given in low doses.  Heparin is  routinely  employed  in
DIC associated with acute promyelocytic leukemia.  Heparin may also be useful
in  those  cases  that  are initiated by thromboplastin.  It is useful in the
Trousseau syndrome  and  in  DIC  associated  with  mucinous adenocarcinomas.
Heparin may reduce the necrosis of purpura fulminans, giant hemangiomas,  and
decrease the bleeding in amniotic fluid embolism and the dead fetus syndrome.
A  trial  of  heparin  in  most  cases is indicated only if there is clinical
deterioration in  spite  of  replacement  and  supportive  measures.  Heparin
should be used in combination with replacement therapy, because heparin alone
can cause an increase in bleeding.   Heparin  is  usually  given  at  500-750
units/hour.   Antithrombin  III  levels  should  be  checked prior to heparin
therapy because heparin is not effective  in the face of severe depletions of
antithrombin III.  If antithrombin III levels are low,  fresh  frozen  plasma
should  be  used  to  raise the levels to > 50%.  The PTT does not need to be
prolonged to be effective when using heparin.  The success of heparin therapy
is monitored by obtaining  fibrinogen  levels,  which  should increase if the
heparin therapy is successful.  Improvement of the platelets may take as long
as 1 week, and fibrin degradation products should decrease over 1-2 days.  In
general, heparin is used in only about 5% of all cases of DIC.  In rare cases
when DIC is complicated by excessive firinolysis, combination  therapy  swith
aminocaproic acid 1 gram IV/hour or tranexamic acid 10 mg/kg IV every 8 hours
may  be used to control the bleeding.  Aminocaproic acid should never be used
without heparin in DIC, as it could cause a fatal thrombosis.

                       -DRUGS AND LUNG DISEASE-
Many drugs are capable of inducing different  types  of  lung  disease.   The
following  categorize  these  drugs  as  to  what  type  of lung disease they
produce:  DRUG  INDUCED  NONCARDIAC  PULMONARY  EDEMA:  Heroin  (occasionally
produces diffuse alveolar infiltrates  and dyspnea), Propoxyphene, Methadone,
Hydrochlorthiazide  (rarely  causes  diffuse  alveolar  infiltrates,   cough,
dyspnea,  fever  and  blood  pressure changes, and seen almost exclusively in
women), Chlordiazepoxide,  Dextran,  Ethylchlorvynol,  Aspirin.  INTERSTITIAL
PNEUMONITIS  AND  FIBROSIS:  Gold  (can  cause  hypersensitivy   pneumonitis,
Bronchiolitis   obliterans  with  organizing  pneumonia  (BOOP)  and  chronic
fibrosis.  Clinically  presents  with  dyspnea,  cough,  fever, eosinophilia,
wheezing and dermatitis.  Chest  x-rays  show  reticulonodular  infiltrates),
D-Penicillamine  (produces  reticular,  and reticulonodular patterns on chest
x-ray, but chest x-ray  can  be  normal.   There may be pulmonary hemorrhage,
hemoptysis and  cough.   Can  also  produce  diffuse  alveolar  infiltrates),
Sulfasalazine (presents as cough, fever, dyspnea and eosinophilia.  Can cause
hypersensitivity    pneumonitis,   BOOP   or   bronchospasm),   Methysergide,
Nitrofurantoin (can present  with  dyspnea,  fever, rash, fatigue, pleuritis,
arthralgia, effusions, cyanosis, and wheezing.  Can cause pleural  effusions,
reticular, nodular or reticulonodular lesions.  Can also cause noncardiogenic
pulmonary  edema),  PLEURAL  EFFUSIONS:  Nitrofurantoin (acute), Methysergide
(chronic), Dantrolene, Chemotherapeutic agents,  and  drug induced SLE.  DRUG
INDUCED PULMONARY INFILRATES WITH  EOSINOPHILIA:  Methotrexate  (Presents  as
fever,  eosinophilia,  pleuritic  chest  pain,  dyspnea,  dermopathy, diffuse
alveolar   infiltrates,   pleural   effusions,   BOOP   or   hypersensitivity
pneumonitis),  Sulfonamides  (causes  diffuse   alveolar  infiltrates  and  a
hypersensitivity  pneumonitis),  Sulphasalazine  (causes  a  hypersensitivity
pneumonitis, BOOP and bronchospasm.  Presents as fever,  dyspnea,  cough  and
eosinophilia),  Nitrofurantoin,  Isoniazid  (presents  with  diffuse alveolar
infiltrates, dyspnea,  fever  and  eosinophilia.   Causes  a hypersensitivity
pneumonitis), Para-aminosalicylic acid (presents  with  fever,  eosinophilia,
dyspnea,   dermatitis,   angioneurotic   edema),   Penicillin,   Salicylates,
Procarbazine (causes dyspnea, eosinophilia, rash, fever, and diffuse alveolar
infiltrates),  Carbamazepine  (can  cause  fever,  dyspnea and eosinophilia),
Ritalin  (causes  chest  pain,  dyspnea,  wheezing,  hemoptysis  and  diffuse
alveolar infiltrates), Cromolyn sodium  (causes  dyspnea and diffuse alveolar
infiltrates), Imipramine (causes diffuse alveolar infiltrates, fever, dyspnea
and eosinophilia), HILAR AND MEDIASTINAL ADENOPATHY:  Dilantin  (can  present
with  diffuse  alveolar  infiltrates, dyspnea, fever, eosinophilia, hilar and
mediastinal    adenopathy),    Methotrexate,    Corticosteroids.    PULMONARY
HYPERTENSION WITH VASOSPASM AND EMBOLI: Oral  contraceptives,  Aminorex,  and
15-Methyl-prostaglandin-F2-alpha.    DRUG   INDUCED  LUNG  GRANULOMAS:  Talc,
Mineral oil, methotrexate, Cromolyn sodium and Bacille Calmette-Guerin (BCG),
RESPIRATORY  PARALYSIS:   Gentamicin,   Kanamycin,   Neomycin,  Streptomycin,
Polymyxin B  and  Colistin.   BRONCHOSPASM:  Beta  blockers,  Nitrofurantoin,
Isoproterenol, Ibuprofen, Aspirin, Fenoprofen, and Indomethacin.

                           -DRUGS AND SLE-
There are several drugs that can induce  a clinical picture of SLE.  The most
common drugs that cause positive ANAs and SLE in over 90%  of  cases  include
diphenylhydantoin,  procainamide,  hydralazine and isoniazid.  However, other
drugs  are  capable,  as  found  in  the  following  list.   ANTICONVULSANTS:
diphenylhydantoin,  carbamazepine,   mephenytoin,  promidone,  trimethadione,
ethosuximde,   and   promidone.    ANTIBIOTICS:   Penicillin,   sulfonamides,
tetracycline  griseofulvin,  and  nitrofurantoin.    ANTITUBERCULOUS   DRUGS:
isoniazid,  streptomycin  and  para-aminosalicyclic  acid.   ANTIHYPERTENSIVE
DRUGS:   Hydralazine,   methyldopa.    ANTIARRHYTHMIC   DRUGS:  Procainamide,
quinidine,  practotol.    PHENOTHIAZINES:   chlorpromazine,  levomepromazine,
perphenazine,  perazine,  thioridazine,  and  promethazine.    OTHERS:   oral
contraceptives,   methylthiouracil,  methysergide,  amoproxan,  anthiomaline,
D-Penicillamine,   tolazamide,    phenylbutazone,    prophylthiouracil,   and
oxyphenisatin.

                      -DUPUYTREN'S CONTRACTURE-
Alcohol abuse, scleroderma, diabetes and hand labor are risk factors for this
diffuse unilateral  or  bilateral  hypertrophy  of  the  palmar fascia, which
results in gradual flexion contractures of  the  fourth  and  fifth  fingers.
Surgical release may be needed but there is a 30% recurrence.

                            -DYSPAREUNIA-
Dyspareunia  refers  to  painful  intercourse.   It  may  be   divided   into
superficial  and deep dyspareunia.  SUPERFICIAL DYSPAREUNIA: Disorders of the
vaginal outlet may be causative.  These include episiotomy scars, infections,
trauma, adhesions, clitoral irritation,  postmenopausal atrophy and decreased
lubrication.   There  may  be   evidence   of   vulvovaginitis,   urethritis,
bartholinitis,  vestibulitis, and trigonitis seondary to fungal, bacterial or
viral causes.   Vaginal  causes  include  infection,  pelvic  relaxation with
rectocele,  cystocele,  uterine  prolapse,  allergy   to   douche   products,
suppositories,  perfumes  or creams, radiation, and congenital malformations.
The  older  patient  may   have   atrophic  vaginitis  or  vulvar  dystrophy.
Medications  such  as  anticholinergics,  and  antihistamines  may   decrease
lubrication.   Vaginismus  is  another  cause  of painful intercourse that is
caused by spasms of the levator ani and perineal muscles.  This is frequently
due to psychogenic illness.  DEEP DYSPAREUNIA: Deep dyspareunia may be caused
by endometriosis, pelvic  inflammatory  disease, pelvic neoplasms, radiation,
ovarian cysts, adhesions secondary from pelvic surgery, ovary sutured to  the
vaginal  cuff, retrodisplaced uterus (can cause dispalcement of an ovary into
the   cul-de-sac),    rectal    pathology,    inflammatory   bowel   disease,
diverticulitis, broad ligament varicosities, cervical  tears  or  scars,  and
psychologic  causes.   Psychologic  dyspareunia  may  be  due to disinterest,
anxiety, fear, feeling  of  guilt  and  hostility,  or from previous negative
experiences such  as  rape.   PHYSICAL:  Physical  exam  should  be  done  by
examining for signs of atrophic vaginitis, urethral syndrome, vulvovaginitis,
cervicitis,  congenital abnormalities, narrowed introitus, scarring, spasm on
examination, cystocele, rectocoele, palpation  for pelvic masses, retroverted
uterus, uterine prolapse,  and  cervical,  adnexal  and  uterine  tenderness.
LABORATORY:  Gonorrhea  and chlamydia cultures, and wet mount preps should be
done.  Urine samples should be  obtained  for UA and culture.  Cystoscopy and
voiding  cystourethrograms  may  be  needed.   If  GI  symptoms  are  present
sigmoidoscopic and colon exams should be carried  out.   PAP  smears  may  be
useful for assessing estrogen status.  Patient may need pelvic ultrasound and
referal  for  laparoscopic  surgery  for  endometriosis,  adnexal  masses and
adhesions.  TREATMENT: All organic  diseases should be addressed.  Inadequate
lubrication can be helped with water soluble lubricants, increasing foreplay,
changing coital positions, and estrogen therapy.  Vulvar  or  introital  scar
tissue  can  be  treated with dilation or surgery.  Surgery may be needed for
adhesions, endometriosis or adnexal masses.  Kegel exercises may be useful in
improving muscles relaxation.  Behavior  modification  is helpful in blocking
and deconditioning the spastic vaginal responses of vaginismus.

                             -DYSPHAGIA-
In  evaluating  dysphagia, the history is very important.  The patient should
be questioned as to whether  liquids,  solids  or  both stick, where does the
food stick, does the  problem  originate  in  swallowing,  is  the  dysphagia
intermittent  or  is  it  becoming  progressively  more  severe, when did the
problem begin, has there been  any  weight  loss,  is there any history of of
cancer, heart problems, AIDS, thyroid  disease,  stroke,  or  diabetes,  what
medications is the patient taking, (such as aspirin, ibuprofen, tetracycline,
potassium  and  quinidine), is the dysphagia associated with change in voice,
muscle weakness, difficulty  walking  or  holding  objects, double vision, or
facial droop.  The patient's subjective localization of the sticking  may  or
may  not  correspond  to  the  level  of  the pathology.  Localization of the
dysphagia in the neck  may  indicate  a  lesion anywhere along the esophagus.
Neuromuscular disorders typically cause dysphagia  for  liquids  and  solids,
whereas mechanical obstruction is typically associated with solids initially,
and   then   liquids  later.   If  dysphagia  develops  rapidly  for  solids,
particularly in an  elderly  patient,  carcinoma  of  the esophagus should be
suspected.  Esophagitis and  peptic  stricture  will  produce  dysphagia  for
solids and is seen in patients with chronic heartburn and antacid usage.  The
history  may  disclose a cerebrovascular accident that is associated with the
dysphagia.  The patient should be  questioned about scleroderma and the CREST
syndrome (Calcinosis, Raynaud's phenomenon,  Esophageal  motilitly  disorder,
Sclerodactyly  and  Telangiectasia).   If the patient appears to be cachectic
with lymphadenopoathy, malignancy  should  be  suspect.   Dysphagia should be
differentiated from odynophagia (pain on swallowing), and  globus  hystericus
(lump  in  the  throat).   LABORATORY:  The  initial test is usually a barium
examination  of  the  pharynx,  esophagus  and  stomach.   This  will  detect
extrinsic lesions such  as  thyromegaly  and  intrinsic lesions as esophageal
rings and webs.  To evaluate the mucosa a  double  contrast  esophagogram  is
done.   Liquid  barium  by itself may not show beginning strictures or occult
esophageal rings.   To  bypass  this  difficulty,  barium  coated  tablets or
marshmallows may be used.  Cine-fluoroscopic examination of the oral  cavity,
pharynx  and  cervical  esophagus  can reveal spasm, gastroesophageal reflux,
aperistalsis and evaluation of  swallowing  function.  If the esophagogram is
negative, an upper GI should be done  to  rule  out  tumors  of  the  gastric
cardia,  which  can  cause  dysphagia.   If the barium studies show a lesion,
upper endoscopy should be done with biopsy and brush cytology.  Both of these
studies are  complimentary.   Endoscopy  should  be  done  initially,  if the
dysphagia is acute from food impaction.  If the barium studies and  endoscopy
are  both  negative,  esophageal  manometry  should be done, which can detect
peristaltic characteristics,  and  evaluate  the  upper  and lower esophageal
sphincters.  It is important to know that manometry will  demonstrate  normal
results  in  about  50%  of patients with dysphagia and may show non-specific
abnormalities that have no  bearing  on  the  dysphagia, such as hypertensive
lower   esophageal   sphincter   and   nutcracker   esophagus.    Provocative
edrophonium, acid infusion and esophageal balloon distention may be  done  in
those  patients that have dysphagia and chest pain.  Ambulatory esophageal pH
and intraluminal pressure  monitoring  can diagnose reflux-induced esophageal
spasm.  OROPHARYNGEAL DYSPHAGIA: Is characterized by the  sensation  of  food
sticking  during  the  act of swallowing with the need to swallow repeatedly.
There may be  associated  nasal  or  oral  regurgitation.   The following are
causes  for  oropharyngeal  dysphagia:  OROPHARYNGEAL   OBSTRUCTIVE   CAUSES:
Intrinsic   causes   include   diverticuli,   esophageal  webs,  tumors,  and
inflammatory  lesions.    Extrinsic   structural   lesions  include  anterior
mediastinal masses and  cervical  spondylosis.   OROPHARYNGEAL  NEUROMUSCULAR
CAUSES:   amyotrophic   lateral   sclerosis,  Huntington's  chorea,  multiple
sclerosis,  stroke,   brainstem   tumors,   Parkinson's   disease,  syphilis,
poliomyelitis,   peripheral   neuropathy,   polymyositis,    dermatomyositis,
cricopharyngeal  achalasia,  muscular  dystrophies,  and  myasthenia  gravis.
Patients  may develop dysphagia years after polio manifested as the postpolio
syndrome.   ESOPHAGEAL  OBSTRUCTIVE  CAUSES  OF  DYSPHAGIA:  Intrinsic causes
consist of strictures, tumors, chemical/radiation/medication induced  causes,
esophageal  webs,  and rings as Schatzki rings, extrinsic lesions as vascular
compression,  enlarged  aorta  or  left  atrium,  and  aberrant  vessels, and
mediastinal masses as substernal  thyroid  and  lymphadenopathy.   ESOPHAGEAL
NEUROMUSCULAR  CAUSES  OF  DYSPHAGIA:  Diffuse esophageal spasm, scleroderma,
achalasia, nutcracker esophagus and  hypertensive lower esophageal sphincter.
Patients that have intermittent dysphagia for solids may have rings or  webs.
Esophageal  webs  occur  most often in the cervical region and present as the
Plummer-Vinson  syndrome.   Rings  can  occur  at  the  distal  esophagus and
gastroesophageal junction.  The Schatzki ring is the  most  common  cause  of
intermittant  dysphagia  for  solids and occurs as a horizontal annular ridge
which projects into  the  esophageal  lumen  at the gastoesophageal junction.
Mucosal rings under 13 mm in diameter will usually cause  dysphagia,  whereas
those  >  20 mm are usually asymptomatic.  Most peptic strictures will have a
smooth tapered appearance  on  x-rays  and  are circumferential.  The patient
will complain of intermittent dysphagia that slowly  progresses.   Esophageal
cancer,  on  the  other hand, is a rapidly progressing lesion associated with
weight  loss.   All  patients   that   have  symptomatology  consistent  with
strictures must have upper endoscopy with biopsy and brush cytology  to  rule
out  Barrett's  esophagus and carcinoma.  Patients with systemic sclerosis or
scleroderma have liquid and solid  dysphagia,  usually  seen in a middle aged
women who complains of heartburn.  Typically, there is  a  hypotensive  lower
esophageal  sphincter  and decreased or ineffective peristalsis in the distal
2/3  of  the  esophagus   causing   gastroesophageal  reflux  and  stricture.
Achalasia produces  dysphagia  for  solids  and  liquids  which  will  slowly
progess.   Most  of the patients indicate that there is an obstruction at the
xiphoid area.  Barium study will show a dilated fluid filled esophagus with a
smooth tapering of the distal esophagus  known as the bird's beak.  Manometry
will confirm that there is elevated lower esophageal sphincter  pressure  and
aperistalsis, with incomplete relaxation of the lower esophageal sphincter on
swallowing.   Pseudo-achalasia may develop in patients that have a gastric or
esophageal cancer or other distant cancers as prostate, lung cancer, hepatoma
and lymphoma.  These  two  types  of  achalasia  must  be differentiated.  In
general malignancy should be suspected if the patient is  >  55,  has  weight
loss,  and  dysphagia  <  1 year, However, about 15% of patients with primary
achalasia will  present  over  the  age  of  55  and conversely, occasionally
pseudo-achalasia will present at a younger age.  Diffuse esophageal spasm can
also cause dysphagia and can be made on manometric evidence  of  simultaneous
high  amplitude  esophageal  contractions  in at least 10-30% of wet swallows
with interval normal peristaltic contractions in a patient having chest pain.
Therapy  for  esophageal  motility  disorders  causing  chest  pain  includes
nitroglycerin .4 mg SL prn, isosorbide  10-30 mg PO qid, dicyclomine 10-20 mg
qid, diazepam 2-5 mg PO qid, doxepin 50 mg PO hs, and trazodone 50 mg PO tid.
If these drugs are ineffective, you  may  try  diltiazem  90  mg  PO  qid  or
nifedipine  10-20 mg qid, or dilatation with a # 50 French dilator as needed.
Achalasia can be treated with pneumatic esophageal dilation, surgical myotomy
of the lower  esophageal  sphincter  or  smooth muscle relaxants.  Esophageal
dilatation is the most common  form  of  therapy  utilizing  a  pneumatic  or
hydrostatic  balloon.   The  major  drawback  to myotomy is the production of
gastroesopohageal reflux, which  may  occur  in  3-52%  and peptic stricture.
Calcium channel blockers and nitrates may also be of some  benefit  in  these
patients.

                       -EATON-LAMBERT SYNDROME-
Eaton-Lambert syndrome is a myasthenic syndrome characterized by fatigability
and  proximal  muscle  weakness,  usually  in  the  pelvic  girdle  and lower
extremities.  Unlike myasthenia gravis, repeated efforts will increase muscle
strength.  Other symptoms may include muscle  pain,  impotence,  paresthesias
and  dry mouth.  The syndrome may precede small cell carcinoma of the lung or
develop  concurrently.   The  syndrome  is  rarely  seen  in  some autoimmune
diseases.  There is a defective  release  of  acetylcholine  following  nerve
stimulation  which  leads  to  the  weakness.   Eaton-Lambert syndrome can be
diagnosed with electromyograms which  will  show  a pathognomonic increase in
amplitude on repetitive stimulation.  Treatment is  with  plasmapheresis  and
immunosuppressive  drugs  as  prednisone  and  azathioprine which can lead to
clinical and electrophysiologic  improvement.   The  prednisone is started at
60-80 mg/day and  azathioprine  in  a  daily  dose  of  2  mg/kg.   Guanidine
hydrochloride  at  25-50  mg/kg/day  in  divided  doses  is also effective in
patients that are severely affected.  However, the drug can cause bone marrow
suppression.  Anticholinesterase drugs such as neostigmine and pyridostigmine
are variably effective.  Successful treatment  of the small cell carcinoma of
the lung will also cause remission of the syndrome.

                         -EBSTEINS'S ANOMALY-
CLINICAL: Ebsteins's anomaly  of  the  tricuspid  valve  is a rare congenital
defect that is  characterized  by  a  downward  displacement  of  a  deformed
tricuspid  valve.   The  anterior  leaflet is usually large and billowy.  The
displaced tricuspid  valve  creates  an  atrialized  ventricular chamber with
tricuspid insufficiency.  Echocardiography will  reveal  enlargement  of  the
anterior  tricuspid  leaflet,  delayed closure of the anterior leaflet, and a
displaced septal leaflet.   The  lesion  is  often  associated  with a patent
foramen ovale with right to left shunting producing cyanosis.  The degree  of
cyanosis  depends  on  the degree of inadequacy of the tricuspid valve, which
can cause insuffiency or  stenosis,  plus abnormal right ventricular function
associated with a hypoplastic right ventricle.  Arrhythmias  may  be  present
due  to  an  accessory  conduction  pathway (Wolff-Parkinson-White syndrome).
Auscultation often reveals a split  S1,  due  to a right bundle branch block,
and S3 and S4.  There is a systolic tricuspid murmur.  The ECG shows  a  wide
RSR'  in  V1,  right  atrial  enlargement  and atrial fibrillation is common.
Chest x-ray will reveal an  enlarged  heart,  especially the right atrium and
decreased pulmonary vascularity.  TREATMENT: Medical  treatment  is  used  in
mildly  symptomatic  patients  and  consists  of treatment for heart failure,
endocarditis prophylaxis,  and  arrhythmias.   Eventually  all  patients will
require surgery.  Fifty percent of patients will die in infancy while  others
may remain asymptomatic until the 7th or 8th decade.  Once the cardiothoracic
ratio  reaches  0.65, surgery is recommended regardless of symptoms.  Medical
therapy should be used  with  caution.   Digoxin  is of questionable value in
predominantly  right  ventricular  failure  and  may  be  contraindicated  in
associated WPW.  Diuretics may compromise  forward  flow  through  the  right
ventricle  and  decrease left ventricular output.  Vasodilator therapy should
only be used in patients with systemic arterial hypertension, as reduction of
afterload could result in  hypotension.   ARRHYTHMIAS: Arrhythmias consist of
supraventricular and ventricular types.   They  should  only  be  treated  if
symptomatic   or   continue  as  a  sustained  tachyarrhythmia.   Syncope  or
presyncopal   episodes   caused   by   these   should   be   investigated  by
electrophysiologic testing.  Sudden death occurs in about  20%  of  patients,
and  can  be due to ventricular or suprventricular types.  Patients that have
atrial tachyarrhythmias  or  pre-excitation  reentrant  tachycardias from WPW
should have these ablated.  Patients usually have multiple by-pass tracts and
ablation of one tract should lead to a search for co-existing by-pass tracts.
Ablation  may  be  by  catheter  or  surgical  means.   Should  ablation   be
unsuccessful,  procainamide  will  slow  conduction through the bypass tract.
Atrial  fibrillation  is   usually   due   to   an   enlarged  right  atrium.
Cardioversion is seldom successful in converting AF to a normal sinus rhythm.
Digoxin  can  control  the   ventricular   response,   but   again   may   be
contraindicated in patients with WPW.  Patients with chronic or paroxysmal AF
should  be  anticoagulated  with  warfarin to prevent embolism.  All patients
will need prophylactic endocarditis therapy.   Any patient that presents with
a febrile illness should have blood cultures done to rule  out  endocarditis.
Even after surgical repair, endocarditis prophylaxis is still indicated.  Any
patient  that has cyanosis and clubbing should be investigated for Ebsteins's
anomaly.  The cyanosis results from right  to left shunting either through an
atrial septal defect or a  patent  foramen  ovale.   Should  this  be  found,
surgical  intervention should follow.  Patients may also develop polycythemia
which is related to the  degree  of  right to left shunting.  Surgical repair
usually suffices, but in those patients who are not candidates  for  surgery,
hematocrits  >  60%  may  be  treated  with  phlebotomy  in  order to prevent
thrombotic  events.   SURGERY:  Surgery  will  be  needed  for  patients with
significant  tricuspid  insufficiency,  moderate  or  severe  cyanosis,   and
congestive  heart failure.  The tricuspid valve should be repaired initially,
if possible.  There should also be plication of the atrialized portion of the
right ventricle with a  posterior  tricuspid  annuloplasty which results in a
unicuspid  valve.   Should  plastic  repair  be  unsuccessful,   a   biologic
prosthesis should be placed, followed by anticoagulation.  The patent foramen
ovale  or  ASD  should  be  closed.   Patients  with WPW should have surgical
ablation of  the  accessory  pathway.   Patients  who  present with Ebstein's
anomaly in infancy do poorly with surgery, and  have  high  mortality  rates.
Cardiac transplantation may be needed in these patients.  In general, surgery
is recommended for patients with Class III symptoms before the cardiothoracic
ratio reaches 0.6-0.65.

                         -ECTOPIC PREGNANCY-
Ectopic pregnancy is a  common  disorder  and  is increasing.  About 40% have
occurred in women between the ages of 20-29.  In the  USA,  in  1987,  88,400
cases  were  diagnosed.  In the last 20 years there has been a two-three-fold
increase in  ectopic  pregnancy  due  primarily  to  an  increase in sexually
transmitted diseases.  In 1970  there  was  4.8/1000  term  births  and  this
increased  to  14.5/1000  in  1980.   Most cases (98%) of ectopic pregnancies
occur in the tube.  55% occur  in  the ampullary portion, 25% in the isthmic,
17% in the fimbrial portion and 2% in the cornual segment.  Ectopic pregnancy
may also occur  in  the  ovary,  peritoneal  cavity  (most  commonly  in  the
cul-de-sac), but occasionally in the omentum, pelvic side walls, and surfaces
of  the  spleen  and  liver.   Cervical pregnancy has also been reported with
implantation occurring below the level  of  the internal os.  Risk factors in
ectopic pregnancy include  previous  pelvic  inflammatory  disease,  previous
tubal pregnancy, use of an intrauterine device, previous surgery of the tube,
pelvic  adhesions,  history  of  endometritis,  history  of  infertility, and
ruptured appendix.  Due to advances in pelvic sonography and the availability
of sensitive urine and  serum  assays  for human chorionic gonadotropin (hCG)
and laparoscopic surgery, the  diagnosis  is  made  much  earlier  with  more
precision.   Radical  surgery  is being supplanted with medical treatment and
laparoscopic surgery.  Ectopic surgery can  now  be diagnosed as early as 4.5
gestational weeks.  Four procedures are now used in the diagnosis of  ectopic
pregnancy.   These  include  a  single progesterone determination, serial hCG
quantitative determinations, vaginal  ultrasonography  and uterine curettage.
CLINICAL: Ectopic pregnancy must always be kept in mind when a woman presents
with abnormal uterine bleeding or spotting and abdominal pain.  This  usually
begins  after  the missed menstrual period.  If there is rupture of the tube,
acute bleeding  will  occur  with  hypotension  and/or  shock.   Sudden lower
abdominal pain seen at 6-8 weeks of pregnancy may  indicate  rupture  of  the
salpinx  with  subsequent  intra-peritoneal  hemorrhage.  Cornual pregnancies
will rupture at a  later  date,  between  the  12-16  week.  Pelvic exam will
reveal an enlarged uterus and there may be a tender mass felt in one  of  the
adnexae.    There  may  be  some  bulging  of  the  cul-de-sac.   LABORATORY:
PROGESTERONE: Only one determination  of  the  serum progesterone needs to be
done.  Progesterone is produced by the corpus luteum and changes very  little
during  the  first  10 weeks of pregnancy.  However, if the pregnancy becomes
endangered the levels of  progesterone  will  fall.   If the level is greater
than 25 ng/ml there is a 97.5 percent sensitivity that there  is  no  ectopic
pregnancy  present.  If the progesterone level is less than 5 ng/ml, there is
a 100 percent sensitivity for non-viability regardless of the location of the
implantation.  If the level is below 5  ng/ml this may be an indication for a
diagnostic uterine curettage.  If the progesterone level is between  5-25  no
diagnostic  assumptions  may  be  made  and  vaginal  sonography  is  needed.
However,  even  if  the  progesterone  is  below 15 ng/ml, only 11 percent of
normal gestations occur in  this  range  while  81  percent of ectopic and 93
percent of abnormal endometrial pregnancies will occur when the cut-off level
for progesterone is below 15 ng/ml.   BETA-hCG:  In  normal  pregnancies  the
beta-hCG  will  double  every  48  hours.   Beta-hCG  levels titers are first
detected about 7 days after ovulation and exponentially rise for the first 38
days following ovulation,  and  finally  reach  about  100,000  mIU/ml at 2.5
post-menstrual months.  If the beta-hCG does not  double  every  2  days  the
pregnancy  is in jeopardy, regardless whether it is ectopic or intra-uterine.
VAGINAL SONOGRAPHY: With the advent  of transvaginal sonography utilizing the
5 mHz probe the sensitivity for  detection  of  the  ectopic  mass  has  been
enhanced  allowing  an  earlier  diagnosis.   The size of the mass can now be
measured more accurately.  Ectopic masses that are  less than 4 cm can now be
treated with methotrexate medical therapy.   Color  doppler  sonography  will
further   increase   the   sensitivity   for   diagnosis   by   demonstrating
characteristic  adnexal  and uterine flow patterns.  Gestational sacs can now
be visualized when  the  hCG  levels  are  above  1500 mIU/ml if transvaginal
sonography is used.  In the past, using transabdominal  sonography,  the  sac
could  only  be  visualized  if  the  beta-hCG  levels were greater than 6500
mIU/ml.  If the gestational sac is  not  seen  at the above levels, it may be
inferred that there may be  an  ectopic  gestation.   Other  less  impressive
diagnostic  sonography  signs for ectopic gestation include cul-de-sac fluid,
endometrial thickening and adnexal  masses.  CULDOCENTESIS: Culdocentesis may
be used to detect non-clotted blood in the peritoneum, which together with  a
positive  pregnancy  test,  suggests  a  99%  chance of an ectopic pregnancy.
UTERINE CURETTAGE:  If  the  serum  progesterone  is  below  5 ng (indicating
non-viability), and/or the beta-hCG  is  plateauing  and  the  sonograms  are
non-diagnostic,  uterine  curettage may be done in order to ascertain whether
the pregnancy represents a spontaneous intrauterine abortion or whether there
is  indeed  an  ectopic  gestation.   If  villi  are  seen  in  the curettage
specimens, this would signify a spontaneous intrauterine abortion.  If  villi
are  not  seen,  a  repeat  beta-hCG should be done about 12 hours later.  If
there is a 15 percent or more decrease  in the beta hCG this would indicate a
completed abortion.  However, in the absence of villi, if the beta hCG titers
plateau or continue to rise, the trophoblast was not  removed  by  curettage,
and  the  gestation  is  ectopic.   In  summary,  a  serum  progesterone  and
quantitative  beta  hCG  should  initially  be  done.  If the Progesterone is
greater than 25 ng/ml or the  beta-hCG  is greater than 100,000 mIU/ml, there
is a viable intra-uterine gestation.  If the  progesterone  is  less  than  5
ng/ml  or  there is a suboptimal rising of the beta-hCG, a diagnostic uterine
curettage should be done.   If  villi  are  visualized  this would indicate a
completed abortion.  If no villi are seen and the beta-hCG is decreasing this
would indicate a completed abortion.  However, if the  beta-hCG  plateaus  or
continues to rise ectopic pregnancy is suggested.  If transvaginal ultrasound
shows  a sac less than 4 cm methotrexate may be used.  For a sac greater than
4 cm, surgical treatment is indicated.  For progesterone levels between 5-25,
transvaginal  ultrasonography   may   demonstrate   a   viable  intra-uterine
pregnancy.  TREATMENT: SURGERY: Most ectopic  pregnancies  can  be  diagnosed
much  earlier  than  20  years  ago  when the patient frequently presented in
shock.  Medical therapy  is  becoming  more  common  using  systemic or local
administration of methotrexate which can conserve  the  tube.   Salpingectomy
via  laparotomy is becoming obsolete with newer laparoscopic techniques being
used such as linear salpingostomy.   In  this  procedure the incision that is
made by scissors, laser  or  elecrocautery  is  left  to  heal  by  secondary
intention  after  the  products  of  conception  are  removed with suction or
forceps.  These newer  techniques  apparently  do  not  increase the risk for
subsequent recurrent ectopic pregnancy and may improve the  patient's  chance
for  a  normal  endometrial pregnancy.  Complications of linear salpingostomy
include post-operative  bleeding  and  persistent  elevation  of the beta-hCG
levels indicating the presence of a viable trophoblast.  Medical therapy  may
used  for this latter complication.  MEDICAL TREATMENT: If the patient has an
unruptured mass that  measures  4  cm  or  less  and  the  patient is stable,
methotrexate may be used.  If the patient has cardiac activity in the adnexa,
acute intra-peritoneal hemorrhage, or a mass  that  is  greater  than  4  cm,
methotrexate  is  contraindicated.   The  dose  of methotrexate is 1 mg/kg IM
every other day on odd days  plus  Leucovorin  .1 mg/kg IM every other day	on
even days.  This combination treatment should be continued until the beta-hCG
levels drop greater than 15 percent in 48 hours, or 4 doses  of  methotrexate
have  been  given.   Serum  beta-hCG  levels should be done weekly until they
become  undetectable.   Liver  enzymes,  CBC  and  platelets  should  also be
followed.  Alternatively, the patient may be given one  dose of  methotrexate
at  50  mg/m2  IM without leucovorin.  With this method, serum beta-hCG level
should be done on days 4  and  7  then weekly until they become undetectable.
Side effects such  as  bone  marrow  suppression,  hepatotoxicity,  alopecia,
photosensitivity,  pulmonary  fibrosis and stomatitis are infrequent with the
dosing schedule described above and experience has shown that there is little
chance for fetal anomalies, subsequent cancers and congential anomalies.  The
physician should  be  aware  that  there  will  be  transient  abdominal pain
following the start of methotrexate	therapy.  This usually  starts  3-7  days
following  methotrexate  with the pain lasting 4-12 hours.  This pain must be
differentiated  from  impending  rupture  which  is  usually  associated with
hypotension, decreased hematocrit, and orthostatic tachycardia.

                           -EHRLICHIOSIS-
Ehrlichiosis, which is often called tick fever, was first reported in the USA
in 1987.  It is similar to Rocky Mountain spotted fever, but the rash is  not
commonly  present.  Originally the disease was thought to be due to Ehrlichia
canis, but subsequently the causative agent  was found to be due to Ehrlichia
chaffeensis in 1991.  A similar illness occurs in dogs and is  caused  by  E.
canis.  Ehrlichia chaffeensis was first isolated from a military base at Fort
Chaffee.   The  majority of cases have been seen along the Atlantic coast and
the south central states, especially in Georgia, Oklahoma and Missouri, but a
paucity of cases have been reported  from  the Rocky Mountain states and from
Washington state.  Most of the cases are seen from  May  to  September.   The
patients  tend  to  be  middle  aged  and  elderly,  but some cases have been
reported during childhood.   The  disease  can  be  mild to life threatening.
Ehrlichia species are gram negative, .2-1.5 um, pleomorphic coccobacilli that
can be found in the cytoplasm of  circulating  leukocytes.   They  appear  as
clumps  consisting of dozens of organisms.  The incubation period ranges from
1-21 days with  a  median  of  7  days.   CLINICAL:  High fevers and headache
predominate.  The temperature is usually greater than  38  degrees  C.  Other
symptoms include abdominal pain, nausea and vomiting, myalgia and arthralgia,
and  diarrhea.   The rash, when present, is either a diffuse macular erythema
or petechial.  However, the rash  only  develops  in about 20% of patients as
compared with RMSF in which the rash develops 80% of the time.  Rash  on  the
palms  and  soles  in  Ehrlichiosis  is  uncommon,  only  seen  in  about 5%.
LABORATORY: Patients may  develop  thrombocytopenia,  leukopenia, and anemia.
Elevated hepatic function tests, and renal insufficiency may also be present.
The diagnosis is confirmed with acute and convalescent  phase  serum  samples
taken  4 weeks apart.  A four fold increase in the antibody titer between the
acute and convalescent samples with a  minimal  titer of 1:64 is required for
diagnosis.  Sometimes, the inclusion bodies in  the  leukocytes  or  the  CSF
mononuclear  cells  may be seen.  TREATMENT:  Human ehrlichiosis will respond
to tetracycline at the same dosing  schedule as Rocky Mountain spotted fever.
Chloramphenicol is used for children under the age of nine.

                           -EHRLICHIOSIS-
Is similar to RMSF and is transmitted by the  brown  dog  tick  Rhipicephalus
sanguineus  and D variabilis, and is identified by polymerase chain reaction.
The incidence is increasing rapidly in some states such as Virginia, Oklahoma
and New  Jersey.   Ehrlichia  chaffeensis  produces  a  rash  in  only 15% of
patients during the first week of illness and is  usually  less  diffuse.   A
rash  eventually  develops in up to 45% of patients.  Symptoms include fever,
headache, nausea, vomiting  and myalagia.  Lymphocytopenia, thrombocytopenia.
anemia and liver damage is  characteristic.   More  than  75%  have  abnormal
transaminase  levels.   Round, dark blue inclusion bodies, called morulae can
be found  in  neutrophils  or  atypical  lymphocytes  and  are diagnostic for
ehrlichiosis as is a four fold or greater increase in titers of  antibody  on
immunofluorescence.    Tetracycline,   doxycycline   or   chloramphenicol  is
effective treatment.  Fatalities can occur if not treated.

                          -EMERGENCY DRUGS-
ACTIVASE: For acute MI (within 6 hours of onset of symptoms: 100 mg IV over 3
hours.  Mix in 100 ml of  diluent  (D5W,  NS).  Administer 10 mg IV bolus (10
ml) over 2-3 min then give 50 mg (50 ml) over first hour followed by 20 mg/hr
for the next 2 hours.  For patients less than 65 kg use 1.25 mg/kg  with  60%
of  dose  in  the  first hour, 20% each hour afterwards.) For acute pulmonary
embolism:  100  mg  IV  over  2  hours.   Contraindications:  active internal
bleeding, history of CVA, recent surgery, severe  uncontrolled  hypertension,
cerebral  neoplasm, aneurysm, or arteriovenous malformation or known bleeding
dIathesis.   Side  effects:  reperfusion  dysrhythmias,  bleeding  and shock.
ADENOSINE (Adenocard): For PSVT: 6 mg (2ml) IV rapidly over 1-2 seconds.  (If
no effect after 2 minutes give 12 mg over 1-2  seconds.   May  repeat  12  mg
bolus  one more time).  Contraindications: 2-3 AV block, sick sinus syndrome.
Side  effects:  Transient  dysrhythmias,   facial  flushing,  dyspnea,  chest
pressure, hypotension, headache, nausea, bronchospasm.  (Adenosine is blocked
by methylxanthines and  is  potentiated  by  dipyridamole.   Pediatric  dose:
0.05-0.2  mg/kg  IV,  IO  up to 6 mg.  May repeat.  ALBUTEROL .5% (Ventolin):
1.25-2.5  mg  (0.25-0.5  ml)  mixed  with   3  ml  of  saline  in  nebulizer.
Contraindications:  tachydysrhythmias.   Side   effects:   tachydysrhythmias,
anxiety,  nausea  and vomiting.  Peds: 0.03 ml/kg nebulized; maximum of 1 ml.
AMINOPHYLLINE INFUSION: Loading dose of  5.6  mg/kg  mixed in 100 ml D5W over
20-30  minutes.   Maintenance  infusion:   0.5   mg/kg/hr.    (Add   250   mg
aminophylline  to  250  ml  D5W.   If this concentration is used then may use
formula:  (.5)  x  (kg)  =  ml/hr.   Contraindications:  dysrhythmias,  Acute
myocardial infarction.   Side  effects:  dysrhythmias, seizures, hypotension,
nausea  and  vomiting,  anxiety.   AMRINONE  (Inocor):  For   acute   severe,
refractory  CHF:  0.75-1  mg/kg  IV slowly over 2-3 minutes (0.15-0.2 ml/kg).
Use original undiluted solution.   May  repeat every 30 minutes.  Maintenance
infusion: 5-10 ug/kg/min.  (Mix 300 mg (3 amps) in 240 ml NS, RL and drip  at
5  ug/kg/min.   (This would be 18 ml/h in a 70 kg person.) Contraindications:
hypotension, IHSS.  Side effects:  hepatotoxicity, fever, chest pain, burning
at infusion site.  Do not mix with dextrose solutions or Lasix.  ANISTREPLASE
(Eminase) (APSAC): For acute MI (Within 6 hours of  onset  of  symptoms):  30
units  IV  over  2-5  minutes  (mix with 5 ml NS).  Contraindications: active
bleeding,  history  of  CVA,  recent   surgery  or  trauma,  intracranial  or
intraspinal surgery, severe uncontrolled hypertension, intracranial neoplasm,
aneurysm,  or  arteriovenous  malformation  and  bleeding  diathesis.    Side
effects:  reperfusion  dysrhythmias,  bleeding,  shock, hypotension, allergic
reaction, chest pain.   BRETYLIUM  (Bretylol):For  VF/VT  (Cardiac arrest): 5
mg/kg IVP; repeat with 10 mg/kg IVP after 15 minutes up to 30 mg/kg.  For  VT
with  a pulse: 5-10 mg/kg IV over 8-10 minutes, (dilute in 50 ml first).  For
a drip add 2 grams Bretylium to 250  ml D5W and drip at 2 mg/min.  (15 ml/h).
Side effects: hypotension, nausea and vomiting, vertigo, dizziness,  syncope;
may  initially  worsen  dysrhythmia.   CALCIUM CHLORIDE 10%: For treatment of
calcium  blocker  toxicity,  hypocalcemia   with  tetany,  hyperkalemia,  and
hypermagnesemia: 200-500 mg IV (2-5 ml) slowly over 5 minutes.  May repeat in
10 minutes.  Contraindications: VF, digitalis toxicity, hypercalcemia.   Side
effects: bradycardia, asystole, hypotension, VF, coronary and cerebral artery
spasm,  nausea  and  vomiting  and  extravasation  causes  necrosis.  Calcium
chloride will precipitate with NaHCo3  in  IV  bag and tubing.  Pediatric: 20
mg/kg IV, IO slowly.  DOBUTAMINE (Dobutrex): For cardiogenic shock  and  CHF:
2.5-20  ug/kg/min.   Mix 250 mg in 250 ml D5W and drip at 10 ml/h for a 70 kg
person.  If the above concentration is used  may use the formula: 0.06 x ug x
kg  =  ml/h.   Contraindications:  tachydysrhythmias,  IHSS.   Side  effects:
tachydysrhythmias, VT, VF,  hypertension,  nausea  and  vomiting,  and  acute
myocardial  infarction.  DOPAMINE (Intropin): For cardiogenic or distributive
shock: 2-20 ug/kg/min.  Add  200  mg  of  Dopamine  to  250  ml D5W.  If this
concentration is used then  use  this  formula:  .075  x  ug  x  kg  =  ml/h.
Contraindications:  tachydysrhythmias.   Reduce dose to 1/10th for patient on
MAO  inhibitors.   Side  effects:  tachydysrhythmias,  VT,  VF, hypertension,
nausea and vomiting, ischemia, acute myocardial infarction, and extravasation
causes tissue necrosis.  EPINEPHRINE 1:1000:For treatment of  asthma:  0.3-.5
mg  (.3-.5  ml)  SQ.   Contraindications:  tachydysrhythmias, coronary artery
disease.  For treatment of allergic reactions:  .3-.5 mg (.3-.5 ml) SQ.  Side
effects: tachydysrhythmias, VT, VF, angina and hypertension.  Pediatric:  .01
mg/kg (.01 ml/kg) SQ.  Maximum of .5 mg.  EPINEPHRINE 1:10,000: For treatment
of cardiac arrest: .5 - 1 mg (5-10 ml) IV, ET every 5 minutes.  For drip: 1-4
ug/min.   Mix  1  mg  in  250  ml  D5W and drip at 1 ug/min or 15 ml/h.  Side
effects:  tachydysrhythmias,  VT,  VF,  angina,  and  hypertension.   ESMOLOL
(Brevibloc):  For treatment of SVT,  atrial fibrillation, atrial flutter: 500
ug/kg for 1 minute.  Follow with maintenance infusion of 50 ug/kg/min.   (Add
2.5  gm  to  250  ml  D5W  and  drip  at  21 ml/h for a 70 kg person).  If no
therapeutic effect after  5  minutes,  repeat  the  loading dose and increase
maintenance   infusion   to   100    ug/kg/min    (Max:    200    ug/kg/min).
Contraindications:  bradycardia, 2-3 degree heart block, cardiogenic shock or
overt heart failure, COPD,  asthma.   Side effects: hypotension, bradycardia,
dizziness, chest pain,  headache,  bronchospasm,  and  nausea  and  vomiting.
ISOPROTERENOL  (Isuprel):  For  treatment  of  symptomatic  bradycardia: 2-10
ug/min.  (Mix 1 mg Isuprel in 250  ml  D5W  and drip at 2 ug/min or 30 ml/h.)
Contraindications: cardiac arrest.  Side  effects:  tachydysrhythmias,  PVCs,
ischemia,  myocardial  infarction.  LIDOCAINE (Xylocaine 2%):For treatment of
VT, VF: 1 mg/kg  IV,  ET;  repeat  0.5  mg/kg  after 8-10 minutes.  Maximum 3
mg/kg.  After conversion to normal sinus rhythm, start drip  at  2-4  mg/min.
(Add  2 gm lidocaine to 250 ml D5W and drip at 2 mg/min or 15 ml/h.  IM dose:
300 mg IM (4 mg/kg) of 10% solution  in deltoid muscle if unable to given IV,
ET.  Contraindications: 2-3 AV  block,  hypotension,  Stokes-Adams  syndrome.
Reduce  all  doses by 50% if patient is > 70 years old, has liver disease, or
is in CHF or shock.   Side  effects: Seizures, slurred speech, altered mental
status.  LORAZEPAM (Ativan): For treatment  of  status  epilepticus:  2-4  mg
slowly  IV  (Dilute  1:1  with  NS,  D5W)  or  IM.  For treatment of anxiety,
sedation: .05 mg/kg up  to  4  mg  IM.  Contraindications: acute narrow angle
glaucoma.   Side   effects:   Apnea,   nausea   and   vomiting,   drowsiness,
restlessness,  delirium; be prepared to ventilate patient.  Pediatrics: .05 -
.2 mg/kg IV (Dilute 1:1 with NS,  D5W) slowly, or IM.  MAGNESIUM SULFATE: For
treatment  of  Torsade  de  pointes,  alcoholic  withdrawal   and   seizures,
eclampsia,  myocardial  infarction,  hypomagnesemia:  1-2  gm  (2-4  ml)  50%
solution  (8-16 mEq) IV bolus over 5-15 minutes, or Magnesium sulfate 1 gm (2
ml) of 50% sln) IM q 4-6h.  Drip: Add 2 gm of Magnesium sulfate to 250 ml D5W
and drip at 3-20 mg/min.  Start at  10  mg/min  or 75 ml/h for 8 hrs then get
magnesium level.  Check patellar reflexes.  Contraindications: renal disease,
heart block, recent  MI.   Side  effects:  respiratory  and  CNS  depression,
hypotension,  cardiac  arrest.  MANNITOL 20%: For treatment of cerebral edema
with increased intracranial pressure: 1-2  gm/kg  IV over 30 min.  May repeat
if no effect.  Contraindications: hypotension, anuria, electrolyte depletion,
dehydration, intracranial bleeding, severe CHF with  pulmonary  edema.   Side
effects:  CHF,  pulmonary edema, hypertension, nausea and vomiting, headache,
seizures,  chest  pain,   tachycardia,  electrolyte  depletion,  dehydration,
hypotension.  Pediatrics: 1 gm/kg  IV,  IO  slowly  over  30  min.   NALOXONE
(Narcan):  For opiate overdose, coma: 2 mg IV, IM, SQ, ET.  Repeat if needed.
Side effects: withdrawal  symptoms  in  the  addicted patient.  NITROGLYCERIN
(Tridil):  Start at 5 ug/min.  Increase by 5-10 ug/min after 5 minutes  until
the desired effect.  (Mix 25 mg of Tridil in 250 ml D5W and start at 5 ug/min
or 3 ml/h.  Use glass IV bottle and non PVC tubing.  NITROPRUSSIDE (Nipride):
For  treatment  of hypertensive crisis, CHF: 0.25-10 ug/kg/min.  Start at .25
ug/min and increase by .5 ug/kg/min  q  3-5 minutes until the desired effect.
(Add 50 mg Nitroprusside to 250 ml D5W).  If this concentration is used  then
use  this  formula:  .3  x  ug x kg = ml/hr.  Contraindications: compensatory
hypertension, hypotension.  Side  effects:  hypotension, tachycardia, cyanide
toxicity.   Wrap  IV  set  in  foil  or  other  opaque  cover.   PROCAINAMIDE
(Pronestyl): For treatment of PVCs, VT, PSVT with WPW: 100 mg IV slowly  over
5  minutes  (20  mg/min);  repeat q 5 minutes until dysrhythmia is converted,
hypotension or QRS/QT widening develops, or 1 gram has been given.  Infusion:
1-4 mg/min (2 gm in 250  ml  D5W).   Drip  at  2  mg/min to start or 15 cc/h.
Contraindications: 2-3  AV  block,  torsades  de  pointes,  lupus,  digitalis
toxicity,  myasthenia  gravis.   Side  effects:  PR, QRS, and QT widening, AV
block,  cardiac  arrest,  hypotension,  seizures,  and  nausea  and vomiting.
Pediatrics: 2-6 mg/kg  IV,  IO  at  less  than  20  mg/minute.   Drip:  20-80
ug/kg/min.   STREPTOKINASE (Streptase): For treatment of acute MI less than 6
hours old.   1.5  MU  infused  over  60  minutes.   Contraindications: active
internal bleeding, recent CVA, recent surgery,  intracranial  or  intraspinal
surgery,  severe  uncontrolled hypertension, intracranial neoplasm, aneurysm,
or AV malformation or  known  bleeding  diathesis.  Side effects: reperfusion
dysrhythmias, bleeding, shock, fever.  VERAPAMIL (Isoptin): For treatment of

                     -ENALAPRIL AND HYPERTENSION-
(Vasotec IV).  1.25-5 mg q6h.  Side effects.  response variable.  precipitous
fall in BP in high renin states.

                           -ENDOCARDITIS-
Native valve penicillin  susceptible  streptococci viridans and Streptococcus
bovis (MIC <.1 ug/ml): Penicillin G 10-20 MU/day continuous infusion  or  q4h
for  4  wks or Penicillin G 10-20 MU/day + gentamicin 1 mg/kg q12h for 2 wks.
Alternative: Vancomycin 30 mg/kg/day divided  into  2 doses or Cefazolin 1 gm
q8h or  Ceftriaxone  1-2  gm  q12h  for  4  weeks.   NUTRITIONALLY  DEFICIENT
STREPTOCOCCI   OR   VIRIDANS  GROUP  STREPTOCOCCI  WITH  RELATIVE  PENICILLIN
RESISTANCE (MIC between .1-.5  ug/ml):  Penicillin  G  20 million U/day for 4
weeks + gentamicin 1 mg/kg q12h during the  first  2  wks.   Alternative:  as
above.   ENTEROCOCCI  (E.  faecalis) (OR VIRIDANS STREPTOCOCCI with MIC > 0.5
ug/ml: Penicillin G 4  million  units  q4h  IV  +  gentamicin 1 mg/kg (not to
exceed 80 mg q8h IV, both for 4-6 wks.  Increase  to  6-8  wks  for  symptoms
longer  than 3 months, prosthetic valve infection or complicated course.  May
substitute ampicillin for penicillin G. For penicillin allergy use vancomycin
15 mg/kg (not to exceed 1 g) q12h  IV  + gentamicin 1 mg/kg (not to exceed 80
mg) q8h IV, both for 4-6 weeks.  Vancomycin peak serum concentrations  should
be  30-45 ug/ml 1 hr after infusion.  Streptomycin 500 mg q12h IM may be used
instead of gentamicin.  Gentamicin should be adjusted to achieve a peak serum
concentration of 3 ug/ml, and  streptomycin  a peak serum concentration of 20
ug/ml.  STAPH AUREUS ENDOCARDITIS: Nafcillin  1.5  g  q4h  IV  for  4  wks  +
gentamicin  1  mg/kg (not to exceed 80 mg) q8h IV for 3-5 days.  This regimen
is  used  for  methicillin  susceptible  strains.   Increase  to  6  wks  for
complicated infection.  Delete gentamicin  for significant renal dysfunction.
Penicillin allergy or methicillin resistant strain: Vancomycin 15 mg/kg  (not
to  exceed  1  g)  q12h IV for 4-6 weeks or cefazolin 2 g q8h IV for 4-6 wks.
Methicillin susceptible  strain,  IV  drug  user,  tricuspid valve infection:
Nafcillin 1.5 g q4h IV for 2 weeks + gentamicin 1 mg/kg (not to exceed 80 mg)
q8h IV for 2 wks.  Prosthetic valve methicillin susceptible strain: Nafcillin
1.5 q4h IV for 6-8 wks + rifampin 300 mg q12h PO or IV for 6 wks + gentamicin
1 mg/kg (not to exceed 80 mg) q8h IV for 2 wks.   For  methicillin  resistant
strain substitute vancomycin for nafcillin.  COAGULASE NEGATIVE STAPHYLOCOCCI
OR  PROSTHETIC VALVE INFECTION: Nafcillin 1.5 g q4h IV for 6-8 wks + rifampin
300 mg q12h PO or IV for 6-8  wks  + gentamicin 1 mg/kg (not to exceed 80 mg)
q8h IV for 2 wks.  Used for methicillin susceptible strain.  Vancomycin  used
in case of uncertain methicillin suceptibility and penicillin allergy.  HACEK
GROUP: Ampicillin 2 g q4h IV for 4 wks + gentamicin 1 mg/kg (not to exceed 80
mg)  q8h  IV for 4 wks or ceftriaxone 2 g daily IV or IM for 6 wks if patient
is allergic to pencillin.  Cephalosporins  should be avoided in patients with
an immediate type hypersensitivity reaction to penicillin.

                  -ENDOCARDITIS (Culture negative)-
The incidence of culture negative endocarditis probably accounts for about 5%
of all cases of culture negative endocarditis that have not received previous
antimicrobial therapy.  This diagnosis should  be entertained if all cultures
are negative and the patient has had fever for at least one week,  a  cardiac
murmur,  splinter hemorrhages, Oslers's nodes, Janeway lesions, splenomegaly,
Roth  spots  and  petechiae.    About   33%   of  patients  will  demonstrate
embolization to the spleen,  kidney  and  brain.   The  largest  etiology  of
negative  blood  cultures is prior antibiotic therapy which is related to the
duration of the  antibiotic  therpay.   If  the  patient  has  only had prior
treatment for about 2-3 days, initial  negative  cultures  will  soon  become
positive, whereas patients that have taken antibiotics for some time may take
several  weeks  before  positive cultures will emerge.  FASTIDIOUS PATHOGENS:
The  HACEK  group   which   is   comprised   of  Hemophilus,  Actinobacillus,
Cardiobacterium, Eikenella  and  Kingella  and  the  nutritionally  deficient
streptococci   are  all  difficult  to  isolate  by  standard  blood  culture
techniques.  They are gram  negative  bacilli  that require specialized media
and prolonged incubation for 3-4 weeks for a positive culture.  They may need
gram staining, subculturing onto chocolate agar, and incubation  of  cultures
in  5-10%  carbon  dioxide.  Nutritionally deficient streptococci may require
media supplemented with pyridoxal hydrochloride or L-cysteine.  They can grow
as satellite colonies on blood  agar  around  a cross streak of Staphylococci
aureus.  Any turbid or flocculent growth  in  standard  blood  culture  media
should  be considered as nutritionally deficient streptococci if the organism
appears to be  non-viable  on  standard  subculture and resemble streptococci
microscopically.  Brucella endocardits  should  be  considered  if  there  is
transmission   by   direct   contact  with  infected  animals,  ingestion  of
contaminated milk products, percutaneous exposure or inhalation of infectious
material by abattoir workers.  Cultures should be carried out using Castaneda
bottles  which  contain  biphasic  soybean-casein  digest  media  with carbon
dioxide atmosphere, for a prolonged incubation  period.   Corynebacteria  are
common  cause  of  culture  negative endocarditis in patients with prosthetic
valves and they again  are  slow  growers.  Legionella endocarditis occurs in
prosthetic valve endocarditis and  negative  blood  cultures.   In  order  to
isolate  Legionella,  buffered  charcoal  yeast  extract is needed along with
serology testing.   In  patients  that  are  IV  drug  abusers, patients with
prosthetic cardiac valves, and those patients who  have  been  on  protracted
antibiotic  therapy  should  be  considered  for fungal endocarditis.  Use of
lysis centrifugation or Castaneda  bottles  can  increase  the yield of blood
cultures.  Mucor  and  Aspergillus  are  rarely  isolated  by  routine  blood
cultures  or culture using fungal isolator media and serology is not helpful.
Patients should  have  ophthalmologic  exams  looking  for chorioretinitis or
endophthalmitis.  Chlamydia psittaci can cause culture negative  endocarditis
in  patients  with  heart  disease and who have been exposed to parakeets and
macaws.  Complement fixation antibodies  are  helpful  in making a diagnosis.
If Coxiella burnetti endocarditis is suspected, serology may  be  useful.   A
phase  I  complement  fixation antibody titer > 1:200 suggests the diagnosis.
Blood cultures  are  negative.   The  disease  is  acquired  by inhalation of
infectious  aerosols  from  domestic  animals  or  pets   or   injestion   of
contaminated  milk.   CLUES:  If  the patient has major embolization, suspect
Coxiella burnetii, Hemophilus species,  or  fungi.   Diagnosis can be made by
histologic and microbiologic examination of  the  embolic  material  and  the
valve  vegetations  using immunofluorescent staining and electron microscopy.
Bone  marrow  culture  and  staining  are  useful  in  diagnosing  Brucella,,
mycobacterial and fungal endocarditis.  Large vegetations found on the valves
via  echocardiography  suggest  fungi,  Hemophilus,  and  Coxiella  burnetii.
TREATMENT: If cultures  remain  negative  after  exhaustive testing as above,
treat patient with Ampicillin + gentamicin which will cover  enterococci  and
the  HACEK  group of organisms.  If the patient becomes afebrile after 1 week
of therapy, continue treatment for 4-6 weeks.  Survival is 92% if the patient
becomes afebrile  afer  1  week;  if  not,  50%.   Brucella  is  treated with
tetracycline or doxycycline + rifampin +/- gentamicin;  Corynebacterium  with
vancomycin + gentamicin; Coxiella burnetii with tetracycline or doxycycline +
co-trimoxazole   +/-  rifampin;  Legionella  with  erythromycin  +  rifampin;
Nutritionally   deficient   streptococci   with   penicillin   +  gentamicin;
Aspergillus with amphotericin B +/- flucytosine; Neisseria with ceftriaxone.

                      -ENDOCARDITIS PROPHYLAXIS-
DENTAL, ORAL OR UPPER RESPIRATORY TRACT: Amoxicillin  3  g  PO  1  hr  before
procedure, then 1.5 g in 6h.  (This is the standard regimen).  Erythromycin 1
g  PO 2 h before procedure, then 0.5 g 6h after initial dose.  (If patient is
allergic to penicillin, use  this  regimen).   Clindamycin  300  mg PO 1 hour
before procedure, then 150 mg 6h after initial  dose.   (If  patient  doesn't
tolerate  erythromycin  or  is  allergic  to  penicillin,  use this regimen).
Ampicillin 2 grams IV or IM 30 min  before procedure, then 1 gram IV or IM 6h
after initial dose.  (Use if unable  to  take  PO  drugs.)  GENITOURINARY  OR
GASTROINTESTINAL  TRACT PROCEDURES: Ampicillin 2 gm IV or IM 1/2 h before the
procedure, then same dose in 6 h +  Gentamicin  80 mg IV or IM 1/2 h prior to
procedure, then same  dose  in  6  hours.   (This  is  the  standard  general
prophylaxis).   Vancomycin  1  gm  IV  over  1  hour starting 1 hour prior to
procedure, then may repeat same dose in 8 hours + Gentamicin 80 mg IV or IM 1
h	before procedure, then may repeat same dose in 8 hours.  (This is for the
penicillin allergic patient).  For  the  low  risk  patient use Amoxicillin 3
grams PO 1 hour before the procedure, then 1.5 grams in 6 hours.

                           -ENDOMETRIOSIS-
Endometriosis consists of aberrant heterotopic islands of uterine endometrial
tissue  located mostly in the pelvis, but other sites can rarely be involved.
The exact incidence of endometriosis is not known, but may be found in 10-15%
of women that are aged 25-44.  Women  that are found to be infertile may have
endometriosis as the cause in 25-50% of cases.   Theories  advanced  for  the
causes  of  endometriosis  include  Sampson's  theory  which  states there is
retrograde  menstruation.   Halban's  theory  is  that  there  is  metastatic
lymphatic and or vascular spread.   Another  theory is that there is coelomic
metaplasia which forms a  functioning  ectopic  endometrium.   CLINICAL:  The
implants  most  commonly  exist  in  the pelvic area.  The most common pelvic
sites in decreasing order of frequency are the ovaries, cul-de-sac, posterior
broad ligaments,  utero-sacral  ligaments,  uterus,  fallopian tubes, sigmoid
colon, appendix and round ligaments.  Other sites may  include  the  ureters,
urinary  bladder,  recto-vaginal  septum, cecum, ileum, abdominal or perineal
scars, umbilicus, vagina, and cervix.  Very  rarely distant sites as the leg,
arm, pleura, lung, diaphragm, kidneys, spleen, spinal canal, stomach, breast,
gallbladder and the mucous membranes  of  the  nose  may  be  involved.   The
patient  may  have  dyspareunia  if  there  are  implants  of  the  posterior
cul-de-sac,  uterosacral  ligaments  or  vaginal  fornix.  Commonly, there is
midline pelvic pain just before  the  menses, during the menses and following
the menses.  If the patient  has  involvement  of  the  bowel  there  may  be
tenesmus,  pain  on  defecation, abdominal bloating, and rectal bleeding with
menses.  If the urinary bladder is  affected  there may be suprapubic pain on
micturition, urgency, frequency and cyclic hematuria.  The patient  may  have
adhesions  causing  the  pain.   Low  back pain is common.  The menses may be
altered.  There may be  irregular  and  heavy  bleeding.   Pelvic exam may be
normal or there may be nodules  that  can  be  felt  on  rectal-vaginal  exam
involving the uterosacral ligaments and rectovaginal septum.  The patient may
have  endometriomas,  but  rarely  can  they  be  felt.   Occasionally  these
endometriomas  rupture and the leakage will cause abdominal pain.  The uterus
may be retroverted  and  fixed  due  to  adhesions.   TREATMENT: Treatment of
endometriosis is usually individualized  to  the  patients  age,  desire  for
pregnancy,  and  the amount and extent of the disease.  In general the aim of
therapy is  to  suppress  ovarian  function  with  hormonal  therapy  such as
nafarelin, progestins and danazol.  Surgery is  done  via  laparoscopy  using
laser  vaporization or fulguration of the implants.  The endometriomas may be
resected and drained  and  the  pelvic  adhesions are interrupted.  Presacral
neurectomy may be done for severe incapacitating pain.  To achieve subsequent
fertility  and  pregnancy  the  patient  may  need  microsurgery,  in   vitro
fertilization  or gamete intrafallopian tube transfer.  Radical therapy would
consist of hysterectomy  with  or  without  removal  of  the ovaries.  If the
patient is young the ovaries or a portion of the  ovary  is  saved.   SYNAREL
(Nafarelin  acetate nasal spray can be used for endometriosis.  Nafarelin has
also been used in the treatment  of uterine myomas, polycystic ovary syndrome
and the premenstrual syndrome.  The side effects are hot flashes,  headaches,
vaginal  dryness, decreased libido and loss of vertebral bone density.  There
may be some elevation of the  alkaline phosphatase, calcium and phosphate and
increases in the urinary excretion of calcium  and  hydroxyproline.   At  the
present  time synarel shouldn't be used for longer than 6 months.  Synarel is
started in the early follicular phase of the menstrual cycle on day 2 or 3 of
the menses.  During the first  two  weeks  of therapy nafarelin will increase
the estradiol.  From the 2-7 week of  therapy  estradiol  will  decrease  and
menses  due  to  estrogen  withdrawal will usually occur.  Once the estradiol
levels are in the range of 20-30 pg/ml no further menses are likely to occur.
The symptoms usually will not  abate until hypoestrogenism has been achieved.
The dose is 200 ug bid sprayed in one nostril.  Using this dose about 50%  of
women  will  be  amenorrheic by 6 weeks of treatment and 90% amenorrheic by 3
months.  If the endometriosis is severe  the  dose  is increased to 400 ug (2
sprays) bid for 6 weeks then 200 ug bid.   Recurrence  of  endometriosis  may
occur  after  the  six  month  course of nafarelin and the patient may need a
second course.  After discontinuing  the  nafarelin, the menses and ovulation
will begin in about 7 weeks.  Some studies have indicated that a  combination
of  a GnRh analogue as nafarelin plus a progestin (norethindrone 1.2 mg/d) is
effective and will partially block  the  bone  loss.  DANAZOL can be given at
400-800 mg per day po for 4-6 months.  The side  effects  include  hirsutism,
hot  flashes, atrophic vaginitis, acne, weight gain, hoarseness, breakthrough
bleeding, edema, cramps in the muscles, decrease in the sizes of the breasts,
liver enzyme changes, carpal tunnel  syndrome, emotional lability and changes
in the lipids.  Danazol works by inhibiting pituitary gonadotropin secretion,
and direct inhibition of endometrial growth.  Danazol will reduce implants if
they are mild or moderate, but adhesions and real large endometrial cysts are
resistant to Danazol.  About 80% will get relief of  pain  within  2  months.
Following   treatment  pregnancy  rates  are  around  40%.   CONTINUOUS  ORAL
CONTRACEPTIVES as Lo Ovral or  Ovral  can  be  given  daily for 4-6 months or
until pregnancy is desired.  Side effects include breast  tenderness,  edema,
nausea,  breakthrough  bleeding,  and  abdominal swelling.  MEGESTROL ACETATE
(MEGACE) 40 mg per  day  for  6-9  months  may be given.  MEDROXYPROGESTERONE
ACETATE (PROVERA) 30 mg per day for 6-9 months also may be used.   Progestins
act  by  inhibiting  endometrial tissue growth by causing decidualization and
then atrophy.  Progestins also  will  inhibit  ovarian hormone production and
pituitary gonadotropin secretion.  Medroxyprogesterone may also be given  100
mg  IM  q  2  weeks  for 2 months, then 200 mg IM monthly for 4 months.  Side
effects are irregular menstrual bleeding, breast tenderness, fluid retention,
emotional lability, depression, nausea, and atrophic vaginitis.  Pain relief,
either partial or full, following  progestins  is very good, approaching 90%.
LEUPROLIDE DEPOT is used at 3.75 mg IM q 30 days.  The side effect profile is
the same as nafarelin.

                   -ENDOCRINE DISEASE AND SURGERY-
THYROTOXICOSIS  poses  a  high risk for surgical complications as high output
CHF, arrhythmias and death.   Thyroid  storm  can  occur in 20-30%.  Patients
should be  treated with antithyroid drugs  or  radioiodine  for  at  least  3
months  until  patient  is  euthyroid before elective surgery.  For emergency
therapy, treat patient  with  propylthiouracil, propranolol, potassium iodide
and hydrocortisone.  HYPOTHYROID patients can have surgery  and  are  at  low
surgical risk.  However, severe myxedema patients need thyroxine replacement,
free    water    restriction   and   diuretics.    DIABETIC   patients   have
cerebrovascular, infection and cardiovascular  risks.   The patient should be
in moderate diabetic control  before  surgery  and  hypoglycemic  agents  are
withheld.  The insulin dose is reduced to 1/2 dose on day of surgery with the
serum  glucose being maintained 150-250 mg/dL in the perioperative period, as
the signs and symptoms of hypoglycemia  may not be recognized by the patient.
If any patient has recieved steroids for 2 weeks  or  more  during  the  last
year, hydrocortisone should be given in the perioperative period.

                 -ENTEROCYTOZOON BIENEUSI AND AIDS-
Metronidazole 500 mg PO q6h.

                       -ENTRAPMENT SYNDROMES-
MEDIAN NERVE NEUROPATHIES: Median nerve entrapment causes the  carpal  tunnel
syndrome  (CTS).   CTS  is the most common of the entrapment syndromes and is
caused by compression of the  median  nerve beneath the flexor retinaculum at
the wrist.   The  causes  of  this  syndrome  include  pregnancy,  rheumatoid
arthritis,  acromegaly,  gout,  myxedema,  amyloidosis,  trauma,  idiopathic,
calcium   pyrophosphate  dihydrate  deposition,  obesity,  multiple  myeloma,
occupational trauma, and  Waldenstrom's  macroglobulinemia.   Symptoms of CTS
include intermittent hand and finger numbness  of  the  first  three  fingers
including  the  thumb,  index,  and  middle  fingers.   There may be pain and
paresthesiae of the  palm  and  fingers  also.   The  pain  may extend to the
forearm and occasionally up to the shoulder.  The pain is typically worse  at
night  time,  or can be precipitated by certain maneuvers as typing, driving,
playing the piano and flexion at  the  wrist.  Patients will typically try to
eradicate the symptoms by shaking the hand, particularly at night  time  when
the  symptoms  are  worse.   Neurologic  exam  of  the  hand  reveals loss of
sensation in the palm, first three fingers, atrophy of the thenar muscle, and
weakness of the thumb pinching mechanism.  Weakness and atrophy of the thenar
muscles are  late  signs.   There  are  three  tests  that  help solidify the
diagnosis.  The first is Tinel's sign which consists of  tapping  the  median
nerve at an extended wrist in an attempt to reproduce the symptoms.  Phalen's
sign  is  reproduction of symptoms with the wrist in flexion for 1 min.  This
test is positive in about  80%  of  cases.   The  third test includes EMG and
nerve conduction velocity studies which will usually diagnose the  condition.
Treatment  consists of wrist splinting, nonsteroidal anti-inflammatory drugs,
focal steroid injection around the  median  nerve and surgical release of the
retinaculum.  PRONATOR TERES OR ANTERIOR INTEROSSEOUS  SYNDROME:  The  median
nerve  as  it  passes  below the elbow gives off a motor branch, the anterior
interosseous nerve which then passes  between  the  two heads of the pronator
teres muscle.  Compression of the median nerve or the  anterior  interosseous
nerve  in the forearm may be caused by osseous deformities, fractures, casts,
trauma, fibrous bands or muscle hypertrophy  in the forearm.  The symptoms of
anterior interosseous nerve involvement are usually sensory loss and weakness
of the pronator quadratus, flexor pollicis longus and  the  flexor  digitorum
profundus  of  the  second and third digits.  Painless weakness of flexion of
the first three fingers can  be  confused with carpal tunnel syndrome.  ULNAR
NEUROPATHY:  The ulnar nerve can become entrapped at two  sites;  either  the
cubital  tunnel at the elbow or in Guyon's canal between the pisiform and the
hook of the hamate at the  wrist.   The  most common site of entrapment is at
the elbow in the medial condylar groove or the  cubital  tunnel  between  the
medial  ligament  of  the elbow joint and the aponeurosis of the flexor carpi
ulnaris.  The ulnar nerve gives sensation  to  the ulnar side of the hand and
the palmar and dorsal sides  of  the  4th  and  5th  fingers.   Motor  supply
controls flexion of the 4th and 5th digits, flexion of the wrist, and flexion
of  the  intrinsic  muscles  of  the  hand.   Causes  of  compression include
displacement of  the  ulnar  nerve  from  a  shallow  nerve groove, prolonged
pressure trauma at the elbow, drug addiction and diabetes mellitus.   At  the
wrist,  symptoms  may  be caused by hand drills, volleyball sports, prolonged
bicycling, ganglions and, trauma.  Symptoms of ulnar compression at the elbow
include pain over the ulnar  side  of  the forearm, weakness of wrist flexion
and weakness of finger adduction and abduction plus paresthesiae of  the  4th
and 5th digits.  There may be atrophy of the first dorsal interosseous muscle
and  hypothenar  wasting.  Diagnosis is made by a positive Tinel's sign along
with EMG and nerve conduction studies.   Conservative measures may be given a
trial, but surgery often times is needed.  THORACIC OUTLET SUNDROME: Thoracic
outlet syndrome (TOS) causes diffuse, poorly localized paresthesiae, weakness
of the arm or hand and vascular changes.  Patients will have sensory loss  in
the C8-T1 distribution with atrophy and weakness in muscles that are supplied
by  the  lower trunk of the brachial plexus.  There may be sensory loss along
the ulnar border of the  arm  and  clumsiness  of  the hand.  The patient may
complain of pain with exercise of the arm or coldness of the extremity.   The
symptoms  may  occur  when  the  arms  are  extended  above  the head or when
excessive weights  pull  the  shoulder  and  arm  downward  as carrying heavy
objects.  Causes consist  of  compression  of  the  neurovascular  bundle  by
hypertrophied  muscle,  fibrous  bands  or cervical ribs as the neurovascular
bundle exits the neck.  The  differential  diagnosis would include median and
ulnar  neuropathies,  cervical  radiculopathies,  sympathetic  dystrophy  and
various vascular syndromes.  Tests include  Adson's  maneuver  (loss  of  the
radial  pulse  when the head is rotated to the opposite side and the involved
arm is abducted,  EMG  and  nerve  conduction  studies,  MRI  of the neck and
angiography.  All of these tests may be performed, but in most instances they
seldom lead  to  a  definite  diagnosis.   Since  the  syndrome  is  somewhat
nebulous,  conservative therapy should be attempted before surgery.  In about
2/3 of the  cases  exercises  adapted  to  elevate  the shoulders will afford
relief of the syndrome.  If  the  patient  doesn't  respond  to  conservative
measures  then  surgical  decompression with rib resection may help.  SCIATIC
NEUROPATHIES: Usually Sciatic radiculopathy  is produced by nerve impingement
in the lumbosacral spine area.  However, entrapment syndromes may  be  caused
by   Baker's   cysts,   tumors,   retroperitoneal  hemorrhage,  intramuscular
injections, emaciation  and  immobility,  and  sciatic  notch  obstruction by
muscle.  The patient usually presents with foot drop, absent ankle  reflexes,
and  sensory  loss  of  the  foot.  EMG is useful in localizing the defect in
order  to  prevent  back   surgery   due   to  erroneous  diagnosis.   RADIAL
NEUROPATHIES: Radial neuropathies usually present as a  painless  wrist  drop
and   inability   to   extend   the  fingers.   Most  cases  can  be  treated
conservatively.  The radial nerve supplies all of the extensor muscles of the
fingers, wrist and forearm.  The  radial  nerve  is usually compressed in the
axilla by crutches, or by hanging the arm  over  the  back  of  a  chair  for
prolonged  periods, and humeral fractures.  Inebriated individuals may injure
the radial nerve in the spiral groove during sleep (Saturday night palsy), in
which  case  there  is  sparing   of   the  triceps  muscle.   The  posterior
interosseous nerve is a  distal  branch  of  the  radial  nerve  and  can  be
compressed  at the elbow by trauma or synovitis which may produce pain in the
forearm and loss of the  ability  to  extend the fingers.  EMG will localized
the lesion.  While conservative therapy will usually alleviate  the  axillary
compression,  surgical decompression is frequently required for entrapment of
the posterior interosseous  nerve.   MERALGIA  PARESTHETICA: Any patient that
complains of burning and  paresthesias  along  the  lateral  thigh  may  have
meralgia  paresthetica.   The  symptoms  are  made  worse  by  standing,  hip
extension,  obesity, lumbar lordosis, pregnancy, diabetics, tight clothing or
seat belts.  Symptoms may be by  relieved by sitting.  The syndrome is caused
by entrapment of the lateral femoral cutaneous nerve, a purely sensory branch
arising from the L2 and L3 roots.  The nerve runs under the lateral aspect of
the inguinal ligament.  There may be  an  anomalous  split  of  the  inguinal
ligament  which  then pinches the nerve.  A diagnostic injection of Xylocaine
may be made just medial to the anterior iliac spine at the inguinal ligament.
If this alleviates the symptoms then cortisone injections in this area may be
of benefit.  However,  the  underlying  causes  should  be  taken  care of as
correction of these will benefit many patients.  Examination of  the  lateral
thigh  area  will  reveal  diminished  sensation in this area.  Again EMG and
nerve conduction studies will  help  differentiate  the condition from lumbar
radiculopathies.  COMMON PERONEAL NEUROPATHIES: Entrapment of this  nerve  as
it  winds  around  the  fibula  may  be  caused by Baker's cysts, high boots,
elastic stockings, post surgical  procedures, casts, leg crossers, bedridden,
emaciated and  immobile  patients.   The  patient  usually  presents  with  a
painless  footdrop.  If the patient has pain of the foot, sensory loss of the
plantar aspect of the foot or weakness of plantar flexion then suspect a more
proximal lesion.  If there  is  any  doubt,  EMG and nerve conduction studies
should be done which will localize the lesion.  Most  patients  will  recover
within  2-12  months  with such conservative measures as bracing of the foot.
TARSAL TUNNEL SYNDROME: Entrapment of the posterior tibial nerve is the cause
of this syndrome.  The tibial nerve, a branch of the sciatic nerve, gives off
the sural nerve and  then  continues  as  the  posterior tibial nerve passing
through the tarsal tunnel behind and below the medial malleolus of the ankle.
The posterior tibial nerve gives off branches to the plantar surface  of  the
toes  and  the  foot.   When  the posterior tibial nerve and its branches are
compressed there is numbness, paresthesias  and  pain over the plantar aspect
of the foot.  The heel is spared and the pain is usually worse at night  just
as  in  the carpal tunnel syndrome.  The differential diagnosis would include
plantar fasciitis, synovitis, peripheral  neuropathy and bursitis.  There may
be a positive Tinel's sign.  Inverting and medially  rotating  the  foot  may
also  reproduce the symptoms.  EMG will confirm the diagnosis if there is any
doubt.   Treatment  includes  non-steroidal  inflammatory  medications,  arch
supports, steroid injections around  the  nerve and surgical decompression of
the posterior tibial nerve or its branches.   FEMORAL  NEUROPATHIES:  Femoral
neuropathy  typically  presents  as  quadriceps muscle weakness, paralysis or
atrophy.  The knee jerk  is  diminished  to  absent and there is anteromedial
thigh sensory loss.  Occasionally there is pain in the groin.  Causes include
trauma, blunt  or  penetrating  injury,  diabetes  mellitus,  retroperitoneal
hematomas, neoplasms or enlarging aortic aneurysms.

                       -ENURESIS (Nocturnal)-
About  15-20%  of  children  that are 5 years of age will wet the bed, and of
these, 15% annually  will  become  dry.   Bed  wetting  is  present in 14% of
children between the ages of 5-13 and tends to run in families.   About  1-3%
at  the  age  of 18 still wet the bed.  Some children have secondary enuresis
where the child is dry for about 3-6 months, and then enuresis resumes.  This
represents about 10-25% of children.   Several theories have evolved in order
to explain nocturnal enuresis.  The first is that there is instability  of  a
small bladder that is immature.  The second states there is an ADH deficiency
that  leads  to an increased volume of dilute urine which is greater than the
capacity of the bladder.  The  third  theory contends that bed wetting occurs
during a sudden arousal from slow wave  or  non  rapid  eye  movement  sleep.
Other factors that may be important are psychologic and developmental delays.
Bed  wetting  can be divided into structural problems that will need surgery,
and those that can be  treated  with medication, observation, dietary changes
and behavioral modification.  STRUCTURAL  CAUSES  (iNCONTINENCE):  Structural
causes  include  a posterior urethral valve that occurs mainly in boys.  This
can cause post-voiding residual  urine  and  detrusor hypertrophy that can be
detected via ultrasound  exam,  or  as  trabeculation  on  cystography.   The
bladder  capacity  is usually below normal.  An ectopic ureter usually occurs
in girls and the ectopic  ureter  usually  drains  the upper pole of a duplex
kidney  (double  collecting  system),   and   carries   urine   through   the
urethro-vaginal  septum to the introitus.  The urinary output has low output,
but causes uncontrollable wetting and odor.  ENURESIS CAUSES: Enuresis causes
should be elicited by history.   The  typical  child  has no infection, has a
good stream and completely empties the bladder.  Sometimes, enlarged  tonsils
or  adenoids  may cause sleep apnea which can cause enuresis.  Food allergies
can  cause  enuresis.   Also,  physical  exhaustion  such  as  overwork,  and
excessive physical exertion may  cause  enuresis  by  causing deep sleep.  Be
sure to rule out diabetes  mellitus  or  insipidus  or  sickle  cell  anemia.
Examine  the  back  for  spinal  deformity  and the buttocks for gluteal fold
asymmetry, angular gluteal furrow, hairy or fatty patch or coccygeal dimples.
These can suggest a neurologic problem as a tethered spinal cord.  Test DTRs.
Check for fecal impaction and  history  of constipation.  Vaginitis should be
ruled out with a check for discharge, evidence of sexual  abuse  and  foreign
body.   Hypercalciuria  and  a  family  history of stones should be elicited.
LABORATORY: Ultrasound should be  used  to  test for hydronephrosis, detrusor
thickening and residual volume after voiding.  Check  the  rectum  for  fecal
impaction.    Do   a   UA   for   infection,   nephropathy  etc.   A  voiding
cystourethrogram to evaluate for obstruction and vesicoureteral reflux can be
done.  Possibly, cystoscopy may need to  be done.  If every thing fails, then
urodynamic  testing  should   be   performed.    TREAATMENT:   PSYCHOTHERAPY:
Psychotherapy  should  be  done  if  there  is any indication of a behavioral
problem.  DIETARY: Try this for 2 weeks.  If diet is instrumental as a cause,
then results should be apparent in  one  week.  Avoid milk and dairy products
after noon and completely eliminate citrus products, foods that have a lot of
sugar, melons, carbonated or caffeinated beverages,  beverages  colored  with
artificial  dyes,  and  vitamin C supplements.  BLADDER STRETCHING EXERCISES:
Bladder stretching exercises may  help  a  child  with a small bladder.  This
would include exercises in prolonging the time between bladder  emptying  and
using  the  Kegel  exercises.   This is effective in only about 30% of cases.
URINE ALARMS: Urine alarms such as PALCO wet-stop.  The sensor is attached to
the underpants and a miniature alarm  is  worn  on the shoulder near the ear.
Many children only wet a small amount and the parent can then take the  child
to  the  toilet  where the child may complete micturition.  Therapy is phased
out after 14 consecutive dry days  and nights which is usually achieved after
3 months.  POSITIVE REINFORCEMENT: Giving small rewards, such as  privileges,
etc  for  elimination  of nocturnal wetting may be beneficial.  DRUG THERAPY:
Ditropan (Oxybutynin) is used if there is a small bladder capacity.  It seems
to enhance the effectiveness  of  the  urine  alarm, but doesn't usually work
alone.  Families are warned that red cheeks, dry mouth, warm palms and soles,
blurred vision, upset stomach and personality changes may occur.   Oxybutynin
chloride  is  used  at a dose of 5 mg bid for ages 6-9 years and 5 mg tid for
ages 10-18.  Use for 2 months  and  then taper.  Imipramine is most effective
for older children.  It should be used with caution  because  of  its  narrow
toxic/therapeutic  window.   Side  effects may be decreased appetite, cardiac
arrhythmias, sleep disturbance and anxiety.   It  should  be stored in a safe
place to prevent overdose.  The drug is effective but relapses are high  when
it is discontinued.  The overall success rate is only about 25%.  The dose is
25-50  mg/day  from ages 6-9 and 50-75 mg from ages 10-18.  Use for about 3-6
months then taper.  Desmopressin  acetate  causes  bed  wetting to remit when
used as a spray, but must be used for a prolonged time, is expensive, and the
child usually relapses after it is discontinued.  Several factors may  impact
on  the success of Desmopressin.  These include a family history of enuresis,
smaller than  normal  bladder  capacity  and  urine  osmolality.   There is a
success rate of 70% when the medication is continued for up to 3 years.   The
recommended starting dose is 20 ug.  However some 81% of children may respond
to  5-10 ug/daily.  One approach would be to start with 40 ug/daily, and then
taper by 10 ug every 2 weeks  in  order  to keep the child dry.  Side effects
are usually limited to rhinitis or  epistaxis.   There  is  a  better  safety
profile   than  imipramine.   FECAL  IMPACTION  Treat  fecal  impaction  with
cleansing enemas and laxatives.  Treat vulvitis with nystatin or triple sulfa
cream.

                           -EOSINOPHILIA-
The absolute eosinophil count is calculated by multiplying the total WBC x  %
eosinophils.   Loffler's endomyocardial syndrome has an absolute count >2000,
hypereosinophilic  syndrome  >1500,  eosinophilic  fasciitis  >1500,  chronic
eosinophilic pneumonia (CEP) count  is variable.  Eosinophilic leukemia shows
blasts.   PARASITIC  CAUSES:  Cysticercus,  ascaris,  filaria,  echinococcus,
schistosoma,  toxocara,  trichinella,   strongyloides.    PULMONARY   CAUSES:
Hypersensitivity  pneumonitis,  Loffler's,  Tropical  eosinophilia,  allergic
bronchopulmonary  aspergillosis,  chronic eosinophilic pneumonia.  AUTOIMMUNE
CAUSES:  Dermatomyositis,   polyarteritis,   Sjogrens   syndrome,  rheumatoid
arthritis, eosinophilic fasciitis, allergic angiitis.  NEOPLASTIC:  Lymphoma,
chronic  myelocytic  leukemia, carcinomatosis, eosinophilic leukemia, mycosis
fungoides, and immunoblastic lymphadenopathy.  DRUGS: Nitrofurantoin, sulfas,
imipramine,   iodides,   erythromycin   estolate,   aspirin,  chlorpropamide,
methotrexate.   INFECTIONS:  Coccidioidomycosis,  tuberculosis,  cat  scratch
fever, hepatitis B, scarlet fever.  IMMUNODEFICIENCY: Hyper IgE syndrome, IgA
deficiency,  combined  immunodeficiency,  graft  vs  host  disease.    OTHER:
atheroembolic  disease,  Addison's disease, pernicious anemia, chronic active
hepatitis,   chronic   dialysis,   acute   pancreatitis,   post  irradiation,
eosinophilic  gastroenteritis,  hypopituitarism,  IV  drug  abuse,  phosphate
poisoning  and  Black  widow  spider  bites.   ALLERGY:  asthma,  hay  fever,
angioedema, atopic dermatitis, serum  sickness,  erythema  multiforme.   SKIN
DISEASE: Pemphigus, scabies, dermatitis herpetiformis, erythema multiforme.

                      -EOSINOPHILIC FASCIITIS-
Is  also  known  as  Shulman's  syndrome.   It  is a rare disease that may be
confused with  systemic  sclerosis.   The  patient  complains  of  aching and
stiffness of the extremities due to skin and subcutaneous edema and fibrosis.
Histology reveals the epidermis to be normal or mildly atrophic.  The  dermis
may  be  thickened  due  to  collagen  deposition,  edema  and  inflammation.
However, most of the inflammation is present in the subcutis and fascia which
is  thickened.   Eosinophils may be seen.  Upper and lower extremities can be
affected causing swelling,  pain  and  tenderness.   There  may be asymmetric
involvment.  The fingers and toes are spared, but the forearms and calves are
affected.  Occasionally the trunk is involved with facial  involvement  being
rare.   It  is  differentiated from scleroderma by the lack of involvement of
acrosclerosis, Raynaud's phenomenon,  and  antinuclear antibodies.  The edema
may be pitting initially, but eventually leads to a wood-like induration.  As
a result carpal tunnel syndrome and joint flexion contractures  may  develop.
Some  patients  can  develop plaques that look like localized scleroderma and
the skin may have a peau  d'orange  appearance.   In  about 50 % of cases the
condition presents after strenous exercise affecting men and  women  equally,
usually  between  the  3rd and 7th decade.  Initially there may be arthralgia
and inflammatory polyarthritis.  Rheumatoid  factor  is usually negative, but
hypergammaglobulinemia is common as well as an elevated  sed  rate.   Rarely,
there  may  be aplastic anemia, thrombocytopenia myelodysplastic syndrome and
leukemia.  There is a marked  eosinophilia  in the early stage, but decreases
with  the  duration  of  the  disease.   The  creatinine  kinase  is  normal.
TREATMENT: There may be spontaneous improvement or complete  remission  after
2-5  years.   Prednisone  30-60  mg daily may result in a partial or complete
response with resolution of  edema.   Softening  of  the  skin takes a longer
time.  The sed rate and eosinophils usually revert to normal.  Rarely,  there
may  a  return  of  the  disease.   Hydroxychloroquine is also useful in some
patients with or without prednisone.

                   -EOSINOPHILIC GASTROENTERITIS-
Eosinophilic gastroenteritis can present in  3 different forms depending upon
the involvement of the GI tract.  There is a marked  peripheral  eosinophilia
and  infiltration  of  the  wall  of  the stomach, small intestine and/or the
colon.  Many patients that develop  this  disease have had allergic rhinitis,
seasonal asthma or eczema.  In the FIRST  FORM,  which  is  characterized  by
involvement  of  the muscle wall, submucosa and subserosa, the gastric antrum
is most commonly affected, but  there  may  be involvement of the small bowel
and the colon.  A full thickness biopsy may be needed for diagnosis.   X-rays
usually  imitate those of malignancy with antral infiltration that looks like
a lymphoma or carcinoma,  but  occasionally  resemble  Crohn's disease of the
stomach and proximal small intestine.  Obstructive symptoms, nausea, vomiting
and pain are common features.  In  the  SECOND  FORM  there  is  mucosal  and
submucosal involvement.  In adults, there is predominantly involvement of the
small  intestine,  but  in  children the gastric mucosa is commonly involved.
Symptoms include diarrhea, malabsorption, abdominal and back pain and protein
loss  edema.   There  may  also  be  iron  deficiency  anemia,  hypocalcemia,
hypoproteinemia, D-xylose malabsorption, and  fat and Charcot-Leyden crystals
in the stools.  Biopsy may reveal focal patches of  mucosal  eosinophils,  or
the  more  diagnostic  sheetlike  aggregates  of  eosinophils or eosinophilic
microabscesses.  In the  THIRD  FORM,  which  is  the  rarest  form, there is
serosal and subserosal involvement  producing  an  eosinophilic  ascites  and
occasionally  an  eosinophilic pleural effusion.  TREATMENT: Prednisone 20-40
mg daily can produce a  sustained  remission  in  2-4 weeks in some patients.
Others require repeated  courses  of  prednisone  or  maintenance  prednisone
therapy at a lower dose.

               -EOSINOPHILIC GRANULOMATOUS VASCULITIS-
Eosinophilic granulomatous vasculitis is also know as allergic granulmatosis,
allergic angiitis, and Churg-Strauss  syndrome.   It was originally described
in 1951 in a group of 14 patients all of whom had asthma.  The  mean  age  of
onset  is  approximately  35-40  years of age and is characterized by asthma,
eosinophilia  >  1500  cells/mm3,  and  systemic  vasculitis  involving  >  2
extrapulmonary organs.  The  typical  patients  presents  with  a prodrome of
allergic rhinitis, exacerbation of asthma, and eosinopilia.   Following  this
the vasculitis phase begins, marked by systemic symtoms such as fever, weight
loss,  malaise  and  pulmonary infiltrates, which may be transient and rarely
cavitate as Wegener's granulomatosis.  About  40% will develop a mononeuritis
multiplex neuropathy.  Other involvements include palpable purpura, diarrhea,
GI bleeding, pericarditis, heart failure, and ECG abnormalities which is  the
commononest  cause  of  death.   Renal  involvement is rare (<5%).  The organ
systems that are most involved  include the respiratory tract (100%), nervous
system (65%), skin (60%), GI tract  (60%),  and  cardiovascular  (25%).   The
patients  may  have  nasal  polyps,  chest  pain from eosinophilic pleuritis,
paresthesias, urticaria, angioneurotic  edema, subcutaneous nodules, cerebral
infarction and hemorrhage, eosinophilic  pericarditis,  coronary  vasculitis,
endomyocardopathy, proteinuria, microscopic hematuria, arthritis, arthralgia,
myositis,  and  lymphadenopathy.   Chests radiographs have a predilection for
involvement of the  lateral  aspects  of  the  chest.   The lateral densities
characteristically have a tendency to regress in portions of the lungs, while
others  increase  in  size  or  new  infiltrates  occur.   This  pattern   of
involvement  may mimic chronic eosinophilic pneumonia and Loffler's syndrome.
However, these latter two may be  ruled  out  as they are not associated with
extrapulmonary vasculitis.  LABORATORY: Patients will have  very  high  serum
IgE.   About  70%  will  have positive anti-neutrophil cytoplasmic antibodies
(ANCA), which is secondary to  anti-myeloperoxidase antibodies and appears as
a perinuclear staining pattern (P-ANCA).  Diagnosis is made by  biopsy  which
demonstrates  a  necrotizing  small vessel vasculitis with the characteristic
collection of mature eosinophils.  TREATMENT:  If the patient is not treated,
the mortality rate is greater than 80-90%.  If the patient  is  treated  with
steroids  and  immunosuppressive therapy the mortality can be reduced to less
than 10%.  Typically the patient  is  initially treated with prednisone 60-80
mg daily with tapering slowly to alternate day therapy over 3-6 months.  Some
neurologic  defects  may  not  be  completely  resolved,  and  for  fulminant
vasculitis therapy may be started  with  IV  methylprednisolone  for  several
days.   The patient's progress should be monitored by ESR, serum IgE, P-ANCA,
and eosinophil counts.  Patients  should  be  treated  for  about 1 year with
prednisone.  Following complete remission, or in those who do not respond  to
prednisone,  cyclophosphamide  is given daily at 2 mg/kg initially.  The dose
is adjusted to avert neutropenia, and the patient is treated for 1 year.

                              -EPILEPSY-
PHENYTOIN:  Phenytoin  (Dilantin)  is  used to treat generalized tonic-clonic
seizures.  It is given at 100-300  mg  PO  qd  or the maintenence dose is 4-7
mg/kg/day.  A loading dose of 15-20 mg/kg can be  given  PO  in  equal  doses
every  2-4  hours  x  3  doses or IV at a rate of 50 mg/minute.  Phenytoin is
available as 125 mg and 30 mg/5ml  suspension in 8 oz bottles, chewable 50 mg
infatabs and 30 mg and 100 mg capsules.  It is also available for IV  use  as
50 mg/ml in 5 ml ampules.  Toxicity results in ataxia, nystagmus, dysarthria,
dystonic  posturing,  cognitive  impairment and seizures.  Allergic reactions
will   manifest   as    Steven-Johnson    syndrome,   nephritis,   hepatitis,
agranulocytosis, lymphoma type syndromes, thyroiditis,  and  SLE.   The  side
effects  are  hirsutism,  gingival hyperplasia and peripheral neuropathy.  IV
phenytoin  should  never  be  given   rapidly  as  hypotension  will  result.
Phenytoin should never be given IM.  Therapeutic levels are between 10 and 20
ug/ml.  Maintenance oral therapy can be given  as  one  daily  dose.   Trough
phenytoin     levels    are    recommended.     Carbamazepine,    cimetidine,
chloramphenicol, isoniazid, disulfiram,  chlorpromazine and propoxyphene will
increase serum phenytoin levels.  Phenytoin can decrease the serum levels  of
digoxin,  thyroid  hormone  and oral contraceptives.  Salicylates and ethanol
may  decrease  the  serum  phenytoin  level.   STATUS  EPILEPTICUS: Lorazepam
(Ativan) 2-3 mg IV stat and  may  be  repeated  in  15  minutes  or  diazepam
(Valium)  5-10 mg IV stat, repeated in 15-30 minutes if necessary.  Phenytoin
(Dilantin) given as an  800-1000  mg  IV  loading  dose,  either by giving 20
mg/min by IV push using 8-10 100 mg prefilled syringes,  each  given  over  5
minutes,  OR  by adding 1 gram of phenytoin to 250 ml of 0.45 NS and dripping
in over  1  hour.   If  patient  persists  in  seizing  give  700-1000  mg of
phenobarbital (10-15 mg/kg) IV push at a rate of 50 mg/min.   Intubation  may
be    needed.     Diazepam,    lorazepam    and   phenobarbital   can   cause
cardio-respiratory depression.   CARBAMAZEPINE:  Carbamazepine  (Tegretol) is
effective for generalized tonic-clonic and partial  seizure  disorders.   The
usual  maintenance  dose  is  10-20 mg/kg/day PO divided into equal doses 2-4
times a day.  The drug is supplied  as 200 mg scored tablets, 100 mg chewable
tablet and 100 mg/5ml oral suspension.  The drug should  be  started  out  as
about  200  mg  BID  in  order  to  obviate  any  GI side effects.  It can be
increased every 3-5 days by 200  mg increments until there is seizure control
and therapeutic levels are attained.  The total dose given per  day  is  1200
mg.   The  side  effects  of  carbamazepine  include drowsiness, diplopia, GI
disturbances, blurred vision,  diplopia,  and headache.  Hematologic toxicity
is a possibility, but is no more common than other  drugs  used  for  seizure
control.   Peak  levels  are usually attained about 2-3 hours after ingestion
and the side effects may coincide with  the peak level.  If this is the case,
divide the total dose into a TID or  QID  schedule.   Allergic  reactions  to
carbamazepine  includes  various  forms  of  rashes.  If the patient takes an
overdose of the drug  the  following  symptoms  may  be present: There may be
confusion, nystagmus, nausea, vomiting, stupor or  coma,  agitation,  tremor,
mydriasis,  abnormal reflexes, flushing and urinary retention.  Carbamazepine
should be used  with  caution  in  those  patients  that have coronary artery
disease and cardiac dysrhythmias.  The  drug  may  also  decrease  the  serum
sodium  due  to  its  antidiuretic  effect  which  may  lead to seizures.  If
carbamazepine is used in  pregnant  patients  the  levels should be monitored
very closely as neural tube defects may occur in the fetus.   Therefore,  the
risks   and   benefits   should   be  reviewed  before  this  drug  is  used.
Carbamazepine  may  decrease  the  effects  of  warfarin  and contraceptives.
Phenytoin and phenobarbital can reduce the effects of carbamazepine.  Calcium
channel blockers, fluoxetine, cimetidine, propoxyphene,  chloramphenicol  and
erythromycin  may  raise carbamazepine levels into the toxic range.  Patients
taking carbamazepine should be  monitored  periodically  every 2-3 months for
the first year of therapy by performing CBCs, liver function tests and  serum
electrolytes.   Thereafter,  every  6  months  is appropriate.  ETHOSUXIMIDE:
Ethosuximide (Zarontin) is indicated for absence seizures.  It is supplied as
250 mg capsules and Zarontin  syrup  250  mg/5ml.   The  adult dose is 500 mg
daily intially or 15-30 mg/kg/day given in two  equal  doses.   This  may  be
increased by 250 mg every 4-7 days as dictated by response.  The maximum dose
is 1.5 grams daily in divided doses.  For children 3-6 years, the dose is 250
mg daily initially.  Over 6 years, give 500 mg initially.  Increase by 250 mg
increments  daily  every  4-7 days in both age groups.  The usual maintenance
dose is 20  mg/kg/day  in  divided  doses.   Ethosuximide  does  not have any
significant interactions  with  other  anti-eptileptic  drugs.   If  toxicity
occurs  at peak levels spread the drug over a TID or QID schedule rather than
BID.  Ethosuximide is not recommended  in  children  under the age of 3. Side
effects  include  drowsiness,  blood  dyscrasias,  ataxia,  hepatic,   renal,
psychological,  behavioral and GI disturbances, SLE, headache, rash, gingival
hyperplasia,  and  Stevens-Johnson  syndrome.   The  patient's  blood,  liver
function and urine should be  monitored.  Ethosuximide may cause tonic-clonic
seizures.  VALPROATE: Sodium divalproex  (Depakote)  is  also  indicated  for
absence seizures and has equal efficacy with ethosuximide.  Sometimes the two
are  used together in order to control petit mal seizures.  Valproate is also
just as effective as  carbamazepine  and phenytoin in controlling generalized
tonic-clonic seizures.  Valproate is considered to be the drug of  choice  in
absence   that  is  associated  with  generalized  tonic-clonic  seizures  or
myoclonic seizures.  Valproate is also  effective in partial seizures, but is
not as effective as carbamazepine.  Divalproex sodium comes as 125 mg, 250 mg
and 500 mg tablets.  There also is a depakote sprinkle that is  available  as
125 mg in coated granules in capsules for children.  The usual dose initially
is  15  mg/kg/day  in  2-3  divided doses with food.  Increase weekly by 5-10
mg/kg/day until response occurs or a  maximum of 60 mg/kg/day.  The sprinkles
capsule may be swallowed or the contents of the capsules may be sprinkled  on
soft  food.   The  usual  maintenance dose is 15-60 mg/kg/day in a TID or QID
schedule.  The therapeutic  serum  level  is  50-140  ug/ml.  Side effects of
Valproate include tremor,  GI  upset,  drowsiness,  hyperammonemia,  elevated
transaminases and platelet dysfunction.  Hepatic failure may occur and can be
fatal.  The risk of hepatic failure is seen mostly in young children that are
taking  several  anti-epileptic  drugs, particularly those children under the
age of 2. FELBAMATE: Felbamate  (Felbatol)  is indicated for partial seizures
with and without generalization in adults.  It is also used as an adjunct  in
Lennox-Gastaut  syndrome  in  children.  It is available as 400 mg and 600 mg
scored tablets.  The  dose  for  adults  over  the  age  of  14  when used as
monotherapy is 1.2 grams/day given in 3-4 divided doses.  It may be increased
by 600 mg every 2 weeks to 2.4 grams/day.  The maximum dose is 3.6 grams/day.
For Lennox-Gestaut syndrome in children from the age of 2-14 years, the  dose
is  15  mg/kg/day  given  in  3-4 divided doses.  There should be concomitant
reduction of other anti-epileptic  drugs  that  are  being used to treat this
syndrome.  Increase the dose by 15 mg/kg/day at 1 week intervals to a maximum
of  45   mg/kg/day.    Felbamate   potentiates   valproate,   phenytoin   and
carbamazepine  metabolites.   It  decreases  the  effects  of  carbamazepine.
Felbamate  is  antagonized  by  carbamazepine  and  phenytoin.   Side effects
include GI disturbances, somnolence, insomnia, headache, dizziness, anorexia,
fatigue, constipation, myalgia,  rash,  chest  pain, fever, upper respiratory
tract infections, and CNS and sensory disturbances.

                       -ERECTILE DYSFUNCTION-
Erectile dysfunction (ED) or impotence is the inability to obtain or  sustain
an  erection that is satisfactory for intercourse and may feature a reduction
in frequency of erection, detumescence during intercourse or complete lack of
tumescence.  Recent estimates are that  there  are  about 20 million men with
erectile dysfunction.  Most of these men are > 65  years  of  age.   However,
erectile   dysfunction   can  occur  at  any  age  and  can  be  psychogenic,
vasculogenic,  medication  induced,  anatomic,  surgery  and  trauma related,
endocrine,  or  neurogenic.   In  some  men  the  cause  is   multifactorial.
ENDOCRINE  CAUSES:  Endocrine  causes  include  diabetes  mellitus  with  its
associated  renal  disease, hypertension, vascular disease, high cholesterol,
and low  HDL.   Primary  testicular  or  hypothalamic-pituitary hypogonadism,
hyperprolactinemia,  hyper  and   hypothyroidism,   Addison's   disease   and
acromegaly   can  also  be  associated  with  ED.   NEUROPATHIC  CAUSES:  Any
alteration of the sacral cord center at S2-S4 and the thoracolumbar center of
T12-L1, cerebrovascular, spinal,  afferent,  and  autonomic systems can cause
impotence.  TRAUMA AND SURGERY: Pelvic surgery and  TURP  can  be  associated
with  ED.   MEDICATION  CAUSES:  This  is a very important class, for indeed,
something definitive can be  done  if  the  offending  drug is removed.  Many
medications  have  been  incriminated  and  include:  alcohol,  amphetamines,
anticancer   drugs,    atropine    sulfate,    caffeine,    chlordiazepoxide,
chlorprothixene,   cimetidine,   digitalis,  ismelin,  imipramine,  levodopa,
lithium,   marijuana,   aldomet,   MAO   inhibitors,   narcotics,   nicotine,
phenothiazines   (particularly    mellaril),    reserpine,   beta   blockers,
barbiturates,    antihistamines,    butyrophenones,    clonidine,    cocaine,
ketoconazole, leuprolide,  methadone,  spironolactone,  thiazides,  tricyclic
antidepressants,  estrogens,  and  antiandrogens.   HISTORY AND PHYSICAL: The
sexual  history  is  needed  to  accurately  define  the  patient's  specific
complaint and to refine what exactly the patient is trying to tell you.  That
is, does he mean erectile  dysfunction, disturbance of orgasm or ejaculation,
or sexual desire.  He should be asked about  the  presence  of  nocturnal  or
morning  erections, details of his sexual techniques, performance anxiety and
what motivation he might have  for rehabilitation and specific treatment.  In
the general, history risk factors should be ascertained such as hypertension,
smoking,  coronary  artery  disease,  intermittent  claudication,   diabetes,
peripheral  vascular disease, pelvic trauma or surgery.  If the patient has a
decreased sexual desire then hypogonadism would be foremost in the diagnosis.
Inquire  about  alcoholism,  multiple   sclerosis,  strokes,  spinal  injury,
radiation and any illicit drugs or medications that he might be taking as 25%
of causes stem from medications.  Ask about any  symptoms  from  prostatitis,
priapism,  voiding  dysfunction  and peyronie's disease.  Ask if there is any
unusual depression or  neurosis.   Physical  exam  should include femoral and
lower extremity pulses, a check on the secondary sexual  characteristics  and
any  evidence  of  Peyronie's  disease,  perianal  sensation, bulbocavernosus
reflex (elicited by squeezing the glans  and  checking for the anal wink) and
sphincter  tone.   LABORATORY:  An  early  morning  testosterone  and   serum
prolactin  should  be  done.  A low testosterone requires that the LH/FSH and
prolactin  be  drawn.   Inappropriately   low   LH/FSH   levels  with  a  low
testosterone level mandates evaluation  for  hypogonadotrophic  hypogonadism.
Elevated  LH/FSH  with  a consistently low testosterone indicates primary end
organ (testes) failure  and  is  treated  by Depo-testosterone.  In addition,
check creatinine, BUN, FBS, UA, TSH,  FT4  or  FTI.   To  help  differentiate
organic  impotence from psychogenic impotence use the 3 ring snap gauge.  The
DacoMed RigiScan is a small device  that allows for the continuous monitoring
of tumescence and rigidity and may  be  used  on  an  outpatient  basis.Three
nights  of data regarding the quality and quantity of erections are stored in
the devices microcomputer.  The  device  is  then  returned to the physician.
The patient may be given a test for adequacy of arterial and  veno  occlusive
function,  and  also  to  differentiate  vascular from neuropathic causes, by
injecting  the  intracavernous  area  with  a  vasodilating  agent.   Doppler
ultrasound that compares the penile  systolic  blood pressure to the brachial
systolic blood pressure with a resultant value  of  less  than  0.7  is  very
suggestive  of  vasculogenic  disease.  Plethysmography will measure the flow
across arteries of the penis and  is  more  accurate than Doppler.  CT of the
pituitary is done if the prolactin is elevated.  Other tests that can be done
at  a  special  medical   or   research   center   include:   pharmacological
pelvic-penile    angiography,   pharmacological   duplex   gray   scale-color
ultrasonography       and        pharmacological       dynamic       infusion
cavernosometry-cavernosography.  TREATMENT: Treatment is unsatisfactory in  a
large  proportion  of  men because of unwillingness to try a treatment and if
started there is a high  drop  out  rate  with  some  of the devices.  If the
patient has psychogenic impotence then psychiatric care should be given.   If
medications  are  causing the ED then discontinue these.  INTRACAVERNOUS SELF
INJECTION  THERAPY-   with   papaverine,   prostaglandin   E1  (alprostadil),
vasoactive intestinal peptide and phentolamine  can  be  tried.   Combination
therapy  of  these can be tried or monotherapy.  Papaverine is being replaced
by prostaglandin E1 as  papaverine  can cause hypotension, reflex tachycardia
and reversible abnormalities on hepatic function tests,  prolonged  erection,
and  corporal  fibrosis.   Informed written consent should always be obtained
with a prior discussion of the  complications.  The injections should be used
only once in a 24 hour period and at the most 3  times  per  week.   Patients
should  be  examined  every  three  months  for  injection  nodules, corporal
fibrosis or hematomata.  Contraindications  to  the procedure include history
of priapism, poor manual dexterity and visual acuity, sickle cell disease  or
any  clotting  disorder.   VACUUM  CONSTRICTIVE  DEVICES-  (ErecAid).   These
devices  work  by pumping blood into the penis by vacuum suction and a rubber
constrictor  prevents  blood  from   flowing   out.   The  drawbacks  include
obstruction of ejaculate and potential ischemic injury related to the wearing
of the constriction rings (It is recommended that the  constriction  ring  be
used  for less than 30 minutes).  Patients and their partners are troubled by
the lack of spontaneity in  their  sexual relationship and general discomfort
of the device leads to a high drop  out  rate.   VASCULAR  SURGERY-  For  the
penile  venous  leak,  venous  ligation  can be done.  However, currently the
tests to  determine  a  venous  leak  are  incompletely  validated.  Arterial
revascularization  is  usually  restricted  to  large  medical  centers   for
congenital or traumatic vascular difficulties.  PENILE PROSTHESES- In general
there  are  three classes of prostheses: malleable, inflatable and semirigid.
The main problems with these  are  mechanical failure, erosions and infection
(particularly common in diabetics and spinal cord  injuries).   TESTOSTERONE-
Should  be  reserved  for the hypoandrogenic patient.  Never use an oral dose
because of hepatotoxicity and elevations in serum lipids.  Give IM once q 3-4
weeks.  Testosterone can improve  libido without improving erectile function.
All patients should have a baseline  PSA  and  rectal  exam  because  of  the
theoretical  possibility  of stimulating growth of an occult prostate cancer.
Don't give testosterone if  the  prolactin  is elevated.  First normalize the
prolactin by discontinuing drugs  that  cause  the  prolactin  elevation,  OR
suppress  prolactin  with  bromocriptine.  Other side effects of testosterone
include gynecomastia, rise in  hematocrit, water retention, hypertension, and
precipitation of CHF.  YOHIMEX (Yohimbine) 5.4 mg  tid  can  be  tried.   The
patient  should  be treated for at least 10 weeks to determine the success or
failure.  Yohimex is contraindicated in renal disease.  It is not recommended
for females and during pregnancy.   Side effects consist of antidiuresis with
water  retention,  central  excitement,  elevation  of  BP  and  heart  rate.
Headache, skin flushing, tremor and  irritability,  and  dizziness  can  also
occur.   If  side  effects  occur  reduce  to 1/2 tab tid followed by gradual
increase to 1 tab tid.  VASODILAN (isuxuprine)- enhances the effectiveness of
yohimbine and the two agents are often used in combination.

                        -ERYTHEMA MULTIFORME-
CAUSES:  Erythema  multiforme  is  actually  an inflammatory polymorphic skin
disorder that can be caused by multiple  factors.  There is no cause in about
50%  of  cases.   Other  causes  would  include  coxackie  and   echoviruses,
brucellosis,   diphtheria,   Yersinia,  tuberculosis,  tularemia,  gonorrhea,
psittacosis, Mycoplasma  pneumoniae,  histoplasmosis, poliomyelitis vaccines,
BCG, and other vaccines.  About 90% of Erythema multiforme  minor  cases  are
due   to   herpes   simplex.    Malignancy,  premenstrual  hormonal  changes,
consumption of beer, Reiter's syndrome and pregnancy have all been associated
with erythema multiforme.  Multiple drugs  are capable of triggering the skin
manifestations.  Common ones  would  include  sulfonamides,  anticonvulsants,
nonsteroidal    anti-inflammatory   drugs,   penicillin,   barbiturates   and
salicylates.   Stevens-Johnson  syndrome  is   the  major  form  of  erythema
multiforme and can be caused by viral infections, fungal infections, collagen
vascular diseases, lymphomas, leukemias and cancer.  CLINICAL: The rash has a
sudden onset with a predilection for the extensor surfaces with  involvement,
oftentimes,  of  the  palms  and  soles.  The skin lesions begin as edematous
papules that may develop into  bullae.   Mucous  membranes can be involved in
about 25% of cases and is usually limited  to  the  oral  cavity.   The  peak
incidence  is in the 20s and 30s.  The disease is rare under the age of 3 and
over the age of 50.  Males are involved  more than females in a ratio of 3:2.
The skin lesions usually resemble a target or iris and are symmetrical.   The
typical  target  lesion  consists  of  a  central erythema or purpura with or
without vesiculation which is  surrounded  by  normal appearing skin and then
the outer ring of erythema.   The  lesions  may  be  associated  with  fever,
arthralgia  and  fatigue.   There  is very little itching.  There may be some
burning.  There seems to be  an  increased  incidence in the spring and fall.
The lesions typically last for about 2-4 weeks.  Some of the lesions  may  be
erythematous papules and wheals which later can turn into the iris lesions or
blisters.   If  there  is a question as to the cause, then biopsy can be done
which shows a keratinocyte  necrosis with perivascular lymphocytic infiltrate
in the upper dermis.  There is spongiosis, intracellular edema  and  vacuolar
changes  at  the  dermal-epidermal junction.  With immunofluorescence studies
there may be IgM and  C3  deposits.   In Stevens-Johnson syndrome the patient
usually has a high fever, many bullae and involvement of two or  more  mucous
membrane  surfaces.   Mucous membranes that can be involved include the eyes,
nose, trachea,  esophagus,  genitalia  and  rectum.   There  are ulcerations,
crusting, bleeding and painful erosions.  The patient may have conjunctivitis
or stomatitis 1-2 days before the onset of the rash.  There may be hematuria,
nephritis, hepatitis, pericarditis, pneumonitis and renal failure.  Mortality
can be high ranging from 5-10%.   The  skin  lesions  may  end  up  as  toxic
epidermal  necrolysis  or Lyell's disease which has a mortality of about 50%.
DIFFERENTIAL DIAGNOSIS: The differential diagnosis can be extensive and would
include the following: necrotizing  vasculitis, contact dermatitis, secondary
syphilis, pemphigus vulgaris and pemphigoid, dermatitis  herpetiformis,  drug
eruptions,   urticaria,   Behcet's   syndrome,   aphthous   ulcers,  herpetic
gingivostomatitis, rocky mountain  spotted fever, meningococcemia, Kawasaki's
disease, viral exanthems, herpes  gestationis,  ringworm,  pityriasis  rosea,
collagen vascular disease, serum sickness, septicemia, granuloma annulare and
lichen  planus.   TREATMENT:  All  medicines that may be implicated should be
discontinued and all  infections  should  be  treated.  Symptomatic treatment
consisting of Burrow's solution or Domeboro solution can be  applied  to  the
lesions.    The   mouth   lesions   may  be  painful,  but  mouthwashes  with
diphenhydramine, xylocaine and kaopectate  may  help.  Oral hygiene should be
meticulous and the patient needs to be hydrated.  In particular, if there  is
corneal  involvement  or  iritis,  the  patient  should  be  referred  to  an
ophthalmologist.   All secondary infections should be treated.  If there is a
rapid progression to Stevens-Johnson  syndrome  then prednisone 1-2 mg/kg/day
may help.  If Mycoplasma  is  the  cause  then  treat  with  a  tetracycline.
Acyclovir 200 mg 5 times daily can be used to treat herpes simplex.

                          -ERYTHEMA NODOSUM-
Erythema  nodosum  is an inflammatory hypersensitivity reaction that produces
tender,  red,  usually  pretibial,  skin   and  subcutaneous  round  or  oval
nonulcerating  nodules.   They  may  occasionally  be  seen  on   the   upper
extremities  or  trunk.   The  nodules  usually  are not greater than 6 cm in
diameter.  These lesions may  be  confused with cellulitis.  Erythema nodosum
is most common in young women.  Causes include sarcoidosis, collagen vascular
disease, inflammatory bowel disease (Crohn's disease,  ulcervative  colitis),
Behcet's syndrome, pregnancy, lymphoma, leukemia, drugs (birth control pills,
sulfonamides,   bromides,   antibiotics),   and   infections   (Streptococcal
infections,   Yersinia   infections,   TB,   blastomycosis,   histoplasmosis,
psittacosis, coccidioidomhycosis, lymphogranuloma venereum, viral infections,
atypical myobacterial infections, and Chlamydia infections).  Many causes are
idiopathic.   If  the patient has no other symptoms other than the nodules, a
minimal  workup  would  include  a  CBC,  sed  rate  and  chest  x-ray.   The
differential   diagnosis   would   include   periarteritis   nodosa,  nodular
vasculitis, erythema  induratum  and  secondary  inflammatory  or  vasculitic
processes   associated   with   underlying  connective  tissue  disorders  or
malignancies.  Biopsy of the lesions  in  erythema nodosum will show a septal
panniculitis with a lymphohistiocytic infiltrate.  The  biopsy  should  be  a
deep  skin  biopsy  including  subcutaneous  fat.   Punch biopsies may not be
adequate.  TREATMENT: The condition is  usually self limited, but the patient
may need support until the lesions resolve.  This  usually  consists  of  bed
rest,  wet  dressings,  support  stockings,  leg  elevation  and nonsteroidal
antiinflammaotry agents, such as indomethacin  25-75  mg TID depending on the
age and size of the patient.  Since indomethacin can cause peptic ulceration,
hemorrhage, and renal insufficiency, the patient should  be  monitored.   The
treatment  is  usually  for  only  2-3  weeks.   If  oral  contraceptives are
responsible,  a  different  contraceptive  in  lower  concentrations  may  be
helpful.  Potassium iodide has  also  been  helpful in idiopathic cases using
potassium iodide 300 mg enteric  coated  tablets  TID  with  meals.   If  the
tablets cannot be found use 5-8 drops of potassium iodide TID orally in juice
or water.  Improvement will usually occur within a few days.  Side effects of
potassium  iodide  include  dyspepsia,  heartburn,  and  a bitter taste.  The
enteric coated tablets can cause  small bowel ulcerations.  Pregnant patients
should  not  be  given  potassium  iodide,  as  they   are   contraindicated.
Hypersensitive  reactions  to  potassium  iodide  occasionally  occur and are
manifested   as   fever,    arthralgia,   angioedema,   lymphadenopathy   and
eosinophilia.  Iodides may also cause salivary gland  enlargement,  increased
salivation,  coryza, swelling of the eyelids, headache, pain in the teeth and
gingiva, pulmonary edema, acne, thyroid adenoma, goiters and myxedema.

                     -ESMOLOL AND HYPERTENSION-
(Brevibloc).  500 ug/kg/min for 4  min,  then  150-300  ug/kg/min  IV.   Side
effect: hypotension.

                    -ESOPHAGEAL VARICEAL BLEEDING-
Bleeding esophageal varices can be a devastating disease with  exsanguination
occurring suddenly.  There may be mortality rates of 50% at 6 weeks following
the  initial  bleed  and  75% at 2 years.  Multiple therapeutic measures have
been employed over the years  to  curb  the  bleeding, but the bottom line is
that the underlying chronic liver disease, rather than the treatment, is  the
prognostic  factor.   Patients with Child's class A have a combined early and
late mortality of 0-5% when  treated surgically.  Patients with Child's class
C have mortality rates of 64-68%.  In genral, most patients that present with
acute variceal  bleeding  should  initially  receive  sclerotherapy  or  band
ligation.   If  rebleedig  occurs,  there  should  be  a  second  attempt  to
endoscopically  control  the  bleeding.  If successful, the patient should be
placed  in  a  program   to   obliterate   their   varices  with  banding  or
sclerotherapy.  Following this, endoscopy should be undertaken every 6 months
for repeat obliteration if there is found to be recurrence.  If sclerotherapy
and banding are unsuccessful, vasopressin and nitroglycerin, or  somatostatin
should  be  attempted.  If bleeding persists following pharmacologic methods,
transjugular intrahepatic portosystemic shunting,  or shunt surgery should be
used.  Balloon tamponade is usually reserved as an emergency measure to  curb
the  bleeding  until  a more definitive therapeutic maneuver can be employed.
The most common  cause  of  portal  hypertension  is  cirrhosis, although any
number of conditions  can  be  associated  with  esophageal  varices.   These
include  prehepatic  disorders  such  as portal vein thrombosis, intrahepatic
disease (usually cirrhosis), and  post  hepatic  obstruction as in vena caval
thrombosis.  Patients that have  persistent  elevation  of  the  protal  vein
pressure greater than 12 mm Hg is commonly associated with the development of
collaterals from the portal to the systemic circulation.  In order to by-pass
the  liver,  the  blood travels through the short gastric and coronary veins,
then coursing through the periesophageal  plexus to the azygous system.  This
will in turn produce dilated  veins  in  the  esophagus  and  fundus  of  the
stomach.   Bleeding  may occur from the esophageal varicies, gastric varices,
or other varices in the GI tract.  The paraumbilical veins may dilate leading
to  abdominal  wall  veins  and  caput  medusae.   Dilation  of  the inferior
mesenteric vein	can result in hemorrhoids with bleeding.  Portal pressure can
be approximated by the hepatic vein gradient, which is the difference between
the wedged hepatic vein pressure and the free hepatic vein  pressure.   About
30%  of  patients  with  esophageal  varices will have bleeding.  The typical
presentation is  with  emesis  of  bright  red  blood.   About  50% will stop
bleeding temporarily, but rebleeds are common at 20-58%.  About 60% will have
rebleeding within the first week.  Endoscopy is the procedure of  choice  for
diagnosis and treatment.  This may reveal active variceal bleeding or oozing,
adherent  clot  to  the varix, erosions over the varices, or overlying cherry
red spots.  THERAPY: GENERAL: The  patient should have nasogastric intubation
to lavage the stomach prior to endoscopy using a large  caliber  Ewald  tube.
Two  large  bore  IV  lines  should  be established.  Abnoromal PTs should be
corrected with vitamin K, fresh  frozen  plasma  or fresh whole blood that is
less than 5 days old.  Blood transfusion should be limited  to  a  hematocrit
goal  of  30-35,  because further expansion can increase portal vein pressure
leading to more bleeding.  Transfusion of 500 ml of whole blood can raise the
portal vein pressure by 5 mm  Hg.  Hepatic encephalopathy should be prevented
or treated with lactulose 30-45 ml TID, or  as  a  retention  enema,  300  ml
diluted  to  1000  ml  with  water.  For overt encephalopthy, neomycin can be
added to provide synergistic support.   Metronidazole  200 mg q6h may be just
as effective as neomycin.  Patients should not receive diuretics or sedation,
as this will lead to encephalopathy and hepatic  coma.   Patients  should  be
continuously  followed for hypoglycemia, alcoholic withdrawal, renal failure,
ascites, septicemia, malnutrition  and  hypoxemia.   H2-receptor blockers are
not beneficial in preventing recurrent variceal  hemmorrhage.   PHARMACOLOGIC
THERAPY:  The  most  commonly  used agent is vasopressin which can be used to
reduce portal pressure by causing vasoconstriction of the splanchnic vessels.
To accomplish this, add  10-15  units  of  vasopressin  to 100-200 ml D5W and
administer over 10-15 minutes, followed by a continuous infusion  of  0.1-0.5
units/min.   (Add 600 units of vasopressin to 250 ml of D5W and deliver at 10
ml/hour, which will give a rate  of  0.4 units/minute).  It has been shown to
temporarily stop variceal hemorrhage in 60-70% of  patients.   It  does  have
several  undesirable  side  effects,  such  as decreased coronary blood flow,
angina,  infarction,   hyponatremia,   bacterial  peritonitis,  hypertension,
oliguria, bacteremia, local gangrene, activation  of  fibrinolysis,  ischemic
bowel  disease,  cardiac  arrhythmias,  and  decreased cardiac contractility.
Side effects occur in 17-35% of  cases,  and a 3% fatality rate.  Vasopressin
has  no  effect  on  survival.   It   is   recommended   that   nitroglycerin
sublingually,  or  IV  nitroprusside be given concurrently.  Nitroprussdie is
given at  1-5  ug/kg/minute  IV.   Somatostatin  and  its  synthetic analogue
octreotide will also decrease splancnic blood flow.   Somatostatin  does  not
have  the  severe side effects associated with vasopressin, and nitroglycerin
is not needed.  However  somatostatin  is  not  commonly  used because of its
cost.  Somatostatin is given as a 250 ug loading dose then 250 ug/hour.  Beta
blockers have not shown consistently reduced rebleeding rates in patients who
have bled from varices.   However,  beta  blockers  such  as  propranolol  or
naldolol  has  shown  reduction  of  first bleeds in patients with esophageal
varices.   TRANSJUGULAR  INTRAHEPATIC   PORTOSYSTEMIC   SHUNT   (TIPS)  is  a
radiologic application of an expandable metal stent  from  a  branch  of  the
hepatic  vein  throught  the  hepatic  parenchyma into a branch of the portal
vein.   TIPS  is  probably  most   valuable   in  patients  who  have  failed
sclerotherapy, and are  not  candidates  for  decompressive  surgery  due  to
advanced  liver  disease,  OR in those patients who bleed while waiting for a
liver transplant.  The success  of  this  procedure  is  about 90% and active
variceal bleeding  can  be  controlled  in  greater  than  90%  of  patients.
However,   rebleeding   rates   of   10-20%  have  been  seen  at  one  year.
Encephalopathy can develop in  25%  of  patients,  particularly  if the 10 mm
stent is used, rather than the  8  mm  shunt.   Other  complications  of  the
procedure  include  shunt  closure  in  10%  and shunt stenosis in up to 15%.
However, this may be corrected  by  balloon dilation, or placement of another
stent.  Migration of the stent, portal vein thrombosis,  hepatic  infarction,
abdominal  hemorrhage  are other complications.  SURGICAL THERAPY: Blood flow
to the liver is  compromised  with  all  shunting  procedures and can lead to
hepatic decompensation.  The selective distal splenorenal shunt  was  devised
in  order  to  preserve  blood  flow  and  thus  decrease the encephalopathy.
However, this has not been the  case,  because  of a high incidence of portal
blood flow reversal with time.  It also has a  high  perioperative  mortality
when  done as an emergency, and is techniqually difficult to perform.  It may
be useful if the  patient  is  a  candidate  for  liver transplantation as it
avoids the hilum of the liver.  Another surgical procedure is transection  of
the   esophageal  varices  with  splenectomy  and  devascularization  of  the
esophagus and stomach (Sugiura procedure).   This procedure has met with some
success.  Portosystemic shunts and esophageal transection should not be  used
in  Child's class C cirrhotic patients who have persistent encephalopathy and
severe  coagulopathies.   BALLOON  TAMPONADE:  Balloon  tamponade  is  only a
temporizing measure.  It can control bleeding  in  90-95%  of  patients,  but
about  60%  will rebleed following balloon deflation.  The 3 lumen, 2 balloon
Sengstaken-Blakemore tube or the Minnesota  tube  which  is a four-lumen tube
may be used to control active bleeding.  The Linton-Nachlas tube, which is  a
3  lumen tube with one gastric balloon is used more for gastric varices.  The
complication rate is high at  about 25-30%, including esophageal perforation,
ulceration and aspiration pneumonia.  ENDOSCOPIC  THERAPY:  Sclerotherapy  is
the  inital  procedure of choice for variceal bleeding.  It can control acute
variceal bleeding in up to 95%  of  cases, with eradication of the varices in
about 75%.  Recurrent bledding will occur in about 33% of patients  that  are
treated  with  sclerotherapy  alone.  Injection sclerotherapy is accomplished
using a catheter  with  a  retractable  needle  which  is  passed through the
operating channel of the endoscope.  Injections can be made directly into the
varices, or in the  paravariceal  area.   The  sclerosing  agents  used  most
commonly  in  the  USA  are  5%  ethanolamine oleate and 3% sodium tetradecyl
sulphate, which  have  equivalent  efficacy.   Injection  sclerotherapy not a
benign procedure.  Side effects  include  esophageal  ulceration,  stricture,
portal  vein  thrombosis, bacterial peritonitis, paralysis, pleural effusion,
fever, chest pain, bacteremia, ARDS, brain abscess, sepsis, and pericarditis.
Sclerotherapy should not be used as  a preventative measure in those who have
not bled from esophageal  varices,  as  it  is  not  consistently  effective.
Because  of  the  numerous  side  effects,  endoscopic  variceal ligation was
developed.  In this  procedure  elastic  bands  are  placed directly onto the
varix.  This procedure is just  as  good  or  better  than  sclerotherapy  in
controlling  bleeding.   Furthermore,  band therapy can eradicate the varices
with a fewer number of  sessions,  and is associated with fewer complications
than sclerotherapy.  The most common side efffects of banding  are  dysphagia
and chest pain.

                      -EXERCISE INDUCED ASTHMA-
Aerosolized  beta2  agonists  as  albuterol  are the most effective drugs for
preventing exercise induced asthma.  Two sprays of albuterol taken 15 minutes
before exercise will control symptoms in  about 90% of patients and will last
for 4-6 hours.  Cromolyn sodium and nedocromil  sodium  also  block  exercise
induced  asthma.   Two  puffs  of a beta agonist and 2 puffs of cromolyn will
prevent acute attacks in 98% of  patients.   For the remaining few who do not
respond to these drugs, adding a rapid  release  oral  theophylline  5  mg/kg
taken  one  hour  before  exercise  may  be beneficial.  Ipratropium bromide,
terfenadine, calcium channel blockers and  furosemide may also be of benefit.
Aerosolized steroids, beclomethasone, flunisolide and triamcinolone  have  no
effect.

                -FACIAL PAIN (Treatment of Atypical)-
Lioresal (Baclofen), a muscle relaxant and antispasmodic  can  be  effective.
Begin  with 5 mg tid, increasing each dose by 5 mg every three days until the
dosage reaches 20 mg tid.  If the patient still has pain in 2-3 weeks, but no
side effects, increase the dosage to 20  mg qid.  To stop therapy, taper by 5
mg  every  three  days.   Permitil,  Prolixin  (fluphenazine)  4  mg  q6h   +
amitriptyline  25  mg  at HS may also be used.  Increase the amitriptyline to
reach a therapeutic dosage of  75  mg/day.   If  the patient has a history of
cardiovascular disorder, substitute Desyrel (trazodone) for amitriptyline  at
150  mg/day initially.  Increase to 250 mg/d in divided doses.  A single dose
or the major portion  of  the  dose  may  be  given  at bed time if excessive
sedation occurs during the day.  Maintain  the  therapeutic  dosage  for  3-4
weeks.  If the patient is pain free after a month of the therapy, taper it to
zero.  A sudden termination can trigger a recurrence of pain.

                         -FASCICULAR BLOCKS-
ANATOMY AND DEFINITIONS: The infranodal ocnduction system is comprised of the
His bundle which divides into the left and right bundle branches.   The  left
bundle  then  bicurcates  into  the  anterior  and posterior fasicicles.  ECG
criteria required for a left  anterior  fascicular  block are a mean QRS axis
less than or equal to -30 degrees with initial R waves in leads II,  III  and
aVF  and  Q  waves  in  leads I and aVL.  Left posterior fascicfular block is
defined by a mean right axis deviation  of  > 110 degrees with Q waves in II,
III, and aVF and  initial  R  waves  in  leads  I  and  aVF.   LEFT  ANTERIOR
FASCICULAR  BLOCKS:  Left  anterior fascicular blocks (LAFB) occur frequently
and  can  be  associated  with  several  cardiac  diseases  such  as systemic
hypertension, aortic valve disease, ischemic  heart  disease,  cardiomyopathy
and  can  even occur without evidence of cardiovascular disease.  Often there
is a combination of  right  bundle  branch  block  in association with a left
anterior or  posterior  fascicular  block.   These  are  termed  bifascicular
blocks.   The  most  common  of  these two are the RBBB in association with a
LAFB.  This latter condition can  result  in  progression to a complete heart
block at the rate of 5% per year.  This rate  is  not  great  enough  to  use
prophylactic  pacing  to  prevent  sudden  death in certain situations.  Some
studies have indicated that sudden  death in these patients with bifascicular
blocks is more commonly due  to  ventriular  tachyarrhythmias  than  complete
heart block.  A trifascicular block can also occur which is defined as a RBBB
+  LAFB  or LPFB + a first degree AV block.  LEFT POSTERIOR FASCICULAR BLOCK:
Conduction block isolated to the  posterior  fascicle  of the left bundle are
rare.  However, when  they  are  present  they  signify  significant  cardiac
disease  and  are  often  in  association with conduction delays of the right
bundle.  These bifascicular blocks progress more frequently to complete heart
block than bifascicular blocks involving  the  left anterior fascicle + RBBB.
This apparently is due to the large amount of myocardial damage necessary  to
produce a RBBB + LPFB.  Isolated RBBB is fairly common on ECGs and has only a
minimal  increased  risk  for  development of complete heart block.  LBBB may
have even less potential development of complete heart block.

                            -FEVER CLUES-
DIAGNOSTIC SIGNIFICANCE BY MAGNITUDE  OF  THE  TEMPERATURE: Extreme pyrexia >
106 F includes CNS fevers (hemorrhagic,  neoplastic,  trauma  or  infection),
drug fever, heat stroke, HIV infection and malignant hyperthemia.  FEVER WITH
RELATIVE  BRADYCARDIA:  CNS  lesions,  Dengue,  drug  fever, Epidemic typhus,
Legionnaires disease, Leptospirosis, lymphomas, malaria, psittacosis, typhoid
fever, and yellow fever.  To find out if there is a relative bradycardia take
the last digit of the temperature  in  Farenheit  and decrase this by one and
then multiply that number by 10 and then add it to 100.  For example  if  the
temperature  is  104,  the  pulse  rate  is calculated as 4-1=3x10 + 100=130.
Therefore, if a patient has a temperature of 104, then a pulse lower than 130
constitutes relative bradycardia.  This works  best if the temperature is 102
or above.  DIAGNOSTIC SIGNIFICANCE OF DURATION AND DEGREE OF FEVER: Prolonged
obscure  fevers  less  than  102  include  any  malignancy,  cirrhosis,   CMV
infection,  hepatitis  (B  or non A-non B), infectious mononucleosis (Epstein
Barr), SBE, TB,  untreated  legionnaires  disease,  Mycoplasma pneumonia, and
Zoonoses.  Prolonged obscure fevers greater  than  102  include  drug  fever,
hypernephroma,  intraabdominal, renal-perinephric or pelvic asscess, Kawasaki
disease, lymphoma, metastasizing  carcinoma  to  the  liver or CNS, pulmonary
hypersensitivity   diseases,   SBE,   TB    (especially    disseminated    or
extrapulmonary).   DIAGNOSTIC  SIGNIFICANCE  OF FEVER IN THE HOSPITAL PATIENT
WITHOUT LOCALIZING SIGNS  AND  TEMP  <  102: Catheter associated bacteriuria,
hepatitis B and non A  non  B,  dehydration,  delirium  tremens,  nonspecific
inflammation,  resolving  hematomas,  postoperative anesthesia related fever,
and thyroid storm.  DIAGNOSTIC SIGNIFICANCE  OF FEVER IN THE HOSPITAL PATIENT
WITHOUT LOCALIZING SIGNS  AND  TEMP  >  102:  Anesthetic  induced  hepatitis,
intraabdominal  or  pelvic peritonitis or abscess, IV line sepsis, prosthetic
valve endocarditis, urosepsis, adrenal  insufficiency, CNS fever, drug fever,
malignant hyperthermia secondary to anesthesia,  transfusion  reactions,  and
vasculitis.   DIAGNOSTIC  SIGNIFICANCE  OF FEVER IN THE HOSPITAL PATIENT WITH
LOCALIZING  SIGNS  AND  TEMP  <  102:  Cholecystitis,  Clostridium  difficile
diarrhea,   decubitus    ulcers,    pharyngitis,    postperfusion   syndrome,
pyelonephritis, uncomplicated wound infection, atelectasis, gout,  myocardial
infarction,   pancreatitis,  phlebitis,  post  pericardiotomy  syndrome,  and
pulmonary emboli.  DIAGNOSTIC SIGNIFICANCE  OF  FEVER IN THE HOSPITAL PATIENT
WITH  LOCALIZING  SIGNS  AND  TEMP  >  102:  Clostridium  difficile  colitis,
cholangitis, intraabdominal or pelvic peritonitis or abscess, IV line sepsis,
nosocomial   pneumonia,   procedure    related    bacteremias,    suppurative
thrombophlebitis, pancreatic abscess, infected pseudocyst, and vasculitis.

                      -FEVER OF UNKNOWN ORIGIN-
INFECTION:   pulmonary   abscess,   empyema,    pneumonia,    bronchiectasis,
endocarditis,  sinusitis,  dental abscess, pharyngeal abscess, brain abscess,
epidural  abscess,   meningoencephalitis,   abdominal   or  hepatic  abscess,
cholangitis, hepatitis, peritonitis, diverticulitis, perinephric or  cortical
abscess,   pyelonephritis,   prostatitis,  septic  arthritis,  osteomyelitis,
decubitus ulcer.   AUTOIMMUNE  CAUSES:  Giant  cell  arteritis, Goodpasture's
disease,  Crohn's  disease,  ulcerative  colitis,  Adult   Still's   disease,
polyarteritis,  relapsing polychondritis, sarcoidosis, rheumative fever, SLE,
Wegener's granulomatosis, vasculitis.  ONCOLOGIC  CAUSES: cancer of the lung,
pleura, GI tract, renal cell carcinoma, hepatocellular cancer.   HEMATOLOGIC:
cyclic neutropenia, hemolytic disease, leukemia, lymphoma, pernicious anemia.
ALLERGIC:  drug  reaction to anitibotics, iodides, phenobarbital, methyldopa,
streptokinase,  quinidine,  cimetidine,  phenytoin,  insect  bites  and horse
serum.  METABOLIC: alcoholic hepatitis and cirrhosis, alcohol withdrawal  and
DTs,  Fabry's  disease,  gout,  familial mediterranean fever, recurrent acute
porphyria,  hyperthyroidism,  hyperlipidemia   type  I,  hypothalamic  damage
secondary  to  infection,  infarct,  tumor,  trauma,   hyperthermic   damage,
neuroleptic  malignant syndrome.  TISSUE PRODUCTS: gangrene, blood collection
in the gut or cavities,  portal vein thrombosis, myocardial infarction, toxic
shock  syndrome,  venous  thrombosis,  pulmonary  embolism   or   infarction.
UNCOMMON BACTERIA: Listerosis, brucellosis, salmonellosis, tularemia, plague.
FUNGAL:  as  coccidioidomycosis,  histoplasmosis.   RICKETTSIAL: SPIROCHETAL:
Leptospira, borrelia,  syphilis.   VIRAL:  as  infectious mononucleosis, HIV,
CMV.  PARASITIC: as amoeba, malaria, filaria, toxoplasma.  MYCOBACTERIAL: TB.

                  -FEVER WITH RELATIVE BRADYCARDIA-
The pulse  should  rise  approximately  10  beats/minute  for  each  degree F
increase  in  temperature.   Exclude  patients  that  take   beta   blockers,
verapamil,   hypothyroidism   and   adrenal   insufficiency.   The  following
infectious disease will  produce  a  fever  with  a low pulse: Legionellosis,
Leptospirosis, Brucellosis, Dengue fever, Psittacosis, Rocky mountain spotted
fever,  Typhoid  fever,   tuberculosis,   yellow   fever.    Also,   consider
non-infectious causes as drug fever, factitious fever, lymphoma, CNS tumor or
trauma causing increased intracranial pressure.

                 -FIBROCYSTIC DISEASE OF THE BREAST-
Fibrocystic disease (mammary dysplasia)  of  the  breast is a common disorder
seen in premenopausal women commonly between the ages of 30-50.  Since it  is
rare  in  post  menopausal  women,  it  has  been suggested that it is due to
fluctuations in hormonal activity.   The  breast  changes are usually benign.
It has been said that mammary dysplasia increases the risk for breast cancer,
but only the variants in which proliferation  of  epitheliial  components  is
demonstrated,  are  at  risk.   Microscopically,  fibrocytic  disease  of the
breasts is characterized by microscopic  and gross cysts, adenosis, fibrosis,
papillomatosis,  and  ductal  epithelial  hyperplasia.   It  is  common   for
fibrocystic  disease  to produce asymptomatic lumps in the breasts.  However,
on occasion,  the  breasts  may  become  painful.   There  may  be associated
discharge from the nipple.  In many cases, the mastalgia is worse around  the
premenstrual  phase  of  the  cycle, at which time the cysts tend to enlarge.
Multiple and bilateral cysts may be present.   The lumps in the brests have a
tendency to fluctuate in size throughout the menstrual cycles.  If a dominant
mass is felt, cancer should be ruled  out.   Diagnosis  is  made  by  biopsy.
Since the disease occurs in younger individuals, the breasts may be too dense
for  mammogram examination.  However, ultrasound is useful in differentiating
a cyst from a solid  mass.   Any  suspicious  lesions should have fine needle
aspiration cytology.  If this is inconclusive, the mass must be  excised  for
microscopic  examination.   The  patient  should  be  advised  to examine her
breasts at frequent  intervals.   The  prognosis  is  usually good.  However,
patients will have exacerbations of pain, tenderness and cyst formation until
menopause.  Any patient that has proliferative or atypical epithelial changes
should be followed closely for development of breast cancer.  TREATMENT: Many
types of treatment have been used.  In general  the  patient  should  wear  a
brassiere  24  hours  a  day for support and protection.  Obese women produce
increased amounts of endogenous  estrogen,  and  should  be encourged to lose
weight.  Danazol, a synthetic androgen, has  been  used  at  100-200  mg  BID
orally for about 6-12 months.  Danazol decreases both prolactin secretion and
estrogen secretion.  Once the patient is improved, the dose is reduced to 100
mg/day.   Danazol is effective, but has several side effects.  Weight gain is
common and amenorrhea will occur  in  about  50%.  Other side effects include
increased skin oiliness, acne, hirsutism, and voice  changes.   The  role  of
caffeine  is  controversial,  but  it  is  usually recommended that caffeine,
theophylline, tea, and cola  drinks  be  discontinued.  Vitamin E, 400 IU/day
may be beneficial.  Thiamine 50-100 mg has been used in the past,  but  there
have  been no good clinical trials to validate the claims.  Approximately 50%
may improve with evening primrose oil  given at 3 grams/day.  Cyclic hormones
using the  low  estrogen-high  progesterone  oral  contraceptives  (Nordette,
Norlestrin  2.5/50,  Loestrin  1.5/30,  Loestrin  1/20) have been helpful.  A
significant number of  patients  will  improve  after  3-4 months of therapy.
There have also been reports of a decreased incidence of cancer  in  patients
taking  oral contraceptives for fibrocystic disease.  Bromocriptine is a long
acting  dopaminergic  drug  that  inhibits  prolactin,  which  has  been used
successfully in the treatment of fibrocystic  disease.   It  does  have  side
effects  such  as  nausea,  vomiting  nasal stuffiness, headache and postural
hypotension.  About 50% will be improved  when taking 5 mg/day.  Tamoxifen is
an antiestrogen  that  is  used  in  breast  cancer.   Since  it  counteracts
estrogen,   it  has  been  used  with  success  in  mastodynia  secondary  to
fibrocystic disease.  Progesterone given at a  dose  of 5-10 mg/day PO a week
before the menses is also effective.  The side  effects  are  usually  minor.
Mild  diuretic  therapy  given  the week before the menses can counteract the
salt and water retention from  hormones,  relieve pressure in the breast, and
decrease pain.

                            -FLUCONAZOLE-
Fluconazole (Diflucan)  is  currently  approved  by  the  FDA for candidiasis
(esophageal, oropharyngeal, urinary, peritonitis, pneumonia), and cryptococcal
meningitis.  About 80% of the drug is excreted in the urine unchanged.  Thus,
dose modification is needed in moderate or severe renal  insufficiency.   CNS
penetration   is  very  good  and  is  about  60-80%  of  simultaneous  serum
concentrations, even without  inflamed  meninges.   Because  of  this it is a
viable alternative to IV  ammphotericin  B  in  treating  fungal  meningitis.
Unlike  ketoconazole,  there  is  no inhibition of adrenal steroidogenesis or
testicular spermatic formation.   Fluconazole  does  interact with phenytoin,
cyclosporin and warfarin.  Adverse effects include GI  irritation  (anorexia,
nausea and vomiting, abdominal pain and diarrhea), pruritic rashes, alopecia,
chapped  lips,  hepatitis (asymptomatic transaminase elevations), exfoliative
dermatitis, thrombocytopenia, leukcopenia  and  headaches.  It is supplied as
50, 100, and 200 mg tablets and in 200 and 400  mg  injections  for  IV  use.
Oral absorption is rapid almost complete within 2 hours.

                            -FLUCYTOSINE-
Flucytosine is  never  used  alone because secondary resistance will develop.
About 90% is secreted by the kidney unchanged.  About 6% will develop GI side
effects (nausea, vomiting, anorexia,  and  diarrhea),  skin rash (7%), and an
asymptomatic increase in the SGOT which is reversible.   Aplastic  anemia  is
extremely rare.  Flucytosine is usually used in combination with amphotericin
B  (Fungizone).   Amphotericin B increases the fungal wall permiability which
will enhance the entry  of  flycytosine  into  the cell.  Flucytosine is used
mainly in cryptococcosis, candidiasis and chromomycosis.  In  cryptococcosis,
amphotericin B given with flucytosin is effective in about 85% of patients if
the   patient  doesn't  have  AIDS.   Patients  with  AIDS  do  not  tolerate
flucytosine, and only about 56% will survive a 6 week course.  Amphotericin B
will reduce renal  function  with  decreased  creatinine  clearance, and will
elevate flucytosine serum levels, which will lead to  cytopenias.   The  main
toxicity  of  flucytosine  is leukopenia and thrombocytopenia which occurs in
about 5% of patients.  These  are  more  commonly seen in those patients with
decreased renal function and correlate well  with  high  serum  concentration
(usually > 100 ug/ml).  Blood measurements should be done to prevent toxicity
in  all  patients  that have decreased renal function.  The usual dose is 150
mg/kg PO divided into  4  equal  doses  daily.  Serum concentrations of 30-40
ug/mL are achieved with this dose.  Patients that have a creatinine clearance
of 20-40 ml/min should be given 37.5 mg/kg bid.  For those with a  creatinine
clearance of 10-20 ml/min, 37.5 mg is given once daily.

                       -FOOT (Benign tumors)-
OSTEOID OSTEMOA: These occur usually in males between the ages of 5-25 years.
They arise in the foot in about 13% of cases.  Young children may limp, while
older  person  demonstrate  swelling or synovitis of a near-by joint.  X-rays
may show marked sclerosis of  the  bone  with a radiolucent nidus.  Bone scan
shows a hot spot.  CT will show the lesion.  MRI should  not  be  done.   The
differential   diagnosis   is  sclerosing  nonsuppurative  osteomyelitis  and
intracortical abscess.  Most patients will  have  night pain that is relieved
by NSAIDs and ASA.  This pattern  is  helful  in  arriving  at  a  diagnosis.
Treatment  is  surgical  excision  with  bone  grafts.   The excision must be
complete as symptoms will reappear if not totally removed.  GIANT CELL TUMOR:
These patients present with a limp,  pain and swelling.  X-rays will reveal a
lytic lesion adjacent to the subchondral bone plate with possible soft  tisse
expansion  of  the  lesion.   There  may  be a pathologic fracture.  The most
common areas of foot involvement  include the calcaneus, metatarsals, and the
distal tibia.  Involvement of the forefoot is extremely rare.   Approximately
1-2%  of  all giant cell tumors will arise in the foot and 3-5% in the distal
tibia.  More than  80%  affect  patients  20  years  and older.  Treatment is
curettage, and adjuvant phenol, liquid nitrogen, or  polymethyl  methacrylate
therapy,  and bone grafting.  Omission of the adjuvant therapy will lead to a
50% recurrence rate.  UNICAMERAL BONE  CYST:  The ilium and calcaneus are the
usual sites of involvement in older patients, while the humerus is  the  most
common  site  for  patients less than 17 year old.  Most of these simple bone
cyst occur in the first 2 decades  of  life.  About 3% of all unicameral bone
cyst occur in the calcaneus.  Occurence  in  other  parts  of  the  foot  are
extremely  rare.   The  patient  usually  has  no symptoms until a pathologic
fracture occurs.  X-rays will  show  a  lytic  lesion with cortical thinning.
Treatment  is  curettage  and  bone  grafting   via   a   lateral   incision.
Alternatively, the cyst may be aspirated followed by steroid injection.  This
will  give  a  good  result.   ANEURYSMAL  BONE CYST: The lesions are usually
asymptomatic until a  pathologic  fracture  occurs.   About 80% of aneurysmal
bone cysts occur in patients younger than 20  years  and  about  11-16%  will
arise in the ankle and foot.  X-ray will show cortical expansion of the bone.
CT  will  show a thin rim of reactive bone around the periphery.  These cysts
may be solitary or superimposed on tumors such as chondroblastoma, giant cell
tumors,  and  chondromyxoid  fibromas.   OSTEOCHONDROMA:  About  1-5%  of all
osteochondromas arise in the foot and usually in the metatarsals.  About  50%
will  present  while  in  the  teens.   The  lesions  are mostly asymptomatic
although  there  may  be   an   indurated   mass,  or  weight  bearing  pain.
Osteochondromas and subungual exostoses may have a similar x-ray  appearance.
However, subungual exostoses are generally located on the dorsum of the great
toe  distal  phalanx.   Surgical  excision  is only indicated for pain, rapid
growth, or functional impairment.   CHONDROBLASTOMA:  About  10% arise in the
foot, but chondroblastomas only account for about  1%  of  all  primary  bone
tumors.  Most of these arise in the calcaneus.  About 66% are males and about
50%  present  between the ages of 10-20.  Clinically, they present with pain,
tenderness and swelling.  X-ray will show a lytic, well circumscribed lesion.
Treatment  is  curettage,  phenol   cauterization  and  bone  grafting.   The
recurrence rate is high.  CHONDROMYXOID FIBROMA: Account for less than 1%  of
all primary bone tumors, but 25% arise in the foot, mostly in the metatarsals
and  calaneus.   Most  are  males  10-30  years  of age presenting with pain,
swelling and possible mass.  X-ray will  show  a lytic lesion that may reveal
cortical expansion.  Treatament is curretage and bone  grafting  with  a  25%
recurrence  rate  without  adjuvant  therapy.  Therefore phenol cauterization
should be used.   PLANTAR  FIBROMATOSIS:  Is  more  common  in men than women
(2:1), and arises within the plantar fascia.  It may be bilateral  in  up  to
25%.   Most patients are > 40 years of age.  The lesions may be asymptomatic,
painful or present as  burning.   Treatment  is  with  orthoses or surgery if
there is intolerable pain and  disability.   Wide  excision  is  needed  with
fasciectomy  and  split thickness skin grafting, since the rate of recurrence
after simple excision is > 50%.  Following surgery, splinting or casting in a
neutral position for several  weeks  should  be  done  to prevent soft tissue
contractures.  BROWN TUMOR FROM HYPERPARATHYROIDISM: Bone lesions present  as
swelling   or  following  a  pathologic  fracture.   X-rays  show  a  diffuse
demineralizatin of bone or focal  resorption  leading to a cystic appearance.
The serum calcium is elevated secondary to  a  solitary  parathyroid  adenoma
which  causes  80%  of  cases  of  hyperparathyroidism.  Women, in their 50s,
account for about 60%  of  cases.   Treatment is parathyroidectomy which will
cause the lesion to heal spontaneously.  Splinting is recommended to  prevent
a  pathologic  fracture.   INFECTIONS:  TB  accounts for 2% of bone and joint
involvment.  X-rays typically show kissing lesions with cystic involvement of
either side of one joint in exactly  the same place.  Cultures of the bone or
joint are positive in about 90%.  Cultures and smears are  both  negative  in
about  5%.   PIGMENTED  VILLONODULAR  SYNOVITIS:  About  30%  of tenosynovial
lesions occur in the  foot  and  ankle,  usually  occurring in patients 20-50
years of age and are either painless  or  with  aslightly  painful  swelling.
They  involve  either  the  tenosynovium  or joint and are characterized by a
diffuse, pigmented proliferation  of  the synovium.  Characteristically there
is a soft mass that may be cystic and bloody if aspirated.   Erosive  changes
may  be  seen  in several bones on x-ray.  MRI will show the heterogeneity of
the lesion.  Treatment is wide  excision  which  usually  leads to a cure for
localized lesions.  Diffuse lesions that involve the whole foot  are  treated
palliatively  with  sole  supports  and a stress relieving shoe.  If there is
extensive involvement of the  forefoot  and  midfoot with associated bone and
joint destruction, amputation may be  needed.   GANGLIONIC  CYST:  Can  arise
anywhere  in the foot, but have an affinity for the dorsum of the foot.  They
tend to arise in close approximation to  tendons or joints.  They may also be
seen in the ankle joint.  Most are patients between 10-40 years of age.   MRI
can  show  the  extent  of  the  lesion.  Aspiration is diagnostic with clear
yellow viscous fluid removed.   The  recurrence  rate after excision is about
10%.

                       -FUNGAL SUPERINFECTIONS-
Fungal  superinfections should be suspected in critically ill patients in the
ICU with multiple IV lines, immunocompromised, and who have received multiple
prolonged antimicrobial therapy.  Blood cultures  are seldom positive and the
physician must have a high index of suspicion in  any  patient  that  is  not
improving  or  deteriorating.   In the past IV lines would be removed and the
patient observed  for  improvement.   Today  transient  candidemia is usually
treated in order to avert later involvement of the eye, bone and heart.   The
patient  is  given a short course of amphotericin-B at 20 mg/day for 10 days.
If amphotericin isn't tolerated fluconazole  is  given  for at least 4 weeks.
Some specialists would  consider  Candida  tropicalis  more  viulent  than  C
albicans.   Any  patient that has positive candida blood cultures should have
ophthalmoscopi examination  at  least  every  3  days,  observing for embolic
candidal showers.

                  -GAIT DISTURBANCES IN THE ELDERLY-
There are multiple causes of gait disorders  in the aged.  Some of these will
be  discussed  in  detail.   Neurological  causes  include  chronic  subdural
hematoma, normal pressure hydrocephalus, cerebellar ataxia,  Etat  lacunaire,
peripheral  neuropathy,  Parkinson's disease, progressive supranuclear palsy,
dementia, vitamin  B12  deficiency,  posterior  column degeneration, cervical
spondylotic myelopathy and cervical tumors.   Endocrinologic  causes  include
hypothyroidism.   Orthopedic  causes  include  osteoarthritis, foot problems,
osteomalacia,  and  fractures.   Other  miscellaneous  causes  include drugs,
senile  gait,  muscle  weakness  of  various   etiologies,   and   depressive
conditions.  ETAT LACUNAIRE OR MULTIINFARCT DEMENTIA: This disorder is due to
hypertensive cerebrovascular disease with resulting hypertonia, impaired fine
movements,  postural  defects,  dementia  and impaired facial movements.  The
main differential in this disorder is that of Parkinsons's disease.  Patients
with multiinfarct dementia have a characteristic gait known as marche a petit
pas.  This  gait  is  slow  with  the  patient  walking  in  shuffling, short
irregular  footsteps.   The  patient  may  also  have   pseudobulbar   crying
(emotional  incontinence).  CT and MRI may demonstrate the multiple infarcts.
PERIPHERAL NEUROPATHY:  Peripheral  neuropathy  may  be  caused  by diabetes,
Guillain-Barre syndrome, and neoplasms.  There is usually  motor  disturbance
with weakness in the distal muscles along with sensory symptoms and autonomic
changes.   The patient may have difficulty in climbing stairs, or may stumble
when attempting to walk.   PARKINSON'S  DISEASE:  These patients present with
rigidity, tremor, postural impairment, autonomic  dysfunction  and  akinesia.
Akinesia  is  characterized  by difficulty in starting movement.  In order to
start a movement the patient may  need  a small lateral push.  The patient is
unable to perform movements that require dexterity.  The patient  walks  with
small  steps  and  retropulsion.   CHRONIC  SUBDURAL  HEMATOMA: Patients with
chronic BILATERAL subdural hematoma, with  little displacement of the midline
brain structures, may present with an  apraxic  gait  in  the  early  stages.
These   patients  may  also  have  minimal  drowsiness.   CT  will  diagnose.
CEREBELLAR  ATAXIA:  Cerebellar  ataxia  in   the  elderly  may  result  from
cerebellar  degeneration,  cerebellopontine  angle   tumors   or   cerebellar
infarction.   The  gait is a staggering, unsteady, wide based gait.  Patients
with cerebellopontine angle tumors may  have frequent falls and poor balance.
NORMAL PRESSURE HYDROCEPHALUS:  In  the  classic  triad  of  normal  pressure
hydrocephalus  there  is urinary incontinence, dementia and gait disturbance.
The gait disturbance  may  antedate  the  full  syndrome  by months to years.
These patients have a small-stepped apraxic gait.  They  have  difficulty  in
maintaining  their  posture.   The  disorder  may be idiopathic, but has been
associated with many neurologic  conditions.  PROGRESSIVE SUPRANUCLEAR PALSY:
This disorder also  known  as  the  Steele-Richardson-Olszewski  syndrome  is
associated  with  abnormality of vertical gaze, bradykinesia, axial rigidity,
dysarthria, progressive dementia  and  a  gait  disorder.   There may also be
cerebellar and corticospinal signs.  VITAMIN B12 DEFICIENCY: Symptoms include
anemia, peripheral neuropathy and subacute combined degeneration of the cord.
The gait is unsteady with dragging of the feet.  There may  be  paresthesiae,
sensory  ataxia  and paraplegia.  Diagnosis is made by low vitamin B12 levels
and  a  positive  Schilling  test.   CERVICAL  SPONDYLOTIC  MYELOPATHY: These
patients may present with gait changes, increased muscle tone, spasticity and
incontinence.  There may be increased tendon reflexes in the limbs.  However,
these may modified in the elderly, to the extent  of  areflexia.   A  lateral
x-ray should be done to assess the spinal canal diameter.  If the diameter is
reduced,  CT  with  contrast,  and  myelography  will  be  needed.   CERVICAL
NEOPLASMS: Cervical tumors may simulate cervical spondylosis, and myelography
will  be  necessary  for a definitive diagnosis.  DRUGS: Many patients may be
taking  benzodiazepines.   These  can  cause  gait  problems  associated with
sedation,  agitation,  and  disorientation.   Tricyclic  antidepressants  can
simulate parkinson like  symptoms.   Salicylates  may  accumulate,  producing
tinnitus,  imbalance,  hearing  deficits  and confusion.  Anticonvulsants can
cause ataxia, blurred vison,  and  slurred  speech.   Meclizine is capable of
causing or enhancing imbalance.  ORTHOPEDIC causes include impacted fractures
of the femoral neck which may be mild and unsuspected in the elderly,  hallux
valgus,  gout,  rheumatoid arthritis, and osteoarthritis of the feet, atrophy
of the plantar pad, onychogryphosis, and  and corns.  WORKUP: The gait should
be observed by the physician.  If there is an apraxic gait,  dementia  should
be   suspected.    Bradykinesia  would  raise  the  question  of  progressive
supranuclear palsy, Parkinson's disease or  drugs  as the cause.  If the gait
is  shuffling,  muscle  weakiness,  multiinfarct  dementia,  depression   and
osteoarthritis  should  be  ruled  out.   A  waddling  gait  may  be  seen in
osteomalacia  and  senile  gait.   Patients  with  an  ataxic  gait  may have
peripheral neuropathy, hypothyroidism, pernicious anemia,  or  drugs  as  the
cause.   Patients  that  tend to lean backwards may have Parkinson's disease,
multiinfarct dementia, senile gait, cerebellar lesions or drugs as the cause.
Next, loss of proprioception should be  assessed.  Loss of position sense may
be seen in posterior column degeneration and stroke.  The patient  or  family
should  be  questioned  about  the  use  of  drugs  such  as benzodiazepines,
tricyclic   antidepressants,   butyronphenones,   phenothiazines,  reserpine,
anticonvulsants,  salicylates,  lithium,   antivertigo   drugs,   and   alpha
methyldopa.   The patient's feet should be examined and testing for cognitive
function and depression  should  be  carried  out.   Laboratory workup should
include T3, T4  ,  TSH  (hypothyroidism),  vitamin  B12  levels,  (Pernicious
anemia), calcium, phosphorus, and alkaline phosphatase (osteomalacia).  CT of
the  head  may be done to rule out chronic subdural hematoma, normal pressure
hydrocephalus,  multiinfarct   dementia,   stroke,   and  cerebellar  ataxia.
Myelography may be needed for cervical spondylotic  myelopathy  and  cervical
tumors.    Radiographic  studies  may  be  needed  for  cervical  spondylotic
myelopathy (lateral cervical  spine),  osteomalacia  (ribs,  femoral neck and
scapulae), unsuspected fracture (femoral  neck  x-rays),  and  osteoarthritis
(hips  and  knees).   EMG  and  nerve  conduction  studies  may be needed for
peripheral neuropathy and muscle disorders.

                   -GASTROESOPHAGEAL REFLUX DISEASE-
Gastroesohageal reflux disease (GERD) is a  very common disease that has been
labeled with various names such as heartburn, water brash, dyspepsia,  reflux
esophagitis,  regurgitation,  and  indigestion.   These  names have different
connatations to the lay and professional population.  GERD is a reflection of
the stomach's production of hydrochloric acid.  Acid aids in the digestion of
food, but its absence  does  not  seem  to  interfere with absorption.  It is
important  for  the  partial  sterilization  of  food  and  water   that   is
contaminated  with  bacteria.  The fundus and the body of the stomach secrete
enormous  amounts  of   hydrochloric   acid   with   each  meal.   Histamine,
acetylcholine and gastrin are all important  mediators  of  acid  production.
There  are  several  defense mechanisms that protect against acid production.
These  consist  of  the  lower  esophageal  sphincter,  luminal clearance and
epithelial  resistance.   Generally  speaking,  most   patients   that   have
complications  secondary  to GERD such as erosive esophagitis, strictures and
Barrett's esophagus  will  have  manometrically  incompetent lower esophageal
sphincters (LES).  Some patients with mild to moderate symptoms of GERD  will
have  normal manometric studies of the esophagus.  The normal median pressure
in the LES	has been reported to be 13 mm Hg.  However, the LES pressure does
not remain constant over time.   Gastric  emptying is important in preventing
reflux by removing from the stomach the noxious substances.  It can be stated
that the basic defect in  most  patients  with  GERD,  is  a  defect  in  the
neuromuscular  control  of  the sphincter, permitting frequent, prolonged LES
transient relaxations, rather  than  an  anatomical  abnormality  in the LES.
Luminal  clearance  is  effected  by  the  upright  position  which   permits
gravitational  drainage  of  noxious  refluxed  material  from the esophagus.
Peristaltic activity is also  important  in  propelling the bolus of refluxed
material back  into  the  stomach.   Swallowed  saliva,  with  its  buffering
capacity,  is  also  important  in  raising  the  esophageal  pH.  Epithelial
resistance is effected  by  epithelial  secretion  of bicarbonate.  CLINICAL:
Heartburn is the msot common complaint in about 50% of patients.  If there is
dysphagia, this implies  a complication of GERD such as a peptic stricture or
carcinoma.  If the patient complains of odynophagia, an  infectious  etiology
should  be  ruled  out  such  as herpes simplex or candida esophagitis.  Some
patients have atypical symptoms manifesting  as non cardiac chest pain.  This
chest pain pain can be due  to  diffuse  esophageal  spasm  or  a  nutcracker
esophagus.   Ambulatory  esophageal pH monitoring has shown that about 50% of
patients have chest pain that  correlates with gastroesophageal reflux.  Some
patients with hoarseness and chronic throat clearing may have  symptoms  that
are  related  to  gastroesophageal and gastropharyngeal relux.  Some of these
patients will respond to antacid  drugs.   Asthma  and chronic cough has also
been associated with GEF.  Bronchospasm may occur as a consequence of  reflux
of  gastric  contents  into  the  airways,  or  by  a reflex pathway from the
esophagus through  the  vagus  to  the  brainstem,  and  then efferent reflex
bronchospasm.  Hiccups, can also be due to  GERD.   LOBORATORY:  X-RAYS:  The
barium  esophagram  suffers  in  that  it is usually normal in the setting of
GERD, even if there is distal imflammation.  Even when using double contrast,
the sensitivity is extremely poor  for  detection of Barrett's metaplasia and
esophagitis.  Shallow erosions may also be non visualized.  Deep  ulcerations
in  the  esophagus may be visualized.  Most strictures and hiatal hernias can
be visualized.  Peptic ucler disease  distal to the esophagus, paraesophageal
hernias and  diverticuli  can  all  be  visualized.   ESOPHAGOSCOPY  is  very
sensitive  for  esophagitis  (peptic,  herpes  simplex,  candida)  and can be
confirmed with biopsy.  Although it  is  safe,  it is invasive and expensive.
AMBULATORY pH MONITORING: This is accomplished by placing a catheter  with  a
pH  probe  through  the  nose into the distal esophagus about 3-5 centimeters
proximal to the  LES.   The  pH  of  the  distal  esophagus  is recorded four
times/second for 24 hours.  The patients keep a diary of their  symptoms  and
its duration.  COMPLICATIONS: STRICTURES: Some patients heal their esophageal
ulceration  with  excessive  fibrous  tissue leading to solid food dysphagia.
Treatment is with omeprazole and dilation of the stricture.  Patients usually
need long term  prophylaxis  because  relpases  are  common.  ULCERATIONS AND
EROSIONS: These usually present with daily complaints of a burning substernal
or epigastric pain that occurs within a few hours after eating a meal.   Deep
esophageal  ulcerations  are  less common than erosions, but can present with
continuous epigastric pain not  unlike  that  of  peptic ulcer disease of the
stomach  or  duodenum.   Some  patients  with  esophageal  ulcers  will  have
odynophagia.  Should the patient have a deep ulceration in the mid esophagus,
Barrett's  metaplasia  should  be  ruled  out  with  biopsy   to   rule   out
adenocarcinoma.   Some  will  report  symptoms  that occur when lying down or
bending over.  Patients with  ulcerations  and  erosions  usually do not have
frank bleeding or iron  deficiency.   BARRETT  ESOPHAGUS:  Barrett  esophagus
occurs  as a consequence of long standing acid reflux permitting the squamous
mucosal lining of  the  distal  esophagus  to  undergo  a transformation into
columnar mucosa that resembles the mucosa in the stomach or small  intestine.
It  can  be  diagnosed  by  endoscopic  exam by observing displacement of the
squamo-columnar junction  more  than  2  cm  proximal  to the esophagogastric
junction.  It has been stated that patients with Barrett's esophagus who have
a life expectancy of 20  years,  has  a  life  time  risk  of  about  10%  of
developing adenocarcinoma.  TREATMENT: Patients are instructed to not eat any
food  within  2  hours  of  retiring  in  order  to  minimize  nocturnal acid
secretion.  Elevation of the head of the  bed by 6 inches has been advocated,
but often times is impractical.  Antacids may be helpful  in  some  patients.
Gaviscon  has  been  shown  to  relieve  symptoms,  reduce  the  duration and
frequency of GER, but does  not  contribute  to the healing of the esophagus.
Standard doses of H2 receptor antagonists have poor rates of complete healing
of esophagitis.  PROTON PUMP INHIBITORS: Omeprazole is a  powerful  inhibitor
of  the hydrogen-potassium ATP'ase located in the canalicular membrane of the
parietal cells.  H2 receptor antagonist  given  in standard doses will reduce
acid output by about 60-70%, but omeprazole given in standard doses of 20  mg
daily  will  reduce  acid  output  by  95%.   It is only available as an oral
preparation.  It has  an  enteric  coated  capsule,  because it is completely
inactivated by acid.  The serum half life is short, but  the  pharamcological
half  life  is  about 36 hours.  The short term safety of omeprazole has been
found to be safe, but the long term therapy has been shrouded in controversy.
The degree of  acid  suppression  with  omeprazole  has  been associated with
moderate to  high  hypergastrinemia,  which  in  rats  can  cause  occasional
carcinoid.    Although   omeprazole   is   capable  of  complete  healing  of
esophagitis, the relapse rate is high.   Eighty percent will relapse within 6
months after complete healing, and maintenance  with  standard  doses  of  H2
receptor  angagonists  do  not  prevent  these  relapses.  Only omeprazole is
effective in  preventing  relapase.   This  presents  a  problem  since it is
recommended that omeprazole be used only for short term  care.   Standard  or
high dose H2 blockers should be used, but there is a high rate of relapse.

              -GASTROINTESTINAL BLEEDING (Acute upper)-
The mortality for acute upper gastrointestinal bleeding is about 8-10% and in
part is due to underlying diseases  of  the liver, kidney, CNS, pulmonary and
neoplastic disease.  CLINICAL:  The  most  common  presentation  is  that  of
hematemesis  and  melena.   Hematemesis  is  suggestive  of  bleeding that is
proximal to the ligament of  Treitz.   Hematemesis may be either frank bright
red blood or "coffee ground".  Bright red blood infers that  the  hematemesis
occurred  immediately  after bleeding, whereas coffee ground emesis is due to
blood that has interacted  with  hydrochloric  acid.   Patients may also have
melena (black, tarry, foul smelling stools).  Melena must  be  differentiated
from those patients that are taking iron, licorice or bismuth.  Melena is due
to  degradation  of  the hemoglobin in the GI tract by bacteria to hematin or
other hematochromes.  Melena can takes several  days to clear after there has
been cessation of the upper GI bleeding.  Approximately 50-100 ml of blood is
needed in  order  to  produce  melena.   PHYSICAL:  Physical  examination  is
important, for it can provide a clue as to the etiology of the bleeding.  For
example,  if  the  patient  has  spider  angiomas,  splenomegaly,  asterixis,
ascites,  testicular  atropy,  jaundice  and  gynecomastia, the possiblity of
esophageal varices or  alcoholic  gastritis  arises.  Abdominal tenderness in
the epigastric area is suggestive of peptic ulcer disease.  Hyperactive bowel
sounds may indicate  that  the  bleeding  is  in  the  upper  GI  tract.   If
hyperpigmented   macules  are  seen  on  the  lips  this  would  suggest  the
Peutz-Jeghers syndrome.  Soft tissue masses  may be associated with Gardner's
syndrome.  Lymphadenopahty, abdominal masses  and  Kaposi's  sarcoma  lesions
would  be  suggestive  of  a  malignant  process  as  the etiology.  Perioral
telangiectasias would  point  toward  hereditary  hemorrhagic telangiectasia,
whereas blue subcutaneous nodules can be assoicated  with  blue  rubber  bleb
nevus syndrome.  History is also important in providing clues as to the cause
of  the  bleeding.   Inquire  as  to the use of NSAIDs, and if the patient is
being treated for peptic ulcer disease.   If the patient had violent coughing
or wretching prior to the GI bleeding, Mallory-Weiss syndrome would be in the
differential diagnosis.  Mallory-Weiss tears are lacerations  that  occur  in
the  gastric cardia or the gastroesophageal junction.  They are usually about
1-2  cm  in  length.   They  typically  occur  with  persistent  vomiting  or
wretching, but have been seen  following heavy lifting, hiccups, straining at
the stool, trauma, asthma,  cardiopulmonary  resuscitation,  childbirth,  and
endoscopy.   In  about  50% of cases no etiology can be found.  Mallory-Weiss
tears account for about 15% of all upper GI bleeding.  Mallory-Weiss bleeding
usually stops spontaneously in greater  than  90% of cases.  If bleeding does
not stop, epinephrine injection and thermal therapy  may  be  effective.   In
patients   who   fail   endoscopic   therapy,  angiographic  embolization  or
intra-arterial vasopressin can be  used,  which  is  effective in 70%.  Also,
inquire about the patient's alcohol use and if there has been  liver  disease
in  the  past,  as  this  would  indicate  that  the bleeding originated from
esophageal variceal bleeding.   A  history  of  previous aortic graft surgery
indicates the possiblity of an aortoenteric fistula.   Aortoenteric  fistulas
are  rare, with most of these occurring in the third portion of the duodenum.
Most of the patients have had Dacron graft surgery.  The fistula may occur at
the suture line  or  into  the  graft.   There  may  be associated sepsis and
positive blood cultures.  The first bleed from  an  aortoenteric  fistula  is
known as the herald bleed, usually is brief, and usually stops spontaneously.
However,  this  is  deceiving, as the bleeding resumes in a few hours or days
and can be massive.  CT  scanning  can  show  air  bubbles in the wall of the
aorta, or evidence of perigraft infection.  Angiography may  not  demonstrate
the  fistula unless there is active bleeding.  Upper endoscopy should be done
in all patients that have had an aortic graft placed and GI bleeding, to rule
out other potential causes for  the bleeding.  LABORATORY: Serial CBCs should
be done.  The initial Hct may be deceiving because  it  does  not  accurately
reflect  the  degree  of blood loss.  However, as the intravascular volume is
restored, the hematocrit will drop.  This  may  take up to 3 days.  Platelets
should be assessed as thrombocytopenia may be due to portal hypertension.  If
patients  are  actively  bleeding,  and  the  platelet  count  is  less  than
70,000/ul, platelet  transfusions  should  be  given.   Prolongation  of  the
prothrombin  time  is  compatible  with  liver  disease  and  is treated with
subcutaneous vitamin K and  fresh  frozen  plasma  if the patient is actively
bleeding.  Elevated BUNs are commonly found in  upper  GI  bleeding,  due  to
absorption  of  blood  proteins and intravascualr volume depletion.  Patients
needing  multiple  blood  transfusions   should  have  frequent  calcium  and
potassium determinations.  DIFFERENTIAL DIAGNOSIS: Most  cases  of  upper  GI
bleeding  are  due  to peptic ulcer disease, with duodenal ulcers more common
than  gastric  ulcers.   The  remaining  causes  consist  mostly  of varices,
Mallory-Weiss lacerations and gastric erosions.  TREATMENT: The first step in
treament is a rapid assessment of the urgency of the bleed.  A  patient  that
presents  with  a  BP  of 95-100 systolic, and tachycardia	suggests that the
patient has lost 50% of blood  volume.   If  the patient is not in shock, BPs
should be checked in the supine  and  upright  postions.   A  systolic  blood
pressure  that  drops  to  less  than 90 mm Hg on standing suggests a loss of
25-40% of the blood volume.  If there  is  a  decrease of 10 mm Hg or more in
the systolic blood pressure, or an increase in heart rate above 120,  a  loss
of  20%  of the blood volume is probable.  Patients that have active bleeding
should be immediately  treated  with  IV  normal  saline or Ringer's solution
administered through two large bore 14  to  18  gauge  peripheral  catheters.
Blood  should  be  obtained for immediate type and cross match, CBC, platelet
count, PT, PTT and chemistries.  ECGs should be done in patients over the age
of 40, those  with  chest  pain,  or  a  history  of coronary artery disease.
Oxygen should be given if large  amounts  of  blood  have  been  lost.   Some
patients   will   need   endotracheal   intubation   to  prevent  aspiration,
particularly those with esophageal  variceal  bleeding.  In some emergenices,
non-crossed matched  O  negative  blood  may  be  necessary.   Patients  with
questionable  bleeding sites will need a nasogastric tube inserted.  A return
of bright red blood indicates active, recent upper GI bleeding.  However, the
absence of a bloody  return  does  not  rule  out  upper GI bleeding, for the
bleeding may be coming from the duodenum, or  the  nasogastric  tube  may  be
curled  in the fundus of the stomach.  Likwise, bile stained aspirates do not
rule out an upper source.  Following the assessment, the nasogastric tube can
be  removed.   GASTRIC  LAVAGE:  In  the  past,  iced  saline  has  been used
extensively.   Recently,  however,  the  effectiveness  of  this   has   been
questioned,   and  studies  have  shown  increases  in  bleeding  times,  and
prothrombin times.  Therefore, iced saline  is probably of no proven benefit,
and,in fact, may be detrimental.  Likewise, the addition  of  epinephrine  to
the  lavage fluid, is of no benefit.  ACID REDUCERS: There has been no single
trial that  has  shown  consistent,  overall  benefit  of  H2 antagnosists in
stopping acute GI bleeding.  Omeprazole, which is a  proton  pump  inhibitor,
has  been  shown  in  some  reports to be successful in stopping GI bleeding.
Other reports have  shown  no  significant  diffferences  between palcebo and
omeprazole in terms of rebleeding, transfusion requirements,  morbidity,  and
the  need  for  surgery.   Tranexamic  acid  has  also  been used in upper GI
blededing with inconsistent data.   Furthermore,  the side effects associated
with the use of tranexamic acid,  has  limited  its  use.   Somatostatin  and
octreotide  (its  analogue)  have  no  proven  benefit  in  active  upper  GI
non-variceal  bleeding.   The  benefits of sulcrafate is also questionable at
the present  time.   Vasopressin  has  not  shown  any  particular benefit in
stopping acute non-variceal upper GI bleeding.  ENDOSCOPIC THERAPY: There are
2 types of endoscopic therapy; the thermal  method,  such  as  heater  probe,
electrocoagulation,  laser  therapy, AND the injection therapy.  Studies have
found that thermal methods  and  injection  therapy  can  reduce the need for
emergency surgery by 60-80%, and  reduce  recurrent  bleeding  when  used  in
patients  with active hemorrhage or visible vessels seen at endoscopy.  Laser
therapy is not used much because  of  its high cost, lack of portability, and
associated technical problems.  Monopolar electrocoagulation  has  been  used
for  coagulation  of  blood vessesl, but there is the potential for sparking,
deep tissue destruction and perforation.  The use of multipolar coagulation ,
however, results in more controlled tissue destruction.  The degree of tissue
destruction is determined by the amount of pressure that is placed on the the
tissue by  the  multipolar  probe.   The  heater  probe,  like the multipolar
coagulation system, controls the amount of destruction by the amount of probe
pressure applied to the tissue.  Endoscopic  injection  therapy  can  achieve
hemostasis  by  using  98%  alcohol,  epinephrine,  sclerosants  and  saline.
Epinephrine  functions by constricting the blood vessels, and producing edema
in the surrounding tissues.   Sclerosants  and 98% alcohol cause inflammation
in the blood vessels with shrinkage of the surrounding tissues which leads to
vessel  thrombosis.   Most  GI   specialists   would   recommend   multipolar
electrocoagulation,  heater  probe  or injection therapy because of their low
cost, efficacy, safety and ease of  use.  Most series show a perforation rate
of less than 1%.  SURGERY AND  ANGIOGRAPHY:  Patients  that  fail  endoscopic
hemostasis  will  need  surgery.   Patients  that are not good candidates for
surgery  and  fail  endoscopic  therapy  can  be  treated  with  angiographic
embolization or intra-arterial vasopressin.

                       -GENITAL DISEASE (Male)-
TORSION  OF  THE  TESTIS  AND SPERMATIC CORD: The incidence peaks between the
ages of 10-16 with the highest frequency  at puberty or age 13.  The onset is
often during the night or vigorous activity and trauma.  Pain is  unremitting
and  very  severe.   Changing  postition  or  elevating  the scrotum does not
relieve the pain as with epididymitis.   There is usually edema and erythema.
The affected testes may be higher in the scrotum  since  there  is  twisting.
The  opposite testicle may be in a horizontal position rather than the normal
vertical position.  The cremasteric  reflex  is  absent on the affected side.
Surgical exploration is the diagnostic choice.  Surgery should be done before
4-6 hours.  For manual detorsion of a  patients  left  testicle  twist  in  a
clockwise   fashion.    For   the   patients   right   testicle  twist  in  a
counterclockwise fashion.  Successful  detorsion  brings about immediate pain
relief.  The patient will  still  need  bilateral  fixation  for  recurrence.
EPIDIDYMITIS:  If  under  the  age  of  35  the usual organisms are Chlamydia
trachomatis, Ureaplasma urealyticum or  Neisseria gonorrhoeae.  Gram neg rods
are usually the cause in age > 40 or instrumentation.  Must look for urethral
stricture, outlet obstruction, or a prostate problem.  A chemical  cause  may
be  secondary  to  straining to lift a heavy object or any Valsalva maneuver.
Infectious causes almost  always  are  associated  with  pyuria.  Usually the
infection starts high in the vas producing pain in the LRQ or LLQ, simulating
appendicitis,  and  diverticulitis.   Doxycycline  is  a   good   choice   of
antibiotic.   The  patient needs absolute bed rest until pain free along with
elevation and ice and Motrin.   Once  pain  free  use scrotal support for 2-3
weeks.  A strenous job can lead to recurrence.  If swelling does not  resolve
in  3-4 weeks then ultrasound should be done to rule out tumor.  STRANGULATED
HERNIA: The parents  usually  bring  in  as  child  who  is  fussy and may be
vomiting.  There is a scrotal mass and there may be  bowel  sounds  over  the
mass.   FOURNIERS  GANGRENE:  Gram  + cocci and gram - rods and anaerobes are
common  and  the  infection  is  often  mixed.   Trauma  and  periurethral or
perirectal abscesses are the usual  inciting  factors,  which  occur  in  the
immunocompromised as diabetics, alcoholics or chronic steroid therapy.  There
is necrotic or gangrenous areas and crepitance.  Treatment is debridement and
IV   therapy   with   clindamycin   or   metronidazole,   penicillin  and  an
aminoglycoside.  TESTICULAR CANCER: Between  10-15% of cancers are associated
with hemorrhage and can cause an acutely painful swelling of the scrotum  and
bilateral  testicular  lymphomas  are  not uncommon in AIDS patients who have
testicular  cancer.   In  10%,  cancer  is  associated  with  gynecomastia or
hydrocele.  So hydrocele without trauma or infectious  cause  is  suspicious.
Also the patient may present with metastatic symptoms rather than the patient
telling  you  about  the  testes  mass.   Anyone who has an abdominal mass or
chronic cough refractory  to  antibiotics  should  have  the testes examined.
Perform an alpha-fetoprotein and beta subunit human  chorionic  gonadotropin,
scrotal  ultrasound  and  chest  x-ray  looking for metastases, and CT of the
abdomen looking  for  retroperitoneal  enlarged  lymph  nodes.  BALANITIS AND
BALANOPOSTHITIS: Diabetes  may  present  with  balanitis.   Most  cases  will
respond   with  topical  antifungal  creams  alone  or  in  combination  with
cephalexin if infection is mixed.   PARAPHIMOSIS: is an emergent situation if
unable to put back the foreskin over the glands,  since  this  will  compress
venous  drainage.   You  may  be  able  to  evacuate  enough  edema  fluid by
compression.  Squeeze the glans and foreskin  for a few minutes and then with
your 2 thumbs at the urethral meatus push the glans back  while  pulling  the
foreskin  forward with your index and long finger.  This may not be effective
and you may need to cut the constricting band after local infiltration before
you can reduce the glans.  Follow with a dorsal slit.  PEYRONIES DISEASE: Can
arise  from  self  injection  for  impotence.   Vitamin  E  may  help  and in
particular help the pain associated with the dorsal curvature  of  the  penis
and  painful  erections.   PRIAPISM:  The  most common causes are sickle cell
anemia and phenothiazine therapy, but  high spinal cord lesions, leukemia and
self injection of papaverine  and  phentolamine  are  possibilities.   Unless
detumescence  occurs fairly promptly fibrosis may develop and cause permanent
impotence.  All patients  should  receive  subcutaneous terbutaline 0.25-5 mg
repeated every 4-6 hours.  Priapism secondary to sickle cell  anemia  usually
responds  to  transfusions  of packed RBCs while drug associated erection may
benefit from injection of phenylephrine into the cavernosa.  When there is no
correctible cause try ice  water  enemas.   If  that fails, irrigation of the
corpora with large bore needles and subsequent shunt surgery may help.

                 -GENTAMICIN AND TOBRAMYCIN DOSING-
Give  a  loading  dose  over  a  one  hour period of 1.75-2 mg/kg (ideal body
weight).  The peak level is determined at  the  end of a 1 hr infusion and is
6-8 mg/L or in pneumonia or Pseudomonas  infection  8-12  mg/L.   The  trough
level  is  done  just  before  the  next  infusion and is .5-2 mg/L.  For the
maintenance  dose,  first  calculate  the  creatinine  clearance=(145-age)  x
kg(IBW)/(70 x plasma creatinine) x .84 (for female).  Once this is calculated
give the following %  of  the  loading  dose  q8h depending on the creatinine
clearance: 90=84%, 80=80%, 70=76%, 60=71%, 50=65%, 40=57%.   30=48%,  25=43%,
20=37%, 17=33%, 15=31%, 12=27%, 10=24%,7=19%, 5=16%, 2=11%, 0=8%.
 
                            -GIARDIASIS-
TREATMENT:   QUINACRINE   (Atabrine):   Quinacrine  comes  in  100  mg  tabs.
Quinacrine  is  contraindicated   in   pregnancy.   Precautions:  history  of
psychosis, elderly,  psoriasis,  porphyria,  hepatic  dysfunction,  and  G6PD
deficiency.  Monitor vision and blood.  Interactions: avoid Primaquine.  Side
effects:  Toxic	psychosis,  seizures,  headache,  dizziness, GI upset, rash,
yellow skin or urine discoloration.  Adults:  100  mg tid after meals for 5-7
days.  Children: 2 mg/kg tid after meals for 5-7 days to a maximum of 300  mg
a  day.   METRONIDAZOLE  Metronidazole (Flagyl) comes in 250 and 500 mg tabs.
Contraindications: Lactation.   Precautions:  CNS  disease.   (Discontinue if
neurologic  disorders  occur)  ,severe  hepatic  disease,  history  of  blood
dyscrasias and Candidiasis.  Monitor leukocytes  before  and  after  therapy.
Pregnancy (cat B).  Interactions: Avoid	alcohol during and up to 24 hrs after
use.   May  potentiate oral anticoagulants, Dilantin and toxic psychosis with
disulfiram.   Side  effects:  Seizures,  peripheral  neuropathy,  leukopenia,
nausea, headache, anorexia,  diarrhea,  cramps, constipation, metallic taste,
rash, dysuria.  Adults: 250 mg tid for 5-7 days.  Children: 5 mg/kg  tid  for
5-7  days.   FURAZOLIDONE  Furazolidone  (Furoxone)  comes in 100 mg tabs and
Furoxone liquid 50 mg/15 ml susp.  Contraindications: Concomitant alcohol (or
within 4  days),  MAOs,  sympathomimetics  or  tyramine  containing foods (or
within  14  days).   Lactation.   Precautions:  G6PD   deficiency,	Pregnancy.
Interactions:  Disulfiram  reaction  with  alcohol.  Potentiates other MAOIs,
hypoglycemics.  Potential hypertensive crisis with sympathomimetics, tyramine
containing  foods  or  levodopa.   Side  effects:  Hypoglycemia,  orthostatic
hypotension,  hypertensive   crisis,   nausea,   emesis,  headache,  malaise,
urticaria, fever,  arthralgia,  rash,  brown  urine,  and  hemolytic  anemia.
Adults:  100  mg  qid for 7-10 days.  Children: 1.25 mg/kg qid for 7-10 days.
All persons harboring Giardia  should  be  treated even if asymptomatic.  The
treatment of choice for both symptomatic and asymptomatic is quinacrine.  The
drug has a 90-95 % cure rate without relapse.  Metronidazole is  also  highly
effective.  Furazolidone has a cure rate of about 80%.  Family members should
be examined as well as sexual contacts and treated.  The incubation period of
giardiasis  is usually 10-17 days, thus some patients may have been home some
time before symptoms occur.  In  contrast,  the viral and bacterial diarrheas
generally have an incubation of 12-48 hrs.  Giardia trophozoites  infect  the
duodenum,  jejunum, and upper ileum.  Encystation occurs in the gut lumen and
cysts passed in the  feces  remain  viable  for  long periods of time.  After
cysts are ingested by the  next  host,  excystation  to  active  trophozoites
occurs  in  the  proximal  small  bowel, completing the life cycle.  A single
diarrheic stool may contain billions of  parasites or hundreds of millions of
cysts.  The mode of transmission is contamination of water supplies with cyst
infested feces from humans or animals; particularly beavers or muskrats,  but
also dogs, racoons, and others.  Campers and backpackers get the disease from
drinking  pristine mountain stream water.  Only rarely does food transmit the
disease.  Giardiasis may be spread by  sexual or other close person to person
contact where fecal contamination may occur such  as  day  care  centers  and
institutions  for  the  mentally  retarded.   Homosexual  males  have  15-25%
infection,  and in day care centers the prevalence has been 25-30%.  CLINICAL
MANIFESTATIONS: Abdominal discomfort  and  persistent watery diarrhea occurs.
Often  the  patients  have  anorexia,  nausea,  vomiting,  foul  eructations,
headache, and malaise.  Occasionally there are chills and  low  grade  fever.
The acute stage usually lasts 3-4 days.  Untreated, the infection can develop
into  a  subacute  or  chronic  infection with waxing and waning of symptoms.
Some proceed  to  malabsorption  syndrome  with  steatorrhea, particularly in
children.   There  is  a  significant  association  between  giardiasis   and
dysgammaglobulinemias with immunodeficiency of both IgA and IgM with variable
levels of IgG.  Eosinophilia doesn't occur.  If 3 or more stool specimens are
examined  Giardiasis will be found in more than 95% of acute cases.  However,
finding giardiasis in subacute or chronic cases is more difficult.

         -GLOMERULONEPHRITIS (Focal glomerular sclerosis)-
CLINICAL: If a  renal  biopsy  is  not  done  in  children with the nephrotic
syndrome the diagnosis may be missed.  Focal glomerular sclerosis FGS)  is  a
cause  of  the  nephrotic  syndrome in 10-20% of children.  There are several
features that point to focal  glomerular sclerosis rather than minimal change
glomerulonephritis.  FGS responds poorly if at all to steroids.  In FGS there
is usually microhematuria and occasionally gross hematuria which is  rare  in
nil  disease.   About  30-50%  will have hematuria and hypertension.  In most
patients with FGS  there  is  associated  hypertension  and evidence of renal
insufficiency.  Both diseases present as heavy proteinuria  and  edema.   The
course  of  FGS  is  usually one of progressive deterioration with continuous
proteinuria to end stage  kidney  disease.   About  50% of patients that have
nephrotic-range proteinuria will be terminal at 10 years with end stage renal
failure.  A subset of patients (20%) with FGS will have  a  malignant  course
with renal failure occurring in 2-5 years.  Spontaneous remissions, mainly in
children,  does  occur.   The  etiology  of FGS is not known, but it has been
associated with heroin use,  AIDS,  and chronic vesicoureteral reflux.  Focal
glomerulosclerosis will recur in 30-40% of renal allografts  within  about  3
weeks to 1 year post-transplantation.  LABORATORY: Light microscopy will show
sclerosis  in  some  areas  (segmental)  of some glomeruli (focal).  Sampling
errors on biopsy may occur due  to  the occurrence of sclerosis in the deeper
juxtamedullary glomeruli.  Immunofluorescence will show IgM and C3  deposited
in  the sclerotic areas in a granular manner.  However, serum IgG, IgM and C3
are all normal.  Electron  microscopy  shows  diffuse foot process fusion and
electron dense amorphous material usually in the  subendothelial  areas  that
are  adjacent  to sclerotic areas.  There may be glycosuria, phosphaturia and
aminoaciduria.   Creatinine  is  elevated.   Proteinuria  in  FGS  is usually
greater than 15 grams/24  hours.   TREATMENT:  Most  of  these  patients  are
steroid  resistant.   However,  in about 20-40% of cases there may be compete
remission with the same dose of steroids that is used in minimal disease.  If
there is  a  good  initial  response  rate,  this  usually  indicates  a good
prognosis.  As in minimal disease there may be relapses that also may respond
to  additional  steroid  therapy.   If,  however,  there  is   no   response,
cycloposphamide  may  be  used  as  in  minimal disease.  Cyclosporine may be
beneficial in some cases but is considered experimental.
 
                     -GLOMERULONEPHRITIS (IGA)-
CLINICAL:  IgA  glomerulonephritis  (Berger's  disease)  is  characterized by
recurrent episodes  of  microscopic  and  macroscopic  hematuria  that may be
persistant or recurrent.  There is usually mild proteinuria that  is  not  in
the  nephrotic  range.  The disease may occur at all ages, but is most common
in children and young adults.  There is an increased incidence in males (6:1)
and  is  rare  in  Blacks.   The  prevalence,  as  compared  with  all  other
glomerulonephritides, is 5%  in  the  USA,  10-20%  in Australia and southern
Europe, and 30-40% in  Asia.   The  disease  is  characterized  by  mesangial
deposits  of  IgA or IgG.  Renal function is normal initially with normal GFR
and normal tubular function.  The  clinical  course and prognosis is variable
with a 20 year survival rate of about 50%.  Only a few patients will progress
to renal failure.  These few that do progress usually acquire the disease  at
an  older  age,  have  heavy  proteinuria, hypertension and have crescents or
segmental sclerosis  on  renal  biopsy.   At  one  time  Berger's disease was
thought to be benign, but now it is known that  up  to  20%  will  eventually
develop  renal  failure  in 10-15 years.  IgA mesangial deposits can occur in
transplanted kidneys also.  About 90%  of involved children will present with
recurring macroscopic hematuria and the remainder as asymptomatic microscopic
hematuria associated with mild proteinuria.  The disease usually  starts  1-2
days  after  an  upper respiratory, sinus or gastrointestinal illness.  Flank
pain may be associated with  the hematuria.  LABORATORY: Approximately 50% of
patients will demonstrate prominent mesangial  IgA  and  C3  deposits  in  an
expanded  mesangium  with  segmental  or  focal  proliferative or necrotizing
lesions.  Mesangial IgA deposits can  also occur in Henoch-Schonlein prupura,
lupus nephritis, and chronic alcoholic  hepatic  cirrhosis.   Proteinuria  is
usually  modest  at  less  than  1  gm/day,  but  between 10-20% will develop
nephrotic syndrome.  Serum complement levels are normal.  TREATMENT: There is
no treatment for IgA  nephropathy.  Corticosteroids and immunosuppressives do
no alter the course of the disease.

                  -GLOMERULONEPHRITIS (MEMBRANOUS)-
CLINICAL: Membranous  glomerulonephritis  (MG)  is  a  disease  of adults and
characteristically presents as the nephrotic  syndrome.   Most  patient  with
membranous  nephropathy are over 35 years of age with a peak incidence in the
fifth decade.  MG may be idiopathic  or associated with systemic diseases and
drugs.  The idiopathic variety accounts for about 30-50% of cases  in  adults
but  less  than 1% in children.  Infectious secondary causes include malaria,
syphilis, chronic hepatitis  B,  filariasis,  and schistosomiasis.  Rheumatic
causes include  Mixed  conective  tissue  disease,  Sjogren's  syndrome,  and
systemic lupus erythematosus.  Neoplastic etiologies include carcinoma of the
stomach,  colon,  lung, kidney, breast, non-Hodgkins's lymphoma, leukemia and
Wilms'tumor.  Drug associated  causes  include primidone, mercury, captopril,
gold and  D-penicillamine.   MG  progresses  at  a  slower  rate  than  focal
sclerosis.  At 10 years about 30-50% of patients will have terminal end stage
kidney  disease, but if followed for a longer period, about 70% will progress
to end stage kidney disease.   Spontaneous  remission can occur in about 30%.
This may be a partial or  complete  remission.   The  disease  may  first  be
detected  as  an  asymtomatic  proteinuria, but about 80% will present with a
massive proteinuria causing  the  nephrotic  syndrome.   Proteinuria of 15-20
grams/day is common.  The protein is  usually  nonselective.   There  may  be
microscopic  hematuria.   When first diagnosed the glomerular filtration rate
is usually normal and may stay normal for the first 4-5 years of the disease.
The fall in Glomerular  filtration  rate  is  gradual  over the years, but is
usually progressive.  If there is sudden diminution of  GFR,  consider  renal
vein  thrombosis or drug induced interstitial nephritis.  The course of MG is
variable with  about  20-30%  of  patients  having  a  long  term spontaneous
remission.   Another  20-30%  will  have  different  degrees  of   persistent
proteinuria  without  uremia.   The rest of the patients will progress to end
stage renal disease,  usually  over  a  5  year  period.  Complications of MG
include  a  hypercoagulable  state  with  renal  vein  thrombosis,  pulmonary
embolism  and  arterial  thrombosis.   Renal  blood  flow  may  develop  with
injudicious use of diuretics.   LABORATORY:  The  classic  finding  on  light
microscopy   is   uniform   basement  membrane  thickening  without  cellular
proliferation and infiltration.  Silver  stains  are  used to demonstrate the
spikes that are seen on the basement membrane.   Four  stages  of  membranous
glomerulonephritis  are recognized pathologically: Stage I will give a normal
appearance by light microscopy and subepithelial electron dense deposits with
electron microscopy.  Stage  II  will  demonstrate  spike  projections of the
basement  membrane  by  light  microscopy  and  variable  basement   membrane
thickening.   Stage  III  shows a thick glomerular basement membrane with the
spikes encircling immune deposits  producing  a  moth eaten appearance of the
GBM.  Stage IV shows segmental or global glomerulosclerosis and thickening of
the capillary wall.  There may also be tubulointerstitial fibrosis.  IgG  and
C3  deposits  are  seen  on  immunofluorescent  microscopy.   Serum C3 and C4
complement are  normal.   THERAPY:  The  best  treatment  has been prednisone
alternating with chlorambucil.  Pulse  methylprednisolone  1  gram  is  given
daily  for  3  days  followed  by oral prednisone at .5 mg/kg/day for about 1
month.  This is then  followed  by  oral chlorambucil (Leukeran) .2 mg/kg/day
for one month.  This alternating monthly regime is carried out for  6  months
or a total of three 2-month cycles.  Using this approach there has been about
20% significant side effects.

            -GLOMERULONEPHRITIS (Membranoproliferative)-
CLINICAL:  Membranoproliferative  glomerulonephritis   is   also   known   as
mesangiocapillary       glomerulonephritis,       or       hypocomplementemic
glomerulonephritis.    Membranoproliferative   glomerulonephritis  (MPG)  may
present as an  acute  glomerulonephritis,  nephrotic syndrome or asymptomatic
hematuria and proteinuria.  Suspect this disease if the serum C3 is low.  MPG
accounts for about 41% of cases of idiopathic nephrotic syndrome in  children
and 30% of cases in adults.  There is an equal distribution between males and
females.   MPG  may  be  idiopathic  or be secondary to SLE, mixed connective
tissue disease, cryoblobulinemia, bacterial  endocarditis, hepatitis B, shunt
nephritis,  visceral  sepsis,  syphilis,  malaria,   sickle   cell   disease,
hereditary  C2  deficiency  and carcinomas.  An acute nephritic syndrome with
hypertension, hematuria and azotemia is  seen  in  about 33%.  Up to 50% will
present as a nephrotic syndrome and have significant, persistent  proteinuria
through the entire course of their illness.  Another 33% will present as only
hematuria  or  proteinuria  found  in  an  otherwise asymptomatic individual.
About 50% of patients will  have  terminal  renal failure after 10 years with
the rate of progression greatest in Type II MPG.  Type II is usually seen  in
children.  Type II will invariably recur in transplanted kidneys  LABORATORY:
There  are  3  pathologic types in MPG as follows: Type I is characterized by
subendothelial  and  mesangial   deposits,   an  intact  glomerular  basement
membrane, mesangial prominence and immunofluorescent positivity for IgG, C1q,
C4, and C2 and properdin.  Type II is characterized  by  intramembranous  and
subeptihelial   deposits  in  50%  of  cases,  mesangial  deposits,  moderate
mesangial prominence with  interpostion  and  immunofluorescence for IgG, C3,
and properdin.  Type II is also known as the dense deposit disease.  Type III
is characterized  by  a  combination  of  the  features  seen  in  membranous
glomerulonephritis and membranoproliferative Type I glomerulonephritis.  Type
I and III may be associated with low or normal C3 complement.  In type II the
C3 level may be extremely low and may be undetectable.  If the C3 is found to
be  low,  MPG  must  be  differentiated  from  lupus nephritis by an ANA, and
differentiated  from  post-streptococcal   glomerulonephritis   by  an  ASOT.
THERAPY:  There is  no  definitive  therapy.   Steroids,  alkylating  agents,
anticoagulants  and  antiplatelet  agents  have  all  been tried without good
success.

               -GLOMERULONEPHRITIS (MINIMAL CHANGE)-
CLINICAL: Minimal change  glomerulonephritis  (MCG)  is  a  nephropathy  that
occurs  mainly in children aged 2-6 years, but it may constitute up to 25% of
adult cases of nephrotic syndrome.  It  has a male predominance of about 3:1,
and is the most common cause of nephrotic syndrome in children.  It  also  is
known  as mil disease, light negative glomerulonephritis or lipoid nephrosis.
The cause is unknown but  rarely  may  develop in Hodgkin's disease and other
lymphomas.   Fenoprofen,  ibuprofen,  naproxen,   tolmetin,   sulindac,   and
indomethacin  have  also  been  known  to  cause a similar syndrome.  Several
factors  as  the  following  point  to  an  immunologic  cause.   It  is very
responsive to steroids; it is associated with Hodgkin's disease; there is  an
increased  prevalence  of  HLA-B12,  and  it  is  frequently  seen  in atopic
individuals.  Almost 75% of cases  present  with  edema and about 33% develop
after an upper respiratory infection.  Hypertension, azotemia  and  hematuria
are  uncommon  in minimal glomerulonephritis.  Hypertenskion occurs in 10% of
children and 35% of adults.  Atotemia occurs  in about 23% of children and in
34% of adults.  Some patients have  an  atopic  history  with  urticaria  and
asthma.   Most  patient  have  a  benign  clinical  course  with  spontaneous
remission  and  relapses being common.  There is an increased susceptibilithy
to infection with Pneumococcus, Klebsiella and Hemophilus, if the proteinuria
is profound.  There also  may  be  thrombosis  of  renal and peripheral veins
secondary to  a  hypercoagulable  state.   LABORATORY:  Typically,  there  is
proteinuria  over  50  mg/kg/day  associated with a serum cholesterol greater
than 300  mg/dl,  and  an  albumin  less  than  2  gm/dl.   In  children, the
proteinuria is highly selective, but is mostly albumin in adults.  There  may
be  Maltese  crosses,  and  lipiduria.  Serum IgG may be decreased, and serum
complement levels are normal.  The glomeruli are normal with light microscopy
and immunofluorescence is  negative.   Electron  microscopy reveals fusion of
the epithelial cell foot processes.  Even  though  there  are  no  glomerular
deposits,  circulating  immune  complexes  have been reported in children and
adults.   TREATMENT:  About  50%  of  patients  with  nil  disease  will have
spontaneous remissions over a 2-3 year period.  However,  without  treatment,
thrombosis  and spontaneous peritonitis may develop.  Therefore, treatment is
initially with prednisone, and the  response  is excellent.  Greater than 90%
will have a complete remission of  the  proteinuria  within  2  months  after
starting  prednisone  at 60 mg/M2 or 1-2 mg/kg/day.  This dosage is continued
for about 4 weeks then  tapered  over  8-12 weeks and eventually discontinued
after the patient has had no proteinuria for about 4 weeks.  When adults  are
treated  in the same manner, the response is only about 75-80% and adults may
need a longer course of therapy  up  to 16 weeks of treatment.  Alternate day
therapy with prednisone gives a good initial response, but there is a relapse
rate that is doubled over the daily regime.  In spite of this, alternate  day
therapy  may  be  used  in  certain  subsets  of  patients such as those with
diabetes mellitus, ulcer disease, chronic  malnutrition and the elderly.  The
relapse rate in children at 1 year is 50% and at 5 years 80%.  In adults, the
relapse rate at 1 year is 30% and at 5 years  50%.   After  a  child  reaches
puberty  the  relapse  rate  is  about  10%.   For those that relapse, or are
initially steroid resistant,  cyclophosphamide  should  be started at 1.5-2.5
mg/kg given daily for  8-10  weeks.   Some  patients  are  steroid  resistant
because  there  is  associated  focal sclerosis.  Because cyclophosphamide is
capable of causing malignancy  and  gonadal  toxicity, the cumulative dose of
cyclophosphamide should be kept less than 250 mg/kg.  The  8-10  week  course
may  be repeated once.  The goal is to keep the total neutrophnil count above
1500/mm3.  Fluids should be forced in  order to prevent hematuria and bladder
irritation.  About 75% of patients will be  off  therapy  and  will  have  no
proteinuria   at   10   years.   There  is  no  mortality  related  to  renal
insufficiency,  but  there  can  be  less  than  5%  mortality  secondary  to
infections and vascular complications.

              -GLOMERULONEPHRITIS (Post-Streptococcal)-
Post-streptococcal glomerulonephritis  (PSG)  is  an  immune  complex disease
secondary to nephritogenic strains (groups 1,2,11,12,49,55 "Red Lake", 60) of
group A hemolytic  streptococci.   There  is  a  15%  occurrence  rate  after
infection  with the nephritogenic strain.  Subclinical cases are probably 4-5
times as common as those that see a physician.  It would be unusual to have a
second   episode   after   the   initial   attack   of   post   streptococcal
glomerulonephritis, because of the protective antibodies that develop against
the nephritogenic antigen.  The streptococci producing the glomerulonephritis
usually begins as a sore  throat  or  skin  infection.   It is most common in
children.  Sixty percent of the cases occur in children 2-12  years  of  age.
Only  10% are older than 40 years of age.  There is a male predominance.  The
streptococcal infection antedates the  renal  lesions  by about 1-3 weeks and
pharyngitis precedes the renal lesions by 1-2 weeks.  CLINICAL:  The  patient
usually presents with edema and possibly hypertension.  However, about 50% of
patients  are  asymptomatic.   If  the  hypertension  is  severe there may be
headaches and visual  disturbances.   There  is  either  gross or microscopic
hematuria  characterized  by  dark  urine.   There  may  be  transient  renal
insufficiency with edema of the face and eyes, feet and  ankles  particularly
in  the  evenings.   Fever  is  rare.   There  may be a diminution of urinary
output.  In severe cases,  there  is hypertensive encephalopathy, uremia with
anuria,  hyperkalemia,  and  heart  failure.   About  30%  will  develop  the
nephrotic syndrome.  LABORATORY: Obtain an anti-streptolysin O (ASOT).   This
is  increased  in  60-80%  of  cases.  The highest titer is at 3-5 weeks, but
increases begin at 1-3 weeks.  The  level  will return to normal in 6 months.
If the patient had a  preceding  sore  throat  then  the  ASOT  is  the  best
indicator  of  an upper respiratory infection.  Antihyaluronidase (AHase) and
antideoxyribonuclease B (ADNase B)  are  good  indicators for a pyogenic skin
infection.  There is proteinuria that varies from .5 to 2  grams  of  protein
per  meter2  per  day OR you can obtain a random sample of urine and obtain a
protein/creatinine ration which is < 2. Serum complement levels (C3, C4, CH50
are usually depressed, initially, and  return  to  normal later at around 6-8
weeks in 80% of PSG.  Circulating immune complexes may be present for  a  few
weeks   and  there  may  be  cryoglobulins  which  can  persist  for  months.
Ultrasound of the kidneys  usually  shows  the  kidney  size  to be normal or
slightly enlarged.  There may be a decrease of  the  glomerular  infiltration
rate  with  an increased serum creatinine.  The U/P creatinine may be greater
than forty and there may be  a  decreased  renin.   RBC casts in the urine is
pathognomonic of glomerulitis, but not specifically PSG.  The  urine  may  be
smoky  colored,  brown  or  grossly bloody.  The urinary sediment may contain
RBC, WBC and renal  tubular  cells.   There  may  also  be WBC casts present.
Examination of the RBCs microscopically will reveal distorted RBCs as opposed
to normal appearing RBCs from a hematuria originating in  the  lower  urinary
tract.   If  biopsy  is  done,  which is rarely necessary, there is a diffuse
proliferative  glomerulonephritis.   On   electron  microscopy  subepithelial
deposits  will  be  seen  and  immunofluorescence  studies  will  reveal   C3
deposition   in   almost   all  cases  with  some  IgG  and  IgM  deposition.
DIFFERENTIAL    DIAGNOSIS:     Differential     diagnosis    would    include
membranoproliferative glomerulonephritis,  SLE,  IgA  nephropathy  and  other
postinfectious  glomerulonephritis  (infected  vascular  prosthesis, visceral
abscess, and  subacute  bacterial  endocarditis  (depressed  complement).  An
important aspect in the differential diagnosis is the serum complement level.
The following diseases will produce low complements  with  the  corresponding
incidence     of     the     hypocomplementinemia.      MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS:   Type   I   mesangiocapillary   GN   (50-80%)   Type  II
intramembranous  dense  deposit  disease  (80-90%)  ACUTE  POST-STREPTOCOCCAL
GLOMERULONEPHRITIS  (>  90%),  SLE:   Focal  (75%)  Diffuse  (90%),  SUBACUTE
BACTERIAL ENDOCARDITIS (90%),  CRYOGLOBULINEMIA  (85%),  VASCULAR  PROSTHETIC
NEPHRITIS  (90%).  TREATMENT:  For  the  majority of patients only supportive
therapy is needed as a low salt  diet.  There is no particular restriction of
activity after the patient improves  clinically.   The  hypertension  may  be
treated  with  hydralazine  .25  to 1 mg/kg given every 6 hours.  If there is
continued infection, treat with penicillin for 10 days.  Edema may be treated
with furosemide 1-2 mg/kg given prn.   PROGNOSIS: In about 1% of children and
10%  of  adults  the   PSG   will   progress   to   a   rapidly   progressive
glomerulonephritis   (RPGN)   with   extensive  extracapillary  proliferation
(Crescents) and necrosis.  However, most children will return to normal renal
function in about 85-95% of the cases.  There may be a persistent proteinuria
and hematuria for months to years  which  may be confusing if the initial PSG
was asymptomatic and a casual UA is done later.  COMPLICATIONS: Complications
would include rapidly progressive glomerulonephritis, chronic renal  failure,
nephrotic   syndrome,   hypertensive   retinopathy  and  encephalopathy,  and
persistent abnormal proteinuria and hematuria.

       -GONORRHEA (Urethral, cervical, rectal, uncomplicated)-
CEFTRIAXONE (Rocephin) 125 mg IM once or cefixime (Suprax) 400 mg PO once  or
ciprofloxacin  (Cipro)  500  mg PO once or ofloxacin (Floxin) 400 mg PO once.
Each of the  above  are  given  with  doxycycline  100  mg  PO  bid  for 7 d.
Alternatives: Spectinomycin (Trobicin) 2 g IM once or  ceftizoxime  (Cefizox)
500 mg IM once or cefotaxime (Claforan) 500 mg IM once or cefotetan (Cefotan)
1  g IM once or cefoxitin (Mefoxin) 2 g IM once or cefuroxime axetil (Ceftin)
1 g PO once  or  cefpodoxime  proxetil  (Vantin)  200  mg PO once or enoxacin
(Penetrex) 400 mg PO once or  lomefloxacin  (Maxaquin)  400  mg  PO  once  or
norfloxacin  (Noroxin)  800  mg  PO  once.   Each  of the above is given with
doxycycline 100 mg PO bid for 7 d.

                     -GRAM NEGATIVE BACTEREMIA-
Urinary tract: Ampicillin 1-2 g q 4-6  hr  or erythromycin .5-1 g every 6h or
ticarcillin-clavulanate 3.1 g q4-8h or vancomycin  1  g  q12h  +  Gentamicin,
tobramycin  3-5  mg/kg/day  divided q8h or amikacin 15 mg/kg/day divided q8h.
Adjust  for  renal   dysfunction.    This  combination  covers  enterococcus.
COMMUNITY      ACQUIRED      PNEUMONIA:       Ampicillin,       erythromycin,
ticarcillin-clavulanate,   or   amikacin   as   above  and  third  generation
cephalosporins as  cefotaxime  1-2  g  q6-8h  or  ceftriaxone  1-2  g q24h or
ceftazidime 1-2 g q8h.  Consider Legionella if  immunosupressed  or  elderly.
Hospital  acquired  pneumonia:  Anti-pseudomonal  beta lactam as pipracillin,
mezlocillin, ticarcillin 3 g q4h or ceftazidime  1-2 g q8h or imipenem 500 mg
q6h    +    aminoglycoside.      INTRABDOMINAL     AND     BILIARY     TRACT:
Ticarcillin-clavulanate  plus  aminoglycoside  or  imipenem + aminoglycoside.
BURNS: Anti-pseudomonal beta  lactam  +  aminoglycoside.  CATHETER INFECTION:
vancomycin + ceftazidime or vancomycin +  aminoglycoside.   GRANULOCYTOPENIA:
anti-pseudomonal   beta   lactam   +   aminoglycoside.   Add  vancomycin  for
Staphylococcus species if intravascular catheter is present.

                      -GUILLAIN BARRE SYNDROME-
Guillain  Barre  syndrome  (GBS)  is  an acute polyradiculoneuropathy with an
acute onset, characterized by muscular  weakness and distal sensory loss that
usually follows a viral illness or some sort of stress.  The cause is unknown
and the patient may have an antecedent infection that precedes the  onset  of
the  disease  by 8 weeks in 65% of cases.  The disease occurs at all ages and
male involvement equals female  involvement.   The  incidence is .6-1.9 cases
per 100,000 annually.  There doesn't appear to be any seasonal preference and
GBS doesn't occur in epidemics.  Pathologic findings usually  show  segmental
demyelination  of  peripheral  nerves  and  axonal  degeneration.   There are
inflammatory changes with lymphocyte  and  macrophage  invasion of the myelin
sheath.  In general, GBS is severe but reversible, and about 80% of  patients
recover  fully.   One  study  showed that weakness reached a maximum within 3
weeks in 84% of  patients.   Patients  may  be  back  to normal in 16 months,
although there may be slight decrease in reflexes, and in some foot drop  may
persist.   Some  20% of patients have long term disability and 10% experience
some form of recurrence.   Mortality  rate  is  about 2-5%.  The syndrome has
been associated with the influenza  vaccination  in  the  USA  in  1976.   In
Finland,   in   1985,  there  were  cases  associated  with  oral  poliovirus
vaccination.  GBS has been associated  with tetanus toxoid therapy, botulinum
toxin therapy, surgery, captopril therapy, myelosuppression  with  cytarabine
(Cytosar-U)  and bone marrow transplantation and head trauma.  Guillain Barre
syndrome has also  been  associated  with  several  conditions as: infectious
mononucleosis, cytomegalovirus infections, herpes zoster, Helicobacter jejuni
infection, Epstein Barr virus,  Haemophilus  influenzae  type  b,  Tularemia,
viral    encephalitis,   Wegener's   granulomatosis,   Hashimoto's   disease,
sarcoidosis,  Schonlein-Henoch  purpura,  myocardial  infarction, mycoplasma,
mumps, lymphomas, serum sickness, AIDs and lyme disease.  CLINICAL:  GBS  may
present  with  varying  levels of muscular weakness that evolves over a short
period of time.  Proximal  weakness  is  more common than distal involvement.
The weakness is always symmetrical.  Both upper and lower extremities may  be
affected.   Some patients have muscular pain but there is no atrophy noted at
presentation.  Cranial nerves are commonly  affected involving the 10, 11,and
12 commonly; 5 occasionally, and 2,3,4,6 rarely.  Facial nerve palsies  occur
in  60%.   There may be sensory findings as paresthesiae and numbness.  There
is a stocking  distribution  sensory  loss  that  is  variable.  There may be
bulbar involvement with bilateral  facial  and  oropharyngeal  weakness  with
difficulty  in  swallowing.   The  patient  may  have  urinary  retention and
inappropriate  ADH  secretion.   The  DTRs  are  absent.   Motor  and sensory
involvement is usually symmetric.  There is usually an ascending aspect to to
the disease, but this feature may not always be present.   Autonomic  changes
are  common  with sinus tachycardia or bradycardia, hypertension, orthostatic
hypotension  and  urinary  sphincter  disturbances.   Rarely,  there  may  be
cardiovascular collapse.  Respiratory failure may occur with decreased forced
vital capacity and flow volume  loop  changes.   The respiratory onset may be
very sudden.  If the patient has less than 12-15 mg/kg forced vital capacity,
mechanical ventilation may be needed.  Some  10-23%  of  patients  will  need
ventilatory  assistance  sometime  during  the illness.  LABORATORY: Cerebral
spinal fluid shows an elevated protein  beginning about 1 week after onset of
the weakness and peaks at 4-6 weeks.  The protein elevations may be high with
greater than 1000 mg/dl.  The cell count is usually normal.  If there is more
than 50 mononuclear cells or more than two polys, then another disease should
be entertained.  Electromyography and nerve conduction studies are useful for
diagnosis  and  prognosis.   Electromyography  may  show   sharp   waves   or
fibrillations  which  would  indicate  axonal  degeneration.   Distal  muscle
compound  action  potential  amplitude  of less than 20% is associated with a
poor outcome.  DIFFERENTIAL  DIAGNOSIS:  Differential diagnosis would include
tick paralysis,  buckthorn  berry  intoxication,  diphtheritic  polyneuritis,
progressive  AIDS  related  polyradiculopathy that is caused by CMV which may
respond to ganciclovir.  Heavy  metals  (as lead, arsenic), carbon disulfide,
acrylamide, trichlorethylene, rapeseed oil, hexacarbons, and  organophosphate
esters   may  all  cause  neuropathies.   Systemic  disease  neuropathies  as
diabetes,  uremia,   porphyria,   SLE,   polyarteritis  nodosa,  amyloidosis,
rheumatoid arthritis, lymphoma, carcinoma,  polio  and  myeloma  may  all  be
included  in  the  differential.   Drugs  as gold, nitrous oxide, disulfiram,
phenytoin,  sulindac,  hydralazine,  nitrofurantoin,  metronidazole, dapsone,
isoniazid and pyridoxine in doses greater than  2  grams/day  may  all  cause
neuropathies.    Vitamin  B12  and  folic  acid  deficiencies  and  alcoholic
neuropathies can mimic GBS.  TREATMENT: In general, corticosteroids have been
disappointing.  Plasmapheresis  has  a  beneficial  effect  in  patients with
chronic inflammatory demyelinating polyneuropathy.  If the patient is  unable
to  walk  at  least  5  meters  unassisted  then  they should be treated with
plasmapheresis as early as possible.   One plasma volume exchange every other
day can be done for a total of 5 treatments.  It has been shown that patients
who needed mechanical ventilation after plasmapheresis spent a  median  of  9
days  on the ventilator as compared with a median of 23 days in patients from
a control group.  Immune  globulin  in  high  IV  doses  may  be given if the
patient can't walk, and have had symptoms for less than 2 weeks.   This  will
help  50% in one month.  The dose is .4 g/kg/day for 5 days.  Patients should
be admitted to the  ICU  where  cardiac  monitoring  and oximetry can be done
continuously.  Physical therapy and use of footboards to prevent footdrop are
important.  Watch  for  and  treat  any  decubitus  ulcers  and  atelectasis.
Observe  the  patient for development of nosocomial infections.  Prevent deep
venous thrombosis with pneumatic  compression  stockings.  Some patients will
need parenteral nutrition with replacement of vitamins B12, B6, A, C,  and  E
and beta carotene as plasmapheresis has been shown to depress these levels.

                            -GUSTO TRIAL-
The  GUSTO  (Global  Utilization  of  Streptokinase  and  Tissue  Plasminogen
Activator for Occluded Coronary Arteries) trial concluded that an accelerated
regimen of t-PA given over 90 minutes instead  of  the  standard  3  hours  +
intravenous heparin, is the best thrombolytic regimen as of this writing.  It
is  postulated that the rapid administration of t-PA probably leads to faster
recanalization  of  the  infarct  related  artery.   In  the  GUSTO  study  4
thrombolytic strategies  in  41,021  patients,  enrolled  at  1,081 sites who
presented to the hospital  within  6  hours  after  the  onset  of  actue  MI
symptoms,  were  compared.   The 4 regimens are as follows: Streptokinase 1.5
million units given IV over  60  minutes + subcutaneous heparin, 12,500 units
twice a day	OR Streptokinase 1.5 million U given IV  over  60  minutes  +  IV
heparin,  given  in  a bolus of 5,000 U and then 1,000 U/hour, OR Accelerated
t-PA (a 15 mg bolus, then 0.75 mg/kg  over 30 min, followed by 0.5 mg/kg over
the next 60 min) + IV heparin given in a bolus  of  5,000  U  and  then  1000
U/hour,  OR a combination of t-PA given at 1.0 mg/kg over 60 minutes with 10%
given as a bolus and streptokinase  1  million  units over 60 minutes with IV
heparin.  The patients also received IV atenolol if  no  contraindication  to
beta  blockers + ASA.  RESULTS: The total mortality with accelerated t-PA was
6.3% compared to  7.2%  with  streptokinase  and  SQ  heparin,  and 7.4% with
streptokinase and IV heparin.  This represents a 14%  decrease  of  mortality
with   accelerated  t-PA  when  compared  to  the  2  streptokinase  regimes.
Accelerated t-PA treated patients had an excess of 2 hemorrhagic strokes/1000
patients compared with streptokinase  and  an  excess of 4/1000 compared with
combination therapy.  T-PA treated patients had fewer	complications as left
ventricular dysfunction, arrhythmias and allergy.  The t-PA group did  better
with  either  anterior  or inferior MIs compared with streptokinase patients.
Benefit was best with anterior MIs.

                          -GYNECOMASTIA-
Gynecomastia is a benign enlargement of  the male breast but can coexist with
numerous other conditions.  Initially, there  is  ductal  proliferation  with
epithelial  hyperplasia  and  an  increase  in  the periductal connective and
stromal tissue.  Later, after  about  1  year, there is stromal hyalinization
and less epithelial proliferation.  The breast enlargement can be unilateral,
bilateral, painless or painful.  Differentiation from fatty breast tissue  is
made by the presence of a disc like mass underneath the breast.  Gynecomastia
occurs  at  3  times during the life of man.  In 60-90% of cases, neonatally,
there is transient enlargement  due  to transplacental transfer of estrogens.
During puberty, with a peak at 13-14 years of age, there is enlargement.  The
last peak is between 50-80 years of age.  CAUSES: Hematomas,  dermoid  cysts,
lipomas,  lymphangiomas,  neurofibromas  are  uncommon  causes.   Male breast
cancer needs  to  be  ruled  out,  which  presents  usually  as  an eccentric
unilateral, hard mass that is fixed.  It can be associated  with  retraction,
crusting  or  nipple  discharge,  dimpling  and  axillary lymph nodes.  Other
causes  include  hyperthyroidism,   liver   disease,  primary  and  secondary
hypogonadism, ectopic production of human chorionic gonadotropin from kidney,
lung and liver.  Additional causes include testicular tumors (  Leydig  cell,
Sertoli  cell  and  germ  cell),  adrenal adenomas or carcinomas, starvation,
kidney  disease  and   dialysis,   idiopathic,   Klinefelter's  syndrome  (In
Klinefelter's there is an increase risk of breast cancer 16 times higher than
normal  men.)  The  following  drugs  can  cause   gynecomastia:   verapamil,
nifedipine,   enalapril,   captopril,   amiodarone,   digitoxin,  methyldopa,
reserpine, diazepam, phenothiazines,  tricyclic antidepressants, haloperidol,
alcohol,   amphetamines,   marijuana,   heroin,   penicillamine,   phenytoin,
ranitidine, cimetidine, omeprazole, metronidazole,  ketoconazole,  isoniazid,
cyproterone,   flutamide,   estrogens   and   estrogen   agonists,  chorionic
gonadotropin, androgens and anabolic steroids, amphetamines, cytotoxic drugs,
isoniazid and spironolactone.  LABORATORY: All  of the following tests may be
done  depending  upon  the  circumstances:  Serum   chorionic   gonadotropin,
testosterone, estradiol, luteinizing hormone, mammography, fine needle biopsy
of  the  breast,  surgical biopsy of the breast, prolactin, liver and thyroid
function,  chromosomal  analysis,  chest  x-ray,  CT  of  chest  and abdomen,
testicular ultrasound, and CT  of  the  pituitary.   During  puberty,  workup
should  be  limited  and  dictates  palpation  of  the testes and history and
physical and follow-up.  The gynecomastia  usually  resolves in a year or so.
In adults, get history of alcohol, drugs, chest symptoms to rule out  cancer,
testes   hypofunction   (decreased   libido   and   impotence),  symptoms  of
thyrotoxicosis, liver and kidney  function.   If  these are all negative then
recheck in about 6 months.  If suspicious, proceed to other lab tests  listed
above.   If a drug is suspected, remove the drug and re-evaluate in one month
at which time there should be less pain.  SPECIFIC WORKUP: Measure serum hCG,
LH, Testosterone, Estradiol.  If  hCG  is  elevated, get ultrasound of testes
and if this is positive, rule out germ cell tumor.  If normal,  rule  out  an
extragonadal germ cell hCG secreting non-trophoblastic tumor and proceed with
a  CT  of  chest and abdomen.  If LH is increased and testosterone decreased,
rule out primary hypogonadism.  If LH is decreased or normal and testosterone
is decreased, measure the serum prolactin  and  if elevated there is a chance
of a prolactin secreting pituitary tumor which would trigger a CT or  MRI  of
the  pituitary.   If  the  prolactin  is  normal,  then  rule  out  secondary
hypogonadism.   If both LH and testosterone are elevated, get T4 and TSH.  If
there is increase of T4 and  decrease  of TSH, hyperthyroidism is likely.  If
T4 and TSH are  both  normal  there  is  probable  androgen  resistance.   If
estradiol  is  increased  and  there  is  a  normal  LH,  perform  testicular
ultrasound.   If  a mass is seen then there could be a Leydig or Sertoli cell
tumor.  If ultrasound is normal, get an  adrenal  CT or MRI.  If mass is seen
then  probable  adrenal  neoplasm.   If  normal  there   may   be   increased
extraglandular  aromatase  activity causing the gynecomastia.  TREATMENT: The
underlying disorder  should  be  corrected.   Discontinue  drugs  that may be
causing the gynecomastia.  Give reassurance for benign  disorders.   Cosmetic
surgery.   If  prostatic  cancer  is  present  and,  patients  are to receive
estrogens  for   treatment,   then   low   dose   radiation   may   be  given
prophylactically.  Tamoxifen 10 mg bid may be given a 3  month  trial.   Side
effects  are  low  and Tamoxifen seems to be safe.  There may not be complete
regression, but an 80% complete  response  has  been noted.  Other drugs that
have been used, but are not as effective,  include  Clomiphene,  Danazol  and
Testolactone.

                        -HAIRY CELL LEUKEMIA-
Hairy cell leukemia accounts  for  <  2%  of  all  leukemias and the cause is
unknown.   Middle  aged  patients  are  affected.   Usually   presents   with
cytopenias   without   constitutional   symptoms  and  splenomegaly  in  90%.
Infections may be present related to the cytopenias.  The hairy cell consists
of cytoplasmic projections  with  multiple  thin  or  blunt projections.  The
cells have a positive TRAP stain (tartrate resistant acid phosphatase).  Most
are B-cells, as demonstrated by light and  heavy  chain  immunoglobulin  gene
rearrangements.    LABORATORY:   anemia,   thrombocytopenia,  neutropenia  or
pancytopenia.   Greater   than   75%   have   anemia,   thrombocytopenia  and
neutropenia.  Hairy cells may or may not be seen  in  the  peripheral  blood.
The  bone  marrow  aspiration  yields  a  dry  tap,  with  bone marrow biopsy
specimens  yielding  a  hypercellular  specimen  with  diffuse  infiltration.
COMPLICATIONS: Infection is the most  common  mode  of  death and a new fever
usually indicates a new infection, such as urinary tract infection, bacterial
pneumonia and skin infections.  There is a higher incidence of fungal, viral,
parasitic and atypical mycobacterial infections, along  with  histoplasmosis,
toxoplasmosis,  coccidioidomycosis  and  pneumocystis.   Other  complications
include  bleeding and vasculitis (joint, skin, erythema nodosum).  TREATMENT:
treatment is indicated if  there  is  bleeding secondary to thrombocytopenia,
splenic infarction, vasculitis, significant cytopenias, serious and recurrent
infections associated with neutropenia and increasing number of hairy  cells.
Treatment  is  with 2-Chlorodeoxyadenosine given as a single 7 day continuous
IV  infusion  and  will  produce  a  complete  remission  in  85-88%.   Alpha
recombinant interferon will only  produce  a  13% complete remission after 18
months of  subq  injections.   2'deoxycorformycin  will  produce  a  complete
remission  in 75%, with a relapse rate of 10%.  Splenectomy is indicated only
for a very  large  spleen  with  patchy  bone  marrow  involvement in a young
patient,  splenic  infarct  and  life  threatening  hemorrhage  secondary  to
thrombocytopenia.  Splenectomy has no effect on the bone marrow but  improves
peripheral blood cell counts.

                   -HANTAVIRUS PULMONARY SYNDROME-
Hantavirus has made its way into the USA.  In Europe and Asia, the hantavirus
causes a hemorrhagic fever/renal syndrome.  However, the hantavirus pulmonary
syndrome is reported  to  be  10  times  more  deadly  than  the  hemorrhagic
fever/renal  syndrome.   The disease was first recognized in the southwestern
portion of the USA in the  summer of 1993.  The hantavirus pulmonary syndrome
is mainly seen in Arizona, New Mexico, Colorado and the western  states,  but
reports  are now coming in from Indiana, Florida, Louisiana, Florida and even
Canada.  The common deer  mouse  (Peromyscus  maniculatus) is the most common
source, but the virus can be carried  by  western  chipmunks,  harvest  mice,
brush  mice,  and  pinon  mice.   The  disease  is  spread  by  inhalation of
aerosolized particles from infected  rodent  feces  and urine.  CLINICAL: The
pulmonary disease begins as a flu-like syndrome with headache, myalgias and a
high fever.  Many patients will also complain of abdominal pain,  nausea  and
vomiting.  These initial symptoms characteristically last for about 2-5 days,
at  which  time  the patient develops cough and shortness of breath.  This is
rapidly followed by  pulmonary  hypoxemia,  pulmonary  edema, hypotension and
shock.  Death may then ensue within 24-72 hours.  The pulmonary edema is  due
to  a progressive capillary leak syndrome.  About 50% will have mild disease,
while the other  50%  will  deteriorate  rapidly  with  or without aggressive
therapy.  LABORATORY: Thrombocytopenia is  usually  the  earliest  laboratory
abnormality  to  develop.  For this reason, it can be used early to help rule
out the syndrome.  There also  is  a  left  shift  in the myeloid series with
production of large immunoblastoid lymphocytes which  represent  activated  T
cells.   Chest  x-ray will show diffuse pulmonary infiltrates.  The physicans
at the University of New  Mexico  have  developed a rapid diagnostic test for
hantavirus.   TREATMENT:  Patients  currently  are  being  treated  with   IV
ribavirin  (Virazole)  which  has  been  used to treat hemorrhagic fever with
renal syndrome.  The usual adult dose  is  a  2  gram IV loading dose, then 1
gram q6h x 4 days,  then  0.5  gm  q8h  x  6  days.   Patients  also  require
supportive  measures such as mechanical ventilation, pressor agents and fluid
management.
  
                       -HEADACHES (TREATMENT)-
MIGRAINE HEADACHES:   ACUTE:  SUMATRIPTAN (Imitrex)....This drug may be given
by  patient  using  6  mg  subcutaneously  in  the  lateral  thigh  using the
autoinjector supplied with the drug.   This  will relieve the headache within
one hour in about 70-80% of patients.  A second dose of 6 mg may be given one
hour later if the headache is unrelieved.  However,  second  doses  have  not
been  found  to  be  very  effective if the pain is not relieved by the first
injection.  The maximum dose  within  24  hours  is  2 injections.  This drug
should not be used if the patient has a history of coronary artery disease as
it can cause coronary spasm.  Sumatriptan should not be  used  until  24  hrs
after  use  of any ergotamine containing drug and the patient should not take
ergot derivatives  until  6  hours  after  sumatriptan.   Other  side effects
include tingling, flushing  and  burning  of  the  skin,  nausea,  tightness,
heaviness  and  pressure  in the chest.  The cost currently is $34.00 for one
injection.  DIHYDROERGOTAMINE MESYLATE (DHE  45)....is  given  either IM at a
dose of 1 mg or IV at a dose of .5 mg.  Because this drug  can  cause  nausea
and  vomiting  the patient may be pre-treated with metoclopramide (Reglan) 10
mg IV,  (unlabeled  use)  if  DHE  is  given  IV.   IF  DHE  is  given IM, no
pre-treatment is necessary.  If  the  patient  has  ischemic  heart  disease,
peripheral   vascular   disease,   liver   disease   or   infection   DHE  is
contraindicated.  PROCHLORPERAZINE (Compazine)....can be given IV at 5 mg/min
for 2 minutes.  KETOROLAC (Toradol) IM 15  or  30 mg/ml....  Give 30 or 60 mg
IM.    ISOMETHEPTENE-DICHLORALPHENAZONE-ACETAMINOPHEN   (Midrin)....Take    2
capsules  immediately  followed by one capsule every 30 minutes not to exceed
five capsules in 24 hours.  DECADRON....If the migraine headaches persist for
more than  24  hours  16  mg  of  decadron  IM  may  be  helpful.  ERGOTAMINE
SUPPOSITORIES  2  mg  (Wigraine,  Cafergot,  Cafergot  PB)....Start  with   1
suppository  per  attack.   May use up to 2 suppositories per attack, but the
maximum ergotamine is 6 mg  in  24  hours  and  no  more than 10 mg per week.
ERGOTAMINE 2 mg SUBLINGUAL (Ergostat, Ergomar)....use 1 sublingually at onset
and  may  repeat  after  30  minutes  to  a  maximum  of  3/day  or   5/week.
MEDIHALER-ERGOTAMINE  metered  dose  inhaler  (.36 mg/inhalation)....Give one
inhalation at onset and repeat after 5  minutes.  The maximum daily dose is 6
inhalations/24  hours  or  15/week.   ERGOTAMINE  1  mg  +  CAFFEINE  100  mg
(Wigraine, Cafergot, Cafergot PB)....Take two tablets at  onset  of  headache
then  one  after 30 minutes.  The maximum is 6/day or 10/week.  ERGOTAMINE .6
mg + BELLADONNA .2 mg  plus  PHENOBARBITAL 40 mg (Bellergal-S)....Take one at
onset with a maximum weekly dose of 16 tablets/week.  ACETAMINOPHEN  325  mg,
ISOMETHEPTENE  65  mg,  DICHLORALPHENAZONE  100 mg (Midrin, Isocom)....Take 2
capsules at onset and then one/hour  if  no  relief  up to 5 capsules in a 12
hour period.   PROPHYLAXIS:  PROPRANOLOL (Inderal)....40-120 mg  bid.   Also,
may  use atenolol, metoprolol, and nadolol as these are equally effective for
prophylaxis.  If the patient has  3  or  more  attacks per month one of these
beta blockers should be started.  The long acting preparations don't seem  to
work  as  well  as  the  short  acting  forms.   VERAPAMIL....80-120  mg  tid
CLONIDINE....   0.1  mg  bid  PERIACTIN....   4-20  mg  /day for adults.  For
children use 4-8  mg/day.   AMITRIPTYLINE....  50-300 mg/day.  PERSANTINE....
50-100 mg/day.  SANSERT....  4-12 mg/day.   NAPROXEN  500  mg  (Naprosyn)  or
NAPROXEN  550  (Anaprox  DS)....Give one tablet at onset with a maximum daily
dose of 1,375  mg.    FOODS  THAT  MAY TRIGGER MIGRAINES:  Nitrates....bacon,
sausage,  hot   dogs,   prepared   hams,   and   lunch   meats.    Vasoactive
amines....Yellow  and  white  cheeses, chocolate, nuts, citrus fruits, onions
and legumes, especially navy and lima beans.  Monosodium glutamate....Chinese
foods,  packaged  soups,  several  commercial  canned  foods  and  soy sauce.
Other....Alcohol, especially red wines and  beer,  yogurt,  eggs,  and  fried
foods.   CLUSTER  HEADACHES:  ACUTE:  SUMATRIPTAN (Imitrex)....is used for an
acute attack only.  Give one 6  mg  injection  in the lateral thigh using the
autoinjector supplied with the drug.  A second dose may  be  given  one  hour
later,  but efficacy for alleviating the headache is diminished following the
second dose.   The  maximum  dose  per  24  hours  is  12  mg subcutaneously.
Sumatriptan should not be used until 24 hours after  use  of  any  ergotamine
preparation,  and the patient should not take ergot derivatives until 6 hours
after sumatriptan.  Other side effects include angina, tingling, flushing and
burning  of  the  skin   with  subcutaneous  injections,  nausea,  heaviness,
tightness and pressure in the chest.  It is contraindicated in ischemic heart
disease because it  may  induce  vasospasm.   ERGOTAMINE  AEROSOL  (Medihaler
Ergotamine)....  0.36-1.08 mg (1-3 inhalations).  Maximum dose in 24 hours is
6  inhalations or 4 mg.  OXYGEN....100% at 8-10 L/min for 10-15 minutes using
a tight fitting mask.  May use  up  to 5 times per day.  LIDOCAINE intranasal
instillation....  1 ml of  a  4%  topical  solution  is  instilled  into  the
affected  side.   For  optimal  results the patient should be supine with the
head extended 45 degrees and  rotated  about  40  degrees  to the side of the
headache.  Decongest the turbinates with intranasal .5% phenylephrine  before
the  lidocaine instillation.  DIHYDROERGOTAMINE MESYLATE (DHE 45)....Give one
mg IM or IV (1 mg/ml) immediately  at  onset of headache and follow with 1 mg
every hour as needed up to 3 mg IM or 2 mg IV.  The maximum dose in one  week
is  6  mg.   The  IV  administration  causes  nausea  and vomiting and may be
preceded with 10 mg  of  IV  prochlorperazine.  PROPHYLAXIS:  ERGOTAMINE oral
tablet [Cafergot (ergotamine 1 mg, caffeine 100 mg); Cafergot PB  (ergotamine
1  mg, caffeine 100 mg, belladonna .125 mg, pentobarbital 30 mg)]....Give 1-2
mg of ergotamine as the initial dose then 1-2 mg q 30 minutes as needed for a
maximum of 6 mg/day or 10 mg/week.  PREDNISONE....40-120 mg po qd for 2 weeks
followed by tapering dose.   METHYSERGIDE  (Sansert)....Give 2 mg bid-tid for
2-3 months.  Maximum daily dose is 8 mg and Methysergide should not  be  used
for   longer   than  6  months.   LITHIUM  CARBONATE....300  mg  po  bid-qid.
VERAPAMIL....80-120  MG   PO   TID-QID   ERGOTAMINE  SUPPOSITORIES....If  the
headaches are known to  occur  at  certain  times  give  a  2  mg  ergotamine
suppository   1   hour   before  anticipated  attack.   MENSTRUAL   MIGRAINE:
ESTRADIOL....  1-5 mg po qd  for  7  days  starting  48 hours before onset of
menses.  NAPROXEN (Naprosyn)....  250 mg bid.  IBUPROFEN (MOTRIN)....  600 mg
tid.  MEFANAMIC ACID (Ponstel)....  600 mg po tid.  BELLERGAL S  (ergotamine,
phenobarbital,   belladonna)....    1  tablet  po  tid.   ERGONOVINE  MALEATE
(Ergotrate)....  0.2 mg po  bid.  TEMPORAL ARTERITIS: PREDNISONE.....  60-120
mg po qd and titrate dose downward according to ESR and symptoms.  EXERTIONAL
HEADACHES: INDOMETHACIN  (Indocin)....   25-50  mg  po  tid  or  Indomethacin
suppository  50  mg  or  Indocin  SR  75  mg  po  qd-bid.   COITAL HEADACHES:
PROPRANOLOL (Inderal)....  40-80  mg  po bid-qid.  INDOMETHACIN (Indocin)....
25-50 mg po tid.  TENSION HEADACHES:  ACUTE:  FENOPROFEN (Nalfon)....  200 mg
every  4-6  hours.   NAPROXEN  (Naprosyn)....    500   mg   bid.    IBUPROFEN
(Motrin)....    400   mg   tid.    KETOPROFEN   (Orudis)....    50   mg  tid.
PROPHYLAXIS:  IMIPRAMINE  (Tofranil)....   50-100   mg  daily.  NORTRIPTYLINE
(Pamelor)....  25-50 mg daily.  AMITRIPTYLINE  (Elavil)....   50-100  mg  per
day.  DESIPRAMINE (Norpramin)....  50-100 mg per day.

                           -HEARING LOSS-
Sudden hearing loss may be caused by  Meniere's  disease,  acoustic  neuroma,
hematologic  disorders  such  as  polycythemia  vera, sickle cell disease and
leukemia.  Multiple  sclerosis,  sarcoidosis  and  AIDS  are  associated with
sensorineural hearing loss.   Coronary  artery  bypass  surgery  may  produce
thromboembolic  events  resulting  in  sudden hearing loss.  Aminoglycosides,
loop diuretics, and cisplatin can  cause  sudden or progressive hearing loss.
Trauma, heavy exertion or lifting and skin diving can cause  a  perilymphatic
fistula  that  results  in  sudden  hearing loss, sensitivity to loud sounds,
roaring tinnitus and vertigo and  disequilibrium.  Allergies to foods such as
dairy products, yeast, ragweed and pollens  can  cause  sudden  sensorineural
loss.     Autoimmune    disorders    as   polyarteritis   nodosa,   Wegener's
granulomatosis,  Bechcet's   syndrome,   Cogan's   syndrome   and  ulcerative
colitis	may all cause sudden hearing loss.  Viral diseases as  mumps,  herpes
zoster   oticus,   measles,   adenovirus,   Herpesvirus  hominis,  Mycoplasma
pneumoniae, Parinfluenza types I and III may all cause sudden hearing loss.

                            -HEART BLOCK-
SECOND DEGREE HEART BLOCK: Mobitz  type  I  (Wenckebach) heart block tends to
occur with inferior wall ischemia or infarction, increased vagal tone  as  in
sleeping,  or  secondary  to  medications  such  as  beta  blockers,  calcium
antagonists  and digitalis.  The site of the block is usually in the AV node,
but rarely can be  in  the  His  bundle.   It  is  characterized by a gradual
prolongation of the PR interval until there is  failure  of  one  P  wave  to
conduct.   The  ratio  of  P  waves  to  QRS  is usually 3:2 or 4:3.  The R-R
intervals will concurrently  decrease  during  these  cycles.   Type I second
degree AV block is usually a benign condition, particularly in those patients
that have no organic  heart  disease.   These  patients  do  no  require  any
treatment   other   than   discontinuing   any   medications  that  might  be
incriminated.  In the  setting  of  acute  inferior  wall  MI, this block may
appear, but usually resolves within 48 hours.  If the rate is < 40 beats  per
minute  and  atropine  is  not  effective  in  raising  the  rate,  temporary
ventricular  pacing  may  be  employed,  particularly if there is significant
congestive heart failure or progression to complete heart block.  In general,
many of the factors that may  cause  a first degree block are instrumental in
producing a Mobitz I block.  MOBITZ TYPE II AV  BLOCK:  This  block  is  less
common  than  the  Mobitz  type  I block, has a more ominous connotation, and
occurs suddenly rather than  after  gradual  prolongation of the PR interval.
However, in contrast to Type I block, the PR interval  is  constant,  without
gradual  lengthening  of  the PR interval.  Type II block may be difficult to
distinguish from type  I  block,  as  type  I  may  present  with very subtle
lengthening of the PR interval.  The presence of a  bundle  branch  block  in
association  with  Type  II  may be a clue, as bundle branch block frequently
accompanies Type II second degree AV  block.   Type II block is almost always
in the His bundle or lower.  Frequent causes  of  this  block  include  acute
anterior myocardial infarction, degeneration of the conduction system, injury
to  the  His  bundle  secondary  to  aortic  valve  surgery.   Class IA drugs
(quinidine,  procainamide,  disopyramide,   and   moricizine)  and  Class  IC
antiarrhythmic drugs (flecanide, and propafenone) are sometimes found  to  be
the  offenders.  It is important to stress that progression to complete heart
block with a very slow escape  rhythm can be sudden and permanent.  Permanent
pacing should be the treatment of choice in patients with a  type  II  block,
even if the patient is asymptomatic.

                      -HEART SURGERY FOLLOW-UP-
During this decade you may have occasion  to  assist  in  the  management  of
repaired congenital heart disease that was done in the mid 1960's when repair
of congenital heart defects became standard practice.  In order to do this it
is  important  to  know  the  diagnosis,  complications  for  that particular
surgery, and the type of surgery performed.  Atrial septal defects and patent
ductus arteriosus  repair  is  usually  considered  curative.   It  is common
practice for non  open  heart  surgery  to  be  performed  in  patent  ductus
arteriosus  and  coarctation  of the aorta while atrial septal defects (ASD),
ventricular septal defects (VSD) and  tetralogy of Fallot (TOF) are corrected
surgically.  COARCTATION OF THE AORTA: If coarctation of the aorta recurs, it
usually does so within the first 6-12 months, but can occasionally  recur  as
late  as  15  years.  Be aware of recurrent BP problems and decreased femoral
pulses, and new nurmurs.  Neonatal  repairs  have  a recurrence rate of about
10-15%.  Most recoarctations become manifest 1-4 years following the  initial
repair.  If the repair was with Dacron patches, aneurysm formation may occur,
some  in  association  with  dissection.   The best method for monitoring for
aneurysm is with MRI every  2-3 years or alternatively with echocardiography.
Those patients that have associated bicuspid aortic valves must be  monitored
for  aortic  valve stenosis or regurgitation.  Physical activity restrictions
are not needed usually  in  the  asymptomatic patient.  ATRIAL SEPTAL DEFECT:
Patients that had their repair prior to the age of 24 have a natural  history
approaching  that  of  a person born without congenital heart disease, if the
pulmonary artery  systolic  pressure  was  not  elevated.  Atrial arrhythmias
usually occur more frequently if the repair was done later  in  life.   These
patients  have  no activity restrictions and follow up is done with an annual
chest  x-ray  for  heart  enlargement,  ECG  and  auscultation  for  murmurs.
VENTRICULAR SEPTAL DEFECT: Patients that  were  operated in the early days of
heart surgery had heart block and required pacemakers,  but  is  now  a  rare
occurrence.   If  a ventriculotomy was done there is a slight increase in the
frequency of ventricular arrhythmias.  As in  ASD, there is no restriction of
activities and follow up is  pursued  with  annual  chest  x-rays  for  heart
enlargement,  auscultation  for  murmurs  and  and ECG.  TRANSPOSITION OF THE
GREAT ARTERIES: Patients that had  the  Senning  and Mustard type repair that
was popular in the 1960's 1970s and the early 1980s have a concern  with  the
durability  of  the  right  ventricle  and  tricuspid valve in supporting the
systemic circulation.   Be  vigilant  for  atrial  tachyarrhythmias as atrial
flutter and sick sinus  syndrome.   A  more  current  surgical  approach  for
transposition  is  an  arterial,  rather  tha a venous switch operation which
actually restores the normal  anatomy  back  to the intended normal positions
which should improve late ventricular function.  These patients should have a
re-evaluation by a cardiologist every 2-4 years, with ECG, Holter monitoring,
echocardiography and chest x-rays.  These patients, if  asymptomatic  usually
have   no   acitvity   restrictions  except  for  high  intensity  athletics.
Antibiotic prophylaxis is necessary.  Periodic  CBCs  should be done to check
on erythrocytosis.  TETRALOGY OF  FALLOT:  Patients  that  were  repaired  in
infancy  usually  have  a  good  long  term  survival, but about 15% may need
reoperation.   Some   of   these   patients   will   develop  pulmonic  valve
insufficiency, right ventricular failure, malignant  ventricular  ectopy  and
heart block.  Patients may need a Blalock-Taussig shunt if pulmonary stenosis
is  severe  and  the  pulmonary  artery  is  small, in order to alleviate the
hypoxia.  The ventricular septal defect is closed with a prosthetic patch and
the right ventricular outflow  tract  obstruction  is reduced by resection of
the infundibular muscle and a pulmonary valvotomy.  If the annulus  is  small
or  there  is  a  hypoplastic  main pulmonary artery, a Dacron or pericardial
patch can be connected from  the  right  ventricular outflow tract across the
pulmonary valve annulus to the pulmonary arteries.  Some  of  these  patients
with  pulmonary  valve  regurgitation  will  experience fatigue and decreased
exercise tolerance, but most do fairly  well.  Sometimes a porcine valve will
be needed to decrease the size of the right ventricle.  Follow  up  of  these
patients  includes  an  annual  chest  x-ray for heart size, auscultation for
murmurs and ECG done every 6-12  months.   Holter monitoring may also be done
periodically because of the late ventricular arrhythmias propensity which can
cause sudden death.  Echocardiograms should be  performed  every  3-4  years.
Activity  restrictions  are  usually  not  necessary  as  these patients have
stable, but suboptimal exercise performance.

                        -HELICOBACTER PYLORI-
Helicobacter pylori is the cause of chronic active gastritis.  The  treatment
of choice for gastric or duodenal ulcerations consists of tetracycline 2 g/d,
metronidazole 750 mg/d and bismuth 8 tablets/day for 2 weeks which results in
an eradication rate of 90%.  In those intolerant of tetracycline, amoxicillin
can  be  substituted  with nearly equal efficacy.  Antibiotics wihout bismuth
results in eradication  of  H  pylori  in  90%  of  patients.  Other regimens
include omeprazole and antibiotics as  amoxicillin  or  clarithromycin  which
result  in  eradication  rates  of  60-80% and appear to be better tolerated.
Reinfection after  eradication  is  unusual  and  maintenance  therapy is not
needed.  Diagnosis can be made by obtaining  a  mucosal  biopsy  and  placing
specimen  into a urea gel or broth that contains a pH detector, most commonly
phenol red (Clotest, Trimed Specialties  Inc, Lenexa, Kansas).  This test can
be read within 2-3 hrs and 2/3 will  be  positive  within  30  minutes.   The
sensitivity and specificity is 90-98%.  False negative results can occur from
sampling  artifact or a low inoculum of bacteria in the sample.  Giemsa stain
of the mucosal  specimen  can  also  be  done  to  detect  H. pylori.  Antral
biopsies give the highest yield.  Culture of the  mucosal  biopsy  will  give
antibiotic sensitivities and the specimen must be placed in chocolate agar to
which  antibiotics  have  been  added to prevent other bacterial over-growth.
The organism requires  a  warm,  humid  microaerophilic  environment for best
growth.  Sensitivity is 70-95% and specificity is 100%.

                             -HEMATURIA-
The  following  lab tests should be done if the coagulation screen is normal,
but the UA  demonstrates  dysmorphic  RBCs  or  casts: Antinuclear antibodies
(ANA) to rule out SLE, antineutrophil  cytoplasmic  antibodies  to  rule  out
Wegner's   and   vasculitis,   cryoglobulins  to  rule  out  essential  mixed
cryoglobulinemia, antiglomerular  basement  membrane  antibodies  to rule out
Goodpasture's syndrome, decreased C3  and  C4  are  seen  in  SLE  associated
glomerulonephritis,          cryoblobulinemia,          membranoproliferative
glomerulonephritis  and  infections.  Dysmorphic changes of the urine RBCs as
seen under interference phase-contrast  microscopy  would suggest a glomerlar
origin.  The presence of RBC casts is compatible with  glomerulonephritis  or
vasculitis.   Patients that have a normal serology, 24 hour urine protein < 1
gram with  a  normal  glomerular  filtration  rate  should  be suspicious for
exercise  hematuria,  malginant  hypertension,  IgA   nephropathy   or   mild
glomerulonephritis.   An IVP may find cysts, masses, stones or be normal.  If
the IVP is normal with normal  shaped RBCs (non-dysmorphic RBCs) and no casts
present, cystoscopy may be done to rule out  tumors  of  the  urinary  tract,
polyps  and prostatic disease.  If pyuria ( > 4 WBCs per high power field) is
seen  on  UA  with  a  negative  culture  interstitial  nephritis  should  be
considered.  Acute  interstitial  nephritis  consists  of  skin  rash, fever,
eosinophilia  and  eosinophiluria  seen  in  association  with   antibiotics.
CHronic  interstitial  nephritis  is  found  in  association with heavy metal
intoxication, metabolic abnormalities and various drugs.  Tuberculosis should
be considered in patients with pyuria and a positive culture.

                          -HEMOCHROMATOSIS-
Hemochromatosis was initially recognized in  western Europeans over 100 years
ago and was called bronze diabetes.  It is a hereditary  autosomal  recessive
genetic  disorder,  whereby  the small intestine absorbs excessive amounts of
iron.  The cells of the duodenal mucosa regulate the dietary iron absorption.
The gene frequency is such that 1  in  20  whites carry the gene and 1 in 400
are homozygotes.  Hemochromatosis is HLA-related with linkage to  HLA-A3  and
HLA-B14 or HLA-A3 and HLA-B7.  The excessive iron is deposited as hemosiderin
in  the  liver  (causing  cirrhosis),  adrenals, Leydig's cells of the testes
(with resultant decreased  testosterone  production), pituitary (resulting in
decreased  production  of  gonadotropins),   kidneys,   synovium   (producing
arthritis),  heart  (cardiomyopathy)  and  islets  of the pancreas (producing
diabetes).  Hemochromatosis can  also  be  seen  in  sideroblastic anemia and
beta-thalassemia.  Excessive transfusions, iron injections and  the  presence
of a portacaval shunt are additional causes.  CLINICAL: Clinical presentation
is  very  often  non-specific  with weakness (83%), abdominal pain (58%), and
arthralgia (43%).  All of these symptoms are so common in the population that
the diagnosis may be over  looked  if  serum iron, transferrin saturation and
ferritin are not done.  It has been  estimated  that  approximately  5  years
elapse  between initial presentation and treatment.  Other signs and symptoms
are loss of libido or  impotence  (38%),  dyspnea on exertion (15%), diabetes
mellitus, hepatomegaly (83%), skin pigmentation  (75%),  loss  of  body  hair
(20%),  jaundice  (10%),  gynecomastia  (8%),  edema (12%), ascites (6%), and
amenorrhea (22%).  The disease is  more  common  in  males > 40 years of age,
because it takes time for deposition  of  the  hemosiderin  and  menstruation
protects  women,  just  as phlebotomy treats hemochromatosis.  There can be a
normal life expectancy if there is  no  cirrhosis, and the patient is treated
with phlebotomies.   Alcohol  will  increase  the  absorption  of  iron,  and
therefore,  alcoholics  are  commonly  affected.   Hepatomas develops in 10%.
LABORATORY: The serum ferritin  is  greater  than  300  mcg/L for men and 120
mcg/L for women.  However, there may be wide fluctuations  in  the  ferritin.
Also,  the  ferritin is an acute phase reactant, and may be elevated in other
conditions.  Probably the best test  is the serum transferrin saturation.  If
greater than 50%, then further evaluation should ensue.  If greater than  70%
then  a  diagnosis  of  hemochromatosis is fairly secure.  Serum iron is also
elevated.  The  TIBC  >60%.   The  transferrin  saturation  is  calculated by
dividing the total iron binding capacity into the serum iron concentration  x
100.   There  is also increased urinary iron and urine hemosiderin.  There is
possible hyperglycemia, decreased  FSH,  LH,  and testosterone.  Liver biopsy
should be the next step  after  the  iron  studies  suggest  hemochromatosis.
There  should  be  large  amounts  of  Prussian  blue  stainable  iron in the
periportal  areas.   The  hepatic  iron  index  [the  hepatic  iron  index is
calculated by dividing the patient's age into the hepatic iron  concentration
(micromoles/gram of dry weight)] can differentiate homozygous hemochromatosis
from  other  iron  storage  diseases.  If the hepatic iron concentration is >
than 400  umol/g  dry  weight  then  cirrhosis  is  almost certainly present.
Alcoholic  disease  is   particularly   difficult   to   differentiate   from
hemochromatosis.   However, in alcoholic liver disease, there is usually more
iron in the Kupffer  cells,  increased  fatty degeneration of the hepatocytes
and an increase of portal inflammatory infiltrates.  If there is evidence  of
cardiomyopathy,  then  an echocardiogram should be done.  CT can estimate the
liver iron load.  Alpha fetoprotein may be increased in hepatoma.  TREATMENT:
Phlebotomy of 500 ml of blood (about 250 mg of iron) once or twice weekly for
about 2-3 years to achieve iron store depletion.  The goal is a hematocrit of
around  37-39%.   When   iron   store   depletion  is  achieved,  maintenance
phlebotomies every 2-4 months are continued.  If phlebotomy is  not  feasible
or  there  is severe heart disease then consider deferoxamine .5-1 g IM daily
or subcutaneously via  pump.   Avoid  alcohol,  and  family members should be
screened.

            -HEMOLYTIC BLOOD MORPHOLOGY BY WRIGHTS STAIN-
HYPOCHROMIC, MICROCYTES, LEPTOCYTES:  Thalassemia,  Hb lepore, sideroblastic,
lead poisoning sideroblastic, iron deficiency.  (Do Hb A2 and F, Fe/TIBC,  Hb
electrophoresis,   bone   marrow,   DNA   probes.    SPHEROCYTES:  hereditary
spherocytosis,  Hb  CC,  burns  and   immune.   (Do  direct  Coombs,  osmotic
fragility,  Hb  electrophoresis).   ELLIPTOCYTES,  POIKILOCYTES:   Hereditary
pyropoikilocytosis,  hereditary  elliptocytosis, myelodysplasia.  (Do osmotic
fragility and membrane  studies).   SICKLE  CELLS:  Hb  SS,  SC,  SA.  (Do Hb
electrophoresis).   STOMATOCYTES:  Hydro-cytosis  or  xerocytosis,  Rh  null,
alcohol, liver disease.  (Do red cell Na/K and water content).  TARGET CELLS:
Hb  AC,  CC,  SC,   obstructive   jaundice,   post   splenectomy.    (Do   Hb
electrophoresis).       ACANTHOCYTES:     Pyruvate     kinase     deficiency,
abetalipoproteinemia,  liver  disease.   (Do  PK  screen  lipid  panel, LFTs.
BASOPHILIC STIPPLING: pyrimidine-5'-nucleotidase deficiency, lead  poisoning.
(Do lead screen and specialized enzyme assay.  SCHISTOCYTES: Kasabach-Merritt
syndrome,  thrombotic  thrombocytopenic  purpura,  DIC, myelodysplasia, heart
valve defects.  (Do  coagulation  tests  and  cardiac auscultation).  BLISTER
CELLS, ECCENTROCYTES: unstable Hb, G6PD deficiency, oxidant  poisoning.   (Do
G6PD screen, test for unstable Hb.  ERYTHROPHAGOCYTOSIS, CLUMPED RBC: immune.
(Do cold agglutinins, Donath-Landsteiner test, direct Coombs).

                     -HEMOLYTIC-UREMIC SYNDROME-
Hemolytic-uremic syndrome is mainly a  disease  of children 1-4 years of age.
It is characterized by prodromal findings of  abdominal  pain,  vomiting  and
diarrhea  which  is followed in about 3-10 days by a sudden onset of oliguric
acute renal failure, Coombs'  negative  microangiopathic hemolytic anemia and
thrombocytopenic purpura.  In children, it is probably the most common  cause
of  acute  renal  failure.   The exact cause of the disease is not definitely
known  but  is  probably  multifactorial  such  as  genetic,  immunologic  or
infectious.  Shigella, Salmonella, E.  coli  strain  O157:H7 and viral agents
may  be  implicated  as  causes  of  the  diarrheal  syndrome.   In   adults,
hemolytic-uremic syndrome can occur with pregnancy, renal transplantation and
metastatic  disease.   The  syndrome  in pregnancy usually occurs following a
normal pregnancy in the early  or  late  post-partum period.  Some cases have
also followed abruptio placentae, retained  placental  fragments  and  septic
abortion.   The  mortality in pregnancy-associated hemolytic anemia may reach
as high as 50% as opposed to the children's hemolytic-uremic syndrome of less
than 5%.  Post-partum hemolytic-uremic syndrome  shares the same clinical and
histologic features as the hemolytic  uremic  syndrome.   It  has  also  been
associated  with the use of oral contraceptives.  The onset is usually sudden
with acute  renal  failure,  thrombocytopenia  and microangiopathic hemolytic
anemia.   The  adult  form  may  also  occur   in   clusters   of   families.
Hemolytic-uremic   syndrome   also   has  overlap  features  with  thrombotic
thrombocytopenic  purpura.   However,   thrombotic  thrombocytopenic  purpura
differs from the hemolytic-uremic syndrome in that there is usually fever and
neurologic abnormalities.  Renal changes are mild and usually do not lead  to
renal failure and young adults are commonly affected.  CLINICAL: In children,
there is acute onset of renal failure that usually lasts about 10 days and is
then followed by recovery in about 90% of cases.  Complete renal recovery may
take  as long as 12-18 months.  In adults, the renal failure is prolonged and
more severe.  There  also  is  a  higher  incidence  of cortical necrosis and
recurrences may occur.  Oliguria is present and there may  be  bleeding  into
the  skin  and  the  gastrointestinal  tract.   Hypertension and seizures can
develop with severe renal failure  and  fluid overload.  There may be scleral
icterus, hepato-spenomegaly, and congestive heart failure.  There is a  triad
of  renal  failure,  thrombocytopenia  and microangiopathic hemolytic anemia.
Peripheral smears will show red  blood  cell fragmentation.  The anemia tends
to  be  severe.   Reticulocytes,  bilirubin,  BUN,  creatinine  and  LDH  are
elevated.   Haptoglobin  is  reduced  and  the   Coombs'test   is   negative.
Coagulation  tests  are  normal,  but here may be elevated fibrin degradation
products.  Rarely, serum  complement  may  be  decreased.  Kidney biopsy will
show intimal hyperplasia, subintimal fibrin  deposition  and  fibrin  thrombi
affecting  the  small  renal  arteries and arterioles.  There may be cortical
necrosis, but immune deposits are not present.  The differential diagnosis of
microangiopathic hemolytic anemia is important in establishing the diagnosis.
The  differential  would   include  disseminated  intravascular  coagulation,
thrombotic     thrombocytopenic     purpura,     malignant      hypertension,
glomerulonephritis,  vasculitis,  metastatic  adenocarcinoma,  and prosthetic
valve hemolysis.  Disseminated intravascular coagulation  may be ruled out by
the presence of normal coagulation studies.  In  thrombotic  thrombocytopenic
purpura,  the  renal  failure  is mild, and neurologic findings are common in
contrast to severe renal failure and  almost lack of neurological findings in
hemolytic-uremic syndrome.   Occasionally  renal  biopsy  may  be  needed  to
exclude  vasculitis  and the various types of glomerulonephritis.  TREATMENT:
In children, the treatment  is  mainly  conservative and supportive since the
disease is self limiting.  Electrolytes and fluid volume should be optimized.
Hypertension may need to be treated.  Red blood cells and platelets may  need
replacement  with  attention  to  preventing fluid overload.  Dialysis may be
needed.  Indications for dialysis  include  fluid  overload which can produce
hypertension  and  pulmonary   edema,   and   hyperkalemia   with   attendant
arrhythmias.   Peritoneal  dialysis  is  usually  the  method  of  choice but
hemodialysis may  be  used  if  the  patient  has  abdominal  signs of severe
colitis.  Treatment in adults may consist of plasmapheresis with  or  without
steroids.   Captopril  may  be  used to treat the hypertension as well as the
renal component.

                            -HEMOPHILIA A-
Hemophilia A (classic hemophilia or factor VIII deficiency hemophilia) is due
to a deficiency of the  coagulation  factor VIII (VIII:C), and is transmitted
as  a  X-linked  recessive  inheritance  pattern.   This  means  that  if   a
hemophiliac male has children from a normal female, all of the daughters will
be  carriers  and  all  of  the  sons will be normal.  On the other hand if a
normal male has children  from  a  female  carrier,  each  daughter has a 50%
chance of being a carrier and each son has a 50% chance of having hemophilia.
Rarely, female carriers are clinically affected if their normal X chromosomes
are disproportionately inactivated.  Most of the cases of hemophilia  A  will
have  a  quantitative  reduction of the factor VIII, but in a small number of
cases the factor VIII protein will  be present by immunoassay, but defective.
Hemophilia A accounts for 85% of the cases of hemophilia.  The remaining  15%
are  accounted  for  by  hemophilia  B  or factor IX deficiency.  The overall
prevalence of hemophilia is 20/100,00 males.  Hemophilia A is the most common
congenital bleeding disorder  after  von  Willebrand's  disease  and the most
common severe bleeding disease.  CLINICAL: At birth there is no bleeding, but
about 50% of males will bleed at the time of circumcision, and bleeding  will
occur  in  3/4  of  severely  affected  infants by the age of 18 months.  The
bleeding  tendency  is  related  to  the  levels  of  factor  VIII:C.  Severe
hemophiliacs have less than 1% factor VIII and will present  clinically  with
hemarthroses, subcutaneous hematomas in the tongue and neck, hematomas in the
GU  and  GI  tract.  The most common sites of bleeding are into joints of the
knees, elbows,  ankles,  shoulders,  hips  and  wrists  (descending  order of
frequency), muscles and the GI  tract.   Spontaneous  hemarthroses  are  very
characteristic   of   the   disease.   Each  time  a  patient  experiences  a
hemarthrosis, hypertrophic and inflammatory changes  occur in the joint which
will eventually lead to erosion of the cartilage and bone.  Eventually,  bone
cysts  will  develop which can communicate with the joint space.  Ultimately,
the joint becomes unstable with  development  of  bony ankylosis of the large
joints and complete destruction  of  the  smaller  joints.   Central  nervous
system  hemorrhage  is  rare  during the newborn period, but a few cases have
been  reported.   Large   hematomas   may  follow  intramuscular  injections.
Hematomas can develop in the retropharyngeal and retroperitoneal spaces.  The
femoral nerve can be compressed by  hemorrhage  and  hematomas.   Very  small
lacerations  can  bleed  for  days, especially if the laceration involves the
oral mucosa.  Muscular bleeding usually begins by 3-4 years of age.  Patients
that are characterized as moderate hemophilia usually have 1-5% of the normal
factor VIII levels.   They  may  occasionally  have spontaneous bleeding, but
bleeding is more commonly associated  with  some  mild  to  moderate  trauma.
Patients  that  are  classified as mild hemophiliacs have 5-25% of the normal
levels of factor VIII, and usually  do  not bleed unless there is moderate to
severe trauma.  However, they may bleed heavily or fatally after  surgery  or
after  dental  extractions  unless  the  factor is replaced prior to surgery.
Mild hemophiliacs may not be  diagnosed  until late childhood, adolescence or
sometimes adulthood.  These patients may have a mild prolongation of the  PTT
which  is  routinely  obtained  prior  to surgery.  High risk female carriers
usually have 30-50% of  the  normal  factor  VIII  level and may bleed during
obstetrical  or  gynecologic  procedures.   About  5-20%  of  patients   with
hemophilia  A  will  develop IgG antibodies (inhibitors) directed against the
functional activity of  factors.   These  antibodies  will destroy any factor
concentrate that is infused, by binding and inactivating the  coagulant  site
on  factor  VIII.   However, in patients with the presence of inhibitors, the
incidence of severe bleeding  is  not  increased.   If  the  inhibitor is < 3
Bethesda units/mL, then treat with higher doses of replacement  therapy.   If
the value is higher than 10 Bethesda units you can attempt to use prothrombin
complex  concentrates  (II,  VII,  IX,  X) (anti-inhibitor coagulant complex,
Feiba  VH,  Autoplex.   Many  patients  that  have  been  exposed  to  factor
concentrates from 1981-1985 have developed the HIV virus.  Since 1985 the use
of virally inactivated, donor  screened  products  have eliminated this risk,
and most factor VIII concentrates now are free of  HIV  and  hepatitis.   HIV
associated  immune thrombocytopenia can aggravate the bleeding in hemophiliac
patients.  LABORATORY: The PTT is  prolonged,  but the PT, bleeding time, and
fibrinogen levels are all normal.  To test for a factor  VIII  inhibitor  the
hemophiliac  plasma  should  be  mixed  with  normal  plasma.   Under  normal
circumstances,  this  will  normalize  the  PTT.  However, if the patient has
developed an inhibitor, the  PTT  will  not  normalize.  Any patient that has
thrombocytopenia  with  hemophilia  A  should  be   investigated   for   HIV.
DIFFERENTIAL  DIAGNOSIS:  Acquired  factor  VIII  deficiency states can occur
idiopathically, post partum, from collagen vascular diseases (SLE, rheumatoid
arthritis,  and  temporal  arteritis),  drug  hypersensitivity (sulfonamides,
penicillin),   old    age,    and    malignancies    (solid    tumors,    and
lymphoproliferative).    The  main  differential  is  with  von  Willebrand's
disease.  This can be  done  by  testing  for  factor  VIII:RA assay.  In von
Willebrand's disease factor VIII:RA is decreased as is  ristocetin  cofactor.
Also  the  bleeding time is usually prolonged in von Willebrand's disease and
normal  in  hemophilia.   TREATMENT:   Treatment   consists  of  factor  VIII
replacement by infusion of  factor  VIII  concentrates  prepared  from  human
plasma  or  by  recombinant techniques.  Each bottle of concentrate will have
the amount of factor VIII it  contains.  The general rule for calculating the
amount needed is to assume that 1 unit of factor VIII/kg of body weight  will
raise  the  recipient's  factor VIII by 2% (.02 units/ml).  For example, if a
severe hemophiliac has a factor level <  1% giving 20 units of factor VIII/kg
would raise the factor VIII level to 40 % (.40 units/ml).  The half  life  of
factor  VIII  is 8-12.  For acute early hemarthrosis, the dose of factor VIII
concentrate is 10 U/kg and  repeat  injection  is seldom necessary.  For late
painful hemarthrosis with limitation of motion, 20 U/kg is  given  initially,
with  20  units/kg  given  every  12  hours.   Hemarthrosis should be treated
immediately.  Failure to  treat  will  result  in progressive disabling joint
disease.  Most hemophiliacs have a "feel" for  early  joint  bleeding.   They
describe  this as a tingling or minimal discomfort before the actual swelling
and pain develop.  This is when  the factor VIII concentrate should be given.
Some patients will have repeated bleeding into the same joint.  This  may  be
treated  by  giving  every other day factor VIII concentrate for at least one
month to interrupt the cycle.   Joint  aspiration is rarely needed and should
only be done in cases with severe pain.  Splinting and rest of  the  involved
joint  is important.  Patients with elbow hemorrhage should be treated with a
sling.  Severe knee bleeds should  be  treated  with a splint.  Early treated
joint bleeding with factor VIII may not  require  a  splint.   Immobilization
should not be for more than a few days in order to prevent atrophy.  Physical
therapy  with isometric exercises is important in order to prevent atrophy of
the quadriceps.  Ice packs  may  be  used.  For intramuscular hemorrhage give
20-30 U/kg and repeat q12h for several days.  The  factor  VIII  concentrates
should  be  given  until  the  muscle  mass begins to soften and the pain has
disappeared.  Iliopsoas hemorrhage will present with vague pain in the groin,
and pain on flexion and extension  of the thigh.  If the iliopsoas hemorrhage
is severe the kidney and ureter can be displaced along  with  compression  of
the  femoral  nerve  and  the  development  of  anemia.  For life threatening
intracranial  hemorrhage,  major  surgery  and  major  trauma,  give  50 U/kg
initially, then 30 U/kg every 12 hours or by continuous  infusion.   Patients
requiring  surgery  should be checked for inhibitors.  The concentrate should
be started 60 minutes prior to  surgery.  After the initial bolus, the factor
VIII is preferably given by continuous infusion at 3 units/kg/hour to achieve
a factor VIII level of 50%.  This should be continued for 7-10 days following
surgery for major surgery.  Some orthopedic procedures may need to be treated
for  4-6  weeks.   Following  discharge,  if  the  patient  still  needs  the
concentrate, IV boluses can be given q12 hours.  For tongue or neck  bleeding
give  40-50  U/kg  initially,  then  20-25  U/kg  q12h.  For tongue and mouth
lacerations given 20 U/kg initially  then  20 units/kg q12h.  To prevent clot
lysis, epsilon  aminocaproic  acid  (EACA)  is  given  at  75  mg/kg  q6h  or
tranexamic  acid  25  mg/kg  q8h for 7-10 days, or until healing is complete.
Most lacerations in the mouth  occur  in  the small children.  These patients
should be hospitilized and treated with sedation, IVs, and nothing by  mouth.
Tongue  lacerations  may  require 3-5 days of therapy in the hospital.  Older
patients and adults may be treated as outpatients.  For severe abdominal pain
30-40 U/kg is given initially,  then  20-25 units/kg q12h.  For extraction of
permanent teeth 20 U/kg is given initially,  followed  by  20  U/kg  q12h  as
necessary  to  stop bleeding.  EACA or tranexamic acid is also given starting
the day before the extraction  and  is  continued for 7-10 days.  Spontaneous
gross hematuria that is painless does not require  factor  VIII  concentrate,
but   other   causes   for   the  hematuria  should  be  ruled  out  such  as
glomerulonephritis.  The patient  is  usually  given  extra  fluids until the
hematuria stops, usually within 7 days.  If it persists for longer,  clotting
factor  concentrate  can be given for 1-2 doses.  EACA should not be given as
clots may occur  at  the  ureteropelvic  junction.   Trauma induced hematuria
requires factor concentrate.  Mild hemophiliacs  may  also  be  treated  with
desmopressin  acetate  (DDAVP) 0.3 ug/kg q24h.  this can be helpful for minor
surgical procedures.  Desmopressin acts by releasing factor VIII:C which will
rasie the level 2-3 fold for  several hours.  Most hemophiliac children > 3-4
years can be treated at home by the parents.  The families are  given  factor
concentrates  that are stored in the refirgerator.  Since multiple donors are
required to make a concentrate,  all  children  may be at risk for hepatitis.
In 1987 more than 60% of hemophiliacs > 10 years  of  age  in  the  USA  were
positive  for  HIV.  Cryoprecipitate carries less risk for hepatitis and AIDS
as it is a single donor component, but is unsuitable for home administration.
TREATMENT OF PATIENTS WITH INHIBITORS:  About 15% of patients with Hemophilia
A will develop inhibitors against factor VIII.  Most of these will develop in
childhood.  Some of these may be low titer inhibitors (<5 units/ml) in  which
case  there  is no problem, and most patients will respond to the factor VIII
concentrates.  However, if  high  titers  develop,  the  bleeding episodes no
longer will respond to factor VIII concentrates.   Most  patients  with  high
titer  inhibitors  are  treated  with  either standard or activated factor IX
complex concentrates (Proplex)(PCC)  at  a  dose  of  75  factor IX units/kg.
These contain variable amounts of prothrombin, as well as activated forms  of
factors VII, IX, and X. Although, this is effective in acute hemarthroses and
early  intramuscular bleeding or soft tissue bleeding, it is not as effective
as factor VIII in a  hemophiliac  without  an  inhibitor.  Since PCC has been
associated with myocardial infarction in young patients between the  ages  of
15-22  years  of age, PCC should not be used if the patient has not responded
after  3  or  4  doses  of  PCC.   There  have  been  reports  of  thrombotic
complications in patients receiving proplex,  although most of these patients
have had liver disease.  Hyate: C, a purified porcine factor VIII concentrate
can be used in patients with high titer inhibitor, but occasionally can cause
anaphylaxis.   For  this  reason,  it  is  usually  only  used  for   serious
hemorrhagic  events  such as acute surgical emergencies, cerebral trauma, and
other life threatening situations, for which  it is very effective.  The dose
is 50-100 units/kg initially with future doses depending upon the factor VIII
level.  While Hyate:C is being used, the platelets  should  be  monitored  as
thrombocytopenia has been an uncommon side effect.

                             -HEMOPTYSIS-
Hemoptysis can be divided into mild, moderate or severe.  Mild is < 20  ml/24
hours,  moderate  is  20-200  ml/24  hours, and severe hemoptysis is 200-1000
ml/24 hours.  Bleeding from the  lung  can  come from the bronichial arterial
circulation or the pulmonary arteries.  Bleeding  is  more  common  from  the
bronchial arteries.  The bronchial circulation is a high pressure system that
provides  about  5%  of the blood to the lungs and originates from the aorta.
The pulmonary artery and its branches  is a low pressure system, constituting
95% of the pulmonary circulation.  Most cases  of  hemoptysis  are  not  life
threatening.    For  example,  inflammation  accounts  for  about  80-90%  of
hemoptysis, with acute or  chronic  bronchitis  being  the most common cause.
Hemoptysis must be differentiated from hematemesis or from blood  originating
in  the nose, mouth or nasopharynx.  Hemorrhage can be classified as follows:
HEMOSTATIC DEFECTS: DIC, thrombocytopenia,  vitmain  K dependent factors (II,
VII, IX, X), heparin therapy, urokinase, streptokinase and other fibrinolytic
therapy.  LUNG PARENCHYMA: pulmonary  infarct,  abscess,  pneumonia,  trauma,
primary  or  metastatic tumor, granulomatous disease (TB, fungus, parasitic),
aspergillus fungus balls,  idiopathic  hemosiderosis, Goodpasture's syndrome,
pulmonary vasculitis.  BRONCHIAL: aortic aneurysm erosion, bronchogenic cyst,
carcinomas  and  adenomas,  broncholithiasis,   erosions   secondary   to   a
caseous-calcific  node, bronchitis, trauma, bronchiecctasis, bronchopulmonary
sequestration.   CARDIOVASCULAR:  Mitral  stenosis,  pulmonary  embolism  and
infarct, left  ventricular  failure,  primary  pulmonary hypertension, atrial
myxoma,  pulmonary  arteriovenous  malformation,  aortic  aneurysms,   fibous
mediastinitis  and  pulmonary vein obstruction, pulmonary artery rupture from
Swan Ganz  catheter,  hereditary  hemorrhagic  telangiectasia,  and pulmonary
artery aneurysm.  Massive hemoptysis (> 600 ml/24 hours) is  usually  due  to
TB,  lung  abscess,  cancer,  bronchiectasis,  fungal  pneumonia,  rupture of
pulmonary artery  by  pulmonary  artery  catheter  balloon.   LABORATORY: The
sputum should be examined for acid fast organisms, malignant cells, bacteria,
and leukocytes.  CBC with differential  is  indicated.   Coagulation  studies
(platelets,  PT,  PTT) should be carried out along with arterial blood gases.
If pulmonary embolism is suspected  the  patient  should have a lung scan and
pulmonary  angiogram.    Pulmonary   angiography   can   also   diagnose   an
arteriovenous   fistula.    Aortography,   CT,   MRI,   and   transesophageal
echocardiograpy   can   demonstrate   an   aortic   aneurysm.   Bronchoscopic
examination  is  crucial.   This   is   usually  accomplished  with  a  rigid
bronchoscope if the bleeding  is  massive.   Bronchial  arterography  can  be
useful for localization of bleeding and bronchial artery embolization.  Chest
x-rays  and  CT of the chest may show cavities, infiltrates, and atelectasis.
The  cavities  are  often  bilateral,  multiple  and  involve  several lobes.
Cavities may be seen in TB, fungal  infections,  and  necrotizing  pneumonia.
Mycetomas  may  also  be  seen.  TREATMENT: 	Patients should be at bedrest
with the suspected side of  bleeding  dependent,  in order to keep unaffected
areas from accumulating blood.  Cough suppresants as codeine should  be  used
judiciously.   If  clotting abnormalites are present they can be treated with
appropriate transufusions such as fresh  frozen plasma, platelets and vitamin
K. Antibiotics may be given (penicillin or clindamycin) if there is suspicion
for bacterial abscess.  Suspected TB  should  be  started  with  at  least  2
effective drugs as isoniazid and rifampin.  Bronchial artery embolization may
be  used if the patient is not a suitable candidate for lung resection and/or
ligation.  Broncholithiasis, bronchial  adenoma  and  cancer are treated with
pulmonary resection.  Hemoptysis secondary to mitral stenosis may respond  to
treatment  for left ventricular failure or mitral valvulotomy.  Most cases of
pulmonary emboli will stop spontaneously.

                     -HENOCH-SCHONLEIN PURPURA-
Henoch-Schonlein  (HS)  is  also  known  as  anaphylactoid  purpura.   It  is
primarily a disease of children, but can also  be  seen  in  adults.   It  is
considered  to  be a vasculitis that attacks the small vessels of the kidney,
gastrointestinal tract, and joints.  If  biopsy  is  done from a skin lesion,
fibrinoid  necrosis  of  the  vessel  walls   will   be   seen   along   with
polymorphonuclear  leukocyte  perivascular cuffing of the vessels.  Biopsy of
the kidney will reveal  deposition  of  IgA.   The  typical renal lesion is a
focal  segmental  proliferative  glomerulonephritis.   Serum  complement   is
normal.  The causes of HS may be beta hemolytic streptococci, drugs, viruses,
foods,  insect bites or other bacteria.  An acute respiratory infection often
precedes the purpura.  Immune complexes  of  IgA  with complement, IgG or IgM
may be found in the serum.  CLINICAL: This disorder usually presents  acutely
in children with purpura and petechiae of various sizes.  At the beginning of
the disease the rash may be urticarial, or maculo-papular which then develops
into  a  palpable  purpura  involving  the  extensor  surfaces of the ankles,
buttocks, feet and elbows  primarily.   The  rash  typically  is on the lower
extremities initially, but may spread to the entire body.   New  lesions  may
continue to develop for up to one month in some cases.  There may be edema of
the hands, feet, periorbital areas and scalp.  In about 66% of patients there
is  a  migrating  polyarthralgia  or  arthritis with periarticular tenderness
affecting the knees, ankles, wrist, elbows  and  hips.  In 50% of cases there
is a colicky abdominal pain which is caused by edema and  hemorrhage  of  the
small  intestine  which  may  go  on to intussusception.  There is associated
abdominal tenderness.  Up to  50%  of  patients  will have involvement of the
kidney with hematuria  or  proteinuria.   Occasionally,  this  will  lead  to
nephrotic  syndrome.   The  hematuria is typically seen in the second week of
illness and is more common  in  older  and male patients.  Most patients will
have fever.  Rarely, testicular torsion occurs.  The disease usually  runs  a
course  over  about  one month with disease free intervals.  It is common for
the disease to recur one or  more  times after the original episode subsides.
In the majority of the patients there is no serious sequelae, but  the  renal
disease,  in  a few, will progress to chronic renal failure.  In these cases,
kidney biopsy will usually demonstrate  a diffuse glomerular involvement with
crescentic changes.  LABORATORY: The platelets, bleeding  time  and  platelet
function  tests  are typically normal.  The urinalysis may show hematuria and
proteinuria.  Stool specimens  may  reveal  occult  blood.   The  ASOT may be
elevated  and  a  throat  culture  may  grow  out  group   A   beta-hemolytic
streptococci.   The  Serum  IgA  also can be elevated.  Anemia is rare unless
there has been gross GI bleeding.   In  the  acute phase of the disease there
may be a moderate polymorphonuclear leukocytosis.  COMPLICATIONS:  About  15%
of  patients with Henoch-Schonlein purpura will develop renal failure with an
attendant mortality of 3%.  Nephrotic syndrome will complicate the disease in
a few patients.  Intussusception of  the  small  intestine may also occur and
may resemble acute appendicitis.   Convulsions  may  rarely  develop  due  to
cerebral  edema.   Respiratory  failure  can also develop due to edema of the
glottis.  DIFFERENTIAL  DIAGNOSIS:  The  rash  of  HS  may  resemble  that of
meningococcemia, but the rash is usually much  more  wide  spread  in  septic
meningococcemia.   Blood  cultures  will  help  to  sort  out  the diagnosis.
Thrombocytopenic purpura can easily be  differentiated from HS because of the
low platelet count  in  thrombocytopenic  purpura  and  the  rash  of  HS  is
palpable.   Berger's  IgA nephropathy must be ruled out, but usually presents
no difficulty because Berger's IgA nephropathy has no extra-renal symptoms as
polyarthralgias, or abdominal pain.  Child abuse may simulate HS disease with
joint pains, hematuria and  abominal  pain.   TREATMENT: There is no definite
treatment for anaphylactoid purpura.  If the throat culture  and/or  the  ASO
titer  are  positive for group A beta-hemolytic streptocci, penicillin should
be initiated for 10 days of therapy.   Prednisone  given at a dose of 2 mg/kg
up to a total of 50 mg/day may be offered if there is severe abdominal  pain,
edema  or  joint  pain.   Steroids have no effect in preventing or curing the
renal lesions.

                              -HEPARIN-
Heparin, in order to function as an anticoagulant, needs  a  cofactor.   This
cofactor  is  antithrombin  III.   Heparin  binds  to  the  lysine protion of
antithrombin III and changes  antithrombin  III  from  a  slow inhibitor to a
rapid inhibitor of  thrombin.   The  heparin/antithrombin  III  complex  then
inactivates thrombin and factor X. The primary function of this complex is to
inhibit  the  thrombin induced activation of factor V and VIII.  Heparin also
can function to inhibit platelet  function.   Heparin  has  a half life of 60
minutes after  a  75  U/kg  IV  bolus  has  been  given.   Heparin  causes  a
thrombocytopenia  in  about  4%  of cases.  Any patient receiving heparin for
more than  3  days  should  have  platelet  monitoring.   Other side effects,
include osteoporosis that usually occurs  after  5  months  of  therapy,  and
alopecia.    If   the   patient  is  receiving  high  dose  IV  nitroglycerin
concurrently, the heparin dose may  have  to  be  increased because of a drug
interaction.  TREATMENT DOSE: In general, the patient is given an IV bolus of
5,000-7,500 U (100 U/kg) as an IV bolus, followed by a continuous infusion of
15-25 U/kg/hour.  This infusion preparation is prepared by adding 20,000 U of
heparin to 500 ml of D5W.  The drip rate in ml/hr can then be  calculated  by
the  following  scheme.  Patients that require 840 U/hour are given 21 ml/hr,
1000 U/hour are given 25 ml/hr,  1120  Units/hr are given 28 ml/hr, 1200 U/hr
are given 30 ml/hr, 1280 U/hr are given 32  U/hr,  1360  U/hr  are  given  34
ml/hr,  1440 U/hr are given 36 ml/hr, 1520 U/hr are given 38 ml/hr, 1600 U/hr
are given 40 ml/hr, 1680  U/hr  are  given  42  ml/hr, 1760 U/hr are given 44
ml/hr, 1840 U/hr are given 46 ml/hr, 1920 U/hr are given 48 ml/hr,  and  2000
U/hr are given 50 ml/hr.  For example, a patient that weighs 70 kg, using the
formula  20  U/kg/hr,  would have a drip rate of about 1400 U/hr, or about 36
ml/hr, if the concentration of 20,000 units  of  heparin per 500 ml of D5W is
used.  The PTT should be monitored 6 hours after the bolus injection and then
adjusted to keep the PTT at 1.5-2.5 times the  mean  control  (usually  60-85
seconds).   If  the PTT is less than 50, another heparin bolus of 5,000 Units
is given and the drip rate is increased  by  5 ml/hour.  If the 6 hour PTT is
50-59, increase the rate by 3 ml/h and repeat the PTT in 6 hours.  If the PTT
is 60-85, no change in the infusion rate is needed, and  the  PTT  should  be
repeated  in the AM.  If the PTT is 86-95, decrease the rate by 2 ml/hour and
repeat the PTT the following AM.   If  the PTT is 96-120, the infusion should
be held for 30 minutes, and then decrease the rate 2 ml/lhour, and repeat the
PTT in 6 hours.  If the PTT is greater than 120, the heparin is  held  for  1
hour, and the infusion rate is decreased by 4 ml/hour and the PTT repeated in
6 hours.

               -HEPATITIS (Chronic active autoimmune)-
The  diagnosis  may be suggested by an acute and recurrent hepatitis pattern,
OR an occult liver disease that  is asymptomatic, but with extrahepatic signs
and symptoms.  Chronic active autoimmune hepatitis is usually  a  disease  of
young  people  with  a female predominance.  Common extrahepatic associations
include skin rashes, polyarthritis and ulcerative colitis.  Renal involvement
and cerebritis  are  not  common.   CLINICAL:  ACUTE  AND RECURRENT HEPATITIS
PATTERN: An acute attack of hepatitis presents as the initial presentation of
this disease in about 25% of cases.  There is malaise,  fatigue,  dark  urine
and  icterus.  There also may be arthralgias and skin rashes.  There may be a
striking fever which  is  unusual  in  viral  hepatitis, unless the hepatitis
presents as a  fulminant  hepatitis.   The  chemical  profile  of  autoimmune
hepatitis  parallels  viral  hepatitis.  The bilirubin is elevated in various
degrees depending on the severity of the disease, and the presence or absence
of an associated hemolytic anemia.   20%  are  anicteric.  The AST is usually
greater than 500 u/ml.  The prothrombin time is usually normal, unless  there
is  severe  injury.  There is a polyclonal hypergammaglobulinemia with values
greater than 3 g/dl being common.   The alkaline phosphatase is elevated, but
not high.   The  patient  usually  does  well  initially,  and  seems  to  be
recovering  when  there  is  a  reoccurrence  of  symptoms and chemical liver
abnormalities.  This sequence of recurrent  hepatitis may be repeated several
times with varying  time  intervals  of  weeks  to  months.   Sometimes,  the
chemical  profile  returns  completely  to  normal.   Finally,  over  time, a
subacute  and  chronic  course  will  follow.   ASYMPTOMATIC  LIVER  PATTERN:
Clinically, the patient may be  asymptomatic  for  liver disease, and this is
the most common type of presentation.  If the  patient  has  no  extrahepatic
manifestations  of  chronic  active  autoimmune  hepatitis, then the abnormal
liver chemical profile  may  be  found  accidentally  by  routine blood work.
Liver biopsy at this point may point to the disease.  ARTHRITIS: Usually  the
wrists,  hands,  knees and ankles are involved in about 20-30% of cases.  The
polyarthritis episodes may be associated  with skin reactions and fever which
may coincide with relapses  of  liver  disease.   The  arthritis  is  usually
non-erosive.   SKIN DISEASE: Many types of rashes have been described.  There
may be maculopapular  rashes,  erythema  nodosum,  ulcers  around the ankles,
alopecia, palpable purpura, pigmentation  and  photosensitivity.   The  malar
rash  of  SLE  does  occur  but  is rare.  It is interesting to note that the
maculopapular rashes  often  coincide  with  exacerbations  of liver disease.
ULCERATIVE COLITIS: Ulcerative colitis  is  associated  with  chronic  active
autoimmune  hepatitis  in about 10-20% of cases, but there is no relationship
between flares of ulcerative colitis  and  flares of liver disease.  Usually,
the patients are asymptomatic as far as liver  disease,  and  abnormal  liver
tests  are  only  found  with  routine blood work performed for an ulcerative
colitis workup HEMATOLOGIC DISEASE: A coombs positive hemolytic anemia can be
part of chronic autoimmune  hepatitis.   There  also may be thrombocytopenia,
leukopenia and anemia.  There may be  an  iron  deficiency  anemia  from  the
ulcerative colitis.  RENAL DISEASE: Renal disease is distinctly uncommon, but
when  present  there  may be two types of renal disease.  The first group may
have  membranous  or  membrano-proliferative  glomerulonephritis,  which  may
present as the nephrotic syndrome  or  mild chronic renal insufficiency.  The
second type of renal disease is renal tubular acidosis  and  an  interstitial
nephritis.   PULMONARY DISEASE: Some patients may have pleuritis with pleural
effusion.  Others will develop  interstitial pulmonary fibrosis which usually
develops years after the onset of the liver disease.  It is  usually  steroid
resistant.   Pulmonary  function  shows  restrictive  lung  disease.   X-rays
commonly   involve  the  lower  lobes  with  a  reticulo-nodular  infiltrate.
Pulmonary hypertension may follow.  ENDOCRINE  DISEASE: Some young women will
present with a picture not unlike  that  of  Cushing's  syndrome.   There  is
amenorrhea,  hirsutism,  acne,  purple  abdominal striae and truncal obesity.
This  may  be  independent  of  steroid  treatment  for  the  liver  disease.
LABORATORY: There are several serological markers that may be associated with
chronic active autoimmune hepatitis.   A  common  finding is elevation of the
gamma globulin.  The levels may be as high as 6-7 grams.   The  elevation  is
polyclonal  and the IgG is most affected.  Most series report an elevation of
ANA in about  50-90%.   The  pattern  is  usually  speckled or diffuse.  Anti
double stranded DNA is almost always  negative.   There  may  be  a  positive
anti-smooth  muscle  antibody  which  is  usually  present in about 20-30% of
cases.  This is a non-specific  finding  as  this  antibody is present in low
titer in many liver diseases.  The  anti-mitochondrial  antibody  is  usually
associated  with  primary  biliary cirrhosis where the antibody is present in
greater than  90%.   About  20-30%  of  chronic  active  autoimmune hepatitis
patients will have a positive  anti-mitochondrial  antibody  present.   Other
serological  markers  that  may  be  present,  but  non-diagnostic,  are  the
rheumatoid factor, positive Coombs test, depressed complement and circulating
immune  complexes.   DIFFERENTIAL  DIAGNOSIS:  SYSTEMIC  LUPUS ERYTHEMATOSUS:
Significant liver disease usually doesn't occur with SLE and if a patient has
elevated liver tests, then chronic  autoimmune hepatitis is much more likely.
Other symptoms, however, are shared  between  the  two  diseases  as  rashes,
photosensitivity,  non-erosive  arthritis,  serositis, proteinuria, seizures,
thrombocytopenia, hemolytic anemia, leukopenia, anemia and positive ANA.  The
frequency of involvement  does  vary  between  the  two  diseases.  Renal and
neurologic symptoms are not prevalent in autoimmune hepatitis.  About 50%  of
SLE  patients  have positive anti- double stranded DNA antibodies, as opposed
to autoimmune  hepatitis  in  which  it  is  rare.   SLE  patients  will have
immunoglobulin deposition at the dermal-epidermal junction in about 50%,  and
only  about 10-15% in chronic autoimmune hepatitis.  Smooth muscle antibodies
are not seen in SLE, but there is a fairly high incidence in autoimmune liver
disease.  CHRONIC DRUG INDUCED  HEPATITIS:  Several  drugs  may be capable of
causing liver changes and a patient's medications should all be checked  when
there  is  evidence  of  liver disease either, overtly, or accidentally found
with blood  work.   Aldomet  is  notorious  as  an  offender.   CHRONIC VIRAL
HEPATITIS: The chemical, clinical, radiographic and  histologic  features  of
chronic  active  autoimmune  disease  may not be separated from chronic viral
hepatitis due to Hepatitis B, (either  alone or in combination with the Delta
virus), or Hepatitis C (non-A, non-B type).  The  distinction  between  these
may  depend  upon  extrahepatic  features,  serological  markers,  as ANA and
hepatitis  serology.    Chronic   active   autoimmune   hepatitis  is  always
progressive if not treated, whereas chronic viral hepatitis is  usually  more
benign  and  doesn't  progress as frequently to cirrhosis.  WILSON'S DISEASE:
Any young person that has  acute  or  chronic  liver disease with a hemolytic
component and  neurologic  features  should  arouse  suspicion  for  Wilson's
disease.   PRIMARY  BILIARY CIRRHOSIS: This disease, if typical, should cause
no confusion.  Typically, there  is  pruritus  and  elevation of the alkaline
phosphatase  in  a  middle  aged  female.   In  addition,  there  may  be   a
keratoconjunctivitis  sicca, hyperpigmentation, steatorrhea or xanthomatosis.
There is a high titer of  anti-mitochondrial antibody and biopsy of the liver
will show  the  destructive  necrotizing  interlobular  cholangitic  lesions.
However,  about  30%  of  patients with primary biliary cirrhosis will have a
positive ANA, and a  few  will  have  a  smooth  muscle antibody.  COURSE AND
PROGNOSIS: Chronic active autoimmune hepatitis is a progressive disease  that
will  progress  to  cirrhosis  within  2  years if treatment is not rendered.
Death may be from  several  associated  situations  such as hemolytic anemia,
ulcerative colitis, pulmonary hypertension, complications of drug  treatment,
liver  failure  as  variceal hemorrhage, infections and ascites.  If patients
are treated early with steroids when they have acute hepatitis, the prognosis
seems to  be  better.   Many  patients,  however,  have  silent liver disease
clinically which progresses without symptoms until significant damage occurs.
TREATMENT: Most cases of chronic active autoimmune hepatitis will respond  to
Prednisone 60 mg or less.  It is rare to increase the Prednisone beyond 60 mg
per  day.   The aim is to reduce the Prednisone to a level that will suppress
liver activity and  thus  suppress  collagenous  repair,  and  to achieve the
lowest possible dose to avert the well-known side affects of steroids.   This
may be impossible.  If high doses of prednisone are needed, then Azathioprine
may  be  added  so  the prednisone dose can be reduced.  A common scheme that
sometimes gives therapeutic  efficacy  with  few  side  effects is Prednisone
10-15 mg per day and azathioprine 50 mg per day.

             -HEPATITIS (Chronic persistent hepatitis)-
CLINICAL: The onset is not unlike that of acute  vital  hepaitis  and  occurs
over   1-2   weeks.    There   may   be  abdominal  pain,  low  grade  fever,
hepatosplenomegaly, mild  constitutional  symptoms.  Extrahepatic involvement
and jaundice are rare.  LAB: The  SGOT,  SGPT  range  from  40-200  IU.   The
bilirubin  is  <  3  mg/100  ml.  The PT and albumin are usually normal.  The
antinuclear antibodies and smooth  muscle  antibodies,  which are positive in
chronic  active  hepatitis,  are  rarely  positive  in   chronic   persistent
hepatitis.  Serum immunoglobulins are normal or slightly elevated.  The HBsAg
is positive in 10-30% of patients.  Liver biopsy demonstrates mild periportal
inflammation,  maintenance of lobular architecture, and very little fibrosis.
No therapy is required  as  the  course  is  not  progressive and there is no
increased mortality.

                      -HEPATITIS (Autoimmune)-
Lupoid   hepatitis   is   now  known  as  type  1  autoimmune  hepatitis  and
demonstration of the LE cell phenomenon  is no longer required for diagnosis.
The presence of smooth muscle antibodies  (SMA)  and  antinuclear  antibodies
(ANA)  in the absence of serologic evidence of viral infection, drug induced,
or other  explanations,  is  sufficient  for  the  diagnosis.   Antibodies to
F-actin are specific for the diagnosis.  Autoimmune hepatitis (AH)  typically
involves   women   in   71%   of   all   patients.    Is   characterized   by
hypergammaglobulinemia,  periportal  hepatitis (piecemeal necrosis) and a 17%
concurrence of extrahepatic immunologic  disorders.   The disease responds to
prednisone alone or in  combination  with  azathioprine,  inducing  clinical,
biochemical  and  histologic  remission  in  70%  of  patients after 2 yrs of
treatment.  If there is  no  cirrhosis  at  presentation life expectancies of
5-10 years will exceed 90%, while patients  with  cirrhosis  at  presentation
have  a  5  year  life  expectancy of 80% and a 10 yr life expectancy of 65%.
TREATMENT is prednisone 10 mg/d + azathioprine 50 mg/d if azathioprine is not
contraindicated by cytopenia, malignancy  or  pregnancy.  Prednisone alone at
20 mg/d is equally effective but  associated  with  more  drug  related  side
effects.   Prednisone  alone  is useful for a short trial of treatment of 3-6
months and in  young  women  considering  pregnancy.   Treatment is continued
until remission,  drug  toxicity,  or  lack  of  remission  after  protracted
therapy, or deterioration despite complaince with treatment.

         -HEPATITIS (Differential Diagnosis by Lab testing)-
Hemochromotosis    (serum    iron,    TIBC,   ferritin),   Wilson's   disease
(ceruloplasmin, urine and serum copper, hepatic copper concentration), Alpha1
antitrypsin  deficiency  (alpha1-antitrypsin),  Hepatitis  B  (HBsAG,  HBeAg,
anti-HBc) Hepatitis C (Anti-HCV),  Autoimmune  chronic active hepatitis (ANA,
anti-smooth muscle antibody), Primary  biliary  cirrhosis  (anti-mitochondral
antibody).

                        -HEPATITIS OVERVIEW-
PREVENTION OF VIRAL HEPATITIS: HEPATITIS A.....Immune serum globulin (ISG) is
effective in preventing or attenuating disease in those who have already been
exposed.  Use 0.02 ml/kg IM within 2 weeks of exposure.  It is  effective  in
80-90%  in  preventing or attenuating disease in those already exposed.  Give
to close personal contacts  but  not  school  contacts unless an outbreak has
occurred.  All exposed to common source such as well water, shell fish should
be immunized.  HEPATITIS B.....Passive  immunization  with  hepatitis  immune
globulin (HBIG) is effective in preventing hepatitis B. It is used for needle
stick exposure and sexual contacts of infected persons and newborn infants of
infected women.  Dose is 5.0 ml IM for adults.  Use .5 ml in neonates.  Prior
to administration of HBIG the recipient may be tested for HBsAg and anti-HBs.
If  either is positive, immunization with HBIG is not necessary.  HEPATITIS B
VACCINE...Is given as a series at 0,  1,  6 months.  It is important that the
patient be  given  the  injection  IM  into  the  deltoid  muscle  and  avoid
inadvertent  subcutaneous  injection.  The vaccine is highly effective with a
90 % seroconversion rate and for  all practical purposes, hepatitis B doesn't
occur in  persons  who  have  seroconverted  with  the  vaccine.   High  risk
individuals  as healthcare workers, patients undergoing dialysis or receiving
chemotherapy, individuals  with  multiple  sexual  partners,  IV  drug users,
institutionalized patients, newborns of  hepatitis  B  positive  mothers  are
candidates  for  the  vaccine.  INFANTS of hepatitis B positive women require
both passive immunization  with  HBIG  (.5  ml)  and active immunization with
vaccine (.5 ml at 0,1,6 months.  If they are not immunized, these children of
infected women have an 85% probability of developing chronic infection.  This
risk is reduced to 10% by immunizing.  Routine testing of pregnant women  for
HBsAg  is recommended.  HEPATITIS C...There is no known immunoprophylaxis for
hepatitis C. TREATMENT OF  HEPATITIS:  ACUTE HEPATITIS...No therapy.  CHRONIC
HEPATITIS...Hepatitis  C  treatment  with  alpha  interferon  has  now   been
approved.   The  usual  dose  is 3 million U given subcutaneously 3X/wk for 6
months.  Approximately 40%  will  respond  with  a return of aminotransferase
levels to normal.  Relapse occurs, however, in 50% of these patients.  At the
present time only symptomatic patients and those with progressive disease are
being treated.  Liver biopsy is required prior to treatment.  Retreatment  is
possible  in  patients  who relapse.  The remission rate for hepatitis B with
interferon is approximately 40% with  most  responders losing the HBeAg.  The
response is generally sustained.  Hepatic transplantation is not as useful in
chronic hepatitis B as in the ACUTE form of the disease.  Hepatitis B usually
recurs  and  shows  an  accelerated  course  of  progression  to   cirrhosis.
Interferon is well tolerated; fewer than 20% of patients have side effects as
myalgias,  headache, and fever.  Platelet counts predictably dropped by about
20% and  neutrophil  counts  were  reduced  in  most  patients.   The cost of
interferon is generally about $300  per  month  for  dosing  schedules  of  3
million  U three times a week.  HEPATITIS B CARRIER STATE: A small number who
contract hepatitis B become so called  "healthy" carriers.  This is likely to
occur in the new born infants of infected women.  Approximately 85% of  these
neonates  develop  chronic  disease,  primarily  the "healthy" carrier state.
Males are more commonly affected than females.  The hepatitis B carrier state
is characterized by the persistence of HBsAg.  Although they have no clinical
signs of disease, they are  susceptible  to the development of hepatocellular
carcinoma.  In those infected from birth, the risk of  developing  cancer  is
increased   200   fold.   CHRONIC  PERSISTENT  HEPATITIS  Chronic  persistent
hepatitis  is  characterized  by  infiltration  of  the  portal  tracts  with
mononuclear cells and  occasionally  by  some  fibrosis.   The margin between
hepatocytes and the  portal  tracts  is  intact  and  liver  architecture  is
undisturbed.   Patients  are  usually asymptomatic, but may present with mild
fatigability, anorexia and URQ  discomfort.   The  physical is normal.  Serum
aminotransferase levels may be elevated  by  3-4  fold,  but  lab  tests  are
otherwise  normal.   Hypoalbuminemia  suggests  progression to chronic active
hepatitis.  After observing for  6  months,  the  diagnosis  is made by liver
biopsy.  Chronic persistent hepatitis has a good prognosis.   Progression  to
CAH  occurs  infrequently  and  patients  should  be reassured that they will
recover, although it may take months to  a  few years.  Because some do go on
to CAH, they must be  followed  to  complete  resolution.   No  treatment  is
needed.   CPH  may occur as a sequel to acute hepatitis B, acute hepatitis C,
or chronic active hepatitis that  is in remission.  CHRONIC LOBULAR HEPATITIS
Biopsy shows infiltration of the portal tracts with mononuclear cells as well
as spotty necrosis and parenchymal inflammation.  Chronic  lobular  hepatitis
is  also  known as prolonged or unresolved hepatitis and most commonly affect
middle  aged  men.   Chronic  lobular  hepatitis  frequently  accompanies the
conversion  from  hepatitis  Be  antigen  to  antiHBe.   Most  patients   are
asymptomatic  although  malaise  and  anorexia  may  be present.  Physical is
normal.   The  course  of  chronic  lobular  hepatitis  is  characterized  by
exacerbations,   which   are   associated   with   3-5   fold   increases  in
aminotransferase enzymes, and remissions.  Biopsy establishes the  diagnosis.
In  rare cases there is spontaneous remission and corticosteroid therapy will
lead to a rapid  and  complete  response.   Chronic lobular hepatitis doesn't
lead to cirrhosis.  CHRONIC  ACTIVE  HEPATITIS  Biopsy  shows  a  mononuclear
infiltration  of the portal tracts which spill out into the parenchyma and is
associated  with  necrosis  of  the  periportal  cells,  so  called piecemeal
necrosis.  Periportal fibrosis is also common.  Men are  affected  more  than
women.   Symptoms include malaise and anorexia but may also develop jaundice.
Aminotransferase   enzymes   are   frequently   elevated   3-10   times.    A
characteristic feature is the  development of hypoalbuminemia.  HBsAg usually
remains  positive  as  does  the  hepatitis  Be  antigen.   The  features  of
autoimmunity seen  with  chronic  lupoid  hepatitis  are  not  usually  seen.
However,  extrahepatic manifestations, such as membranous glomerulonephritis,
polyarteritis and acrodermatitis, are  seen.   A significant proportion go on
to develop cirrhosis and ultimately liver failure.   There  is  now  evidence
that chronic hepatitis may be a disease of interferon deficiency resulting in
absence  of a normal immune response to the virus.  HEPATOCELLULAR CARCINOMA:
In the USA, hepatitis C is  an  important  cause of HCC with 70% of afflicted
patients being anti HCV positive.  Chronic hepatitis B patients also  are  at
risk  for  HCC  and  yearly ultrasound exam, measurement of alpha-fetoprotein
should be done.  Preliminary  information  suggest that with early detection,
some cases of HCC may be surgically curable.  HEPATITIS C PROFILE: Previously
known as non-A, non-B hepatitis.  It is caused by an RNA virus  and  accounts
for  80-90%  of  transfusion  hepatitis.   Only  5%  of  cases  are caused by
Hepatitis B. It  is  transmitted  the  same  as  hepatitis  B, but sexual and
vertical transmission are not very efficient.  The virus is cytopathic.   The
virus  does  attach  to the bone marrow stem cell thereby leading to aplastic
anemia in a significant portion  of  affected  patients.  There is waxing and
waning elevation of aminotransferase enzymes.  Hepatitis  C  may  or  not  be
associated  with  symptoms.   The  return  of the aminotransferase enzymes to
normal does not  necessarily  signal  complete  remission.   Patients must be
followed for 2-3 years after acute infection to assure that chronic infection
hasn't developed.  Fulminant hepatitis develops only rarely.   The  diagnosis
is  based  on  finding  anti  HCV  antibody.   False positives are common.  A
positive test must be repeated  by  a  confirmatory test.  Since the antibody
develops late in the course of the disease,  this  test  is  better  for  the
detection  of  chronic  rather  than  acute  hepatitis  C. HCV seroconversion
typically occurs at 20 to  22  weeks  following exposure.  Major risk factors
for the development of chronic HCV infection are IV drug  abuse,  receipt  of
blood   products   (eg  hemophiliacs),  and  occasionally  occupational  (eg,
healthcare work) exposure.  Yet about 30-40% of persons who are found to have
anti HCV  have  no  evidence  of  parenteral  exposure;  their infections are
referred to as sporadic or community acquired and are less likely to progress
to CAH or chronic liver disease.  Routine testing of blood products for  anti
HCV  should  greatly reduce the incidence of post transfusion hepatitis.  50%
of patients who develop acute hepatitis C develop chronic hepatitis and about
50% of these ultimately  develop  cirrhosis.  Chronic hepatitis C predisposes
to hepatocellular carcinoma and in the  USA  is  more  important  cause  than
hepatitis  B. DELTA HEPATITIS PROFILE: Delta hepatitis is a partial virus and
depends on hepatitis B for its survival  and consists of linear RNA and the D
antigen encapsulated with  HBsAg.   Diagnosis  is  based  on  finding  the  D
antibody  in  serum  or the antigen in liver biopsy.  The disease occurs most
commonly in IV drug users and  male homosexuals.  It is highly infectious and
virulent and can induce severe hepatitis in  an  HBsAg  positive  individual.
20%  of  fulminant hepatitis is caused by delta and hepatitis B co-infection.
The outcome is very  variable  and  ranges  from  resolution with immunity to
simultaneous chronic HDV and  HBV  carrier  states  to  fulminant  hepatitis.
HEPATITIS  E PROFILE: Hepatitis E is caused by a RNA virus that is endemic to
Asia.  Only a few  cases  have  been  reported  in  USA.  Infection is spread
enterically.  Affected children and pregnant  women  have  a  high  mortality
rate.   Chronic  disease  doesn't occur.  There is no marker for detection of
hepatitis E. HEPTATITIS A PROFILE: Hepatitis A  is caused by a RNA virus with
sources of infection being water and  food  contaminated  with  human  feces.
Incubation  is  about  20  days.   Children  are  more commonly affected than
adults.   Clinically,  it  behaves  as  a  flu  like-illness  associated with
anorexia, malaise, myalgias, and  occasionally  abdominal  discomfort.   Dark
urine,  light  stools  and  jaundice  occur  in  10-20%.  Most patients don't
develop jaundice and  the  disease  goes  unnoticed.  Most recover completely
without  sequelae  although  a  few  will  experience  relapse  or  recurrent
prolonged  cholestasis.   Fulminant  hepatitis  occurs  only   rarely.    The
aminotransferase  enzyme  levels are elevated into the hundreds or thousands.
The disease is  confirmed  with  HAV  IgM  antibody.   There  is no effective
vaccine at the present time  because  the  virus  is  not  very  immunogenic.
HEPATITIS  B  PROFILE: Hepatitis B is caused by DNA virus.  It is transmitted
by IV drug abuse, sexual and  vertical transmission; i.e., mother to new born
infant.   Non-percutaneous  person  to  person   transmission;   eg,   within
households,  is  also  known  to  occur.   In approximately 40% of cases, the
source remains unknown.  The incubation  period ranges from 30-150 days.  The
diagnosis is made by detection of hepatitis  B  surface  antigen  (HBsAg)  or
hepatitis  core  antibody  (anti-HBc  IgM) in the serum.  The first serologic
marker to appear is HBsAg which  is  evident within 3-5 weeks of exposure and
prior to the development of the clinical illness.  This is  followed  by  the
hepatitis  B  surface antibody (anti-HBs).  There is a period when neither of
these two are detectable in the serum.  During this window one can detect the
anti-HBc IgM which can be used  to  diagnose hepatitis B. With the appearance
of the hepatitis B surface antibody, there is recovery from the  illness  and
development  of  long lasting immunity.  The hepatitis Be antigen is a fairly
good marker  of  infectivity  and  is  usually  associated  with active viral
replication.  Its clearance and development of the anti HBe usually  portends
an  end  to  the  infection.   A few patients, usually those who are anti-HBe
positive, develop fulminant hepatitis which  has a rapid downhill course with
encephalopathy.  The mortality is greater than 70%.  The hepatitis B virus is
not usually cytopathic and the clinical outcome is  dictated  by  the  immune
response  to  the  virus.  About 6-10 % develop some form of chronic disease.
Most patients with acute hepatitis  B  recover completely with development of
antibodies to HBsAG and hepatitis B core antigen.

                 -HEPATITIS B NEONATAL IMMUNIZATION-
Children who acquire the hepatitis B  virus are more likely to become chronic
carriers than develop clinically symptomatic acute hepatitis.  Any child that
is less than 5 years of age is at risk for a chronic carrier state.  Those at
risk include Alaskan natives, Pacific islanders and infants of imigrants that
come from endemic areas.  Most cases of hepatitis B occur in adolescents  and
adults.  At the present time about 300,000 new casees are reported every year
in  the  USA,  and  about 1.25 million persons are chronic carriers.  Chronic
carriers may be just as  infectious  to  other  as acute hepatitis B. Chronic
hepatitis patients  can  develop  hepatocellular  cancer  and  chronic  liver
disease.   IMMUNIZATION  SCHEDULE:  The  newborn  is  now  given  hepatitis B
vaccine.  At 2 months hepatitis B,  DTP-HIB  and  OPV are given.  At 4 months
DTP-HIB and OPV are given.  AT 6  months  DTP-HIB  is  given.   At  9  months
hepatitis B is repeated.  AT 15 months MMR, DTP-HIB, and OPV are given.  At 5
years DTaP, and OPV is given.  AT 10-12 years MMR is repeated and at 15 years
Td  is  given.   Infants  of HBsAg negative mothers and children less than 11
years of age are given 2.5 ug  (0.25ml)  of Recombivax HB or 10 ug (0.5ml) of
Engerix-B.  Infants of HBsAg positive mothers  are  given  5  ug  (0.5ml)  of
Recombivax  HB or 10 ug (0.5ml) of Engerix-B.  Teenagers that are between the
ages of 11-19 years of age are given  5  ug (0.5ml) of Recombivax HB or 20 ug
(1.0 ml) of Engerix-B.  Adults that are older than 19 years of age are  given
10  ug  (1.0) of Recombivax or 20 ug (1.0ml) of Engerix-B.  Patients that are
immunocompromised or on dialysis are given  40 ug (1.0ml) of Recombivax HB or
40 ug (2.0ml) of Engerix-B.  Recombivax HB is safe to  use  in  pregnancy  as
well  as  in  lactation.  Hepatitis B vaccine is given as three intramuscular
injections.  In most cases the  second  injection  is given 1 month after the
first and the third dose is given 6 or more  months  after  the  first  dose.
Longer intervals between the second and the 3rd dose, at least 4 months, will
result  in  higher anti-HBs titers.  The vaccine is about 80-95% effective in
preventing hepatitis B infection.   All  pregnant  women should be tested for
HBsAG early in pegnancy adn repeated again later in pregnancy if they are  at
high  risk.   Regardless of maternal hepatitis status, all neonates are given
hepatitis B vaccine.  If the mother is positive for HBsAg, hepatitis B immune
globulin should be given at  0.5  ml  IM  +  the first vaccine dose within 12
hours of life.  Infants of mothers with an unknown status should receive  the
vaccine.  If after testing the mother for HBsAG, she is found to be positive,
hepatitis  B  immune globulin should be given.  Household contacts of mothers
that are positive for HBsAg should  be tested for hepatitis B antibodies.  If
they do not possess antibodies, they should be  vaccinated.   Separate  sites
should  be  used  for  combination  vaccine  +  HBIG or combination vaccines.
Hepatitis  B  vaccine  can  be  given   with  other  vaccines,  in  the  same
anterolateral thigh in children (sites must be  separated  by  at  least  1.5
inches),  but the vaccines or immune globulin should not be mixed in the same
syringe.  The buttocks should  not  be  used.   Hepatitis  B vaccine does not
interfere with the immunogenicity of other  vaccines.   If  the  patient  has
received  the  first  dose of the vaccine and has not followed up, the second
dose should be given as soon as possible, followed by the third dose which is
separated by at least 4  months  or  longer  from the second dose.  The first
dose should never be repeated.  It is permissible to switch  from  Recombivax
HB to Engerix-B or from Engerix-B to Recombivax HB.

                       -HEPATITIS B TREATMENT-
Treatment  of  typical  CHRONIC hepatitis: In patients with HBeAg and HBV DNA
positivity, interferon alpha therapy, 5 million units daily for 16 months has
resulted in normalization of aminotransferase levels, sustained disappearance
of HBeAg and viral DNA,  improvement  in histology and improvement in quality
of life in about 30-40%.  About 1/3 have lost HbsAg.   The  remissions,  when
followed  long  term  (mean  4.3  years), 2/3 have lost HbsAg.  Predictors of
response include those who  have  high  transaminase levels, (if transaminase
levels are < 100 IU/L pretreatment with prednisone improves the response rate
slightly), a low HBV DNA titer < 100 pg/ml and early chronic hepatitis B that
is < 6 mo.  Patients that have AIDS, post transplant or are  immunosuppressed
by pharmacological agents respond less well.  The usual dose is 5 MU SQ daily
or  10  million  units  three  times/week of interferon alpha for 4-6 months.
Liver biopsy before  treatment  is  recommended,  but  not necessary.  Weekly
leukocyte and platelet counts are needed for the first month of  therapy  and
should  be  monitored  monthly thereafter along with monthly thyroid function
tests and liver  enzymes.   Decompensated  cirrhosis  and  a  past history of
depression are relative contraindications with interferon alpha therapy.  The
endpoint of response is the loss of HBV DNA and HBeAg.  Both of these can  be
quantitated.   SIDE  EFFECTS  OF  INTERFERON  ALPHA: Early flu-like symptoms,
headaches, myalgia,  diarrhea  and  nausea.   Late  effects  include fatigue,
depression, loss of concentration, thrombocytopenia,  leukopenia,  appearance
of  autoantibodies,  and autoimmune disease such as thyroiditis and hemolytic
anemia.  Interferon alpha may worsen  the disease in patients with autoimmune
features.   With  therapy,  the  patient's  hepatic  inflammation   increases
temporarily.   Patients  with  typical ACUTE	hepatitis B should not receive
interferon alpha.  Patients with mild chronic hepatitis B or the asymptomatic
HBsAg carrier state with normal aminotransferase  , in general, should not be
treated with interferon.  Interferon alpha therapy for patients with  chronic
hepatitis   B   and   cirrhosis  should  be  reserved  for  those  with  mild
decompensation by giving  2-5  MU  three  times  weekly.   Some patients have
atypical serology in that they have positive HBV DNA, but lack HBeAg.   These
patients  are  rare in the USA and northern Europe, but found most frequently
in Greece, Italy and parts of Asia.  In general these e-minus mutants respond
less frequently and relapses are common.

                      -HERPES SIMPLEX SYNDROMES-
Herpes simplex virus types  1  and  2  are  double  stranded DNA viruses that
replicate in  mucosal  and  skin  surfaces  producing  the  typical  lesions.
Following  this,  they travel retrograde along the sensory nerves back to the
sensory ganglia where  they  again  replicate.   After  a latent or quiescent
period they then travel anterograde back to the skin  and  mucous  membranes.
Most  type  I lesions occur above the waist, while type 2 lesions occur below
the waist, but there can be  some  variation in this pattern.  The incubation
period varies from 1-26 days with an average  of  about  6-8  days.   PRIMARY
GENITAL   HERPES   SIMPLEX:   Most  Herpes  simplex  type  2  infections  are
asymptomatic, and many  individuals  will  have  antibodies to herpes simplex
type 2. Either type 1 or 2 can  cause  primary  genital  disease.   The  main
lesion  is  a  painful  vesicular  lesion  that  can occur at any site on the
external genitalia.  The differential  includes Behcet's syndrome, chancroid,
and syphilis.  Most women will have infection of the cervix which can  appear
erythematous,  friable,  ulcerated,  or even normal.  Women may also have the
lesions in  the  urethra.   The  vagina  is  less  commonly  involved.  These
vesicles will eventually ulcerate, and then heal with crusting.  The  lesions
are  usually  completely  healed  in about 3 weeks.  Patients may complain of
malaise, fever, headache, dysuria, and there may be regional lymphadenopathy.
In about 30% of women, and  about  10%  of men, aseptic meningitis can occur.
Other  rare  complications  include   urinary   retention   (1%),   cutaneous
dissemination   of   HSV-1   or   HSV-2  in  eczema  patients,  and  visceral
dissemination in immunocompetent  and  pregnant  patients.   The treatment of
choice for primary HSV is acyclovir 200 mg PO five  times/day  for  10  days.
RECURRENT  GENITAL  HERPES  SIMPLEX: Genital herpes simplex type 2 is usually
involved in recurrent  herpes,  and  the  recurrent  variety  is usually less
painful.  With time, the frequency usually decreases.  Clinically,  recurrent
herpes  presents  as  itching or burning, followed in a day or so by a sparse
outbreak  of  vesicles.   These  usually  resolve  in  about  10  days.  Most
patients, unlike primary herpes, do not  have  systemic  symptoms.   Patients
that  have  6  or  more episodes/year of recurrent herpes may be treated with
prophylactic acyclovir 400 mg PO tid.  Patients are encourged to wear condoms
at all times to reduce  exposure  during asymptomatic episodes.  PRIMARY ORAL
HERPES SIMPLEX INFECTIONS: The majority of these occur in children and  young
adults,  are  asymptomatic,  and  involve  HSV-1.  Patients that present with
HSV-1 gingivostomatitis develop painful vesicles on the soft and hard palate,
gums, tongue, buccal  mucosa,  around  the  mouth,  and  on  the lips.  These
subsequently ulcerate and heal without scars.  Healing takes about 2-3 weeks.
Patients may have headache, malaise,  myalgias,  irritability,  anorexia  and
cervical  adenopathy.   Patients can also develop herpetic involvement of the
tonsillar pillars and pharynx with  exudative and ulcerative lesions in these
areas.  Tzanck smears may be  usefjul  in  demonstrating  the  multinucleated
giant  cells.   Oral  acyclovir  usually only shortens the healing by about 1
day.   RECURRENT  ORAL  HERPES  SIMPLEX:  These  patients  develop  recurrent
vesicles and ulcerations around  the  mouth,  lips  and mucosa.  If there are
more than 6 bouts/year, suppressive oral acyclovir  at  400  mg  bid  may  be
helpful.  Patients that are immunosuppressed may have severe recurrences with
dissemination.   PRIMARY  OCULAR  HERPES  SIMPLEX  INFECTION:  Primary ocular
herpes is due to HSV-1  in  almost  all  cases  and involves the eyelids with
vesicles, crusting and edema.   Eyelid  involvement  may  be  complicated  by
conjunctivitis  and  keratitis,  manifested  as  tearing,  photophobia, pain,
decreased visual acuity,  and  unilateral  redness.   Patients  may have have
cervical  lymphadenopathy.   Patients  with  corneal  involvement  will  need
topical trifluridine 1% drops to prevent corneal scarring.  RECURRENT  OCULAR
HERPES SIMPLEX INFECTION: Patients who have had primary ocular herpes have an
estimated  recurrence  rate of about 40% in 5 years, and with each recurrence
the  chances  of  corneal  scarring  increases.   HERPES  GLADIATORURUM: This
syndrome occurs in wrestlers, and is transmitted  by  infected  HSV-1  saliva
into  a  bite  or abrasion of the skin.  HERPETIC TRACHEOBRONCHITIS: Herpetic
tracheobronchitis is usually seen in  elderly patients with bronchospasm, who
do not respond to standard medications.  It has the  potential  for  a  fatal
outcome.   The diagnosis depends on detection of the necrotizing lesions seen
in the trachea  and  large  bronchi.   Accompanying thick fibrinous exudative
membranes are also frequently seen on bronchoscopy.  The lesions are cultured
for diagnosis.  Treatment is with IV acyclovir for about 10  days.   HERPETIC
WHITLOW:  Herpetic whitlows are commonly acquired by autoinnoculation.  It is
common in  children  with  herpetic  gingivostomatitis  who  then  suck their
thumbs.  It may also be seen in women with genital herpes who  autoinnoculate
themselves.   Health  care  workers are also at risk.  These patients present
with painful vesicles at  the  end  of  a  finger, lymphaangitis and regional
adenopathy.  The incubation period is 3-7 days.  Oral acyclovir can  be  used
for  primary or recurrent disease.  HERPES SIMPLEX ENCEPHALITIS: About 70% of
herpes simplex encephalitis arises  from  reactivation  of quiescent HSV-1 in
the trigeminal or olfactory ganglia.  Clinically, these patients present with
headache, nausea, vomiting, fever, chills and myalgia.  Following this,  they
become disoriented and confused.  They can develop seizures, speech problems,
and  hallucinations.   As  the disease progresses, the patients may fall into
coma.  The diagnosis mahy be obscure  early  in the disease.  The CT, MRI and
EEG may all be normall early on.  However,  as  the  disease  progresses  the
typical temporal lobe involvement may become evident.  The CT may demonstrate
low density lesions with or without contrast enhancement.  The EEG may show a
spike  and  slow  wave activity in the temporal lobe.  CSF analysis should be
done for HSV cultures,  even  though  the  yield  is  low.   The CSF WBCs are
usually less than 500/mm3, and there may be increased RBCs and protein.   HSV
antibody  titers  should  be  done  initially  and  at 14 days.  Patients are
treated with IV acyclovir  at  10  mg/kg  q8h  for 10-14 days.  Patients with
renal insufficiency should have a lower  dose.   It  is  important  to  start
acyclovir  as  early  as possible in order to have a successful outcome.  The
mortality  without  treatment  exceeds  70%.   HERPES  SIMPLEX  INFECTION  IN
PREGNANCY: Primary genital infection  of  the  mother  occurs  in about 1% of
pregnant women.  Neonatal infection occurs in about one  of  every  1500-5000
live  births  due  to passage through the birth canal and through exposure to
oral HSV-1.  The relatively low occurrence in neonates may be due to maternal
HSV placental antibody transfer to the infant.  Many of these mothers will be
asymptomatic  for   herpes.    These   infants   may   develop  encephalitis,
disseminated infection  or  infection  of  the  skin  and  mucous  membranes.
Primary  infection  in  the  first trimester can end in spontaneous abortion.
Treatment of infants with  herpes  is  with  IV  acyclovir.  Acyclovir is not
approved for use in pregnancy, and the major thrust  is  identifying  mothers
with  genital  herpes,  and preventing exposure to the neonate.  DISSEMINATED
HERPES SIMPLEX VIRUS  INFECTION:  Those  patients  at  risk for dissemination
include  patients  with  congenital  or  acquired  immunodeficiency  disease,
including those on immunosuppressive mdedications.  Transplant recipients are
particularly at potential risk.   Most  of  these  patients  start  out  with
routine  infections of the oral or genital area and then subsequently spread.
Treatment  is  with  acyclovir   400   PO   five  times  daily  or  acyclovir
intravenously.  Patients that are  immunosuppressed,  should  be  immediately
started  on  acyclovir when the initial lesions are evident, in order to help
prevent dissemination.  HERPEX SIMPLEX PROCTITIS: These patients present with
anorectal pain, malaise,  tenesmus,  constipation,  anal discharge and fever.
They  may  have  urinary  retention,  impotence   and   sacral   paresthesia.
Superimposed bacterial infection may occur.  HSV proctitis is most frequently
acquired  with  anal  intercourse.   Examination  will  reveal  vesicles  and
ulceration  in  the  perianal and anal area which may extend into the sigmoid
colon.   Diagnosis  is  made  by   cultures  and  biopsy  with  detection  of
multinucleate giant cells.  The duration of the herpes is typically  about  3
weeks.   Treatment  is  with  acyclovir  400  mg PO five times daily.  HERPES
SIMPLEX VIRUS AND AIDS: Mild  mucocutaneous:  Acyclovir 200 mg PO 5 times/day
for 10 days.  Severe mucocutaneous: Acyclovir (15 mg/kg/day IV or  Vidarabine
(15  mg/kg/day)  IV  or  Foscarnet  (90  mg/kg/day) IV.  Maintenance therapy:
Acyclovier 200 mg PO tid Visceral:  Acyclovir  (30 mg/kg/day) IV for at least
10 days or Vidarabine (15 mg/kg/day) IV for 10 days.

                      -HERPES ZOSTER AND AIDS-
Dermatomal: Acyclovir 800 mg PO 5 times daily or Acyclovir (30 mg/kg/day) IV.
Ophthalmic, disseminated, visceral: Acyclovir (30 mg/kg/day) IV.

                           -HERPES ZOSTER-
Herpes  zoster  is  caused  by  reactivation  of  the  same virus that causes
chickenpox, the varicella-zoster  virus.   It  can  cause acute and recurrent
infections.  The varicella-zoster virus is latent in the dorsal root  ganglia
and  is  activated  by  systemic  disease  such  as  Hodgkins's disease or in
patients  that  are  immunosuppressed  by  disease  or  medications  such  as
corticosteroids, cyclosporine and azathioprine.   Herpes  zoster may occur at
any age, but has a peak between the ages of 50-70.  The older the patient  is
when  he acquires the disease the more likely he is to develop a postherpetic
neuralgia.  In those older than 60 years  of  age there is a 40% incidence of
postherpetic neuralgia.  In some cases, the virus may affect the anterior and
posterior horns of  the  gray  matter,  dorsal  and  ventral  roots  and  the
meninges.   The geniculate ganglion may be affected producing the Ramsay Hunt
syndrome.  In this syndrome there  is  pain  in  the ear and facial paralysis
which usually isn't permanent.   On  examination  of  the  external  auditory
canal,  the  anterior  pillar of the fauces and the soft palate you will find
the vesicular eruption.  There is pain  in  the  ear on the affected side and
there may be loss of taste in  the  anterior  2/3  of  the  tongue.   Another
variant  involves  the gasserian ganglion producing ophthalmic herpes zoster.
There is a  vesicular  rash  over  the  ophthalmic  divison of the trigeminal
nerve.  If vesicles appear on the tip of the nose, the nasociliary branch  of
the  5th  nerve  and  the cornea are affected, producing corneal ulcerations.
Sometimes there is  a  3rd  nerve  palsy  also.   CLINICAL:  Often there is a
prodrome where the patient complains of a radicular pain and paresthesia  for
2-3  days before the typical dermatomal eruption.  This prodrome may at times
simulate an acute condition such  as  myocardial infarction until the typical
lesions appear.  At first there is a maculopapular eruption which is followed
by clusters of vesicles.  These vesicles proceed to pustulation, and continue
to form for about 3-5 days.  Scabbing starts around 7-10 days  and  there  is
complete  resolution between 2-4 weeks.  Cutaneous and visceral dissemination
is uncommon in immunocompetent patients.   Herpes zoster may be confused with
herpes simplex.  Herpes zoster is  a  unilateral  disease  and  there  is  no
history of previous eruption in the same area.  Herpes simplex tends to occur
in  the same location.  Recurrent zoster is rare in immunocompetent patients.
Genital lesions may not necessarily be herpes simplex.  If in doubt, scraping
from the base of a lesion  should  be studied with fluorescent antibody tests
for herpes simplex and varicella-zoster.  Culture of the herpes simplex virus
may also be done with results seen in  2-3  days.   COMPLICATIONS:  The  most
common  complications  of  herpes  zoster  are postherpetic neuralgia, ocular
complications  of  ophthalmic  zoster  (keratitis,  uveitis,  optic neuritis,
scleritis), bacterial superinfection and  scarring.   Uncommon  complications
include  cutaneous dissemination, pneumonitis, hepatitis, herpes gangrenosum,
hemiparesis due to granulomatous  CNS  vasculitis, myelitis, encephalitis and
motor  neuropathies.   If  the  patient   is   immunosuppressed   with   HIV,
lymphoproliferative disorders, radiation or chemotherapy, the zoster tends to
be  much more severe in the primary dermatome.  Patients with HIV disease and
co-infection with herpes zoster  have  a  high  incidence of trigeminal nerve
involvement and recurrences are frequent.  They tend  to  have  a  black  and
necrotic  lesion  known as ecthymatous zoster, or hyperkeratotic lesions that
resemble warts.  Healing is delayed and new lesions appear for a longer time.
If the patient has  cutaneous  dissemination,  10-50%  of patient may develop
visceral involvement.  Mortality is high with  visceral  involvement  (5-15%)
with  the  majority  dying  from  pneumonia.   TREATMENT:  Treatment  is with
acyclovir 800 mg orally 5 times/day for 7-10 days.  Acyclovir should be given
within the first 3  days  of  onset  to  be  effective.   If the patient does
present after the 3 day limit, but is still producing lesions, acyclovir  may
still  be offered.  If the patient is young and immunocompetent, acyclovir is
optional.  However, all patients that  have herpes zoster ophthalmicus should
be treated with acyclovir, as ocular complications are frequent.   In  severe
cases,  the IV preparation should be used giving 5-10 mg/kg every 8 hours for
5-7 days in adults, and  500  mg/m2  every  8  hours  for 7 days in children.
Acyclovir may cause acute renal failure if given by rapid  IV  infusion.   In
order  to  circumvent  this  complication  give the infusion over 1 hour with
hydration.  Since 85% of the drug is excreted by the kidneys, the dose should
be adjusted for the  creatinine  clearance.   If  the creatinine clearance is
greater than 25 mL/min, 800 mg may be given orally every  4  hours,  5  times
daily.  For a creatinine clearance between 10-25 mL/min the dose is 800 mg po
every  8  hours  and  if  the creatinine clearance is 0-10 mL/min give 800 mg
every 12 hours.  Most  patients  tolerate  acyclovir well.  Occasionally, the
patient may report headaches, nausea, vomiting and malaise.   No  teratogenic
effects  have  been  reported, but acyclovir in pregnancy is investigational.
In some  patients  with  HIV  infection  the  varicella-zoster  virus becomes
resistant to acyclovir.  The benefits of acyclovir include decreased shedding
of the virus, earlier scabbing and healing of the lesions  and  reduction  of
pain.   Prednisone  is  controversial,  but  when  given  as 40-60 mg/day and
started within the first week  of  the  eruption,  it  may reduce the risk of
postherpetic neuralgia in elderly patients.  Corticosteroids are the treament
of choice for geniculate herpes (Ramsay  Hunt  syndrome).   Burow's  solution
(aluminum  acetate 5%) may be diluted 1:20 and applied as gauze dressings for
2-3 hours every  4-6  hours  to  decrease  the  oozing  and  soothe the skin.
Secondary infections should be treated with antibiotics.  The  treatment  for
postherpetic    neuralgia   includes   amitriptyline,   narcotics   and   the
administration of topical capsaicin (Zostrix)  cream 0.075%.  This is applied
to the healed lesions bid for 10 days.

                           -HERPES ZOSTER-
Is  most  commonly  seen  in  the  elderly,  but  also  with  lymphoreticular
malignancies  as  Hodgkin's disease and HIV.  Patients with herpes zoster can
transmit the varicella-zoster to people  who  have not had chicken pox.  They
should avoid people that have immunocompromise and pregnant women.  They  are
contagious  until  lesions are crusted.  The Tzanck test cannot differentiate
between herpes zoster  and  simplex.   Treatment:  Topical  wet dressing with
Burow's solution 1:40.  Use hydroxyzine for itching.  Give analgesic  without
hesitation.  Giving oral acyclovir within the first 72 hrs, 800 mg five times
a  day  for  10  days  will alleviate the acute pain and acccelerate healing.
Immunocmopromised patients are given IV acyclovir,  30 mg/kg a day in divided
doses.  Side effects are nausea and  vomiting.   Adjust  for  renal  failure.
Corticosteroids  to  prevent  postherpetic  neuralgia  is not recommended for
immunocompromised  patients  as  dissemination  may  occur  and  is  also not
recommended for young patients as the risk for postherpetic neuralgia is low.
Vesicles appearing at at distant  dermatome  from  the  original  may  herald
cutaneous  and visceral dissemination and may lead to hepatitis, penumonitis,
uveitis and encephalitis.  Cranial nerve  zoster ccan cause ocular and facial
muscle  palsies.   Cervical  zoster  can  lead  to  unilateral  diaphragmatic
paralysis and thoracolumbar  zoster  can  cause  trunk  and  limb  paralysis.
Sacral  zoster  can cause sphincter dysfuntion.  Herpes zoster oticus (Ramsey
Hunt syndrome) is characterized by facial nerve paralysis, dizziness, hearing
impairment and a zoster infection  on  the  pinna or in the external auditory
canal.  About 70% of  patients  with  zoster  ophthalmicus  can  have  ocular
involvement.   Vesicles  on  the  tip  of  nose  indicates involvement of the
nasociliary   branch   of   the   ophthalmic   nerve.    Keratitis,  uveitis,
conjunctivitis, scleritis and optic neurits, lid retraction and ocular muscle
palsies all can occur.  Treatment is usually with  topical  and  occasionally
systemic  steroids.   Postherpetic  neuralgia  (pain  lasting for more than 3
months after onset) will affect 70%  of  zoster  patients over the age of 70.
Is especially severe after zoster ophthalmicus.  Postherpetic zoster  usually
resolves or abates within 3 months, but can persist indefinitely.  Prednisone
40-60  mg/d  is  given  for  3  wks  if  patient  is  >  50 years old and not
immunocompromised, in order decrease the incidence of postherpetic neuralgia.
Amitriptyline in doses of  50-100  mg  may  also  help,  starting at 10-25 mg
daily.  Low dose amitriptyline may be augmented with fluphenazine 1  mg  tid.
Alternatively carbamazepine may be given for non responders to amitriptyline.
Capsaicin  .025% cream topically applied 5 times/d may be effective after 2-3
weeks of  application.   Intralesional  injections  of  procaine and regional
sympathetic nerve blocks with methylprednisolone can also help.

                             -HIRSUTISM-
Hirsutism  is  due  to  increased  androgen  production and can be defined as
excessive coarse terminal  hair  accumulation  on  the  face, abdomen, chest,
lower back and thighs.  Terminal  hair  on  the  lower  abdomen,  around  the
areolae and even on the face may be normal.  This must be differentiated from
hypertrichosis  which is an excess of thin vellus hair, which depends on race
and familial background.  Androgens include testosterone, androstenedione and
dehydroepiandrosterone sulfate (DHEAS).   In  women,  the ovaries and adrenal
glands produce androgens.  Circulating testosterone is  derived  from  direct
ovarian  secretion  (60%)  and  by peripheral conversion from androstenedione
(40%.  Androstenedione is secreted  in  equal  amounts  by  the ovary and the
adrenal.  DHEAS is only secreted by the  adrenals.   DHEA,  DHEA-sulfate  and
androstenedione   are  produced  by  the  adrenal  gland.   Testosterone  and
androstenedione are secreted  from  the  ovary,  and  androstenedione must be
converted  to  testosterone  in  order  to  produce  an  androgenic   effect.
Testosterone  is  98%  bound.   Only  the  free  testosterone  can  exert  an
androgenic effect.  Testosterone is converted to dihydrotestosterone (DHT) in
the  skin  which can then stimulate the hair follicle.  Cushing's syndrome is
produced by excessive  ACTH,  either  by  the  pituitary  or ectopically, and
usually is not a common cause of hirsutism.  The dexamethasone screening test
can be initially used, or the 24 hour urinary collection  for  free  cortisol
can  be  performed for diagnosis.  Ovarian tumors such as Sertoli-Leydig cell
tumors,  dysgerminomas,   hilar   cell   tumors   and   arrhenoblastomas  may
occasionally cause hirsutism.  Most tumors of the ovary are palpable  on  the
pelvic  exam.   Polycystic  ovary  syndrome  may  present  with amenorrhea or
oligomenorrhea, infertility, dysfunctional bleeding, obesity and anovulation.
The obesity is only  seen  in  about  50%  of  cases.  Usually the polycystic
ovaries are enlarged 2-5 times, with multiple follicular and  atretic  cysts,
but  not  always.   There  may  be  a family history which is inherited as an
autosomal dominant pattern.  The testosterone  is often elevated.  The LH:FSH
ration is > 2.0.  By far, polycystic ovary syndrome and idiopathic  hirsutism
are the most common causes of hirsutism.  The onset is at or near the time of
puberty.  If the DHEA-S is elevated, but below 700 ug/dl and the testosterone
is  elevated,  but  less  than  200 ng/dl suspect PCO.  Adrenal carcinoma can
cause virilization which can be  quite  striking.  DHEA-S values greater than
700 ug/dl are usually due to adrenal tumors.  A CT  should  be  done.   If  a
tumor  is  not  seen,  adrenal  hyperplasia  can occasionally cause very high
levels of DHEA-S.   Some  adrenal  tumors  are  palpable.  Congenital adrenal
enzyme defects such  as  a  21-hydroxylase  deficiency  can  cause  ambiguous
genitalia and hirsutism in female patients.  The 21-hydroxylase deficiency is
the  most  common,  but there may be 11-hydroxylase and 3 beta hydroxysteroid
dehydrogenase deficiency.  About 1.2 -  6%  of  adult patients have a partial
defect in adrenal 21-hydroxylase that can cause hirsutism.  In these patients
you should measure the early morning 17-hydroxyprogesterone level  as  it  is
usually  elevated.   Idiopathic hirsutism has no detectable hyperandrogenism.
Most of these patients have  regular  menses  but  can be irregular.  In this
subset, there is increased hair follicle sensitivity to androgens with normal
androgen levels.  If the DHEA-S is elevated, but below  700  ug/dl,  and  the
testosterone  is  elevated,  but  less  than  200  ng/dl,  suspect idiopathic
hirsutism.    About    25%    of    women    with    prolactinoma   and   the
amenorrhea/galactorrhea syndrome  have  idiopathic  hirsutism  or  polycystic
ovarian  syndrome.   DRUGS  CAUSING  HIRSUTISM: The following drugs can cause
hirsutism: Minoxidil, dilantin,  diazoxide, androgens, steroids, cyclosporin,
danazol, ACTH, metyrapone,  anabolic  steroids,  and  progestins.   Prolactin
elevation  can  cause  hirsutism,  and  the  following  drugs can elevate the
prolactin:  Tranquilizers  (thioxanthenes,   butyrophenones),  Narcotics  (as
morphine and heroin), Antidepressants (as MAO inhibitors),  Antihypertensives
(as  aldomet,  guanethidine  and reserpine), Antiemetics (as metoclopramide),
Antihistamines (as  tagamet,  meclizine  and  tripelennamine)  and estrogens.
Diseases  capable   of   causing   prolactin   elevation   are   sarcoidosis,
histiocytosis,   hypothyroidism,   renal   failure   and  hepatic  cirrhosis.
LABORATORY: 1. Free Testosterone...may be  elevated due to adrenal or ovarian
overproduction, or increased  peripheral  conversion  of  androstenedione  to
testosterone.   In  women  with  idiopathic  hirsutism  or Polycystic ovarian
syndrome the serum  testosterone  is  often  elevated.  (70-80% in polycystic
ovarian syndrome).  Levels of total testosterone greater than 200  ng/dl  are
frequently  present  in  patients with ovarian and adrenal tumors, but rarely
above 200 with idiopathic or  polycystic  ovarian syndrome.  If patients with
polycystic  syndrome  are  put  on  the  "pill"  (estrogen-progesterone)  the
testosterone will normalize, but will not normalize with ovarian  tumor.   2.
Prolactin...may  be  elevated.  If elevated, then MRI of the pituitary may be
in order.  If there is  galactorrhea  or menstrual disturbance then this test
should be ordered.  If the level  is  twice  normal  then  evaluation  for  a
pituitary  tumor should be done.  Values less than this are commonly elevated
in idiopathic hirsutism and  polycystic  ovary syndrome.  3. DHEAS-S...may be
elevated in adrenal overproduction.  Extremely high levels of DHEA-S  greater
than 700 ug/dl may be found in adrenal tumors.  Lesser elevations between 450
and  700  ug/dl  may  be  seen in idiopathic hirsutism and polycystic ovarian
syndrome, congenital adrenal hyperplasia  and some virilizing adrenal tumors.
The DHEAS-S is not a good test for  congenital  adrenal  hyperplasia  as  the
levels  are  usually  normal.   4.  LH:FSH  RATIO...is typically increased in
polycystic ovary syndrome.  5.  17-OH progesterone...is typically elevated in
congenital adrenal  hyperplasia  (21-OH  deficiency).   6.  ACTH  stimulation
test...Basal  levels  of 17 OH progesterone may be normal, but elevated 17 OH
progesterone levels in late onset  21  OH  deficiency  may be seen after ACTH
stimulation.  0.25 mg of synthetic ACTH is  given  IV  and  then  the  17  OH
progesterone  level is measured in 1 hour.  7. 17-OH corticosteroids and free
cortisol in  24  hour  urine  samples  is  done  for  diagnosis  of Cushing's
syndrome.  The 24 hour urinary free cortisol is the  method  of  choice.   8.
17-Ketosteroids...usually markedly elevated in adrenal cancer.  9. CT scan of
adrenals  may  reveal an adrenal mass.  Pelvic Ultrasound may show polycystic
ovaries or  ovarian  mass.   10.   Dexamethasone  suppression  test...If DHEA
sulfate is increased to > 700 ug/dl, then do this test using .5 mg qid for  3
days,  then  repeat DHEA-S.  If the DHEA-S is suppressed, this would indicate
congenital adrenal hyperplasia.   Tumors  of  the  adrenal will not suppress.
TREATMENT: 1. Aldactone (Spironolactone) 100  to  200  mg  daily  in  divided
dosage may be beneficial.  2. Birth control pills are effective in only about
30%.   3.  Flutamide  (Eulexin)  is  being  investigated  for  hirsutism.  4.
Dexamethasone .5 mg at h.s.  is effective for congenital adrenal hyperplasia.
5. Any drug that is  causing  the  hirsutism  should be discontinued.  6. All
secondary diseases that have caused the  hirsutism  should  be  treated.   7.
Shaving, waxing, depilatories, electrolysis and bleaching all can be used.

                  -HISTOPLASMA CAPSULATUM AND AIDS-
Amphotericin B .6 mg/kg IV  qd  or  Itraconazole  200 mg PO bid.  Maintenance
therapy: Itraconazole 100 mg PO bid.

                          -HISTOPLASMOSIS-
Histoplasmosis,  caused  by  Histoplasma capsulatum, a soil saprophyte, is an
oval budding  cell  found  in  the  Ohio  Valley  and  causes  three  type of
infection: Acute primary pulmonary, Chronic pulmonary  cavitary  disease  and
the  progressive,  disseminated  form.   This  organism  has a propensity for
affecting  the   elderly.    Histoplasmosis   capsulatum   has   a  worldwide
distribution.  The fungus exists in mycelial form in nature and  yeast  phase
when  exposed to mammalian temperatures.  The spores may remain active for up
to ten years.  Exposure to bat  or  bird excrement will promote growth of the
fungus.   Risk  factors  include:  cleaning  chicken  coops,  excavation   in
proximity to bird roosts, spelunking, exposure to decayed wood or dead trees,
immunosuppression,  and  remodeling  and  demolition  of  old buildings.  The
occurrence in AIDS patient  is  about  2-5%.   THE  ACUTE PULMONARY FORM: The
acute pulmonary form is self limited and may cause mild  pneumonic  symptoms.
Chest  x-rays  often  times  show calcification after the acute form.  If the
acute form is symptomatic there is  a  mild influenza like illness that lasts
about 4 days.  There may be  fever,  cough  and  mild  chest  pain.   CHRONIC
CAVITARY FORM: Chronic cavitary pulmonary histoplasmosis occurs in the middle
aged  to  elderly  who  have  a  significant smoking history.  Having chronic
obstructive lung disease seems  to  be  an essential substrate for developing
this form.  The disease can present just as pulmonary tuberculosis  with  the
same  symptoms  and  chest  findings.   There is fever, weight loss, fatigue,
night sweats, cough, hemoptysis, and sputum production.  The chest x-ray will
show the underlying  chronic  obstructive  pulmonary disease as hyperlucency,
flat diaphragms and maybe some bullous disease.  Superimposed on this is  the
unilateral  or  bilateral  multiple thick walled cavities in the upper lobes.
In general, there is no  disseminated  disease concomitant with the pulmonary
involvement.  DISSEMINATED FORM: Disseminated disease  causes  fever,  cough,
hepato-splenomegaly,  lymphadenopathy,  bone  marrow  invasion  (with anemia,
leukopenia and thrombocytopenia),  chronic  meningitis, diarrhea in children,
ulcerative enteritis of the distal ileum and colon,  endocarditis,  fibrosing
syndromes  of  the mediastinum (causing pulmonary hypertension, superior vena
cava  syndrome   and   bronchial   obstruction),   erythema   nodosum,  focal
chorioretinitis,  macular  choroid  inflammation  and  hemorrhage,  skin  and
ulcerative mucous membrane involvement (the oral lesions are common  and  are
found  on  the  tongue, palate, buccal mucosa, and oro-pharynx), weight loss,
and fatigue.  The  disease  is  uncommon  (<  .05%  with  about 1/3 affecting
infants < 1 year of age and the remainder in the  elderly)  and  affects  the
reticuloendothelial  system  with widespread involvement.  The adrenal gland,
in particular, is  a  target  and  can  cause  an acute adrenal insufficiency
(50%).  Other causes for an addisonian crisis would have to be ruled  out  as
lymphoma,  Hodgkin's disease, leukemia and sarcoidosis.  The disease is fatal
if not treated and may be  difficult  to diagnose.  Liver involvement is seen
on  biopsy  as  a  granulomatous  intracellular  fungus  with  calcification.
LABORATORY: Culture should be done on specimens  from  sputum,  lymph  nodes,
bone  marrow,  liver  biopsy,  blood, urine and oral ulcerations.  Buffy coat
samples may improve  the  yield.   Obtain  tissue  for staining with Gomori's
methenamine silver stain and periodic acid Schiff stain.  In  AID's  patients
one  may  see H. capsulatum in polymorphonuclear or mononuclear leukocytes in
the peripheral blood  on  Wright  or  Giemsa  stains.  Histoplasmosis antigen
assay has a sensitivity of greater then 90% for disseminated disease in  AIDS
patients.   Complement  fixation tests have a sensitivity of 95% in pulmonary
disease, but only  70%  in  disseminated  histoplasmosis in immunocompromised
patients.  Complement fixation antibodies  at  titers  of  1:8  or  1:16  are
presumptive  for  diagnosis.   Titers of 1:32 is very suggestive as is a four
fold increase.  There may  be  a  false  positive complement fixation test if
previous skin tests have  been  done.   The  skin  test  is  not  helpful  in
diagnosis,    for   reactivity   stays   for   years   following   infection.
Bronchoalveolar lavage and  cerebrospinal  fluid  studies  may  be helpful in
diagnosis in the progressive form.  TREATMENT:  For  self  limited  pulmonary
disease,   no   treatment   is  usually  needed.   For  disseminated  disease
Amphotericin B is indicated in a  total  dose  of 1-2 grams.  Relapses can be
common especially in AIDs patients  in  which  ketoconazole,  fluconazole  or
itraconazole  can  be  given  after  the  initial  IV amphotericin B therapy.
Maintenance therapy with ketoconazole 400  mg daily, or Amphotericin B 50-100
mg IV weekly can be used with good results in  AIDs  patients.   For  chronic
cavitary  disease, Amphotericin B, 2-2.5 grams cumulative or ketoconazole 400
mg daily for  6-12  months  might  be  used.   Mediastinal granulomata may be
treated with  Amphotericin  B.  Mediastinal  granuloma  may  mimic  fibrosing
mediastinitis (fibrosing mediastinitis does not respond to treatment).

                         -HOARSENESS CAUSES-
Infectious:   viral   laryngitis,   bacterial   tracheitis   or   laryngitis,
papillomatosis, croup.  Neoplastic  and  dysplastic:  leukoplakia, vocal cord
cancer, supraglottic cancer with  muscle  invasion.   Traumatic:  vocal  cord
polyp,  vocal  cord  nodules  (screamers  nodules), smoke irritation, chronic
cough,  external  laryngeal   trauma,  gstroesophageal  reflux.   Functional:
hysterical  aphonia.   Neurologic:  tumor   compression   (thyroid,   glomus,
pulmonary,  esophageal), Arnold-Chiari malformation, trauma to nerves, neural
tumors, neuromuscular disease, dystonia.

                        -HODGKINS'S DISEASE-
The  cause   is  unknown,  but  about  20-50%  have  the  Epstein-Barr  virus
incorporated into the genome.   The  diagnosis  is  based  on the presence of
Reed-Sternberg cells which have 2 or more  nuclei  with  prominent  nucleoli,
which  gives the appearance of owl's eyes.  COTSWOLDS STAGING CLASSIFICATION:
Stage I: involvement of  a  single  lymph  node region or lymphoid structure.
Stage II: involvement of 2 or more lymph node regions on the same side of the
diaphragm.  The mediastinum is considered a single site and hilar lymph nodes
are considered bilaterally.  Stage III: involvement of lymph node regions  or
structures  on  both  sides  of  the diaphragm.  Stage III-1: with or without
involvement of splenic, hilar,  celiac,  or  portal nodes.  Stage III-2: with
involvement  of  para  aortic,  iliac,  and  mesenteric  nodes.   Stage   IV:
involvement  of  one or more extranodal sites in addition to a site for which
the designation "E" has been used.  A: no symptoms.  B: fever > 38 degrees C,
drenching night sweats, unexplained loss  of  >  10%  of body weight with the
preceding 6 months.  X: Bulky disease (widening of the  mediastinum  by  more
tha  1/3  or  the presence of a nodal mass with a maximal dimension > 10 cm).
E: involvement of a single extranodal  site that is contiguous or proximal to
the  known  nodal  site.   CS:  clinical  stage.   PS:  pathologic  stage  as
determined by laparotomy.  The  histologic  subtype  is  not  an  independent
prognostic  marker  if  appropriate  therapy  is given.  RADIATION TREATMENT:
Stage IA: radiation therapy (mantle and para-aortic) gives a 93% freedom from
progression.  Stage IIA: radiation,  extended  field (mantle and para-aortic)
gives an 82% freedom from progression.  Stage IIIA1: radiation.  CHEMOTHERAPY
TREATMENT: Stage IIIA2, IIIB, IV:  chemotherapy.   Complete  remission  rates
with  chemotherapy  are  70-90%.  Trials have shown higher complete remission
rates with ABVD, MOPP-ABVD,  and  MOPP-ABV than MOPP.  MOPP=nitrogen mustard,
vincristine  (Oncovin),   prednisone   and   procarbazine.    ABV=doxorubicin
(Adriamycin),  bleomycin  and  vinblastine  (Velban).  Autologous bone marrow
transplanation may be done if there  is failure to achieve complete remission
with chemotherapy, progressive disease during initial therapy, relapse in < 1
year of treatment with chemotherapy, B  symptoms  at  relapse,  more  than  2
relapses,   and   relapse  after  initial  treatment  of  stage  IV  disease.
Thirty-three percent of  these  have  a  3  year  disease free survival.  The
regimens that are commonly used are CBV (cyclophosphamide, carmustine (BCNU),
etoposide (VP16), and cyclophosphamide and total body irradiation.  The death
rate from toxicity is 7-15%.  COMPLICATIONS: Patients that  have  splenectomy
have  a 7% incidence of pneumococcal sepsis.  Other complications of survival
include    preleukemia    or    dysmyelopoietic    syndromes,   anthracycline
cardiomyopathy, diffuse aggressive lymphomas, acute  nonlymphocytic  leukemia
in   3.3-10%,   hypothyroidism,  infertility,  thyroid  carcinoma,  avascular
necrosis and solid tumors of the lung and stomach.

                   -HODGKIN'S DISEASE AND MOP-BAP-
Nitrogen mustard 6 mg/m2 IV on day 1. Vincristine (Oncovin) 1.4 mg/m2 IV (max
2 mg) on days 1 and 8. Procarbazine 100 mg/m2 PO on days 2-7 and days 9-12.
Bleomycin 2 mg/m2 IV on days 1  and & 8. Doxorubicin (Adriamycin) 30 mg/m2 IV
on day 8. Prednisone 40 mg/m2 on days 2-7 and days 9-12.

                    -HODGKIN'S DISEASE AND MOPP-
Nitrogen mustard 6 mg/m2 IV on days 1 and 8. Vincristine (Oncovin) 1.4  mg/m2
IV  on  days  1 and 8. Procarbazine 100 mg/m2 PO on days 1-14.  Prednisone 40
mg/m2 PO on days 1-14.

                  -HODGKIN'S DISEASE AND MOPP-ABV-
Nitrogen mustard 6 mg/m2 IV on day 1. Vincristine (Oncovin) 1.4 mg/m2 IV (max
2  mg)  on day 1. Procarbazine 100 mg/m2 PO on days 1-7.  Prednisone 40 mg/m2
PO on days 1-14.  Doxorubicin (Adriamycin) 35 mg/m2 IV on day 8. Bleomycin 10
mg/m2 IV on day 8. Vinblastine 6 mg/m2 IV on day 8.	Repeat every 4 weeks.

                    -HODGKIN'S DISEASE AND ABVD-
Doxorubicin (Adriamycin) 25 mg/m2 IV on day  1 and 15.  Bleomycin 10 mg/m2 IV
on days 1 and 15.  Vinblastine 6 mg/m2 IV on  days  1  and  15.   Dacarbazine
(DTIC)  375  mg/m2  IV  on  days  1  and  15.   This regimen is used for MOPP
failures.  MOPP/ABVD is given as  monthly coureses alternating the 2 regimes.
MOPP/ABVD has shown superior results to MOPP alone in one trial.

               -HODGKIN'S DISEASE STAGING PROCEDURES-
LABORATORY: CBC with differential, sed rate, bilateral bone marrow aspiration
and  biopsy,  liver  function, serum albumin, Lactate dehydrogenase, calcium.
SPECIAL PROCEDURES:  ultrasound,  MRI,  gallium  scan,  technetium bone scan,
liver spleen scan, and laparotomy.  IMAGING  PROCEDURES:  CT  of  the  chest,
abdomen  and  pelvis,  bipedal lymphangiography and chest x-ray.  HISTORY AND
PHYSCIAL: identify B symptoms, such as  fever (>38 degrees C.), night sweats,
loss of > 10%  of  body  weight  within  the  preceding  6  months.   STAGING
LAPAROTOMY:  is  done if radiation therpay is contemplated.  Is not indicated
in clinical stage IIIB to IVB.   Patients should not have a large mediastinal
mass which is  an  adverse  feature  for  relapse.   The  risk  of  abdominal
involvement  in females < 35 years with nodular sclerosing Hodgkin's and high
cervical nodes is low.

      -HUMAN PAPILLOMAVIRUS (External genital/perianal warts)-
Cryotherapy  with liquid nitrogen or a cryoprobe or podofilox (Condylox) 0.5%
topical  solution  (self  treatment  for  external  genital  warts  only)  or
Podophyllin     10-25%     or      Trichloroacetic     acid     80-90%     or
electrodesiccation/electrocautery.

                   -HYDRALAZINE AND HYPERTENSION-
(Apresoline).   10-20  mg  IV  or  10-50  mg  IM.   Side  effects:  flushing,
tachycardia, headache, aggravation of angina, vomiting.

                           -HYPERCALCEMIA-
This article will deal with the acute treatment of hypercalcemia (HC).  HC is
most  commonly  caused  by  cancer and primary hypoparathyroidism.  In cancer
patients the parathyroid hormone  is  low, and in primary hyperparathyroidism
the parathyroid is  high.   Hypercalcemia  in  cancer  patients  and  primary
hyperparathyroidism  is  due  to  parathyroid-like  hormone  and  parathyroid
hormone,  respectively  ,which  stimulates  osteoclast  reabsorption of bone.
Also, these two  hormones  stimulate  renal  tubular  reabsorption of calcium
which further elevates the calcium.  The hypercalcemia itself interferes with
reabsorption of sodium and water and this leads to polyuria and  dehydration.
Moreover,  many  cancer  patients are immobilized which further increases the
calcium.  SYMPTOMS OF  HYPERCALCEMIA:  HC  can  be divided traditionally into
Gastrointestinal (anorexia, nausea, vomiting, constipation and pancreatitis),
Renal (polyuria, polydipsia and  nephrocalcinosis),  CNS  (drowsiness,  coma,
apathy)  and Cardiovascular (short QT interval on EKG, digitalis sensitivity,
and  hypertension  depending  on  degree  of  hydration).   OTHER  CAUSES  OF
HYPERCALCEMIA: Sarcoidosis, histoplasmosis, coccidioidomycosis, tuberculosis,
leprosy, lithium, thiazide  diuretics,  estrogens and antiestrogens, multiple
myeloma, Vitamin A and D toxicity, familial hypocalciuric hypercalcemia, milk
alkali syndrome,  immobilization,  acute  and  chronic  renal  insufficiency,
parenteral nutrition, pheochromocytoma, thyrotoxicosis, vasoactive intestinal
polypeptide  hormone-  producing  tumor  and  thyrotoxicosis.   If  the serum
calcium after being corrected for albumin is 14 mg/dl, then immediate therapy
is indicated.  If the albumin is elevated then the calcium should be adjusted
downward.  If the albumin is low, then the calcium should be adjusted upward.
TREATMENT OF HYPERCALCEMIA: The decision to treat is usually clear-cut if the
calcium is 14 or greater.  However, calcium levels between 10.5 and 14 depend
on several factors such as age,  concomitant conditions, stage of cancer, and
symptoms.  There are  four  classes  of  treatment  and  include:  hydration,
enhance  the renal excretion of calcium, inhibit bone resorption and treating
the underlying condition.  These  will  subsequently be discussed.  Hydration
with isotonic saline is usually the first step.   Various  amounts  and  time
schedules have been used, but in general give 2.5 to 4 liters of saline daily
with  attention  to the cardiovascular and renal status.  When there has been
restoration of  intravascular  volume  then  one  could  reasonably  expect a
diminution of 1.6 to 2.4 mg reduction of  the  calcium  level.   This  occurs
because of increased renal calcium clearance, decreased calcium absorption in
the   proximal   renal   tubule,  and  obligatory  caluresis  with  increased
presentation of sodium and water  to  the distal renal tubule.  Furosemide is
usually given along with isotonic saline in order to inhibit reabsorption  of
calcium in the thick ascending loop of Henle, and to protect the patient from
saline  overload.  Thiazide diuretics should never be given as they increased
the absorption in the distal tubule.   Always precede loop diuretic agents as
furosemide with saline hydration, because furosemide depends on the  delivery
of  calcium  to  the  loop.   Depending  on  the  degree of hypercalcemia and
symptoms, the furosemide needs to  be  adjusted  possibly  from 20 mg every 6
hours to 80  mg  every  two  hours.   Careful  attention  must  be  given  to
electrolyte  depletion.   Etidronate  works  by  inhibiting osteoclasts.  The
reduction in calcium begins at about  2  days  and  has a peak reduction at 7
days.  The patient should be well hydrated as  the  etidronate  works  better
under this situation.  The dose is 7.5 mg/kg IV over a four hour period daily
for  3-7  days.  The length of treatment depends on the response.  Etidronate
is safe with transient increases in creatinine and phosphate.  Pamidronate is
more potent than etidronate.  Giving a single 24 hour IV infusion of up to 90
mg will normalize the serum calcium  in 70-100% of patients.  Other schedules
include giving a slow IV infusion of 15-45  mg  daily  for  up  to  six  days
depending  on  the response.  Pamidronate can also be given orally as 1200 mg
daily for up  to  5  days,  but  many  hypercalcemic  patients  are unable to
tolerate orally because of nausea and vomiting.  Onset  of  action  and  peak
action is about the same as Etidronate.  Side effects are mild with transient
increase  of  temperature  which  is usually less than 2 degrees C, transient
hypophosphatemia and leukopenia.   Plicamycin  is  given  at 25 micrograms/kg
over a 4-6 hour period and can be repeated at 1-2 day intervals depending  on
limiting  side effects of the drug which include: hepatic and renal toxicity,
thrombocytopenia, and cellulitis with  extravasation  of the drug.  The onset
of lowering the calcium  starts  at  12  hours  and  peaks  at  48-72  hours.
Calcitonin is usually given as salmon calcitonin at 4 units/kg every 12 hours
and  is  the  drug  of choice if a rapid reduction of calcium is needed.  The
calcium starts to drop after a few hours and the peak drop is at 12-24 hours.
The drawback is that calcitonin is  fairly weak and doesn't lower the calcium
to degrees that the bisphosphonates and plicamycin do.   In  spite  of  this,
severe  hypercalcemia  can  be treated with a combination of calcitonin which
can be given  for  1  to  2  doses  and  either plicamycin, bisphosphonate or
gallium nitrate.  Calcitonin also possesses pain relief properties  that  can
relieve  metastatic  bone  pain.   Calcitonin is safe and causes mild nausea,
flushing, abdominal cramps and  allergic  reactions  to salmon.  Skin testing
with 1 unit of salmon calcitonin prior to therapy  is  recommended.   Gallium
nitrate  is  given as a continuous IV infusion at 200 mg/square meter of body
surface in 1 liter of fluid  daily  for  5  days.  Gallium appears to be more
effective in lowering the calcium to normal and prolonging this  effect  than
calcitonin.  However, normal calcium levels are not obtained until the 5 days
of  therapy  is  completed and the lowest levels are at 3 days post infusion.
Also,  it  appears  that  gallium   is  more  effective  than  etidronate  in
normalizing the calcium by about 50%.  The main side effect is nephrotoxicity
and should not be given if renal insufficiency is present.   Patients  should
not  be given other renal toxic drugs as aminoglycosides and hydration should
be maintained.  Decreased hemoglobin and phosphates can also occur.  Steroids
are  useful  if  the   patient   has  multiple  myeloma,lymphoma,  vitamin  D
intoxication, or  granulomatous  disease  and  is  given  as  200-300  mg  of
hydrocortisone IV daily for 3-5 days.

                       -HYPERCOAGULABLE STATES-
Hypercoagulable  states maybe be due to hereditary causes or acquired causes.
Hereditary causes include antithrombin  III deficiency, Protein C deficiency,
Protein S deficiency, dysfibrinogenmeia, factor XII  deficiency,  plasminogen
deficiency,  plasminogen  activator deficiency, and homocystinuria.  Acquired
causes include  antiphospholipid  antibody,  malignancy, pregnancy, nephrotic
syndrome, hematologic diseases, sepsis, trauma and surgery.  ANTITHROMBIN III
DEFICIENCY: is inherited through autosomal dominant genes and affects females
and males equally.  The incicidence is 1:2000.  Antithrombin III is a protein
that is made by the liver, megakaryocytes and vessel endothelium.   Its  role
is  as  an  anticoagulant by binding and inactivating thrombin and factor Xa.
The biologic half life of  antithrombin  III  is  about  2 days.  There are 2
types  of  antithrombin  III  deficiency.   The  first  is  low   levels   of
functionally  normal  antithrombin  III,  and  the second is normal levels of
dysfunctional antithrombin III.  The first type  is much more common than the
second.   The  thrombotic  and  thromboembolic  events  usually  start  after
puberty.  Heterozygotes have antithrommbin levels 25-60% of normal,  and  the
homozygous   state   is   not  compatible  with  life.   Most  patients  with
antithrombin III deficiency  will  present  with  recurrent DVT and pulmonary
embolism.  However, the patient may present with mesenteric vein  thrombosis,
portal  vein  thrombosis, splenic vein thrombosis, disseminated intravascular
coagulation, and axillary  or  subclavian  vein  thrombosis.   About 40% will
occur spontaneously, but about 60% will have  an  inciting  factor,  such  as
estrogen  therapy,  pregnancy,  surgery,  trauma or delivery.  The patient is
treated with  heparin  100-150  units/kg  IV  loading  dose,  followed  by an
infusion of 1500 units/hour  IV.   Antithrombin  III  activity  is  increased
100-1000  times  when  heparin or endothelial heparin sulfate is present.  If
heaprin is  ineffective  antitrhombin  III  concentrate  purified  from human
plasma may be given at 50 units/kg.   Giving  this  amount  would  raise  the
plasma  antithrombin III levels to about 120% of normal in a patient that had
a baseline level of 50%.  The  patient must be treated lifelong with warfarin
in those patients that have  had  a  thrombotic  or  thromboembolic  episode.
PROTEIN  C AND PROTEIN S DEFICIENCY: Most patients will have a thromboembolic
episode before the age  of  35.   Venous  thrombosis  is the most common, but
arterial thrombosis can occur.  Both protein C and S are vitamin K  dependent
plasma  proteins that inhibit coagulation.  They are both manufactured in the
liver.  Protein C deficiency is inherited  as an autosomal dominant gene, and
is seen in about 1:300, but clinically is not that common.  Patients with the
homozygous state may have neonatal purpura fulminans, which can be lethal  if
not  treated  with  anticoagulation.   The heterozygote states have protein C
levels of  50-60%.   Protein  S  deficiency  is  inherited  as  a co-dominant
autosomal disorder.  Patients with Protein C and  S  deficiency  may  present
with  DVT,  pulmonary embolism, superficial thrombophlebitis, mesenteric vein
thrombosis, splenic  vein  thrombosis,  portal  vein  thrombosis, axillary or
subclavian  vein  thrombosis,  and  disseminated  intravascular  coagulation.
Treatment is with heparin initially.  During  heparin  therapy,  warfarin  is
started  at  5-10  mg/day for 2-3 days.  The PT ratio is then kept at between
1.5 and  2  times  control.   Dermal  necrosis  can  occur, particularly with
protein C which has a shorter half life	than protein  S.  Warfarin  causes  a
decreased  level  of  protein C which can result in a temporary activation of
factors V and VIII,  leading  to  a  hypercoagulable state and skin necrosis.
This   can   be   prevented   by   completely   heparinizing   the   patient.
ANTIPHOSPHOLIPID  ANTIBODY:  This  is  an   acquired   autoantibody   against
phospholipids  that  may be seen in about a quarter of patients with SLE.  It
is also known as  lupus  anticoagulant.   However,  most of the patients that
have the antibody will not have SLE.  Furthermore, many of the patients  with
the  antibody  do  not  suffer  any ill effects.  Anticardiolipin antibody is
another antiphospholipid antibody.   The  causes of antiphospholipid antibody
is thought to be genetic or drug  induced.   Drugs  that  may  be  implicated
include  phenytoin,  procainamide, quinidine, hydralazine and chlorpromazine.
Patients that  have  drug  induced  antiphospolipid  antibodies  may have IgM
antibodies, and usually do not develop thromboembolic events.  Patients  with
antipospholipid   antibodies   will  have  a  prolonged  PTT.   There  is  an
association between  the  antipospholipid  antibody  and recurrent abortions.
Some patients with the antibody may  also  have  thrombocytopenia.   Patients
usually  present  with venous and arterial thrombosis, such as DVT, pulmonary
emboli,  disseminated  intravascular  coagulation,  mesenteric  vein, splenic
vein, portal vein, axillary or  subclavian  vein  thrombosis.   Patients  are
treated  with  lifelong  warfarin.   Patients  that  are  not  candidates for
warfarin may have some protection with  ASA 80-325 mg daily + dipyradamole 50
mg QID.  PREGNANCY:	Pregnant patients have increased factors VII, IX, and  X.
There   also   are   increased   levels  of  fibrinogen,  increased  platelet
adhesiveness and decreases  in  fibrinolysin.   The  greatest  risk is in the
later stages of pregnancy and the first 6 weeks after delivery,  particularly
in patients that are greater than 35 years of age, those with preeclampsia or
eclampsia,  those  women  postpartum from C-section, and those who are at bed
rest.  The most common presentation  is  with  DVT.  DVT may be detected with
duplex ultrasound.  Impedance plethysmography may given false positive  tests
due  to  compression  of  the iliac veins by the gravid uterus.  Diagnosis of
pulmonary embolism is difficult in pregnancy  due to the risk of radiation to
the fetus.  The best test is the ventilation/perfusion  scan.   If  pulmonary
angiograms  are  needed,  the  abdomen  should  be  shielded by a lead apron.
Treatment is with heparin 100-150 units/kg  IV  as a loading dose followed by
an infusion of 1500 units/hour IV.  Warfarin is contraindicated in pregnancy.
Therefore, heparin is used subcutaneously following  the  IV  therapy,  using
7,500-15,000  units  SQ  every  12 hours to maintain the PTT at 1.5 times the
control.  MALIGNANCY: Trousseau first  described  the Trousseau syndrome as a
migratory   venous   thrombophlebitis   in   malignancy   in    1865.     The
thrombophlebitis  is peculiar in that it can occur anywhere, affects the deep
and superficial veins and does  not  respond readily to usual anticoagulation
therapy.  The thrombosis is more common  in  patients  with  mucin  producing
tumors  which  are  metastatic.   The  best  treatment  is  treatment  of the
underlying malignancy, since heparin and warfarin usually are ineffective and
may be harmful by causing bleeding in necrotic tumors.  Anticoagulants should
not be used in those  patients  with  CNS  or pericardial tumors.  ASA may be
used at doses of 80-325 mg daily plus  dipyridamole  50  mg  QID.   NEPHROTIC
SYNDROME:  Patients  with  nephrotic  syndrome  are susceptible to renal vein
thrombosis  as  well  as  other  thromboembolic  disease.   The  patients are
hypercoagulable due to increased synthesis  of  procoagulants  in  the  liver
stimualted  by  hypoalbuminemia, and due to urinary losses of anticoagulants.
Nephrotic syndrome  patients  have  peripheral  edema  and  this  may make it
difficult to diagnose DVT.  SURGERY AND TRAUMA: These patients  are  at  risk
for   thromboembolic   disease  due  to  immobilization  and  tissue  damage.
Postoperative venous thrombosis occurs in  about 70% of elderly patients with
hip fractures, 50% of patients who have  elective  hip  replacement,  30%  of
general  surgical  patients  and  about  15%  of  patients  who  have  had  a
hysterctomy.    Prevention   for   patients   being  surgically  treated  for
neurosurgical  and   urologic   disease,   is   with  pneumatic  compression.
Prevention in other types of surgery are benefited by elastic stockins, early
ambulation and low dose heparin such as heparin 5000 units every  8-12  hours
SQ.   High  risk  orthopedic  patients  may  be treated with low dose heparin
keeping the PTT at the upper  limits  of normal, or by using warfarin keeping
the PT 1.2-1.5 times the control.  POLYCYTHEMIA VERA: The most  common  event
in  polycythemia vera is a thrombotic CVA.  It is caused by abnormal platelet
function and hyperviscosity.  About  30%  of  Polycythemia vera patients will
have a thrombotic event.  The treatment is phlebotomy  to  decrease  the  red
cell   volume  and  the  use  of  myelosuppressive  agents  to  decrease  RBC
production.  SEPSIS: Patients that are septic, particularly from gram neative
organisms are prone to a hypercoagulable state due to endotoxin injury to the
endothelium  and  activation  of  clotting  factor  XII  which  initiates the
clotting cascade.

                           -HYPERKALEMIA-
Calcium gluconate 10%: 10-30 ml IV.  Lasts 30-60 min.  Glucose  and  insulin:
50  grams  glucose  hourly  and 5 units regular insulin q 15 min.  Duration 2
hrs.  Sodium bicarbonate: 50-100 mEq IV.  Duration 3-6 hrs.  Albuterol: 10-20
mg by inhaler.  Duration  2  hrs.   Sodium polystyrene sulfonate (Kayexalate)
15-60 gms with sorbitol PO or 50-100 gms with  retention  enema  (retain  for
30-60  min).   Furosemide: 40-240 mg IV over 30 min.  Ethacrynic acid: 50-100
mg IV over 30 min.  Bumetanide:  1-8  mg  over 30 min.  Hemodialysis which is
much more effective than peritoneal dialysis.

                    -HYPERPIGMENTATION (Causes)-
Hemochromatosis,  Addison's  disease,  primary  biliary  cirrhosis, porphyria
cutanea  tarda,   Wilson's   disease,   Scleroderma,   pregnancy   and   oral
contraceptives,  vitamin  B12  and  folate  deficiency, acromegaly, pituitary
secreting adenomas  (melanin  stimulating  hormone),  drugs as antineoplastic
agents, busulfan, quinacrine, chloroquine, chlorpromazine, cachexia, arsenic,
silver, bismuth,  gold,  mercury  and  long  term  antipsychotic  drugs  with
prolonged exposure to sunlight.

                         -HYPERPROLACTINEMIA-
Prolactin's main role is to induce lactation via increased secretion  by  the
pituitary.   Serum  prolactin  levels  will  increase during pregnancy from a
normal level of less than 20  ng/mL  to  as  high as 600 ng/mL.  The elevated
prolactin, along with increased estrogen and  progesterone  leads  to  breast
enlargement  and  formation  of milk.  Following delivery, the estrogen drops
precipitously due to  placental  delivery  which  induces  secretion of milk.
Suckling  by  the  infant  continues  to  keep  a   high   prolactin   level.
Hyperprolactenemia  has also been seen in a variety of other conditions, some
of   which    are    physiologic    and    some    pathologic.    PHYSIOLOGIC
HYPERPROLACTINEMIA: causes include pregnancy, postpartum, nipple  stimulation
in  men  and  women,  stress, sleep, sexual intercourse with organism in some
women, infancy (up  to  3  months),  hypoglycemia,  and food ingestion.  DRUG
INDUCED HYPERPROLACTINEMIA:	Estrogen, butyrophenones (such  as  haloperidol),
phenothiazines,    pimozide,   tricyclic   antidepressants,   metoclopramide,
pargyline, reserpine, verapamil,  alpha  methyldopa, cimetidine, pentazocine,
methadone, morphine, heroin, and oral contraceptives.  PATHOLOGIC  CAUSES  OF
HYPERPROLACTINEMIA:    Prolactinomas,    Cushing's    disease,    acromegaly,
sarcoidosis,   craniopharyngioma,   granulomas,   head  trauma,  empty  sella
syndrome, pituitary stalk section,  epileptic and electroconvulsive seizures,
hypothalamic  tumors,  Hand-Schuller-Christian  disease  (histiocytosis   X),
postencephalitis,  primary  hypothyroidism, chronic renal failure, chest wall
(scars, mastectomy, herpes zoster, neoplasms, trauma), bronchogenic carcinoma
(ectopic production of  prolactin  usually  from  small cell undifferentiated
carcinoma), hypernephroma, Addison's disease, chronic alcoholism,  polycystic
ovary   syndrome,  liver  disease,  and  spinal  cord  lesions.   Women  with
hyperprolactinemia  usually  present   with   amenorrhea,  galactorrhea,  and
infertility.  Men usually  present  with  decreased  libido,  impotence,  and
infertility.    Three   syndromes   have   been   described   in  women  with
galactorrhea\amenorrhea.      The     Chiari-Frommel     syndrome     is    a
galactorrhea\amenorrhea  syndrome  that  persists   after   pregnancy.    The
Ahumada-del  Castillo  syndrome is a galactorrhea\amenorrhea syndrome that is
unassociated with pregnancy  and  the  Forbes-Albright  syndrome,  which is a
galactorrhea\amenorrhea syndrome that is caused by a chromophobe  adenoma  of
the  pituitary.   Women  with  galactorrhea\amenorrhea frequently complain of
estrogen deficiency such as  dyspareunia  and  hot flashes.  However, in most
cases the estrogen is normal and there may be increased androgens.   It  also
must  be  stressed  that  in  these  galactorrhea\amenorrhea  syndromes,  the
amenorrhea  is  much  more  common than galactorrhea.  When galactorrhea does
accompany the hyperprolactinmeia, it can  be stopped or decreased by lowering
the serum prolactin concentration.  Hyperprolactenemia in premenopausal women
has also been associated with osteopenia.  Hyperprolactinemia that is  severe
is  almost  always associated with infertility.  Lowering of the prolactin to
or near normal will  usually  normalize  ovulatory menses and fertility.  The
infertility in men may also be corrected, but the success rate  is  lower  in
men  than  in  women.   Men with microprolactinomas or macroprolactinomas are
managed similary to women.   With  bromocriptine therapy, testosterone levels
increase, as the prolactin decreases.  It  sometimes  takes  3-6  months  for
restoration  of normal sexual function in men.  It has been estimated that of
all  women  with   nongestational   secondary   amenorrhea,  about  30%  have
hyperprolactinemia.  Of all of the causes, the most important cause of a high
serum prolactin is a pituitary tumor.  About 65% of all pituitary tumors  can
be  associated  with  hyperprolactinemia.   The  prolactinomas  can  be small
(microadenomas-less  than  1  cm   in  diameter)  or  large  (macroadenomas).
Macroadenomas  usually  have  higher   levels   of   serum   prolactin   than
microadenomas and are more commonly associated with decreased secretion of LH
and  FSH.   Macroadenomas can produce enlargement of the sella.  The level of
the prolactin is extremely important.  Serum prolactin levels > 150 suggest a
pituitary tumor.  Modest elevations of between 30-100 ng/ml can be due to the
many nonpituitary tumor  causes  as  listed  above.   Levels greater than 250
ng/mL are almost always diagnostic of prolactinoma, if renal failure  is  not
present.   Patients  with persistent hyperprolactinemia not induced by drugs,
hypothyroidism, or pregnancy should have a  high  resolution CT or MRI of the
pituitary.  In a small number of cases no cause  for  the  hyperprolactinemia
can  be  found  and  it is labeled idiopathic hyperprolactinemia.  TREATMENT:
Currently there  are  4  methods  of  approaching  hyperprolactinemia.  These
include  simple  observation,  surgery,  prolactin  lowering  drugs  such  as
bromocriptine,   and    radiotherapy.     OBSERVATION:    In    women    with
hyperprolactinemia  without  evidence  of  an  adenoma  or  in  those  with a
microadenoma (less than 1  cm)  who  do  not desire pregnancy close follow-up
with no drug treatment is an option.  This is supported by the fact that less
than 10% of microadenomas grow to the size of macroadenomas,  and  about  30%
will  disappear  spontaneously.   In  women  with  hyperprolactinemia  and  a
microprolactinoma,   desiring   pregnancy  or  restoration  of  menstruation,
bromocriptine (Parlodel) is indicated.   Bromocriptine  is a dopamine agonist
and  will  restore  prolactin  to  normal  in  about  85%  of  patients  with
microadenomas.  Ovulatory menses will usually be  restored  in  the  first  2
months  of  treatment,  and  galactorrhea  will  usually stop in a few weeks.
Besides lowering the prolactin, bromocryptine  will  also shrink about 75% of
prolactin secreting tumors.  Shrinkage of the tumor may be seen on CT or  MRI
within  2-4  weeks.  Some tumors, especially the large macroadenomas that are
associated with severe hyperprolactinemia  can  continue to shrink for months
or years with continued treatment.  If the drug is stopped, there is  usually
reoccurrence   of   the   hyperprolactinemia,   and   some  degree  of  tumor
re-expansion.   The  degree  of  the  decrease  of  serum  prolactin  is  not
neccessarily related to the degree  of  tumor shrinkage, as a large reduction
in prolactin may occur with hardly any change  in  the  size  of  the  tumor.
However,  many  are  started  on bromocriptine in order to reduce the risk of
osteoporosis   associated   with   estrogen   deficiency.    In   women  with
macroprolactinomas > 1 cm, bromocriptine will reduce the prolactin to  normal
in  70-80%, and decrease the tumor size to 50% of the original size in 50% of
the cases.  Bromocriptine is supplied as 2.5, and 5 mg tablets.  The starting
doses is 1.25 mg given with food  at  bedtime to minimize the side effects of
nausea, vomiting and postural hypotension.   The  dose  should  be  gradually
increased  until  milk secretion has stopped or until the menstrual cycle has
returned to normal.  The dose, after a  few days (3-7 days), may be increased
from the starting dose  of  1.25  at  bedtime	to  1.25  mg  BID,  and  then
gradually  increased  to  a  maintenance dose of 2.5 mg TID in most patients,
with a range of 5-15 mg/day.  The prolactin is measured about 2-6 hours after
the last dose.  Nausea is the  most  common side effect of bromocriptine, and
will occur in about 33% of patients initially.  However, with time, this will
decrease.  Postural hypotension is common after the  first  or  second  dose.
Since  bromocriptine  is  an  ergot  derivative, digital vasospasm can occur.
Other side  effects  include  constipation,  nasal  stuffiness, psychosis and
cardiac arrhythmias.  Patients that require butyrophenones or  phenothiazines
should  not  be  treated with bromocryptine.  Pergolide (Permax) is the other
drug that may be used  for  hyperprolactinemia.   It has a longer duration of
action and may be given once daily.  Currently, pergolide is  only  indicated
for  Parkinson's  disease in the USA, but has been used in Europe extensively
with a  success  rate  approximately  equal  to  bromocriptine.  SURGERY: The
enthusiasm for surgery has declined, because long  term  studies  have  shown
that there has been recurrence in patients that originally were considered to
be   surgically   cured.    Recurrence   is   defined   as  a  recurrence  of
hyperprolactinemia and not reexpansion of the tumor.  Since bromocriptine has
a good success  rate  in  shrinking  prolactinomas  and  in loweing prolactin
levels,  plus  the  fact  that  most  microadenomas  do   not   progress   to
macroadenomas,  and  the  fact  that  with  large  pituitrary tumors and high
prolactin concentration, the  cure  rate  surgically  is  <  50%, surgery has
fallen in disfavor.  One particular  indication  for  surgery  might  be  the
treatment of macroadenomas in women who desire pregnancy.  These patients are
at  risk for visual field compromise as the tumor grows during pregnancy.  In
pregnant  women  with   microprolactinomas,   the   bromocriptine  should  be
discontinued once pregnancy is confirmed.  The patients  should  be  followed
clinically  during  pregnancy.   Complications  occur  in  <  5%  of pregnant
patients and may be  safely  treated  with reinstitution of bromocriptine, if
needed.  The desires of the patient may be instrumental in  deciding  between
medical management or surgical management.  Most prolactinomas are approached
by  the  transsphenoidal  route  which is associated with a low morbidity and
mortality.  Pituitary tumors that  have suprsellar extension with involvement
of the optic chiasm may be approached by the transfrontal route.   RADIATION:
Radiation is not used much due to the fact that the fall in prolactin is very
slow,  and  there  is  a  high  incidence of hypopituitarism in the long run.
There also is an increased  incidence of ocular palsies, blindness, lethargy,
memory impairment, and post-radiation sarcoma.  The  current  indication  for
radiotherapy  is in very large tumors that would be unacceptible for surgery,
or in whom surgery has been unsuccessful, and in those patients that have not
shown   a   gratifying   shrinkage   with   bromocriptine.    PREGNANCY   AND
PROLACTINOMAS: If  the  patient  has  a  microadenoma  and desires pregnancy,
bromocriptine	should be started in order to restore  ovulatory  memses  and
decrease  the  hyperprolactinemia.   There  is no evidence that bromocriptine
treatment during pregnancy has any  harmful  effects  on  the fetus or on the
outcome  of  the  pregnancy.   Once  pregnancy  has   been   confirmed,   the
bromocriptine is discontinued and the patient is observed.  Complications due
to  tumor  expansion  occurs  in  <  5% of patients during pregnancy.  If the
patient has a macrodadenoma,  the  complications  are higher if treated soley
with bromocriptine.  Therefore, macroadenomas are usually treated by  surgery
prior   to   the   desired   pregnancy.   If  the  surgery  is  unsuccessful,
bromocriptine may be started.  Should  the patient develop progressive visual
field reductions during pregnancy, bromocriptine should be started.

                      -HYPERTENSION (Pediatric)-
The  following  drugs  can  be used in pediatric hypertension: HCTZ 1-2 mg/kg
bid, Lasix .5-2 mg/kg bid, Aldactone  1-2 mg/kg bid, Lopressor 1-4 mg/kg bid,
Tenormin 1-2 mg/kg daily, Minipress .5-7 mg/kg tid, Catapres  .05-  .4  mg/kg
bid,  Aldomet  5-10  mg/kg bid, and ACE inhibitors: < 6 months of age .05- .5
mg/kg  tid  and  >  6  months  of  age  .5-2  mg/kg  tid.   LABORATORY: Renal
ultrasound, digital intra-arterial angiography, CBC, UA, urine  culture,  Na,
K,  Cl,  BUN,  creatinine,  uric  acid, plasma renin activity, echocardiogrm,
cholesterol and  triglycerides.   CAUSES:  NEWBORN:  Renal artery thrombosis,
renal artery stenosis, coarctation.  INFANCY TO 5  YEARS:  Renal  parenchymal
diseases,  coarctation of the aorta, renal artery stenosis.  SIX TO 10 YEARS:
Renal artery  stenosis,  renal  parenchymal  diseases,  primary hypertension.
ADOLESCENCE: Primary hypertension and renal parenchymal diseases.

                     -HYPERTENSION (Secondary)-
There are many causes of secondary hypertension.  Some of these are  obvious.
Others  are  rare.   Only  the  more  common causes will be discussed in this
summary.   ADRENAL  DISEASE:  Cushing's  syndrome,  pheochromocytoma, primary
hyperaldosteronism,  mineralcorticoid  excess,   and   11,   17   hydroxylase
deficiency.     THYROID    DISEASE:   Hypothyroidism   and   hyperthyroidism.
HYPERPARATHYROID DISEASE: Hyperparathyroidism.  PITUITARY DISEASE: Acromegaly
and  Cushing's  syndrome.   RENOVASCULAR  DISEASE:  Fibromuscular  dysplasia,
atherosclerosis,  polyarteritis   nodosa.    RENAL   TUMORS:   Wilm's  tumor,
pericytomas and adenocarcinoma.  RENAL DISEASES: Polycystic kidneys,  chronic
glomerulonephritis,  Gordon  and  Liddle  syndrome,  obstructive  uropathies.
DRUGS:   Contraceptives,   glucocorticoids,   anabolic   steroids,  licorice,
amphetamines,  cocaine,  and  ethanol.   NEUROLOGIC  DISEASES: Guillain-Barre
syndrome,  increased  intracranial  pressure,  quadriplegia,   and   familial
dysautonomia.   MISCELLANEOUS:  Stress,  pain, pregnancy, aortic coarctation,
porphyria  and  drug  or  ethanol  withdrawal  states.    HYPERALDOSTERONISM:
Primary hyperaldosteronism is uncommon in  Blacks.  In this disease, which is
caused by an adrenal adenoma in 60% or bilateral adrenal gland hyperplasia in
40%, the abnormal levels  of  aldosterone  may  cause  hypokalemia.   If  the
patients are taking diuretics the hypokalemia may be severe.  The hypokalemia
is dependent on the salt intake.  If there is normal salt intake about 75% of
patients will have a serum potassium of 3.5 or less.  The supine plasma renin
activity  (PRA)  is  usually low in about 75% of patients, but in about 12.5%
the PRA  is  normal,  and  high  in  about  15%  without  diuretic therapy or
malignant hypertension.  One of the better diagnostic tests is the oral  salt
loading  test.   The  patient  is  given  250-300  mEq/d  of salt for 3 days.
Following this, a  24  hour  urinary  aldosterone  is  collected.  If this is
greater than 14 mcg/24hr, and/or the supine  plasma  aldosterone  is  greater
than  22  ng/dl,  hyperaldosteronism  can  be diagnosed with a specificity of
about 96%.  If there is also  hypokalemia,  and a decreased PRA the diagnosis
should be secure.  An additional test will point to an adrenal adenoma as the
cause.    An   8:00    am    supine    plasma    aldosterone    and    plasma
18-hydroxycorticosterone  (18-OHB) are drawn.  At noon, after the patient has
been upright for 4 hours, the  aldosterone and 18-OHB are repeated.  If there
is a decrease in the plasma aldosterone	and 18-OHB at noon from the  markedly
elevated  8:00  am  levels,  adrenal adenoma is a strong possibility.  If the
noon levels of  aldosterone  and  18-OHB  increase  from  the 8:00 am levels,
bilateral hyperplasia is a possibility.  CT and MRI will detect about 75%  of
adrenal  adenomas  that are greater than 1 cm.  If they are smaller than this
they will be missed.   Radionuclide  iodocholesterol  scanning is positive in
only about 50%.  Adrenal vein sampling  for  aldosterone  will  localize  the
tumor  in  > 90%.  Typically, there is a 2-3 times increase of aldosterone on
the  involved  side.   Surgery  is  the  treatment  of  choice  for adenomas.
Hyperplasia  is  treated  with  spironolactone,   amiloride,   bromocriptine,
cyproheptadine, triamterene and nifedipine.  CUSHING'S SYNDROME: Hypertension
is  associated  with  Cushing's  syndrome  in  about 80% of cases.  Diagnosis
depends on history and physical  and  6  basic lab tests.  Physical exam will
reveal the typical moon face,  plethora,  striae,  acne,  hirsutism,  truncal
obesity,  ecchymosis,  muscle atrophy and edema.  The overnight dexamethasone
screening test is performed by  administering  1 mg of dexamethasone at 11:00
pm with subsequent measurement of plasma cortisol at 8:00  am  the  following
morning.  Most normal patients will suppress their morning plasma cortisol to
<  5  ug/dL, whereas most patients with non pituitary Cushing's syndrome will
continue to secrete cortisol.  The  second  test  is the 24 hour urinary free
cortisol.  A level > 100 mcg is abnormal.  Normal values  for  free  cortisol
are  20-100  ug/24h.   The free cortisol test is the best assay for Cushing's
and is elevated in Cushing's syndrome.   This test is subject to only minimal
elevation in obese patients.  The third test is the  low  dose  dexamethasone
suppression test and is performed by giving .5 mg of dexamethasone po q6h for
2  days.   Normal  persons  will  suppress  a subsequent 24 hour urinary free
cortisol to less than 25  mcg  and a 24 hour urinary 17-hydroxycorticosteroid
to less than 4 mg.  Non-suppression suggests Cushing's syndrome and should be
followed by the high dose dexamethasone suppression test  in  order  to  help
separate  pituitary  from  non-pituitary  causes  of Cushing's syndrome.  The
fourth  test  is  the  high  dose  dexamethasone  suppression  test  which is
performed after the low dose dexamethasone suppression test, and is performed
by giving 2 mg of dexamethasone po q6h for 2  days  followed  by  a  24  hour
urinary  free  cortisol and a 24 hour urinary 17-hydroxycorticosteroid level.
If   the   24   urinary   free    cortisol    and   the   24   hour   urinary
17-hydroxycorticosteroid  are  less  than  40%  of  the  baseline  levels,  a
pituitary  cause  is  suggested.   If  greater  than  40%  of   baseline,   a
non-pituitary  cause  such  as  adrenal  or  ectopic  ACTH producing tumor is
suggested.  If there is an indication that  the latter is the case ordering a
plasma ACTH  may  differentiate  between  adrenal  causes  and  ectopic  ACTH
producers.   The  fifth  test  is  the  plasma  ACTH  test.  The ACTH will be
markedly elevated if there is an ectopic ACTH syndrome.  The value is usually
> 200 pg/mL and will be too  low  to  measure in Cushing's syndrome due to an
adrenal tumor.  The sixth test is the CT test.  CT of the head,  abdomen,  or
chest can help find pituitary, adrenal and ectopic tumors.  PHEOCHROMOCYTOMA:
Pheochromocytoma  is  very  rare  occurring  in  .05-.02%  of  patients  with
hypertension.   Pheochromocytoma  also  occurs  as  a  part  of  the multiple
endocrine neoplasia syndromes IIa and IIb.  Most commonly pheochromocytoma is
seen in the  fourth  and  fifth  decades.   Ten  percent  of these tumors are
malignant, 10% bilateral and 10% familial.  About  50%  of  pheochromocytomas
have  paroxysmal  hypertension  and  40%  have  sustained  hypertension.  Any
patient that has hypertension  and palpitations, sweating, headaches, pallor,
tremor, weight loss, orthostatic hypotension and glucose  intolerance  should
be  suspect  for  pheochromocytoma.   There  are 6 basic tests for diagnosing
pheochromocytoma.   The   24   hour   urinary   vanillylmandelic  acid  (VMA)
determination has less sensitivity and specificity than the other  tests  but
is  usually included in the battery of urinary tests.  Levels of greater than
10 mg are suggestive of  pheochromocytoma.   The 24 hour urinary metanephrine
level has an 80%  sensitivity  and  greater  than  90%  specificity.   Levels
greater  than  1.3 mg are suggestive of pheochromocytoma.  The resting plasma
catecholamines (epinephrine  and  norepinephrine)  are  highly  sensitive and
specific and a level greater than 2000  pg/mL  will  essentially  clinch  the
diagnosis.  However, values between 1000-2000 pg/mL are only suspicious.  For
values  in  this  intermediate  range  the  clonidine suppression test may be
useful.  The clonidine  suppression  test  is  performed  by  giving .3 mg of
clonidine po.  Three hours after this, plasma norepinephrine and  epinephrine
are  drawn.   A  decrease  of  >  500  pg/mL  in  plasma  norepinephrine  and
epinephrine is considered normal.  If this decrease is not seen then consider
pheochromocytoma.   The  glucagon  stimulation  test  can be done in marginal
cases, but may be relatively dangerous.  The patient is given 1-2 mg glucagon
IV.  If there is  a  threefold  increase  in  the plasma catecholamines, or a
level  >  2000  pg/ml  then  this  would  suggest  pheochromocytoma.    Tumor
localization  is  accomplished  with  MRI  which  has  a 100% sensitivity for
adrenal  and   90%   for   extra-adrenal   tumors.     RENOVASCULAR  DISEASE:
Renovascular hypertension may be induced by unilateral or  bilateral  disease
of  the renal arteries and its branches.  It accounts for less than 2% of all
cases of hypertension.  To be  hemodynamically  significant the lumen must be
decreased by at least 60%.  In the elderly, renal artery ostial  stenosis  is
the  usual cause and accounts for about 66% of renovascular hypertension.  It
is more common  in  males  that  have  diabetes,  hyperlipidemia and smokers.
Fibromuscular dysplasia is  usually  seen  in  younger  female  patients  and
accounts  for  about 33% of renovascular disease.  Physical exam should check
for involvement of  other  atherosclerotic  sites  as  coronary, cerebral and
peripheral vascular disease.  Abdominal bruits may be present and hypokalemia
may be found.  A difference in kidney height of  1.5  or  more  if  the  left
kidney  is larger and 1 cm if the right kidney is larger may be a significant
clue to renovascular  hypertension.   The  Captopril  test  may  be useful in
diagnosing unilateral renovascular disease, but has limitations  in  patients
that  are  elderly,  black  or  have  renal  insufficiency.  In this test the
patient is given 25-50 mg of Captopril.   Sixty minutes later a PRA is drawn.
If any  of  the  following  results  are  found  there  is  a  suggestion  of
renovascular  disease:  A  PRA > 12 ng/mL/hr, an absolute increase in PRA >10
ng/mL/hr and a 150% increase in PRA  or  400% increase in PRA if the baseline
was <  3  ng/mL/hr.   The  captopril  test  may  also  be  incorporated  into
radionuclide  renography.   In  this  test  captopril  is  given  followed by
radionuclide renography.  The test is considered positive if there is greater
flow to the uninvolved kidney  which  is enhanced with captopril.  Anatomical
delineation  of  the  renovascular  stenosis	is  best  achieved  by  using
intra-arterial digital subtraction angiography which will provide good detail
with minimal contrast.  Intravenous digital subtraction  angiography  suffers
from  poor  detail  and  uses  large amounts of contrast.  Rapid sequence IVP
isn't of much help and  is  rarely  used  any  more.   In order to assess the
functional significance of the demonstrated stenosis, renal vein renin assays
should be done.  Therapy for  atherosclerotic  ostial  stenosis  may  require
bypass  grafting.   Percutaneous  transluminal angioplasty may be required in
fibromuscular dysplasia.  Recurrence  of  the  stenosis  occurs more often in
atherosclerotic lesions than with fibromuscular dysplasia.   ALCOHOL  INDUCED
HYPERTENSION:  Alcohol  may induce hypertension by acting as a direct pressor
or possibly by increasing  intracellular  calcium.   At any rate, ethanol may
account for about 10% of cases of hypertension in men.   Women  are  also  at
risk.   It has been shown that women ingesting 20-34 grams of alcohol/day had
a 1.4 relative risk of developing hypertension.  If this is increased to > 35
grams/day, the relative risk  increases  to  1.9.  ORAL CONTRACEPTION INDUCED
HYPERTENSION: Most women that take oral contraceptive pills  will  have  mild
increases  of systolic and the diastolic BP.  The mechanism for the elevation
may be partly explained by  an  increase  in  plasma renin substrate and salt
retention caused by both estrogen and progestin.  It is interesting  to  note
that  women  taking  less  than 30 mcg of estrogen and 1 mg of progestin very
rarely have elevation of  the  BP.   Also,  it  has  been observed that women
discontinuing oral contraception will have a

               -HYPERTENSION (Treatment of Secondary)-
PHEOCHROMOCYTOMA: The treatment of choice is surgery because these tumors are
resistant to medical  treatment,  and  about  10%  can become malignant.  The
patient should be started on an  alpha  adrenergic  blocking  agent  such  as
prazosin,  doxazosin,  terazosin, labetalol or phenoxybenzamine about 10 days
prior to surgery in order to control intraoperative paroxysms of hypertension
and postoperative hypotension.  About 6 hours  prior to surgery IV fluids may
be given to avert  hypovolemia  that  is  frequently  associated  with  these
tumors.    During   surgery   paroxysms   of  hypertension  that  occur  with
manipulation of the tumor,  and  anesthetic  induction are controlled with IV
nitroprusside or phentolamine.  Arrhythmias are controlled with IV esmolol or
propranolol.  Beta blockers should not be used without prior  alpha  blockade
because   of   induction  of  paradoxical  hypertension.   Following  surgery
hypotension can be treated with fluids.  The operative mortality rate is less
than 2%, and the hypertension  cure  rate  is about 80%.  CUSHING'S SYNDROME:
Cushing's  syndrome  can  be  caused  by  three  mechanisms:  Pituitary  ACTH
producing tumors (70%); ectopic producing tumors such as small cell carcinoma
of the lung (13%), and by hyperplasia, carcinoma, or adenoma of  the  adrenal
cortex  (17%).   Transsphenoidal  pituitary  surgery  is  done  for pituitary
tumors.  The cure rate  is  about  80-95%,  with  a  mortality < 1%.  Ectopic
tumors should be removed, unilateral adrenalectomy for adenomas or carcinoma,
and bilateral adrenalectomy for patients with bilateral hyperplasia that  are
ACTH  independent.   PRIMARY  ALDOSTERONISM:  Medical  treatment  is used for
patients that  have  bilateral  adrenal  hyperplasia  as  a  cause  for their
hypertension, or for patients that refuse surgery or are unacceptable because
of operative risks.  In these patients treatment is with a thiazide/potassium
sparing diuretic such as amiloride or  spironolactone.   Should  the  patient
need  further  medication to control the hypertension, calcium antagonists or
beta blocker may be  used.   ACE  inhibitors  are usually not very effective.
Surgical removal of an adrenal tumor will result in hypertensive  control  in
about  60-80% with a mortality rate of < 1%.  ATHEROSCLEROTIC RENAL STENOSIS:
Transluminal  angioplasty,  in  general,  is  better  than  revascularization
because of the advanced  age  of  these  patients  with cerebral and coronary
atherosclerosis.  The lesions are  frequently  bilateral,  the  mortality  is
higher  with  revascularization  and the cure rate for hypertension is lower.
Many  patients  will   not   be   candidates   for  angioplasty  because  the
atherosclerotic plaques are at the ostia.  The recurrence rate is  higher  in
atherosclerotic  lesions than in fibrous lesions, and may approach 30% within
one  year.   Because  of  the  above  reasons,  medical  therapy  is  usually
preferable if there is no impairment of renal function.  Calcium antagonists,
diuretics, beta blockers and selective  alpha1 adrenergic blockers are useful
in atherosclerotic renovascular disease.  ACE inhibitors are  effective,  but
should  not  be used in bilateral stenosis or in renal stenosis of a solitary
kidney.  Renal function and Technetium-99m DTPA  flow scans should be done at
reasonable intervals to detect progression of the stenosis.  For those  cases
of  resistant  hypertension  with short lesions 1-2 cm distal to the orifice,
angioplasty should be done.   ASA  and/or  dipyridamole may be used following
angioplasty.  FIBROUS RENOVASCULAR DISEASE:  Angioplasty  or  saphenous  vein
bypass  grafting  is usually the treatment of choice in these young patients.
Cure rates can be up to  85%  if  renal  vein renin activity is higher on the
side of the lesion, the lesion  is  unilateral,  the  hypertension  has  been
present  for  less  than 5 years, and the technetium-99m DTPA shows decreased
function on the  side  of  the  lesion  with slower perfusion.  Complications
include  dissection,  rupture,  and  thrombosis  of  the  renal  artery.   If
hypertension persists, in spite of  successful  angioplasty,  beta  blockers,
calcium antagonists, diuretics and selective alph1-adrenergic blockers may be
used.   For incomplete patency or restenosis, stents may be used or saphenous
vein  bypass  grafting  may  be   done.   PRE-ECLAMPSIA  AND  ECLAMPSIA:  ACE
inhibitors are contraindicated and diuretics or nitroprusside are  relatively
contraindicated.   Hydralazine  10-20  mg  IV  is  ued  for  BP  > 150/105 or
methyldopa given at 250 mg BID-QID.  Magnesium  is given as a loading dose of
2-4 grams over 5 minutes IV followed by an  infusion  of  1-2  grams/hour  to
prevent  or  treat seizures.  Diazepam 5-10 mg may also be used IV to control
convulsions.  C-section or induction of  labor  should be carried out as soon
as is feasible.  CHRONIC RENAL  DISEASE:  Hypertension  in  this  setting  is
usually  due to volume expansion and treated with diuretics.  If the GFR is <
30 ml/min,  furosemide,  bumetanide,  metolazone  or  indapamide  may be used
initially.

                     -HYPERTENSION AND SURGERY-
If hypertension is stable and the diastolic is  <  110  mm  Hg,  surgery  can
proceed.  If diastolic is > 110, surgery should be postponed for several days
until the BP is stablilized.

                        -HYPERTENSIVE CRISIS-
NITROPRUSSIDE: Give 0.5-1.5 ug/kg/min to start with, then maintenance  up  to
10  ug/kg/min.   Add 50 mg of reconstituted sodium nitroprusside to 250 ml of
either 5% dextrose in water or normal saline.  The solution should be covered
with an aluminum foil or paper  bag  to protect it from light.  Nitroprusside
has its onset of action within 3-5 min.  It acts directly on vascular  smooth
muscle  producing  mostly  arterial, and to a lesser extent, venous dilation.
The heart rate (HR), cardiac  output  (CO)  and extracellular fluid (ECF) all
may increase or have no change.  There is a decrease of  systemic  resistance
(SVR).   The  pulmonary capillary wedge pressure (PCWP) will decrease or have
no change.  There will be an increase of the plasma renin activity (PRA), and
angiotension II  (ANG  II).   SIDE  EFFECTS:  Side  effects  are  cyanide and
thiocyanate  toxicity.   Clinical  signs  of  thiocyanate  toxicity   include
headache,   nausea   and   vomiting,  tremulousness,  confusion,  drowsiness,
psychosis and coma.  Deaths due to  cyanide poisoning are extremely rare.  If
the patient is given an infusion of nitroprusside for  more  than  24  hours,
serum  thiocyanate levels should be done daily.  Concentration > 10 mg/dL are
associated with toxicity; >  20  mg/dL  could  be  fatal.  Always monitor the
renal  status  as   thiocyanate   is   excreted   via   the   kidney.    Oral
antihypertensives  should  be  started  as soon as possible; usually when the
diastolic reaches 100 mm  Hg.   If  needed  hemodialysis is used for treating
thiocyanate toxicity.  Nitroprusside is indicated for hypertension associated
with CNS events, CHF, and aortic dissection and hypertensive  encephalopathy.
LABETALOL: Use 20 mg IV over 2 minutes to start with by bolus.  If a response
is  not  seen,  then double the dose q 10 min to a total of 300 mg.  Onset of
action is in minutes and lasts  for  4-6  hours.  A labetalol infusion may be
prepared by adding 200 mg of labetalol  (40  mL)  to  160  mL  of  either  5%
dextrose  in  water or normal saline.  The infusion rate is 0.5 mg/min.  This
is then titrated  to  obtain  the  desired  blood  pressure.   In most cases,
hypertension is under control when labetalol is given at a dose of 2  mg/min.
Infusion  rates up to 4 mg/min may be used.  There is a decrease or no change
in the HR and CO.  There  is  a  decrease  of  the SVR.  The PCWP and ECF may
either increase or have no change.  There is a decrease in both the  PRA  and
ANG  II.   Labetalol  is a sympatholytic agent and is unique in that there is
both post synaptic  non-cardioselective  Beta  blockade  and Alpha1 blockade.
Since there is an oral form, the patient can be switched  to  oral  labetalol
after BP is controlled.  SIDE EFFECTS:There is a relative contraindication in
patients with CHF, bradydysrhythmias, and bronchospastic lung disease.  Watch
for  paradoxical  hypertension that occasionally happens.  Also, there may be
orthostatic dizziness.  Labetalol  is  useful in hypertensive encephalopathy,
angina, renal failure,  pheochromocytoma,  antihypertensive  withdrawal,  and
interactions   between   monamine  oxidase  inhibitors  and  drugs  or  food.
PHENTOLAMINE: Give a test dose of  1  mg  IV  over 2 minutes.  If there is no
marked hypotension then give 5-10  mg  (.1-.2  mg/kg  IV)  over  the  next  4
minutes.   It  can  be  given  every 5-15 minutes.  Phentolamine is useful in
hyperadrenergic states such as  pheochromocytoma,  but  has a very short half
life and the BP will start to rise again in 10 minutes,  at  which  time  the
phentolamine  can  be  given  in intermittent boluses or a drip of 100 mg/hr.
Because of a reflex tachycardia, a  beta blocker should be used.  ENALAPRILAT
(Vasotec): Start with 1.25 mg (1 ml of a 2 ml vial) given  over  a  5  minute
period.  Increase to 5-10 mg as needed, then give q 6 hours.  The peak effect
usually  is seen in 30 minutes, but may not be until 4 hours.  Hypotension is
very infrequent but can be  treated  with fluids.  Diuretics will enhance the
effect.  Enalaprilat has no effect on the HR but does cause a decrease in the
SVR, PCWP, and ECF.  The CO is increased.  The PRA is increased and  the  ANG
II   is  decreased.   Enalaprilat  is  excreted  primarily  by  the  kidneys.
Enalaprilat is useful in CHF.  HYDRALAZINE:  The  initial dose is 10-20 mg IV
ever 20 minutes as needed or 10-50 mg IM (onset  of  action  in  30  minutes)
every  6  hours  IM.   The  peak  effect  occurs  at  about  60  minutes.  If
hydralazine is used as a continuous  infusion,  200  mg of drug is added to 1
liter of 5% dextrose in water or normal saline, and  infused  at  0.2  mg/min
initially,  and  subsequently  titrated.   The  onset of action by continuous
infusion occurs within  10  to  20  minutes.   Peak  effect  is seen at 20-40
minutes  with  continuous  infusion.   Hydralazine  should  not  be  used  in
myocardial ischemia.  It is  most  useful  in  pre-eclampsia  and  eclampsia.
Hydralazine is a direct acting arterial vasodilator.  It exerts little effect
on  the  venous  system.   Reflex  tachycardia,  increased  myocardial oxygen
consumption and increased cardiac output  are  the major effects.  There is a
decreased SVR and increase in PCWP and ECF.  The PRA  and  ANG  II  are  both
increased.  Hydralazine is metabolized primarily by the liver by acetylation.
Some  patients, genetically, are rapid acetylators and metabolize hydralazine
rapidly, and therefore a more  frequent  dosing schedule may be needed.  SIDE
EFFECTS: Side effects include headache, palpitations,  orthostatic  dizziness
and  edema.   There  may  be  exacerbation  of  angina.   Drug  induced lupus
erythematosus occurs  rarely  with  parenteral  administration  and much more
commonly with oral hydralazine.  In this syndrome there may be  rash,  fever,
arthralgias,   arthritis,   serositis,   elevated   sedimentation   rate  and
antinuclear  antibodies.   NITROGLYCERIN:  Nitroglycerine   is  given  as  an
infusion of 5-100 ug/min by adding 50 mg/250 ml of 5% dextrose and water  and
then  titrating  to  desired BP.  Can give up to 300ug/min.  Nitroglycerin is
useful  in  myocardial  infarction,  pulmonary  edema,  and  unstable angina.
NIFEDEDPINE: Can be given as  10  mg,  and  then  biting  and  swallowing  or
sublingually.   The  peak effect is seen in 30-45 minutes.  Nifedipine should
be avoided in  unstable  angina  or  evolving  MI  as  it may lower perfusion
pressure.   Nifedipine  maintains  or  increases  the  cerebral  blood  flow.
Nifedipine causes an increase  or  no  effect  in  the  cardiac  output,  and
conduction  in  the  sinoatrial  node and atrioventricular node.  There is an
increase in the HR and coronary blood flow.  There is a decrease or no change
of myocardial contractility.  There is  a  fairly marked decreased in PVR and
an increase in sodium retention.  There is a lack of a  predictable  response
to  nifedipine.  The duration of response is 2-6 hours.  CLONIDINE: Clonidine
is given initially as .1-.2 mg orally followed by .1 mg/hr to a total dose of
0.6 - 0.7 mg over 6-7 hours.  The  onset  of action is at 30-60 min and peaks
at 2-4 hours.  It does not cause reflex tachycardia and can be  used  in  CHF
and  myocardial  ischemia.   It  can  be  useful in hyperadrenergic states as
cocaine  toxicity,  clonidine   withdrawal,   MAO  inhibitors  with  tyramine
ingestion and  phenylpropanolamine.   The  major  disadvantage  is  sedation.
Therefore,  it  shouldn't  be used in hypertensive encephalopathy, stroke, or
subarachnoid hemorrhage.  It  can  cause  significant bradycardia and rebound
hypertension if stopped abruptly.  CAPTOPRIL: Give as  a  25  mg  tablet  and
onset  will  occur  in  15  minutes  and  peak  in 2-3 hours.  There may be a
precipitous  drop  if  used   in   patients  with  CHF,  scleroderma  crisis,
renovascular disease and those on diuretics and vasodilators.  Lisinopril and
enalapril have slower onsets and shouldn't be used when a rapid reduction  is
needed.   It  doesn't  cause  reflex  tachycardia or salt retention.  It will
maintain cerebral blood flow.  It  is  useful in malignant hypertension, CHF,
renovascular and cerebrovascular disease.  There is an increase in the CO and
PRA and a decrease in SVR, PCWP, ECF and ANG  II.   Side  effects  are  rash,
agranulocytosis,  and angioedema.  MINOXIDIL: The initial dose is 5 mg with a
repeat dose in 6 hours if needed.  It  should be used with a beta blocker and
diuretic.  It doesn't cause a rapid decrease in blood pressure and should not
be used with CHF, myocardial ischemia  or  pheochromocytoma  because  of  the
reflex  tachycardia.   DIAZOXIDE:  Diazoxide  can  be given at 50-150 mg (1-2
mg/kg) IV over a 5-10 second period,  and can be repeated every 10-15 minutes
as needed, or can be given as a 7.5-30 mg/min IV  infusion.   Diazoxide  acts
directly  on  vascular  smooth muscle.  There is an increase of HR, CO, PCWP,
ECF, PRA and ANG II.  There is  a  decrease in SVR.  There is onset of action
within 5 minutes and a peak effect within 3-5  minutes  if  given  as  an  IV
bolus.  The duration of effect ranges from 4-12 hours.  SIDE EFFECTS:The most
serious  effect  is  prolonged hypotension.  This occurs less frequently when
mini boluses are given rather than the  full  300 mg given as a bolus.  There
may be palpitations  and  tachyarrhythmias  and  peripheral  edema.   It  may
produce   hyperglycemia   by   inhibiting   Beta  islet  cell  function.   If
extravasation occurs there  may  be  superficial thrombophlebitis, cellulitis
and  necrosis  as  diazoxide  is  very  alkaline.   TRIMETHAPHAN   CAMSYLATE:
Trimethaphan  can  be started as a .3 -.5 mg/min IV infusion by adding 500 mg
in 500 ml of 5% dextrose  in  water  and then titrating to the desired level.
In most patients  the  hypertension  is  controlled  by  giving  1-4  mg/min.
Trimethaphan  is  a  ganglionic  blocking agent and will decrease the HR, CO,
SVR, PCWP  and  increase  the  ECF.   SIDE  EFFECTS:  Trimethaphan  can cause
postural hypotension and patients should be kept  at  bed  rest  and  may  be
placed  in  a  15  degree  reverse  Trendelenburg  position  to  optimize the
hypotensive effect.   Other  side  effects  include  adynamic  ileus, urinary
retention and mydriasis.  In very high doses of greater than 5

           -HYPERTENSIVE CRISIS AND SPECIFIC DRUG THERAPY-
Most  hypertensive  crisis  can  be  controlled  with  the  following  drugs:
Nitroprusside,  labetalol,  diazoxide,  nimodipine,  nitroglycerin,   calcium
antagonists,  nicardipine and hydralazine.  However, it is important that the
appropriate drug be matched up  with the condition producing the hypertensive
crisis, and that certain drugs not  be  given  as  they  may  exacerbate  the
hypertension or underlying disease.  In most cases hypertensive crisis can be
defined as an elevation of the diastolic pressure greater than 120.  However,
this rule needs to be modified in some cases depending on whether the patient
has had pre-existing hypertension or normal blood pressure.  If a patient has
had normal blood pressure in the past, and then suddenly develops a diastolic
BP  of  100-110	 this rapid change could be disastrous.  On the other hand,
if a patient has chronic elevation  of the BP and suddenly develops elevation
of the diastolic pressure the results may not be  as  severe  with  diastolic
pressures  greater  than  120  mm  Hg.   Hypertensive  crisis usually affects
patients that have pre-existing elevation of the BP.  Blacks, smokers and men
tend to be affected.  Hypertensive  crisis,  to place it in perspective, will
only  occur  in  about  1-2%  of  those  that  have   hypertension.    AORTIC
DISSECTION:   In this disease the blood pressure should rapidly be reduced to
around 120/80 in order to reduce the  shearing force and reduce the chance of
further dissection.  Aortic dissection is suspected if the patient has chest,
back or abdominal pain associated with abnormal abdominal  pulsation,  aortic
regurgitation,  peripheral pulse deficits, and widening of the mediastinum on
chest  x-ray.   Aortic  dissection  of  the  ascending  aorta  is  a surgical
emergency whereas dissection beyond the left  subclavian  artery  is  treated
medically.   MRI,  transesophageal  echocardiography,  CT and angiography all
have  been   used   for   diagnosis.    Recently   MRI   and  transesophageal
echocardiography have emerged as the procedures of  choice.   DRUGS  USED  IN
AORTIC  DISSECTION:  Beta  blockers  plus  nitroprusside  or trimethaphan, OR
labetalol  used  alone.   Avoid   hydralazine  and  diazoxide.   SUBARACHNOID
HEMORRHAGE: Subarachnoid hemorrhage may be due to rupture of a berry aneurysm
or  an  arteriovenous  malformation.   Reduction  of  BP  in  the   face   of
subarachnoid   hemorrhage  is  somewhat  controversial  because  of  possible
induction of cerebral spasm.   However,  if  the  BP  is severely elevated, a
cautious, slow reduction over several hours may be attempted  to  reduce  the
pressure  to  around  170/100  or 20% of the patient's BP.  Nimodipine is now
standard therapy in  subarachnoid  therapy  as  it  has  been shown to reduce
death, disability and the vegetative state by  about  40%.   Nimodipine  will
help  reduce  the cerebral spasm, but in the recommended oral dose, the BP is
not significantly lowered.  DRUGS USED IN SUBARACHNOID HEMORRHAGE:Nimodipine:
60 mg po  QID  for  21  days.   Start  within  96  hours  of the subarachnoid
hemorrhage.  Nitroprusside and labetalol may be used.  Avoid  beta  blockers,
diazoxide,  clonidine, and methyldopa.  ISCHEMIC STROKE: The same precautions
for reduction of hypertension in  ischemic  stroke  should be followed as for
subarachnoid hemorrhage because decreases can precipitate decreased  cerebral
perfusion.   Reduce  slowly and by about 20%.  DRUGS USED IN ISCHEMIC STROKE:
Nitroprusside and labetalol.  Avoid diazoxide, methyldopa, clonidine and beta
blockers.  INTRACEREBRAL HEMORRHAGE: Treatment should only be given if the BP
is exceedingly high such as  greater  than 200/130.  The outcome prognosis is
usually poor with intracerebral bleeds and treatment doesn't  usually  change
the  course.   TREATMENT FOR INTRACEREBRAL HEMORRHAGE:Treat with Labetalol or
nitroprusside only if BP is greater than 200/130.  Otherwise, no treatment is
required.  ISCHEMIC HEART DISEASE OR  MYOCARDIAL INFARCTION: An effort should
be made to decrease peripheral vascular resistance, sympathetic activity  and
increase  coronary  perfusion  which will in turn decrease oxygen demands and
wall  tension.   TREATMENT   OF   ISCHEMIC   HEART   DISEASE  AND  MYOCARDIAL
INFARCTION:Nitroglycerine is the drug of  choice  and  should  be  given  IV,
titrated  to reduce the ischemic pain and/or reduction of diastolic BP to 100
mm Hg.  Labetalol given IV as  well  as  calcium channel blockers may also be
used as they will  favorably  influence  the  BP.   Nitroprusside  should  be
reserved  for  those  that  are  refractory  to  the  above  measures.  Avoid
hydralazine and  diazoxide.   LEFT  VENTRICULAR  FAILURE:  Treatment  of left
ventricular failure associated with a hypertensive crisis should  be  treated
with drugs that will reduce preload and or afterload.  TREATMENT USED IN LEFT
VENTRICULAR  FAILURE:Nitroprusside and nitroglycerin are the drugs of choice.
Avoid beta blocker  and  labetalol.   HYPERADRENERGIC STATES: Hyperadrenergic
states can  be  caused  by  cocaine  overdose,  pheochromocytomas,  clonidine
withdrawal  and  amphetamines.  All of these conditions can cause arrhythmias
and    myocardial    ischemia.     TREATMENT    USED    IN    HYPERADRENERGIC
STATES:Phentolamine, labetalol, and  nitroprusside  are  the drugs of choice.
Reinstitution of clonidine is  used  for  clonidine  withdrawal.   ECLAMPSIA:
TREATMENT  FOR  ECLAMPSIA:  Hydralazine,  magnesium  sulfate,  labetalol  and
calcium  antagonists.   Avoid  diuretics,  ACE  inhibitors,  and timethaphan.
POST-OPERATIVE  HYPERTENSION:  TREATMENT   FOR  POST-OPERATIVE  HYPERTENSION:
Labetalol,   nitroglycerin,   nitroprusside,    and    nicardipine.     Avoid
trimethaphan.    ACUTE   RENAL   INSUFFICIENCY:  TREATMENT  FOR  ACUTE  RENAL
INSUFFICIENCY Labetalol, nitroprusside, and nicardipine.  Avoid beta blockers
and trimethaphan.  SPECIFIC  DRUGS:   Propranolol  (Inderal):  Give a loading
dose of 1-10 mg, then 3 mg/hour  IV  followed  by  80-640  mg/day  orally  in
divided  doses.  Nitroprusside (Nipride): 0.25-10 ug/kg/min IV with titration
to desired BP.   (Add  50  mg  to  250  ml  of  D5W).  Trimethaphan camsylate
(Arfonad): Give 2-4 mg/min  IV  infusion.   (Add  500  mg  to  500  ml  D5W).
Labetalol (Trandate): Give 20 mg IV bolus (0.25 mg/kg), then 20-80 mg boluses
IV  every  10  minutes  and titrate to desired BP.  (maximum of 300 mg).  For
infusion give 0.5-2 mg/min.  (max 300 mg/day).  Follow orally with 100-400 mg
po BID.  Magnesium sulfate: Give 1-2  grams  (2-4 ml) 50% solution (8-16 mEq)
IV bolus over 5-15 minutes.  For infusion drip,  add  2  grams  of  Magnesium
sulfate  to  250 ml of D5W and drip at 3-20 mg/min.  Start at 10 mg/min or 75
ml/hour.  Hydralazine (Apresoline): 10  mg  IV  every  20 minutes prn to keep
diastolic below 100.  Nicardipine: 20 mg tid initially po.  Maximum of 120 mg
daily.  Nicardipine SR (Cardene): 30-60 mg bid.  Nitroglycerin: 5-100  ug/min
IV,  titrated  to desired BP up to 300 ug/min.  Add 50 mg of nitroglycerin to
250 ml of D5W.  Nimodipine: 60 mg  QID  for 21 days.  Diazoxide: 50-150 mg IV
over 5-10 seconds, repeat every 10 minutes as  needed  or  give  infusion  at
7.5-30  mg/min  IV.   Phentolamine  (Regitine): Give 5-10 mg IV and repeat as
needed up to 20 mg.  Clonidine (Catapres): Give .2 mg po initially,

                    -HYPERTHYROIDISM (Treatment)-
Before embarking upon treatment, an accurate diagnosis must be made.  Grave's
disease and  multinodular  goiter  account  for  more  than  90%  of cases of
hyperthyroidism.  Other causes would include toxic adenomas, excessive iodine
ingestion, neonatal hyperthyroid disease,  pituitary  adenoma,  De  Quervains
subacute thyroiditis, silent subacute thyroiditis and postpartum thyroiditis.
Make  sure  that  you  are  not  treating  thyroiditis  that tends to cause a
transient hyperthyroidism which will spontaneously resolve without treatment.
Currently antithyroid drugs  and  radioiodine  are  the treatments of choice.
Surgery is rarely used any more, except in certain  situations.   Surgery  is
recommended  when  antithyroid  therapy and radioiodine are not acceptible in
children because of drug allergies, poor response, and is not accepted by the
patient.  Surgery in adults is  only  indicated  when  the goiter is large or
when thyroid cancer is present.  By using  antithyroid  drugs  initially  you
have  the  opportunity  to see if the patient will have a remission after the
patient has been on the medication  for about 1-2 years.  Unfortunately, only
about 50% will have a  remission  and  about  20%  will  develop  spontaneous
hypothyroidism.   Radioiodine will cause permanent hypothyroidism in virtualy
all patients.  Radioiodine has been shown  to have no detrimental outcomes as
far as reproduction or fertility when given to  women  of  childbearing  age.
Radioiodine  has  replaced  surgery,  in  most  instances,  for  treatment of
hyperthyroidism in children, and adolescents as a second line treatment after
failure with antithyroid  drugs.   ANTITHYROID  DRUGS: Propylthiouracil (PTU)
and methimazole (Tapazole) are both available to treat  hypothyroidism.   The
usual  starting dose of PTU is 300 mg daily, given as two 50 mg tablets every
8 hours.  It should not be given  as  a single dose because it has short half
life.  Methimazole is usually started at 20-30 mg  given  as  a  single  dose
daily.  As the patient becomes euthyroid, the dose is decreased to the lowest
dose  that  will  maintain  the  T4  and  T3  at  normal  levels.  The dosage
adjustments should be based upon the  T4 and T3 and clinical response, rather
than normalization of the TSH (The TSH  remains  suppressed  long  after  the
serum  T4  returns  to  normal).   Most hyperthyroid patients taking PTU will
require about  6-12  weeks  to  become  euthyroid,  and  about  4-6 weeks for
methimazole.  For patients that have troublesome symptoms of  hyperthyroidism
during   the   interim   before   the   antithyroid  drugs  have  established
euthyroidism, beta blockers may be given.  This is accomplished by using such
long   acting   beta   blockers   as   atenolol,   metoprolol,   nadolol  and
propranolol-LA.  Both  PTU  and  Tapazsole  function  by  inhibiting  thyroid
hormone  biosynthesis.   They  do this by blocking the utilization of trapped
iodide.  The coupling of  mono  and  diiodotyrosine  may also be inhibited by
these durgs.  PTU also has the ability to inhibit  T4  to  T3  conversion  in
peripheral  tissues, a propertiy not shared by methimazole.  PTU also crosses
the  placenta  to  a   lesser   extent,   and   appears  in  breast  milk  in
smaller	quantities than methimazole.  This makes PTU the preferred  treatment
for  breast feeding and during preganancy.  Also, propylthiouracil has little
or no teratogencity.  Side effects of antithyroid drugs occur in less than 5%
of patients.  Some of these are  minor such as nausea, skin reactions, slight
decreases in leukocytes, and bitter taste.  These do  not  require  that  the
drug  be  discontinued.   Sometimes  changing  to  an  alternate drug will be
helpful.   More  severe  reactions  include,  arthhritis,  urticaria, diffuse
erythema,  fever,  and  angranulocytosis   (occurs   in   less   than   .5%).
Agranulocytosis  development  usually  occurs  suddenly, sometime less than 3
months after starting the drug,  and  is probably not preceded by leukopenia.
Agranulocytosis probably develops as frequently in  PTU  as  in  methimazole.
Once  the  drug is discontinued, the hematologic changes will usually resolve
within 7-10 days.  Patients that develop a sore throat and fever while taking
these drugs  should  immediately  discontinue  the  drug  and  be  started on
antibiotics.  The administration  of  granulocyte-colony  stimulating  factor
(G-CSF)  may  help  resolve the leukopenia.  In most cases, antithyroid drugs
are given for about 1-2 years and  then tapered and discontinued, in order to
ascertain whether the patient will remain euthyroid.  Unfortuantely, there is
no reliable way to predict which patients will obtain a  permanent  remission
after  discontinuance.   In  general,  about 50% will achieve remission, with
remission rates higher  in  patients  that  have  mild hyperthyroidism, small
goiters, and those treated for longer periods  with  the  antithyroid  drugs.
The  remissions  may  not be permanent, so life long monitoring is necessary.
If a remission is not achieved, the patient may need a second course of drugs
or radioiodine.  RADIOIODINE:  	Radioiodine  is  the preferred treatment for
Graves's disease, toxic multinodular goiter and toxic  nodules.   Radioiodine
has  been in use since the 1940s.  The usual dose of radioiodine is 5-15 mCi.
This typically would give ovarian radiation  in  the order of about 1-2 rads.
This is well within the range that is considered  normal,  and  there  is  no
evidence  that  radioiodine  used in this manner is harmful to women or their
progeny.  There has been  no  problem  with radiation induced thyroid cancer,
leukemias or genetic disorders with about 40 years of use.   In  fact,  there
has  been  no increased teratogenicity in the offspring of patients receiving
high doses of radioiodine  for  cancer  of  the  thyroid.  It takes about 4-6
weeks for symptoms to improve, and about 6-8 weeks for the  thyroid  function
tests  to  improve.  If, after this amount of time, the thyroid gland has not
decreased in size, there has not been a decrease in symptoms, weight gain and
a return of the T4 and T3  to  normal,  the patient will need to be retreated
with radioiodine with an amount that is equal to, or greater than the initial
dose.  In most patients the abnormal thyroid function tests  will  normalize.
Because  of  this delay, beta blockers are used to ameliorate any symptoms of
hyperthyroidism.  In a minority of  patients, the symptoms of hyperthyroidism
have been exacerbated by radioiodine, due to  the  development  of  radiation
thyroiditis,  but  this  can  be  controlled with beta blockers.  The thyroid
tenderness can be controlled  with  ASA.   Elderly patients and patients with
heart disease are usually pretreated with antithyroid drugs before  receiving
radioiodine.   Otherwise,  pretreatment is not required.  The major draw back
of radioiodine therapy is  the  development  of hypothyroidism.  About 50% of
patients will develop hypothyroidism within the first year with a  subsequent
incidence of 2-3%/year.  Virtually all patients will become hypothyroid after
10-20  years  and  must  be followed.  Radioactive iodine is the treatment of
choice in patients with toxic multinodular or toxic solitary nodules, because
antithyroid	drugs  will  not  induce   a  spontaneous  remission.   In  these
patients, the development of hypothyroidism is less common  than  in  Grave's
disease,  because  the  radioiodine  is  concentrated  mainly  in  the toxic,
functioning nodules, while the remaining suppressed thyroid tissue is spared.
There is still  controversy  in  whether  adolescents  should be treated with
radioiodine even though there has been no evidence of teratogenicity or  long
term  genetic damage.  Some studies have suggested that there is an increased
incidence  in  the  exacerbation  or  development  of  Graves ophthalmopathy.
SURGICAL TREATMENT: Surgery is now only  used  in  special  circumstances  in
which  children  or adolescents have failed with thionamides, are allergic or
noncompliant, patients who  refuse  radioiodine,  and  in  patients with very
large goiters.  Side effects of surgery include laryngeal  nerve  damage  and
hypoparathyroidisim.  Hypothyroidism will develop in about 10-60% immediately
with  an  additional  1-3%/year.   For many years patients were prepared with
antithyroid drugs + iodine, 5-10 drops/day  of Lugol's solution, for 4-7 days
prior to surgery.  Pretreatment with thionamides should  be  continued  until
the  serum  T4 and T3 are normal.  Recently, patients are being prepared with
beta adrenergic blockers with  or  without  the addition of potassium iodide.
The advantage of this method is that the patient becomes prepared faster than
the usual waiting period of 4-12 weeks with the thionamides.  Propranolol  is
usually  given  in  doses of 160-240 mg/day to obtain a resting pulse of less
than  80  beats/minute.   With  this   method,  the  patient  doesn't  become
euthyroid, even with the addition of iodine, and the patient may require beta
blockers following surgery.  Since there  has  been  a  higher  incidence  of
postoperative  problems,  such as fever and tachycardia, in patients prepared
with beta blockers, most patients are  still prepared with PTU or methimazole
until the patient is euthyroid, plus SSKI 1-3 drops/day for 10 days prior  to
surgery.   PREGNANCY  AND HYPERTHYRODISM: Antithyroid drugs are the treatment
of choice in pregnant patients.  PTU is  the preferred agent because it has a
decreased transplacental transfer as compared with methimazole.  Furthermore,
methimazole has been associated with the development of a scalp defect  known
as aplasia cutis.  PTU is usually initially started as 300 mg/day in pegnancy
and  reduced  to  100 mg or less later in pregnancy.  When giving these drugs
the free thyroxin  index  should  be  kept  in  the  upper  part of normal or
slightly thyrotoxic as many patients will spontaneously  improve  during  the
last  months  of pregnancy.  Therefore, the dose of the antithyroid drugs can
be  lowered  later  in  the  pregnancy.   The  main  side  effect  of  giving
antithyroid drugs is neonatal  thyroid  suppression.   Doses of PTU below 150
mg/day have been shown to rarely cause fetal thyroid dysfunction.   Following
delivery  there  is often an exacerbation of the hyperthyroidism which can be
controlled with  beta  blockers.   Beta  blockers  can  also  be  used during
pregnancy as they are considered to be safe.  PTU  can  be  used  in  nursing
mothers, but the neonate should be monitored.  Surgery is rarely indicated in
pregnancy,  but  if  needed may be done in the second trimester.  Radioactive
iodine is contraindicated in pregnancy,  as  well as in the postpartum period
during breast feeding.

                           -HYPOMAGNESEMIA-
ACUTE CAUSES:  include  alcoholic  withdrawal,  acute  pancreatitis,  insulin
administration,   respiratory   alkalosis,  and  IV  glucose  administration.
CHRONIC CAUSES: Cisplatin therapy  will  cause defective tubular reabsorption
of magnesium and enhance renal excretion of magnesium.  Other causes  include
hypercalcemia,       hyperthyroidism,      hypoparathyroidism,      postrenal
transplantation, postacute tubular  necrosis, nasogastric suction, intestinal
malabsorption, chronic diarrhea, laxative abuse, inflammatory bowel  disease,
short bowel syndrome, loop diuretics, hyperaldosteronism, hypervitaminosis D,
poor intake and alcoholism.

                            -HYPOTHERMIA-
Systemic  hypothermia  occurs  because  of an imbalance between heat loss and
heat production.  Heat loss  occurs  by conduction, convection, radiation and
evaporation.   Heat  production  is  mediated  through  shivering  which  can
increase heat production by 2-3 fold.   As  hypothermia  develops,  the  body
undergoes several changes in the cardiac, CNS, pulmonary, GI, and GU systems.
Systemic  hypothermia,  for  practical  purposes  may  be  divided into early
hypothermia  (35-37  C   with   shivering,   cool  cyanotic  extremities  and
tachycardia), Mild hypothermia (33-35 C with hyperventilation, confusion, and
disorientation),  Moderate  hypothermia  (30-33  C  with   lethargy,   atrial
fibrillation, J wave formation, and amnesia), and Severe hypogthermia (< 30 C
with  ventricular  fibrillation,  asystole,  apnea,  coma, dilated pupils and
absent shivering and absent tendon reflexes).  CARDIOVASCULAR CHANGES include
atrial fibrillation, and  bradycardia  which  develop  when terperatures drop
below 32 C. Ventricular fibrillation and asystole develop  when  temperatures
drop below 25 C. Osborne waves (J point elevation and ST positive deflection)
may  develop  in  80%  of  cases  when the core temperature drops below 34 C.
Initially the PR, QRS and  the  QT  intervals lengthen with T wave inversion.
Myocardial creatine phosphokinase levels may increase.  CNS CHANGES include a
decrease in cerebral blood flow of about 7% for every  1  degree  C  drop  in
temperature.   As  the  temperature  continues  to  drop, the patient becomes
lethargic and may progress to  coma.  CIRCULATORY CHANGES include an increase
of the hematocrit secondary to splenic contraction and plasma loss,  decrease
of  leukocytes  and  platelets,  increase  of  viscosity  and  a shift in the
oxyhemoglobin dissociation curve to  the  left.   Coagulopathies may occur at
temperatures below 28 C. ENDOCRINE CHANGES include hypoglycemia (depletion of
glycogen stores), decrease of insulin production (hyperglycemia), increase of
thyroxine,  corticosteroids,  and   norepinephrine,   and   a   decrease   of
antidiuretic  hormone  release.   PULMONARY  CHANGES include hypoventilation,
bronchorrhea and respiratory depression.  The respiratory rate drops by about
50% for every fall  of  8  C  in  core  body  temerature.  As the temperature
approaches 24 C, respiratory arrest can occur.  The PO2  drops  by  7.2%  for
every   1   C  drop  and  the  PCO2  drops  by  4.4%  for  every  1  C  drop.
GASTROINTESTINAL CHANGES include  abdominal  distention, ileus, constipation,
bowel hypomotility, abdominal muscle rigidity, pancreatitis, and decrease  of
bowel  sounds.  Systemic hypothermia can be divided into primary (accidental)
or secondary causes.   Secondary  hypothermia  may  be secondary to Addison's
disease,  myxedema,  malnutrition,  old  age,  hypoglycemia,  hypoadrenalism,
hypopituitarism,   immobilization,   burns,    exfoliative    erythrodermias,
Parkinson's  disease, cerebellar lesions, Wernicke's encdephalopahty, basilar
skull fractures,  chronic  subdural  hematomas,  anorexia  nervosa, bacterial
endocarditis, pneumonia,  brucellosis,  gram  negative  sepsis,  miliary  TB,
syphilis,   uremia,  diabetic  ketoacidosis,  portal  vein  thrombosis,  CHF,
cerebrovascular   disease,   acute   pancreatitis,   infections,  septicemia,
myocaridal infarction, stroke and drugs (barbiturates, phenothiazines, carbon
monoxide,  benzodiazepines,  tricyclic  antidepressanst,  heroin,  clonidine,
glutethimide, organophosphates, and antidepressants.   Hypothermia  may  also
occur  during  surgery  or  in the immediate postoperative period, because of
large transfusions  of  cold  blood,  cold  irrigating  solutions,  open body
cavities, and vasodilation secondary to anesthetics.  CLINICAL: Early on,  in
systemic  hypothermia,  the  skin  is  cold due to vasoconstriction, there is
diuresis, and shivering is  usually  present  except  in the elderly.  If the
hypothermia is corrected at this point, recovery is rapid.  However,  as  the
core  body  temperature  drops  further,  the  patient  becomes  disoriented,
hallucinates,  muscles  stiffen,  shivering decreases, there is a drop in the
heart rate, respiratory rate, cardiac output and blood pressure.  Bradycardia
is usually present  at  core  body  temperatures  (CBT)  of  32 C, myocardial
irritability at 30 C, atrial fibrillation with a slow ventricular response at
27-30 C, ventricular fibrillation below 27 C, and hyporeflexia  and  impaired
pupillary reflexes at below 30 C. Death is usually ushered in by hypotneison,
arrhythmias,  depressed  cardiac output, CHF and cardiac arrest.  Temperature
should be monitored with  electronic  temperature sensing devices as standard
thermometers have a low temperature limit of 32-33 C. Temperature  should  be
recorded  rectally,  sublingually  and  in the axillary areas.  Rectal probes
should be inserted 15 cm and esophageal thermistors should be inserted 43 cm.
Rectal temperature changes  can  lag  behind  esophageal changes.  Electronic
systems also can moniotr the temperature in the esophagus, tympanic membrane,
pulmonary artery and bladder.   The  differential  diagnosis  should  include
alcohol   toxicity,   hypoglycemia,  drug  overdose,  diabetic  ketoacidosis,
myxedema and hyperosmolar coma.   The  patient  should  also be monitored for
such complications as acute tubular necrosis and renal failure, pancreatitis,
coagulopathies,   GI   bleeding,   ileus,   pulmonary    edema,    hemolysis,
myoglobinuria,  seizures,  and hypotension.  Continuous cardiac monitoring is
very  important.   Ventricular  arrhythmias  are  somewhat  refractory  to DC
countershock and drugs in  systemic  hypothermia.   It  is  recommended  that
defibrillation  be  used  only when the core temperature is > 31 C. Bretylium
has been particularly  effective  for  ventricular fibrillation.  LABORATORY:
The platelets and WBCs may be decreased secondary to  splenic  sequestration.
The hematocrit and hemoglobin are elevated due to hemoconcentration secondary
to  decreased  volume.   Arterial  blood gases will show a metabolic acidosis
and/or  respiratory  acidosis.    There   may   be   hyper  or  hypoglycemia,
hyperamylasemia and electrolyte alterations.  TREATMENT: There are 3 types of
rewarming: passive rewarming, active external rewarming and  active  internal
rewarming.   Patients with mild hypothermia (32 C without any serious cardiac
or metabolic alterations should be treated with passive rewarming using wraps
such as blankets  or  plastic  wraps.   Room  temperatures  should be kept at
25-32.9 C. Rewarming rates of .5-2 C/hour are appropriate.   Active  internal
core  rewarming is achieved by colonic, gastric or bladder lavage with heated
saline, pleural lavage, peritoneal  lavage  and cardiopulmonary bypass.  This
method  of  rewarming  is  somewhat  slow,  but  is  effective  in   moderate
hypothermia.   Active external rewarming is performed by wrapping the patient
in electric warming blankets, or by  immersion  in  a  warm 40 C bath.  It is
more effective in raising the termperature than passive  rewarming,  but  has
several drawbacks.  Active external warming can cause hypovolemic shock in an
already volume depleted patient by inducing external vasodilation.  It is not
effective   in   patients   with  chronic  hypothermia  and  increasing  skin
temperature can cause shivering to  stop  and interfere with heat production.
Furthermore rapid warming can result in vasodilation with sudden shunting  of
cold  blood  to  an already cold heart with the possibility of producing more
arrhythmias  such  as  ventricular  arrhythmias.   Peritoneal  dialysis  with
dialysate heated to 43 C can  be  used  at  6 liter/hour which can produce an
hourly rise of 1-2 C. Peritoneal dialysis is contraindicated in patients with
previous abdominal surgery.  Hemodialysis, alternatively, can produce a  more
rapid  rewarming,  but  requires  a  shunt.   GI and colonic lavage with warm
solutions has also been used.  IV  fluid warming is useful as a complementary
procedure, but should not be used alone.  The fluid is warmed using  a  blood
warming  coil  at  37-45 C. Cardiopulmonary bypass has been very effective in
severe  hypothermia.   By  external  warming  of  the  blood  to  40  C, core
temperature elevations can rise at the rate of 10-12  C/hour.   However,  the
patient  requires systemic heparinization, which may be a contraindication in
those with severe trauma.   Humidified,  heated  oxygen  is  also useful as a
complementary method of core rewarming.  The oxygen is  100%  humidified  and
heated to 42-46 C. This can produce rewarming rates of 1-2.5 C/hour.

                          -HYPOTHYROIDISM-
CAUSES  OF  HYPOTHYROIDISM: Primary hypothyroidism most commonly is caused by
an autoimmune disease,  usually  following  Hashimoto's  thyroiditis, and may
present as a goiter or as an atrophic gland.  Post-therapeutic hypothyroidism
can follow surgery, radioactive iodine, or propylthiouracil, methimazole  and
iodides.   Goitrous hypothyroidism can occur secondary to inheritable defects
in hormone biosynthesis or  Hashimoto's  thyroiditis.  A deficiency of iodine
will decrease thyroid hormonogenesis, with an increase  of  TSH  producing  a
goiter  with  avid trapping of iodine.  This type of hypothyroidism is almost
never see in the USA because  of  iodized salt.  Ingestion of goitrogens such
as thiocyanates, rutabagas and lithium may also cause hypothyroidism.   Viral
subacute  thyroiditis  with  a  painful  thyroid  gland can cause a transient
hypothyroidism.    Postpartum   thyroiditis    may    produce   symptoms   of
hyperthyroidism followed by hypothyroidism about 3-  6  months  post  partum.
Secondary hypothyroidism may occur with failure of the hypothalamic-pituitary
axis,  due  to  decreased secretion of TRH from the hypothalamus or deficient
secretion of TSH  from  the  pituitary.   Adult hypothyroidism usually occurs
over the age of 40 with females predominating.  CLINICAL: Hypothyroidism  can
produce  a  host  of  non-specific symptoms such as constipation, drowsiness,
fatigue, memory  impairment,  menstrual  changes,  somnolence, arthritis, dry
skin,  intolerance  to  cold,  muscle  cramps,  psychosis,   slowed   speech,
hoarseness,  puffiness  of  the eyes, drooping eyelids, coarse dry skin, hair
loss, weight  gain,  anemia,  brittle  hair,  bradycardia, dementia, enlarged
tongue, loss of the lateral 1/3 of the eyebrows, carotenemia of the palms and
soles, cardiomegaly, pleural, pericardial and abdominal fluid  accumulations,
paresthesiae  of  the  hands  and  feet, carpal/tarsal tunnel syndromes, slow
reflex relaxation times, and hypothermia.   LABORATORY:  In a full blown case
of hypothyroidism you may expect the T4 to be less than 3.5  ug/dL,  T3  less
than  .8  ng/dL, Free T4 index to be low, Radioactive T3 resin to be low, and
the Radioactive uptake decreased  to  less  than  10%  over  24 hours, TSH by
radioimmunoassay to be elevated in primary  hypothyroidism,  and  the  plasma
cholesterol  to  be  elevated.  However, over the spectrum of hypothyroidism,
all of these lab findings  may  not  be  found.  The most accurate and widely
used test for hypothyroidism is the highly  sensitive  TSH  assay.   The  new
immunoradiometric  assay  can  detect TSH levels as low as .1 uU/mL while the
lowest level of detection  of  conventional  TSH radioimmunoassays is about 1
uU/mL.  About 13% of hypothyroidism would be missed by using the conventional
TSH rather than the highly sensitive assay.  If the TSH is  greater  than  20
and  the  T4  is  low  or  borderline  one  can  diagnose hypothyroidism with
certainty.  If the TSH  is  between  5.1  and  20  with  a  low or normal T4,
hypothyroidism is possible, but not definite.  If the TSH is between .3-5 and
the T4 is low, the patient has Euthyroid sick syndrome.  If the TSH  is  less
than .3 and the T4 is low, the patient has possible hypothalamic or pituitary
dysfunction.   If  the  TSH  is  below .3 and the T4 high, hyperthyroidism is
present.  Other thyroid  function  tests  that  may  be  used in diagnosis of
hypothyroidism, but not entirely accurate include the following: The free  T4
by  immunometric  techniques  can  be  influenced by serum lipids, drugs, and
proteins.  It may be more useful than  the  free T4 index.  The free T4 index
is an estimate of the free T4, and is calculated by multiplying the  RT3U  by
the  total  T4.   This  corrects  for  alteration  in  the  thyroxine binding
globulin.  The free T4 by equilibrium  dialysis  is considered to be the gold
standard.  The total T4 will measure all T4 bound to plasma proteins and  the
concentration  will  depend  on  changes  in plasma proteins.  The RT3U is an
indirect measurement of thyroxine  binding globulin.  DRUGS AFFECTING THYROID
FUNCTION TESTS: Estrogens will increase thyroxine binding globulin which will
then falsely increase total T4.  Phenytoin interferes with the binding of  T4
to  plasma  proteins,  decreases  total  T4  levels  and may decrease free T4
levels.  Lithium will block secretion  of T4 and T3 producing hypothyroidism.
Amiodarone will cause hypothyroidism or hyperthyroidism by  interfering  with
T4   metabolism.    Cough  medicines,  if  they  contain  iodine,  can  cause
hypothyroidism.   Dopamine  can  decrease  TSH,  high  dose  salicylates will
interfere with binding of T4 to plasma proteins, and will decrease  total  T4
levels,  but  not  free T4.  Steroids can suppress TSH and decrease thyroxine
binding globulin  and  block  T4  to  T3  conversion.   TREATMENT:  For overt
hypothyroidism the patient should be treated preferably  with  levothyroxine.
Drugs such as desiccated thyroid, liothyronine, and liotrix should be avoided
as they are less physiologic.  In healthy young individuals the starting dose
is usually 100 ug.  If the patient is elderly and has coronary artery disease
the  drug  should  be started around 25 ug/day and increased slowly every 4-6
weeks as tolerated up to an  optimal  dose  of 75-150 ug.  Improvement in the
symptoms and signs of hypothyroidism should occur after 2 weeks of treatment,
but total resolution takes about 3-6 months.  Treatment should be guided with
TSH determinations, starting about  4-6  weeks  after  equilibrium  has  been
established.   However,  TSH  may  remain  elevated  for several months after
replacement has been started.  Subclinical hypothyroidism, with a TSH between
5.1 and 20 uU/mL and a normal  or  slightly  low T4 is most common in elderly
females.  Some would recommend  treatment  in  this  group  even  though  the
patient  is  asymptomatic  because  of improvement in cardiac function, lipid
profiles, and clinical hypothyroidism may develop is some of these.  Patients
with a goiter or high titers of  microsomal antibodies are at risk for future
development of  overt  hypothyroidism.   The  risk  of  treating  subclinical
hypothyroidism  includes  worsening of cardiac disease as arrhythmias, angina
and myocardial infarction, osteoporosis,  and  liver enzyme elevations.  Most
patients can be controlled with 175 ug or  less  of  levothyroxine.   If  the
patient  still  has  an  elevated  TSH after about 3 months of therapy and is
taking 200 ug of T4 daily, compliance  should be an issue.  If the patient is
non-compliant, a total dose of T4 of 1000 ug can be given once a week  as  an
outpatient.   Generic  T4  can  also  be the problem with continued high TSH.
Simply  changing  the  preparation  will  solve  the  problem.  Malabsorption
patients also have an increased requirement for T4.  High soy-bean diets  may
reduce T4 absorption.  In patients that have nephrotic syndrome there is loss
of protein-bound T4 in the urine, and this raises the requirements of T4.  If
levels  of  TSH  remain  high  in  spite of elevated FT4 and T3, there may be
resistance of  the  pituitary  and  peripheral  tissues  to  thyroid hormone.
Hypothyroidism occurring in pregnancy may need increased doses  of  T4.   The
TSH  should  be used as a guide for therapy.  The doses will vary.  Some will
require no change, others a small amount, perhaps 25 ug daily, and others may
need 2-3 times the usual requirement.  Following delivery, the dose should be
reduced, if  it  has  been  increased  during  pregnancy,  in  order to avert
hyperthyroidism.  Surgery is fairly well tolerated in  hypothyroid  patients,
but  there  is  an  increased  incidence  of  perioperative  ileus, increased
sensitivity  to  anesthetic  drugs,  sedatives  and  opiates  and psychiatric
problems.  Post-operative infections may be increased and there is less of  a
chance  to  mount  a  temperature  increase  with  hypothyroidism.  Emergency
surgery should not be  delayed  because  of  hypothyroidism, but if elective,
replacement therapy  should  be  initiated  prior  to  surgery.   Subclinical
hypothyroidism  may  have surgery without any major complications.  Transient
hypothyroidism  following  the  thyrotoxic  phase  of  subacute  thyroiditis,
postpartum thyroiditis or painless  thyroiditis  usually needs no therapy, as
these  are  self  limiting  diseases.   Occasional  hypothyroidism  following
postpartum  thyroiditis  becomes  permanent  and  will  need  T4  replacement
therapy.  Any patient that has questionable  hypothyroidism  and  yet  is  on
replacement therapy may be handled by temporarily reducing the T4 to about 50
ug  daily, and then re-evaluating the patient at about 10 weeks.  During this
time span some patients  will  redevelop hypothyroid symptoms suggesting that
they were correctly diagnosed as hypothyroid, or the TSH will still  be  high
while  on 50 ug after the 10 week waiting period.  If the TSH is normal after
this period the thyroid is  further  reduced  or discontinued and the TSH and
clinical status are again evaluated  after  about  6  weeks.   COMPLICATIONS:
Hypothyroidism  causes  an increased susceptibility for infection.  Megacolon
has been described.  If maintenance therapy with large doses of levothyroxine
are used, bone demineralization  can  occur.   Very rarely adrenal crisis has
been precipitated with vigorous treatment of pituitary or  primary  myxedema.
Infertility  can  be  caused by hypothyroidism.  Pituitary tumors can produce
sellar enlargement with  hyperprolactinemia  and  galactorrhea.  With thyroid
replacement therapy the tumors will decrease in size.  Cardiac  disease  with
CHF,  angina and arrhythmias can be produced by over ambitious treatment with
thyroid  hormone.   Myxedema  coma  can  follow  severe  hypothyroidism  with
hypoventilation,   hypothermia,   hypotension,   hyponatremia,   convulsions,
hypercapnia and hypoxia.  It may be  ushered  in by infection, and is usually
seen in elderly women with a high mortality.   DRUG  INTERACTIONS:  Once  the
hypothyroid  state has been corrected, increases in the requirements for oral
hypoglycemics and insulin may be be needed to control diabetes mellitus.  The
effects of digitalis, beta blockers,  diuretics,  sedative and opiates may be
decreased.   Cholestyramine,  colestipol  will  decrease  the  absorption  of
thyroid.  Thyroid hormone should be given either 2 hours before or 4-6  hours
after  these  resins.   If  the  patient  is taking phenobarbital, phenytoin,
carbamazepine or rifampin, the thyroid dose  may have to be increased because
of  increased  catabolism  of  the   thyroid   hormone.    The   effects   of
anticoagulants are increased.

                    -HYPOTHYROIDISM AND THE HEART-
CLINICAL:  The  patient with hypothyroidism may have enlargement of the heart
due  to  pericardial  effusion,  but  rarely  is  clinically  significant  as
tamponade is  not  a  common  feature.   There  may  also  be some myocardial
dysfunction with decreased cardiac output.  Sinus  bradycardia  is  a  common
finding  and  there  may  be  elevation of the diastolic blood pressure.  Low
density lipoprotein cholesterol is  typically  elevated.  The main problem in
treating hypothyroidism is that replacement thyroid will cause  an  increasse
in  pulse  rate,  cardiac  output,  and myocardial oxygen consumption so that
patients with coronary artery disease, myocardial disease or valvular disease
are at risk for  exacerbation  of  arrhythmias, ischemia and congestive heart
failure.  TREATMENT: The treatment of choice is  with  preparations  such  as
Synthyroid  or  Levothroid.  Generics should not be used.  Desiccated thyroid
or purified thyroglobulin  preparations  of  animal  origin  are not suitable
because they have large amounts of T3 which is rapidly  absorbed  with  early
peak levels, followed by subnormal levels later.  The potency of preparations
derived from animal sources also has a tendency to fluctuate in various lots.
Euthyroid  and  Thyrolar  which  have combinations of synthetic T4 and T3 are
older preparations that  have  no  place  in  the treatment of hypothyroidism
because they have a 4:1 ratio of T4 to T3 which  is  not  physiologic.   Most
circulating  T3  is derived from peripheral conversion of T4 rather than from
direct  secretion  from  the  thyroid  gland.   Treatment  in  patients  with
hypothyroidism  and  co-existing  coronary  artery  disease,  arrhythmias, or
congestive heart failure should be started at low doses of .0125-.025 mg/day,
and increased by a similar dose every 1 month  if  tolerance  is  acceptable.
Monitoring  for  optimal amounts of thyroid replacement is with T4 and TSH at
monthly intervals initially until the  patient becomes euthyroid.  Should the
patient develop angina, arrhythmias or CHF, the thyroxine should be  withheld
for  a few days while the patient's symptoms are treated with antianginal and
antiarrhythmic medications.  After control of symptoms, lesser amounts of the
thyroxine should be restarted.  Beta blockers may be useful to control angina
and arrhythmias, but should  be  used  at  lower  doses, because of decreased
clearance in hypothyroidism.  Patients with advanced coronary artery  disease
should   have   coronary   revascularization  prior  to  replacement  thyroid
treatment.

            -IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS-
Is a congenital lesion, but presents in adolescence.  Ejection mumur is harsh
and loudest near the apex and  is intensified by standing after squatting and
Valsalva maneuver.

                   -IDIOPATHIC PULMONARY FIBROSIS-
Is mainly a disease of the elderly with the average age of onset at 60 years.
Starts insidiously with  dypsnea  and  nonproductive cough.  Late inspiratory
crackles at lung bases and exercise induced cyanosis are  typical.   Clubbing
occurs  in  90%,  in  contrast  to  the  10%  incidence  in  hypersensitivity
pneumonitis,  sarcoidosis and connective tissue disease.  Chest x-ray shows a
diffuse reticular  or  reticulonodular  infiltrate  with  accentuation at the
bases and sparing of the apex.   Honey-combing  corretlates  with  end  stage
fibrosis.    High   resolution   CT  may  show  subpleural  linear  opacities
representing septal fibrosis.  There is  no  specific serologic test for IPF.
About 30% of patients have rheumatoid factor, with titers as high as  1:1000,
while the antinuclear antibodies may be positive in 15% with DNA negative.  A
polyclonal  gammopathy  is  present  in  75%.  About 50% have an elevated sed
rate.  Open lung  biospy  is  the  only  method for diagnosis.  DIFFERENTIAL:
Sarcoidosis usually occurs at a younger age.  Collagen vascular disease, drug
induced disease, pneumonconiosis, and CHF need to be  ruled  out.   Home  and
work  environment  exposure  to  respiratory pathogens or irritants should be
sought.  Neoplasm, granulomatous disease, histiocytosis X, pulmonary alveolar
proteinosis can be  excluded  by  fiberoptic bronchoscopy with transbronchial
lung biopsy.  TREATMENT: Progressive  disease  is  treated  with  prednisone,
alone   or  given  with  azathioprine  or  cyclophosphamide.   Prednisone  is
ineffective in about  80%  of  patients,  but  in  those  who do respond, the
response is usually rapid, with improvements in pulmonary function by 2 weeks
and maximum response by 1 month.  Prednisone is  then  gradually  tapered  to
every  other  day maintenance.  Start with prednisone 1.5 mg/d (not to exceed
100 mg/d), followed by tapering by 20 mg  every 2 weeks to a dose of 40 mg/d.
Then decrease by 5-10 mg/d every 2 weeks until a maintenance dose of 20  mg/d
is   reached.    Then  give  15-30  mg  every  other  day.   Patients  taking
azathioprine or cyclophosphamide need  CBCs  every  2  weeks  for the first 3
months.  If CBC stays stable, the CBC can be done at monthly intervals.   UAs
should  be  done if taking cyclophosphamide when frequent urination, dysuria,
hematuria  and  urgency  develop.   Liver   function  tests  are  done  also.
Azithioprine can be given at a dose of 3 mg/kg/d (not to  exceed  200  mg/d).
Vital  capacity,  DlCOsb and arterial blood gases (resting and breathing room
air) are done every 3 months.   Patients  will  show > 10% increase in FVC, >
20% improvement in DlCOsb and a 5 mm Hg or more decrease in P(A-a)O2 if there
is improvement.  COMPLICATIONS: pulmonary infection, thromboembolic  disease,
pneumothorax,  heart failure can develop.  Mortality is 50% within 4-6 years.
Ten percent of patients  will  develop  lung  cancer  with an equal amount of
adenocarcinoma and squamous cell carcinoma.  Steroids can cause osteoporosis,
myopathy, aseptic necrosis, cataracts,  hypertension,  peptic  ulcer,  weight
gain  and  hyperglycemia.   Cyclophosphamide  can cause hemorrhagic cystitis.
Azathioprine and chyclophosphamide cause  bone marrow suppression.  All drugs
used can predispose the patient to infection.

                      -INCONTINENCE (Overflow)-
Is characterized by a diminished and interrupted urinary  stream,  post  void
dribbling,  double  voiding, straining and a sensation of incomplete emptying
with  post  void   residual   urine   volume   >   500  ml.   Causes  include
pharmaceuticals, stool impaction,  restricted  mobility,  outlet  obstruction
from  BPH,  prostate  cancer, stricture, impaired detrusor contractility, and
neurogenic causes such as  diabetes  mellitus,  Parkinson's, CVA, spinal cord
damage  and   peripheral   nerve   injury.    Treatment   includes   catheter
decompression   for   about  one  week  and  renal  ultrasound  to  rule  out
hydronephrosis.  Bethanacol may improve  detrusor contractility and terazosin
may also be used as well as finasteride.  Clean intermittent  catheterization
can be used long term.  Surgery may be needed for BPH.

                       -INCONTINENCE (Stress)-
Is very  common  in  females,  in  particular  multiparous  females  who have
relaxatioon of the pelvic sturctures with hypermobility  and  malposition  of
the  bladder  neck.   There  may  be  irritative  symptoms with frequency and
urgency along  with  the  leakage.   Pelvic  floor  (Kegal  exercises) may be
helpful.  Teach the  patient  by  having  them  voluntarily  interrupt  their
urinary  stream  while  urinating.  The  exercises should then be done qid by
performing a series of 10 successive  10 second contractions of the sphincter
muscle.  Improvement usually takes about 6 weeks.  Phenylpropanolamine  25-75
mg  bid  or imipramine 10-25 mg tid may enhance sphincter function.  Estrogen
supplement is helpful in menopausal  women.  If conservative measures are not
helpful, open and endoscopic bladder neck suspension may be  done  with  long
term success rates that are excellent.

                        -INCONTINENCE (Urge)-
These patients do not experience the  prelinary  sensation  of  filling  that
warns  them  that  they  are approaching bladder capacity, which results in a
precipitous and unsuppressible  urge  to  void.   The  typical  patient has a
post-voiding residual (PVR) < 150 ml.  Treatment is  regular  timed  voiding,
modulation  of  fluid  intake and drugs such as low dose Propantheline 7.5 mg
qid or oxybutynin 2.5-5 mg  tid.   Imipramine  10-25  mg  at hs to tid may be
added.  Urge incontinence patients that have a PVR between 150-500  ml  is  a
clinical   challenge   as   incomplete  emptying  can  result  from  anatomic
obstruction	from BPH, prostate cancer,  stricture or a functional obstruction
due to inappropriate sphincteric  contraction  usually  due  to  spinal  cord
damage.   Another  possibility  is that the bladder fails to empty because of
poor detrusor contractility  (this  is  usually  the  cause  in women, and is
treated with propantheline,  oxybutynin  and  imipramine,  but  men  must  be
evaluated  for  obstruction).  Alpha blockers as terazosin 1 mg hs increasing
to 5-10 mg  hs  will  decrease  contractile  tone  at  the bladder outlet and
facilitate improved detrusor contractility.  In urge  incontinence  with  PVR
between   250-500   ml,   renal   ultrasound  should  be  done  to  rule  out
hydronephrosis as they are at high risk for urinary retention.

                      -INCONTINENCE (Urinary)-
Urinary incontinence is  typically  divided  into  4 different classes: Urge,
Stress, Overflow and Functional incontinence.  There may be a combination  of
these   that   is   operative   in  a  particular  patient.   URGE  (DETRUSOR
INSTABILITY): Urge incontinence is probably the most common of the four types
and accounts for about 65%  of  cases.   It  is characterized by a leakage of
urine caused by involuntary bladder contractions.  Once a sensation  to  void
occurs,  the  patient  can't  delay  voiding.  Causes would include cystitis,
urethritis, bladder tumors  and  stones,  diverticuli,  stroke, dementia, and
Parkinson's disease.  Some elderly patient will have a  sub-variety  of  urge
incontinence known as detrusor hyperactivity with impaired contractility.  In
this entity there is incomplete emptying of the bladder with a residual urine
greater than 50 ml.  Normally, in urge incontinence the residual post voiding
volume   is   normal.    STRESS   INCONTINENCE:  Stress  incontinence  occurs
predominantly in elderly women, although  it  can occur in men following TURP
and radiation therapy.  It occurs when there is coughing,  laughing  sneezing
or  other  activities  that  increase the intra-abdominal pressure.  There is
oftentimes a weakness of the pelvic  floor with hypermobility of the urethra,
weakness of the urethral sphincter  or  both  of  these.   The  post  voiding
residual  is normal as in urge incontinence.  OVERFLOW INCONTINENCE: Overflow
incontinence only accounts  for  about  10%  in  elderly  patients.  There is
either an anatomical or neurogenic  outflow  obstruction,  a  hypocontractile
bladder  or  use  of  certain  medications.   Causes include diabetic induced
bladder  neuropathy,  urethral  stricture,  fecal  impaction, anticholinergic
medication, detrusor-sphincter dyssynergia and low spinal cord disease.  Most
patients will complain of a  painful  bladder  distention  except  for  those
patients  that  have  an  impaired  sense.   There  is increased post voiding
residual urine found on catheterization.  FUNCTIONAL INCONTINENCE: Functional
incontinence occurs when the patient can't get  to the toilet or is unable to
get to the toilet.  LABORATORY: A voiding record  should  be  kept.   Inquire
into  past surgical procedures and current medications (prescription and over
the counter).  Post voiding residual  urine should be assessed.  Check DTR's,
perianal sensation, lower extremities sensory changes, and  rectal  sphincter
tone.   Palpate and percuss the abdomen for urinary bladder distention, check
prostate and examine for fecal  impaction.   In  women, pelvic exam should be
done for atrophic changes, cystoceles or rectoceles.  Have the patient  cough
while  supine  and  standing  to  ascertain  if  there  is any urine leakage.
Urinalysis, cultures, calcium, BUN, glucose  and serum electrolytes should be
done to rule out diseases that produce  polyuria.   Ultrasound  can  help  in
searching  for a distended bladder, enlarged kidneys, and prostate size.  The
voiding cystourethrogram can  evaluate  for  the  descent  of the bladder and
urethra at rest and when straining in the upright position.  This latter test
is useful in stress incontinence  and  men  who  have  had  a  prostatectomy.
MEDICATIONS  CAUSING INCONTINENCE: Diuretics, ephedrine, phenylpropanolamine,
Minipress, Hytrin,  Probanthine,  antihistamines,  calcium  channel blockers,
antidepressants, sedatives,  analgesics,  tranquilizers  and  antipsychotics.
TREATMENT:  URGE:  Oxybutynin  bid  or  tid  is  effective in 2/3 of cases of
detrusor instability.   It  has  a  depressant  effect  on  smooth muscle and
moderate anticholinergic action.  Propantheline 15-30 mg bid or tid  is  more
effective  if  taken  fasting.   The  side  effects  include  blurred vision,
constipation and dry mouth.   It  is  contraindicated in patients with narrow
angle glaucoma and bladder neck obstruction.  Imipramine  25  mg  qd  to  tid
decreases  bladder  contractility  and  increases  bladder outlet resistance.
Side  effects   include   those   of   anticholinergic  medications,  cardiac
arrhythmias, postural hypotension, fatigue and malaise.  Flavoxate 100-200 mg
tid to qid comes in 100 mg  tabs  and  there  are  side  effects  of  nausea,
vomiting,   anticholinergic,   vertigo,   headache,   drowsiness,  urticaria,
confusion, dysuria, tachycardia, hyperpyrexia,  and  blood dyscrasias.  It is
contraindicated in GI obstruction, obstructive uropathies and achalasia.  Use
precaution in glaucoma, elderly and cardiovascular  disease.   Transderm-Scop
patch  every  3  days  and  Dicyclomine 10-20 mg tid to qid can also be used.
STRESS: Pseudoephedrine 15-30 mg  bid  to  tid,  Imipramine  25 mg qd to tid,
Estrogen (oral 0.625 mg daily or intravaginal 0.5-1 g 2 or 3 times a week  or
transdermal  patch  .05  mg  every other day.  May take up to 2 months before
improvement  is  seen),   and   Phenylpropanolamine   (use  with  caution  in
cardiovascular disease because of increased heart rate  and  blood  pressure.
It  increases  urethral  resistance).   OVERFLOW:  Prazosin  1 mg bid to tid,
Terazosin 1 mg qd, Bethanechol  10  mg  tid (this cholinergic agent increases
the bladder pressure and stimulates bladder contractions.  It should  not  be
used  with  obstruction.   Side  effects  are  bronchoconstriction, abdominal
cramps  and  diarrhea),  and  Finasteride   5  mg  qd.   MECHANICAL  DEVICES:
Contraceptive diaphragm will help in stress incontinence,  particularly  with
high  impact  aerobics.   The  vagina  must  be  large  enough to contain it.
However, it may cause recurrent  urinary tract infection.  Weighted cones may
be useful in about 30% of women with mild to  moderate  stress  incontinence.
The  patient  continually  contracts  the  periurethral muscles to retain the
cone.  When  the  cone  can  be  successfully  retained  it  is replaced with
progressively heavier cones.   BEHAVIOR  MODIFICATION:  Kegal  exercises  are
effective  for  mild  to  moderate stress incontinence.  Patients practice by
stopping and starting urine flow.  After  this they contract the rectum about
5-80 times per day.  By doing this, it is effective in about 60-90% of stress
incontinent patients.  Alternatively, the patient may insert  a  finger  into
the  vagina and contract down on this.  This procedure takes about 3-6 months
before significant benefit is  seen.   Obese  patients should lose weight and
smokers with a chronic cough should stop smoking.  Biofeedback is helpful  in
about 25% of cases.  Bladder retraining drills are effective in patients with
diminished sensory awareness.  Patients are advised to urinate every 2 hours.
As  the  patient  improves the interval is increased by 30 minute increments.
SURGERY: Periurethral  injection  of  polytef  paste  or glutaraldehyde cross
linked collagen is injected into the periurethral tissue to provide increased
resistance to the outflow of urine.  More than  80%  become  continent  after
only  two  treatments.   It  is  well  tolerated  by  all  ages.   Only local
anesthesia is needed.   It  is  especially  useful  in  elderly patients with
incontinence caused by bladder outlet or urethral incompetence.  For overflow
incontinence caused by a large prostate, TURP,  balloon  dilatation,  bladder
neck incision and microwave tissue destruction may be used.

                      -INCONTINENCE (Urinary)-
Reversible   causes:   Delirium   associated   with   new   meds,    illness,
hospitilization,  acute  urinary  tract infection, atrophic vaginitis in post
menopausal women,  Drugs  as  narcotics,  hypnotics,  anticholinergics, alpha
adrenergic agonists, pschotrophics meds which can cause urinary retention and
overflow  incontinence,  Excessive  urine  output  from   excessive   intake,
diuretics, concentrating defects, restricted mobility and stool impaction.

                 -INFECTIVE ENDOCARDITIS MANAGEMENT-
LIKELY  ORGANISMS  IN INFECTIVE ENDOCARDITIS: SUBACUTE ENDOCARDITIS (indolent
course): Streptococcus  viridans,  Group  D  streptococci  (non enterococcus)
(Streptococcus bovis), Enterococcus  (Streptococcus  faecalis,  Streptococcus
faecium),     Haemophilus     aphrophilus,     Haemophilus    paraphrophilus,
Actinobacillus,  Actinomycetes  comitans,  Cardiobacterium  hominis, Eikenell
corodens, Kingella sp., Staphylococcus  epidermidis,  Staphylococcus  aureus.
ACUTE  ENDOCARDITIS  (Aggressive  course):  Staph  aureus,  Groups  A  B  C G
streptococci,    Haemophilus    parainfluenzae,    Haemophilus    influenzae,
Streptococcus   pneumoniae,    Enterococcus    sp,   Neisseria   gonorrhoeae.
ENDOCARDITIS IN  IV  DRUG  ABUSERS:  Staph  aureus,  Pseudomonas  aeruginosa,
Enterococcus   sp.,   Pseudomonas  cepacia,  Candida  sp.   PROSTHETIC  VALVE
ENDOCARDITIS: Staph epidermidis,  Staph  aureus,  Candida  sp.  Gram negative
bacilli,   Viridans   streptococci,   Enterococcus   sp.    Aspergillus   sp.
ENDOCARDITIS PROPHYLAXIS:  DENTAL AND UPPER RESPIRATORY PROCEDURES:  ORAL....
Amoxicillin  3  grams  1  hr before procedure and 1.5 grams 6 hrs later.  For
pediatric, amoxicillin 50 mg/kg, 1  hr  before  procedure, and 25 mg/kg 6 hrs
later.   If  allergic  to  penicillin,  erythromycin  1  gram  2  hrs  before
procedure, and 500 mg 6 hrs later.  For pediatric, erythromycin  20  mg/kg  2
hrs  before  procedure,  and  10  mg/kg  6  hrs  later.  GASTROINTESTINAL AND
GENITOURINARY  PROCEDURES:  PARENTERAL....Ampicillin  2  grams  IM  or  IV 30
minutes before procedure PLUS gentamicin 1.5 mg/kg IM or IV 30 minutes before
procedure.  If allergic to penicillin, vancomycin 1 gram  IV  infused  slowly
over  1  hr beginning 1 hr prior to procedure PLUS gentamicin 1.5 mg/kg IM or
IV 30 minutes before procedure.  For pediatrics, ampicillin 50 mg/kg IM or IV
30 minutes before procedure  PLUS  gentamicin  2  mg/kg  IM  or IV 30 minutes
before procedure.  If allergic to penicillin, vancomycin 20 mg/kg IV  infused
slowly  over  1 hr beginning 1 hr before procedure plus gentamicin 2 mg/kg IM
or  IV  30  minutes   before   procedure.   CULTURE  NEGATIVE   ENDOCARDITIS:
PENICILLIN G, 3 million units IV q 4h for 4 weeks PLUS gentamicin 1 mg/kg  IV
q  8h  for 4 weeks.  EMPIRICAL THERAPY WITH PROSTHETIC VALVE:  VANCOMYCIN 1 G
IV q 12h PLUS GENTAMICIN 1 mg/kg q 8 hrs.  EMPIRICAL THERAPY IN IV DRUG ABUSE
WITH NATIVE VALVE:  PENICILLIN G, 4  million  units IV q4h PLUS NAFCILLIN 2 g
IV q 4h PLUS GENTAMICIN 1 mg/kg q8h.   STREPTOCOCCAL  PATHOGENS  IN   ADULTS:
Aqueous  penicillin G, 10-20 million units/24h IV either continuously or in 6
equally divided doses for 4 weeks.   Also  may use Procaine Penicillin G, 1.2
million  U  IM  q6h,  OR  Aqueous  Penicillin  10-20  million   U/24   either
continuously  or  in  6  equally  divided doses for 2 weeks PLUS Gentamicin 1
mg/kg IM or IV (not to exceed 80  mg) q8h for 2 weeks.  OR Aqueous Penicillin
G 10-20 million U/24 h IV either continuously or in 6 equally  divided  doses
for  4 weeks PLUS Gentamicin 1 mg/kg IM or IV (not to exceed 80 mg) q8h for 2
weeks.  STREPTOCOCCAL PATHOGENS & PATIENT ALLERGIC TO PENICILLIN: Cefazolin 1
g IM or IV q8h for 4 weeks.  OR  Vancomycin 30 mg/kg/24h IV in 2 or 4 equally
divided doses not to exceed 2 g/24h, unless serum levels are monitored, given
for 4 weeks.  (Peak serum levels should be obtained 1 h  after  infusion  and
should  be in the range of 30-45 ug/ml for bid dosing and 20-35 ug/ml for qid
dosing).  ENTEROCOCCI  OR  STREPTOCOCCAL  VIRIDANS  WITH  A  MIC  > .5 UG/ML:
Aqueous Penicillin G 20-30 million U/24h  given  IV  continuously,  or  in  6
equally divided doses, for 4-6 weeks PLUS Gentamicin 1 mg/kg IM or IV (not to
exceed  80  mg)  q8h  for 4-6 weeks.  OR Ampicillin, sodium 12 g/24h IV given
continuously or in 6 equally  divided  doses  for 4-6 weeks PLUS Gentamicin 1
mg/kg IM or IV (not to exceed  80  mg)  q8h.   ENTEROCOCCI  OR  STREPTOCOCCAL
VIRIDANS  WITH  A  MIC  > .5 ug/ml, AND ALLERGIC TO PENICILLIN: Vancomycin 30
mg/kg/24h IV in 2 or 4  equally  divided  doses  not to exceed 2 g/24h unless
serum levels are monitored, PLUS Gentamicin 1 mg/kg IM or IV (not  to  exceed
80  mg)  q8h  for  4-6  weeks.   STAPHYLOCOCCI  IN  THE ABSENCE OF PROSTHETIC
MATERIAL: Nafcillin, sodium 2 g IV q4h for 4-6 weeks.  OR Oxacillin, sodium 2
g IV q4h for 4-6 weeks  PLUS  OPTIONAL  Gentamicin  1  mg/kg IM or IV (not to
exceed 80 mg) q 8h  for  3-5  days.   STAPHYLOCOCCI  &  PATIENT  ALLERGIC  TO
PENICILLIN  AND  DOESN'T HAVE PROSTHETIC MATERIAL:   Cefazolin 2 g IV q4h for
4-6 weeks PLUS OPTIONAL Gentamicin 1 mg/kg IM or IV (not to exceed 80 mg) q8h
for 3-5 days.  STAPHYLOCOCCI  &  PROSTHETIC  MATERIAL & METHICILLIN RESISTANT
STAPH:  Vancomycin 30 mg/kg/24h IV in 2 or 4 equally  divided  doses  not  to
exceed  2  g/24h unless serum levels are monitored for at least 6 weeks, PLUS
Rifampin 300 mg po q8h for at at least 6 weeks, PLUS Gentamicin 1 mg/kg IM or
IV (not to exceed  80  mg)  q8h  for  2  weeks.  (Rifampin is recommended for
therapy of infections due to coagulase negative Staphylococci.   Its  use  in
coagulase  positive  Staphylococcal  infection  is  controversial.   Rifampin
increases  the  amount  of  warfarin  required  for  antithrombotic therapy).
STAPHYLOCOCCI & PROSTHETIC  MATERIAL  AND METHICILLIN SUSCEPTIBLE:  Nafcillin
or Oxacillin 2 g IV q4h for at least 6 weeks, PLUS Gentamicin 1 mg/kg  IM  or
IV  (not  to  exceed  80 mg) q8h for 2 weeks PLUS Rifampin 300 mg po q8h (For
coagulase neg Staph).If patient  allergic to penicillin substitute Vancomycin
at 30 mg/kg/24 h IV in 2 or 4 equally divided doses not to  exceed  2  g/24h,
unless serum levels are monitored, for 4-6 weeks.

    -INFLAMMATORY BOWEL DISEASE (Extraintestinal manifestations)-
Arthritis  occurs in 10-20% and is usually monoarticular of the large joints.
The joints usually flare when the  colitis flairs and improves as the colitis
improves.  Ankylosing spondylitis, related to HLA-B27, and  sacroiliitis  are
usually progressive and do not improve as the colitis improves.  SKIN lesions
occur  in  10%  and  consist  of pyoderma gangrenosum, aphthous ulcers of the
mouth and erythema nodosum and usually  improve as the colitis improves.  EYE
lesions occur in 5% and consist of episcleritis and uveitis, which improve as
the colitis improves.  LIVER disease occurs  in  5%,  as  primary  sclerosing
cholangitis and is more common in ulcerative colitis than in Crohn's disease.
If  the  alkaline  phosphatase is elevated obtain ultrasonography, endoscopic
retrograde cholangiopancreatography  and  liver  biopsy  to  rule out primary
sclerosing cholangitis.  RENAl STONES OCCUR IN 5-15%.  Calcium oxalate stones
occur in Crohn's disease with malabsorption.   while  uric  acid  stones  are
secondary  to  dehydration and loss of bicarbonate in the stool in ulcerative
colitis.

                     -INTRA-ABDOMINAL INFECTIONS-
Intra-abdominal   infections,   especially   in    the   elderly,   such   as
diverticulitis, liver abcess,  appendicitis,  malignancies,  cholangitis  and
diverticular  abscess may be difficult to diagnose.  Elderly patients may not
mount an elevated white count and  the  findings may be subtle.  CT and chest
x-ray may be helpful.  Enterococcus  faecium  is  particularly  difficult  to
treat because of multiple resistance.  Anaerobes are usually involved and may
be  treated  with  clindamycin,  selected  beta-lactams  with or without beta
lactamase inhibitors, imipenem and metronidazole.

                         -ISCHEMIC COLITIS-
Ischemic  colitis  is  probably  the  most  common of the intestinal ischemic
syndromes.  It is usually  much  milder than mesenteric artery insufficiency.
There is mucosal hemorrhage and edema followed by mucosal ulcerations.   Most
patients  will  heal  after  these  initial insults without scarring.  A few,
however, will go on to transmural infarction.  Some will heal with stricture.
Ischemic colitis has been associated  with  colon cancer and abdominal aortic
aneurysm repair.  Ischemic  colitis  is  common  following  abdominal  aortic
aneurysm repair.  Many will have post- operative diarrhea, but some will have
signs  of  sepsis.   The  most  frequent sites of involvement are the splenic
flexure  and  the  sigmoid  colon.   The  rectum  is  a  very  rare  site  of
involvement.  CLINICAL: The patient  usually  first  notices a sudden mild to
moderate abdominal pain and cramping in the lower abdominal area.  Then there
usually is a loose stool with some blood mixed in  with  it.   There  may  be
localized  tenderness  overlying  the  involved  area.   If  the  patient has
transmural  involvement  the  patient  will  develop  hypotension,  fever and
peritonitis with rebound tenderness.  LABORATORY: X-rays of the  abdomen  may
show  thumbprinting  and  bowel distention.  If a barium enema is done, edema
and submucosal hemorrhage may be seen as thumbprinting.  If the patient has a
repeat X-ray in a few weeks, the barium enema may show stricture or eccentric
sacculation, or it may be entirely  normal.   If a colonoscopic exam is done,
friable, edematous submucosal hemorrhage will be seen  that  alternates  with
blanched  areas.   There may be large and irregular ulcerations seen later in
the  course  of  the  disease.   The  differential  diagnosis  would  include
inflammatory  bowel  disease  and  pseudomembranous  colitis.   TREATMENT: No
treatment is usually necessary, except  in  those  rare  cases  that  develop
peritonitis.  After a few weeks, a follow up colon X- ray may be done to rule
out  stricture.   Other  rare  causes  of  intestinal  ischemia  will  not be
discussed  in  detail   but   would   include  mesenteric  venous  thrombosis
(associated  with  abdominal  malignancy,  hypercoagulable  states  (due   to
antithrombin   III   deficiency,  protein  C  and  S  deficiency,  and  Lupus
anticoagulant), portal hypertension,  splenectomy, and abdominal infections),
inflammatory  bowel  disease,  portal  hypertension  and   sclerotherapy   of
esophageal  varices.   Mesenteric  arteritis  caused by polyarteritis nodosa,
rheumatoid arthritis and  SLE  can  cause  intestinal  ischemia.  Cocaine, by
causing  vasoconstriction  occasionally  may  lead  to  abdominal  pain   and
diarrhea.   Marathon  runners  commonly  have diarrhea and abdominal cramping
which often times can be attributed to ischemic colitis.

                      -ISOSPORA BELLI AND AIDS-
Trimethoprim-sulfamethoxazole, one double strength  tablet  q6h  x  10  days.
Maintenance   therapy:  Trimethoprim-sulfamethoxazole,  one  double  strength
tablet three times weekly.

                            -ITRACONAZOLE-
Itraconazole (Sporanox) has a FDA approval for blastomycosis  (pulmonary  and
extrapulmonary)  and  histoplasmosis  (disseminated, nonmeningeal pulmonary).
It was originally released in 1992  and  is available in 100 mg capsules.  It
does require gastric acidity for absorption.  The oral  absorption  is  about
55% and increases with food.  Peak serum levels are 0.3 ug/ml after 200 mg PO
with  food.   Most  patients are treated with 200 mg/day given with food.  If
400 mg is given, it should be administered as 200 mg bid with food.  Patients
are usually treated for 6 months to one year depending on the disease, extent
of disease and the  response.   Itraconazole  appears  to  be less toxic than
ketoconazole.  Side effects of itraconazole  include  GI  (nausea,  vomiting,
abdominal  pain,  diarrhea)  in  10%,  skin  rashes  (9%, but higher in HIV),
Cardiac (hypertension) in 3%,  CNS (headache, dizziness, somnolence), Hepatic
(increase in liver function tests which is usually  asymptomatic  and  rarely
hepatic  injury),  decreased libido, decreaesd potassium, edema, albuminuria,
gynceomastia, and  adrenal  insufficiency.   At  daily  doses  up  to 400 mg,
testosterone and corticosteroid inhibition does not  occur  (however,  higher
doses  can).  Patients taking itraconazole and cyclosporine or digoxin should
have serum  levels  of  these  monitored,  as  both  cyclosporine and digoxin
concentration  are  raised.   Serious  arrhythmias  have  been  reported   if
itraconazole  is  used  with astemizole or terfenadine.  Phenytoin, rifampin,
and carbamazepine will lower  levels  of itraconazole, resulting in treatment
failure.

                   -JUVENILE RHEUMATOID ARTHRITIS-
Juvenile rheumatoid arthritis (JRA) is  not  a single disease but is composed
of  several  subsets  of  arthritis  that  each  have  their   own   set   of
characteristic  symptoms.   If  all of these subsets are considered, at least
75%  of  children  with  JRA  will  eventually  enter  remissions  and become
functional adults without  significant  lasting  disability.   They  are  all
associated  with  a  chronic synovitis that may cause painful, swollen, warm,
erythematous joints.   The  synovitis  can  be  present  for  months or years
without causing  joint  destruction.   However  some  patients  will  develop
cartilage  and  subchondral  bone damage.  Extra-articular manifestations are
common in some of  the  subsets.   Criteria for juvenile rheumatoid arthritis
include objective arthritis in 1 or more joints for  6  or  more  consecutive
weeks.   The  arthritis is characterized by swelling of a joint or limitation
of motion with heat,  pain  or  tenderness  (pain  or tenderness alone is not
enough to make a diagnosis of arthritis).  Onset of JRA must occur before the
age of 17.  Other known causes of arthritis must be ruled out as inflammatory
bowel disease, infectious arthritis, other rheumatic  diseases,  nonrheumatic
conditions  of  joints  and  bones,  neoplastic  disease  including leukemia,
hematologic diseases and  psychogenic  rheumatism.   SYSTEMIC ONSET JRA: This
subset may present with extra-articular findings such  as  high  intermittent
fevers  >  103  F  that  usually  occur  once  or  twice  daily,  chills  and
erythematous  fleeting  rashes  which are most prominent during the fever and
may exhibit  a  Koebner  response  (occur  in  scratch  marks).   This subset
includes about 20% of children with JRA and affects males slightly more  than
females.   The  rash  is  present  in  about 95% of patients and the fever is
present in 100%  of  patients.   There  may  be  hepatomegaly associated with
abnormal liver  function  tests,  lymphadenopathy,  splenomegaly,  pleuritis,
pericarditis,   myocarditis,   anemia,   leukocytosis,   abdominal  pain  and
peritonitis.  Patients with  systemic  JRA  may  have  arthralgia, myalgia or
transient   arthritis   as   the   disease   begins.    The   arthritis    is
characteristically   polyarticular,   affecting   small   and  large  joints.
Typically, the midtarsal and midcarpal  joints are affected causing prominent
swelling of the wrists and ankles.  About 20% of the  arthritis  will  become
severe.   The  above symptoms are usually self limited, lasting up to about 6
months regardless of therapy.  However, recurrences may occur months or years
later, but rarely  after  the  child  reaches  adulthood.  This arthritis may
remain active into the adult years.   The  ANA  and  RF  are  both  negative.
RHEUMATOID  FACTOR-NEGATIVE  POLYARTHRITIS: This subset affects females:males
in a ratio of 8:1 and represents 25%  of the children with JRA.  It can begin
at any age.  These children  have  arthritis  in  multiple  small  and  large
joints,  but  do not have the systemic manifestations as the systemic subset.
About 25% will  have  a  positive  ANA  while  the  RF remains negative.  The
patient may have a low grade fever, malaise and mild anemia.   About  10%  of
the  arthritis  becomes severe.  This subset is often mild and may not result
in extensive subjoint destruction.  RHEUMATOID FACTOR-POSITIVE POLYARTHRITIS:
This subset is present in  about  5%  of  all JRA patients.  It rarely begins
before the age of 8 and females are more affected than males in  a  ratio  of
6:1.   It  can  be  considered  the  childhood equivalent of adult rheumatoid
arthritis.  The arthritis affects multiple joints, large and small with > 50%
developing severe  arthritis.   Many  of  these  patients  will develop joint
destruction in the first year of the  disease.   There  may  be  mild  fever,
malaise,  anemia  and subcutaneous rheumatoid nodules	occurring over pressure
points.  Sometimes the patient will develop Sjogren's syndrome (dry mouth and
eyes, and  parotitis),  Felty's  syndrome  (splenomegaly  and leukopenia) and
rheumatoid vasculitis.  The ANA is positive in 75% and the RF is positive  in
100%  PAUCIARTICULAR  JRA TYPE I: This group comprises about 40% of the cases
of JRA, usually develops prior to the age of 5, and affects females more than
males in a ratio of 7:1.  The affected joints are predominantly large such as
the knees, ankles and  elbows.   The  hips  and sacroiliac joints are usually
spared.  The  arthritis  can  affect  one  or  more  joints  and  is  usually
asymmetrical.   Constitutional  symptoms  are uncommon and iridocyclitis will
develop in 30-40%.  The  iridocyclitis  is  not necessarily related to active
joint disease.  It is usually not associated with early symptoms or signs and
may occur up to 10 years after the onset of the disease.  The ANA is positive
in 60%.  The RF is negative.  This subset remains mild and is  limited  to  a
few  joints  in  about  80% of affected children.  In about 20% there will be
additional joint involvement that  occurs  over  the years with the resulting
polyarthritis being severe.  PAUCIARTICULAR  JRA  TYPE  II:  This  subset  of
arthritis  is  related  to  the spondyloarthropathies and typically occurs in
children > 8 years of age.  Boys  are  affected more than girls in a ratio of
10:1.  This group accounts  for  about  15%  of  JRA.   These  patients  have
arthritis  in a few large joints, usually in the lower extremities.  Hips and
sacroiliac joints are  commonly  involved.   The  arthritis  may be acute and
occur in episodes or may be chronic and relatively  indolent.   Iridocyclitis
occurs  in  5-10%.   Fever  occasionally  occurs.   During  the course of the
disease,  the  patient  may   develop   symptoms   of  Reiter's  syndrome  or
inflammatory  bowel  disease.   Commonly,  there  is  a  family  history   of
ankylosing  spondylitis  or  one of the other spondyloarthropathies.  The ANA
and RF are both negative.  Some  of  these patients will have long remissions
while  others  will  develop   features   of   chronic   spondyloarthropathy.
TREATMENT: The main treatment of JRA are salicylates.  Doses of 100 mg/kg/day
are  given  for  children  up  to  25 kg of weight, divided into 3 or 4 equal
doses.  The total  dose  for  older  children  ranges  from 2400-3600 mg/day.
Blood levels should be kept between 20-30 mg/dl.  Salicylates should be taken
with food and should be discontinued if there is any exposure to influenza or
varicella because of the possiblity  of  acquiring  Reye's  syndrome.   Liver
function   and   CBCs  should  be  monitored  while  the  patient  is  taking
salicylates.  Tolmetin (Tolectin) is  the  only  NSAID that has been approved
for use in children in the USA.  However, tolmetin probably has no  advantage
over  ASA  except  for  treatment  of arthritis in adults particularly in the
spondyloarthropathies.  Gold, d-penicillamine and hydroxychloroquine have not
proven effective for JRA.   Methotrexate  is  effective  in JRA, but the long
term effects of methotrexate are not known completely in  treating  children.
If methotrexate is given it is used at 10-15 mg/m2 once weekly, either orally
or  intramuscularly.   CBC  and liver function testing should be done every 2
weeks initially.  Prednisone therapy  is  controversial.  Some would say that
the side effects outweigh the benefits in children since  corticosteroids  do
not  cure  the  arthritis, but only mitigate the symptoms.  However, they are
probably the agents of choice in systemic JRA that is life threatening and in
iridocyclitis if topical steroids  are  ineffective.   Suffice it to say that
the lowest dose and the shortest duration of prednisone therapy should be the
goal.

                         -KAWASAKI SYNDROME-
Kawasaki  syndrome  is  a disease of unknown etiology that occurs in children
usually less than 5  years  of  age  and  presents with a rash, mucocutaneous
changes, lymphadenopathy and polyarteritis.  The disease may last  from  2-12
weeks or longer and there may be relapses.The syndrome was first described in
Japan  in the 1960s.  Males are affected more so than females.  The arteritis
affects large and medium sized  arteries  with coronary aneurysms often times
found in about 20% of cases.  There is a seasonal incidence in the  USA  with
more  cases  found in the winter and spring.  Epidemics sometimes occur every
2-4 years.  SYMPTOMS AND SIGNS: The  temperature is usually quite high around
103-104 F and persists for > 5 days.  If the disease is not treated with  ASA
the  temperature  can  last an average of 12 days or longer.  If treated with
ASA the  temperature  will  resolve  in  2-  3  days.   There is conjunctival
injection with limbal sparing around the iris.  There is erythema, fissuring,
crusting of the lips, diffuse oropharyngeal erythema and  strawberry  tongue.
A  non-pitting  induration  of  the  dorsum of the hands and feet is present.
There are only two  other  diseases  in  the differential that are associated
with peripheral edema.  These are Rocky  Mountain  spotted  fever  and  Toxic
shock  syndrome.   Scarlet  fever  doesn't cause hand and feet swelling.  The
rash in KD starts within a  day  of  the  onset of the fever and is primarily
truncal, but may extend to the face and hands.  The rash is  an  erythematous
deep red rash, often times with pruritic plaques or morbilliform erythematous
papules.   In a few cases the rash is a scarlatiniform erythroderma or rarely
erythema marginatum.  In some, it  may  present as an erythema multiforme and
be urticarial.  You should check especially for a  peri-anal  rash  which  is
quite  characteristic.  There is an erythema or purplish red hue of the palms
and  soles,  with  subsequent  desquamation  of  the  fingertips  and toetips
appearing about 2 weeks after onset of disease.  There may be pallor  of  the
proximal  part  of  the fingernails and toenails (leukonychia partialis) that
develops during the first  week  of  illness.   Transverse grooves across the
fingernails may develop about 2-3 months after  the  onset  of  the  disease.
Cervical  lymphadenopathy  develops  in  about 50% of patients and is usually
unilateral.  The nodes are > 1.5  cm.  Inflammatory heart disease may develop
in about 30% of cases.  There may be pericardial  effusions,  myocardial  and
valvular  dysfunction,  arrhythmias and giant aneurysms > 8 mm.  These can be
very serious as they can thrombose.  There can be transient mitral, aortic or
tricuspid insufficiency.  Tachycardia is common and CHF and cardiogenic shock
may develop.  Coronary aneurysms  develop  in  about  20%.   The mean time to
first coronary artery  aneurysmal  development  is  10  days  post  onset  of
illness,  but  can be as early as 5-6 days.  CNS abnormalities develop in 90%
of patients  (aseptic  meningitis  (20%),  irritability,  emotional lability,
lethargy and even a semi-comatose state may develop).   Inflammation  of  the
urethra  with  a  sterile  pyuria  develops in 70% and boys may have a meatal
ulcer that bleeds causing hematuria.  Arthritis  of the small or large joints
can develop in 40%.  Hepatic dysfunction and gallbladder hydrops may occur in
10%  and  and  severe  abdominal  pain  and  diarrhea  in  20%.   LABORATORY:
Leukocytosis with an intense release of bands is common.  There may be a mild
anemia, increased sedimentation rate and  thrombocytosis  in  the  second  or
third  week.   Ekg  may  show  arrhythmias, left ventricular hypertrophy, and
decreased voltage due to pericardial fluid.  Echocardiogram should be done in
all patients around the 5th week of  illness in order to detect any aneurysm.
DIFFERENTIAL   DIAGNOSIS:   Stevens-Johnson    syndrome,    scarlet    fever,
leptospirosis,  measles, RMSF, staphylococcal exfoliative syndromes, measles,
toxoplasmosis,  juvenile  rheumatoid  arthritis  and  infantile periarteritis
nodosa.  PROGNOSIS: A low mortality is associated with KD of about  1%.   The
deaths  are  not  predictable.   About  50% occur during the first month, 75%
within  2  months  and  95%  within  6  months.   Aneurysms  tend  to undergo
resolution within one year accounting for the good prognosis after 6  months.
Most fatalities are due to cardiac complications.  In general, if no coronary
artery  aneurysm  is  found  the prognosis is excellent.  THERAPY: ASA 80-100
mg/kg/day in 4 divided  doses  until  day  14  then  after day 14 in afebrile
patients give ASA 3-5  mg/kg/day  in  a  single  dose  for  6-8  weeks  after
confirming  the absence of coronary abnormalities.  If coronary abnormalities
are found then continue the ASA  for several months.  Follow serum salicylate
levels and try to keep the level around 25  mg/dL.   ASA  has  apparently  no
detectable  effect  on  reversing  the  cardiovascular  events  but does help
prevent thrombosis.  Intravenous immunoglobulin  at  a  dose of 400 mg/kg/day
plus ASA for 4 days has  demonstrated  fewer  coronary  artery  lesions  than
treating with ASA alone.  An equivalent response has been found with one dose
of 2 grams/kg of IV immunoglobulin.

                            -KETOCONAZOLE-
Ketoconazole   is   a   good   antifungal  drug,  but  has  a  potential  for
hepatotoxicity.  Symptomatic  hepatotoxicity  occurs  in  1  in 10,000-12,000
treatment courses.  There also is a dose related inhibition  of  testosterone
and  adrenal  corticosteroid  synthesis.   Suppression of testosterone may be
accompanied by decreased sperm  count, impotence, gynecomastia, decreased and
libido.  Azospermia and decreased libido are more common in those receiving >
800 mg/day.  However, these are  reversible  if  the  drug  is  discontinued.
Ketoconazole  requires  gastric  acidity for adequate absorption.  If gastric
acidity is present it is well  absorbed orally.  Cimetidine and antacids will
interfere with absorption and should not be given until  2  hours  after  the
administration of ketoconazole.  Patients that have achlorhydria may dissovle
the  ketoconazole  tablet  in 4 ml of 0.2 N HCL and drink with a straw.  Peak
serum levels will occur at 1-6  hours post ingestion.  Ketoconazole is mostly
excreted by the heptatobiliary route.  Very little is excreted in the  urine.
Ketoconazole  has  some  important adverse drug interactions, especially with
cyclosporin.  Keotoconazole  will  increase  blood  levels  of cyclosporin A.
Therefore, cyclosporin blood levels should be  monitored.   Ketoconazole  can
increase the anticoagulant effect of coumarin like drugs.  If ketoconazole is
given  with  phenytoin,  both  ketoconazole  and  phenytoin  levels should be
monitored, since the metabolism  of  one  or  both  drugs may be altered when
taken together.  Hypoglycemia has also been reported in  patients  that  take
hypoglycemic  agents  and  ketoconazole.   Other side effects of ketoconazole
include gynecosmastia (3-8%), pruritus (1%), nausea, vomiting (3%), abdominal
pain  (1%),  elevated   SGOT   (2-5%),   headache,  somnolence,  photophobia,
dizziness, fever, rash, diarrhea,  hypoesthesia,  and  adrenal  insufficiency
(Addisonian crisis may occur).  The initial dose of ketoconazole (Nizoral) is
200  mg/day.   If  treating coccidioidomycosis 400 mg/day or even more may be
needed, up to 1200 mg/day.

                    -LABETALOL AND HYPERTENSION-
(Normodyne, Trandate) 20-80 mg IV bolus every 10 min or 2 mg/min IV infusion.
Side effects: scalp tingling, vomiting, throat burning, postural hypotension,
nausea, dizziness.

                          -LEAD POISONING-
It is estimated that about 17%  of  preschoolers in the USA have blood levels
of lead >15 mcg/dL.  Most cases occurs in the 1-5 year age range with  adults
being  affected less.  RISK FACTORS: Chips of paint, lead glazed ceramic ware
that comes in contact with acidic  foods  and beverages such as tomato juice,
fruit juice, fruits, wine, cider,  burning  of  wood  impregnated  with  lead
paints  or battery casings in fireplaces and stoves, leaded glass, fruit tree
sprays,  solder,  brass  alloys,  illegal   whiskey  or  wine  that  is  lead
contaminated, inhalation of leaded gasoline,  food  stored  in  plastic  bags
printed  with  colored  ink, colored comics, residence in housing before 1970
that is deteriorating with leaded  paints,  lead dissolved in water from lead
soldered plumbing, glazed pottery making, stained glass manufacturing, car or
boat repair, target shooting at firing ranges, lead soldering, preparing lead
shot, fishing  weights  and  certain  occupations.   Other  occupations  that
renders one vulnerable to lead poisoning include shipbuilders, printers, lead
smelters  and  refiners,  plastic manufacturers, plumbers, lead miners, glass
manufacturers, pipe fitters,  auto  repairers,  battery manufacturers, rubber
product manufacturers, gas station  workers,  policemen,  steel  welders  and
cutters,  construction workers, and bridge reconstruction workers.  CLINICAL:
Symptoms depend on the blood  lead  concentration  (PbB).  The risk starts to
increase when these levels > 60-70 ug/dL  of  whole  blood.   Encephalopathic
presentations  usually  occur  with  levels  >  100  ug/dL,  but are somewhat
unpredictable.  In children the  onset  is  somewhat acute appearing over 1-5
days as sustained and projectile vomiting, ataxia, and neurologic symptoms of
seizures, changes in the level of consciousness and ultimately coma.  Chronic
changes in children consist of pica, aggressive behavior, seizure  disorders,
mental  retardation,  hyperactivity,  loss  of  acquired  skills  and delayed
development.  In adults clinical signs and  symptoms develop over a period of
several weeks such as  headaches,  anorexia,  non  specific  abdominal  pain,
vomiting,  constipation  and personality disorders.  It is rare for adults to
have encephalopathy.   The  abdominal  discomfort  is  usually colicky.  Some
patients will complain of paresthesias or  actually  develop  foot  or  wrist
drop.   Depression  may develop.  In adults a blue black discoloration of the
gingiva may develop particularly  in  those  with  poor dental care.  This is
known as the lead line.  Children seldom  develop  this.   Exam  of  the  eye
grounds  may  reveal  papilledema  if there is elevated intracranial pressure
from the encephalopathy.  Scout  abdominal  x-rays may show radiopaque flecks
in those children that have pica or when there  is  accidental  ingestion  of
lead.   X-ray  of  the  long bones may demonstrate increased densities of the
metaphyseal  lines  in  children.   This  isn't  seen  frequently  in adults.
LABORATORY:  Basophilic stippling and eosinophilia may  be  seen.   There  is
usually  a  mild  hypochromic  microcytic anemia and perhaps a non-autoimmune
hemolytic  anemia  with  increased   reticulocytes.   Urinalysis  may  reveal
glycosuria and proteinuria.   A  Fanconi  syndrome  may  develop  with  renal
tubular  acidosis and aminoaciduria.  The BUN and creatinine may be elevated.
The uric acid may  be  elevated  with  symptomatic gout present, because lead
tends to reduce the excretion of uric acid.  A good screening test  for  lead
is the free erythrocyte protoporphyrin (FEP).  FEP levels above 15 in healthy
individuals  are  uncommon.   If the value is above 35, this an indication of
lead poisoning.  FEP is a  sensitive  indicator  of active lead found in soft
tissue and bone.  It is a direct measurement of the toxic effect of  lead  on
heme  synthesis.   The  FEF  may  be elevated also in iron deficiency states.
Whole  blood   lead   determinations   indicate   exposure   to  lead.   Lead
concentrations of < 20 ug/dL are  usually  not  associated  with  significant
clinical symptomatology.  Lead levels above 25 ug/dL in children are evidence
of  increased  lead  absorption  and  levels  above  40  ug/dL  in adults are
significant.  These levels may be investigated with the calcium disodium EDTA
(ethylenediaminetetraacetic  acid)  lead  mobilization  test.   The  test  is
performed by giving 1 gram for adults  and 25 mg/kg in children which is then
infused over 1-2 hours with 250 mL to 1000 mL of normal saline.  Fluid intake
should be encouraged during this test.  The urine is collected for  24  hours
for  lead,  or  3 days if there is abnormal renal function.  If the number of
micrograms of lead excreted is more  than the number of milligrams of edetate
calcium disodium given, the test is positive.  TREATMENT: For a Class I  lead
poisoning  with  the  PbB  10-19  ug/dL and the FEP less than 35 ug/dL, there
should be an examination of the  environment and efforts directed at reducing
exposure.  If the PbB is 20-24 ug/dL and the FEP 35-220 ug/dL the PbB  levels
should  be monitored with a full work up for lead poisoning and all hazardous
environments should be corrected.  For  a  Class  II the risk is moderate and
the PbB is 25-44 ug/dL.  If the FEP < 35 ug/dL there  is  minimal  Pb  burden
whereas if the FEP is 35-220 ug/dL there is an increased Pb burden.  At these
levels there is consideration for treatment.  For Class III lead poisoning it
is  mandatory that treatment be given.  The risk is high and the PbB is 45-69
ug/dL.  FEP less than 35 ug/dL are not  seen.  If the FEP is 35-220 ug/dL the
lead burden is excessive.  Succimer (Chemet) is 2,3  Dimercaptosuccinic  acid
or  DMSA  is indicated in children at a dose of 10 mg/kg (350 mg/m2) every 8h
for 5 days, then 10 mg/kg every 12 hours  for 2 weeks.  This is a total of 19
days.  If after two weeks off Chemet the lead level is not  below  15  mcg/dL
the  course  may be repeated.  Courses of dimercaprol and calcium edetate may
still be used, but are not the treatment of choice.  Side effects of Succimer
include nausea, vomiting, diarrhea,  metallic  taste, nasal congestion, rash,
diarrhea, appetite loss and serum transaminase  increases.   Vitamins  should
not  be  given  with  oral chelation.  Class IV is characterized as an urgent
risk category with the patient being  asymptomatic, but with PbB 70-100 ug/dL
and FEP > 250 ug/dL indicating lead toxicity.  Treatment for  this  class  is
CaEDTA  1000 mg/m2/day (50-75 mg/kg/dose IM every 12 hours) for 5 days.  This
may be repeated only after  5  days because continuous treatment will deplete
essential metals, in particular zinc.  An alternative treatment is  to  start
BAL  at  the  same  time as the CaEDTA at a dose of 3-5 mg/kg/dose IM every 4
hours, but discontinue The BAL after 48  hours and continue the CaEDTA for an
additional 3 days at a reduced dosage of 50-75 mg/kg/day divided  into  equal
doses  and  given  IM  every 8-12 hours.  The rationale for this is that EDTA
given alone can liberate  lead,  and  transiently  raise brain levels with an
increase in symptoms.  Intramuscular injection of CaEDTA is  more  convenient
in  children  than  adults.   In  adults CaEDTA may be given IV as a constant
infusion, but phlebitis may develop when the concentration is greater than .5
mg/mL.  For IM injections,  Procaine  should  be  added, injections should be
deep IM, and the injection  sites  rotated.   Class  V  is  characterized  by
encephalopathy  or  impending  encephalopathy  with  PbB  levels > 100 ug/dL.
Treatment consists of combination therapy  of  BAL and CaEDTA.  For the first
dose, inject BAL only, deep IM.  Then beginning 4 hours  later  and  every  4
hours  thereafter,  inject  BAL  and CaEDTA simultaneously at separate sites.
The dose of BAL is 3-5 mg/kg/dose  IM  q  4 hours.  The dose for CaEDTA is 25
mg/kg/dose IM q 4 hours.  If  patients  are  anuric,  the  CaEDTA  should  be
withheld  as  EDTA  isn't metabolized but is excreted unchanged by glomerular
filtration.   Side  effects  of  CaEDTA  consist  of  proteinuria, hematuria,
elevated BUN, fever, diarrhea, and  hypercalcemia.   The  renal  toxicity  is
usually  reversible.   There  may  be increased excretion of copper, zinc and
iron with CaEDTA.  BAL  can  cause  a  moderate to severe acute intravascular
hemolytic state in patients that have a G6PD deficiency.  BAL cannot be given
with iron, but iron may be given with  CaEDTA  and  penicillamine.   BAL  can
cause   nausea,   vomiting,  headache,  fever,  transient  hypertension,  and
hepatocellular  damage.   BAL  may  produce  sterile  abscesses,  and febrile
responses are not unusual.   All  chelating  agents  are  contraindicated  in
asymptomatic  patients  that have liver and kidney disease.  In patients that
are markedly symptomatic, the benefit/risk  ratio must be taken into account.
After chelation, check for rebound lead level in 7-10 days  and  follow  with
monitoring   biweekly  or  monthly.   Courses  of  chelation  are  frequently
associated with rebound  in  PbB  secondary  to  redistribution of lead.  The
rebound can be suppressed with oral D-penicillamine  starting  after  2  days
following  CaEDTA treatment.  D-Penicillamine is not FDA approved.  If given,
the dose is 10-20 mg/kg bid  which  may  be mixed with chilled apple juice or
sauce and given on an empty stomach 2 hours before meals.   Penicillamine  is
available  as  250  and  125  mg  capsules.   Side effects of D-penicillamine
include  GI  upset,   granulocytopenia,   liver   abnormalities,  rash,  iron
deficiency, renal failure, and drug induced lupus syndrome.  If  the  patient
is  allergic  to  penicillin,  D-penicillamine  should not be given.  Therapy
should be continued until the lead level  drops < 25 ug/dL.  There is maximal
lead excretion during the first 3-5 days of chelation therapy.  Rest  periods
must  follow  the  5  days  of  therapy  before  there  will  be  any further
significant excretion of lead.  This  rest  period is usually 2-7 days.  Most
lead poisoned patients will survive, and symptomatic lead  poisoning  without
encephalopathy usually improves with chelation, but there may remain some CNS
toxicity.    If  patients  that  have  encephalopathy,  25-50%  will  develop
sequelae,  with  seizure   disorders,   mental  retardation,  hemiparesis  or
blindness.  Lead exposure during pregnancy can produce a  low  weight  infant
and premature birth.  Cerebral edema may be treated with mannitol or steroids
in   patients   with   encephalopathy.   Diazepam  may  be  used  to  control
convulsions.  For acute lead  poisoning  activated charcoal and cathartic are
indicated.  If large amounts of lead are visible on abdominal x-rays, such as
fish weights, etc.,  cathartics,  whole  bowel  irrigation  ,  endoscopy  and
surgical removal may be necessary.

                       -LEGIONNAIRES' DISEASE-
In 1976 there  was  an  outbreak  of  an  acute  febrile pulmonary illness in
Philadelphia among members of the American  Legion.   Investigation  of  this
outbreak   culminated   in   discovery   of  a  bacterium  called  Legionella
pneumophila.  Legionella is found in ponds  and streams and has been cultured
from potable  hot  water  systems.   Outbreaks  of  legionellosis  have  been
associated with shower heads and faucets, air conditioning cooling towers and
contaminated  water sources.  The mechanism of transmission is most likely by
aerosols, direct inoculation into the  lung by respiratory tract manipulation
and aspiration.  Person to person transmission  has  not  been  demonstrated.
There  are  more than 30 species of Legionella and about 19 species can cause
pneumonia in man.  The most common cause  is L. pneumophila, but others as L.
micdadei, L. longbeachae, L. bozemanii, L. jordanis, L. feeleii, L.  dumoffii
and  L.  gormanii  have all been implicated.  Legionellosis has a spectrum of
presentation.  There may be asymptomatic  seroconversion, a self limiting flu
like disorder without pneumonia known as Pontiac fever, Legionnaire's disease
and a  rare  form  that  presents  as  a  localized  soft  tissue  infection.
Legionnaires'  disease  may  account  for  10%  or more of community acquired
pneumonias.  Legionnaires' disease is  more  common in smokers, COPD patients
and those that are immunocompromised such as transplant patients,  alcoholics
and  those  on  steroids.   Many  cases  occur in late summer and early fall.
CLINICAL: Legionnaires' disease has  been  classified  as one of the atypical
pneumonias because Gram stained smears  of  the  sputum  will  not  show  the
organism.  The usual incubation period is 2-10 days.  Most patients have been
middle  aged  males.   Patients  can  present with chills, fever, malaise and
cough that doesn't become  productive  until  several  days into the illness.
The  fever  is  high  and  associated  with  a  relative  bradycardia.    The
temperature  may  be  as  high  as  105  degrees F. Cough occurs in 80-90% of
patients.  Gross  hemoptysis  is  unusual.   Diarrhea,  nausea,  vomiting and
abdominal pain may be present.  There may be neurologic changes  as  headache
and  altered  mental status with confusion, delirium and lethargy.  The chest
x-ray  early  shows  a   unilateral,   patchy  segmental  or  lobar  alveolar
infiltrate.   With  progression  of  the  disease  there  may  be   bilateral
involvement  with  pleural  effusions and pleuritic pain.  Some patients will
develop lung abscesses and many round lesions that may suggest septic emboli.
Most cases of Legionnaires'  disease  will  have a moderate leukocytosis with
WBC counts from 10,000 to 15,000/uL.  There may be  abnormal  liver  function
tests,  hyponatremia, and hypophosphatemia.  Some patients may have hematuria
and renal dysfunction.  CSF studies are  usually normal even though there are
neurological symptoms.  LABORATORY: Dieterle's silver staining of tissue  and
pleural  fluid  can  detect  Legionella species.  Direct fluorescent antibody
stains and indirect fluorescent  serologic  testing is less sensitive because
this will detect only infection caused by L. pneumophila serotype  1.  Direct
fluorescent  antibody  staining  of  sputum  can detect the organism in a few
hours.  A single elevated  serologic  titer  greater  than 1:128 may indicate
active disease.  Culture using charcoal-yeast extract agar has a  sensitivity
of  80-90%  for  diagnosis  and  in  addition  can  detect  other species and
serotypes than L. pneumophila serotype 1. However, this takes about 3-5 days.
Gram's stain of the sputum is negative for the organisms, but may demonstrate
numerous neutrophils.  The urinary antigen  and  DNA  probe of the sputum are
very good tests.  TREATMENT: Treatment for Legionella is with  500  mg  to  1
gram  of  erythromycin  given  intravenously  every 6 hours.  Rifampin can be
added if the disease is severe  by  giving  600  mg  po or IV every 12 hours.
Rifampin should never be used  alone  because  resistance  may  develop  very
rapidly.    Rifampin  can  cause  liver  function  alterations,  particularly
elevation of bilirubin.  Less common  side effects of rifampin include fever,
hemolysis, rash, anemia and leukopenia.  After the acute symptoms  and  fever
have  resolved  IV therapy may be changed to oral erythromycin 500 mg every 6
hours.  Treatment should  continue  for  about  3  weeks to prevent relapses.
Most patients treated with erythromycin will respond, but the response may be
slow.  X-ray abnormalities will usually persist for  greater  than  1  month.
The  high  dose  of  erythromycin  can  cause  hearing  loss,  but usually is
reversible when the dose is  lowered  or  discontinued.  The hearing loss and
tinnitus  may  begin  about  5-7  days  after  beginning  the   erythromycin.
Erythromycin  may  also  produce phlebitis, nausea and vomiting.  The dose of
erythromycin should be reduced if there  is hepatic or renal disease.  If the
patient  is  unable  to  take  erythromycin  and  rifampin  due  to  allergy,
Trimethoprim-sulfamethoxazole 160/800 mg IV every 6  hours  or  ciprofloxacin
400  mg  IV  every  12 hours may be substituted.  Perhaps, using these two in
combination, rather than each alone, would be better as there have been cases
that fail when each of these is  used  alone.  Doxycycline 100 mg IV every 12
hours may also be tried if there  is  therapeutic  failure  with  the  above.
Azithromycin  and  Clarithromycin  have  shown good in vitro activity against
Legionella and may be useful.

                       -LEGIONNAIRE'S DISEASE-
Is  caused by a fastidious gram negative bacillus occurring as a community or
nosocomial acquired  disease  from  contaminated  water  supplies.  CLINICAL:
Fever, dry cough initially with progression to a slightly  productive  cough,
weakness,  diarrhea (which may precede other symptoms), pleuritic chest pain,
diffuse bilateral rales,  bradycardia,  and  patchy,  usually bilateral chest
infiltrates.  There may be low a  sodium  and  phosphorus,  leukocytosis  and
abnormal  liver funtion tests.  If suspected, start treatment before serology
tests  are  available.   A  single  titer  >  1:256  is  suggestive,  but not
diagnostic.  A four fold increase  requires  2-6  weeks.   The  best  way  of
diagnosing  is  with  culture, fluorescent antibody test of sputum, open lung
biopsy, and bronchoalveolar  lavage  fluid.   TREATMENT: erythromycin with or
without rifampin PO or IV for 2-3 sweeks.  If patient can't take erythromycin
use doxycycline or ciprofloxacin.  Legionella micdadei occurs in  hosptilized
immunosuppressed  patients receiving high dose steroid therapy.  It is a gram
negative bacillus and can be  diagnosed  by  stains  and culture of open lung
biopsy tissue or bronchoalveolar lavage fluid.   L.  micdadei  is  moderately
resistant  to  erythromycin  but  is  the  drug  of  choice.  Cotrimoxazole +
rifampin is also effective.

                        -LEG PAIN (RADIATING)-
SPINAL CAUSES: Spinal stenosis:  The  patient  describes pain descending from
the body through one or both legs.  It worsens during prolonged  standing  or
walking.   The  vascular  status  is  usually  normal.   It  is  caused  by a
combination of degeneration, narrowing and posterior bulging of the vertebral
disk, degeneration and enlargement of  the  facet joints and a thickening and
infolding of the ligamentum flavum.  It is confirmed by CT or MRI.  The  pain
is  relieved  by sitting and recumbency.  Disk herniation is another cause of
radiating  leg  pain.   Tumors:  (intraspinal,  metastatic).   In particular,
tumors of the breast, lung, prostate, kidney and thyroid may  metastasize  to
the  spine.   HIP  DISEASE:  Primary hip disease such as osteoarthritis.  The
patient can't sleep because  of  pain  on  lying  on the affected side.  Pain
affects the groin and down the front of  the  thigh.   Aseptic  or  avascular
necrosis  can  cause pain in the hip, groin, and anterior thigh.  The patient
may limp.  Plain  x-ray  of  the  hip  will  detect.  Insufficiency fractures
affect elderly women with osteopenia.   Typically,  this  will  not  show  on
X-ray,  and bone scan must be done which will show a stress fracture.  X-rays
done a few months later  will  show  bone healing.  Metastatic disease to the
hip or pelvis will need a bone scan or CT for detection.  PERIPHERAL VASCULAR
DISEASE: The patient can have pain in the  buttocks,  thigh  and  calf.   The
patient  can't  climb  stairs  because  they  develop pain.  There is pain on
walking which is relieved by sitting  and standing and disappearing at night.
Check the pulses, do a Doppler and arteriogram if necessary.  Check to see if
the patient smokes.  Males have a higher incidence.  In  general,  there  are
two   types:   femoralpopliteal   occlusive   disease   which  produces  calf
claudication and the less common  aortoiliac occlusive disease which produces
buttocks and thigh and calf pain.  If the patient has absent  femoral  pulses
then  he  has  aortoiliac occlusive disease.  If all pulses are normal, check
for spinal origin of pain.  DIABETIC/LUMBAR POLYRADICULOPATHY: These patients
have night pain which also occurs  in association with spinal cord malignancy
or advanced diabetic peripheral neuropathy.  There  is  a  burning  pain  and
weakness.  EMG will confirm diabetic polyradiculopathy also known as diabetic
amyotrophy.  Patients are typically over the age of 50 and have a non insulin
dependent  late  onset  diabetes often with only a very mild elevation of the
blood sugar.  About 10%  of  patients  with  identical symptoms have a normal
blood sugar, then the disorder  is  referred  to  as  lumbar  or  lumbosacral
plexopathy.   There is a triad of features: progressive weakness, weight loss
(the pain is so severe,  there  is  a  loss  of appetite), night pain that is
severe and frequently described as burning.  EMG, which is diagnostic,  shows
bilateral denervation, both acute and chronic with multiple root involvement.
In  about  1/3  to  50%  of  cases the symptoms will run their course in 6-18
months, although some  weakness  or  numbness  may  persist.   About 1/3 will
experience persistent pain.  Treat with pain control,  physical  therapy  and
optimal  tratment  of  diabetes.  Surgery is not indicated.  RETROPERITONEAL,
PELVIC  AND  PERIPHERAL  MASSES:  These  patients  usually  have  night pain.
MERALGIA PARESTHETICA: These patients have numbness and burning of the  thigh
that  is  localized to above the knee.  Pain is not associated with movement.
There is decreased sensation to  pin  touch  of  the lateral thigh.  There is
entrapment of the lateral femoral cutaneous nerve near the inguinal ligament.
It is more common in younger adults and obese persons, or  persons  who  wear
heavy  belts  or  other confining attire.  Treatment is with weight reduction
and  avoid  certain   garments.    The   differential   diagnosis   is  a  L3
radiculoopathy.  Motor and reflex exam are normal.  The pain is  confined  to
the  anterior  and  lateral  thigh.   IDIOPATHIC CLAUDICATION: Is rare and no
cause can be found.  CT, MRI of the back, CT of the abdomen and pelvis, x-ray
of the hip and  pelvis,  bone  scan,  Doppler  and arteriogram, EMG and nerve
conductions studies will rule in or out the above entities.

                           -LEPTOSPIROSIS-
Leptospirosis is a fairly rare disease  that  can be easily missed because of
its not-specific symptoms.  About the only clues are a conjunctival suffusion
and perhaps a patchy erythema that sometimes occurs on  the  lower  legs.   A
history is very important in this disease.  It can be an occupational disease
and as such farmers, sewer and abattoir workers are at risk.  In the USA many
patients   are   exposed   during  recreational  activities  as  swimming  in
contaminated water.  Any patient that has  come  in contact with the urine of
rats, dogs and farm  animals  can  become  infected.   There  are  about  170
serotypes   of   Leptospira.    Some  of  the  common  organisms  include  L.
icterohaemorrhagiae of rats, L. canicola of  dogs and L. pomona of cattle and
swine.  In an epidemic occurring during World War II at Fort Bragg there  was
an  outbreak  caused by Leptospira autumnalis which caused a pretibial patchy
erythema and a generalized rash with  the fever.  The leptospiral organism is
a gram negative spirochete and takes up residence in foxes, skunks,  rodents,
dogs,  frogs, and domestic livestock.  The disease is transmitted by drinking
contaminated water, exposure of  skin  wounds  and  by the handling of animal
tissues.  The disease is self limiting, but there may be a mortality of  10%.
CLINICAL:  This infection can occur at any age and about 75% of the cases are
in males.  The incubation period is usually 7-13 days but can range from 2-20
days.  The disease typically presents  as  two phases.  In the initial phase,
which is termed the leptospiremic phase, there is abrupt onset over 2-3 hours
of headache, chills,  fever  and  myalgias.   On  the  third  or  fourth  day
conjunctival suffusion occurs.  The temperature may be as high as 104 degrees
F.  There  may  be  abdominal  pain.   Leptospira can be isolated from blood,
tissues and CSF.  Toward the  end  of  this phase, defervescence occurs which
heralds the second phase.  In the second phase, which usually appears on  the
6th  to  12th  day,  there  is  recurrence  of fever, chills and myalgias and
meningitis may appear.  The CSF exam  on  the 7th day may show pleocytosis in
50% of patients.  There may be optic neuritis, peripheral  neuropathy,  rash,
adenopathy,  and  iritis.   If a pregnant women acquires the disease abortion
may occur.  During  this  phase  antibodies  appear.   There  is an important
subset  of  Leptospirosis  known  as  Weil's  syndrome,  usually  caused   by
Leptospira  icterohaemorrhagiae.   This  is a severe form of the disease that
can cause a mortality of 10%.   In  this subset there are continuous symptoms
without defervescence and biphasicity.  There is jaundice  and  azotemia  and
there  is  hepatic  and  renal  dysfunction.   The  UA  may show proteinuria,
hematuria, and pyuria.  There may  be thrombocytopenia.  LABORATORY: There is
usually a leukocytosis and often it is intense reaching 50,000 in some cases.
Neutrophils may predominate which would be against a viral presentation.  The
bilirubin is usually less than 20 mg/dL, but in severe infection can rise  to
40.   The  azotemia  is  characterized by a rise in the BUN to levels usually
less than 100  mg/dL.   The  UA  may  show  proteinuria, hematuria, bile, and
casts.  If there is meningeal involvement, the organisms may be seen  in  the
CSF  by  darkfield  exam of the CSF and blood during the first 10 days of the
disease.  Cultures take from 1-6  weeks  to become positive.  Cultures can be
done by inoculation onto FLetcher's, EMJH, or Tween 80-albumin media.  If the
BACTEC 460  system  is  used,  detection  of  leptospires  in  blood  can  be
determined  after  2-5 days of incubation.  Cultures can be obtained from the
urine from the 10th day to  the  sixth  week.   Serology for IgM by the ELISA
method may aid in a rapid diagnosis.  Acute and convalescent serology  should
be done.  The serum CPK is usually elevated.  DIFFERENTIAL DIAGNOSIS: Several
diseases would have to be ruled out because of the non-specific nature of the
disease.   Some  of  these  would  include  dengue,  adenovirus, toxic shock,
rubella,   rubeola,    Kawasaki's    syndrome,    influenza,   enteroviruses,
cytomegalovirus,  infectious  mononucleosis,  Borrelia,  malaria,  hepatitis,
arboviruses and tick diseases.  TREATMENT: Treatment is with tetracycline and
doxycycline.  Also these drugs can be  used  for  prophylaxis.   The  patient
should  be  treated  for  about 7 days.  In severe illness, penicillin G 6-12
million units per day IV or ampicillin 500-1000 mg q 6 hours IV.

                   -LEUKEMIA (Chronic lymphocytic)-
Chronic   lymphocytic   leukemia  (CLL)  is  a  neoplastic  proliferation  of
differentiated lymphocytic cells which produces  a lymphocytosis of the blood
and bone marrow.  In the majority of cases, it is a clonal  malignancy  of  B
lymphocytes  which  runs  an  indolent  course.   Rarely  are  T  lymphocytes
involved.   The  peak  incidence  is over the age of 65.  It is about 3 times
more common in men than in women.   The incidence of CLL rises from less than
1/100,000 before the age of 45 to a peak of 36/100,000 after the age  of  85.
Most cases are asymptomatic when the diagnosis is made.  Patients may present
with  anemia, adenopathy, and/or splenomegaly, infections or thrombocytopenic
bleeding.   There  may  be  fatigue,  weight  loss,  anorexia,  and  dyspnea.
Physical findings include  generalized  lymphadenopathy,  enlargment of liver
and spleen, pallor, and petechiae.  In the 5% that  present  as  T  cell  CLL
there  may  be  skin  infiltration.  Because of the hypogammaglobulinemia and
granulocytopenia, these patients are at risk for bacterial infection.  As the
disease progresses, viral and fungal infections may intervene.  There are two
major staging systems that can be  used for prognosis and treatment.  The Rai
classification is as follows: Stage 0=blood lymphocytes only,  Stage  1=blood
lymphocytes  +  enlarged  nodes,  Stage  2= blood lymphocytes + splenomegaly,
Stage  3=blood  lymphocytes  +  anemia,   and  Stage  4=blood  lymphocytes  +
thrombocytopenia.  Patients with Stage 0 have a  median  survival  of  >  150
months,  stage  1  (105 months), stage 2 (71 months), stage 3 (19 month)s and
stage  4  (19  months).   The  Binet  staging  system  is  as  follows: Stage
A=lymphocytosis more than 15,000/uL, and fewer than 3  areas  of  lymph  node
involvement  (liver,  spleen,  cervical,  axillary  and  inguinal  lymph node
regions), Stage B=lymphocytosis and at  least  3  out  of 5 areas of leukemic
involvement, and Stage C=lymphcytosis and anemia with a hemoglobin < 10 g/dl,
thrombocytopenia (platelet count < 100,000/uL) or all  of  these.   In  about
10-15%  CLL  is  associated with an autoimmune hemolytic anemia or autoimmune
thrombocytopenia.  LABORATORY: The hallmark  of  CLL  is a lymphocytosis that
may  vary  between  14,000/mm3  to  100,000/mm3  with  about  75-98%  of  the
circulating    cells    representing    lymphocytes.      The     lymphocytes
characteristically appear as small, mature lymphocytes with condensed nuclear
chromatin.   Initially,  the  platelets  and hematocrit are normal.  The bone
marrow is  typically  infiltrated  with  small  lymphocytes.   The monoclonal
markers of lymphocytes include surface immunoglobulins, usually IgM  or  IgD,
CD5, CD19, CD20, and HLA-DR.  The immunophenotype of CLL is unique, such that
it  co-expresses  B  lymphocyte  lineage  markers  such  as  CD19  with the T
lymphocyte marker  CD5.   Other  B  cell  malignancies  do  not  express CD5.
Hypogammaglobulinemia is present in about 50% of patients, which increases in
incidence as the disease progresses.  There may also occasionally be a  small
amount of IgM paraprotein found in the serum.  Chromosomal changes may show a
trisomy  12,  and  tr14q+:6q.  The changes in lymph nodes are essentially the
same as that found in  diffuse small cell lymphocytic lymphoma.  DIFFERENTIAL
DIAGNOSIS: Viral infections  that  produce  lympocytosis  should  present  no
difficulty  when  correlated  with  the clinical findings and the presence of
fever.  Other  lymphoproliferative  disorders  such  as  hairy cell leukemia,
Waldenstrom's macroglobulinemia, and lymphoma in the leukemic  phase  can  be
differentiated  by  the  morphology  of  the circulating lymphocytes and bone
marrow study.  Waldenstrom's macroglobulinemia  consists of increased numbers
of plasmacytoid, pleomorphic lymphocytes in the blood and bone marrow.  It is
a  hybrid  disorder  that  falls  between  CLL  and  multiple  myeloma.   The
peripheral blood  will  show  monoclonal  serum  IgM,  which  can  produce  a
hyperviscosity  syndrome leading to retinal hemorrhages and veno-constriction
of retinal veins, and heart  failure.   Waldenstrom's is also associated with
an  increased  incidence  of  neoplasms,  especially   in   the   GI   tract.
Waldenstrom's  macroglobulinemia is treated with chlorambucil and prednisone,
cyclophosphamide  and   prednisone,   or   melphalan   and  prednisone.   The
hyperviscosity syndrome is  treated  with  plasmapheresis.   T  cell  CLL  is
similar to B cell CLL.  It usually has a shorter survival and responds poorly
to  therapy.   Human T cell lymphotropic virus-1 (HTLV-1) is characterized by
atypical large T  lymphocytes  in  the  blood  and  bone  marrow  that can be
identified by monoclonal antibodies.  In addition, hypercalcemia, lytic  bone
lesions,  skin  lesions,  hepatosplenomegaly  and lymphadenopathy are common.
Survival is typically about 1-2 years.  Therapy consists of CHOP or induction
therapy that is used in  acute lymphoblastic leukemia.  Sezary syndrome, also
known as mycosis  fungoides  also  has  lymphocytosis  of  the  blood  (large
atypical   T   lymphocytes   which   have   cerebriform  nuclei  on  electron
examination).  The bone marrow  is  typically spared initially.  Skin changes
are characteristic (desaquamating erythroderma, plaque and tumor  formation).
As  the  disease  advances there is involvement of the bone marrow, GI tract,
kidney, CNS, heart, lymph nodes, spleen, liver and lung.  The median survival
is  about  8  years.   Skin   lesions  are  treated  with  nitrogen  mustard,
photochemotherapy with psoiden and ultraviolet A light, whole  body  electron
beam  therapy  and  CHOP.   The  bone  marrow  in CLL will show more than 30%
lymphocytes, and bone marrow biopsy  will  demonstrate  1  of 4 stages of the
disease: Stage 1 represents early lymphocytic infiltration without distortion
of marrow architecture, Stage 2, paratrabecular lymphoid aggregates, Stage 3,
replacement  of  marrow  fat  and  stage  4,   diffuse   lymphocytic   marrow
replacement.  CLL VARIANTS: Most cases of CLL will pursue an indolent course,
but  occasionally  there  will be a rapidly progressive disease that presents
with larger, less mature appearing  lymphocytes.   These patients will have a
clinical variant known as prolymphocytic leukemia.  This is usually a B,  but
occasionally  a  T  cell  variant.   It  can  present  de  novo  or  may be a
transformed chronic leukemia.  There  are increased numbers of prolymphocytes
(large single nucleoli and increased cytoplasmic content).  The mortality  is
very  high in prolymphocytic leukemia.  Hairy cell leukemia is also a variant
of CLL.  It is a proliferation  of  lymphocytes  that have B cell features, T
cell features and some histiocytes.  In this syndrome, the  patients  usually
presents with nonspecific symptoms as fever, malaise, and weight loss.  There
is adenopathy, anemia, splenomegaly, malaise and weight loss.  The peripheral
blood  will  show  hairy  cells,  while the bone marrow will show the typical
hairy features defined by their tartrate resistant acid phosphatase activity.
The most common  karyotypes  are  14q+  or  chromosome 12 abnormalities.  The
treatment of hairy cell leukemia is splenectomy, which is usually  done  when
the  patients becomes symptomatic.  Alfa interferon, Chlordioxyadenosine, and
Desoxycorfomycine also have been found helpful.  There has also been reported
a splenic form of CLL in  which splenomegaly, anemia and thrombocytopenia are
the main features.  These patients can be helped by  splenectomy  which  will
lead to decreased transfusions.  TREATMENT: Treatment of CLL is not indicated
until  the patient becomes symptomatic or there is evidence of progression of
the disease.  Indications  include  anemia, thrombocytopenia, and progressive
fatigue.  Most of these patients will have progressive  stage  2  disease  or
stage  3  and  4. The initial treatment usually consists of chlorambucil .6-1
mg/kg	monthly, or chlorambucil .1-.2 mg/kg  daily,  or .4 mg/kg every other
week.  About 70-75% will respond to chlorambucil.  Patients are treated until
the WBC is reduced to about 20,000/uL.  For patients that  are  resistant  to
chlorambucil,   cyclophosphamide   may  be  given  daily  or  intermittently.
Deoxycoformycin (pentostatin) may be given as  4 mg/m2 every 1-2 weeks.  This
drug inhibits  adenosine  deaminase  and  has  a  response  rate  of  35-55%.
Fluoro-AMP (fludarabine) given at 20-30 mg/m2/day for 5 days gives a response
rate  of 45-70%.  Young Patients that have bulky disease, may be treated with
more   aggressive   combination   chemotherapy   such   as  cyclophosphamide,
doxorubicin, vincristine and prednisone (CHOP) therapy.  This has been  shown
to  increase  the  median  survival  from  2  to  4  years.   CHOP + cytosine
arabinoside (CHOP-A) may improve survival  for  as long as 8 years.  Patients
that develop significant immune thrombocytopenia or Coombs' hemolytic  anemia
can  be  treated  with  prednisone at 1 mg/kg/day, Splenectomy may be used in
those patients who fail to respond to chemotherapy.  However, splenectomy and
steroid administration can  significantly  increase  the  patients chance for
life threatening infections.   Patients  with  hypogammaglobulinemia  can  be
treated  with  IV  immune  globulin  at  .4/kg every 3 weeks.  PROGNOSIS: The
median survival of patients with  B  cell  CLL is about 6-10 years.  However,
patients in  stage  0-2  may  survive  from  5-20  years  without  treatment.
Patients with stage 3 or 4 have a median survival of less than 2 years.

                        -LEUKEMOID REACTIONS-
Leukemoid  reactions  can  sometimes occur if the patient has an inflammatory
disease, cancer or infection.  It may be seen in hemolysis, burns, eclampsia,
toxic reaction to chemicals,  following  hypoxia  such as cardiac arrest, non
hematologic malignancy, Hodgkin's disease, toxic megacolon,  pseudomembranous
colitis, bacillary dysentary, and bone marrow infiltration.  It has also been
seen  in  alcoholic hepatitis, and when it is present in alcoholic hepatitis,
the prognosis is worsened.   It  may  also  be  seen  in pulmonary edema, and
overuse of nasal sympathomimetic drugs.  It is usually characterized by white
counts  ranging  from  20,000-50,000/uL.    This   degree   of   neutrophilic
leukocytosis   imposes   a   differential  diagnosis  that  usually  includes
corticosteroid   administration,    and    chronic   granulocytic   leukemia.
Glucocroticoids can cause a marked leukocytosis which may persist  for  weeks
after  the  medication  has been terminated.  The bands usually never account
for more than 6%  in  patients  with  steroid induced leukocytosis.  The main
differential is with chronic granulocytic leukemia (CML).  In CML  there  are
immature  myeloid  cells  predsent with frequent eosinophilia and basophilia.
The leukocyte count is  usually  greater  than 70,000, the leukocyte alkaline
phosphatase  is  decreased,  the  serum  vitmain  B12  binding  capacity   is
increased, splenomegaly is usually present, Philadelpia chromosome is present
in  90%  of cases, the uric acid is frequently increased, and the bone marrow
myeloid to erythroid ratio is usually  greater than 10:1.  On the other hand,
leukemoid reactions usually have mature PMNs and bands,  increased  leukocyte
alkaline  phoasphatase, normal serum vitamin B12 binding capacity, WBC counts
less than 50,000, absent Philadelphia  chromosome studies, variable uric acid
and splenomegaly, and bone marrow myeloid to erythroid ratios less than 10:1.

                    -LEUKOCYTOCLASTIC VASCULITIS-
CAUSES: This is  also  known  as  a  hypersensitivity  vasculitis or palpable
purpura and can be associated  with  multiple  etiologies.   The  disease  is
probably  idiopathic in about 50 % of cases and is self limiting in about 2-3
weeks  usually.   However,  drugs  are  a  strong  contender  in  causing the
vasculitis; especially in the elderly.  Most drug induced  purpura  does  not
involve  autoantibodies  and  doesn't  produce  urticaria.   Quinidine is one
exception, in that it can  induce  antibodies that can destroy platelets that
have quinidine on their surface, and this  can  result  in  thrombocytopenia.
Diuretics  and  cardiac  drugs  are  common  offenders.   One should not only
question  the   patient   about   prescription   drugs  but  over-the-counter
medications.  Also, ask about medications that are inhaled and rubbed on  the
skin.   Ask  about  vitamins,  food  supplements, diet pills, sleeping pills,
relaxants, birth control  pills  and  medications  that  may  have been taken
belonging to another person.  Interrogate for IV drug abuse that can cause an
endocarditis   with   embolic   purpura.    Aspirin   and   non-    steroidal
anti-inflammatory  agents  can  cause interference with platelet function and
cause petechiae or ecchymoses.  Systemic  causes for purpura consist of mixed
cryoglobulinemia syndrome, hepatitis, embolic disease and  connective  tissue
disease as SLE, rheumatoid arthritis, and Henoch-Schonlein purpura (usually a
pediatric  disease).   CLINICAL:  If  SLE is being considered, ask about hair
loss and  sun  sensitivity,  fetal  loss  and  hypertension during pregnancy.
Physical exam may provide clues, as a  malar  rash,  mouth  sores  and  scalp
lesions  may  point  toward  SLE.   A heart murmur suggests endocarditis with
embolism.   Splinter  hemorrhages  can  suggest  endocarditis  or  a  primary
systemic  vasculitis.   Funduscopic  exam  may  show  emboli  or  vasculitis.
Leukocytoclastic vasculitis produces a palpable purpura, usually of the lower
extremities, that can  be  painful.   Purpura  due to platelet abnormalities,
either quantitative or qualitative  is  not  painful  and  is  not  palpable.
Non-palpable  purpura  can be seen in senile, steroid or amyloidosis purpura.
Thrombotic thrombocytopenic purpura TTP) would  have  to be ruled out as well
as ITP.  LABORATORY: UA may show hematuria, and proteinuria associated with a
renal vasculitis.  Sedimentation rate, platelets, bleeding time,  creatinine,
liver  function  tests  and  CPK  should  be  done.  If there is a history of
sinusitis, then get  sinus  x-rays  and  chest  x-ray  to  rule out Wegener's
granulomatosis.  EKG may show pericarditis with SLE or  coronary  vasculitis.
ANA,  rheumatoid  factor, cryoglobulin and hepatitis serology should be done.
Skin biopsy may  show  cholesterol  crystals  from an ulcerating atheromatous
plaque or material from a cardiac myxoma.   Transesophageal  echocardiography
can  be  done  if  the  patient is very ill and embolism is high on the list.
Transesophageal echo is the method of  approach, as it is much more sensitive
and can also show the aortic arch and  descending  aorta.   Serum  and  urine
electrophoresis    and    immunoelectrophoresis    may   be   helpful.    The
immunoelectrophoresis may show a monoclonal paraprotein spike that isn't seen
on the serum protein  electrophoresis  and  point  to a gammopathy of unknown
significance that can progress in 10-30 % of cases  to  multiple  myeloma  or
Waldenstrom's  macroglobulinemia.   An  antineutrophil  cytoplasmic  antibody
assay   could   be  done  that  will  help  in  the  diagnosis  of  Wegener's
granulomatosis and periarteritis  nodosa.   A  bone  marrow biopsy may reveal
multiple myeloma.  TREATMENT: If idiopathic, no treatment is  needed,  unless
the  lesions  are  very painful.  Then, a short course of prednisone might be
indicated.   Hepatitis   B   and   C   have   been   associated   with  mixed
cryoglobulinemia with immune complex deposition.  This may respond  to  alpha
interferon  with  a  disappearance  of  the  hepatitis antigen and subsequent
resolution of the cutaneous  vasculitis.   The  underlying disease is treated
depending upon the diagnosis.  In general,  steroids,  cytotoxic  agents  and
plasmapheresis are used.

                           -LIMPING CHILD-
This article will discuss the most likely causes of limping  in  a  child  at
various  age  levels.   0-2  YEARS:  This  age  group  will  encompass septic
arthritis, toddler fractures of the  tibia and juvenile rheumatoid arthritis.
SEPTIC ARTHRITIS: Septic arthritis represents the most  important  orthopedic
infection  in  this  age  group.   In  this  disease you may get a history of
respiratory or other bacterial  diseases.   Most  of these children will look
ill and most will have fever.  Some of these may have  already  been  treated
partially  with  antibiotics  and their clinical appearance may be deceiving.
The child may hold his  hip  in  an  abducted, flexed and slightly turned out
position.  The child usually won't allow you to move the  leg.   If  you  are
able  to move the leg then the range of motion is decreased.  X-rays may show
some joint  space  widening  and  soft  tissue  swelling.   The  bone scan is
variable.  It may be hot, cold or normal.  Since there is no  definite  test,
aspiration is mandatory.  The aspirate is then cultured, gram stained and the
fluid  is  checked for glucose, leukocytes and protein.  TODDLER FRACTURE: In
this condition it is mandatory  that  you  palpate  the shaft of the tibia to
isolate the area of involvement.  The child will refuse to bear any weight on
the foot.  An x-ray may demonstrate a hair line fracture near the proximal or
distal metaphysis of the tibia, or the x-ray may be normal depending  on  the
time course.  If the initial exam is negative, re-x-ray about 2-3 weeks later
may  show  a  periosteal reaction.  This periosteal reaction may give concern
for osteosarcoma, osteomyelitis or  Ewings  sarcoma.   A biopsy at this point
may be easily confused with osteogenic sarcoma.  3-5 YEARS: In this group are
growing pains, toxic synovitis, Kohlers disease (tarsal navicular), diskitis,
juvenile  rheumatoid  arthritis,  leukemia,  cerebral  palsy   and   muscular
dystrophy.   TOXIC  SYNOVITIS:  The nomenclature for this disease is actually
erroneous because the child is not toxic.  Toxic synovitis may also go by the
name of transient synovitis of the hip  or observation hip.  It is the number
one cause of hip pain and limp in childhood in the USA.  The typical  history
is that the child woke up in the morning and refused to put the foot down and
walk.   If  a careful exam is done and the child will cooperate, the range of
motion is nearly normal.  Septic  arthritis  is  never like this with passive
movement.  Fever is uncommon and lab is normal.  The child doesn't  look  ill
as  in  septic  arthritis,  but may be irritable.  Bed rest is used for a few
days, unless the hip needs to  be  aspirated.   A  follow up in 3-6 months is
essential to check for range of motion.  If this is reduced  then  x-rays  of
the    hip    must    be    done    to   rule   out   Legg-Perthes   disease.
DISKITIS/OSTEOMYELITIS: Diskitis/Osteomyelitis  is  rare  before adolescence,
but diskitis is common until the age of five or six.   In  this  disease  the
child  may  again refuse to walk or walks very gingerly.  Diskitis can easily
be confused with hip pathology.  The  child  may  complain of pain in the low
back, posterior hip, thigh,  or  around  the  groin  or  lower  abdomen.   If
diskitis is suspected then order a bone scan as it will show increased uptake
early  on.   The  diskitis  can  occur  between  T10  to L5.  X-rays may show
narrowing and end plate irregularities late in the disease.  Aspiration isn't
usually done, but if  it  is  the  fluid  is  usually sterile.  Most of these
children do well with bed rest and immobilization in a spica cast  or  brace.
However,  the  acute symptoms may take several weeks to subside.  If there is
no improvement with  a  persistent  fever,  elevated  WBC  and  sed rate then
aspiration  and  antibiotics  should  be  considered.   JUVENILE   RHEUMATOID
ARTHRITIS:  The  hip  is rarely the initial site of involvement.  The knee is
commonly involved.  There is little  or  no  pain  and range of motion may be
fairly good.  The gait may be stiff legged.  4-7 YEARS: Legg-Perthes  disease
is common in this age group.  It is an avascular necrosis of the femoral head
and affects boys more than girls.  It is usually unilateral and painless, and
most  children will remain active.  However, there is a limp.  On examination
you won't be able to spread the legs fully apart or log roll the affected hip
internally.  Bone scan is the best test.  X-rays may show one femoral capital
epiphysis to be flatter, denser  and  more  irregular or wider than the mate.
The differential  diagnosis  of  Legg-Perthes  would  include,  previous  hip
dislocation,  hemoglobinopathies  as  sickle cell, steroid therapy, Gaucher's
disease and SLE.  Treatment includes  home  traction, bracing, surgery on the
femur or acetabulum and exercise.  10-15 YEARS:  Diseases to suspect in  this
group   include:   slipped  capital  femoral  epiphysis,  subluxing  patella,
chondromalacia, Osgood Schlatter disease,  stress fracture, tarsal coalition,
Severs   disease   (os   calcis),   growing   pain,   internal   derangement,
spondylolisthesis and bone tumor.  SLIPPED CAPITAL FEMORAL EPIPHYSIS: Slipped
capital femoral epiphysis patients usually present with pain in the  anterior
knee or thigh and not in the hip.  Many will not have any pain.  Many present
with  a  limp  that  has  become  increasingly  more pronounced over weeks or
months.  There is obligatory external rotation  of the hip when it is flexed.
An immediate x-ray of the hip should be obtained with AP and lateral views of
the hips.  Most of these children are  obese  and  the  children  often  look
younger  than  the  actual  age.   Slipped  capital  femoral  epiphysis is an
orthopedic emergency because of femoral  head  migration off the femoral neck
with subsequent avascular necrosis.  There  should  be  prompt  referral  for
surgical  treatment.   OSTEOMYELITIS:  Most children in this age group do not
complain of back pain, so if  the  child  reports back pain in this age group
consider osteomyelitis.  There may or not be a limp.  You should also  search
for  pain  and  tenderness  at  the femoral neck, distal femur and sacroiliac
joint as infections of the long  bones  are commoner than septic arthritis in
adolescents.  GROWING PAINS: Growing pains are usually between the joints and
typically involve the tibia, back of the calf and back  of  the  thigh.   The
pains  often occur at the end of the day and often awaken the child 2-3 hours
after going to sleep, and upon awakening the child has no symptoms.  The pain
is usually bilateral but there may a ping-pong effect between the two legs.

                        -LIPIDEMIC DISORDERS-
ELEVATED  TG  LEVELS: Patients with triglycerides > 1000 mg/dL have a greater
incidence of  pancreatitis.   These  patients  should  be  treated by alcohol
restriction, aerobic exercise, weight reduction and termination  of  smoking.
When the triglycerides are lowered, there often times will be an elevation of
HDL.   Should  non-pharmacologic  measures  fail,  treatment with niacin or a
fibric  acid  derivative  is  indicated.   Reductase  inhibitors  are  not as
effective.  The  bile  acid  sequestrants  are  not  indicated  for  isolated
hypertriglyceridemia as they may actually increase serum TG levels.  Niacin +
fibric  acid  derivatives used together, should only be used in patients with
severe hypertriglyceridemia  that  is  refractory  to  diet  and  single drug
therapy,  as  this  dual  drug  therapy  can  cause  myopathy  and  myositis.
Increased  TG  can  be  caused  by  drugs   such   as   thiazide   diuretics,
glucocorticoids,   beta   antagonists,   estrogens  and  ethanol,  and  renal
insufficiency, diabetes mellitus, inactivity,  and obesity.  Modificatiion of
these factors may improve TG levels.  DECREASED  HDL  LEVELS:  Decreased  HDL
levels  promotes atherosclerosis.  All secondary factors should be corrected.
Drugs such as anabolic  steroids,  progestational agents and beta antagonists
can lower HDL levels.  Other conditions leading to low HDL include  cigarette
smoking, estrogen deficiency, hypertriglyceridemia.  The Helsinki Heart Study
found  that every 1% increase in serum HDL levels would reduce coronary heart
disease by 2%.  Since niacin is capable  of lowering TG also, it is effective
in raising HDL levels (decreasing TG, will inversely raise HDL  levels).   If
niacin  cannot  be  tolerated, gemfibrozil should be used.  HMG-CoA reductase
inhibitors as lovastatin,  pravastatin  and  simvastatin,  are less effective
than niacin or the fibric acid derivatives.  ELEVATED LDL LEVELS:  	Elevated
LDL  levels  can  be  a  consequence  of  drug therapy such as progestational
agents, glucocorticoids, thiazide  diuretics,  anabolic  steroids, as well as
diseases such as hypothyroidism, nephrotic syndrome, diabetes  mellitus,  and
obstructive  liver  disease.  First line therapy for elevated LDL level would
include HMG-CoA  reductase  inhibitors  OR  bile  acid  sequestrants  such as
cholestyramine and colestipol.  Some authorities  would  recommend  the  bile
acid  sequestrants  as  first line therapy because	they have long term safety
and the ability  to  reduce  cardiovascular  mortality.   Other experts would
contend that reductase inhibitors should be first  line  therapy  because  of
their greater efficacy and a more acceptable side effect profile.  Niacin has
the  potential to lower LDL levels paralleling the sequestrants, but has many
side  effects.   The  fibric   acid   derivatives,  such  as  clofibrate  and
gemfibrozil are less effective, and  are  not  recommended  as  monogtherapy.
Probucol has shown to slow the incorporation of LDL plques and may be used in
high  risk  patients  with  elevated LDL refractory to other drugs.  Estrogen
replacement  in  menopausal  patients   will   lower  LDL.   In  some  cases,
monotherapy may not be effective in lowering LDL and combination therapy  may
be  necessay.  In trials it has been found that using a bile acid sequestrant
with either niacin or an  HMG-CoA reductase inhibitor lowered LDL cholesterol
32-66% with an average  of  50%.   However,  it  must  be  noted  that  using
combination  therapy  may  result  in  an adverse safety profile.  Niacin can
cause hepatocellular toxicity and  myopathies.   The reductase inhibitors can
also cause liver enzyme elevations and myopathy.  Gemfibrozil can also  cause
mild elevations of liver transaminase levels in about 1-3%, but rarely causes
myositis.   However,  when  combined with a reductase inhibitor the incidence
rises to about  5%,  and  when  combined  with  niacin  rises  to about 3-5%.
Therefore, gemfibrozil should only be used  in  combination  with  niacin  or
reductase  inhibitors  in  patients  that  are refractory to other therapies.
ELEVATED LDL AND TG LEVELS: Niacin will reduce LDL and TG levels, but may not
be tolerated.  The fibrates  such  as  gemfibrozil  will  lower both, but the
reduction in LDL is only about 3-8%.  The reductase inhibitors have  most  of
their  effect  on  LDL,  while  lowering TG only modestly.  Bile sequestrants
should not be used as they may  actually increase TG levels.  SIDE EFFECTS OF
LIPID LOWERING DRUGS: BILE ACID SEQUESTRANTS: Constipation, nausea, bloating,
diarrhea, abdominal pain, esophageal reflux, and hemorroid bleeding.  HMG-CoA
REDUCTASE  INHIBITORS:  Headaches,  insomnia,  hepatic   dysfunction,   rash,
abdominal  discomfort,  and  myopathy.   FIBRIC  ACID  DERIVATIVES: myopathy,
hepatic dysfunction, bile lithogenesis, nausea.  NIACIN: Glucose intolerance,
peptic ulcer, gout, hepatic dysfunction, myopathy, and flushing.

                              -LITHIUM-
Lithium is used primarily for bipolar disorders (manic-depressive), but  also
is used in unipolar disorders (depressive).  When used in unipolar  disorders
it  is  used  in conjunction with other antidepressant drugs to enhance their
effects.  It tends to  be  more  effective  in  bipolar disorders that have a
frequency rate of no more than 2 episodes/year.   In  this  type  of  bipolar
subset,  the patient usually can be treated with lithium alone, although some
will need sustained or  intermittent  use  of carbamazepine, neuroleptic, and
antidepresant medications.  Patients that have frequent swings between  manic
and  depressive  episodes usually respond slowly to the drug, but can improve
if  the  lithium  is  continued.   Lithium  may  also  be  effective  in some
schizoaffective disorders.  The response rate in bipolar disorders  is  about
70-80%  after  about  1-2  weeks.   Lithium  carbonate is available as 300 mg
tablets and also as lithium citrate syrup (5 ml/300 mg).  Lithium is absorbed
well, and peak serum levels will  occur  within  1-3 hours.  About 50% of the
total body lithium will be excreted in 18-24 hours (95% in the  urine).   The
blood  levels  for  treating  acute  attacks  is  from  1-1.6  meq/L, and the
prophylactic dose  is  .4-1  meq/L.   This  usually  means  initial  doses of
1200-1800 mg/day.  For maintenance  therapy,  doses  of  900-1500  m/day  are
typical,  in order to keep the plasma concentrations between .6-1 mmol/liter.
The dose is usually divided in BID  or TID doses to minimize the side effects
of tremor and nausea.  Blood levels should be done 12 hours  after  the  last
dose  in the morning.  The plasma half life of lithium is about 24 hours, and
steady state plasma concentrations  are  not  reached until 4-5.5 half lives.
Therefore, measurements should not be made for 5-6 days after a dose  change.
During maintenance it is appropriate to obtain blood levels every 3-4 months,
or  more  frequently,  if  there have been any intervening factors that might
affect the levels (volume  depletion  such as diuretics, diarrhea, vomiting).
The thiazide diuretics cause increased lithium reabsorption from the proximal
tubules of the kidney which leads to increased  serum  lithium  levels.   For
example, if the patient is taking lithium with hydrochlorothiazide diuretics,
the  lithium  dose  should  be  reduced  by  25-40%.   Loop diuretics such as
furosemide, bumetanide  and  ethacrynic  acid  do  not  alter lithium levels.
Potassium sparing diuretics such as spironolactone, triamterene and amiloride
can increase serum  lithium  levels.   Also  patients  that  are  taking  ACE
inhibitors  will  need  a  50-75% downward adjustment of the lithium.  It has
been shown that higher  doses  of  lithium  may  be  required in active young
males, those who have a large muscle mass, high sodium intake, and those  who
have  shorter  sleep  periods.   Prior to starting lithium the patient should
have baseline levels of  CBC,  UA, serum creatinine, electrolytes, thyroxine,
TSH, and ECG (patients over 50 years of age).  During treatment, the patients
should have a serum creatinine, thyroxine, free thyroxine, TSH, and UA  every
6-12  months.   DRUG  INTERACTIONS: FACTORS THAT INCREASE LITHIUM LEVELS: ACE
inhibitors,   indomethacin,   urea,   mannitol,   ibuprofen,  phenylbutazone,
piroxicam, mefenamic acid, sulindac, spironolactone, triamterene,  amiloride,
phenylbutazone,   sodium   bicarbonate,  thiazide  diuretics,  tetracyclines,
theophylline,  aminophylline,   dehydration,   kidney   disease,  and  aging.
DECREASED LEVELS OF LITHIUM: Valproic acid,  calcium  channel  blockers,  and
pregnancy.   The combined use of carbamazepine or haloperidol and lithium can
increase neurotoxicity.  The combined  use  of  metronidazole and lithium has
caused renal toxicity.  Beta blockers  can  be  used  to  treat  the  lithium
induced  tremor.   SIDE  EFFECTS:  Early  side effects such as tremor, muscle
weakness,  lethargy,  irritabilty,  poor  concentration,  nausea  and slurred
speech can occur when the levels are between 1-1.5  mmol/liter.   When  blood
levels  reach  1.6-2.5,  the  patient  may  exhibit confusion, unsteady gait,
disorientation, drowsiness,  restlessness,  dysarthria,  vomiting  and muscle
fasiculations.  Levels greater  than  2.5  will  lead  to  delirium,  ataxia,
extrapyramidal   symptoms,   convulsions,   fasciculations,,  impaired  renal
function and coma.  Patients  with  blood  levels  greater than 2.5 meq/L are
treated with emesis and gastric lavage.  If renal function is normal, osmotic
or saline diuresis will enhance renal lithium clearance.  Sodium  bicarbonate
will   decrease   lithium   reabsorption  in  the  proximal  tubule  as  does
acetazolamide.  Aminophylline will increase the glomerular filtration rate of
lithium.  Patients may need  to  be  treated with hemnodialysis or peritoneal
dialysis if the ingested dose has been large.   The  most  common  neurologic
side  effect  of  lithium  is tremor, which occurs in 25-50% of patients.  It
tends to diminish with time, reducing  the dose of lithium, or treatment with
a beta blocker.  About 33% will have increased urination and excessive thrist
which may lead to nephrogenic diabetes insipidus.  Giving the  lithium  as  a
single  dose  at  bedtime  may  dimish  the  polyuria.   Nephrogenic diabetes
insipidus may be  treated  with  a  thiazide  or  amiloride.  About 10-20% of
patients will develop an elevation of the TSH, but clinical hypothyroidism is
less frequent.  Lithium interferes with the synthesis of thyroid hormone  and
its  release  from  the  gland, and also may increase antithyroid antibodies.
About 3% will develop a  thyroid  goiter  that is euthyroid.  Patients taking
lithium and carbamazepine or iodide concomitantly increases the  chances  for
hypothyroidism  and goiter.  Lithium induced hypothyroidism is more common in
women, and can be treated with  thyroid hormone while maintaining the lithium
therapy.  Lithium frequently causes non specific T wave flattening or T  wave
inversion  on  the  ECG.   Sino  atrial  block  can  occur, especially in the
elderly.  Widening of the QRS  may also occur.  Gastrointestinal side effects
include nausea, diarrhea, epigastric pain,  salivary  changes,  and  salivary
gland  enlargement.   Dental  caries  can  develop  if  the  patient develops
xerostomia and consumes a lot  of  sugar.  Hepatotoxicity is rare.  About 50%
will gain and average of 5-10 kg.  Some  patients  will  develop  a  metallic
taste.   Other side effects include hair thinning, pedal edema (be careful in
treating  with  diuretics),   folliculitis,   worsening  of  acne,  nephrotic
syndrome, folate deficiency, hyperthyroidism, headache, pseudotumor  cerebri,
leukocytosis,   exacerbation   of   psoriasis,  extrapyramidal  signs,  renal
interstitial fibrosis,  glomerulosclerosis,  and  tubular  atrophy, decreased
memory, hypercalcemia and elevated parathyroid hormone.   Patients  that  are
exposed  to  lithium  early  in  pregnancy  have  an  increased  incidence of
congenital anomalies,  particularly  Ebstein's  anomaly.  Teratogenic defects
are the highest during the first trimester, particularly between 8-12  weeks.
Fetal  ultrasound and echocardiography is useful in assessing lithium induced
malformations.  Women  using  lithium  should  be  told  to  avoid pregnancy.
Breast feeding should not be done, as lithium concentrations in  breast  milk
are 33-50% of the serum level.

                         -LIVEDO RETICULARIS-
Livedo reticularis may be either symmetric or asymmetric.  Patients that have
an  asymmetric, patchy involvement is suggestive of systemic vasculitis, SLE,
rheumatic  disease,   hyperparathyroidism,   hypoparathyroidism,  malignancy,
pancreatitis, drug reactions  (as  amantidine),  infections  (syphilis,  TB),
emboli,   and  hematologic  diseases  as  thrombocythemia.   Skin  biopsy  is
indicated in  these  diseases.   Patients  that  have  fixed symmetric livedo
reticularis with leg ulcerations should be suspect for arteritis  obliterans,
SLE, polyarteritis nodosa, and dermatomyositis.  It is also seen as a variant
in  women  <  40  years  of  age.  It is usually enhanced by cold conditions.
Workup should include a CBC, ESR, ANA, skin biopsy and renal tests.

                     -LIVER DISEASE AND SURGERY-
Patients with progressive  chronic  liver  disease  and  failure  have a high
operative risk.  The nutrition, electrolyte disturbances, abnormal  clotting,
ascites and encephalopathy should all be optimized.

                       -LIVER FAILURE (Acute)-
Acute liver failure is  manifested  as  encephalopathy  and/or  coagulopathy.
Cardiac  failure  and  the  hepatorenal syndrome can also develop in patients
with primary liver failure.   Acute  liver  failure  is not very common, with
about 2000 cases occurring yearly in the USA.  The mortality  is  about  80%.
Most  cases  are  due to viral hepatitis or drug induced liver injury.  Acute
hepatitis accounts for up  to  72%  of  cases,  but  viral hepatitis leads to
hepatic failure in only less than 1%.  Hepatitis A is a rare cause  of  liver
failure, and is only seen in .35% of cases, and those that do develop it have
a  greater  than 60% survival.  Acute hepatitis B may account for about 1% of
patients, and accounts  for  about  70%  of  virus associated disease.  About
33-50% of patients with  acute  hepatitis  B  will  become  seronegative  for
hepatitis B surface antigen within a few days.  Hepatitis C is extremely rare
as  a cause of liver failure, based on the detection of hepatitis C antibody.
However,  hepatitis  C  may  be  superimposed  on  hepatitis  B,  producing a
fulminant disease.  Hepatitis D, (delta hepatitis) by  definition,  can  only
occur in those who are carriers of hepatitis B, or who have acute hepatitis B
infection.   Hepatitis  D  is  more  frequently  seen  in  IV  drug  abusers.
Hepatitis  E  is  a  rare  entitiy  in  the USA.  Other causes of acute liver
failure  include  acetaminophen,  Amanita  phalloides,  carbon tetrachloride,
Wilson's disease, Reye's syndrome, acute fatty liver  disease  of  pregnancy,
veno-occlusive  disease,  malignant infiltration , heatstroke,, idiosyncratic
drug reactions,  and  ischemia.   Drugs  that  are  capable  of causing liver
failure include, phenytoin,  halothane,  disulfiram,  amiodarone,  isoniazid,
valproate,   sulfonamides,   dapsone,  and  propylthiouracil.   Certain  drug
combinations may  have  an  increased  proclivity  for  development  of liver
failure, such  as:  acetaminophen  and  isoniazid,  rifampin  and  isoniazid,
alcohol and acetaminophen, amoxicillin/clavulanic acid, and trimethorprim and
sulfamethoxazole.   Other  drugs  that are extremely rare causes of fulminant
liver  failure   include,   ketoconazole,   lisinopril,   niacin,  flutamide,
carbamazepine,  ofloxacin,  labetalol,   interferon   alfa,   etopside,   and
imipramine.   Aminita  phalloides, a poisonous mushroom, is responsible for a
number of deaths in  California  each  year  due  to novice mushroom pickers.
Patients  present  with  sweating,  vomiting  and  diarrhea,  prior  to   the
development  of  liver  failure.   Glue sniffers and those persons exposed to
industrial cleaning solvents are also at risk for acute liver failure, due to
hepatic  and  renal  injury   from  trichloroethylene  and  tetrachloroethane
fluorinated hydrocarbons.  Acetaminophen is a common cause of  liver  failure
in  the  United  Kingdom,  and  a  fairly  common cause in the USA.  Although
acetaminophen toxicity  is  dose  dependent,  alcohol,  starvation, and those
drugs that induce  its  cytochrome  P-450  isoenzyme,  puts  the  patient  at
additional  risk  for  acute liver failure.  Ischemic causes of hepatic liver
failure include, myocardial  infarction,  cardiomyopathy,  cardiac arrest and
pulmonary embolism which can produce centrilobular necrosis of the liver with
subsequent   liver   failure.    Wilson's   disease   with   liver    failure
characteristically  present  with  very  high bilirubin levels, often greater
than 30 mg/dl, and decreased  serum alkaline phosphatase.  CLINICAL: Patients
usually present with  malaise,  and  nausea  which  rapidly  is  followed  by
jaundice  and  encephalopathy.   Patients  may  present  in various Grades of
hepatic encephalopahty.  Grade  I  is  characterized  by drowsiness, impaired
psychomotor function, concentration and intellectural function, but  coherent
and  arousaeable.   Grade  II patients exhibit disorientation, confusion, and
increasing drowsiness, but are  arouseable  and capable of conversing.  Grade
III patients are disoriented, drowsy, agitated,  and  will  only  respond  to
simple commands.  Grade IV patients are unresponsive, or will only respond to
noxious  stimuli, and papilledema can be present.  About 80% of patients will
have increased intracranial pressure.   Patients  with cerebral edema usually
have hypertension  and  bradycardia  due  to  Cushing's  reflex.   They  have
increased muscle tone which develops into decerebrate rigidity and posturing,
and  usually  pupillary dilation.  Coagulopathy is the second feature that is
characteristic for fulminant liver  failure.   The  PT  and PTT are prolonged
secondary to decreases in factors II, V, VII, IX,  and  X.  Antithrombin  III
levels  are  decreased,  and greater than 2/3 of patients will have platelets
below  100,000.   GI  hemorrhage   is   common  as  the  platelets  decrease.
Hypoglycemia is common due to decreased gluconeogenesis.  Patients  may  also
develop  hyponatremia, hypophosphatemia, and hypokalemia.  Most patients will
have  hypotension,  hypovolemia,   decreased  systemic  vascular  resistance,
increased cardiac output and increased interstitial edema.   About  50%  will
develop  oliguric  renal  failure.   Bacteremia  is  common,  involving  gram
positive  organisms  such  as staphyloccus aureus and streptococci.  THERAPY:
Therapy  is  mainly   supportive.    Patients   will  require  10%  dextrose,
ceruloplasmin and acetaminophen levels, PT, and hepatitis profile.  Pulmonary
artery monitoring is useful for guiding  fluids.   H2-receptor  blockers  are
given  to  prevent  GI ulcerations.  Patients with platelets below 50,000 may
require platelet transfusions.  Cerebral edema  is treated with 100-200 ml of
a 20% solution of mannitol (.3-.4 grams/kg) given rapidly IV,  which  may  be
repeated  in  several  hours.   Dexamethasone  and  hyperventilation  are not
effective in cerebral  edema  secondary  to  acute  liver failure.  Since the
mortality for acute liver failure is greater than 80%, the only hope  is  for
orthotopic  liver  transplanatation.   The  survival  rate  at  one  year for
patients with acute  liver  failure  that  have  had liver transplantation is
greater than 60%.  However, only about 10% of  patients  will  receive  liver
transplants due to the many obstacles that must be overcome.

                        -LIVER FUNCTION TESTS-
ALKALINE PHOSPHATASE: Alkaline phosphatase is an  enzyme  that  is  found  in
liver,  bone,  kidney,  intestine,  placenta,  and  red  blood  cells.   Most
commonly, the liver and bone isozyme fractions are elevated.  If the alkaline
phosphatase  if  elevated  along  with  other liver chemistries such as gamma
glutamyl transpeptidase (GGTP), and  5  nucleotidase,  this would suggest the
elevated alkaline phosphatase has a liver origin.  There are also  situations
when  an elevated alkaline phosphatase can be normal, such as in the neonatal
period, adolescence, the  aged  and  pregnancy.   In  most cases, the highest
elevation  of  alkaline  phosphatase  in  seen  in  either  intrahepatic   or
extrahepatic  obstruction of the biliary tree.  It is a rare situation to see
below-normal alkaline phosphatases.  However,  in Wilson's disease associated
with hemolysis, excess  copper  can  replace  zinc  (a  cofactor  needed  for
alkaline  phosphatase  activity),  resulting  in  an  abnormally low alkaline
phosphatase.  HEPATOBILIARY CAUSES OF ALKALINE PHOSPHATASE ELEVATION: Primary
biliary cirrhosis, hepatitis, cirrhosis  of  the liver, bile duct obstruction
(from  tumors,  stones,  strictures,  sclerosing  cholangitis),  intrahepatic
cholestasis, and infiltrative or mass lesions  (from  sarcoidosis,  leukemia,
amyloid, primary or secondary metastatic tumors).  NONHEPATIBILIARY CAUSES OF
AN  ELEVATED  ALKALINE PHOSPHATASE: Diabetes mellitus, chronic renal failure,
renal cell carcinoma, periods of  bone growth, bone disease, placental enzyme
production, and intestinal disease.  GAMMA  GLUTAMYL  TRANSPEPTIDASE  (GGTP):
GGTP  is  an  extremely  sensitive  test  albeit  without specificity.  It is
elevated in hepatobiliary disease, and  when  elevated along with an elevated
alkaline phosphatase would steer one toward liver disease  rather  than  bone
disease.   NONHEPATOBILAIRY  CAUSES  OF  AN ELEVATION OF GGTP: Alcohol, renal
disease,  cardiac  disease,   pancreatic   disease,  hypelipidemia,  diabetes
mellitus, anorexia nervosa,  neurologic  disease,  porphyria  cutanea  tarda,
radiotherapy,   and   drugs  such  as  oral  contraceptives,  anticoagulants,
tricyclic antidepressants, phenytoin,  phenobarbital, and acetaminophen.  THE
AMINOTRANSFERASES: The aminotransferases (transaminases) consist  of  alanine
aminotransferase  (ALT)  and  aspartate aminotransferase (AST.  Elevations of
these  enzymes  are  indicative   of   hepatic  injury.   Elevations  of  the
transaminases that are extreme,  such  as  20  times  normal,  usually  means
hepatocellular  rather  than  cholestatic  of infiltrative disease.  However,
acute extrahepatic biliary duct obstruction  can produce transaminases in the
thousands which will  fall  with  time  even  if  the  obstruction  persists.
Patients  with  acute  viral  hepatitis, drug or toxic induced hepatitis will
cause  marked  elevations  of  the   transaminases.   There  is  no  clinical
correlation with the degree of elevation of the transaminases.  For  example,
falling  transaminases  may  be  seen  in patients with fulminating hepatitis
which is a reflection of  the  extensive loss of hepatocytes.  Also, patients
that are undergoing dialysis may have false decreases of the transaminases in
the presence of hepatitis.  ALT elevations  are  rather  specific  for  liver
disease  (but  may be elevated in muscle disease).  AST, however, is found in
liver, skeletal muscle, heart, pancrease,  kidney  and RBCs.  In general, AST
elevations are more sensitive and ALT elevations are more specific for  liver
disease.   In  most  cases, the ALT and AST are elevated in parallel, but the
following cases may be exceptions when  the AST/ALT ratios are examined.  The
AST/ALT ratio is helpful in identifying alcoholic hepatitis.  If both AST and
ALT are below 300 IU/L and the ratio is greater than 2,  this  would  suggest
alcoholic   hepatitis.    Also,  in  massive  hepatic  failure  secondary  to
hepatocytes necrosis, the ALT may  be  higher  than the AST.  In cirrhosis of
the liver, the AST is usually greater than the ALT.

                          -LUPUS NEPHRITIS-
Lupus nephritis (LN) is a serious  complication  of  SLE that can lead to end
stage renal disease.  Renal disease occurs in SLE in about 60%  of  patients.
There  are  4  histologic types of renal disease as follows: Mesangial, focal
proliferative, diffuse proliferative  and  membranous.  Patients that present
with    focal    proliferative,    diffuse    proliferative     and     mixed
membranoproliferative  nephritis  usually  need aggressive therapy.  Patients
with  primarily  pure  membranous  or  mesasangial  nephritis  have  a better
prognosis and can be treated with high dose steroid therapy.   Patients  that
show  irreversible  glomerular  sclerosis or interstitial inflammation have a
poor prognosis and will eventually  need dialysis.  Any patient that presents
with proteinuria and an active urinary sediment should have a  renal  biopsy,
C3,   C4,   CH50  (total  hemolytic  complement),  anti-double  stranded  DNA
(anti-dsDNA), creatinine, BUN,  and  24  hour  collection  of urine for total
protein and creatinine.  Patients with  elevated  anti-dsDNA  and  low  serum
complement  have active renal disease.  MESANGIAL NEPHRITIS: Has an incidence
of 10%,  with  mild  mesangial  proliferation  on  light  microscopy, diffuse
mesangial deposits of Ig (mostly IgG, but also IgM and IgA) and complement on
immunofluorescence, and mesangial deposits  on  electron  microscopy.   These
patients   usually   do   not   have  hypertension,  renal  insufficiency  or
hypocomplementemia.  They occasionally  have  an  active urinary sediment and
have a 1+ proteinuria.  Mesangial lupus has a very good  prognosis  and  very
rarely  progresses  to end stage renal disease.  The 5 year survivial is 100%
and steroids are rarely needed  for  the kidney disease.  FOCAL PROLIFERATIVE
NEPHRITIS: Has a 20% incidence, with focal segmental  proliferation  and  +/-
necrosis on light microscopy, diffuse mesangial and occasional capillary wall
deposits  of Ig and complement on immunofluorescence, and mesangial with some
subendothelial and  subepithelial  deposits  on  electron  microscopy.  These
patients have an active urinary sediment and hypocomplementemia.  They have a
2-3+ proteinuria and may or may not have hypertension or renal insufficiency.
These patients are treated with moderate dose steroids that  are  capable  of
causing  a  reduction  or  complete  remission of the proteinuria in > 50% of
patients.  With this, the  renal  function  stabilizes and these patients can
enjoy  a  5  year  renal  survivial  of  about  90%.   DIFFUSE  PROLIFERATIVE
NEPHRITIS:  Has  an  incidence  of   40-60%,   with   diffuse   endocapillary
proliferation  with necrosis found on light microscopy, diffuse mesangial and
capillary wall  deposits  of  Ig  and  complement  on immunofluorescence, and
large, diffuse, mesangial, subendothelial,  and  subepitherlial  deposits  on
electron  microscopy.   These  patients  have  hypertension,  active  urinary
sediment,  hypocomplementemia  and  renal insufficiency and a 3+ proteinuria.
Treatment is with high  dose  steroid  therapy  and  cytotoxic agents such as
cyclophosphamide.  The prednisone is given as 1 mg/kg/day, either as a single
or  divided  dose  up  to  a  maximum  of  80  mg/day.   If  the  patient  is
deteriorating rapidly, large boluses of methylprednisolone (Solu-Medrol)  can
be  givden  at 1 gram/day for 3 days.  Cyclophosphamide (Cytoxin) is given as
intravenous boluses of 500-750 mg/M2  monthly.   If the patient doses well on
this, the boluses can be given every 2-3 months for 1-2 years.  Some patients
will  be  able  to  stop  taking  the  cyclophosphamide  after  this  period.
Cyclophosphamide can also be given orally at 1-2 mg/kg/day with results  that
are not as beneficial as giving the drug IV.  Patients that do not respond to
cyclophosphamide  may  be  tried  on azathioprine (Imuran) at a daily dose of
1-2.5 mg/kg.   Cyclophosphamide  is  associated  with  an  increased  risk of
infections, bladder cancer and  herpes  zoster.   MEMBRANOUS  NEPHRITIS:  has
mesangial  expansion  with  diffuse thickening of the capillary wall on light
microscopy, intense staining for Ig  and complement along capillary walls and
the mesangium on immunofluorescence, and mesangial and diffuse  subepithelial
deposits  on  electron  microscopy.   These  patients  usually  do  not  have
hypertension,  renal  insufficiency  or  an active urinary sediment.  They do
have a 4+ proteinuria and  may  or may not develop hypocomplementemia.  These
patients  develop  nephrotic  syndrome  which  is  treated  with  high   dose
prednisone  for  2  months  with  remission  rates  of about 30%.  The 5 year
survival rate is 90%, due to the slow progression of the renal function.  Any
patient that presents with a  mild  form  of lupus nephritis and subsequently
becomes worse,  should  have  another  renal  biopsy  for  re-evaluation  and
histologic confirmation.

                           -LYME DISEASE-
Lyme  disease  is  a  caused  by  the  spirochete  Borrelia  burgdorferi, and
transmitted mainly by the  Ixodes  dammini  tick  bite.   This same tick also
spreads babesiosis.  Lyme disease occurs most commonly in children  under  15
and  the 25-44 year age group.  The prevalence in the USA varies, but is more
frequent in the Mid Atlantic  area,  followed  by the New England area, North
Central states, the Pacific states and  the  Southeast  and  Southwest.   The
mountain  region  has  the  lowest rate.  The highest incidence is during the
summer months from May to September.   Typically, the disease is divided into
3 stages as follows: STAGE 1: Stage 1 is  characterized  by  a  an  expanding
painless,  non- pruritic, erythematous annular rash that gives the appearance
of a bull's eye.  This rash  is  known  as Erythema migrans.  The rash occurs
3-30 days after the bite of the tick, and occurs in about 60-80% of patients.
Arthralgias (98%), malaise (80%), headache (64%), fever (60%), and stiff neck
also occur.  Some patients rarely can be  asymptomatic.   STAGE  2:  Stage  2
consists of cardiac and neurologic abnormalities.  There can be a lymphocytic
meningitis   (15%  and  meningoencephalitis,  peripheral  sensory  and  motor
neuropathies, facial nerve palsies  (7%),  myocarditis (8%), heart block, and
pericarditis.  STAGE 3: There is recurrent arthritis and chronic neurological
symptoms manifested as memory loss,  dementia,  depression,  sleep  disorder,
headache,  confusion,  fatigue,  poor  concentration, carpal tunnel syndrome,
motor, sensory and autonomic neuropathies.   There  also may be iritis, optic
neuritis, keratitis and  retinal  vasculitis.   DIFFERENTIAL  DIAGNOSIS:  HIV
encephalopathy,  various myopathies, Alzheimer's disease, amyotrophic lateral
sclerosis, myositis, depressive and psychological disorders all must be ruled
out.  Ebstein-Barr disease may simulate  Lyme disease.  If the temperature is
> 102 F, the diagnosis of EBV infectious mononucleosis must  be  entertained.
Both diseases may produce rash.  Lyme disease occasionally gives a malar rash
like  SLE in place of the typical erythema chronicum migrans rash.  Bilateral
posterior cervical adenopathy  occurs  with  mononucleosis,  but  not in Lyme
disease.  Atypical lymphocytosis would favor mononucleosis.  Viral meningitis
can mimic Lyme meningitis.  Both occur in the summer time.   If  the  patient
has  photophobia, and diarrhea then a viral origin would be favored.  Fatigue
and intellectual impairment  would  point  toward  Lyme  disease.  The CSF in
viral meningitis usually shows a lymphocytic predominance below 100,  whereas
in  Lyme disease there usually is a higher cell count of around 200 cells per
mm3.  Septic arthritis in  adults  must  be  considered.  Synovial glucose is
decreased in septic arthritis and normal in Lyme disease.  Cryoglobulins  are
increased  in  the  synovial  fluid  in  Lyme  disease,  and normal in septic
arthritis.  Also,  Juvenile  rheumatoid  arthritis  must  be  excluded in the
differential.  If there is not a high incidence of  Lyme  disease  where  you
practice,   and   you   suspect   Lyme   disease,  recovering  the  tick  for
identification, and testing can  be  helpful.   Tick  bites are painless, and
many patients are not aware of the presence of ticks on the their body.   The
sensitivity  of  lab  tests  is  not  presently good, especially early in the
disease.  However, there promises to  be  better, more sensitive and specific
tests becoming available in the future.  Presently, the ELISA IgG and IgM can
be done.  If you can get a culture of the advancing edge of the rash  with  a
punch  biopsy, then histology changes consistent with erythema migrans may be
seen.  If silver stains, such as a modified Dierterle or Bosma-Steiner stains
are done, the pathologist may be able to see the spirochetes.  The yield from
biopsies, however, is low.   TREATMENT:  Early treatment with antibiotics can
shorten the duration of symptoms and prevent the later complications  of  the
disease.   Response  to antibiotics in the later stages is variable.  Because
the spirochete can cross the  placenta, pregnant patients with disease should
be treated  with  IV  antibiotics.   Doxycycline  is  contraindicated  during
pregnancy.   STAGE  1  TREATMENT:  Doxycycline  100  mg  po  bid is typically
recommended but 100 mg tid may be more effective.  Give at least for 3 weeks.
Do not use in pregnancy or children  under  the  age of 12.  Do not take with
milk or antacids.  If patients are on warfarin, the warfarin may need  to  be
adjusted   downwards.    Oral   contraceptives   may  not  be  reliable,  and
photosensitivity is a problem.  Amoxicillin  is  given  at  1 gram tid for 21
days.  In children give 25-100 mg/kg/day.  Cefuroxime 500 mg bid,  Cefadroxil
1  g  daily,  and  Cefixime  400  mg  daily  also  may  be  used for 3 weeks.
Azithromycin 500 mg daily for at least  10 days appears to be effective also.
STAGE 2 TREATMENT: For recurrent or multiple Erythema migrans,  Bell's  palsy
or peripheral neuritis use Doxycycline or Minocycline 100 mg bid for 30 days.
For  Meningoencephalitis or carditis, in order of preference, give oral or IV
Minocycline 100-200 mg q 12  hours  for  30  days  OR Penicillin G 24 million
units per day in 6 divided doses for 30 days OR Ceftriaxone 2 grams every  12
hours  for  30 days OR Cefotaxime 3 grams every 4 hours for 30 days.  A short
course of steroids may be beneficial.  STAGE 3 TREATMENT: Can be treated with
oral Amoxicillin 500 mg tid with  probenicid  500 mg tid.  If this fails then
use IV ceftriaxone 2 grams qd or Cefotaxime 2 grams q 8  hours,  both  for  3
weeks.  PREVENTION- Permethrin and DEET.

                           -LYME DISEASE-
Caused by Borrelia burgdreri.  Vector is  Ixodes ticks.  Occurs in summer and
fall.  Is most common in  the  mid-Atlantic  states,  coastal  Massachusetts,
Oregon,  Northern  California  and the Upper Midwest.  STAGE 1: Presents with
flulike illness and erythema migrans in  60%,  about 3-32 days after the tick
bite.  The rash usually enlarges and resolves in 3-4  weeks.   There  may  be
meningismus  and  adenopathy.  STAGE 2: Occurs weeks to months after stage 1.
In  about  10-15%   neurologic   abnormalities   occur  such  as  lymphocytic
meningitis, facial neve palsy, chorea, encephalitis,  radiculitis,  myelitis,
peripheral  neuropathy.   Carditis,  (reversible  AV  block) develops in 10%.
Also, dilated cardiomyopathy  has  been  reported.   May  also  be iritis and
conjunctivitis.  STAGE 3: Occurs months to years after the initial infection.
Monarticular or oligoarticullar arthritis will develop in 50%  if  they  have
not been treated.  The arthritis becomdes chronic in 10-20% and is related to
HLA-DR2 and HLA-DR4.  Dementia, which is diagnosed by spinal fluid antibodies
against  B. burgodrferi, acrodermatitis chronica atrophicans, and progressive
chronic encephalitis may  also  develop.   MRI  can show demyelination.  Most
have positive serum antibodies.  DIAGNOSIS:  ELISA  antibodies  are  positive
after  2-6  weeks,  but  may  be  diminished by antimicrobial therapy.  False
positives occur with rheumatoid  arthritis, SLE, mononucleosis, echovirus and
spirochetal disease.  Do Western blot if false positive or  diagnosis  is  in
doubt.   TREATMENT: Doxycycline 100 mg bid for 10-21 days, amoxicillin 500 mg
tid  for  10-21  days  or  cefurxoime  axetil  500  mg  bid  for  10-21 days.
Amoxicillin is used for children and pregnant women.   Erythromycin  is  less
effective.   For Lyme carditis with a first degree AV block, PR itnerval > .3
seconds, ceftriaxone 2 g/d for 14-21  days  or penicillin G 20 MU/d for 14-21
days.  The outcome is usually good.  For facial  palsy,  without  meningitis,
and radiculoneuritis use doxycycline or amoxicillin orally.  Steroids are not
indicated.    The  outcome  is  usually  good.   If  meningitis  is  present,
ceftriaxone 2 g/d for 14-21 days or  penicillin G 20 milion units/d for 14-21
days is given.  Treatment for encephalopathy and  encephalomyelitis  are  the
same  as  for  meningitis.   Peripheral neuropathy and radiculoneuritis often
occur with meningitis and have  a  tendency to chronicity.  Lyme arthritis is
treated  with  doxycycline  100  mg  bid  for  30  days  OR  amoxicillin  and
probenecid, 500 mg each qid for 30 days, OR ceftriaxone 2 g/d IV for 14 days.
PREVENTION: Empiric treatemtn after a tick bite is not indicated.  Protective
clothing and repellents should be used.

                 -LYMPHOMA (Central nervous system)-
Both  Hodgkin's  disease  and  non-Hodgkin's  lymphoma can affect the nervous
system with about the same  incidence.   CNS involvement occurs most commonly
with lymphoblastic lymphoma, followed by  diffuse  undifferentiated  lymphoma
and  diffuse  histiocytic  lymphoma.   Most of these tumors are bulky and are
contiguous with the ventricles  or  meninges.   They can be demonstrated with
silver reticulum stain.  Immunohistochemical stains will differentiate B cell
from  T  cell  lymphomas.   Electron  microscopy  will  show  an  absence  of
junctional complexes (desmosomes).   Involvement  of  the  CNS  is  rare  and
usually occurs secondary to spread from nodes or extranodal areas.  Secondary
CNS  involvement usually occurs late in the course.  Primary lymphoma is very
rare.  Approximately 25% of all non Hodgkin's lymphomas present in extranodal
areas, but only 1% present  in  the  CNS.  These lymphomas have a pedilection
for the cerebral  hemisphers,  followed  by  the  cerebellum  and  brainstem.
PRIMARY   LYMPHOMA  comprises  about  0.2-2%  of  malignant  lymphomas.   The
incidence  is  increasing,  and  will  probably  exceed  that  of  low  grade
astrocytomas and approach that of meningiomas.  The reason for this is due to
the increasing number of  AIDS  and  transplant  patients.  The median age at
diagnosis is 52 years, unless the patient is immunocompromised  (34  year  of
age).   There  is  an  increased  incidence in the inherited immunodeficiency
diseases such  as  ataxia  telangiectasia  and  the Wiskott-Aldrich syndrome.
Other patients at risk include those with Sjoren's syndrome, SLE,  rheumatoid
arthritis,   and   those   with  Epstein  Barr  virus.   There  is  a  slight
preponderance of males versus females.  Primary lymphomas commonly affect the
frontal lobes  supratentorailly,  corpus  callosum,  septum pellucidum, basal
ganglia, and periventricular area.   Bilateral  cerebral  involvement  occurs
through   the   corpus   callosum.    Patients  can  present  with  dementia,
convulsions, papilledema, and long tract  signs.   The cerebellum is the most
common site infratentorially.  The most common types are of B cell origin  in
the  high  grade  category  of  non-Hodgkin's  disease.   CLINICAL:  Clinical
presentation  tends  to  be  similar  whether  due  to  primary  or secondary
lymphoma.  These consist of generalized  seizures (9%), mental status changes
(33%), symptoms of increased intracranial pressure such as  headache,  nausea
and  vomiting.   Patients may also develop aphasia, visual field defects, and
hemisensory or hemimotor deficits.  CT or MRI imaging will reveal invovlement
in one or more of the cerebral lobes in the grey or white matter.  CT imaging
is probably slightly better than  MRI  imaging.   About 25% will occur in the
septum pellucidum, corpus callosum and basal ganglion.  Approximately 25% are
located below the tentorium, and 10-30% will have  multiple  lesions  at  the
time  of  presentation.   On the other hand, secondary involvement of the CNS
from a systemic  lymphoma  have  a  tendency  to  present with leptomeningeal
involvment  instead  of  parenchymal  tumors.   If  there  are  homogeneously
enhancing lesions in the central gray or  corpus  callosum,  a  CNS  lymphoma
should  be  suspected.   Typically,  90%  of  these  tumors will enhance with
contrast material.  Lymphomas do  not  contain calcifications.  About 60% are
hyperdense and 10%  dense.   Radiation  necrosis  is  indistinguishable  from
recurrent  tumor,  and  may  require biopsy.  Angiography is not useful.  CSF
findings are non specific.  Cytology  is  only positive for lymphoma cells in
about 10%.  The sensitivity is higher in  those  with  secondary  involvement
(leptomeningeal  involvement),  and  in  AID's  patients.   Patients with CNS
lymphoma should have CT of  the  chest  and abdomen, chest x-ray, bone marrow
biopsy, testicular ultrasond and physical examination.  MENINGEAL AND  SPINAL
CORD INVOLVEMENT: Patients get extradural involvement from direct spread from
the   post  mediastinal  spaces  and  retroperitoneal  area  by  way  of  the
intervertebrtal foramina, or by  extension  from  an affected vertebral body.
Compression of surrounding vessels can cause an  ischemic  myelopathy.   Back
pain  and radicular spread, which is usually worse on lying down can develop.
Patients  may  develop  sphincter  problems  with  incontinence,  and spastic
paraparesis.  Nerve  root  involvement  can  cause  cervical  or  lumbosacral
radiculopathy.   Paraneoplastic  syndromes (peripheral neuropathy, cerebellar
cortical degeneration, acute  necrotizing  myelopathy, progressive multifocal
leukoencephalopathy,   polymyositis,   encephalomyelopathy)	has   also   been
reported.  TREATMENT: Following brain biopsy, radiation  therapy  is  usually
given at 4000-5000 cGy total, with 180-300 cGy daily fractions.  Chemotherapy
can  be  combined  with radiation therapy and tends to prolong survival.  The
median survival with radiation  therapy  alone  is  10 months.  The long term
survival is dismal with 47%  1  year  median  survival,  16%  2  year  median
survival,  8% 3 year survival, and 3% 5 year survival.  The prognosis is even
worse in AIDs patients, with a  median  survival of 3-5 months.  About 20-50%
of patients with AIDS and CNS lymphoma  will  have  complete  remission,  but
deteriorate rapidly due to opportunistic infections.

                      -MAGNESIUM IN CARDIOLOGY-
ARRHYTHMIAS:  Magnesium  has  been  used  successfully  in  several  types of
arrhythmias.  In patients that have  chronic CHF treated with loop diuretics,
oral magnesium chloride  has  been  shown  to  decrease  ventricular  ectopy.
Patients  that  have  sustained  monomorphic  ventricular  tachycardia may be
converted with magnesium sulfate 2 grams IV given over 1 minute with up to an
additonal 3 grams  if  needed.   In  patients  with  torsades de pointes with
prolonged QT intervals, successful conversion has been accomplished  using  2
grams  of  IV  magnesium sulfate given over 2 minutes followed by a 50 mg/min
infusion over a 1 hour period.  If  the torsades de pointes has not converted
after 30 minutes of treatment another 2 gram IV bolus may be given.  When the
arrhythmia converts, the drip may be reduced to  5-10  mg/min  until  the  QT
interval  is  <  0.5 seconds.  Magnesium levels should be checked frequently.
Magnesium has also been  helpful  in  converting AV nodal reentry tachycardia
and reciprocating reentry tachycardias associated with a bypass tract,  using
2  grams  of magnesium sulfate IV bolus and repeated x1 if needed.  Magnesium
apparently blocks the AV  node  terminating  the reentry circuit.  Multifocal
atrial tachycardia (MAT) has  always  been  difficult  to  treat.   Magnesium
sulfate given as a 2 gram IV bolus followed by an infusion of 1 gram/hour for
a  total  of 5-10 grams may be effective in treating this elusive arrhythmia.
Digitalis intoxication may be  improved  by giving magnesium which stimulates
the enzyme sodium-potassium-ATPase.  This enzyme is inhibited  by  digitalis.
Treat with 2 grams of IV magnesium sulfate bolus given over a 2 minute period
and  repeat  x1  if necessary.  Following cardiac surgery, magnesium has been
useful in the treatment  of  atrial fibrillation, suprventricular arrhythmias
and ventricular ectopy,  coronary  vasospasm  and  hypertension.   MYOCARDIAL
INFARCTION:  There  have  been  8  major studies done with regard to survival
using  magnesium,  and  all  have  consistently  demonstrated  a  decrease in
mortality.  However, the ISIS-4 study has  shown  no  benefit  in  preventing
death  using  IV  magnesium  after  MI.   The final word may not yet be in on
magnesium and its  potential  benefits  in  reducing  mortality in myocaridal
infarction.  Until the results of the ISIS-4 study were in magnesium promised
new therapy for reducing post-MI mortality.  There were two studies  in  1993
that found that adding magnesium to standard thrombolytic treatment would cut
the  number  of  post-MI  deaths  by  at  least  24%.   At the American Heart
Association  meeting  in  November  of   1993   it  was  announced  that  the
International Study of Infarct Survival  (ISIS-4)  study  did  not  show  any
benefit  for  IV magnesium in preventing deaths after an MI.  A meta-analysis
composed of  seven  major  randomized  trials  consisting  of  1,301 patients
suggested that IV magnesium may lower mortality by about 50% within the first
few weeks by reducing ventricular arrhythmias.  The difference  in  mortality
between  magnesium treated patients and placebo was found to be statistically
significant.   The   Leicester   Intravenous   Magnesium  Intervention  Trial
(LIMIT-2) represented the eighth major clinical  trial  and  consisted  of  a
randomized  double  blind,  placebo-controlled trial of 2,316 enrollees.  The
results of this study  also  demonstrated  a highly statistically significant
increase in survival using  IV  magnesium  sulfate  with  support  for  early
reduction  of  mortality following MI that was independent of thrombolytic or
antiplatelet therapy.  There was a  24% reduction of left ventricular failure
in the magnesium treated group, but little benefit in  reducing  arrhythmias.
The only major contraindication in using magnesium is with moderate to severe
renal  failure, where the dose will have to be adjusted along with monitoring
of  the  potassium  level.   Side  effects  of  magnesium  include  transient
flushing, occasional nausea and pain at the site of injection.  Some of these
adverse effects can  be  minimized  by  diluting  the  solution  to 10 mL and
injecting the magnesium over a 10-15 minute period.  So, in summary magnesium
can be used to treat or prevent arrhythmias and possibly improve MI outcome.

                -MALIGNANT LYMPHOMA AND CHOP THERAPY-
Cyclophosphamide  750 mg/m2 IV on day 1. Doxorubicin (Adriamycin) 50 mg/m2 IV
on day 1. Vinscristine (Oncovin) 1.4 mg/m2  IV on day 1. Prednisone 100 mg IV
on days 1-5.  CHOP is used for intermediate grades of unfavorable  histologic
subtypes. Repeat every 21 days.

               -MALIGNANT LYMPHOMA AND C-MOPP THERAPY-
Cyclophosphamide  650  mg/m2  IV  on  days 1 and 9. Vincristine (Oncovin) 1.4
mg/m2 IV on days 1 and 9. Procarbazine 100 mg/m2 PO on days 1-14.  Prednisone
40 mg/m2 PO on  days  1-14.   C-MOPP  is  used  for patients with unfavorable
histologic types who have pre-existing heart  disease,  when  doxorubicin  is
contraindicated.  Repeat every 28 days.

                -MALIGNANT LYMPHOMA AND CVP THERAPY-
Cyclophosphamide 400 mg/m2 PO on days  1-5.   Vincristine 1.4 mg/m2 IV (max 2
mg) on day 1. Prednisone 100 mg PO on days 1-5.  CVP is the most  often  used
for favorable histologic subtypes of malignant  lymphoma.   Repeat  every  21
days.

                         -MARFAN'S SYNDROME-
Marfan's syndrome is an  inherited  connective  tissue  disease  that  has  a
prevalance  of  4-6/100,000.  It affects the skeletal, cardiovascular, ocular
and cutaneous systems.  Celebrities  that  have  been affected over the years
include Abraham Lincoln, Paganini, Rachmaninoff, and Flo  Hyman  (an  Olympic
volleyball  player).   It  is  inherited as an autosomal dominat pattern with
incomplete penetrance.  It  is  important  to  make  a  diagnosis in order to
prevent the cardiac sequelae that often lead  to  a  33%  reduction  in  life
expectancy.   The average age at death is 32 years, mostly due to aortic root
dilatation with dissection, rupture,  aortic  and mitral regurgitations.  The
diagnosis may be difficult, as there  is  a  great  variability  in  clinical
presentatiion  with  new  mutations  occurring in 5-35% of patients without a
family history  of  the  syndrome.   There  is  no  ethnic,  racial or sexual
susceptibilty.  With newer diagnostic  methods  and  medications  it  is  now
possible  to  decrease  the  risk  for  these cardiac complications.  Antoine
Marfan first observed and described  the  syndrome  in 1891 in a young female
that had long fingers and skeletal abnormalities.  In 1955, it was found that
aortic dissection  constituted  the  majority  of  deaths.   The  chromosomal
mutation  that  causes  the  syndrome  has  been  localized  in  eight  three
generations.   The  gene  has been isolated on the long arm of chromosome 15,
which  codes  for  the   type   1   collagen  receptor,  chondroitin  sulfate
proteoglycan 1 core protein,  and  cardiac  muscle  alpha  actin.   CLINICAL:
SKELETAL: The most common skeletal abnormality is arachnodactyly (long spider
like,  thin  fingers).   Arachnodactyly produces two signs.  The first is the
thumb sign, which is considered  positive  when the thumb projects beyond the
ulnar border of the clenched hand.  The second sign is the wrist  sign  which
is considered positive when the thumb and the little finger overlap when they
are   circled   around   the  opposite  wrist.   False  postives  may  occur.
Dolichostenomelia (long extremities) and  tall  stature are common.  There is
an increased length of the limbs as compared with the trunk.  There may be  a
low upper segment:lower segment ratio of at least 2 standard deviations below
the  normal,  adjusted  for  age,  race and gender.  The arm span tends to be
greater than the height.   About  1/3  of  patients will have kyphoscoliosis.
There may be pectus excavatum (deformity of the sternum),  pes  planus,  high
arched narrow palate, and hyperextensible joints.  Less commonly, the patient
may  dvelop  prognathism, prominent supraorbital ridges, protrusio acetabuli,
thoracic lordosis, and dislocation of the patella superiorly.  CARDIOVASCULAR
INVOLVEMENT: The most common cardiovascular  finding is mitral valve prolapse
associated  with  mitral  regurgitation.   Patients  also  have  aortic  root
dilatation, aortic regurgitation, aortic aneurysm,  dissection  and  rupture,
that  can lead to sudden death.  The histologic changes in the aorta resemble
those of Erdheim cystic  medial  necrosis.   The  disorder may be complicated
with  endocarditis.   CUTANEOUS  INVOLVEMENT:  About  25%  of  patients  with
Marfan,s syndrome have striae, usually found on  the  deltoid,  pectorial  or
thigh  areas.   The  patient  may  also  have  keratotic papules that have an
annular configuration,  known  as  elastosis  perforans  serpiginosa.  OCULAR
INVOLVEMENT: Ocular abnormalities are  frequently  found  early  in  life  in
Marfan's  syndrome.  Patients may be myopic.  Bilateral dislocated lenses may
be found in about 80% of cases.  Most of these can be found before the age of
5 years of  age.   Dislocated  lenses  may  be  found on ophthalmoscopy which
usually shows a superior displacement of the lens.   For  a  more  definitive
exam,  a  slit  lamp  examination  should  be done.  The main differential in
dislocated  lens  is  homocystinuria,   but   this  displacement  is  usually
inferiorly, and homocystine can be found in the urine.  Cataracts and retinal
detachments can occur later in life.  WORKUP: Any patient that is suspect for
Marfan's syndrome should be questioned  about  a  family  history.   Physical
examination  should  search  for mitral valve prolapse, skeletal, ocular, and
cutaneous abnormalities.   An  echocardiogram  with  doppler  can demonstrate
aortic dilatation, aneurysm, mitral valve prolapse,  and  aortic  and  mitral
regurgitation.  X-rays can demonstrate pectus excavatum, kyphosis, scoliosis,
and  a  decrease  in  the  soft  tissue in the limbs.  An eye exam can reveal
myopia  and  lens  dislocation  with  slit  lamp  examination.   DIFFERENTIAL
DIAGNOSIS: Homocystinuria  has  characteristic  downward  dislocation  of the
lens, normal aorta, mental retardation, cutis reticulata, and is  transmitted
as  an  autosomal  recessive pattern.  Ehlers-Danlos syndrome has normal body
proportions, but  there  is  skin  hyperextensibility.   The  patient bruises
easily and there is poor healing of wounds.  Marfanoid hypermobility syndrome
has joint laxity and skin hyperextensibility, but there is a normal aorta and
normal lens.  THERAPY OF MARFANS'S SYNDROME: Patients should be monitored  at
frequent  intervals.   This consists of an echocardiogram that should be done
annually.  When the aortic root, corrected  for body surface area exceeds the
upper limit of normal by 50%, the echocardiograms  should  be  done  every  6
months.   When  the aortic root becomes greater than 60 mm, surgery should be
performed.  Elective and emergency surgery  carries an operative mortality of
less than 2% and the 5 year survival rate  is  greater  than  85%.   Pregnant
patients  with  Marfan  syndrome  should  have  a  therapeutic  abortion  for
significant  aortic  dilation  greater  than  40-45 mm.  It is preferable for
women to have their pregnancy early in their life before there is aortic root
dilatation.  Beta blocker should be instituted during pregnancy, and patients
may be delivered with forceps with prophylaxis for endocarditis.  The highest
risk of aortic rupture during pregnancy  is the 3rd trimester.  Patients that
have  mitral  valve  prolapse  with  regurgitation  should  get  prophylactic
anitbiotics to prevent endocarditis.  Patients should have annual examination
of the skeletal abnormalities to detect  scoliosis,  along  with  annual  eye
examinations.   Propranolol, or other beta blockers are given to decrease the
force of cardiac contraction in order  to delay the progression of the aortic
dilatation.  The dose should be adjusted to achieve a resting rate of  60/min
with  a  rise to no more than 80/min after moderate exercise.  Females may be
given estrogen and progesterone in order  to induce precocious puberty by the
age of 10, so that the ultimate height can be reduced.   All  contact  sports
should  be  interdicted,  as well as isometric exercises, and weight lifting.
For patients that want  to  engage  in  some  type  of exercise, swimming and
biking are recommended, as they  minimize  the  stroke  volume  and  increaed
cardiac  output  during  exercise.   All patients and families should be have
genetic counseling.
 
                         -MEDIASTINAL MASSES-
Mediastinal masses can be  divided  into  various  compartments of the chest.
Conventionally, they are divided into  the  anterior,  posterior  and  middle
compartments.   The  various  masses that occur in these compartments have an
affinity for one of these  compartments.   Most  of the masses are located in
the anterior and the middle compartments.   Most  patients  with  mediastinal
masses  are  asymptomatic,  but  they  can  present  with  cough, chest pain,
dyspnea, vocal cord paralysis or dysphagia.  Most of these masses do not have
any diagnostic features when seen on chest x-ray and will need chest CT.  The
CT scan can  differentiate  between  cystic,  vascular,  fatty, calcified and
noncalcified soft tissue masses.  CT guided perucutaneous  needle  aspiration
is  capable  of diagnosing about 90% of mediastinal carcinomas, but lymphomas
cannot be classifed in about 50%.  Lymphomas and other benign masses may need
a larger tissue sample that  can  be  acquired by percutaneous needle biopsy.
Mediastinoscopy, median sternotomy and anterior thoracotomy will be  required
in  these  cases.   MRI  may  be  useful in that is can differentiate between
vessels and  masses,  does  not  need  contrast  media,  and  there is better
delineation of hilar structures.  MRI is also capable of imaging in  multiple
planes.   Doppler  sonographhy or venography of brachiocephalic veins and the
superior vena cava, and barium swallow  of  the esophagus all can be helpful.
The mediastinum  has  boundaries  consisting  laterally  of  the  mediastinal
parietal  pleura,  superiorly  by  the bony thoracic inlet, inferiorly by the
diaphragm, anteriorly by the sternum  and  dorsally  by the chest wall in the
paravertebral gutters.  The anterior compartment is bounded by  the  sternum,
pericardium,  thoracic inlet, and the anterior margins of the brachiocephalic
vessels, and contains the  thymus  gland,  prevascular lymph nodes, displaced
parathyroid glands, retrosternal projections of the thyroid tissue and  loose
mesenchymal  tissue.   The  posterior  mediastinum is bounded by the anterior
vertebral bodies to the dorsal chest wall and contains the sympathetic chain,
lymph nodes and the thoracic spine.  The middle compartment is bounded by the
anterior compartment  and  the  anterior  margin  of  the  thoracic spine and
inludes the heart, aorta, major vessels, trachea, mainstem bronchi, vagus and
phrenic nerves, esophagus, lymph nodes and  the  pulmonary  hilum.   ANTERIOR
COMPARTMENT:  THYMOMA:  Thymomas have a peak incidence between 40-60 years of
age.  About  25-50%  are  associated  with  myasthenia  gravis.  Symptoms may
suggest cancer.  The mass is smooth  or  lobulated,  round  or  oval  with  a
homogeneous  density,  and  may  have a calcified rim.  It is the most common
anterior mediastinal  mass  and  is  diagnosed  by  CT,  needle aspiration or
surgical biopsy.  THYROID MASSES: Thyroid masses can present at any  age  and
are  uncommon.   They  may be associated with hyper or hypothyroidism, may be
asymptomatic  or  cause  airway  obstruction.   Diagnostic  tests  include an
enlarged thyroid, deviated trachea and positive thyroid scans.  They  present
as  smooth lobulated homogeneous densities.  calcification is common and they
will move  with  swallowing.   PARATHYROID  MASSES:  They  present as smooth,
lobulated masses and rarely cause anterior  mediastinal  masses.   TERATOMAS:
Teratomas  are  not  common,  have  a peak incidence in patients less than 35
years of age,  and  are  asymptomatic.   Radiographic  features  consist of a
smooth or lobulated, round or oval homgeneous density, with  teeth  and  bone
sometimes  present.   LYMPHOMAS: Have a peak incidence of between 20-30 years
of age, are common and may  present  with fever, weight loss, cough and pain.
MIDDLE COMPARTMENT: LYMPH NODE ENLARGEMENT: Is a common cause of  mediastinal
masses,  and  may  be  unilateral  or  bilateral.   Causes  include lymphoma,
leukemia, sarcoidosis, bronchogenic  carcinoma, and granulomatous infections.
BRONCHOGENIC CYSTS: Bronchogenic cysts may  be  round  or  oval,  have  sharp
margins  and  appear  near the carina or the main bronchi.  The peak ages are
less than 35 years of  age.   They  are rare and usually asymptomatic.  There
may be expectoration of their  contents,  and  they  may  become  secondarily
infected.    PERICARDIAL   CYSTS:   Pleuropericardial   cysts   are   usually
asymptomatic,  occur  mostly  at the cardiophrenic angles (more common on the
right side), and the fluid  contents  will  shift  with a change in position.
They can occur  at  any  age  and  are  the  most  common  mediastinal  cyst.
METASTATIC CANCER: May be asymptomatic or symptomatic.  It occurs in patients
>  35  years of age.  SARCOIDOSIS: Is common and occurs in patients less than
35 years of age.  Requires a tissue biopsy from the lung or skin.  FORAMEN OF
MORGAGNI HERNIA: Abdominal  contents  may  be  seen  on chest x-ray.  Usually
occurs on the right side of the pericardium as a round or oval mass.   It  is
usually  asymptomatic.   PULMONARY ARTERY ENLARGEMENT: There may be pulmonary
hypertension,  stenosis  or  aneurysm.   CT   or  angiography  can  make  the
diagnosis.  DILATION OF THE SUPERIOR VENA CAVA: Occurs on the right side as a
smooth walled density.  The azygos vein is usually dilated also.  Chnages  in
intrapleural  pressure  will  alter  the  size.   DILATION  OF  THE AZYGOS OR
HEMIAZYGOS VEINS: Presents as a  round  or  oval smooth walled density at the
angle of the right tracheobronchus.  It may be confused with an azygos  lymph
node  which can be differntiated by a Valsalva maneuver.  AORTIC ANEURYSM: Is
a common  mass  that  occurs  in  persons  >  50  years  of  age.   It may be
asymptomatic or cause chest pain with dissection.  Calcification  is  common.
CT  or  angiography  can diagnose.  POSTERIOR COMPARTMENT: NEUROGENIC TUMORS:
These comprise 20% of all primary  mediastinal tumors.  They can occur at any
age, are  usually  asymptomatic,  but  occasionally  present  with  pain  and
dyspnea.   Radiographically,  they  occur  in  a  paravertebral location, are
usually unilateral, and have a  round  or  oval homogenous density with sharp
margins.  They can be diagnosed via CT, and  myelogram.   ESOPHAGEAL  TUMORS:
Barium  swallow is required to aid in the diagnosis.  The patient may present
with dysphagia, substernal  pain  and  bleeding.   MENINGOCELE:  These may be
solitary or multiple with a slight predilection for  the  right  side.   They
have  sharp  margins  and  usually occur in middle aged adults, and are often
associated with neurofibromatosis.   FORAMEN  OF  BOCHDALEK HERNIA: These are
more common on the left side.  Radiographically, they may be  round  or  oval
and  are  usually seen in children.  Strangulation can occur.  Barium studies
may be helpful.   THORACIC  BONEY  TUMORS:  Bony tumors produce paravertebral
round soft tissue masses with occasional destruction of the  vertebra.   Back
pain   is   common.    CT  and  tomograms  can  be  helpful.   EXTRAMEDULLARY
HEMATOPOIESIS: These patients are usually asymptomatic.  The patient may have
chronic hemolytic anemia with splenomegaly.   They occur as smooth, lobulated
multiple homogeneous densities.

                       -MEGALOBLASTIC ANEMIAS-
The  megaloblastic  anemias  are  usually  due  to  folic acid or vitamin B12
deficiency (90%), caused by  defective  DNA  synthesis, but other causes from
drugs such as methotrexate,  sulfa,  and  hydroxyurea  may  be  instrumental.
VITAMIN  B12  DEFICIENCY:  May be caused by decreased production of intrinsic
factor (Pernicious anemia,  gastrectomy),  blind  loop syndrome (GI bacterial
overgrowth), chronic pancreatitis, fish  tapeworm  (Diphyllobothrium  latum),
surgical resection of the terminal ileum, and Crohn's disease.  CLINICAL: The
patient  should  be  questioned  about a family history of pernicious anemia,
stomach and bowel surgery and whether there are any other autoimmune diseases
present.  There may also be glossitis, jaundice and splenomegaly.  Neurologic
symptoms consist of decreased  vibratory  and  positional sense, ataxias, and
paresthesia due to posterolateral column degeneration.   There  may  also  be
symptoms  of confusion and dementia, particularly in elderly patients.  It is
important to realize that  neurologic  symptoms  may  occur in the absence of
anemia and may not normalize completely with treatment.  LABORATORY: The  CBC
and  RDW  are  usually  increased  with  a  macrocytic  anemia.  There may be
neutropenia  and   thrombocytop;enia.    The   peripheral   smear   can  show
poikilocytosis, polymorphonuclear leukocytes with 5  or  more  nuclear  lobes
(hypersegmented),  aniscocytosis,  and  macroovalocytes.   These  changes may
occur months before the  development  of  the  anemia.  The serum vitamin B12
level is decreased and there may elevation of the LDH and bilirubin.  Vitmain
B12 < than 100 pg/ml is usually  always  associated  with  clinical  disease.
Normal  values are 200-900 pg/ml.  If the vitamin B12 levels are equivocal, a
serum  methylmalonic  acid  (MMA)  and  homocysteine  can  be  useful  in the
diagnosis.  Both  MMA  and  homocysteine  can  be  elevated  in  vitamin  B12
deficiency  while the homocysteine will be elevated in folic acid deficiency.
The Shilling test  will  show  reduced  vitamin  B12  absorption which can be
corrected by giving intrinisc factor in those patients with Pernicious anemia
and gastrectomy.  The bone marrow is hypercellular with erythroid hyperplasia
and megaloblastic maturation affecting all three cell lines.  The bone marrow
is useful in ruling out myelodysplastic syndromes and hematologic  malignancy
which  can resemble megaloblastic anemia in the peripheral blood.  Antibodies
to intrinsic factor may be found  in approximately 20% of cases of pernicious
anemia.  Patients that  have  pernicious  anemia  will  need  to  have  upper
endoscopy  because  of  the  high  incidence  of  gastric cancer.  TREATMENT:
Treatment for vitamin B12 deficiency is  vitamin  B12, 1000 ug given IM daily
for 7 days at least, and longer in patients with severe  neurologic  defects,
then  weekly  for  1-2  months followed by 1000 ug monthly.  The reticulocyte
count should peak at 1 week, and an elevation of the Hb should occur over 6-8
weeks.  There may be a  concurrent  iron  deficiency in patients with vitamin
B12 deficiency, and if the patient fails to respond to  the  B12  injections,
iron  deficiency  anemia  should  be addressed.  Megaloblastic anemias should
never be treated empirically with  folic  acid  because the anemia of vitamin
B12 may respond, but the neurologic abnormalities will continue to  progress.
The serum potassium level should be monitored during early treatment in order
to  avoid  hypokalemia.   FOLATE  DEFICIENCY: The causes of folate deficiency
include dietary deficiency (the daily  requirement  of folate is 100-200 ug).
Folic acid is found in most of the leafy vegtetables, yeasts and to a  lesser
extent  in most meats.  However, if the food is overcooked, the folic acid is
destroyed.  Dietary  deficiency  can  occur  in  elderly  patients  with poor
dentition,  alcoholics,  and  those  who   overcook   their   food.    Folate
requirements   are   increased  in  those  patients  with  hemolytic  anemia,
pregnancy, cancer patients,  and  exfoliative  skin  diseases.  Drugs such as
sulfasalazine, phenobarbital, estrogens and phenytoin can also interfere with
folate absorption.  Folic acid deficiency can  also  occur  in  malabsorption
states  such  as  sprue.   The  clinical  symptomatology and lab findings are
similar to vitamin B12 deficiency.   In  addition, the serum folic acid level
is low, usually less than 3 ng/ml.  Normal is > 6 ng/ml.   Serum  levels  may
not  be accurate since a meal containing folate can normalize a low value.  A
more accurate test that should be  done  in  all  cases is the red blood cell
folate level.  A level < 150 ng/ml will make the diagnosis.  The vitamin  B12
level  in  folic acid deficiency is normal.  Other macrocytic anemias such as
those   associated   with   liver   disease,   marrow   dyscrasias,   use  of
antimetabolites and alkylating can be differentiated by a  low  serum  folate
level.   AIDS  patients  that  are  being treated with zidovudine may develop
macrocytosisas as well  as  alcoholics  with  anemia  of liver diseae.  These
patients do not develop megaloblastic morphology.   TREATMENT:  Treatment  of
folic  acid  deficiency  is  with  folic acid 1 mg PO daily.  The response by
reticulocytosis  and  anemia  imporvement  is  the  same  as  in  vitamin B12
deficiency.  It should be noted that large doses of folic acid will produce a
hematologic response in those patients with vitamin B12  deficiency,  but  do
not  correct  the neurological abnormalities.  Therefore, a precise diagnosis
must be made.

                              -MELANOMA-
The  incidence of melanoma has been increasing greatly, but survival has also
been improving.  Melanoma now is  the  eighth  most common cancer in the USA.
It can rapidly progress from a superficial lesion of  the  epidermis  (nearly
100%  curable) to a rapidly invasive cancer that is incurable.  Therefore, it
is incumbent upon the patient  and  the  physician  to carry out an extensive
search including axilla, scalp,  palms  and  soles,  skin  covered  by  hair,
subungual areas, genitalia, interdigital web spaces, perineum, perianal skin,
sclera,  iris,  conjunctiva, retina, oral mucosa, and nares.  Early melanomas
are usually flat or slightly  raised  and  thin. Advanced melanomas are thick
with irregular surfaces, and ulcerated.   About  90%  of  melanomas  are  now
diagnosed  in  stages  I and II, with the median tumor thickness at diagnosis
less than 1 mm compared with  2.5  mm  about 40 years ago.  Nodular melanomas
are becoming less common and superficial  spreading  melanomas  more  common.
Melanomas also are being found less on the head and neck and more on the arms
and  legs.  The microstaging of melanomas is based on two systems.  The Clark
system indicates the depth of the tumor  in the different layers of the skin.
Level I melanoma  is  confined  to  the  epidermis.   Level  II  invades  the
papillary  dermis; level III fills the papillary dermis; level IV invades the
reticular dermis and level V penetrates  the subcutaneous fat or deeper.  The
Breslow system measures tumor thickness from the top of the granular layer to
the deepest invasion.  Once the microstaging has been accomplished,  clinical
staging  must  be  done  for  proper  treatment  of  the  disease.   Physical
exmanination  is  carried out to ascertain if there is a second primary tumor
which occurs in  about  1-2%  and  to  see  if  there is regional metastases.
Metastasis most commonly occur to the lymph nodes, liver, lung, GI, brain and
breast in women.  GI metastasis is associated with bleeding and anemia.   Lab
should  include a CBC, platelets, liver function and a chest x-ray.  Patients
that are at high risk for metastasis, such as those with a primary tumor 5 mm
thick or regional lymph node involvment  should  have a CT of the abdomen and
MRI of the brain with biopsy of any suspicious lesions.  Enlarged lymph nodes
can be sampled by fine  needle  aspiration  of  excisional  biopsy.   If  the
patient  has hemoptysis, cough, or dyspnea, CT of the chest should be done to
rule out mediastinal, pleural  or  pulmonary  metastases.   Bone scans may be
helpful for metastatic bone lesions which  present  with  localized  pain  or
pathologic fractures.  Genitourinary metastasis can be investigated with IVP,
cystoscopy  or  CT scans.  The thickness of the tumor in stage I or II is the
best prognosticator for  local  recurrence  and  metastasis.  Survivor can be
considered excellent for patients with superficial lesions, but about  5%  of
patients  with  thin  lesions not greater than .75 mm have recurrences within
about 3.6  years.   Unfortuantely,  metastases  can  occur  10-15 years after
excision of a primary tumor.  The best predictor for stage III is  the  tumor
burden  which  is  measured  by  the  percentage and number of positive lymph
nodes.  Other predictors in Stage  III  for survival consist of the thickness
of the primary tumor, presence or absence of  ulceration  and  the  location.
Melanomas  occurring  on  the  neck,  trunk  and head have a worse prognosis.
Patients that present as stage  IV  have  a  dismal prognosis with an average
survival of 6-18 months.  Liver metastases probably has the worst  prognosis,
but  lung  metastases  has a survival of about 11 months.  TREATMENT: STAGE I
AND II.  Surgical excision with adequate  skin  margins of 0.5 cm for in situ
melanoma, 1 cm for melanomas < 1 mm thick and 2 cm for melanomas 1-4 mm thick
should be carried out.  However, more conservative surgery may  be  necessary
on  the face.  Wedge resection will give the best result when melanomas occur
on  the  outer  ear  or  lip.   Melanomas  occurring  subungually  and  acral
lentiginous melanomas require amputation  of  the interphalangeal proximal to
the tumor.  Lymph node dissection in stage I and II is controversial, as many
patients will have systemic meastases with no regional nodes  involved.   For
patients with lesions less than 1 mm thick or greater than 3-4 mm thick, many
physicians  would  not  perform  regional  node  dissection.   Stage  III  is
characterized  by  regional  lymph  node involvement with all suspicios nodes
sampled and excised.  Alternatively,  local  radiation  can be carried out or
regional venous or intraarterial perfusion  with  cisplatin  or  dacarbazine.
Stage  IV  may  be  treated palliatively with surgery or radiation.  Response
rates  with  chemotherapy  is  poor  at  between  10-25%  in  general.  These
responses are short.  Dacarbazine is the best for monotherapy.  If  tamoxifen
is added to dacarbazine the response rate and median survivals are increased.
Tamoxifen  may also be added to the combination of dacarbazine, cisplatin and
carmustine, with this combination  giving  the  best results currently.  High
dose chemotherapy and autologous bone marrow transplantation  has  also  been
used, but yields only a median survival of 15.2 months in responders.

                            -MENINGITIS-
Common causes  of  meningitis  by  age:  Neonatal:  E  coli  50-60%;  Group B
streptococcus 20-40%; Listeria  monocytogenes  2-10%.   Children:  Hemophilus
influenzae  40-60%,  Neiserria  meningitidis  10-35%  S.  pneumoniae  10-20%;
Adults:  S  penumjoniae 30-50%, N. meningitidis 10-35%, Gram negative bacilli
10-20%, Listeria 5-10%.  Patients with otitis/sinjusitis/mastoidits are prone
to S.  pneumoniae,  H.  influenzae.   With  CSF  rhinorrhea  S. penumonaie is
common.  Closed  head  trauma  may  lead  to  S.  pneumonaie,  H.  influenzae
meningitis.   Penetrating  head  trauma  can  cause  S. aureus, Gram negative
bacilli meningitis.  Asplenic patients  are  suseptible  to S. pneumonaie, N.
meningitidis, H. influenzae, Sickle cell anemia patients are  more  prone  to
Salmonella, H. influenzae, S. pneumoniae.  Alcoholic patients are susceptible
to  Klebsiella  and  S. pneumoniae.  HIV infection can cause meningitis by C.
neoformans, Toxoplasma, L. monocytogenes, Cytomegalovirus.  (Immunosuppressed
patients are subject to  L.  monocytogenes  and C. neoformans.  Neurosurgical
procedure can  be  complicated  by  S.  aureus,  and  gram  negative  bacilli
meningitis.   Differential:  Herpes  encephalitis  is nonseasonal, may have a
focal neurologic defect, seizures and  temporal  lobe lesions on MRI/CT scan.
Sarcoid meningitis causes cranial nerves palsies and there will  be  evidence
of  systemic  disease.   Viral  meningitis mahy produce a maculopapular rash,
diarrhea and is seasonal.  Chemical meningitis  will have a history of spinal
anesthesia or tap.  Bacterial endocarditis have septic emboli, positive blood
cultures and heart murmur.  Early TB meningitis shows  a preponderance of PMN
leukocytes initially followed by lymphocytes, cranial nerve abnormalities and
the chest x-ray is abnormal  in  50%.   Amebic  meningoencephalitis  gives  a
history  of  freshwater  swimming.   Parameningeal  infection  will  show the
lesions on MRI/CT imaging.   Carcinomatous  meningitis  usually has no fever,
but cranial nerve involvement common, and patient  has  known  cancer.   Lyme
disease is  seasonal, history of tick bite, cranial nerve 7 palsy and flulike
symptoms.

                        -MENINGITIS (Causes)-
CAUSES: Hemophilus is the leading cause in children.  Pneumococcus is the top
cause in adults.  Occurs suddenly, and frequently presents with  seizures  or
coma.   Meningococcus  patients  present with a characrteristic rash, but the
rash may be seen with ECHO  and  staphylococcus.  Listeria is usually seen in
immunosuppressed patients.  Tuberculosis usually  presents  as  a  smoldering
subacute  or  chronic  disease.   Cranial  nerve involvment is common.  Viral
patients  usually  have  a  viral  syndrome.   Most  will  have  a  short and
uncomplicated  course.   Most  are  caused  by  enteroviruses  as  ECHO   and
Coxsackie.   Gram  negative  meningitis  is usually associated with trauma or
following surgery.  Klebsiella, E. coli  and Pseudomonas are the most common.
Cryptococcus is seen in immunosuppressed patients.  Coddidiodes is present in
the southwest USA.  Candida may also cause.  Neoplastic  disease  can  result
from  metastases  to the CNS or leukemia.  Sarcoid and SLE meningitis are not
common.

                        -MENINGITIS (Chronic)-
Chronic meningitis is defined as meningitis that presents less acutely over a
period of weeks to months.  The  syndrome may be caused by bacterial, fungal,
parasitic or viral pathogens.  Noninfectious causes  may  also  be  a  fault,
secondary   to  malignancy  (lymphoma,  melanoma,  breast  and  lung  cancer,
leukemia,  carcinomas),  sarcoidosis,   vasculitis,  and  Bechet's  syndrome.
Patients  with  noninfectious  etiologies  can  mimic  a  chronic  infectious
meningitis  syndrome.   Many  of  these  patients  will  have  cranial  nerve
abnormalities.  The CSF cytology may  be  positive  for  malignant  cells  in
50-80%  of  cases.  CSF lactic dehydrogenase is also helpful in the diagnosis
of noninfectious disease.  CT and MRI  are usually positive.  The most common
infectious agents  are  Mycobacterium  tuberculosis,  atypical  mycobacteria,
Cryptococcus,  Coccidioides,  Histoplasma,  Borrelia  burgdorferi,  Treponema
pallidum,  and  Brucellosis.   Diagnosis  of  T.  pallidum,  B.  burgdorferi,
Toxoplasma  gondii,  and  Brucella  meningitis is usually made with serologic
assays for these  organisms.   Chronic  meningitis  presents insidiously with
headache, fever, lethargy, nausea, vomiting and nuchal rigidity.  The patient
may   have   been   ill   for   several   weeks   prior   to    presentation.
Characteristically, the CSF will show 100-400 WBC/mm3  with a prepondrance of
lymphocytes,  moderate  or  severe  elevation  of  the protein, and decreased
glucose.  TUBERCULOSIS MENINGITIS: Symptomns include fever between 99-103 F.,
headache, and lethargy.  Meningeal signs  are  present in about 50% of cases.
The peripheral WBC may range from low normal up to greater than 20,000.  Acid
fast stains of the CSF are positive in only about  10-20%  of  patients,  and
cultures  are  positive  in  about 60-80% of cases.  In order to increase the
sensitivity of these latter two  tests,  large amounts of spinal fluid (20-40
ml) should be submitted  for  smear  and  culture.   Most  will  have  a  CSF
lymphocytic  pleocytosis,  protein  greater  than 50 mg/dl and some will have
glucose levels of 40 mg/dl or less.   Other tests that have been developed to
increase the sensitivity and specificity  include  CSF  adenosine  deaminase,
radioimmunoassay   for   Mycobacterium   antigen,   and  latex  agglutination
immunoassay.  The mortality can  be  high  if  there  is  a delay in therapy.
Treatment is with isoniazid, rifampin, and  pyrazinamide  or  ethambutol.   A
response is usually seen by one month and the patient is treated for 1 years.
Since  rifampin  has a broad spectrum of activity, a response is not specific
for tuberculosis meningitis.   Steroids  are  controversial, but may decrease
the risk of herniation.  COCCIDIOIDOMYCOSIS  MENINGITIS:  Blacks,  Filipinos,
and  pregnant  women  are  more  at  risk  for  developing  dissemination and
meningitis following pulmonary infection.  About 66% of patients that acquire
C.  immitis  meningitis  have  no   risk  factors.   Those  at  risk  include
individuals that reside in southern Calfironia, Arizona, New  Mexico,  Texas,
Mexico,  Central  America,  Nevada, and Utah.  It is acquired by inhaling the
spores of Coccidioides immits.  Other  clues  may come from concomitant skin,
lung, or bone lesions.  CSF includes a positive complement fixing antibody in
75-90%.  Coccidioides immitis is rarely seen  on  smear.   and  cultures  are
positive  in  about 50%.  Culture plates must be handled with extreme care as
they are very  infectious.   Some  patients  will exhibit a polymorphonuclear
leukocyte pleocytosis rather than the usual lymphocytic.   Large  volumes  of
CSF  should  be  collected.   Treatment  is  with IV amphotericin for a total
dosage of 3-4 grams.   Most  would  also  use  an Ommaya resorvoir instead of
repeated  intrathecal  injections,  which  can   result   in   arachnoiditis.
CRYPTOCOCCAL  MENINGITIS: Cryptococcal meningitis has become more common with
the introduction of AIDS.  It has  a  presentation that is similar to that of
tuberculosis.  Those at risk include those with AIDS, sarcoidosis,  lymphoma,
renal  transplantation,  and  SLE.   About  20-50%  will have no predisposing
etiology.  Cultures should be  obtained  from  the CSF, sputum, skin lesions,
and bone marrow.  CSF cryptococcal antigen is p;ositive in  80-90%  by  latex
fixation testing.  Culture of the CSF is positive for Cryptococcal neoformans
in  90%  of  cases,  but  multiple  spinal  taps may be needed to attain this
percentage.  India ink preparations are postive in 50-75% of patients.  There
is CSF pleocytosis.   Patients  that  have  low  CSF  glucose, high titers of
cryptococal antigen, high CSF opening pressure , fewer than  20  WBC  in  the
CSF,  a  low  CSF  glucose  and  underlying  lymphoma  have a poor prognosis.
Ampnhotericin and flucytosine are usually the drugs of choice.  Patients with
severe disease are treated  for  about  6  weeks,  while  mild disease may be
treated for only 4 weeks.   Flucytosine  usually  cannot  be  given  in  AIDS
patients, as bone marrow suppression may develop or already be present.  Long
term  fluconazole prophylaxis is given to AID's patients.  Some patients have
been  treated  successfully   with   fluconazole  rather  than  amphotericin.
Intraventricular amphotericin  therapy  may  be  needed  in  those  that  are
resistant   to   IV   amphotericin.    BLASTOMYCES  DERMATITIDIS  MENINGITIS:
Meningitis will develop in about  33%  of patients with disseminated disease.
Cultures should be  obtained  from  sputum,  bone,  joint  fluid,  skin,  and
prostatic  secretions,  as  the organisms are rarely seen on culture from the
CSF.   Serologic  tests  are  not  beneficial  for  extrapulmonary infection.
Amphotericin B is  the  drug  of  choice  with  or  without  intraventricular
therapy.   HISTOPLASMOSIS MENINGITIS: Cultures are positive in about 50%, and
CSF antibodies are positive in 90%.  Culture of other sites may be needed for
diagnosis.  Treatment  is  with  amphotericin  B.  SYPHILITIS  MENINGITIS may
present only with a headache usually within 2 years of the  acute  infection.
Neurosyphylis  presentation  has  changed over the years.  Many of these will
not have the classic signs  of  teritiary  syphilis such as pupillary changes
and tabes dorsalis.  Fever may not be present.  Diagnosis  can  be  aided  by
positive  treponemal tests and postitive CSF VDRL.  ACTINOMYCOSIS MENINGITIS:
Not only can actinomycosis cause meningitis, it may also cause brain abscess,
epidural  abscess  and  subdural  empyema.   These  may  present  with  focal
neurologic signs.  Some patients  may have underlying mastoiditis, sinusitis,
dental infection or skin infections.  The CSF  usually  shows  a  lymphocytic
pleocytosis.    The  basilar  meningitis  may  be  mistaken  for  tuberculous
meningitis.   Actinomycoses  grows  slowly,   are  fastidious  gram  positive
filamentous  bacteria,  and  have   anaerobic   or   microaerophilic   growth
requirements.    Treatment  is  with  high  doses  of  penicillin.   NOCARDIA
ASTEROIDES CHRONIC MENINGITIS is unusual without brain abscess.  Treatment is
with sulfonamides.  BORRELIA BURGDORFERI  MENINGITIS: Lyme meningitis usually
presents in the second  stage  of  Lyme  disease  months  after  the  initial
infection.   Patients  often  present after long standing symptoms.  Fever is
frequently absent.  Symptoms include  headache, stiff neck, photophobia.  The
patient may also have Bell's palsy and radiculopathies.  CSF findings include
a low glucose (15%), pleocytosis, and elevated protein.   The  CSF  VDRL  may
show a false positive response, but treponemal tests are negative.  Treatment
is  with  ceftriaxone  or high dose penicillin IV.  BRUCELLOSIS MENINGITIS is
rare.    Patients    with    brucellosis    present    with   night   sweats,
hepatosplenomegaly, and lymphadenopathy.  Patients should have blood and  CSF
agglutination  titers  and  cultures.  The cultures require special media and
need to be incubated  for  2-4  weeks.   Treatment  is with tetracycline with
rifampin or streptomycin.  BEHCET'S MENINGITIS: About a quarter  of  patients
will  develop  meningoencephalitis.   These  patients typically have oral and
genital ulcers,  uveitis,  and  skin  lesions.   The  CSF  glucose is usually
normal, but protein is elevated and  there  is  a  pleocytosis.   SARCOIDOSIS
MENINGITIS:  Sarcoidosis may present with neurologic symptoms in about 50% of
cases.  Patients may have peripheral neuropathy, cranial nerve abnormalities,
and cerebral and spinal lesions may be present.  Diagnosis is usually made by
biopsy of liver, lymph nodes, salivary gland, or parotid gland.

                     -MENINGITIS (CSF Profiles)-
BACTERIAL: The leukocyte count  is  >500  with  a  predominance of PMNs.  The
protein is increased.   The  glucose  is  decreased  while  the  pressure  is
increased.   Gram  stain  will  be positive in 80%.  FUNGAL, TB AND PARTIALLY
TREATED BACTERIAL: The leukocyte is < 500 with a predominance of lymphocytes.
The protein is normal or slightly  increased.  The glucose is decreased.  The
pressure is normal or increased.  Mycobacteria are rarely seen.  India Ink is
positive for cryptococcus.   VIRAL:  The  leukocyte  count  is  <500  with  a
predominance  of  lymphocytes.   The protein is normal or slightly decreased.
The  glucose  is  normal,  while   the   pressure  is  normal  or  increased.
Microscopic  exam  is  negative.   Elevated  protein  with   no   other   CSF
abnormalities,  including a normal cell count can be seen in stroke patients,
diabetics, chronic alcoholics and uremic patients.

                       -MENINGITIS CSF TESTS-
Bacterial: cell count usually 1000-5000 with  >  80%  granulocytes.   Protein
100-500.   Glucose  < 40.  Gram stain positive 75-80%.  Culture 70-85%.  Acid
fast, india ink, cytology,  wet mount negative.  Counterimmunoelectrophoresis
positive.  Lactate positive at > 35 mg/dl.  Limulus lysate positive  in  gram
negative   meningitis  >  90%.   Cryptococcal  antigen  negative.   Adenosine
deaminase negative.   Cyclic  adenosine  monophosphate  decreased.  LDH often
elevated.  Aseptic meningitis: Cell count usually 100-500 with less than  50%
granulocytes, but may be > 50% in early tuberculous, amebic, fungal, viral or
spirochetal  meningitis.   Protein 100-500.  Glucose is normal but may be low
in meningitis secondary to M.  tuberculosis,  C. neoformans, and other fungi,
chemicals, sarcoidosis, neoplasms, syphilis, and subarachnoid hemorrhage.  In
viral meningitis it is < 40 in less than 5% of viral cases, especially  mumps
and  lymphocytic  choriomeningitis.   Gram  stain  is  negative,  but  may be
positive  in  fungal  meningitis  (40%  with  Candida  species).   Culture is
negative, but is positive in > 80% in tuberculosis  and  cryptococcal  (50%),
and rarely with viral.  The acid fast stain is positive in TB in 15 to > 60%.
The india ink is positive in cryptococcal meningitis in 50-75%.  Wet mount is
positive  in  amebic  meningitis.   CIE,  Limulus  lysate,  and  lactate  are
negative.    Cryptococcal   antigen   is  positive  in  cryptococcal  (>95%).
Adenosine deaminase is positive in TB (>80%).  LDH is often elevated.

                    -MENINGITIS (Meningococcal)-
Meningococcal meningitis (MM)  can  be  a  severe illness, with uncomplicated
meningococcal meningitis causing death in about 10-20%.  If  the  disease  is
fulminant  the  mortality  may  reach  over 50%.  The incidence in the USA is
about 1.2 cases /100,000.   MM  is  caused  by Neisseria meningitidis, a gram
negative, oxidase  positive,  nonmotile,  non  spore  forming  organism  that
contains  endotoxin  in  the  cell  wall.   The  organism  will  grow well on
chocolate agar with 2-5% carbon dioxide.  It is distinguished by metabolizing
glucose, and usually  maltose  but  not  lactose.   Group  B  now is the most
important serogroup which accounts for approximately 40% of cases.   Group  C
accounts  for  30%,  group  Y  for 20% and Group A 2%.  The peak incidence of
meningococcal disease is  late  winter  and  early  spring  and  is spread by
droplet contamination.  The risk is highest in crowded areas such as day care
centers, school classrooms  and  army  camps.   Most  of  the  cases  involve
children  or  adolescents.  About 40% of of the population are nasopharyngeal
carriers of meningococci, but  fewer  than  1%  of  carriers will develop the
disease.   Meningococcal  infection  may  take  on   several   presentations.
Meningococcemia  is  a  fulminant  form  of  septicemia and may occur with or
without  meningitis.   There  may  also  be  chronic  meningococcemia, septic
arthritis,   pneumonia,   pericarditis,   otitis   media,   vaginitis,    and
conjunctivitis.   CLINICAL:  MENINGOCOCCEMIA:  Meningococcemia usually starts
with an  upper  respiratory  infection  and  is  then  followed  by headache,
hypotension and fever.  Petechiae, and purpura develop over the trunk, palms,
soles and extremities very rapidly.  CHRONIC MENINGOCOCCEMIA:  Patients  with
chronic   meningococcemia  have  episodic  fever,  headaches,  arthritis  and
arthralgia, and bouts of petechiae.   Between  these episodes the patient may
have no symptoms and appear non-toxic.  Splenomegaly  may  be  present.   The
mean duration of this disease is about 6-8 weeks.  FULMINANT MENINGOCOCCEMIA:
Fulminant   meningococcemia,   also   known  as  the  Waterhouse-Friderichsen
syndrome, occurs in  10-20%  of  patients  with  meningococcemia,  has a high
fatality rate and  is  characterized  by  shock,  disseminated  intravascular
coagulation   and  extensive  mucosal  and  skin  hemorrhage.   MENINGOCOCCAL
MENINGITIS: Meningococcal  meningitis  is  the  second  most  common cause of
bacterial meningitis after the neonatal period.  In childhood it is second to
H. influenza and in the adult it is  second  to  pneumococcus.   The  patient
usually  presents with chills, headache, high fever, abdominal and back pain,
and vomiting.  There is nuchal rigidity with a positive Brudzinski and Kernig
signs.  Cranial nerve palsies,  especially  the third, fourth, sixth, seventh
and eighth cranial nerves are common complications which usually resolve with
treatment, but hearing deficits may not resolve.  The skin rash  consists  of
patches  of  ecchymosis,  petechiae  and  purpura.   DIFFERENTIAL  DIAGNOSIS:
HENOCH-SCHONLEIN   PURPURA:  Henoch-schonlein  purpura  (HSP)  is  an  immune
vasculitis that also presents with  purpura.   It is usually seen in children
but may be seen in adults.  HSP will often follow a viral  infection.   There
is  microscopic  hematuria,  fever,  abdominal  pain and polyarthralgia.  The
purpuric skin rash characteristically  affects  the  extensor surfaces of the
feet and legs, buttocks and the extensor surfaces of the  arms.   There  also
may  be  swelling  of  the ankles, hands, knees, wrists and elbows.  SYSTEMIC
LUPUS ERYTHEMATOSUS WITH LUPUS  ANTICOAGULANT:  Some  lupus patients are very
ill when first seen and may have  purpura.   There  may  be  widespread  skin
necrosis  with  secondary  hemorrhage.   GONOCOCCEMIA: One shouldn't have too
much difficulty in  diagnosing  gonococcemia  because the characteristic skin
lesions  are  scattered  pustulopapules  rather  than  extensive  hemorrhagic
purpura.  ROCKY MOUNTAIN SPOTTED FEVER AND ENTEROVIRUS  INFECTION  These  two
diseases   may   simulate  meningococcemia  and  would  be  included  in  the
differential diagnosis.  LABORATORY: The patient  will need a lumbar puncture
which will show the CSF to be cloudy  or  purulent  with  increased  protein,
decreased  glucose  and elevated pressure.  The cell count is usually greater
than 1000 cells/uL with a  predominance  of polymorphonuclear cells with gram
negative intracellular diplococci.   Latex  agglutination  for  the  capsular
polysaccharide  antigen  is  positive  in  about 60-80%.  This antigen may be
detected in the CSF, urine or  serum.   The  organism may be seen by smear or
culture of the CSF, blood or aspirated petechiae.  Blood culture is  positive
in  about  2/3  of  the  cases of meningococcemia with or without meningitis.
Gram stain of the buffy coat  may  show  the  gram negative cocci if there is
fulminant meningitis.  Isolation of N. meningitidis from the  nasopharynx  is
not helpful because of the high incidence of colonization.  Any adult patient
that develops invasive meningococcal disease should be suspected of having an
immunoglobulin  defect  or  abnormality  of  the  complement  system.   Total
immunoglobulins,  IgG2  subclass,  C3,  and total hemolytic complement (CH50)
should be done.  If DIC  is  present  the  prothrombin time is prolonged, the
platelets are decreased  and  the  fibrinogen  levels  are  low.   TREATMENT:
Treatment  is  with  IV  aqueous  penicillin G 2 million units every 2 hours,
given until the patient has been afebrile for about 5-7 days.  If the patient
is allergic to penicillin, chloramphenicol  should  be used at 1-1.5 grams IV
every 6 hours.  Patients should be in isolation for the  first  24  hours  of
treatment.   PROPHYLAXIS:  Close  contacts  and family members should receive
prophylaxis with rifampin for 2 days.  In  the  adult use 600 mg po bid.  For
children from 5-12 years give 10 mg/kg bid and for neonates 3-12 months use 5
mg/kg bid.  Meningococcal  vaccine  is  used  to  control  epidemics  or  for
travelers to epidemic areas.

                       -MENINGITIS (Treatment)-
The following is the  IV  empiric  therapy  of meningitis directed at various
levels of age and special situations: In all  of  the  following  situations,
ceftriaxone  may be substitued for cefotaxime, with the exception of neonates
< 1 month, in which  ceftriaxone  is  not recommended because it can displace
bilirubin from albumin binding sites.  The pediatric dose for ceftriaxone  is
100  mg/kg  in  divided doses q12h.  The adult dose of ceftriaxone is 2 grams
given in divided doses q12h.   NEONATAL  (<  1 month): Ampicillin is given at
200 mg/kg in divided doses every 4 hours + gentamicin 7.5 mg in divided doses
q8h (or tobramycin 6 mg/kg in divided doses  q8h  or  amikacin  20  mg/kg  in
divided  doses q8h).  Alternatively, cefotaxime given at 200 mg/kg in divided
doses q4h + aminoglycoside can be  given.   This treatment will cover Group B
streptococcus, Listeria monocytogenes, and Escherichia  coli.   INFANTS  (1-3
months):  Ampicillin 200 mg/kg in divided doses q4h + cefotaxime given at 200
mg/kg in divided doses q4h  OR  alternatively ampicillin 200 mg/kg in divided
doses q4h + aminoglycoside (amikacin  20  mg/kg  in  divided  doses  q8h,  or
gentamicin  7.5  mg  in  divided  doses q8h, or tobramycin 6 mg/kg in divided
doses  q8h).    These   antibiotics   will   cover   Haemophilus  influenzae,
Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis, and
Group B streptococci.  CHILDREN 3 months- 7 years: Cefotaxime  200  mg/kg  in
divided doses q4h, OR alternatively ampicillin 200 mg/kg in divided doses q4h
+  chloramphenicol  75  mg/kg  in  divided doses q6h (monitor serum levels of
chloramphenicol).   These  antibiotics  will  cover  Haemophilus  influenzae,
Neisseria meningitidis, and  Streptococcus  pneumoniae.   OLDER CHILDREN (> 7
years) AND ADULTS: Penicillin G 250,000 U/kg in divided doses q4h (Pediatric)
or 24 million U  given  as  divided  doses  q4h  (ADULT),  OR  alternatively,
cefotaxime 200 mg/kg given in divided doses q4h (Pediatric) or 12 grams given
in  divided  doses  q4h  (ADULT).  This will cover Neisseria meningitidis and
Streptococcus pneumoniae.  CSF SHUNTS: Vancomycin  10 mg/kg q8h + ceftazidime
150 mg/kg given in divided doses q8h (Pediatric) or 6 grams in divided  doses
q8h (Adults).  This will cover Staphylococcus aureus and epidermidis and Gram
negative  bacilli.   Consideration  must  be  given  for  shunt  removal  and
intraventricular  vancomycin).   ASPLENIA:  Cefotaxime  200  mg/kg in divided
doses q4h (Pediatric), or ceftazadime 12  grams in divided doses q4h (Adult).
This  will  cover  Neisseria  meningitidis,   Haemophilus   influenzae,   and
Streptococcus pneumoniae.  POST NEUROSURGICAL PROCEDURES: Nafcillin 200 mg/kg
in  divided  doses q4h (Pediatric) or Nafcillin 12 grams in divided doses q4h
(Adults) +  ceftazadime  150  mg/kg  in  divided  doses  q8h  (Pediatric), or
ceftazadime  6  grams  in  divided  doses  q8h  (Adult).   This  will   cover
Pseudomonas  aeruginosa,  Staph  aureus  and  epidermidis,  and Gram negative
bacilli.  CLOSED HEAD TRAUMA: Penicillin G  250,000 U/kg in divided doses q4h
(Pediatric), or Pencillin G 24 million U in divided doses q4h (Adult).   This
will  cover  Streptococcus  pneumoniae.   TRANSPLANT PATIENTS: Ampicillin 200
mg/kg in divided  doses  q4h  (Pedatric),  or  Ampicillin  12  grams given in
divided doses q4h (Adult) + aminoglycoside  (Amikacin  20  mg/kg  in  divided
doses  q8h  (Pediatric) or Amikacin 15 mg/kg in divided doses q8h (Adult), OR
Gentamicin 7.5 mg/kg in divided doses q8h (Pediatric)	or Gentamicin 5 mg/kg
in divided doses q8h  (Adult),  OR  Tobramycin  6  mg/kg in divided doses q8h
(Pediatric), or tobramycin 5 mg/kg in divided doses q8h (Adult).   This  will
cover  Listeria  monocytogenes.   ALCOHOLIC PATIENTS: Penicillin G 24 million
units in divided doses q4h + cefotaxime 200 mg/kg in divided doses q4h.  This
will cover Streptococcus  pneumoniae  and  Gram  negative bacilli.  RECURRENT
MENINGITIS: Penicillin G 250,000 U given in divided doses q4h (Pediatric), or
Penicillin G 24 million U in divided doses  q4h  (Adult).   This  will  cover
Streptococcus  pneumonaie.   ELDERLY  PATIENTS:  Penicillin g 24 million U in
divided doses  q4h.   This  will  cover  Streptococcus  pneumoniae.  TERMINAL
COMPLEMENT  DEFICIENCY:  Penicillin  G  250,000  U  in  divided   doses   q4h
(Pediatric),  or  Penicillin  G  24  million U in divided doses q4h (Adults).
This will cover  Neisseria  meningitidis.   TREATMENT  BASED ON MORPHOLOGY BY
GRAM STAIN: Gram positive bacilli could represent Listeria monocytogenes  and
is   treated   with   ampicillin   +/-   aminoglycosides,   or  alternatively
trimethoprim-sulfamethoxazole.  Gram negative cocci could represent Neisseria
meningitidis, and is treated  with  Penicillin G or alternatively cefotaxime,
ceftriaxone or chloramphenicol.  Gram positive  cocci  in  short  chains  and
pairs  could represent Streptococcus pneumoniae, or Group B streptococci, and
is treated with Penicillin G,  or alternatively with cefotaxime, ceftriaxone,
or  chloramphenicol.   Gram  positive  cocci  in  clusters  could   represent
Staphylococcus  aureus,  and  is treated with nafcillin or alternatively with
vancomycin  (has  variable  CSF  penetration).   Gram  negative  coccobacilli
represents  Haemophilus  influenzae,  and   is  treated  with  cefotaxime  or
ceftriaxone,  or  alternatively  with  ampicillin  +  chloramphenicol.   Gram
negative  bacilli  could  represent  Pseudomonas  aeruginosa  or   Klebsiella
(treated  with  ceftazidime  +  aminoglycoside), or Escherichia coli (treated
with cefotaxime or alternatively  with Trimethoprim-sulfamethoxazole).  If no
Gram stain organisms are seen, treat empirically with ampicillin + cefotaxime
or ceftriaxone.

                      -MENINGITIS (Tuberculous)-
TUBERCULOUS MENINGITIS is  due  to  spread  from  rupture  of  a  superficial
tubercle,  or  from  dissemination through the blood stream.  It is uncommon,
potentially lethal, but treatable.  It  usually  occurs by itself, but can be
associated with TB elsewhere.  Patients with  miliary  tuberculosis  have  an
increased chance for rupture of a juxtaependymal tubercle.  Infants and young
children  are  particularly at risk for progressive hematogenous tuberculosis
following the primary infection.  In  locales where TB is common, tuberculous
meningitis usually occurs bertween ages 1-5.  Most cases, however, are  found
in  the  elderly, representing reactivation of an infection that was acquired
many years ago.  Patients  with  alcoholism,  HIV, lymphoma, and those taking
immunosuppressant drugs  can  lead  to  reactivation  of  latent  infections.
Pathology  is  usually most marked at the base of the brain and consists of a
proliferative inflammatory meningeal exudate, and vasculitis that can produce
thrombosis and hemorrhagic  infarction.   With  extension of the inflammaotry
process to the basilar cisterns, a communicating  hydrocephalus  may  develop
due to interrruption of CSF circulation and resorption.  CLINICAL: Initially,
during   the   prodromal   stage,  the  patient  will  complain  of  malaise,
intermittent headache, low grade  fever  and personality changes.  Within 2-3
weeks the patient develops an unremitting  headache,  meningismus,  vomiting,
cranial  nerve  palsies,  confusion, and long tract signs.  The sixth cranial
nerve is most  commonly  involved,  followed  by  the  third  and the fourth.
Internuclear ophthalmoplegia (adduction  paresis  of  one  or  both  eyes  on
lateral  gaze) may also be demonstrated.  The patient will have a stiff neck,
and Brudzinski's sign.  The confusion  is  followed  by stupor and coma along
with seizures.  Hemiparesis or hemiplegia can also  develop.   Patients  that
develop  hydrocephalus  will  have headache, papilledema, visual disturbances
and diplopia.  If intervention is not  established after 5-8 weeks, death may
ensue.   Other  patients  may  have  an  indolent  course  that   is   slowly
preogressive  over  several  weeks  to  months.   The  indolent course may be
manifested by a  progressive  dementia,  personality  change, loss of libido,
memory problems and social withdrawal.   Symptoms  in  children  are  somehat
different.   Headaches  are  less common and vomiting is more prominent.  The
child is irritable,  anorexic  and  restless initially.  Generalized seizures
are more common  in  children  which  can  be  an  early  sign.   LABORATORY:
Diagnosis  is  made  by examinatiion of the CSF.  The glucose is usually less
than 50% of the  serum  glucose,  the  protein  is  elevated,  and there is a
pleocytosis consisting mostly of lymphocytes.  Early,  patients  may  present
with  a  preponderance of neutrophils.  The cell count varies between 100-500
cell/uL.  However, in about 15% of cases the cell count will be less than 100
cell/mm3, and 20% will have  cell  counts between 500-1500 cell/mm3.  Stained
smears, and even cultures may be negative.  Cultures are negative in  25%  of
cases,  and those that are positive, require 6 weeks for growth.  The opening
pressure is usually elevated.  If the  CSF  is left standing, a web like clot
may develop.  The fluid may  be  clear  or  yellowish.   CSF  protein  varies
between  100-500  mg/dl in the majority of patients, but can be less than 100
mg/dl in 25%, and more than 500 mg/dl in 10%.  It is extremely important that
repeat examinations  of  the  CSF  be  carried  out,  as  the sensitivity for
detection increases with serial specimens.  The initial examination may  have
a  yield  of  only  37%, but following 4 serial specimens the sensitivity for
detection can increase to  87%.   This  sensitivity  includes those that have
been started on antituberculous therapy.  It is  recommended  that  suspected
cases  receive  daily  lumbar punctures for 3-4 days.  Suspected cases should
not have a delay  in  the  use  of antituberculous medications.  Giving these
early in the course will not materially affect the diagnostic yield from  CSF
studies.   About  10-15 ml of CSF fluid should be obtained.  The fluid should
be centrifuged, and examination  carried  out  on  .02  ml of the centrifuged
deposit by preparing a slide which is stained by  the  Ziehl-Neilsen  or  the
Kenyon  stain.   If  no  clot  forms  on  standing, 2 ml of 95% alcohol, will
produce a good protein precipitate  which  can be centrifuged, depositing the
bacilli at the bottom of the  tube.   This  portion  can  then  be  examined.
Polymerase  chain  (PCR)  and enzyme linked immunosorbent assay (ELISA) tests
may also be useful.  CT is useful in helping to establish a diagnosis as well
as predicting prognosis.   CT  can  demonstrate  the basilar arachnoiditis as
well as the extent, hydrocephalus, cerebral edema and infarction secondary to
the vasculitis.  If only hydrocephalus is demonstrated, the  prognosis  tends
to  be  good.   Demonstration  of  hydrocephalus  with  basilar arachnoiditis
carries a poor prognosis.  CT can  also  be  used to establish the benefit of
steroids and shunt procudures.  MRI is superior to CT for defining lesions in
the  brainstem,  basal  ganglia,  diencephalon,  infarcts,  and  epidural  or
intradural tuberculous  involvement.   DIFFERENTIAL  DIAGNOSIS:  The  gradual
onset,  presence  of  lymphocytic  pleocytosis  of the CSF and evidence of TB
elsewhere is stronly suggestive of  TB  meningitis.  However, the findings of
elevated protein, low glucose, and lymphocytic pleocytosis can be  caused  by
syphilis,  fungal  infections,  brucellosis,  as well as tuberculosis.  Other
considerations  in  the  differential   include  herpes  simplex  and  mumps,
lymphomatous and carcinomatous meningitis, CNS  sarcoidosis,  pyogenic  brain
abscess, partially treated bacterial meningitis, histoplasmosis, coccidiodal,
blastomycosis, and cryptococcal meningitis.  TREATMENT: Patients suspected of
having TB meningitis should always be started on treament early.  Even if the
cultures  are  negative  initially, treatment should be started in suspicious
cases.  It is fatal if  untreated.  Treatment consists of rifampin, isoniazid
and pyrazinamide all of which penetrate well into the CSF.   The  penetration
of  ethambutol  is  variable,  but  therapeutic  CSF  levels can be achieved.
Isoniazid is given as 300 mg/day, and rifampin 600 mg/day.  Both of these are
given for 6 months.   Pyrazinamide  is  given  at  25  mg/kg/day in 2 divided
doses, and ethambutol, 15 mg/kg/day, both for the first 2 months of theraqpy.
Alternatively, isoniazid and rifampin can be given for 9 months.   Pyridoxine
50 mg/day will prevent isoniazid induced peripheral neuropathy, and should be
given  if  the patients is at risk (diabetics, alcoholics, HIV patients).  If
the dose of ethambutol is  kept  below  15 mg/kg/day, toxicity is uncommon in
the patient with normal renal function.  Patients  should  be  monitored  for
hepatitis,  rash,  and  GI  disturbances.   Patients  with focal deficits and
mental changes can be treated  with  prednisone  60  mg/day in adults and 1-3
mg/kg/day in children for about 1-2  weeks  with  tapering  over  a  1  month
period.   Clinical  results  are  usually  experienced  within  a  few  days.
Patients  most  likely  to  respond include those with cerebral edema, spinal
block, hydrocephalus, and basilar  optochiasmic pachymeningitis as visualized
on CT.  Streptomycin, even in the presence of  inflamed  meninges  penetrates
the  CSF poorly.  It is most effective when given as 1 gram IM/day plus 50 mg
in 15 ml saline intrathecally.  It may  be used in certain situations such as
multidrug  resistance,  when  hepatitis  precludes   the   use   of   certain
antituberculous  drugs,  and  in  those  patients  that are not responding to
conventional therapy.  Ethionamide, a  second  line agent that penetrates the
CSF well, should be considered in  cases  of  suspected  or  known  isoniazid
resistant  infections.   Surgical  shunting  should be considered in patients
with hydrocephalus and symptoms of increased intracranial pressure.

                         -MENINGITIS (Viral)-
Viral meningitis  is  a  syndrome  characterized  by  headache,  stiff  neck,
photopobia,  fever, nausea and vomiting.  In the USA, enterovirus is the most
common  cause  of  viral   meningitis   (80%).    Enteroviruses  are  in  the
picornavirus family and are  small  30  nm  RNA  viruses.   They  consist  of
echoviruses  and  coxsackie  viruses.   They typically cause viral meningitis
during the late summer and  early  fall  season,  cause epidemics, and have a
worldwide distribution.  They can  survive  in  water  and  sewage,  and  are
transmitted  by  hand  to  mouth, or by fecal-oral routes.  Enteroviruses can
cause  a  host  of  symptoms   such  as  pericarditis,  myocarditis,  rashes,
herpangina,  orchitis,  myalgia,  arthritis,  polymyositis,  nephritis,   and
hemolytic  uremic syndrome.  Viral meningitis is often discussed with aseptic
meningitis.  Aseptic meningitis includes  viral meningitis, but also includes
Leptospira icterohaemorrhagiae, Mycoplasma  pneumoniae,  Treponema  pallidum,
Toxoplasma  gondii,  and  parameningeal  infections.  The yearly incidence of
aseptic meningitis varies  from  11-27  cases/100,000  individuals.  The most
common Coxsackie viruses are A7, 9, B2-5.  The most common Echoviruses are 4,
6, 9, 11, 16, and 30.  Other common viruses include the Arboviruses (epidemic
and sporadic, such as St Louis, California, and  Colorado  tick  fever),  and
Herpes  simplex  virus  type  2.  Uncommon  causes include mumps, lymphocytic
choriomeningitis, and Human  immunodeficiency  virus.  Mumps viral meningitis
usually occurs in outbreaks, and is associated with parotid swelling.  Herpes
simplex is sporadic and  may  occur  in  association  with  genital  herpetic
lesions.   Arboviruses  (Togaviruses) typically cause outbreaks in the summer
and fall, and are associated  with myalgias.  Lymphocytic choriomeningitis is
acquired from an infected pet, mice, hamsters or laboratory  animals.   Human
immunodeficiency  virus  has an increased incidence in homsexuals and IV drug
abusers, and causes an  associated  mononucleosis like syndrome, rash, fever,
and  adenopathy.   CLINICAL:  Patients  classically  have  headache,   fever,
meningeal irritation, malaise, myalgia, anoreixa, nausea, vomiting, abdominal
pain  and  diarrhea.  The headache is typically frontal or retro-orbital, and
is usually associated with photophobia and  pain upon moving the eyes.  There
may be different degrees of nuchal rigidity.  Some will have severe, and some
will have mild neck stiffness.  Kernig's and Brudzinski's signs  are  usually
absent.   LABORATORY:  Examination  of  the  CSF  is  critical  in  making  a
differential   diagnosis  of  viral  versus  nonviral  meningitis.   Computed
tomography without contrast should precede  the  spinal  tap.  If there is no
evidence of any shift of midline structures, hydrocephalus, or massive edema,
then a lumbar pncture can safely  be  performed.   Both  the  CT  and  lumbar
puncture  should  be  done  within one hour of presentation.  The typical CSF
profile consists of a lymphocytic  pleocytosis, slightly elevated protein and
normal glucose.  Organisms are  not  seen  on  Gram's  or  acid-fast  stained
smears,  and  india ink wet mounts are negative.  The elevated protein rarely
exceeds 250 mg/dL.  The CSF  fluid  is  clear  and colorless, and the opening
pressure is usually normal or slightly elevated.  The CSF white  cell  counts
range  from  between  100  and  1000  per  mm3, but are usually less than 300
cells/mm3.   About  5%  of  cases  will   not  reveal  any  cells.   The  CSF
leukocytosis usually abates in a few days, but can remain for some months  in
some  patients.   RBCs,  and  xanthochromia  should  not  be present in viral
meningitis.  If they are  found  a  necrotizing  vasculitis of herpes simplex
encephalitis should  be  suspected.   Polymorphonuclear  neutrophils  usually
predominate  in  the  first 48 hours of illness, especially in Eastern equine
virus and some echovirus 9 meningitis.  Any patient that has a persistent PMN
distribution  should  prompt  a  suspicion  for  a  bacterial  meningitis  or
parameningeal infection.  Therefore, patients  that  are suspicious for viral
meningitis should have a repeat spinal tap within 8-12 hours to disclose  the
transition  from  the PMN to lymphocytic profile.  The CSF glucose is usually
normal, but mildly  depressed  levels  may  be  seen  in patients with mumps,
varicella zoster, herpes simplex  type  2  and  lymphocytic  choriomeningitis
viruses.   If  the  CSF glucose is below 25 mg/dl, bacterial or fungal causes
should be considered.  CSF levels  of tumor necrosis factor can differentiate
bacteria from viral meningitis.  Tumor necrosis factor is found in up to  74%
of  cases with bacterial meningitides, and is absent in patients with aseptic
meningitis.  Viral culturing of the  blood,  urine,  feces, and throat can be
done, but usually are not helpful in the acute situation.  Enteroviruses  and
mumps  virus  can  be  isolated  from  throat  swabs  or  stool,  lymphocytic
choriomeningitis  virus  from  urine,  and herpes simplex virus type 2 from a
genital herpetic lesion.  Serological studies  done on acute and convalescent
serum separarated by  3-6  weeks,  can  be  helpful  in  defining  meningitis
secondary  to mumps, arbovirus, human immunodeficiency virus, and lymphocytic
choriomeningitis.  All patients  should  have  a  CBC, platelets, hematocrit,
ESR, liver function tests, glucose, electrolytes, creatinine,  BUN,  creatine
kinase,  amylase, lipase, and aldolase.  DIFFERENTIAL DIAGNOSIS: MUMPS: Mumps
usually occurs in the late winter or early spring and is more common in males
(3:1).  Any patient that  has  parotitis, oophoritis, orchitis, pancreatitis,
and elevations in serum lipse and  amylase  should  be  suspicious.   If  the
patient  has  a  history of mumps in the past, this would exclude mumps as an
etiology of meningitis, as mumps  infection confers lifelong immunity.  A low
glucose in  the  CSF  occurs  in  mumps  in  10-30%  of  cases.   LYMPHOCYTIC
CHORIOMENINGITIS:  Lymphocytic  choriomeningitis  occurs  in the late fall or
winter and is associated with  exposure  to  house mice, laboratory rodents ,
and hamsters,  and  acquire  the  infection  through  their  excreta.   These
patients  may  have  thrombocytopenia,  leukopenia,  abnormal  liver function
tests, pulmonary infiltrates, parotitis,  myopericarditis, and orchitis.  The
lymphocytic pleocytosis is particularly marked  (usually  greater  than  1000
cells/microliter),  and  less  than  30%  will  have a depressed CSF glucose.
ENTEROVIRUS: Enterovirus infections  cause  viral  meningitis in greater than
80% of cases.  Viral  meningitis  due  to  enteroviruses  usually  occurs  in
younger  patients in the late summer and early fall.  However, sporadic cases
may be seen year  round.   A  careful  search  should be made for herpangina,
exanthems,  hand-foot,  disease,  hemorrhagic  conjunctivitis,   pleurodynia,
pericarditis  and myocarditis, as these are signs of enterovirus.  ARBOVIRUS:
Arbovirus meningitis typically occurs  in  the  summer months, have a typical
geographic  distribution,  and  tend  to  occur  in   epidemics.    Arbovirus
meningitis  should  be  suspected  when  there  are  clusters  of  meningitis
occurring  in  a  typical  geographic  area  during  the summer or early fall
months.  There may be a history tick exposure or travel to one of the endemic
areas.  If so, this may suggest  Colorado tick fever virus, Lyme disease, and
Rocky mountain spotted fever.  HERPES SIMPEX VIRUS: Any patient  that  has  a
primary  or  secondary  genital  infection should be suspected.  EPSTEIN BARR
VIRUS: Epstein Barr  meningitis  may  be  suspected  if  there is evidence of
atypical lymphocytes in the peripheral blood or the CSF fluid.  Mononucleosis
symptoms may or may not be present.  HIV INFECTION; HIV meningitis can follow
primary exposure to HIV or be associated with  HIV  seroconversion.   Cranial
nerves palsies are common in HIV meningitis, usually involving cranial nerves
5, 7, and 8. SYPHILITIC MENINGITIS: Syphilitic meningitis can be confirmed by
blood  and  CSF serologies.  Syphilitic meningitis can present as an acute or
subacute disease.   The  CSF  usually  shows  changes  suggestive  of a viral
meningitis, although the glucose will be depressed in  about  50%  of  cases.
LYME  MENINGITIS:  The CSF findings in those who present in a subacute manner
are similar to those with  viral  meningitis,  but  the number of white cells
tend to be lower (less  than  100  WBC/mm3).   It  is  usually  diagnosed  by
detecting   antibodies   to   B.   burgdorferi  in  the  CSF.   MYCOBACTERIUM
TUBERCULOSIS  MENINGITIS:  TB  meningitis   usually  presents  as  a  chronic
meningitis, but can be  abrupt  as  that  of  viral  meningitis.   OTHER  NON
INFECTIOUS  CAUSES:  Nonsteroidal  antiinflammatory agents such as ibuprofen,
and sulindac, lymphoma, carcinomas, trimethoprim-sulfamethoxazole, epidermoid
cysts, craniopharyngiomas, sarcoidosis, Behcet's disease, SLE, and Mollaret's
meningitis.   TREATMENT:  In  the  usual   case  of  viral  meningitis,  only
symptomatic  treatment  is  needed,  with  the  exception  of  patients  with
deficient humoral immunity, and those neonates  with  severe  infection.   In
this  subset of patients, intravenous gamma globulin may be of benefit.  Most
adult patients will recover fully from viral meningitis.  A few patients will
continue to have persisting  headache,  incoordination, mild mental problems,
and asthenia for weeks to months.  Neonates less than 1 year  may  have  more
severe  lingering  problems  such as learning disabilities, hearing loss, and
intellectual problems.

                             -MENOPAUSE-
Use  Premarin  0.625  mg  or  Estrace (estradiol) 1 mg, or Ogen (estropipate)
0.625 mg or Estraderm  (estradiol  transderm)  .05  mg  twice  a week patch +
Provera (medroxyprogesterone) 2.5 mg.  Give both of these daily 365 days  per
year.   A variation of the above would be to take both tablets Monday through
Friday without taking the tablets on Saturday and Sunday.  With both of these
methods,  most  patients  will  experience  some  intermittent  spotting  and
bleeding.  With  the  Monday-Friday  plan  there  is  probably less bleeding.
Every patient should be warned, and to expect some  bleeding.   Normally,  it
takes from three to six months for the hormones to thin out the lining of the
uterus  (endometrial  atrophy)  to  a degree where it no longer bleeds.  Once
this is  achieved,  the  patient  can  enjoy  all  the  benefits  of hormonal
replacement therapy without having to worry  about  nuisance  bleeding.   The
Provera 2.5 mg may cause mild but annoying premenstrual-like symptoms such as
bloating,  depression,  irritability,  fluid retention and breast tenderness.
If it does, substitute 2.5 mg of Aygestin (norethindrone).  Use 1/2 of a 5 mg
tablet  of  Aygestin  or  1/2   tablet   of  Norlutate  or  two  of  Micronor
(norethindrone)  tablets.   Avoid  generic  drugs.   These  are   too   often
subpotent.   If  after starting the above program, bleeding persists beyond 6
months then it  is  advisable  to  send  the  patient  to  a gynecologist for
endometrial biopsy.  First, before you  start  hormonal  replacement  therapy
make  sure the patient is menopausal by obtaining a FSH level which should be
> 30 pg/ml.  Be sure  the  patient  has  had  a mammogram within the previous
year.  Contraindication  to  HRT  include  unexplained  vaginal  spotting  or
bleeding,  chronically  impaireed  liver  function, acute vascular thrombosis
with or without embolus and a  history  of  breast cancer.  A past history of
phlebitis or embolism alone  is  no  longer  considered  a  contraindication,
unless  the  patient was on hormone replacement or birth control pills at the
time.  Unlike contraceptives, low  dose  HRT  does  not appear to alter blood
clotting factors in a clinically  significant  way.   Moreover,  hypertension
and/or  coronary  artery  disease  do  not  preclude HRT as once was thought.
Virtually every large epidemiological study  has shown no association between
postmenopausal  estrogen  use  and  hypertension.   In   fact,   nearly   all
prospective  clinical  trials have demonstrated a reduction of blood pressure
in estrogen users.

                    -MENSTRUAL DISORDERS (Clues)-
SECONDARY AMENORRHEA: For secondary amenorrhea obtain a pregnancy test,  FSH,
prolactin and thyroid panel.  If the pregnancy test is negative, give Provera
10  mg  for  10  days.   If  patient bleeds then problem is hypothalamic or a
pituitary defect meaning  that  the  uterus  is  normal  and  the ovaries are
producing estrogen.   The  causes  include  athletes,  dieters,  bulemia  and
anorexia  nervosa.  If the patient fails to respond to Provera, then could be
early menopause.  If this is the  case  then the FSH will be elevated.  Also,
may want to get chromosomal studies for a mosaic Turner's syndrome or  any  X
chromosome  variant  that  would  cause  the patient to run out of eggs.  The
other group that fails  to  respond  to  Provera  with bleeding have elevated
prolactin  usually  greater  then  20-30.   Medicine  may  be   causing   the
hyperprolactinemia   such   as  oral  contraceptives,  conjugated  estrogens,
phenothiazines,    amphetamines,    opiates,    cimetidine,    tranquilizers,
propranolol, neuroleptic agents and  methyldopa.  If hypothyroidism is found,
treat for this.  If the thyroid is normal get CT of sella turcica to rule out
pituitary tumor.  If found then could treat  with  bromocriptine  which  will
lower  the  prolactin  and  restore  mentrual periods.  IRREGULAR PERIODS AND
INFERTILITY: Take daily basal morning  temperature over several months.  Over
the counter ovulation kits also can detect an ovulatory surge of  luteinizing
hormone   from   the   pituitary.   Another  approach  is  to  measure  serum
progesterone in the midluteal phase about one week before menses is expected.
A level of 15 mg is  reassuring:  levels  of 3-10 indicate ovulation, but not
necessarily an adequate luteal phase.  An endometrial biopsy  in  the  second
half of the cycle can determine if ovulation occurred and if the progesterone
is sufficient.  If the patient is not ovulating or progesterone is low try to
enhance  ovulation  with  pergonal  or clomiphene.  If LH and FSH are normal,
give  clomiphene.   The  clomiphene  carries   a  6%  incidence  of  multiple
gestations, pergonal  a  10-30%  incidence.   POLYCYSTIC  OVARY  SYNDROME:  A
lifetime  of  irregular  periods  (oligomenorrhea) is the hall mark of POS in
which ovulation is only  partly  suppressed.   May have abnormal hair growth,
acne, oily skin and obestiy.  Obtain a free testosterone  level.   Typically,
the  free  testosterone is elevated even if the total testosterone is normal;
the LH is higher than the  FSH  by  a  2:1 ratio.  A serum testosterone > 200
points  to  an  ovarian  tumor.   An  elevated  dehydroepiandrosterone  level
suggests an adrenal source.  Treatment depends whether she wants to  conceive
or not.  If not then give low dose oral contraceptive to regulate her cycles.
If  she does, then induce ovulation with clomiphene citrate.  HEAVY BLEEDING:
Two things must  be  ruled  out  initially;  the  first  is a complication of
pregancy such as incomplete abortion or  ectopic  pregnancy  and  the  second
condition  is  a malignancy.  Do a speculum exam looking at the cervix to see
where the blood is coming.  Look at  the cervix for color change from pink to
blue for pregnancy and note if the cervix is  dilated  and  any  products  of
pregnancy  protruding  through  the os which indicates a miscarriage.  If you
see products protruding pull out  and  send  to  pathology.  Do a bimanual to
rule out fibroids or ultrasound.  Any post menopausal bleeding needs  biopsy.
May also have an endometrial polyp.  A surgical D&C is usually necessary if a
fibroid  is  present  or  alternatively  could  use  a gonadotropin releasing
hormone.  BLEEDING OFTEN TO EVERY  FEW  DAYS  WHICH IS A SIGN OF ANOVULATION:
Estrogen is unopposed by progesterone that leads to a  buildup  of  a  shaggy
estrogen  rich  endometrium that doesn't bleed down to the basal layer.  This
may cause cystic or  adenomatous  hyperplasia  and possibly even cancer.  The
treatment is medical D&C with Provera 10 mg for 10 days,  or  100  mg  of  IM
progesterone,  or 1 birth control pill qid for 5 days.  After the patient has
quit bleeding start birth control pills for  a few cycles.  If the patient is
over 30 years of age do endometrial biopsy.  If patient fails to  respond  to
Provera or birth control pills qid, the uterine lining may be so denuded that
it  will  actually  require  estrogen  to stop the bleeding.  Give 5-10 mg of
conjugated estrogen for several week or  25  mg  of IV estrogen every 4 hours
until the bleeding slows followed by Premarin and Provera.  If  the  bleeding
fails to stop, then will require a surgical D&C.

                       -MERALGIA PARESTHETICA-
Characterized   by   numbness   and   painful  burning  or  tingling  in  the
anterolateral thigh, and aggravated  by  prolonged or recurrent hip extension
or by tapping on the nerve where it pierces the ligament.  Hip  flexion  will
relieve  pain.  Pregnancy, obesity and tight garments or belts may aggravate.
The  nerve  originates  from  the  second  and  thrid  lumbar  roots, travels
retropoeritoneally, penetrating  the  inguinal  ligament  near  the  anterior
superior  iliac spine and then runs down the anterolateral thigh to the knee.
Must exclude lesions  of  the  lumbar  roots,  lumbosacral  plexus or femoral
nerve.  The lateral femoral cutaneous nerve is only sensory, so  there  never
is  weakness,  atrophy,  loss  of  reflexes  or electromyographic denervation
potentials in meralgia  paresthetica.   Hip arthritis, trochanteric bursitis,
lumbar spondylosis or inguinal lesions can cause  referred  thigh  pain,  but
these  lesions  do  not  produce  sensory loss.  Treatment is to lose weight,
giving  birth,  avoiding  tight   garments   and  minimizing  hip  extension.
Injections of of a local anesthetic or steroids near the site  of  entrapment
may help.  If this fails surgical decompression may be done.

                        -MESENTERIC ISCHEMIA-
Ischemia in the Superior mesenteric artery (SMA) may be due to  occlusion  or
non-occlusion.  In non-occlusion, the cause is usually due to low flow states
as  cardiogenic  shock.   Probably  embolization  from  the heart is the most
frequent occlusive cause, followed  by  thrombus and then non-occlusive.  The
heart as a source for the embolus  should  be  assessed  for  valvular  heart
disease.  Any patient with decompensated congestive heart failure, history of
previous  embolic  disease, treatment with digitalis and vasopressors, recent
myocardial  infarction,  burns,  sepsis,  bleeding  and  dialysis  should  be
considered at risk for SMA ischemia.   CLINICAL: If embolus is the cause, the
abdominal pain is sudden, and often times  the  pain  is  cramping  and  very
poorly  localized.  Therefore, always remember that pain out of proportion to
the abdominal findings is mesenteric  ischemia until ruled out.  Always check
for atrial fibrillation as a cause  of  the  embolization.   The  patient  is
usually  over  the  age of 50 and may have a history of other atherosclerotic
events as myocardial infarction, stroke,  claudication,  etc.  There may be a
history of intestinal ischemia preceding the mesenteric event, such  as  pain
after  eating.  About 1/3 of patients will have this history.  There may be a
history of emboli to other organs as brain, kidney, etc.  There may be nausea
and vomiting in about  half  the  cases,  GI bleeding and diarrhea.  Physical
exam may show hyperactive peristalsis, mild non specific diffuse  tenderness,
and  abdominal  distention.   Later, as the ischemia and infarction advances,
there is fever, hypotension and tachycardia, transmural ischemia with rebound
tenderness,  and  peristalsis  which  is  now  hypoactive.   LABORATORY:  Lab
findings are non-specific and not helpful.   The WBC is elevated in about 3/4
of patients and the phosphorus, CPK  and  LDH  may  be  elevated.   Abdominal
x-rays may show thumbprinting, pneumatosis intestinalis, and demonstration of
generalized  dilatation  of the small and large bowel.  There may even be air
in the portal venous system.  Endoscopy may show submucosal hemorrhage, edema
and superficial ulceration.   CT  and  Sonography  may  show small amounts of
ascites and bowel edema.  Also CT can show air in the  portal  venous  system
and  air in the bowel wall.  ARTERIOGRAPHY is very important in the diagnosis
and management of SMA ischemia.  In the  first place, if the exam is negative
then another cause should be sought.   Next,  infusion  of  vasodilators  can
prevent  or  even reverse arterial spasm.  Surgery alone results in mortality
rates of about 80%.  An  initial  flush  arteriogram is usually done with the
patient in the lateral position to assess the ostia of the  celiac  and  SMA.
If nothing is found, then selective angiograms are made to look for thrombus,
embolus  and  spasm.   If  there is spasm, Tolazoline 25 mg can be given, and
then a continuous drip using  papaverine infused at 60 mg/minute.  TREATMENT:
If the patient still has  peritoneal  signs  with  rebound  tenderness  after
arteriography, the patient is taken to surgery.  If the patient improves with
the  papaverine  drip,  then surgery may be deferred and a repeat arteriogram
can be done  in  24  hours.   If  EMBOLUS  has  been found via arteriography,
embolectomy is done and  necrotic  bowel  is  resected.   The  papaverine  is
continued following surgery and at 48 hours after surgery heparin is started.
If  the  arteriogram,  prior  to surgery, shows THROMBOSIS and the collateral
circulation is good without  spasm  and  vasoconstriction, the patient can be
followed medically if there are  no  peritoneal  signs.   If  there  is  poor
collateral  circulation, the patient is taken to surgery.  Thrombosis usually
occurs at the  origin  of  the  SMA  and  embolus  more distally.  At surgery
revascularization    is    performed    and    infarcted    bowel    removed.
Revascularization is done if the bowel appears ischemic, but not necrotic, or
if the area of necrosis is limited.  An antegrade bypass  from  the  proximal
aorta  to  an artery that is distal to the obstruction using a saphenous vein
or  Dacron  graft   can   be   used.    Multiple   bypasses  may  be  needed.
Alternatively, endarterectomy  may  be  done.   Bowel  viability  is  checked
following  revascularization  by  arterial  pulsations,  color,  and  Doppler
ultrasound  and  Fluorescein  dye  with  Woods  light.   Again papaverine and
heparin are  used.   In  NON-OCCLUSIVE  ischemia,  arteriography  is done for
diagnosis, and papaverine may obviate the need for surgery if  there  are  no
peritoneal  signs.   If  peritoneal  signs  are  present, take the patient to
surgery for necrotic bowel  resection.   Streptokinase infusion has been used
to establish patency after an embolic event, but clot  lysis  is  very  slow.
Angioplasty  also  has  been  used.   After  surgery,  if  the circulation is
considered marginal, a second look  surgery  should  be performed in about 24
hours.  Routine measures as replacement of  intravenous  fluids,  nasogastric
suction and antibiotic therapy should be instituted.

                            -MESOTHELIOMA-
RADIOLOGY:  Uusually  shows  a  unilateral  pleural  effusion,   often   with
mediastinal  shift  to the affected side.  Pleural thickening may be present.
Cardiac enlargement may be present due to pericardial effusion from secondary
invasion from the pleura.  CT  is  limited in accurate determination of chest
wall involvement, mediastinal lymph node enlargement, diaphragmatic  invasion
and peritoneal studding by tumor, especially with masses smaller than 2 mm in
diameter.   Sometimes  there  is thrombocytosis and elevated sed rate greater
than 100.  Thoracoscopy  with  multiple  biopsies  has  a lower morbidity and
higher success  rate  (up  to  80%)  in  obtaining  satisfactory  tissue  for
histology  than  does  needle  biopsy.   Both  needle biopsy and open pleural
biopsy may be hazardous because  of  the propensity of malignant mesothelioma
to invade needle tracks and scars.  Diagnosis  for  malignant  versus  benign
mesothelioma versus secondary adenocarcinoma of the pleura is difficult.

                      -METHAMPHETAMINE TOXICITY-
SIGNS AND  SYMPTOMS:  The  patient  may  present  with  CNS  symptoms such as
agitation, anxiety, choreoathetoid disorders, delirium,  hallucinations,  and
seizures.   Cardiovascular  symptoms  consist of arrhythmias, cerebrovascular
accidents,   chest   pain,   dyspnea,   hypertension,   myocardial  ischemia,
palpitations   and   tachycardia.    Miscellaneous   symptoms   consist    of
hyperthermia,  loss  of consciousness, and rhabdomyolysis.  TREATMENT: Haldol
is the tranquilizer of choice,  although  Valium  can  be used.  The dose for
Haldol is 2-5 mg either IV or IM.  Hypertensive crisis can  be  treated  with
phentolamine  or  nitroprusside.   Arrhythmias  can  be  treated with beta or
calcium channel blocker.

               -METHANOL AND ETHYLENE GLYCOL POISONING-
If  pH  is  decreased  with  an anion gap > 12 or osmolal gap > 10, then this
could represent methanol or ethylene  glycol  poisoning.  If so, give ethanol
(10% infusion) with a loading  dose  of  10  ml/kg  and  maintenance  of  1.5
ml/kg/hr  to  keep  the  ethanol  level at 1000-13000 mg/L.  If patient is on
hemodialysis, double the maintenance dose.  Give bicarbonate to maintain pH >
7.3.  For Methanol poisoning given Folate 50  mg  IV q4h until the level < 20
mg/dl.   Hemodialysis  is  indicated  if  there  is  renal  failure,   vision
impairment  or persistent acidosis or peak level > 50 mg/dl of Methanol.  For
Ethylene glycol  give  Thiamine  100  mg  IV  and  pyridoxine  100  mg IV qd.
Hemodialysis is indicated for  renal  failure,  pulmonary  edema,  persistent
acidosis  or peak level > 50 mg/dl.  The anion gap=Na-Cl + HCO3.  The Osmolal
gap=2(Na) +  glucose/18  +  BUN/2.8.   Methanol  symptoms:  decreased vision,
abdominal pain, lethargy, confusion and neurologic  sequelae.   There  is  no
odor  from  Methanol  or  Ethylene  glycol.   Ethylene  glycol  symptoms: CNS
depression early and CHF 12-26 hrs and renal failure at 2-3 days.  LAB: urine
and blood drug screen, and methanol and ethylene glycol levels.

             -METHICILLIN RESISTANT STAPH AUREUS (MRSA)-
Nosocomial infections by MRSA are  associated  with IV drug abuse, burns, use
of multiple antibiotics and other hospital acquired infections.  The drug  of
choice  is  vancomycin  with or without gentamicin or rifampin.  Also, may be
susceptible to cotrimoxazole and ciprofolxacin or minocycline with or without
rifampin.

                        -MITRAL REGURGITATION-
Mitral regurgitation (MR) may be  divided  into acute and chronic causes, and
associated  causes.   Associated  causes  include   atrial   septal   defect,
hypertrophic   cardiomyopathy,   Marfan's,   Ehler-Danlos,  and  congenitally
corrected transposition.  About  50%  of  Marfan's  syndrome will have mitral
clicks or murmurs, and about 70% have echo evidence of mitral valve prolapse.
One of 8 Marfan's will progress to severe MR by the third decade.  The mitral
annulus is usually dilated with chordae redundancy, which are susceptible  to
rupture.   The  ACUTE  causes  include  myocardial  infarction with papillary
muscle dysfunction, rupture  of  the  papillary  muscles,  and rupture of the
chordae tendineae.  Mital valve prolapse can suddenly deteriorate to  produce
rupture  of  chordae  tendineae  with  rapid  progression  of  the  prolapse.
Endocarditis  may  present suddenly with acute endocarditis.  In acute severe
MR, the left ventricle is overloaded and cannot compensate for this diastolic
volume olverlaod.  This  leads  to  increased  left  ventricular wall stress,
dysfunction, and eventually pulmonary edema and hypotension.  Ischemic mitral
regurgitation is  seen  in  less  than  5%  of  acute  transmural  myocardial
infarctions, usually in posterior MI.  The ischemic wall motion abnormalities
and  left  ventricular  dilatation  leads  to  misalignment  of the papillary
muscles with inability to  completely  coapt.   The  anterior leaflet is most
commonly involved.  Papillary muscle rupture occurs in  about  .1%  of  acute
MIs.   The  patient  typically  presents  in pulmonary edema with a new onset
systolic murmur  within  the  first  week  of  the  infarction.   It  is seen
classically in posterior MI with intact left ventricular ejection  fractions.
Ventricular  septal  rupture  is the main differential.  Most cases of MR are
CHRONIC, and due to  rheumatic  disease,  subacute endocarditis, mitral valve
prolapse, SLE, Takayasu's arteritis, scleroderma, Marfan's,  Ehler's  Danlos,
myxomatous, annular calcification, dilatation of the mitral annulus or the LV
cavity,  perivalvular  prosthetic leak, cardiomyopathies, post-valvuloplasty,
and congenital or infantile  causes  such  as  anomalous left coronary artery
arising from a pulmonary artery, endocardial  fibroelastosis,  floppy  valve,
and cleft valve with or without an endocardial cushion defect.  Functional MR
occurs  from  left  ventricular dilatation and dysfunction from any etiology.
The dilatation leads  to  enlargement  and  malalignment  of the mitral valve
apparatus  and  a  decrease  in  left  ventricular   and   papillary   muscle
contractility.   As  long as the left ventricle is able to compensate for the
left ventricular diastolic  overload,  the  patient  will be asymptomatic for
many years.  Eventually, however, the LV is overwhelmed and left  ventricular
systolic dysfunction occurs.  Patients may tolerate a mild to moderate degree
of  MR for 10 years or more without CHF.  PHYSICAL EXAM: The patient may have
Marfan's syndrome.  Observe  for  an  increased  arm span, tallness, thiness,
hyperextensible joints, kyphoscoliosis, pectus deformity, high arched palate,
and lax skin.  In severe MR the carotid pulses have a brisk  upstroke,  there
is a LV heave with a displaced, diffuse and sustained PMI.  A systolic thrill
also indicates significant MR.  A grade 4/6 or louder murmur with a thrill is
characteristic  of  severe  MR.   A  right ventricular heave is indicative of
pulmonary hypertension and  associated  tricuspid regurgitation.  The jugular
pulse is normal unless  there  is  pulmonary  hypertension  and  right  heart
failure.  In severe MR, S1 is soft, S2 is increased if pulmonary hypertension
is  present.   The  S2  is  usually  widely  split,  unless  severe pulmonary
hypertension has developed.  The murmur is a high ptiched holosystolic murmur
that radiates to the left axilla.  It is usually loudest at the apex.  If the
murmur is due to papillary muscle dysfunction it may crescendo to S2.  If the
murmur is due to posterior ruptured  choardae, it can radiate into the second
right interspace and carotids and simulate the murmur of aortic stenosis.  If
the murmur is due to anterior ruptured chordae, it can radiate to  the  spine
and  the top of the head.  There may be a diastolic flow rumble in severe MR.
If there is mitral valve prolapse,  an  associated click murmur may be heard.
The murmur of mitral regurgitation increases  with  squatting  and  decreases
with  the strain phase of the valsalva maneuver, and after amyl nitrite.  The
patient may have an S3 and S4 that may  be heard in severe MR.  The S3 may be
followed by a diastolic inflow murmur if the MR is severe.   ECHOCARDIOGRAPHY
is  useful  in assessing the cause of the MR.  In acute MR, a flail valve may
be seen due to chordae or  papillary  muscle rupture, vegetations may be seen
secondary to endocarditis, and associated  finding  of  LV  and  left  atrial
dilatation.   Annular  calcifications  can be visualized.  Color flow doppler
can ascertain the extent and  severity of the regurgitation.  CATHETERIZATION
DATA: Pure MR may produce an early to mid-diastolic gradient between the left
atrium and the left ventricle.  If there is an end diastolic gradient, mitral
stenosis usually co-exists.  Determination of the  mean  pulmonary  capillary
wedge  pressure  can estimate the severity of MR by the height of the V wave.
Acute MR is  characterized  by  an  elevated  LV  end  distolic and pulmonary
capillary wedge pressure + a prominent  V  wave.   The  highest  left  atrial
pressures  occur  with  ruptured choardae since the left atrium and ventricle
cannot dilate with the sudden regurgitant volume.  Severe MR with a normal LV
ejection fraction usually causes  a  small  increase  in the LV end diastolic
pressure.  If there is a large increase in the LV end diastolic pressure,  LV
dysfunction  or  aortic  valve disease may be present.  LV cineangiography is
capable of determining the severity  of  the MR, regional wall abnormalities,
LV function, and left ventricular dilatation.  The regurgitant  fraction  can
be  calculated  from  the  thermodilution  cardiac  output  + quantitative LV
cineagniography.  This  is  done  by  using  the  formula: regurgitant stroke
volume/total stroke volume.  The total stroke volume  is  calculated  by  the
formula:  LV  cine  end-diastolic  volume minus the end-systolic volume.  The
rugurgitant stroke volume is calculated  by  the formula: total stroke volume
minus the forward stroke volume (cardiac  output/heart  rate).   CHEST  X-RAY
will  show  an  enlarged left atrium and ventricle in moderate and severe MR.
The ECG will show  signs  for  left  atrial and ventricular overload.  Atrial
fibrillation is common when the left atrium enlarges beyond 4.5 cm.   If  the
patient  has  sinus  rhythm  and  symptomatic  MR,  suspect an acute event as
ruptured chordae.  MEDICAL TREATMENT: Chronic mitral regurgitation is usually
well tolerated and patients will have  no symptoms for years.  However, as LV
function declines, symptoms ensue secondary to a decrease of forward  cardiac
output.   Exertional dyspnea, fatigue and weakness are common complaints.  As
the left  atrium  enlarges  atrial  arrhythmias  will  develop.   Mild mitral
regurgitation that is asymptomatic requires no  treatment  except  antibiotic
prophylaxis.   Early  symptomatic  mitral  regurgitation  may be treated with
afterload reducing agents  in  order  to  increase  forward stroke volume and
reduce the regurgitation.  Digoxin and diuretics  are  useful  in  congestive
heart  failure.  Maintenance of sinus rhythm is not as important as in mitral
stenosis and rate may be controlled with  digitalis as the patient is left in
atrial fibrillation.  Mitral regurgitation  can  be caused by rheumatic heart
disease,  mitral  valve  prolapse,   endocarditis,   annular   calcification,
papillary muscle dysfunction secondary to coronary artery disease, rupture of
chordae  or  papillary  muscles,  connective  tissue  disorders as rheumatoid
arthritis and SLE,  endocardial  cushion  defects and dilated cardiomyopathy.
SURGICAL TREATMENT: Timing of surgery for chronic severe mitral regurgitation
should be before irreversible LV dysfunction occurs.   As  the  LV  enlarges,
there  is development of LV dysfunction and there is a point where surgery is
no longer effective.  If the end diastolic dimension is greater than 7 cm and
the fractional  shortening  is  reduced  or  low  normal,  there  may  not be
improvement afforded by surgery such as reduction of LV volume and mass.   If
there  is  borderline or reduced LV function, surgery should be contemplated,
even if the patient is  only  mildly symptomatic.  With ejection fractions of
0.30 or less there is increased operative mortality and  poor  post-operative
results.   Patients  that  have  post-operative ejections fractions of 0.5 or
greater have better long term  results  than  those that have < 0.5  ejection
fractions.  Predictors for postoperative ejection fractions of .5 or  greater
include preoperative LV end systolic volume indices of no more than 50 ml/m2,
and absence of pulmonary hypertension.  Trends are developing which encourage
mitral  valve repair rather than replacement.  LV function may be better with
repair  and  complications  associated  with  prosthetic  insertion,  such as
embolization, is less with repair.

                          -MITRAL STENOSIS-
Mitral valvular stenosis  can  be  congenital  or  acquired.  Rheumatic heart
disease is the most common acquired form.  Other causes include mitral  valve
annular  calcification,  mitral  valve  obstruction  by  myxoma, endocarditis
vegetations,  ball   valve   thrombus,   valve   infiltration   secondary  to
mucopolysaccharides  and  carcinoid,  and  chronic  valvulitis  secondary  to
systemic lupus erythematosis, carcinoid  and  amyloid.   Rheumatic  fever  is
caused  from  strep  viridans,  but  not  all  individuals  acquire rheumatic
valvular disease.  Risk factors  include  multiple attacks of acute rheumatic
fever, female sex, and living in the tropical environments.  Patients develop
chronic inflammation  of  the  mitral  valve  leaflets,  cusps,  commissures,
annulus,  chordae, and papillary muscles, which eventually leads to fibrosis,
calcification, and valvular distortion.   The  mitral  valve is most commonly
involved with aortic , tricuspid and pulmonic valves (in that  order),  being
involved.  There is a clinical latent period of 5-20 years before the patient
becomes  dyspneic  on  exertion.   Any cause of tachycardia (exercise, fever,
pregnancy,   supraventricular   tachycardia,    atrial   fibrillation),   can
precipitate symptoms by shortening the diastolic filling period, which  leads
to increased left atrial pressures.  As the disease progresses and the mitral
valve  area  decreases  to  1-1.5 cm2, dyspnea on exertion increases, and the
patient becomes a class II-III.   Mitral  valve  stenosis  less than 1 cm2 is
usually accompanied by pulmonary hypertension which is a physiologic response
to chronic left atrial pressure > 25 mm Hg.  Initially,  the  development  of
pulmonary  hypertension is protective from increased blood flow into the left
atrium, and may  temporarily  ameliorate  the  symptoms of dyspnea.  However,
ultimately the pulmonary hypertension restricts cardiac output  which  causes
fatigue   and  exercise  limitations.   As  the  patient  develops  pulmonary
hypetension and right heart  failure,  paroxysmal nocturnal dyspnea develops.
Right heart failure eventually may lead to ascites, hepatomegaly,  edema  and
tricuspid  regurgitation.  Atrial fibrillation develops in about 80% of cases
with subsequent loss of  the  atrial  kick,  which  further increase the left
atrial pressure.  Atrial fibrillation is associated with a 20%  incidence  of
thromboemboli, which can be multiple and recurrent.  Approxiamtely 50% of the
emboli  lodge in the brain.  Hemoptysis in rheumatic mitral valvular stenosis
may be due to pulmonary  edema,  or  rupture  of  a bronchial vein, due to an
acute rise in left atrial pressure.  Angina may occur in 10-15%  of  patients
due  to  coronary artery embolism, right ventricular subendocardial ischemia,
or coronary artery disease.  PHYSICAL EXAMINATION: Patients with longstanding
moderately severe mitral stenosis may  develop  a malar flush.  The apex beat
is tapping in quality, but usually not displaced.  There may be a lower  left
parasternal lift or heave, secondary to right ventricular hypertrophy.  There
also  may be a diastolic thrill localized to the apex which can be felt.  The
pulmonary second sound (P2) is accentuated, and  this may also be felt due to
a vibration of the pulmonary valve closure.  The jugular venous pressure  may
be  elevated  suggesting pulmonary hypertension.  The A wave may be increased
due  to  right  ventricular  hypertrophy.    A  V  wave  indicates  tricuspid
regurgitation due to right ventricular failure or rheumatic  disease  of  the
tricuspid valve.  Mitral stenosis causes a low pitched diastolic rumble which
begins  with the opening snap, peaks at middiastole and can be accentuated at
presystole.  It is best heard with  the patient in the left lateral recumbent
position at the apex.  The murmur is often localized to an area the size of a
coin and can be missed.  If the mitral stenosis is critical  the  transmitral
flow  is  severely  decreased and the murmur may be barely audible.  Exercise
can accentuate the murmur.   As  the  valve  orifice  decreases, the more the
murmur becomes pandiastolic.  The severity of mitral stenosis correlates best
with the length of the murmur, rather  than  the  intensity  of  the  murmur.
There  may be an increase in S1 if the mitral valve is pliable.  If the valve
is not pliable S1 is soft.  If  an opening snap is heard, this would indicate
pliable leaflets.  The opening snap is a sharp high  pitched  sound  that  is
best heard with the diaphragm just medial to the apex and occurs from .04-.14
seconds  after  the  second heart sound.  The shorter the duration between A2
and the opening snap correlates with  severity of the mitral stenosis, as the
increased pressure  gradient  opens  the  valve  sooner.   In  severe  mitral
stenosis,  the  opening snap is typically less tha .08 sec.  The opening snap
may disappear if there is heavy  calcification of the valve.  To compound the
problem, other murmurs may heard.  The Graham-Steel murmur  is  a  murmur  of
pulmonic  regurgitation  and  reflects  severe pulmonary hypertension.  There
also may be  a  murmur  of  mitral  regurgitation.  A tricuspid regurgitation
murmur due to right heart failure or rheumatic involvement of  the  tricuspid
valve  may  also  be  present.   THE  EKG  may  show  broad  bifid  P  waves,
particularly  in lead 2, and an increase in the P terminal forces as measured
in V1, due to left atrial  enlargement.   Right axis deviation may be present
secondary to right ventricular hypertrophy due  to  severe  mitral  stenosis.
Right  ventricular  hypertrophy may  be  seen  on the ECG.  Right ventricular
hypertrophy is seen in 50%  and  90%  of those with pulmonary artery systolic
pressures greater than 70 mm Hg and greater than  100  mm  Hg,  respectively.
Atrial fibrillation (usually coarse) is common in patients with a left atrial
size  greater  than  4.5  cm.  CHEST X-RAY will show left atrial enlargement,
mitral valve calcification,  pulmonary  venous  congestion  (Kerley B lines),
enlarged pulmonary arteries, right ventricle  and  right  atrium.   There  is
straightening  of  the  left  heart  border (left atrial enlargement), double
density seen through the right  half  of  the cardiac silhouette (left atrial
enlargement), elevation  of  the  left  main  stem  bronchus  (enlarged  left
atrium),  venous  redistribution  (dilation  of  the  upper  lobe vessels and
diminution of the lower lobe vessels).   The  heart size is usually normal on
the PA film,  but  the  lateral  film  may  show  enlargement  of  the  right
ventricle.  The ECHOCARDIOGRAM will demonstrate left atrial enlargement which
can  be  accurately measured.  Calcification of the mitral valve leaflets and
annulus  may  be  seen.   Oftentimes,  there  is  decreased  movement  of the
posterior leaflet of the mitral valve.  Right ventricular enlargement can  be
seen  and  measured.   The  left ventricle is usually small in the absence of
significant mitral regurgitation.  Doppler  can  assess  the degree of mitral
regurgitation.  Quantification of  the  mitral  valve  orifice  area  can  be
assessed, and the mitral diastolic gradient can be defined.  There is usually
a  flat  E  to  F  slope  of  the anterior leaflet of the mitral valve.  ECHO
DOPPLER  can   accurately   document   the   severity   of  mitral  stenosis.
Transesophageal echo (TEE) may be used to determine if left  atrial  thrombus
is  present,  used  prior  to  balloon  valvuloplasty,  or  performed  if the
transthoracic echo  is  suboptimal.   Doppler  pressure  half  time (the time
needed for initial mitral flow velocity to decrease by 50%) can  be  used  to
determine  the  degree  of  obstruction  when  mitral regurgitation coexists.
Prolongation of the doppler pressure  half  time indicates delayed blood flow
through  the  obstructed  mitral  valve.   Patients  with   combined   mitral
regurgitation  and mitral stenosis may have an overestimation of the pressure
gradient by  peak  velocity  due  to  increased  valve  flow  from the mitral
regurgitation.  Catheterization is now only used  to  evaluate  the  coronary
arteries  in those suspected to be at risk, or when there is a discrepancy in
clinical findings versus echo  findings.   Catherization  is seldom needed if
the patient is less than 40  years  of  age,  if  there  is  isolated  mitral
stenosis,  and  there  is no risk for coronary artery disease.  Patients that
have associated valvular  disease,  coronary  artery  disease, or significant
mitral regurgitation may require catheterization.  CATHETERIZATION  DATA  can
demonstrate  a  decrease  in cardiac ouput if there is severe mitral stenosis
and  pulmonary  hypertension.   The  pulmonary  capillary  wedge  pressure is
elevated, the Y descent is decreased, the LV end-diastolic pressure is normal
or low, and there is a pandiastolic gradient between the PCW and the LV.   If
a prominet V wave is seen, this would indicate a noncomplaint left atrium +/-
mitral  regurgitation.  The right atrial pressure is increased with pulmonary
hypertension with an increase in the  A  wave if there is RV hypertrophy, and
an increase in the V wave if there is tricuspid regurgitation.  If  the  left
atrial pressure is greater than 25 mm Hg there is usually increased pulmonary
artery pressure.  MEDICAL TRATMENT: In most cases of mitral stenosis there is
a  long  interval  where  the  patient is asymptomatic.  However, when atrial
fibrillation intervenes, the patient  may  become symptomatic.  Conversion to
normal sinus rhythm is most successful when the left atrium has a diameter of
less tha 4.5 cm and the atrial fibrilation has been  present  for  less  than
6-12  months.   Digitalis and class I or III antiarrhythmic agents are useful
in controlling the ventricular rate in atrial fibrillalion, particularly with
exercise.  Beta adrenergic  blockers  should  be  used  with caution in those
patients  that  also  have  aortic  stenosis  and  impaired  LV  dysfunction.
Diltiazem and digoxin is a useful combination.   Diuretics  may  be  used  if
there  is evidence of pulmonary congestion.  Once atrial fibrillation begins,
the patient should  be  placed  on  warfarin  anticoagulation,  even if sinus
rhythm is restored as  20-30%  of  these  patients  will  have  embolization.
Conversion  of atrial fibrillation should be attempted by placing the patient
on warfarin about 2-3 weeks  prior  to  cardioversion, and then maintained on
digitalis and quinidine.  Women should consider becoming  pregnant  early  in
the course of mitral stenosis as pregnancy is usually well tolerated in early
mitral  stenosis.  Patients should have prophylaxis against endocarditis even
though the incidence is  rather  low  in  isolated mitral stenosis.  SURGICAL
TREATMENT: For young patients  with  a  pliable  mitral  valve,  open  mitral
commissurotomy  is  indicated  for functional class III or IV, and even in II
because  of  the  low  morbidity  and  mortality  of  mitral  commissurotomy.
Surgical mortality is less  than  1%  and  the  results  are excellent if the
patient has no substantial mitral regurgitation.  Mortality at 10 years is  <
5%  and  the  thromboembolism  rate  is  2%/year,  with  the reoperation rate
0.5-4.5%/year.  If  symptoms  return  after  commissurotomy, suspect impaired
myocardial function, suboptimal surgical relief, and other valvular  lesions.
Indications  for  surgery  include  recurrent emboli despite anticoagulation,
with moderate or severe stenosis, limitation  of activity in spite of optimal
medical therapy, pulmonary hypertension with RVH  and  hemoptysis,  pulmonary
edema  and  orifice  <  1.2  cm2.   Balloon  valvuloplasty has short term low
complication rates, and may be  the  procedure of choice for younger patients
with a pliable valve.  Ideally,  the  patient  should  have  a  noncalcified,
mobile  valve  without  subvalvular  fibrosis, and should have a mitral valve
area less than 1  cm2.   It  may  also  be  useful  in those patients who are
inoperable (elderly, and those with other debilitating  disease),  and  those
where  prosthetic valves may not be desirable (females of child bearing age).
The same results may be  expected  as  that from commissurotomy with a lesser
incidence of morbidity and mortality.  Balloon valvuloplasty can decrease the
pressure gradient by 50%, increase cardiac output by 20% and increase  mitral
valve  area  by  50-100%.  Following balloon valvuloplasty more than 90% will
have valve areas greater than 1  cm2.   The  survival at 3-5 years is greater
than 95%.  Complications include thromboemoblism of 1-4%, mortality of  about
1%,  severe  mitral  regurgitation  requiring  mitral valve replacement 1-3%,
iatrogenic atrial septal defect in 20%, transient heart block and pericardial
tamponade of about 1%, emergency  valve  replacement of 4%, and restenosis of
16%.  Contraindications  for  catheter  balloon  valvuloplasty  include  left
atrial  thrombus,  moderate to severe mitral regurgitation, bleeding disorder
(abnormal  PT,   PTT,   increased   bleeding   time),   recent  embolization,
cardiothoracic deformity, severe  multivalvular  disease,  active  or  recent
infective  endocarditis and coronary artery disease requiring bypass surgery.
Transesophageal echo plays an important role  in deciding if the patient is a
candidate for balloon valvuloplasty.  TEE can detect calcification, mobility,
thickening and subvalvular fibrosis.  It also  is  very  good  for  detecting
atrial  or left atrial appendage clots, and can evaluate the magnitude of the
iatrogenic  atrial  septal  defect  following  the  procedure.   MITRAL VALVE
REPLACEMENT may be needed if there is moderate to severe mitral regurgitation
along with the mitral stenosis.  It may also be  indicated  in  those  valves
that  are  heavily calcified and non pliable.  In general, a mechanical valve
is usually preferred in the mitral  position.  Many patients will have atrial
fibrillation and require anticoagulation anyway.   Porcine  valve  replacment
may  avoid  anticoagulation, and is therefore useful in pregnancy, but on the
other hand, there is accelerated calcification with bioprosthetic valves that
will necessitate a future  replacement.   However,  a mechanical valve can be
used  in  patients  who  wish  to  become  pregnant  by  discontinuing   oral
anticoagulants  and  using heparin SQ for the first 4 months of pregnancy and
again for the last 3 weeks.

                       -MITRAL VALVE PROLAPSE-
Is associated with other  congenital  heart  defects and connective tissue or
skeletal abnormalities.  There is a mid to late  systolic  click  heard  best
with  the  diaphragm at or medial to the apex, frequently followed by a short
crescendo  or  crescendo-decrescendo  murmur  of  mitral  regurgitation.  The
murmur is often high frequency, loud and scratchy.  Loud whistles also may be
heard.

                       -MITRAL VALVE PROLAPSE-
Mitral  valve  prolapse  (MVP)  is  usually  a benign condition affecting the
mitral valve, and most commonly seen in  young females between the ages of 20
and 40 with an incidence of about 3-4% of the general population.   CLINICAL:
Most  patients  will  have  no  symptoms  in  association  with  mitral valve
prolapse.  If symptoms do occur  the  most common are non-specific chest pain
that is poorly relieved with nitroglycerin and is non-exertional.  The  chest
pain has been described as sharp, stabbing and evanescent.  Rarely, the chest
pain will simulate angina pectoris.  The patient may complain of non-specific
dizziness,  fatigue, palpitations and syncope.  Occasionally you may elicit a
sudden  death  in  the  family.    Infrequently,  mitral  valve  prolapse  is
associated with  an  audible  whoop  which  can  be  heard  by  the  patient.
Palpitations  may  be  present  and are probably due to arrhythmias, although
ambulatory monitoring  in  some  has  shown  no  correlation.   Sometimes the
arrhythmias occur only during exercise.  For some time it has been known that
MVP is associated with  neuropsychiatric  symptoms  such  as  panic  attacks,
migraine  headaches,  hyperventilation,  agoraphobia, depression, anxiety and
other personality profiles.  Modification  of  life  style may help alleviate
some of  these  symptoms.   Embolic  events  are  occasionally  seen  causing
transient  cerebral  or  retinal  circulatory  changes  that may culminate in
stroke.  The  origin  of  the  embolic  thrombi  can  be  from  a degenerated
myxomatous mitral valve or thrombi in the left atrial area.  If  the  patient
has  concomitant  atrial  fibrillation  this would increase the embolic risk.
The most distinctive finding on  auscultation  is the mid-systolic click that
is highly variable as to intensity, positioning  during  systole  and  actual
presence  or absence.  The click has been described as a high frequency sound
such as a snapping, popping or clicking.  There can be beat to beat variation
in the click and the  click  may  be  single  or  multiple.  The click may be
associated with or without a murmur that usually follows the click,  but  not
always.   The  murmur  is  best  heard  at the apex or the lower left sternal
border.  Sometimes the murmur  is  holosystolic proceeding through the click.
The variability is probably explained by the size of the  left  ventricle  at
end  diastole  and left ventricular contractility.  If the patient is supine,
the click may disappear, decrease in intensity and change to a later position
in systole.  The murmur, if  present,  may  reduce in intensity, disappear or
shorten if auscultation is carried out in the supine position.  All of  these
findings  are  reversed if the patient is examined in the sitting or standing
position.  Other bedside maneuvers such  as handgrip and valsalva strain will
produce characteristic changes in the timing of  the  click  and  the  murmur
characteristics.   Handgrip changes are identical to examining the patient in
the supine or squatting position  with  the  click occurring later in systole
and the murmur shortening.  On the other hand, Valsalva strain  will  produce
findings equivalent to examining the patient in the standing position with an
earlier  systolic  click  and  longer  murmur.   Physical  examination of the
patient is important because  it  may  provide additional clues.  The patient
may have a straight back with loss of the normal thoracic kyphotic curve  and
there  may  be Marfan changes such as a high arched palate.  Pectus excavatum
may  also  be  present.   LABORATORY:  The  EKG  usually  shows  non specific
abnormalities that may be present on the resting EKG or may only  occur  with
continuous  ambulatory  monitoring  or  exercise  testing.  The most frequent
findings are T wave inversions  seen  in  the infero-lateral leads.  PVCs are
the most frequent arrhythmic findings, but occasionally there will be  atrial
tachycardia, atrial fibrillation, or rarely, ventricular tachycardia.  M mode
echocardiography may show the characteristic posterior	left atrial bowing of
either  mitral  leaflet in systole.  The bowing is usually more than 2 mm and
may  be  holosystolic,  but  is  usually  in  middle  to  late  systole.   2D
echocardiography  will  show  the   superior-posterior  displacement  of  the
leaflets and also can evaluate the  leaflets  for  thickening.   Doppler  can
ascertain   the   presence  and  degree  of  mitral  regurgitation.   Cardiac
catheterization is helpful to assess the status of the coronary arteries as a
cause for the chest pain in a  patient with mitral valve prolapse.  Also, the
presence and degree of mitral regurgitation and left ventricular function can
be studied  with  left  ventriculography.   For  patients  that  complain  of
dizziness,  syncope, palpitations and tachyarrhythmias, continuous ambulatory
monitoring is done.  Stress electrocardiography is usually done to assess the
arrhythmias  that  occur  with  exercise.   False  positives  are  common for
ischemic changes in  patients  with  mitral  valve  prolapse,  and  therefore
Thallium  should  be  used  in  conjunction with the exercise testing.  Chest
x-ray is usually normal, but  may  show  pectus excavatum or a straight back.
If there is severe mitral regurgitation there may  be  left  ventricular  and
left  atrial  enlargement  along  with  possible  CHF findings.  DIFFERENTIAL
DIAGNOSIS: The murmur of  mitral  valve  prolapse must be differentiated from
other etiologies  of  mitral  regurgitation,  aortic  stenosis,  hypertrophic
cardiomyopathy  and  benign  murmur.  The click that is heard in mitral valve
prolapse must be  differentiated  from  the  clicks  heard in bicuspid aortic
valves,  pulmonary  and  aortic  stenosis.   COMPLICATIONS  OF  MITRAL  VALVE
PROLAPSE: There are 5 complications that may develop  during  the  course  of
MVP.   In  most  cases, these complications will not occur, but you should be
aware  of  these.   The  first  complication  is  mitral  regurgitation  that
progresses.  This occurs in  about  8%  of  patients.  Most of these patients
will have redundant myxomatous changes in the leaflets.  Either valve  repair
or  insertion  of  a  mechanical  valve with life long anticoagulation may be
necessary in this group.  The  second and third complications are development
of endocarditis and chordae tendineae rupture, and  for  this  reason  it  is
prudent  to  give  antibiotic prophylaxis for dental work, before surgery and
procedures involving the upper  respiratory,  GI or genitourinary systems and
possibly before  vaginal  delivery.   It  is  recommended  that  3  grams  of
amoxicillin  be  given  orally  one  hour  before the procedure and 1.5 grams
orally 6 hours  after  the  initial  dose.   If  the  patient  is allergic to
penicillin, erythromycin stearate 1 gram orally 2 hours is given  before  the
procedure, or clindamycin 300 mg orally one hour before the procedure and 150
mg 6 hours after the initial dose.  The fourth complication is arrhythmia and
sudden  death.  Only about 2 percent will be vulnerable to sudden death.  The
patient at greatest risk is  the  patient  who  has an abnormal EKG, multiple
arrhythmias on ambulatory monitoring with a very pronounced prolapse of  both
mitral  leaflets  into  the  left  atrium.   Some of these patients will have
ventricular tachycardia that evolves into ventricular fibrillation and death.
Beta blockers are used if the patient has symptomatic PVCs, paroxysmal atrial
tachycardia,  and  PACs.   If   the   patient  has  paroxysmal  or  sustained
ventricular tachycardia, he or she will need electrophysiologic  testing  for
determination  of  the  most appropriate treatment.  The last complication is
thromboembolism.  Patients at highest  risk  for  embolization are those with
atrial fibrillation, enlarged left atrium, myxomatous mitral valve and mitral
regurgitation.  The prevalence rate of cerebral infarction is about  4  times
greater  than  normal  patients.   ASA  at  325  mg  daily or warfarin may be
beneficial  in  this  group.   TREATMENT:  For  most  patients  that  have no
complications or high risk factors for  development  of  complications,  beta
blockers  may  be used for the chest pain, supraventricular tachyarrhythmias,
PVCs and palpitations.  Endocarditis  prophylaxis, particularly in those with
a  murmur,  should  be  instituted  prior  to  surgery,  dental   procedures,
respiratory,  genitourinary  and GI procedures and possibly vaginal delivery,
using amoxicillin or erythromycin  as  outlined  above.  Patients that are at
risk for, or have transient ischemic attacks, should be treated  with  either
ASA	or ticlopidine (Ticlid).

                      -MONOARTICULAR ARTHRITIS-
There are  numerous  causes  of  monarticular  arthritis  (MA),  but the most
devastating is septic arthritis.  A mis-diagnosis can cause rapid destruction
of the joint.  Once the bacteria enter the joint an inflammatory response  is
set  up  causing  migration  of polymorphonuclear leukocytes into the joints.
They, in turn, release  lysosomal  enzymes  that  can destroy the subchondral
bone  and  articular  cartilage.   About  85%  of  non-gonococcal   bacterial
infections  are  monoarticular.  Most of these will develop from hematogenous
dissemination and a primary site should be sought.  It is helpful to know the
most common  pathogens  that  occur  at  various  age groups.  Staphylococcus
aureus and E. coli are most common  from  0-6  months  of  age.   Haemophilus
influenzae  is  common from 6 months to 2 years.  From 2 years to adolescence
gram  positive  cocci  predominate.   From  adolescence  to  early  adulthood
Neisseria gonorrhoeae  will  be  the  cause.   If  the  patient  is  over 40,
Staphylococcus aureus again is the most common pathogen.  About  80%  of  the
infections  are  caused  by  gram  positive  aerobes.   Staphylococcus aureus
accounts for  about  60%.   S.  aureus  septic  arthritis  may  arise  from a
cellulits, endocarditis, cutaneous abscess and all of these may be caused  by
IV  drug  use.   Non-group  A  beta-hemolytic  streptococci and Streptococcus
pneumoniae are other gram positive  aerobic  microbes that cause infection of
the joint.  If pneumococcus is isolated  from  a  joint  the  origin  may  be
pulmonary,  sinusitis,  or otitis media.  If the patient is an IV drug abuser
or is immunocompromised suspect anaerobes  and gram negative bacteria such as
E. coli or Pseudomonas aeruginosa.  Also, if the patient has a GI  malignancy
anaerobic  infection  is  more common.  In children less than 2 years of age,
Staphylococcus aureus, Escherichia coli and  gram negative bacilli are common
organisms causing infectious arthritis.  From adolescence until  the  age  of
40, Neisseria gonorrhoeae is common.  A complete history is very important in
arriving  at a diagnosis.  If the onset is rapid, an acute infection, crystal
induced arthritis and trauma are  good  bets.  Aspiration of the joint should
be carried out.  If the synovial fluid WBC is less than 2000 the effusion  is
probably  non-inflammatory;  if greater than 5000, an inflammotory process is
probably ongoing.  These figures  are  not  arbitrary and there is definitely
overlap   in   inflammatory   and   non-inflammatory   categories.     Viral,
mycobacterial  and  fungal  infection  of  joints  are more likely to cause a
polyarticular arthritis.  Polyarticular involvement may occur more frequently
if the patient  has  an  underlying  condition  such as rheumatoid arhtritis.
CLINICAL: An exhaustive history should be done such as recent travel, history
of gout or pseudogout,  history  of  tick  bites,  IV  drug  use  and  sexual
practices.   If  there  has  been diarrhea, rash, urethritis or uveitis, this
would suggest a reactive arthritis.   Question the patient for recent trauma,
coagulopathies such as hemophilia, and anticoagulant  therapy.   Examine  the
patient  for  ulcers  in the mouth that would suggest Reiter's syndrome, SLE,
and Behcet's syndrome.  Reiter's syndrome  may  also produce other skin clues
such as keratoderma blennorrhagicum which affects  the  feet.   If  there  is
erythema nodosum rule out sarcoidosis, inflammatory bowel disease or systemic
lupus  erythematosus,  all  of  which  can  produce  arthritis.   If splinter
hemorrhages are  seen  rule  out  bacterial  endocarditis.   Check  for small
patches  of  hidden  psoriasis  paricularly  behind  the  ears  or   in   the
intergluteal  fold  of  the  buttocks.   Cultures  and  Gram stains should be
carried out when  appropriate  of  cervix,  urethra,  blood, skin, ulcers and
synovial fluid.  HIV and Lyme antibodies may be of ancillary help.  Uric acid
and rheumatoid factor  is  usually  not  that  helpful.   SYNOVIAL  ANALYSIS:
Synovial  fluid is normally clear yellow and is viscous.  In inflammatory and
infectious arthritis the  viscosity  is  decreased.   Normal white blood cell
count is less than 200/uL with most of these mononuclear cells.  The fluid is
non-inflammatory if less tha 2000 cells per cubic millimeter  are  seen.   If
more  than  2000 cells are counted the fluid is inflammatory.  Synovial fluid
that contains more than  100,000  leukocytes  per cubic millimeter is septic.
Only about 1 ml of synovial fluid is needed to perform a leukocyte count  and
differential,  culture, Gram stain and examination for crystals.  These tests
can be done with a few drops  if  there is difficulty in obtaining fluid.  In
some joints as the sacroiliac and hips the procedure  may  have  to  be  done
under  CT,  sonography  or  fluoroscopic guidance.  If there is more than 90%
polymorphonuclear cells seen, strong consideration should be given to sepsis,
particularly if the white count is  low.  About 80% of gram positive bacteria
can be seen on Gram stain  if  the  cultures  are  positive.   However,  gram
negative  bacteria  are not seen as frequently and Neisseria meningitidis and
gonorrhoeae are very rarely  seen.   If  fungus or mycobacteria are suspected
special stains should be employed.  Polarized microscopy should be  performed
for  crystals.   The  presence  of  yellow  needle  shaped  crystals when the
crystals are parallel to the red compensator  and blue at right angles to the
compensator is typical of mono-sodium urate crystals  associated  with  gout.
In  85%  of  cases these crystals can be seen in gout.  Calcium pyrophosphate
crystals seen in pseudogout are rhomboid in  shape and have a blue color when
parallel to the compensator and  yellow  when  perpendicular.   Fat  droplets
would  suggest  a  fracture.   Biopsy  of  the  synovium  may be necessary to
diagnose diseases as sarcoidosis,  pigmented villonodular synovitis, tumor or
amyloidosis.  X-rays  are  most  helpful  for  fractures,  chondrocalcinosis,
osteoarthritis.   MRI  may be useful in sacroiliitis.  CAUSES: GONOCOCCAL: In
any patient from  adolescence  to  adulthood  suspect disseminated gonococcal
infection.   Disseminated  gonococcal  infections  may  be  associated   with
deficiencies  of the late components of the complement system.  Dissemination
usually occurs during menstruation or  during pregnancy in women.  Women have
a frequency 2-3 times that of men.  In men, the infection in  the  anogenital
area,  or  pharynx  may  be silent, yet there is dissemination to the joints.
During the bacteremic stage  the  patient  may  have  chills, fever, rash and
migratory  polyarthralgia,  tenosynovitis,  positive  blood  cultures  and  a
systemic leukocytosis.  Following this stage monoarticular arthritis  becomes
predominate,  but  the patient may still have polyarticular arthritis.  Joint
fluid and blood should be  cultured  on  gonococcal  base agar with a XV like
supplement.  However, these cultures are positive in less than 50 % of cases.
Anogenital cultures should use Thayer-Martin media.   Gram  staining  of  the
joint  fluid  will  occasionally  show  the organisms.  The synovial fluid is
usually turbid  with  a  leukocytosis  from  several  thousand  to  more than
100,000/mm3 with a predominance of polymorphonuclear leukococytes.  In  about
33%  of patients a characteristic skin lesion appears on the distal aspect of
the extremities.  It is a small  reddish macule that evolves into a petechial
or vesicular lesion.  The vesicular lesion may be pustular  with  a  necrotic
dark  center.   Culture  of  these  lesions  is  very rarely positive for the
organism.  However, the fluorescein conjugated antibody test may be positive.
The  differential  must   include,  Neisseria  meningitidis,  Streptobacillus
moniliformis and H. influenze.  Because the cultures  are  positive  in  less
than 50% of cases one must rely on the clinical combination of characteristic
rash,  arthritis,  positive  pharyngeal or anogential culture and the typical
rapid response to antibiotics.  Treatment  is  with either ceftriaxone 1 gram
IM or IV every 24 hours, cefotaxime 1 gm IV every eight hours or  ceftizoxime
1  gram  IV  every 8 hours.  If the patient is allergic to beta-lactam drugs,
spectinomycin should be used at a dose of  2 grams IM every 12 hours.  If the
blood culture sensitivity includes penicillin  or  ampicillin  these  may  be
given.   Ampicillin may be given at grams 1 IV every 6 hours.  Oral treatment
may be started with  either  ciprofloxicin,  or  cefuroxime if the patient is
treated as an  outpatient.   NON-GONOCOCCAL  MONOARTHRITIS:  Most  cases  are
monoarticular,  but  occasionally  2  or  3 joints may be involved.  The most
common organisms are streptococci and  Staphylococcus aureus, but there is an
increasing frequency of gram negative pathogens.  These patients have  a  low
grade  temperature,  pain  and  tenderness, and swelling of the joint.  Again
blood cultures and joint fluid  cultures  are  needed.  The synovial fluid is
turbid with a decreased viscosity and the leukocytes are usually greater than
50,000/mm3.   Gram  stains  are  positive  in  about  60%  of  cases.   OTHER
INFECTIOUS CAUSES: Mycobacterial infections can affect the  joint.   Most  of
these   are  chronic  in  nature  rather  than  acute.   There  may  also  be
periarticular  involvement  as  well   as  synovial  infection.   Concomitant
pulmonary infection is only present in about 50 % of the cases.   Skin  tests
are  usually  positive but may be negative and cannot be relied upon.  If the
patient   is   immunocompromised   or   has   had   frequent   injections  of
intra-articular steroid injections atypical mycobacterial infection should be
suspected.   Lyme  disease  may  present  as  a  chronic   monoarthritis   or
intermiitent  arthralgias  with  oligoarthritis.   The arthritis is caused by
Borrelia burgdorferi which is  a  spirochete  transmitted  by the tick Ixodes
dammini.  Common hosts of the tick are white footed mice and deer.   Most  of
the  cases  have  been  seen  in  the  Northeast,  Wisconsin,  Minnesota  and
California.  Lyme disease at the present time is a clinical diagnosis for the
Lyme  IgG  and IgM tests are not reliable and may not be positive for several
weeks and some titers may persist indefinitely after infection.  Suspect Lyme
disease if there is a  history  of  tick  bite and erythema chronicum migrans
which is an erythematous papule that enlarges with a pale center.  There  may
be  headache, fever, stiff neck, fatigue and malaise.  If the Lyme patient is
not treated, the  acute  oligoarthritis  may  start  months after the initial
infection in about 60 % of  patients.   Although  arthritis  may  occur  very
early,  or  as  late  as  2  years following the infection, the usual time is
around six months.  Usually the knee or other large joints are affected.  The
joint may be swollen and  painful  which  comes  and goes.  Treatment for the
arthritis is with doxycycline 100 mg bid for 30 days.  Children less  than  8
years  of  age  should  be treated with amoxicillin 20 mg/kg a day in divided
doses for 20 days.  Pregnant women  should be treated with amoxicillin 500 mg
qid for 30 days.  If allergic to penicillin erythromycin 250 mg  tid  for  20
days  may  be  used, but is somewhat less effective.  If the patient does not
respond to the above therapy, IV ceftriaxone  2  grams per day for 14 days or
penicillin G 20 million units/day for 14 days may be  given.   HIV  can  also
cause  a  monoarthritis  or  oligoarthritis.   It  may be caused by the virus
itself or be secondary to immunosuppression and involvement with organisms as
atypical mycobacteria, Sporothrix schenckii and  S. aureus.  There also is an
increased frequency of Reiter's syundrome  and  psoriatic  arthritis  in  HIV
disease.   Hepatitis  B, rubella, arbovirus, adenovirus, varicella-zoster and
infectious  mononucleosis  have  all  bee  associated  with  arthralgias  and
arthritis.  The involvement,  however,  is  usually  polyarticular and acute.
PSEUDOGOUT: Pseudogout is also  known  as  calcium  pyrophosphate  deposition
disease.  Attacks of this usually are monoarticular and intermittent that can
last for several days to weeks.  The knee is the most common joint with other
large   joints   being   affected   such   as  the  wrist.   Even  the  first
mdetatarsophalangeal  joint  may  be  affected  simulating  gout.   When  the
inflammation recurs it is often in  the  same  joint.  More than one joint is
involved in about 10% of cases.  Pseudogout affect middle  aged  and  elderly
patients.   Fever may be present during the symptomatic episodes.  Sepsis may
co-exist with pseudogout.  The episodes  may  be punctuated with surgery such
as parathyroidectomy or trauma.  Other metabolic causes are  hemochromatosis,
hypomagnesemia,  acromegaly, hyperparathyroidism and hypothyroidism.  Calcium
pyrophosphate crystals are rod  shaped  and  are weakly positive birefringent
when seen with a polarizing lens.  X-rays may reveal calcium in the cartilage
and is known as chondrocalcinosis.  They are typically seen in  the  meniscal
cartilage  of  the  knee,  the  radiocarpal  joint of the wrist and the pubic
symphysis.  Treatment  of  pseudogout  is  with nonsteroidal antiinflammatory
agents as indomethacin and aspiration  of  the  joint.   Some  patients  will
respoond to IV colchicine.  GOUT: Gout typically affects the first metatarsal
joint,  ankle or knee.  Men and postmenopausal women are frequently affected.
The episodes develop acutely with  joint  swelling, erythema and severe pain.
The disease may simulate cellulitis of the joint.  Fever and leukocytosis may
be present.  Check for a history of alcohol use, diuretic  therapy,  previous
episodes  of  gout  and  provoking stress such as recent surgery.  Polarizing
microscopy should be done to seek out the monosodium urate crystals which are
seen in the leukocytes of the synovial fluid or outside the leukocytes.  They
are strongly negatively biregringent with a red compensator.  X-rays and uric
acid levels are not useful.  The  uric  acid  may be low, normal or high.  If
the patient has a history of chronic gout, x-rays may  show  calcified  tophi
and punched out lesions.  Treatment is with non steroidal antiinflammatories.
Indomethacin  may  be  given as 50 mg tid.  If this therapy is only partially
effective ACTH  or  or  steroids  may  increase  the efficacy.  HEMARTHROSIS:
Hemarthrosis is usually  secondary  to  a  congential  or  acquired  clotting
abnormality  such as hemophilia or patients on anticoagulant therapy.  It may
also occur from trauma and in  a neuropathic joint.  It must be distinguished
from a traumatic tap.  Pigmented villonodular synovitis is an indication  for
a  synovial  biopsy.   SYSTEMIC  DISEASES:  Systemic  diseases  can  cause  a
monoarthritis, but should really only be considered after the above have been
excluded.    Reiter's   syndrome,  Psoriatic  arthritis,  inflammatory  bowel
disease,  sarcoidosis,  serum  sickness,  hyperlipidemia,  cancer, hepatitis,
rheumatoid arthritis, systemic and lupus erythematosus may all rarely present
as a monoarthritis.  In summary, if the patient is not immunocompromised,  he
or she should be treated for streptococci and Staphylococcus aureus infection
if  sepsis  is  suspected.   Ceftriaxone  is  usually employed for gonococcal
arthritis  because  penicillin  resistant  strains  are  increasing.   If the
patient is immunocompromised treat for  gram  negative  and  anaerobes  also.
Closed  drainage  should  be carried out daily as long as fluid persists.  If
this is unsuccessful open  drainage  and  arthroscopic  drainage can be done.
Patients with S. aureus sepsis should be treated for longer periods of  time,
particularly if this infection is superimposed on rheumatoid arthritis.

                       -MONOCLONAL GAMMOPATHY-
Momoclonal gammopathy (MG)  is  characterized  by  a  monoclonal  protein  (M
protein)  in  the  serum  or  the urine.  MG can be seen in several different
diseases and consist of one  or  more  of  the immunoglobulins, a heavy chain
and/or light chain.  If a MG is seen, the patient should have  a  CBC,  serum
protein      electrophoresis,      urinary      protein      electrophoresis,
immunoelectrophoresis,  quantitative immunoglobulins, chemistry profile, bone
survey (x-rays), bone marrow biopsy/aspiration, and beta2-microglobulin.  The
M protein may be IgG, IgA,  IgD,  or IgE.  Patients with these elevations may
have a solitary or extramedullary plasmacytoma, multiple myeloma, amyloidosis
or a monoclonal gammopathy of unknown  significance  (MGUS).   Patients  that
have  an  elevated  IgM  can have Waldenstrom's macroglobulinemia, MGUS, or a
lymphoproliferative disorder.   Most  patients  with  a monoclonal gammopathy
will have MGUS (64%); Multiple myeloma (16%), amyloidosis (8%), non-Hodgkin's
lymphoma  (6%),  chronic  lymphocytic  leukemia   (2%)   and   Waldenstroms's
macroblobulinemia  (2%).   SOLITARY  PLASMACYTOMA  usually presents with no M
component in the serum  or  the  urine.   However,  occasionally it does, and
presents as a single area  of  bone  destruction,  normal  bone  marrow.   It
comprises  5%  of patients with plasma cell disorders.  The diagnosis is made
by examining the  tumor  histologically  and  finding  plasma  cells that are
identical to  those  seen  in  multiple  myeloma.   The  treatment  is  local
radiotherapy  of  4000 rads and is curative in about 30%.  Fifty percent will
be alive at 10 years.  However,  the  disease free interval is only about 20%
because many patients will develop multiple myeloma.  Therefore, all patients
should  be  followed  by  serum  and  urine   protein   electrophoresis   and
immunoelectrophoresis.   EXTRAMEDULLARY PLASMACYTOMA most frequently involves
the upper respiratory tract (nasal  cavity, sinuses, nasopharynx and larynx).
These patients, as  in  solitary  plasmacytoma,  usually  do  not  have  a  M
component  in  the  serum  or  urine.   The bone marrow is not involved as in
multiple myeloma and no lytic lesions  are seen on bone survey.  Treatment is
radiation therapy which is curative in > 50% of patients.   MULTIPLE  MYELOMA
is  characterized  by  >  10%  bone marrow plasma cell infiltration, multiple
osseous lesions, serum M component >  3  g/dl and usually light chains in the
urine > 1 g/24hours.  MGUS is  typical  for  the  absence  multiple  myeloma,
solitary  and  extramedullary plasmacytoma, amyloidosis, macroglobulinemia or
other lymphoprolierative disorders.  It is characterized by a M component < 3
g/dl, (IgG < 3 gm/dl and IgA  <  2.5 gm/dl), no lytic lesions on bone survey,
normal CBC,  normal  blood  chemistries,  normal  levels  of  the  uninvolved
immunoglobulins,  normal  beta 2 microglobulin, and absence of hypercalcemia.
The M component must remain stable  with some time without the development of
features indicative of the other disorders  mentioned  in  the  differential.
MGUS  has  an  incidence  of  10%  in  patients greater than 80 years of age.
Typical  findings  may  include  the  following:  M  component  .3-3.2  g/dl,
immunoelectrophoretic IgG (74%), IgA (10%), and IgM (16%), urinary monoclonal
gammopathy (6%),  and  bone  marrow  plasmacytosis  1-10%.   Over  the years,
multiple    myeloma,    amyloidosis,     macroglobulinaemia     and     other
lymphoproliferative  disease  will develop in about 22%.  Of these, about 68%
of patients  will  develop  multiple  myeloma  in  2-21  years.   Most of the
patients with MGUS will be asymptomatic, but there may be associated problems
such as peripheral neuropathy, renal  disease,  and  immune  hemolysis.   All
patients  should  be followed for transition of the disease.  AMYLOIDOSIS can
be diagnosed with rectal,  skin,  tongue,  and gingival biopsy, and/or needle
fat aspiration of the  abdomen.   Patients  may  present  with  weight  loss,
weakness,   paresthesias,   syncope,  peripheral  neuropathy,  carpal  tunnel
syndrome,  arthralgia,  periorbital   purpura,  macroglossia,  carpal  tunnel
syndrome,  diarrhea  and  malabsorption  syndrome,  orthostatic  hypotension,
nephrotic syndrome, cardiac conduction defects, bleeding in the skin  and  GI
tract,  CHF and ankle edema.  There is no treatment for amyoidosis.  Patients
that present with a  M  component  of  <  3  g/dl associated with significant
adenopathy should have a lymph node biopsy to rule  out  lymphoma,  as  these
patients  frequently  have  an underlying B-cell neoplasm.  Lymph node biopsy
can  be  used  to  exclude  non-Hodgin's  lymphoma  and  chronic  lymphocytic
leukemia.  About 17% of patients with  IgM  MGUS will develop lymphoma with a
median duration from presentation to the development of lymphoma of  4  years
(range  .4-22  years).  Patients with an elevated IgM > 3 g/dl, bone marrow >
10% lymphoplasmacytoid cells, hepatosplenomegaly and hyperviscosity will have
Waldenstrom's macroglobulinemia.  These patients  also have bleeding, blurred
vision, dyspnea, weight loss, paresthesisas, weakness, recurrent  infections,
epistaxis,  fatigue,  lymphadenopathy, and retinal lesions (sausage appearing
lesions).  Rouleaux formation and positive Coombs's  test are common, as is a
normocytic  and  normochromic  anemia.   Hyperviscosity   is   treated   with
plasmapheresis.   About  80%  of patients will respond to chemotherapy with a
median survival of > 3 years.  Chlorambucil is the drug of choice.

                            -MUCORMYCOSIS-
Mucormycosisis is caused by fungal  species  of Rhizopus, Mucor, and Absidia.
In humans these organism appear as mycelia which are nonseptated hyphae  that
branch  at  90  degrees.   They  grow  in most routine culture media, and the
genera can be differentiated well on  Sabouraud's glucose agar at 37 degrees.
They stain well  with  hematoxylin  and  periodic  acid-Schiff  preparations.
Mucormycosis is ubiquitous and found in soil, manure, fruits high in glucose,
and  decaying vegetation world wide.  Characteristically, disease is acquired
by inhalation of the fungal spores which results in invasion of blood vessels
leading to infarction and  necrosis.   Person-to-person transmission does not
occur.  It has similar pathological features as aspergillosis.   Mucormycosis
is  a  rare  infection  and  depends  on  patients that are immunosuppressed,
patients with malignant hematologic  disorders, profound granulocytopenia and
diabetics.   There  are  5  major  forms  of  the  disease   which   includes
rhinocerebral, pulmonary, disseminated, gastrointestinal and localized forms.
The  rhinocerebral  syndrome usually occurs in patients with ketoacidosis and
those on corticosteroids.  The patients  may present with ocular pain, facial
pain or numbness, bloody nose, nasal stuffiness, diplopia,  loss  of  vision,
sinusitis,  and  altered  consciousness.   Direct  examination  of  the nasal
tissues will  reveal  ulcerating  lesions  with  areas  of  central necrosis.
Radiographic studies of the sinuses will reveal  nodular  mucosal  thickening
without  air  fluid levels, and spotty destruction of the bony walls.  As the
disease advances there is a predilection to invade the deep tissues extending
into the orbit where it causes impaired ocular movement, proptosis, chemosis,
diplopia, and blindness.  Following  this,  if the disease becomes unchecked,
there is invasion into the frontal lobe and the  cavernous  sinus  which  can
lead  to  death.   The differential diagnosis includes suppurative sinusitis,
septic cavernous thrombosis or  other  bacterial  or fungal infections of the
palatal area which are capable of producing necrotic  black  lesions  of  the
palate  and  nasal  mucosal.   Organisms  capable of this include Aspergillus
niger, Pseudomonas aeruginosa, and Petriella boydii.  Sinus films are usually
normal with these organisms.  Patients  that have septic cavernous thrombosis
have deep ocular pain initially with  conjunctival  and  lid  edema,  orbital
congestion,  exophthalmus  and  visual  loss.  PULMONARY MUCORMYCOSIS usually
occurs in patients with  hematologic  malignancies, those on myelosuppressive
chemotherapy  or  high  dose  glucocorticostetroids,  renal  transplantation,
diabetics, and those in renal insufficiency.  Chest x-ray will reveal  patchy
infiltrates,  bronchopneumonia,  nodules,  and  cavitation.  GASTROINTESTINAL
MUCORMYCOSIS  occurs  in   those   with  malnutrition,  uremia,  kwashiorkor,
amebiasis and those with typhoid.  They will  present  with  abdominal  pain,
bloody  diarrhea and vomiting.  There may be signs of intestinal obstruction.
Ulceration typically occurs in the terminal  ileum and the colon resulting in
thrombosis and gangrene.  LOCALIZED MURCOMYCOSIS  can  occur  in  those  with
burns,  contaminated  elastic  bandages with Rhizopus, wounds, and prosthetic
vascular  graft  infections.    Presentation	is   usually   with  a  rash.
DISSEMINATED MUCORMYCOSIS  occurs  as  a  complication  of  pulmonary  or  GI
mucormycosis.   Occasionally  it  may be precipitated by burns, and drug use.
Central nervous system involvement is  common  and  there may be skin lesions
that resemble ecthyma gangrenosum.  LABORATORY: Sputum cultures are  positive
in  only about 10-40% of invasive infections.  In the rhinocerebral form, the
CSF may demonstrate up to  500  white  cells  with equal numbers of polys and
mononuclear leukocytes.  Protein is increased  and  the  glucose  is  usually
elevated  reflecting the underlying hyperglycemia from diabetic ketoacidosis.
A low glucose is very rare.  Red  cells  are common.  Cultures of the CSF and
hyphae are usually always negative.  Tomographic studies and  CT  scans  will
demonstrate the bony involvement of the sinuses.  Carotid angiograms may show
filling  defects,  aneurysms,  occlusion  or evidence of emboli.  In order to
diagnose mucomycosis,  biopsy  is  necessary,  which  will  reveal the hyphae
invading the blood vessels and causing hemorrhagic thrombosis and infarction.
Serologic and skin tests are not available.   Bronchoscopy  and  percutaneous
needle  aspiration  biopsy  will  be  needed  to diagnosis invasive pulmonary
mucormycosis.  TREATMENT:  Amphotericin  B  is  the  drug  of choice, usually
giving a total dose  of  30-40  mg/kg  given  over  2-3  months.   Adjunctive
surgical  debridement  will  be  necessary  also.   The  mortality with these
measures may still be 30-50%.

                         -MULTIPLE MYELOMA-
Multiple myeloma is an abnormal  proliferation of transformed plasma cells in
the bone marrow that are capable of secreting an M-protein that  can  replace
the  bone  marrow with production of anemia, and also incite bone destruction
with bone pain, osteoporosis,  lytic  lesions  and pathologic fractures.  The
incidence of myeloma is estimated at 2 to 3 per  100,000  persons.   Men  and
women  are  affected  equally  and  the  median  age is 60 years of age.  The
incidence increases  with  age.   There  is  a  higher  incidence  in blacks.
CLINICAL: Any elderly anemic patient that complains of back pain or rib  pain
should  be suspect for Multiple Myeloma.  A normocytic normochromic anemia is
present in almost all patients  as  a consequence of tumor related inhibition
of erythropoiesis and bone marrow crowding.  There may be a shortening of red
cell survival, iron deficiency and blood loss.   If  the  patient's  multiple
myeloma  is  treated  the  anemia will improve.  Myeloma cells are capable of
elaborating osteoclast activating  factors  which causes osteoclastic induced
osteoporosis and lytic lesions.  Pain can be the presenting symptom  in  over
70%  of  patients.  The pain in the back and thoracic area is unlike the pain
of metastatic carcinoma which is worse at night.  The pain of myeloma is made
worse by movement.  If there is sustained pain this may indicate a pathologic
fracture.   Patients  with  multiple  myeloma  are  susceptible  to increased
infections usually involving  the  lungs  and  kidneys.   The  most  frequent
bacteria  causing  pyelonephritis  are  Escherichia  coli  and  gram negative
organisms.  Pneumonias  are  caused  by  Staphylococcus aureus, Streptococcus
pneumoniae  and  Klebsiella  pneumoniae.   The  presenting  symptom  may   be
recurrent  pneumonias  which  is  a tip off as to the etiology.  Pneumococcal
vaccine may be some benefit.  Renal  failure  occurs in about 1/5 of patients
and is due to to a combination of L chains, uric acid, infection, calcium and
amyloid.  Calcium nephropathy may be the most common cause  but  Bence  Jones
proteinuria   is   important.    Hypercalcemia   as  a  result  of  increased
osteoclastic  activity  in  bone  can   cause  symptoms  as  confusion,  etc.
Hyperviscosity  may  cause  mucosal  bleeding,  visual  disturbances,  mental
alterations and vertigo.  However, these symptoms are  less  common  than  in
Waldenstrom's  macroglobulinemia.   Coagulopathies,  by binding of factors I,
II, V, VII, or VIII with  the  M-protein, may occur.  Spinal cord compression
may occur in conjunction  with  the  lytic  bone  lesions  producing  typical
symptomatology.   LABORATORY:  Patients  almost  always  have  a normochromic
normocytic anemia.  Patients suspected of  myeloma should have both serum and
urine   protein   electrophoresis   (24   hour   quantitative   urine)    and
immunoelectrophoresis evaluated.  Most patients (80%) will have a paraprotein
M  spike  in  the  beta  or  gamma  globulin  region  of  the  serum  protein
electrophoresis.   If  there  is  no  evidence of the spike on serum then the
urine protein and  immunoelectrophoresis  will  demonstrate either a complete
immunoglobulin or light chains, and the serum  protein  electrophoresis  will
demonstrate  a  hypogammaglobulinemia.   Sixty  percent  of  multiple myeloma
patients will have an IgG paraprotein, 25%  an IgA and 15% light chains only.
Just finding a spike does not make a diagnosis of  multiple  myeloma  as  the
spike  may  represent a benign monoclonal gammopathy (( monoclonal gammopathy
of  unknown  significance  (MGUS)),   or   a   spike  produced  by  malignant
lymphoproliferative  diseases   as   lymphomas,   primary   amyloidosis   and
Waldenstrom's  macroglobulinemia.   Most patients with MGUS have a monoclonal
IgG spike of less than 2.5 g/dL  and  the height of the spike remains stable.
Most patients that have an IgG spike greater than 3.5 g/dL have  myeloma  and
an  IgA  spike  of  greater  than  2 g/dL is usually due to multiple myeloma.
Dipstick determinations of protein are  useless  in detecting the Bence Jones
protein, but sulfosalicylic acid and toluene sulfonic acid  can  be  used  as
screening  tests.  Bone marrow exam usually shows increased numbers of plasma
cells at various stages of maturation  numbering  from 5% to 100%.  Sheets or
clusters of plasma cells may occur, but myeloma is a  patchy  disease.   Bone
scans  are  of  no  help  as  the  lesions  are  osteolytic.   The Westergren
sedimentation rate is often elevated to  levels above 100 mm/h.  The BUN, and
creatinine may be elevated if there is renal involvement.  The uric acid  may
be  elevated  along  with  the calcium.  There may be a low anion gap and the
beta-2 microglobulin is usually  elevated  which  may reflect the myelomatous
burden.   TREATMENT:  The  patient  may  be  treated  with  Melphalan   given
intermittently at 0.25 mg/kg/day for 4 days q 4-6 weeks or continuously, 0.09
to  0.14  mg/kg/day for 8-10 days followed by 0.03 mg/kg/day for maintenance.
Prednisone is usually given with  this,  intermittently, at 1 mg/kg/day for 4
days q 6 weeks.  This protocol will result in an objective response in  about
60%  of  patients.   The  dose  will  have  to  be titrated as leukopenia and
thrombocytopenia will develop.   Bone  marrow transplantation is experimental
in young persons.  If there is hypercalcemia between 10.5 and 12  mg/dl  then
hydration  with  IV saline and furosemide can be given.  If renal function is
normal  and  there  is  no  hyperphosphatemia  then  oral  bisphosphonates as
etidronate may be used.  Calcium levels greater than  12  usually  need  more
aggressive  treatment with hydration, IV etidronate or pamidronate or gallium
nitrate and calcitonin.  The patient  should  avoid immobilization as much as
possible.  For localized pain that does not respond to  chemotherapy  and  is
intractable, low dose palliative radiation may be given.  Also, patients with
impending  or pathologic fractures should have these fractures stabilized and
tumor removed.  If there is  back  pain and tenderness, and neuropathies then
the possibility of cord compression must be entertained.  MRI and myelography
will aid in the diagnosis.  If cord compression is found, emergency radiation
and steroids should be given.  Patients may have permanent paralysis if there
is a delay in the diagnosis greater than 12 hours.  Plasmapheresis should  be
used  for  reducing  the  serum  viscosity.   This  will  rapidly reverse the
bleeding  and  neurologic  abnormalities.   PROGNOSIS:  With  treatment, many
patients will survive for greater than  5  years.   Before  chemotherapy  was
available  patients survived for less than 1 year.  For those that do relapse
or do not respond to  conventional  chemotherapy a trial of VAD (vincristine,
adriamycin  and  dexamethasone)  or   BCNU   (cyclophosphamide,   carmustine,
vincristine and prednisone) may be given.

                        -MULTIPLE SCLEROSIS-
Multiple  Sclerosis (MS) is a slowly progressing demyelinating disease of the
young, involving the white  matter  of  the  brain  and  spinal cord, that is
characterized by remissions and exacerbations.  Any young female between  the
ages  of  16  and  40  who  develops  paresthesiae  in  one  or  more  of the
extremities,  trunk  or  face,  clumsiness  of  a  leg  or  hand,  or  visual
disturbances  such  as  diplopia,  dimness  of  vision,  scotomas  or partial
blindness, should be suspected  of  having  MS.   Histologically,  there  are
characteristic  sclerotic  plaques  that occur throughout the white matter of
the brain and  spinal  cord.   The  plaques  are  areas of demyelination with
oligodendrocytic and  glial  cell  proliferation.   The  neurons,  axons  and
vascular  structures  are  relatively  spared.  Up to 20% of MS patients will
have another relative with the disease.   The  disease peaks in the third and
fourth decades and northern European  descent  have  a  higher  incidence  of
disease  than  Blacks  or  Asians.  The cause is unknown but several theories
have evolved.  One is the autoimmune theory which is supported by immunocytes
in the plaques, changes in  the  peripheral blood immunocytes, the hereditary
pattern, and HLA linkage.  The second theory is the  viral  theory  which  is
supported  by  the  higher  incidence  of  the  disease  at higher latitudes,
geographical clusters, animal studies  of  infectious diseases of myelin, and
clusters of cases within families.  The third theory is that there may be  an
environmental  exposure to a toxin or virus in early life which might trigger
an autoimmune disorder.  CLINICAL:  Exacerbations  of the disease occur.  The
length between the exacerbations  may  be  months  or  years  initially,  but
usually  shorten  as  the  disease progresses.  The episodes last at least 24
hours.  The behavior and course  of  the disease is unpredictable.  About 20%
will have little difficulty with infrequent exacerbations.   About  25%  will
have  more  frequent  relapses  and a mild to moderate disability.  About 40%
have frequent exacerbations, and about  15% will have a sustained progressive
deterioration.  VISUAL DISTURBANCES: About 50% will  develop  optic  neuritis
with  acute  loss  of  visual  acuity.   There  may be double vision, blurred
vision, loss of vision in a  single  eye  and ocular paralysis.  There may be
partial optic nerve atrophy with temporal pallor, and changes in  the  visual
fields  with  central  scotoma, transient ohthalmoplegia with diplopia due to
internuclear involvement of the 3,4  and  6th nerve nuclei.  Nystagmus may be
present and is caused by cerebellar or vestibular  nucleus  damage.   Seventy
percent  of women who develop optic neuritis will eventually develop MS up to
15 years later.  This happens  in  about  34%  of men.  MOTOR SYMPTOMS: Motor
symptoms consist of  clumsiness,  dysarthria,  hand  paralysis,  hemiparesis,
incoordination,  clonus,  spasticity, weakness and flexor spasms of the legs.
Deep tendon reflexes are  increased  and  there  may  be a positive Babinski.
Superficial  reflexes  of  the  upper  and  lower  abdomen  are   diminished.
Cerebellar  lesions  may  cause  an intention tremor, ataxia or vertigo.  The
patient may have  a  drunken  gait  due  to  involvement of the corticospinal
tracts.  There may be scanning speech characterized by very slow  enunciation
with  hesitation  at  the  beginning of a word or syllable.  This is due to a
cerebellar   lesion.    SENSORY   DISTURBANCES:   There   may   be  numbness,
paresthesiae, hyperesthesia and disturbance of vibratory and  position  sense
of  the  hands  or  legs.   Trigeminal  neuralgia  may  develop.   AUTONOMIC:
Involvement  of  the  autonomic pathways may produce urinary incontinence and
urgency, fecal incontinence  or  urgency,  constipation and impotence.  OTHER
SYMPTOMS: Fatigue may be very prominent.  Cognitive changes  include  apathy,
lack  of  judgment,  emotional  lability  with periods of euphoria mixed with
depression.  There may be weeping or laughter.  Seizures have been noticed in
about 1-8% of cases.  These may be preceded by sensory symptoms.  Lhermitte's
sign is an electric  sensation  that  radiates  down the spine or extremities
when the neck  is  flexed.   LABORATORY:  Evoked  potentials  are  electrical
responses  to  simulation  of  a sensory system.  Visual evoked responses are
abnormal in 75-97%.  Somatosensory  evoked  potentials are abnormal in 72-96%
of cases.  Brain stem auditory-evoked responses are  abnormal  in  57-65%  of
cases.  There is an approximate 10% false negative brainstem evoked potential
in  early  MS.  MRI changes are found in 85-90% of cases of MS.  There may be
some false positives.  The  characteristic  plaques  are  seen as high signal
intensity lesions of the white matter on T2 weighted studies.  CT scanning is
not  as  sensitive.   In  patients  presenting  with  myelopathy  an  MRI  or
myelography may be useful in excluding a congenital lesion and  in  examining
the  foramen  magnum  region  to  rule  out  the possibility of Arnold-Chiari
malformation.  In this condition there is  a downward herniation of the lower
brain stem and cerebellum into the cervical canal which may produce pyramidal
and cerebellar symptoms which can simulate multiple sclerosis.  CSF: CSF  may
show  oligoclonal  bands  in 90-98% of cases.  These are non-specific as they
can be found  is  several  neurological  diseases.   Myelin  basic protein is
common in the CSF  (90%),  and  also  can  be  found  in  several  neurologic
disorders.   There  also  may be elevated IgG > 13% or an elevated IgG index.
There can be an abnormal  colloidal  gold curve, mild mononuclear pleocytosis
of less than 40 cell/mL.  The protein  is  normal  or  slightly  elevated  to
between  50-100  mg/100  mL.   There  is  a  negative  serology for syphilis.
DIFFERENTIAL DIAGNOSIS: Vasculitis of  the  small  vessels  of the CNS may be
confused  with  multiple  sclerosis.   These   would   include   sarcoidosis,
meningovascular  form  of  syphilis,  SLE, polyarteritis nodosa, and Behcet's
disease.   Multiple  small  strokes  may  simulate  MS.   Amyotrophic lateral
sclerosis, pernicious anemia, brain stem tumors, CNS  infections,  cerebellar
tumors,     leukodystrophies,     spinal    cord    tumors,    syringomyelia,
neurofibromatosis, Friedreich's and hereditary  ataxias  would all have to be
ruled out.  TREATMENT: There is no definite treatment for multiple sclerosis.
Therefore, treatment of the symptoms is given.  The tremor and ataxia may  be
treated  with  Clonazepam  (Klonopin),  Primidone  (Mysoline), or Propranolol
Inderal).  The vertigo  may  respond  to  Scopolamine  transdermal patches or
Meclizine.  The pain  and  dysesthesia  can  be  treated  with  Carbamazepine
(Tegretol),  Amitriptyline  or  nortriptyline and Clonazepam (Klonopin).  The
urinary incontinence and urgency can be treated with Oxybutynin (Ditropan) or
Propantheline (Pro-Banthine).  If the  patient  has  a large flaccid bladder,
then Bethanechol (Urecholine) may be useful.  Fatigue has been  treated  with
Amantadine  (Symmetrel) or Pemoline (Cylert).  Spasticity can be treated with
Diazepam (Valium), Baclofen (Lioresal), Clonazepam (Klonopin), or Dantrolene.
Immunomodulating therapy may  be  used  and  would  consist  of prednisone 60
mg/day or methylprednisolone  IV  500mg  for  5-7  days  for  acute  attacks,
especially in retrobulbar neuritis.

                        -MULTIPLE SCLEROSIS-
Usually occurs between 20-40 years  of  age.   Common symptoms are blurred or
reduced  vision,  usually  in  one  eye,  ataxia,  double  vision,   fatigue,
constipation,  impotence,  loss  of balance, paresthesias, loss of bladder or
bowel control, spasticity,  slurred  or  slow  speech,  paresthesias, loss of
sensation in the arms and legs, tic like facial pain, vertigo,  weakness  and
tremor.  Particularly watch for trigeminal neuralgia in a young person, optic
neuritis  and  an  isolated useless hand, all do to demyelination.  There may
also be an electric shock  sensation  down  the  spine on flexion of the neck
(Lhermitte's sign).  Internuclear ophthalmoplegia (have patient look  to  the
right  or left.  The abducting eye shows nystagmus and the adducting eye will
not cross the midline) may  be  present.   There  may be a Marcus-Gunn pupil.
CSF will show an elevation of immunoglobulin G (IgG) with 80-90% of  patients
showing  oligoclonal  bands on electrophoresis.  Typically there are no white
blood cells and normal protein in the CSF.  Visual, auditory or somatosensory
evoked response testing may show  slowed  conduction.  MRI is also useful for
diagnosis.  In general, patients with primarily sensory symptoms as numbness,
dizziness, visual blurring and tingling do better than those  with  motor  or
cerebellar  problems.   A  poor  prognosis  may  be  suggested  with  ataxia,
decreased  cognition,  and  weakness  of the lower extremities.  Twenty years
after diagnosis, about 66% remain ambulatory.   About 50% will live more than
35 years after the diagnosis.  The  average  life  span  is  only  5-7  years
shorter  than  people without the disease.  Acute attacks may be treated with
methylprednisolone 1  g  IV  q24h  for  3-5  days  and  will shorten attacks.
Following this pulse therapy, the prednisone is decreased over  a  one  month
period.  Only use this therapy if there is significant impairment of walking,
dressing, coordination, feeding and grooming.

                 -MURMURS AND DIAGNOSTIC MANEUVERS-
AORTIC STENOSIS: standing  and  squatting  produce  no  change in the murmur.
Handgrip, valsalva (5-6 beats into the strain) will both decrease the murmur.
Valsalva (5-6 beats after release) will increase the  murmur.   Amyl  nitrate
and  post-extra  systolic  beats  will  increase  the  murmur.   HYPERTROPHIC
CARDIOMYOPATHY:  Standing,  amyl nitrate and valsalva (5-6 beats into strain)
will both increase  the  murmur.   Squatting,  handgrip,  valsalva (5-6 beats
after release) will decrease the murmur.  MITRAL  VALVE  PROLAPSE:  standing,
amyl  nitrate,  valsalva (5-6 beats into strain) will increase the murmur and
move the click earlier.   Squatting  will  decrease  the  murmur and move the
click later.  Handgrip, post-extra systolic beats, valsalva (5-6 beats  after
release)  will  move  the  click  later.   MITRAL  REGURGITATION:  Squatting,
handgrip  and  valsalva  (5-6  beats after release) will increase the murmur.
Amyl nitrate and  valsalva  (5-6  beats  into  the  strain) will decrease the
murmur.  No change  with  post  extra  systolic  beats.   PULMONIC  STENOSIS:
Inspiration, post extra systolic beats and valsalva (5-6 beats after release)
will  increase the murmur.  Standing and valsalva (5-6 beats into the strain)
will decrease the murmur.   VSD  (small):  squatting, handgrip, valsalva (5-6
beats after release) will increase the murmur.  Amy  nitrate,  valsalva  (5-6
beats   into   strain)  will  decrease  the  murmur.   AORTIC  REGURGITATION:
Squatting, handgrip and valsalva (5-6  beats after release) will increase the
murmur.  Amyl nitrate, valsalva (5-6 beats into  strain)  will  decrease  the
murmur.  MITRAL STENOSIS: Squatting, amyl nitrate, handgrip and valsalva (5-6
beats  after release) will increase the murmur.  Valsalva (5-6 beats into the
strain) will decrease  the  murmur.   PULMONARY  REGURGITATION: Valsalva (5-6
beats after release) will increase the murmur.  Amyl nitrate,  valsalva  (5-6
beats into the strain) will decrease the murmur.

                         -MUSHROOM POISONING-
Severe mushroom poisoning in the USA is rare with an average of about 200-350
cases reported annually.  Of these, there may be 50  deaths/year.   Poisoning
is  more  common in the spring, summer and fall, and children are affected in
about 50% of all cases.  There  are  more than 5000 varieties of mushrooms in
the USA, but only about 100 account for severe toxicity.  Most cases  produce
only  a  self  limited  form of gastroenteritis that may be mild to moderate.
There are about 500 species  of  mushrooms,  of which only 10 are potentially
fatal if ingested.   The  most  dangerous  species  are  Amanita  phalloides,
Amanita  verna, Aminita virosa, Gyrometra esculenta and the Galerina species,
all of which elaborate amatoxin.  AMANITA PHALLOIDES, A. OCREATA, A. VERNA, A
VIROSA, and some LEPIOTA and GALERINA  species: These mushrooms have a latent
interval of about 6-12 hours before symptoms begin.  Common symptoms  include
vomiting,  abdominal  cramps,  profuse  diarrhea,  bloody vomitus and stools,
followed within 24  hours  by  hepatic  necrosis,  hepatic encephalopathy and
renal failure.  Liver transaminases  are  often  greater  than  10,000  units
initially,  but  then  fall  rapidly  as  the  bilirubin and prothrombin time
increase.  Fatality can  occur  in  30-50%  of  ingestions.  The symptoms are
caused by amatoxins.  The amatoxins are among the most potent  toxins  known.
The  minimum  lethal  dose is about 0.1 mg/kg and one Amanita cap can contain
10-15 mg.  Galerina species contain much  less toxin, and it would take about
15-20 caps to produce a fatality in an adult.  Early  death  can  be  due  to
massive  fluid  loss  from  the  gastroenteritis, while later death is due to
hepatic failure.  The Meixner test  can  detect  the presence of amatoxins in
mushrooms that  are  brought  in.   In  this  test  a  drop  of  concentrated
hydrochloric  acid is added to the dried juice from the mushroom cap that has
been dripped onto newspaper or other unrefined paper.  The presence of a blue
color is  suggestive  of  amatoxins.   Treatment  is  largely supportive with
replacement of fluids, electrolytes and glucose for hypoglycemia.  Monitoring
of the central venous pressure or pulmonary artery pressure may  be  helpful.
Orthotopic  liver  transplantation is lifesaving in those with severe hepatic
encephalopathy.   Hemoperfusion  may   be   useful  in  removing  the  toxin.
GYROMETRA (HELVELLA) ESCULENTA species: Symptoms are due to  the  elaboration
of  gyromitrin  which is converted in vivo to monomethylhydrazine toxin which
produces    diarrhea,     vomiting,     seizures,     weakness,    hemolysis,
methemoglobinemia, and hepatitis.  Symptoms usually occur after 8-12 hours of
ingestion.  Less  than  10%  of  ingestions  are  fatal.   Treatment  of  the
neurologic   symptoms  such  as  convulsions  and  coma  is  with  pyridoxine
hydrochloride given  IV  at  25  mg/kg.   Methemoglobinemia  is  treated with
methylene  blue  1  mg/kg  IV.   AMANITA  MUSCARIA,  A.  PANTHERINA   produce
anticholinergic  symptoms  such  as  flushed skin, excitement, incoodination,
dizziness, dilated  pupils,  hallucinations,  muscular  jerking, tremors, and
delirum that begins about 1-2 hours after ingestion.  The  toxins  elaborated
are  ibotenic  acid  and muscimol.  CLITOCYBE DEALBATA, C. CERUSATA, INOCYBE,
OMPHALOTUS OLEARIUS produces a cholingergic toxidrome consisting of sweating,
bradycardia,  hypotension,  abdominal   cramping,  salivation,  bronchospasm,
lacrimation, diarrhea, vomiting and miosis after about 1-2  hours.   Symptoms
usually  resolve withing 24 hours.  Severe cases can be fatal and are treated
with atropine sulfate 1-2 mg every  2-6 hours, titrated against the symptoms.
Muscarine is the offending toxin.  COPRINUS ARMAMENTARIUS, CLITOCYBE CLAVIPES
producea a disulfiram-like syndrome with alcohol that may persist  for  days.
Symptoms  include  flushing,  vomiting  and  hypotension  after  ingestion of
alcohol.  Treatement is supportive  and  abstinence  from alcohol for about 4
days.  PSILOCYBE AND PANAEOLUS  species  produce  a  hallucinogenic  syndrome
which  is usually visual, along with nausea, vomiting, hyperkinetic activity,
muscle  weakness  and  mydriasis  that  occurs  1-2  hours  after  ingestion.
Fatalities  are  rare.   The  toxins  are  psilocybin,  psilocin  and related
indoles.  Treatment is supportive with diazepam for  agitation.   CORTINARIUS
ORELLANUS  produces tubulointerstitial nephritis and acute renal failure from
the toxin orellanine after an  incubation  period of 1-12 days.  Treatment is
supportive.  Hemodialysis may be needed for renal failure.

                         -MYASTHENIA GRAVIS-
Myasthenia gravis is due to  an  antibody mediated autoimmune disease against
the acetylcholine receptors at the neuromuscular junctions.  These antibodies
will reduce the quantitiy of functioning acetylcholine receptors.   Moreover,
cellular  immune  activity  against  the receptor is also found.  Clinically,
this translates into weakness  with repeated activity and improvement	with
rest.  The  external  ocular  muscles,  facial,  pharyngeal  and  masticatory
muscles   are   frequently   involved  with  occasional  involvement  of  the
respiratory and limb muscles.  It occurs at  all ages and has a prevalence of
50-125 cases per million population or about 25,000 affected persons  in  the
USA.   It is most common in young women with HLA-DR3.  However, if associated
with  thymoma,  older  men  are  more  commonly  involved.   It  is sometimes
associated with thyrotoxicosis, rheumatoid arthritis and lupus erythematosus.
Women have a peak incidence in the second  and  third  decades  and  men  are
affected  in  the  sixth and seventh decade.  The onset is usually insidious,
but may be brought on by an  infection, just prior to menstruation and during
or just after pregnancy.  CLINICAL:  Many  patients  present  with  diplopia,
ptosis,  difficulty  in  chewing  or  swallowing,  and  weakness  of limb and
respiratory muscles.   These  difficulties  may  intermittently  come and go.
There also may be diurnal fluctuations in the intensity of the symptoms,  but
inexorably   progresses  to  respiratory  complications  such  as  aspiration
pneumonia.  The ocular palsies and  ptosis  are commonly asymmetrical and the
weakness may remain localized to the extraocular and eyelid muscles in  about
15%  of  patients.  The patient may have difficulty in swallowing and chewing
and may have nasal speech.  Generalized weakness will develop in about 85% of
patients.  The neck extensors may  be  involved  and the proximal muscles are
usually involved if the limb muscles  are  affected.   There  are  no  reflex
changes and sensation is intact.  DIFFERENTIAL DIAGNOSIS: Botulism produces a
generalized  weakness  with  ophthalmoplegia and dilated pupils.  There is an
incremental response on  repetititive  nerve  stimulation.  The Lambert-Eaton
syndrome  produces  areflexia,  fatigue  and  weakness  and  about  60%   are
associated  with  oat  cell cancer.  There is an antibody to calcium channels
present,  and  there  is   an   incremental   response  on  repetitive  nerve
stimulation.  Aminoglycosides, quinine, procainamide  and  curare  can  cause
weakness in the normal person and also exacerbate myasthenia, but recovery is
usually  seen  when  the  drug  is  discontinued.  Hyperthyroidism produces a
generalized weakness and can make myasthenia worse.  Grave's disease produces
a diplopia and exophthalmos.   Penicillamine can induce autoimmune myasthenia
with  recovery  taking  place  weeks  after   the   drug   is   discontinued.
Intracranial  masses  can  compress the cranial nerves causing ophthaloplegia
and  cranial  nerve  weakness.   These  can  be  detected  with  MRI  and CT.
Progressive  external   ophthalmoplegia   produces   ptosis,   diplopia   and
generalized  weakness,  but  mitochondrial abnormalities are usually present.
LABORATORY: Patients should have testing for SLE (ANA), rheumatoid factor and
antithyroid antibodies.  Chest MRI or  CT  should be done of the mediastinium
along with chest x-ray for detection of thymoma.  Pulmonary function testing,
glucose, TB test, thyroid function  tests  and  bone  densitometry  in  older
patients, all should be done.  Serum acetylcholine receptor antibodies should
be  determined as they have a sensitivity of 80-90%.  However, if the patient
only has involvement of  the  ocular  muscles,  the sensitivity is reduced to
50%.  The test is done by radioimmunoassay using detergent solubilized  human
acetylcholine  receptor  labeled  with  [125I]alpha-bungarotoxin.  Repetitive
nerve stimulation is  done  at  a  rate  of  3/sec  and action potentials are
recorded from surface electrodes over the muscle.  A rapid reduction  in  the
amplitude of the evoked muscle action potential (decremental response of 15%)
is a positive response.  Single fiber electromyography will detect delayed or
failed neuromuscular transmission in pairs of muscle fibers that are supplied
by  branches of a single nerve fiber.  The diagnosis can usually be confirmed
by using edromphonium (Tensilon) IV in  a  dose  of  10 mg (1 ml).  Two mg is
given IV initially, with the remaining 8 mg given in about 30 seconds if  the
test  is  tolerated.   If  the patient has myasthenia gravis there will be an
improvement  in  muscle  strength  which  will  last  for  about  5  minutes.
ASSOCIATED DISORDERS: Thymic  tumors  occur  in  about  12%  in patients with
Myasthenia  gravis.   The  thymus  is  usually  normally  seen  until   about
mid-adult-hood  or the age of 40.  Hyperthyroidsim occurs in about 3-8%.  The
patient may also have  other  autoimmune disorders as thyroiditis, rheumatoid
arthritis,  Grave's  disease,  and  SLE.   Conditions  that  can   exacerbate
myasthenia    gravis    include    occult   infection,   hypothyroidism   and
hyperthyroidism,   and   various   medications   as   antiarrhythmic  agents,
aminoglycosides and quinine.   Diabetes,  tuberculosis,  GI  bleeding,  renal
disease,   osteoporosis,  asthma,  hypertension  and  peptic  ulcer  can  all
interfere with therapy.   TREATMENT:  Anticholinesterase drugs as neostigmine
and pyridostigmine can be used.  Neostigmine is usually given  as  7.5-30  mg
QID  (average  15  mg)  OR  pyridostigmine  30-180  mg  (average  60 mg) QID.
Thymectomy should be considered in  patients  that  are younger than 60 as it
will lead to improvement.  It is preferable to delay thymectomy until puberty
because of the development of the immune system by the thymus.   In  patients
with  pure  ocular  symptoms,  thymectomy  has  also been beneficial.  Thymic
tumors should be  completely  removed  surgically  as  they  are invasive and
spread locally, but do not metastasize.  If it cannot be removed  completely,
or  it  becomes  invasive,  radiation  should  be given postoperatively.  The
mortality rate for thymectomy  with  experienced  surgeons approaches that of
general anesthesia.  Immunosuppresive drugs should not be used preoperatively
because they can increase the risk of infection.  For vital  capacities  <  2
liters,  plasmapheresis  should  be carried out prior to surgery to establish
independent respiration in the post  surgical  period.  The thymic tissue and
related fat is removed via a sternal splitting approach with exploration into
the neck.  Mediastinoscopy with a cervical incision  can  be  done,  but  the
thymus  gland may not be completely removed.  Epidural morphine will decrease
pain  and  not  interfere  with  respiration.   Postoperatively,  the patient
usually does not require as much anticholinesterase  medication,  using  only
about  75%  of  the preoperative dose.  The benefits of thymectomy may not be
realized until months or years  following surgery.  In general, acetylcholine
receptor antibody levels will fall following thymectomy.  For  patients  that
do  not  respond  to  anticholinersterase  drugs, or thymectomy, steroids are
indicated.  Steroids should be started  while  the patient is in the hospital
as  initially  there  may  be  paradoxical  muscle  weakness  which   usually
stabilizes  afer  2-3  weeks.   This  risk  of  exacerbation  is decreased by
starting with low doses of  prednisone  of  15-20  mg daily and increasing by
about 5 mg every 2-3 days until the patient improves, or a total  daily  dose
of  60  mg/day.   Maximal benefit is usually seen after 6-12 months with some
improvement seen as  early  as  2-4  weeks.   After  about  3 months of daily
dosing, an alternate day treatment program can be instituted.  There may need
to be supplementation given on the off days.  The dose is slowly reduced, but
most patients will need some prednisone.  Treatment with azathioprine is also
effective giving 2-3 mg/kg/day (total dose 100-250 mg/day).   It  is  usually
given  in  those  patients  in whom steroids are contraindicated, or in those
patients who have responded incompletely to steroids, or given in conjunction
with steroids to  reduce  the  dose  of  steroids.   About  10%  will have an
idiosyncratic reaction of fever, myalgias and malaise that will  prevent  its
use.   It  also has a slow onset to time of therapeutic effect (3-12 months),
with the maximal effect not until  1-2  years.  The white cell counts must be
monitored to achieve <3500/mm3.   Treatment  with  azathioprine  (Imuran)  is
started  by  giving 50 mg daily for 1 week and if this is tolerated, increase
to 2-3 mg/kg/day.  If allopurinol is used with azathioprine, the azathioprine
must be reduced by as  much  as  75% and monitored frequently.  Most patients
will require life long therapy with azathioprine.  Cyclosporine is also being
used more frequently in myasthenic patients.  Cyclosporine has a faster onset
of action (2-12 weeks) with maximal therapeutic effect at 3-6 months.  It  is
given at 5 mg/kg/day given in 2 divided doses (total dose is 125-200 mg BID).
The  blood  pressure,  serum  creatinine,  BUN and trough plasma cyclosporine
levels should  be  monitored.   The  side  effects  consist  of hypertension,
nephrotoxicity, and  should  not  be  used  in  uncontroled  hypertension  or
pre-existing  renal disease.  Cyclosporine is very expensive.  Plasmapheresis
can be used to stabilize  patients  who  demonstrate myasthenic crisis, or in
those patients planning to have a thymectomy.  Usually 5 exchange  treatments
of  3-4  liters  each  are  performed  over a 2 week period.  The results are
immediate with improvement the same  day as the plasmapheresis.  The results,
however, usually only last a few weeks.   Complications  include  a  risk  of
infection  from the indwelling catheter, hypotenison, and pulmonary embolism.
Intravenous  immune  globulin  may  be   used  for  the  same  situations  as
plasmapheresis is used.  It is given as 400 mg/kg/day for 5 successive  days.
The   improvement   is  slower,  approaching  4-5  days  when  compared  with
plasmapheresis and may be as much as about 73%.  The improvement may last for
weeks to months.  Side  effects  of  immune  globulin include fluid overload,
headache, and renal fialure which is rare.   Immune  globulin  is  also  very
expensive.

                   -MYCOBACTERIUM AVIUM AND AIDS-
Clarithromycin (Biaxin) 1 gm PO  bid  +  rifampin  600  mg PO qd or rifabutin
300-450 mg PO qd + ethambutol 15-25 mg/kg PO qd + Clofazimime 100-300  mg  PO
qd + ciprofloxacin 750 mg PO bid +/- amikacin 7.5 mg/kg IV or IM qd.

                     -MYELODYSPLASTIC SYNDROMES-
In  the  myelodysplastic  syndromes  there  is  impairment  of  maturation of
hematopoietic precursors  that  leads  to  progressive  peripheral cytopenias
which is the result of neoplastic transformation of a  cell  at  a  level  of
differentiation  that  is  close to the hematopoietic stem cell.  Ultimately,
there is a fatal pancytopenia  or  progression  to an acute leukemic disease.
The disease may be seen  after  treatment  of  multiple  myeloma  or  ovarian
carcinoma  with  melphalan,  and  procarbazine  for  Hodgkin's  disease.  The
syndrome usually develops after 3-7 years following chemotherapy.  Some cases
follow exposure to benzene and  irradiation.   It  is  a rare disease with an
incidence of about 1/100,000/year or higher.  The  median  age  of  onset  is
usually  at  around  60  years  of  age, but has been seen in young children.
Symptoms may include fatigue, infection, bruising, bleeding and pallor due to
bone marrow failure.   About  15-20%  will  have  splenomegaly.  Many will be
diagnosed while asymptomatic due to an incidental examination of  the  blood.
The  disease  may  cause  weight  loss,  fever, and debility with an indolent
course.  LABORATORY: The MCV may  be normal or increased and macro-ovalocytes
may be seen in the peripheral blood.  The reticulocytes are decreased.  There
is anemia and the WBC can be normal or  reduced,  usually  with  neutropenia.
The  neutrophiles  may show bilobed nuclei (Pelger-Huet), with a reduction of
granules.  Blasts and promyelocytes may be seen in the peripheral smear.  The
platelet count is normal  or  reduced  with  a  reduction  of granules in the
platelets.  Clonal chromosomal abnormalities are found in 50-75% of  patients
with a loss of part or all of chromosome 7, trisomy 8, isochrome 17, 5q-, and
20q-   being   the  most  common.   The  bone  marrow  is  characteristically
hypercellular with  erythroid  hyperplasia,  and  megalobastic  changes.  The
prussian blue stain  may  show  ringed  sideroblasts.   There  is  usually  a
leftward  shift  of  the  myeloid  series  with variable increases in blasts.
Abnormal or  deficient  granules  may  be  seen.   Dwarf  megakaryocytes with
unilobed nuclei amy be seen.  Myelodysplastic syndromes may be  divided  into
several  different  syndromes.   Refractory  anemia  is characterized by < 5%
marrow blasts, < 1% peripheral blood  blasts, with < 15% ringed sideroblasts,
and monocytes < 1000/ul.  Refractory anemia with ringed sideroblast  has  the
same  profile,  except  the ringed sideroblasts are > 15%.  Refractory anemia
with excess blasts is characterized  by  5-20% marrow blasts, < 5% peripheral
blood blasts,  with  or  without  ringed  sideroblasts  >15%,  and  monocytes
<1000/ul.    Refractory   anemia   with   excess   blasts  in  transition  is
characterized by 20-30% marrow blasts, >  5% peripheral blood blasts, with or
without ringed sideroblasts > 15%, and with or without monocytes  >  1000/ul.
Chronic  myelomonocytic  anemia is characterized by < 20% marrow blasts, < 5%
peripheral blood blasts,  with  or  without  ringed  sideroblasts  > 15%, and
monocytes > 1000/ul.  The myelodysplastic syndrome ultimately is fatal,  with
patients  dying  from  infections  or  bleeding.   It  may transform to acute
myelogenous leukemia.  Patients with myelomonocytic  leukemia or an excess of
blasts have short survivals, usually < 2 years, and  have  a  20-50%  greater
risk  of  developing  an  acute leukemia.  Those who have a particularly poor
prognosis include those with > 10% blasts  in the marrow, platelets < 40 x 10
to the ninth power/L or with granulocytes < 1.0 x 10 to  the  ninth  power/L.
These  patients  will  survive  less  than  one  year.   Also,  deletions  of
chromosomes  5  and 7 have a poor prognosis.  Patients with refractory anemia
can survive many years with a low risk of leukemia less than 10%.  TREATMENT:
Patients that  have  primarily  anemia  are  treated  with  RBC transfusions.
Erythropoietin  can  reduce  the  red  cell  transfusion  in  some  patients.
Patients with severe thrombocytopenia or neutropenia, or  those  with  severe
symptoms can be treated with low dose chemotherapy consisting of subcutaneous
cytosine  arabinoside at 20 mg/m2/day.  This will give a complete response of
about 15%,  but  overall  survival  is  not  altered.   Intensive combination
chemotherapy, similar to that used in acute myelogenous leukemia will  result
in  a complete response of about 30-60%.  Patients only respond for less than
12 months usually and only a few may be cured.  Myeloid growth factors GM-CSF
(sargramostim) and C-CSF (filgastrim) can  elevate the neutrophil count which
will reduce the incidence of infections.  Otherwise, they do not  affect  the
course  of  the disease.  Young patients under the age of 55 are treated with
ablative chemotherapy and allogeneic bone marrow transplantation if a matched
HLA sibling can be found.  Cure rates are typically 30-50%.

               -MYOCARDIAL INFARCTION AND DRUG THERAPY-
MORPHINE:  Morphine has important properties when used in MI.  It is used for
the pain of acute MI as well as to decrease preload and afterload by dilating
peripheral venous and arterial beds.  Morphine is given IV at 2-5 mg IV q5-30
min for pain.   Morphine  should  not  be  used  in  severe chronic pulmonary
disease, as it can cause respiratory depression.  If  it  is  used  and  side
effects  are  prominent, it can be reversed by giving naloxone 0.4-2.0 mg IV.
OXYGEN: Oxygen is usually given routinely,  but  there is no definite data to
support its use.  It can increase vascular resistance.  It is  given  as  1-4
liters  by  nasal  cannula.   ASA: All patients with MI should be immediately
started on ASA using 160-324 mg/day.   The  first dose should be chewed.  The
first dose has been shown to increase patency and  reduce  reocclusion  after
lysis.    Long   term  therapy  with  ASA  has  also  been  shown  to  reduce
reinfarction, and mortality,  stroke  and  death.   BETA BLOCKERS: ACUTE USE:
Beta blockers are indicated in all patients with acute MI except  those  that
have  bronchospasm,  severe  heart  failure,  hypotension or bradycardia.  By
giving the beta blocker acutely, there  has been a limitation of infarct size
along with a reduction in  mortality  of  13%.   Beta  blockers  also  reduce
ventricular   fibrillation,   reinfarction,   intracranial  hemorrhage  after
thrombolytic therapy, and cardiac  rupture.   Two drugs are used.  Metoprolol
is given at 5 mg IV q2min x3, followed in 15 minutes by 50 mg PO bid x2, then
100 mg po bid as tolerated.  Alternatively atenolol can be given as  5-10  mg
IV followed by 100 mg PO qd.  CHRONIC USE OF BETA BLOCKERS: All patients with
high  risk should be maintained on beta blockers.  Long term beta blockade in
these cases reduces the rate of reinfarction and death (sudden death) up to 6
years post MI.  Patients  that  have  had  revascularization  such as PTCA or
CABG, and are asymptomatic, without exercise induced  ischemia,  are  usually
not  placed on long term beta blockers.  Beta blockers are contraindicated in
patients with heart block,  asthma,  hypotension and symptomatic bradycardia.
Propranolol is given as 60 mg TID-QID.  Timolol is  given  as  20  mg  daily.
Beta  blockers  should be continued for at least 2 years.  Patients that have
good LV function  without  angina,  ischemia,  or  arrhythmias during post MI
treadmill testing, usually have an excellent survival, and  may  not  benefit
from  beta  blockers.   NITROGLYCERIN: ACUTE USE: IV nitroglerin can decrease
infarct size and mortality if used within  4 hours of anterior MI, but should
not be used in right ventricular MIs or  in hypotensive patients.   Tolerance
may  develop  if  used  more  than  one  day.   CHRONIC USE: Oral and topical
nitrates are usually not given.   Oral  nitrates  started the day after an MI
has not changed the mortality at 1 month.  LIDOCAINE: Prophylactic  lidocaine
is  no  longer recommended as studies have shown a 38% increase in mortality,
mostly due to asystole.  Lidocaine  is  indicated for sustained, or recurrent
hemodynamically significant nonsustained ventricular tachycardia.   Lidocaine
is  given  IV  as a loading dose of 1 mg/kg, followed by .5 mg/kg bolus in 10
minutes.  An infusion is then  started  at  1-4 mg/min.  Patients that are in
CHF or who are elderly  should  have  the  dose  reduced.   Side  effects  of
lidocaine  include  perioral  numbness,  confusion, seizures, drowsiness, and
respiratory depression.  HEPARIN:  Heparin  is  always  indicated when tPA is
given and in those patients with  an  acute  anterior  MI,  left  ventricular
thrombi,  low cardiac output and atrial fibrillation.  Heparin used for these
indications is given as an IV bolus  of 100 mg/kg, followed by an infusion of
1,000-1,300 units/hour adjusted to obtain a PTT  2-2.5  times  normal.   High
dose  IV  heparin or subcutaneous heparin (12,500 units) will reduce the risk
for left ventricular  thrombus  after  an  anterior  MI.   IV heparin is also
needed  to  achieve  a  1%  mortality  benefit  of   accelerated   tPA   over
streptokinase.   Following  tPA  IV  heparin  should be given for 5-7 days in
order to diminish reocclusion  rates.   Routine  heparin may not be necessary
after Streptokinase or APSAC, because it has not been  shown  to  reduce  the
rates  of  reinfarction or death, and there has been an increase in bleeding.
Subcutaneous heparin is indicated during  periods of immobilization to reduce
deep venous thrombosis.  It is given  SQ  as  5,000  units  q12h.   WARFARIN:
Warfarin  is indicated chronically in any patient that has had a LV thrombus,
or in those patients  who  are  at  increased risk for thromboembolic events,
such as low cardiac output, atrial fibrillation and prolonged immobilization.
Longterm anticoagulation has been shown to decrease the rate of recurrent  MI
and  death,  but  when  compared to ASA, warfarin has not shown a decrease in
reocclusion.   Warfarin  is  given  to   achieve  an  INR  of  2.5-4.5.   ACE
INHIBITORS: ACE inhibitors are indicated in patients  that  have  symptomatic
cardiac  failure,  and  in those asymptomatic patients post-MI, with ejection
fractions less than 40%.  ACE inhibiotrs  have been shown to reduce the rates
of recurrent MI, decrease short  and  long  term  mortality  in  asymptomatic
patients  post  MI  with  LV  ejection  fractions  less  than 40%, reduce the
progression to heart failure, and reduce the need for rehospitilization.  ACE
inhibitors should be started at low  doses  within a few days after the acute
MI,  titrated  upwards,  and  continued  indefinitly.   Captopril  is   given
initially  as  6.25  mg  and  then titrated to 50 mg BID or TID as tolerated.
Lisinopril is given as a maintenance  of  10  mg daily.  Ramipril is given as
2.5-5 mg orally  BID.   MAGNESIUM:  Magnesium  therapy  has  had  conflicting
reports  as  to  its  efficacy.   It  is  usually not given, but may decrease
ventricular arrhythmias.  CALCIUM CHANNEL  BLOCKERS: Calcium channel blockers
are only indicated in non-Q-wave myocardial  infarctions,  if  there  are  no
contraindications  such  as  severe  LV dysfuntion.  Calcium channel blockers
that do no slow the  heart  rate,  such as nifedipine and nicardipine, should
not be used.  Nifedipine should not be given unless it is  used  concurrently
with  a beta blocker, as is is associated with an increased rate of recurrent
infarction and death.  Diltiazem has been shown to prevent early reinfarction
and angina in patients with non Q  wave MI, but increased mortaality in those
patients with severe LV dysfunction and congestive heart failure.   Verapamil
has  also  been associated with a trend toward decreased rreinfarction, and a
marginal effect on mortality.  Diltiazem is given as 90 mg q6h.  Verapamil is
given as 120 mg TID.  Both should  be  started early in non Q wave MIs within
2-5 days and continued for one year.

            -MYOCARDIAL INFARCTION AND MYOCARDIAL ENZYMES-
In the  age  of  thrombolytic  therapy  it  is  crucial  that  the patient be
accurately diagnosed for acute  myocardial  infarction  within  the  first  6
hours.   In the past this has been somewhat difficult if the immediate ECG is
not positive, because the creatine kinase  (CK) and the CK-MB (the myocardial
specific isoform) are usually  not  detectable  during  the  first  6  hours.
Conventional  assays  for CK-MB may take up to 12 hours to reliably reflect a
myocardial  infarction.   Furthermore,  the   specificity  of  the  CK-MB  is
decreased in patients that have had IM injections, electrical  defibrillation
and  chest massage.  Accordingly, many unwarranted expensive hospitilizations
have occurred, many of these being  triaged  to the acute coronary care unit.
It has been shown that less than 30% of patients  admitted  to  the  coronary
care  unit will be found to have a myocardial infarction.  This translates to
about 4 billion dollars/year.   Recently,  CK-MB  subforms have been found to
accurately diagnose acute myocardial infarction within  the  first  6  hours.
This  could  reduce  the admission to cornary care units by 50-70%.  CK-MB is
the only enzyme that is  released  from  the myocardium.  This is released as
CK-MB2, which is immediately cleaved  into  the  CK-MB1  molecule  by  lysine
carboxypeptidase.   Normally,  these  two  subforms exist in equilibrium.  By
measuring the CK-MB2 level and the  ratio  of CK-MB2 to CK-MB1, criteria have
been established for a rapid diagnosis of acute  myocardial  infarction  that
takes  about  30  minutes,  and  is no more costly than the conventional, old
assays.  The criteria  for  diagnosis  of  myocardial  infarction is a CK-MB2
level greater than 1.0 U/liter and a ratio of CK-MB2:CK-MB1 greater than  1.5
occurring  within  six  hours  after  the  onset  of  symptoms.   This  has a
sensitivity of 95.7% and a  specificity  of  93.9%.  The subform procedure is
simple, reproducible, requires no extra personell, and can  be  performed  in
any  community  hospital.   The procedure is based upon high voltage (1450 V)
electrophoresis rather than  the  conventional  (150) V electrophoresis.  The
subforms can be separated within 6 minutes, with a total completion  time  of
about  30 minutes.  The cost for performing the subform testing is comparable
to the conventional CK-MB  assays.   Most  patients  may be diagnosed with an
acute myocardial infarction within two hours after arrival in  the  emergency
room.   In  summary,  it  may  now be possible to render intelligent decision
making within the  first  6  hours  of  myocardial  infarction,  based on the
routine  measurement  of  CK-MB  subforms,  resulting  in  up  to  70%  fewer
admissions to the coronary care unit.

                -MYOCARDIAL INFARCTION (An Overview)-
Most patients with AMI  will  have  chest  pain.   About 25% will have silent
MI's.  Most will have retrosternal or precordial chest pain that  is  intense
which requires IV narcotics.  The pain is capable of radiating to the throat,
jaws,  either or both arms and back.  The duration is at least 30 minutes and
may extend if untreated.  The  patient  describes  the pain as a deep, heavy,
aching or burning pain which may feel as  if  someone  were  sitting  on  the
chest.   In  addition  there  may  be dyspnea caused by pulmonary congestion,
syncope due to arrhythmias which  curtail cerebral perfusion, weakness due to
decreased cardaic output, anxiety and nausea.  Most cases  are  secondary  to
atherosclerosis  and thrombosis which is due to plaque rupture.  The ruptured
plaque can occlude the lumen by  itself  or expose the underlying collagen to
the flow of blood that sets up a thrombosis.  If the coronary obstruction  is
incomplete,  but  severe, a subendocardial infarction can occur.  If there is
total occlusion,  a  transmural  infarction  is  possible.   The magnitude of
damage depends on whether the occlusion is proximal or  distal,  whether  the
vessel  is  large  or small, and the state of the collateral circulation.  In
general, anterior MI's  are  larger  and  associated  with  a poorer outcome.
Inferior MIs may also cause infarction of the right ventricle as well as  the
inferior  and  posterolateroal  aspect  of the LV.  Small inferior MI's, even
with right ventricular infarction  usually  have  a good prognosis.  PHYSICAL
EXAM:  Most  patients  have  a  normal  blood  pressure,  but  there  may  be
hypotension secondary to cardiogenic shock or more commonly  from  activation
of  the  Jarisch-Bezold  reflex),  or  hypertension  secondary  to  increased
adrenergic  discharge.   The  jugular  venous pressure may be elevated in the
face of an inferior infarction with concomitant right ventricular infarction.
Acute LV failure initially  does  not  cause  elevation of the jugular pulse.
With LV failure, bibasilar crackles may develop in the lungs.  There  may  be
only  the  presence  of  an  atrial  sound  (S4) which reflects diminished LV
compliance and can be best heard  at  the  cardiac  apex with the bell of the
stethoscope.  If atrial fibrillation is present, the S4 will  not  be  heard.
The  third  heart  sound  (S3)  is  heard  less frequently and indicates more
advanced LV failure.  There may be  a visible and palpable systolic pulsation
over the precordium indicating a dyskinesis of the infarcted area, especially
in anterior MIs.  Systolic murmurs secondary to papillary muscle  dysfunction
may   be   heard  which  can  cause  mitral  regurgitation.   A  loud  apical
holosystolic murmur would suggest rupture  of a papillary msucle, with severe
mitral regurgitation.  If this same murmur is heard maximally  at  the  lower
left  sternal  border,  rule  out  rupture  of  the  interventricular septum.
Pericardial friction rubs may also be  heard with transmural MIs.  These rubs
have 3 components  with  a  loud  scratchy  quality.   LABORATORY:  Diagnosis
depends upon the ECG and serum enzyme levels.  The creatine kinase (CK) level
rises  within  4-8 hours following the onset of AMI, peaks within 24-36 hours
and falls to baseline in  about  3-4  days.   Since skeletal muscle and brain
contain CK, the isoenzyme of the myocardial component (CK-MB) must  be  used.
Lactic dehydrogenase levels (LDH) are also elevated and may stay elevated for
about  10  days.   Echocardiography may demonstrate a wall motion abnormality
reflecting hypokinesis or akinesis of the  infarcted area.  Clots may be seen
in the left ventricle, particularly with infarction of the  LV  apex.   About
30%  will  develop  a  mural  thrombus.   TREATMENT:  All  patients should be
monitored in the coronary care unit as fatal ventricular arrhythmias are very
common during the early hours  of  infarction  and account for many deaths in
this period.  Venous access should be secured early  in  order  to  given  IV
analgesia and antiarrhythmic therapy.  Hypotension and respiratory depression
may  develop  from  IV narcotics, but can be reversed.  The patient should be
made pain  free.   Bed  rest  is  prescribed  for  about  24-48  hours and if
hemodynamically stable, mobilization can  be  achieved  at  this  time,  with
transfer  to  a  stepdown  telemetry  unit and allowed to ambulate gradually.
Discharge from the hospital in  the uncomplicated AMI is usually accomplished
within 7 days.  THROMBOLYSIS: With thrombolytic agents, lysis of the clot can
be achieved in about 75% of patients.   Therapy  should  be  initiated  early
preferably  within three to four hours.  The addition of ASA to streptokinase
and heparin to tPA have shown definite benefit in clinical trials.  Immediate
revascularization  with  PTCA  will  be  necessary  if  the  patient  becomes
hemodynamically unstable, or develops  symptoms of recurrent ischemia, either
clinically  or  by  low  level   exercise   testing   prior   to   discharge.
ANTICOAGULATION:   About   10%   of  hospital  deaths  are  due  to  systemic
embolization from  an  acute  MI.   At  risk  are  those  patients with large
infarctions involving the anteroapical wall.  About 33% of  patients  can  be
shown  to  have  mural thrombi in this situration.  The embolization tends to
occur early, especially with  sessile  thrombi.  Other potential patients for
systemic embolization would include patients with peristent congestive  heart
failure,   patients   with   atrial   fibrillation  or  history  of  previous
thromboembolism, and those patients with massive infarction located elsewhere
in the left ventricle.  These types  of  patients should be treated with full
dose heparin followed by warfarin given PO to prolong the PT to  a  level  of
1.2-1.5  times  control  for  at  least  3 months post infarction.  Long term
warfarin therapy is  used  for  patients  with  atrial fibrilaltion, previous
thromboembolism,  pulmonary  hypertension  and  persistent  CHF.   Low   dose
heparin,  5000  units subcutaneously every 12 hours will reduce the incidence
of pulmonary embolism and should  be  used  routinely in all AMIs.  NITRATES:
Nitrates have been shown to reduce mortality by 15-20% in AMI when given  IV.
Nitrate  use  is  only  recommended  in  special situations such as recurrent
ischemia, LV failure,  mitral  regurgitation,  and uncontrolled hypertension.
Hemodynamic monitoring is usually not needed when nitrates  are  used  unless
the  patient  is  hemodynamically  unstable.   Start  nitroglycerin  IV at 10
micrograms/min  and  adjust  by  5   mitrograms/min  every  5  minutes  until
hypotension develops or the clinical effect is reached.  LIDOCAINE: Lidocaine
is not routinely recommended for prophylaxis in  acute  MI,  as  no  clinical
trials  have  conclusively  demnostrated  a  reduction  in  mortality.   BETA
BLOCKERS:  Beta blockers have been shown in several clinical trials to reduce
acute and  long  term  mortality  in  MIs.   No  single  agent  appears to be
superior, but all of the clinical  trials  have  been  associated  with  beta
blockers  that  produce  bradycardia.   Therefore,  beta  blockers  that have
intrinsic sympathomimetic activity should not be used.  IV beta beta blocker,
such as metoprolol and atenolol are used initially followed by the oral form.
IV beta blockers have also been shown to reduce pain and are probably just as
effective  in  controlling  malignant   ventricular  arrhythmias.   They  are
contraindicated in severe bronchospasm, AV conduction disturbances and severe
LV failure.  ACE INHIBITORS: Recently, a large  clinical  trial  demonstrated
the  utility  of  using ACE inhibitors a few days following AMI.  They have a
salutory effect  on  preservation  of  ventricular  function  with  a lowered
mortality result.  Myocardial infarction, especially large ones,  unfavorably
alter the configuration and shape of the left ventricle.  ACE inhibitors will
modify  this  process.   ANTIARRHYTHMIC  THERAPY:  No  study  has  ever shown
convincing  evidence  that  antiarrhythmic   agents  will  reduce  long  term
mortality after  MI,  with  the  exception  of  beta  blockers  and  possibly
amiodarone.   The  CAST  study  showed  an increase mortality with the use of
encainide, flecainide and moricizine.  Encainide  has now been withdrawn from
clinical use.  CALCIUM ANTAGONISTS: These agents are not  routinely  used  in
AMI,  except  for  recurrent ischemia that has not responded to nitrates, and
patients that  have  suffered  a  non-Q  wave  infarction  without  CHF where
diltiazem has been shown to be of benefit.  REVASCULARIZATION:  Routine  CABG
is  not  indicated in the first few hours following MI.  Instead, medical and
PCA revascularization is  now  used.   Emergency  surgery  should  be used in
patients with ruptured septum or papillary  muscle,  and  cardiogenic  shock.
Revascularization  is  also indicated in patients who have recurrent ischemia
in spite of  optimal  medical  therapy  and  in  whom  PTCA  is not possible.
Surgery is best done at least 7-10 days post MI, or preferably 1  month  post
MI  if  possible.   Primary  angioplasty of the infarct related artery can be
done in centers that are equipped for this situation.  In general, it is best
reserved  for  patients  in   the   early   hours   of  infarction  who  have
contraindications to thrombolysis, and also has a role in the  management  of
cardiogenic shock.

                -MYOCARDIAL INFARCTION COMPLICATIONS-
VENTRICULAR  TACHYCARDIA,  VPBs:  For  hemodynamically  unstable  ventricular
tachycardia (VT), D.C.  cardioversion should be given at 100-200 Joules.  For
stable VT lidocaine should be strated with a loading dose of 1 mg/kg which is
repeated  in  5  minutes,  followed  by  an  infusion  of 2-4 mg/min.  If the
arrhythmia cannot be suppressed with lidocaine, procainamide is started using
100 mg boluses over 2 minutes every 5  minutes up to a total dose of 750-1000
mg, which is then maintained by an infusion of 20-80  ug/kg/min.   Watch  for
hypotension,  myocardial  dysfunction  and  conduction  disturbances  as side
effects  of  procainamide.   Causes  of  ventricular  arrhythmias  should  be
corrected  as  hypokalemia,  hypoxemia,  digitalis  toxicity  and ventricular
aneurysm.  Bretylium tosylate given at 5 mg/kg IV over a 5 minute period  and
repeated  in 20 minutes, if necessary, followed by an infusion of 1-2 mg/min,
may be tried if the  above  are  unsuccessful.   Amiodarone given IV has also
been very effective, but its use in the USA is limited.  VPBs are not treated
unless they become multifocal, frequent, fall on the ascending limb of the  T
wave,  occur  in  couplets or as non-sustained VT.  If these scenarios occur,
start prophylactic lidocaine  as  above  and  watch  for confusion, seizures,
tremor, and anxiety.  Accelerated idioventricular  rhythm  often  accompanies
thrombolytic  therapy as reperfusion occurs.  This rhyrthm is a wide QRS one,
with a regular rate  between  70-100/min  and  is  usually not treated if the
patient is stable, but treatment is  controversial.   POST  MI  ISCHEMIA  AND
EXTENSION:  About  30%  of  patients will have postinfaction angina, which is
twice as common in  non-Q  wave  infarcts  and thrombolytic therapy which has
residual vulnerable myocardium.  Diltiazem given at 60-90 mg QID will  reduce
postinfarction  extension  in  non-Q  wave  infarcts.   Recurrent  infarction
usually  will  occur  in the first 2 weeks.  It may be silent, or heralded by
CHF, chest pain, or  found  with  cardiac  enzymes  and ECG.  In general, the
patient should be treated as for unstable angina  with  beta  blockers,  ASA,
heparin, ntirates, and calcium channel blockers.  If the patient proves to be
refractory to these, catheterization should be done followed by possible PTCA
or  CABG.  Chest pain in MI typically improves after about 24 hours following
acute  MI.   Chest  pain  following  this  includes  pericarditis, pneumonia,
pulmonary emboli and recurrent ischemia secondary to  suboptimal  blood  flow
through  a recanalized artery of reocclusion.  LEFT VENTRICULAR FAILURE: Left
ventricular failure is characterized by diffuse rales, arterial hypoxemia and
dyspnea and should be  monitored  with right heart catherterization measuring
pulmonary capillary wedge pressures.  Furosemide given IV in doses  of  10-40
mg  or  bumetanide  .5-1  mg  IV  is  used  because of rapid onset of action.
Morphine sulfate 4 mg given initially  followed by 2 mg increments is helpful
if there is pulmonary edema.   For  mild  LV  failure  sublingual  isosorbide
dinitrate 2.5-10 mg every 2 hours or nitroglycerine ointment 6.25-25 mg every
4  hours may decrease the PCWP.  For severe LV failure nitroprusside is given
at an initial dose of.25  ug/kg/min  and increased by .5 ug/kg/min increments
every 5 minutes up to 5-10 ug/kg/min until the PCWP is < 18  mm  Hg  and  the
cardiac  index  is > 2.5.  Keep the mean BP > 65-75 mm Hg.  Nitroprusside may
have to be  given  with  dobutamine,  if  additonal  inotropy is needed.  The
initial dose is 2.5 ug/kg/min, increasing by 2.5 ug/kg/min increments  up  to
15-20  ug/kg/min, given at 5-10 minute intervals.  This will increase cardiac
output, and decrease the  PCWP,  but  watch for hypotension, arrhythmias, and
tachycardia.  If the patient is hypotensive with LV failure, dopamine may  be
preferred  over  dobutamine,  but  will  not decrease the PCWP as well as the
dobutamine.  Dopamine is given at 5-15 ug/kg/min  IV and titrated to a CI >2,
CO >4 and a systolic  BP  >  90.   Milrinone  is  a  positive  inotropic  and
vasodilator  that  has  fewer  side  effects  than  amrinone.   Milrinone  is
initiated  at  a  loading  dose  of  50 ug/kg over 10 minutes, followed by an
infusion of .375-.75 ug/kg/min.  Do  not  use digitalis for acute LV failure.
It may be used in atrial fibrillation to slow  the  ventricular  rate.   LEFT
VENTRICULAR  ANEURYSM: Left ventricular aneurysm will develop in about 10-20%
of patients with an acute myocardial infarction.  Aneurysms may develop after
a few days or weeks  or  months  and  are most prevalent after large anterior
myocardial infarctions.  They do not rupture but are troublesome because they
predispose to recurrent ventricular arrhythmias, mural thrombi with  systemic
embolization  and  CHF.  Suspect aneurysm after an anterior Q wave infarction
when  there  is  paradoxical   precordial  movement,  persistent  ST  segment
elevation on the ECG or a bulge on chest x-ray.  The wide neck  aneurysm  can
be seen with echocardiography, contrast angiography or scintigraphy.  Surgery
is  the  treatment  of  choice  if  the  above  are  persistent.   CONDUCTION
ABNORMALITIES:  No  treatment  is  needed for first degree AV blocks.  Second
degree AV Mobitz type I blocks are  seen in inferior infarctions in about 20%
of  cases  and  do  not  require  treatment  unless  there   is   symptomatic
bradycardia.   Then atropine may be helpful using an IV bolus of 1 mg.  Watch
for dry mouth, blurred vision and  psychosis.  If refractory to atropine then
persistent temporary transvenous pacing may be needed.   Complete  AV  blocks
occur  in  about  5%  of  inferior  infarcts,  are usually transient, but may
persist for  weeks,  with  the  escape  rhythm  originating  in  the AV node,
inscribing a narrow QRS complex  on  ECG  and  rates  of  30-50/minute.   Low
cardiac  output  and  hypotension may be treated with atropine, but temporary
pacing may be  required  if  patient  is  hemodynamically unstable.  Anterior
infarcts produce second degree AV Mobitz type II blocks originating below the
AV node due to damage of the His Purkinje and  bundle  branches  and  may  be
sudden in onset and thus require ventricular pacing as these wide QRS rhythms
are  unstable.   Temporary  pacing  is  also  indicated  for  new  conduction
disturbances such as bifascicular or bundle branch block with first degree AV
block,  or  bilateral  bundle  branch  block.   SUPRAVENTRICULAR ARRHYTHMIAS:
Causes for sinus tachycardia should include hypovolemia, pump failure, sepsis
or thyroid hormone excesses.  Atrial  fibrillation, atrial flutter and atrial
premature beats occur in approximately 10% of MI patients and can  be  caused
by  atrial  infarction,  electrolyte abnormalities, hypoxia, and theophylline
and  are  precursors  to  atrial  fibrillation.   APBs  may  be  treated with
digitalis, calcium antagonists, and beta  blockers,  providing  there  is  no
heart  failure.   Atrial  fibrillation can be treated with esmolol 500 ug/kg,
followed  by  50-200  ug/kg/min  infusion,  verapamil  IV  given  in  2-5  mg
increments to a total of 20 mg,  or  digoxin .5 mg initially, followed by .25
mg every 2 hours up to a total of 1.25 mg as a loading dose, and then .25  mg
daily,  providing  there  is normal renal function.  If the patient has AF in
the presence of heart  failure,  hypotension or ischemia, emergent electrical
cardioversion should be given starting at 100 J. After patients  converts  to
sinus rhythm, procainamide, verapamil, beta blocker or digoxin can be used to
maintain  sinus  rhythm.   SINUS  BRADYCARDIA: Sinus bradycardia is seen with
inferior MIs and rarely requires  treatment  other  than atropine if there is
decreased cardiac output secondary to  very  low  heart  rates.   CARDIOGENIC
SHOCK:  Cardiogenic shock is characterized by symptoms of decreased perfusion
such as  low  urine  output,  cold  extremities,  diaphoresis, confusion plus
tachycardia and hypotension.  It is usually associated  with  large  anterior
MIs  and  carries with it a mortality tha can be > 65%.  Swan Ganz monitoring
is necessary.  Hypovolemia contributing to the shock should be ruled out such
as beta  blockers,  diuretics,  calcium  antagonists,  nitrates, vomiting and
diaphoresis.  Thrombolytic therapy may  result  in  hemorrhagic  pericarditis
producing  cardiac  tamponade,  right  ventricular infarction and ventricular
rupture should all be excluded.  If the  BP  is > than 90 mm Hg, cautious use
of  nitroprusside  using  .1-.2  ug/kg/min  IV  increasing  by  5  ug/kg/min.
Dopamine may  be  combined  with  nitroprusside  at  an  initial  dose  of  2
ug/kg/min,  increasing  at  5  min  intervals  to achieve a cardiac index >2,
cardiac output > 4 and systolic  BP  >  90.  Doses < 5 ug/kg/min will improve
renal blood flow, doses 2.5-10 ug/kg/min  stimulates  cardiac  contractility,
while doses > 10 ug/kg/min results in vasoconstriction.  Intra-aortic balloon
counterpulsation  should  be used to unload the left ventricle during systole
and increase  diastolic  coronary  artery  filling pressures.  Intra-coronary
thrombolytic therapy and angioplasty may be life saving in  some  cases,  but
CABG  has  been  shown  to be ineffective.  RUPTURE OF PAPILLARY MUSCLE, IVS:
Sudden development of hypotension or severe  heart failure coupled with a new
loud systolic murmur and thrill over the left chest occurring over the  first
3-7  days with either an anterior or inferior infarction should suggest these
two conditions.  The diagnosis  can  be  confirmed by echocardiography or the
presence of high O2 saturation from a right atrial blood sample will  confirm
a  ventricular  septal  rupture  with  left  to  right  shunting.   Pulmonary
capillary  wedge  pressure  tracings  that  demonstrate  a  large  v wave are
suggestive  of  papillary  muscle  rupture.   Nitroprusside  and intra-aortic
balloon will reduce the mitral regurgitation or IVS shunt  allowing  time  to
surgically  repair  the  defects.   MURAL  THROMBUS: Mural thrombus occurs in
about 20-60% of large anterior  infarcts with arterial embolization occurring
in about 10% of LV thrombi.  Diagnosis can  be  made  with  echocardiography.
Treatment  is with heparin, followed by 3 months of warfarin, keeping the INR
between 1.5 and 2.5.

               -MYOCARDIAL INFARCTION IN THE ELDERLY-
This topic will deal with the various therapeutic modalities that can be used
in patients with myocardial  infarction.   Although the treatment is somewhat
standardized in those patients under  75  years  of  age,  the  treatment  of
patients  >  75  has  been more tenuous, because of complications that can be
incurred in this group.   BETA  BLOCKER  THERAPY:  The ISIS-1 showed a 22.7%
reduction in mortality in older patients that  were  treated  with  atenolol.
The Goteborg trial showed a 45% reduction with metoprolol.  These studies for
EARLY  treatment  in  MI  with  beta  blockade  is much better for older than
younger patients,  who  obtained  no  mortality  benefit  from beta blockers.
Three pooled studies for LONG TERM reduction in mortality from beta  blockers
in the 65-75 year-old group have demonstrated a 40.1% reduction in mortality.
The  reduction  for younger patients was only 28.3%.  Also, diabetic patients
that have MI will benefit  from  beta  blockers.  With the proven benefits in
beta blockade then why isn't the therapy used more in older patients?   There
are  several  side  effects that may not be tolerated in older patients, even
though it is known that some patients in congestive heart failure may benefit
from beta blockers.  THROMBOLYTIC THERAPY: Older patients can derive benefit
from thrombolysis as much as  younger  patients.   There  is a slight rise in
hemorrhage in the elderly, but overall,  the  benefits  are  greater  in  the
elderly than in the young.  In the ISIS-2 study, treatment with streptokinase
accounted  for  a  15.7%  reduction  in  mortality  in  those  >  70.  If the
streptokinase was combined  with  ASA  the  mortality  was  reduced to 33.7%.
There was a 41.2% reduction in those > 80 years of age when streptokinase was
used.  The GISSI study  also  demonstrated  a  reduction  in  mortality  with
streptokinase  in the elderly that was greater than younger patients.  Pooled
data from the GISSI-1 study for  patients  75  years and older AND the ISIS-2
study, for patients 80 years and older, showed a reduced mortality  of  19.7.
The  ASSET  and  the AIMS trials showed similar survival with thrombolysis in
the elderly.  Only one study, the ISAM study, showed an increase in mortality
of 35.4% in the elderly using  thrombolysis.   The pooled data from the above
would indicate that thrombolysis decreased mortality from  8.4%  to  6.2%  in
younger  patients  and  a  reduction  in mortality from 20.7% to 17.2% in the
elderly.  PTCA and CABG:  The incidence of peri-infarction complications with
emergency CABG is fairly high in the elderly with, strokes, infections, renal
insufficiency and arrhythmias.  Complications  are  more common in women.  In
spite of this, CABG may be used in preference to  PTCA  in  some  subsets  of
patients,   because   of   increased  tortuosity  of  the  coronary  vessels,
multivessel disease and low ejection  fractions.  If there is one significant
lesion seen with multi-vessel disease, then PTCA  may  be  more  appropriate.
Emergency CABG has a very high morbidity and mortality in the elderly.  It is
much  better, if feasible, to stabilize the elderly patient and then possibly
proceed with coronary artery bypass grafting.  ANTICOAGULANTS: Since Heparin
has been  used  with  different  thrombolytics  and  antiplatelet agents, and
Heparin has been used both subcutaneously and intravenously,  there  is  much
ambiguity  as to its utility in treatment of acute myocardial infarction.  In
the  GUSTO  trial  the  best  results  were  seen  in  patients  treated with
accelerated t-PA and immediate and continuous IV heparin.  Long term  therapy
with  oral warfarin has yielded good benefits.  In the Warfarin Re-infarction
study, whose mean age was 62,  mortality  was reduced by 24%, reinfarction by
34% and cerebrovascular  events  by  55%.   The  question  is  whether  these
patients  would  have  the  same  benefit  with  low  dose oral aspirin.  ACE
INHIBITORS: It is  well  known  that  angiotensin  II can constrict coronary
arteries which will increase afterload.  Without ACE inhibitors, the post  MI
heart  can  dilate,  and  become  more  ischemic  because  of the wall stress
secondary to the increased  afterload.   The  SAVE trial showed a significant
reduction in post MI mortality with captopril.  ACE inhibitors are useful for
reducing post-infarction remodeling and subsequent heart failure.  NITRATES:
Nitrates, in many trials, have shown  benefit  for  decreasing  ischemia  and
altering  the  hemodynamic response in patients with MI.  They can be used to
advantage, but one  should  be  aware  of  possible  hypotension in the aged.
CALCIUM CHANNEL BLOCKERS: Most studies indicate no clear  benefit  by  using
calcium channel blockers in MI patients.  There have been 18 clinical studies
where  calcium  channel blockers were used early and late in MI patients, and
there was no  decrease  in  mortality,  infarctions, reinfarctions or infarct
size.  The main benefit  for  calcium  channel  blockers  is  in  non-Q  wave
infarction  patients,  and in patients without impaired systolic or diastolic
function.  The Danish Verapamil  infarction  trial  II study, however, showed
decreased 16 month re-infarction and mortality in non-Q wave and  Q  wave  MI
patients.   Patients  were  not  taking  beta blockers in this study that has
obscured the results of  other  trials.   ASA:  Using  ASA in the elderly is
associated with a higher incidence of side effects than the younger  patient.
Using  low dose ASA has however, circumvented some of these side effects, yet
still preventing thrombus formation.   There  was  a decrease in mortality of
21% in the ISIS-2 study, and a decrease of  non-fatal  re-infarction  of  44%
when  ASA  was  given at a dose of 160 mg/day for 30 days after MI.  The RISC
trial has shown that  even  reducing  the  ASA  to  75  mgt/day resulted in a
decreased rate of non-Q MI and unstable angina.

                   -MYOCARDIAL PERFUSION IMAGING-
Myocardial perfusion imaging is  an  important  part  of the nuclear medicine
armamentarium.  Today, you have the option of using Thallium 201 or Sestamibi
(Cardiolite) for imaging agents.   These  agents  may  be  used  with  planar
imaging  or single photon emission computed tomography (SPECT).  These agents
are used in conjunction with exercise testing or pharmacologic agents such as
dipyridamole, adenosine or dobutamine.   In  SPECT  imaging the planar images
are obtained in a 180 degree arc around the patient  and  then  reconstructed
into three dimensions that are evaluated in the short axis, the vertical long
axis  and the horizontal long axis.  This method has an advantage over planar
imaging because there can be  separation  of the coronary artery territories.
This is  not  possible  in  planar  imaging.   In  planar  imaging  there  is
superimposition  of  the  various coronary artery territorial images.  Planar
imaging uses views of the  left  anterior oblique, anterior, and left lateral
positions.  Technetium 99m Sestamibi imaging is useful because of its  unique
physical  and  pharmacokinetic  properties.   Sestamibi  has  essentially  no
redistribution  as  thallium  does  and  therefore  scintigrams represent the
status of  heart  at  the  time  of  injection.   It  is  distributed  in the
myocardium in proportion to blood flow.  Excellent myocardial perfusion scans
can be obtained with both planar imaging and single photon emission  computed
tomography  (SPECT).  In contrast to Thallium, Sestamibi doesn't redistribute
into ischemic areas and is  not  a potassium analogue as thallium.  Sestamibi
is taken up into  the  myocardium  by  passive  diffusion.   There  is  rapid
clearance  of  Tc99m  Sestamibi from both the blood and extracardiac tissues.
Hepatobiliary clearance of the complex is completed in about 70 minutes.  The
clinical use of TC99m  Sestamibi  can  be  used  to differentiate viable from
scarred myocardium and when used in combination with exercise testing  or  IV
dipyridamole  the  location  and  extent  of ischemic areas can be evaluated.
First pass  radionuclide  ventriculography  can  be  performed  with a single
injection of TC99m Sestamibi in order to study  left  and  right  ventricular
perfusion  and  function  with  the  patient  at  rest  and  during exercise.
Assessment of cardiac wall thickness  and  motion  can be studied using gated
perfusion image acquisition.  The protocol for Tc99m Sestamibi imaging can be
done in one day or two day studies.  Using the one day protocol,  rest-stress
images  are  done  using  8-9 mCi of Tc99m Sestamibi.  The rest image is done
about 60-90  minutes  after  injection.   This  is  followed  by  a 22-25 mCi
injection during exercise or with IV  dipyridamole  and  then  imaging  after
another  60-90 minutes.  The two day stress-rest imaging procedure is done by
injecting 22 mCi of technetium  99m  during  exercise or IV dipyridamole, and
then obtaining images 60-90 minutes later.  Subsequent rest  day  images  are
acquired  after a 22 mCi dose of the radioactive agent is given, with imaging
done 60-90 minutes later.  Thallium 201 is passively and actively taken up by
myocardial cells in a linear relationship  to the degree of regional coronary
blood flow.  Because of its long half life only a small amount of  about  2-3
mCi  of thallium 201 can be given.  After this radioactive element enters the
heart cells there is a  continuous  washing  in  and out across the membrane.
The normal washout is about 30% 2.5 hours after an injection during exercise.
Images done immediately after an injection demonstrate regional  distribution
of myocardial blood flow while those done 2-24 hours later reflect myocardial
viability.   These  delayed  studies  will  show the reversibility or lack of
exercise induced ischemic defects.  Visual  appreciation  of a normal scan is
characterized by a homogeneous distribution of  the  radioactive  agent.   If
there  is  a localized decrease in uptake this is considered a defect.  Fixed
defects do not redistribute after  the  initial exercise defect and represent
scarring for the most part.  Visual interpretation can be  supplemented  with
graphic  displays  using  a  transverse or circumferential profile which will
show the  relative  distribution  of  the  radioactive  agent.   The size and
reversibility  of  the  defects   can   also   be   quantified   for   better
reproducibility.    CLINICAL   APPLICATIONS:  DETECTION  OF  CORONARY  ARTERY
DISEASE:The sensitivity and specificity of  planar thallium stress imaging by
visual interpretation is about  83  and  90  per  cent  respectively.   Using
computer processing and image quantification will increase the sensitivity to
90%.   SPECT  imaging  has  a  greater  than 90% sensitivity for detection of
coronary artery disease but suffers lack of specificity, ranging from 60-70%.
This disparity is probably due  to  referral  bias and false positive results
are common.  Most patients that have triple vessel disease, and  severe  left
main  disease  will  have abnormal scans.  False negative scans usually occur
with single vessel disease, and disease in the left circumflex artery may not
be detected by planar imaging.  The  presence and extent of perfusion defects
using exercise/redistribution thallium imaging can be used for  prognosis  of
future  cardiac  events.   These  findings  are  superior to exercise testing
alone, or extent  of  angiographic  involvement.  Abnormal increased thallium
uptake in the lungs after exercise is  related  to  severe  left  ventricular
dysfunction  from  any cause.  Abnormally increased thallium lung uptake also
is a significant  predictor  of  future  cardiac events.  Increase lung/heart
thallium  ratios  have  been  correlated  with   exercise-induced   pulmonary
congestion,  the number of diseased vessels seen with angiography, resting LV
function, low double product  during  exercise, increased pulmonary capillary
wedge pressure and  clinically  evident  resting  congestive  heart  failure.
PREOPERATIVE  RISK:  It  has  been  known  for  many  years  that there is an
increased risk for patients undergoing non-cardiac surgery after a myocardial
infarction, or in those who have uncontrolled congestive heart failure.  Now,
patients being  considered  for  vascular  surgery,  can  have a dipyridamole
perfusion image prior to surgery  if  they  are  unable  to  exercise.   Many
patients  that  have  peripheral vascular disease are unable to exercise, and
since it is well known that  patients with peripheral vascular disease have a
high occurrence of coronary artery disease it may be  prudent  to  perform  a
pharmacologic   stress   perfusion  study  with  dipyridamole,  adenosine  or
dobutamine prior  to  surgery.   However,  the  study  is  most applicable in
patients that have an intermediate risk profile rather than one with advanced
symptomatic coronary artery disease.  There  are  now  several  studies  that
document   that   transient  thallium  perfusion  defects  can  prognosticate
perioperative myocardial events, based  on  the number of reversible defects,
and the size of the defects.  MYOCARDIAL PERFUSION IMAGING  AND  THROMBOLYTIC
THERAPY:   It   may  now  be  practical  to  obtain  a  myocardial  perfusion
TC99m-Sestamibi  scan  prior  to  the   start  of  thrombolytic  therapy  for
myocardial infarction.  Since sestamibi does not undergo redistribution,  the
Tc99m-sestamibi can be administered prior to or with the thrombolytic therapy
and  then  imaged  3-4  hours  later.   The  image  obtained  at that time is
indicative of  the  state  of  the  coronary  arteries  at  the  time  of the
injection, prior to thrombolytic therapy, even though the image  is  obtained
3-4  hours  later.   Following this, an estimate of myocardial salvage can be
made after a repeat scan.  For  example,  if the patient has a large residual
defect following the second image, he  or  she  may  need  revascularization.
THALLIUM IMAGING AND ACUTE MYOCARDIAL INFARCTION: Acute myocardial infarction
can  be  visualized  with thallium scanning if the agent is injected within 6
hours after the onset  of  chest  pain.   This  is  valid  if the patient has
sustained a Q wave or non-Q wave  infraction.   If  the  patient  is  scanned
outside  the  6 hour window, some of the patients will have normal scans.  If
sequential  scans  are  performed  over   the  evolution  of  the  myocardial
infarction, it has been shown that the size  of  the  perfusion  defect  will
decrease  in  size, probably related to lysis of the coronary thrombus in the
associated artery.  POST MYOCARDIAL INFARCTION PERFUSION IMAGING: There is no
standard consensus whether arteriography  or  non  invasive testing should be
done following myocardial infarction patients at  risk.   Factors  associated
with  increased  risk  after  MI  include  a  history  of multiple myocardial
infarctions, congestive heart  failure,  complex ventricular arrhythmias, and
recurrent ischemic chest pain within 24-48  hours.   Short  term  outcome  of
myocardial  infarction  patients  can be determined by exercise testing which
can detect ST segment depression or  elevation, induced angina, or failure to
obtain an adequate workload or blood pressure response.  If you  add  delayed
thallium imaging and lung/heart thallium ratios the predictive value for late
myocardial  events  is  improved.   Some  studies  have  shown that transient
exercise induced defects that  are  in  areas  of  myocardium remote from the
infarct zone are more accurate prognosticators than ST segment depression  or
exercise  induced angina.  Since sub-maximal stress exercise testing is often
done after myocardial infarction, if may  be  more appropriate to use post MI
dipyridamole-thallium imaging  to  increase  the  sensitivity  of  the  test.
Sub-maximal  stress  testing  has  a  lower  sensitivity  than maximal stress
testing.  Transient  perfusion  defects  can  then  be  used  to predict late
cardiac events.  CORONARY ANGIOPLASTY AND MYOCARDIAL PERFUSION IMAGING: There
is an incidence of  from  20-40%  coronary  stenosis  following  angioplasty.
Using  single  photon  emission  computed  tomography  thallium scintigraphy,
restenosis can be detected.  When  a  post angioplasty SPECT thallium scan is
done at 4-6 weeks and there is a positive scan,  85%  of  these  have  had  a
documented  restenosis  within  6  months  and 96% within 1 year.  Therefore,
routine SPECT thallium scans may be indicated in asymptomatic and symptomatic
patients after  angioplasty  in  order  to  predict the anatomically-involved
affected vascular bed.  If the thallium scan is done between 4-18  days  post
MI,  the results are not as clear cut as the the perfusion image may still be
abnormal.  SIGNIFICANCE OF A NORMAL  EXERCISE THALLIUM SCAN: In patients that
have atypical chest pain and prove to have a normal exercise  thallium  scan,
the  prognosis  is  excellent.   The  prognosis is still relatively benign in
patients  that  have  exercise-induced  ST  segment  depression, angiographic
coronary artery stenosis and typical angina in the face of a  normal  maximal
exercise  Thallium scan.  Dipyridamole-thallium images also indicate the same
relative good prognosis as  the  exercise  thallium.  In summary, any patient
that has transient perfusion defects seen on a thallium image is at a  higher
risk  for  cardiac  death  and  myocardial infarction.  Dipyridamole-thallium
imaging  carries  the   same   diagnostic   and  prognostic  implications  as
stress-exercise thallium imaging and can be used for those patients that  are
unable  to  exercise,  or  exercise  maximally as in recent post MI patients.
However, if the  patient  has  a  normal  maximum exercise thallium perfusion
scintigram there is a low risk of cardiac  death  and  myocardial  infarction
even if the

       -MYOCARDIAL PERFUSION IMAGING (Pharmacological Stress)-
Many  patients  are  unable  to  complete  a maximal exercise protocol due to
multiple reasons.  There  are  three  pharmacologic  agents  that are used in
conjunction  with  Thallium  201  or  technetium  99m  sestamibi   myocardial
scintigraphy.   These  are  IV  or  oral  dipyridamole,  IV adenosine, and IV
dobutamine.  INDICATIONS: Pharmacologic stress perfusion imaging is indicated
for the diagnosis of  coronary  artery  disease  (CAD)  in patients unable to
perform  exercise  testing   such   as   those   with   physical   handicaps,
deconditioning  or  the  effects  of  anti-anginal  drugs that the patient is
taking.  Other  indications  include  exclusion  of  suspected  CAD  in those
patients with ventricular pacemakers, or left bundle branch block,  and  risk
stratification  prior  to  peripheral  vascular  surgery  or after myocardial
infarction.  DIPYRIDAMOLE: Dipyridamole is given at a dose of 0.146 mg/kg/min
over 4 minutes  IV.   Five-ten  minutes  later  Thallium  201 is injected IV.
About 50% of patients will  experience  side  effects  such  as  chest  pain,
flushing,  headaches,  and dizziness.  These may persist for 20-30 minutes if
not reversed by IV theophylline.  The  half  life of dipyridamole is about 10
minutes.  It is  estimated  that  about  10-30%  of  patients  will  need  IV
theophylline.   The  sensitivity of IV dipyridamole-thallium 201 scintigraphy
is 90% with a specificity  of  70%  using in most cases, planar scintigraphy.
Sensitivity  and  specificity  is  similar  between   exercise-thallium   and
dipyridamole-thallium   imaging.    ADVANTAGES   OF   DIPYRIDAMOLE   IMAGING:
Dipyridamole  is  easy  to  administer, has a good safety record, will rarely
cause AV block  and  has  been  used  extensively  in risk stratification and
diagnosis of CAD.  (IV dipyridamole was approved by  the  US  Food  and  Drug
Administration  for  use  with  perfusion  imaging in 1992, but has been used
extensively  for  this   purpose   abroad.   DISADVANTAGES  OF  DIPYRIDAMOLE:
Theophylline is often needed to reverse the side effects of dipyridamole, the
peak effect occurs only minutes afer administration, dipyridamole may produce
less consistent dilation of the coronary arteries  than  adenosine,  and  the
long half life of about 10 minutes causes symptoms to persist for about 20-30
minutes  post-infusion.   DOBUTAMINE: High dose dobutamine acts by increasing
the  heart  rate  which  will   approximate  that  of  sub-maximal  exercise.
Dobutamine is a beta1-adrenergic agonist and when given at a  low  dose  will
increase  cardiac  contractility, but when given at high doses, there will be
an increase  of  myocardial  oxygen  demand  by  increasing systolic arterial
pressure and heart rate and coronary blood flow.  When given at a dose of  20
ug/kg/min,  coronary  flow will increase about 2 times that of baseline.  One
protocol is to start the  dobutamine  at 5 ug/kg/min, followed by incremental
increases of dobutamine at 3 minute intervals to 10, 20, 30 and 40 ug/kg/min.
One minute after the 40 ug/kg/min is started Thallium-201 is injected IV  and
this  dose  of  40  ug/kg/min  is  sustained  for  another  2  minutes before
terminating.   Sensitivity  and  specificity  has  varied  from  97%  and 80%
respectivity in one study when using doses up to 20  ug/kg/min,  to  80%  and
78%, respectively in another series of 80 patients using high dose dobutamine
infusion.   Side  effects occur in about 80% of patients, consisting of chest
pain, ischemic ST segment  changes  on  ECG, supraventricular and ventricular
arrhythmias  which  are  more  frequent  than  dipyridamole   or   adenosine.
ADVANTAGES  OF  DOBUTAMINE:  Dobutamine  can be used in patients with asthma,
severe heart failure, or damaged  AV  conduction, myocardial viability can be
assessed with low doses by radionuclide angiography or echocardiography,  and
the  dynamic  effects  produced  with  dobutamine  are  similar  to  those of
submaximal  exercise.   DISADVANTAGES  OF   DOBUTAMINE:  Dobutamine  must  be
administered by infusion  pump,  arrhythmias  are  more  frequent  than  with
dipyridamole  or  adenosine,  myocardial  ischemia is also more frequent than
with dipyridamole or adenosine, and  there is less experience with dobutamine
than with adenosine or dipyridamole.  ADENOSINE: Adenosine is a very  poweful
coronary   vasodilator.    Dipyridamole   works   indirectly  as  a  coronary
vasodilator by blocking the  facilitated  cellular transport and re-uptake of
adenosine which causes more adenosine to be available  for  interaction  with
adenosine  A2  receptors  located  in  the cell membrane, resulting in smooth
muscle relaxation and coronary vasodilatation.  When adenosine is given IV at
a dose of 140 ug/kg/min there is about a 4.3 times increase in coronary blood
flow velocity over the baseline.  At  doses  of 75-100 ug/kg/min there is a 3
fold enhancement of coronary blood flow velocity, but the flow rates are  not
steady  at  this  lower  dose  and  may  vary  over time.  When adenosine was
compared with dipyridamole by using  Doppler  catheter,  it was found that IV
adenosine at a dose of 140 ug/kg/min produced a greater decrease in  coronary
resistance  than  did  IV  dipyridamole  using  a  dose of 0.146 mg/kg/minute
infused over a 4 minute  period.   One  protocol  for giving the adenosine IV
consists of giving a continuous 140 ug/kg/min dose over a 6 minute period and
giving the IV Thallium-201 at  3  minutes  into  the  6  minute  infusion  of
adenosine.   Using  this  protocol  has  shown to be effective, safe and well
tolerated.  The side effects of adenosine  consist of essentially the same as
dipyridamole,  such  as  chest  pain,  flushing,  dizziness,  headaches   and
lightheadedness.   However,  the  frequency  and  intensity  are greater with
adenosine than with dipyridamole, but  adenosine  has  a very short half life
with resolution of the symptoms in about 1-2 minutes.  Because of this  short
half  life  and spontaneous resolution, theophylline, the antidote, is rarely
used.      The     sensitivity     and     specificity     of    quantitative
adenosine-thallium-201, single photon emission computed tomography  has  been
reported  to be about 87% and 90% respectively, for the detection of coronary
artery disease.  Adenosine can  also  be  used in combination with technetium
99m sestamibi scintigraphy and teboroxime imaging.  ADVANTAGES OF  ADENOSINE:
The  advantages  of  using  adenosine  in  conjunction  with  thallium 201 or
technetium 99m sestamibi are numerous.  The  half-life is less than 2 seconds
which translates  into  rapid  onset  and  termination  of  its  effects  and
consequently   rapid   rsolution   of   side  effects,  good  safety  record,
theophylline is  rarely  needed  to  counteract  the  side  effects, there is
consistent, maximal coronary vasodilatation  with  adenosine,  and  the  peak
effect  is demonstrated during its infusion.  DISADVANTAGES OF ADENOSINE: The
disadvantages of adenosine are  few  and  consist of the following: adenosine
will slow AV conduction, must be administered with an infusion pump, and  has
a  higher frequency and intensity record than dipyridamole.  However, because
of its ultra short  half  life,  the  side  effects are dissipated within 1-2
minutes spontaneously without the necessity  of  administering  theophylline.
At  the  time  of  this  writing,  FDA  approval  has  only  been granted for
dipyridamole perfusion scintigraphy.

                            -NECK MASSES-
THYROGLOSSAL  DUCT  CYSTS  AND FISTULAS: Clinically, a thyroglossal duct cyst
presents as an asymptomatic  single  soft,  sometimes moveable, midline mass.
It may be found anywhere along the course of the  thyroglossal  duct  between
the  foramen  cecum and the suprasternal notch, but the commonest location is
in the region of  the  hyoid  bone.   It  moves  up  during swallowing and on
protrusion of the tongue because of its attachement to  the  hyoid  bone  and
foramen  cecum.   Although  most  often  are diagnosed in children, it may be
found in patients of any age.   Thyroglossal duct cysts or fistulas may cause
swelling or  may  cause  recurrent  infection.   The  differential  diagnosis
includes  dermoid  tumors,  epidermoid  cysts,  lipomas,  enlargement  of the
pyramidal  lobe  of  the  thyroid,  pyramidal  lobe  cysts,  branchial  cleft
abnormality  that  approaches  the  midline,  inflammatory  lymphadenitis and
ranulas (cystic masses of the floor of the mouth caused by obstruction  of  a
duct  of  the sublingual gland.  Thyroglossal duct cyts are often swollen and
bluish and are not as solid  to palpation as pyramidal lobe cysts.  Branchial
cleft cysts should be distinguisable from  thyroglossal  duct  cysts  because
most branchial cleft cysts are located laterally along the anterior border of
the  sternocleidomastoid  muscle.   Rarely, pressure on the thyroglossal duct
cysts causes expression of fluid from  the  foramen  cecum at the base of the
tongue.  A thyroglossal duct cyst must be differentiated from ectopic thyroid
tissue.  Therefore, thyroid function tests and a thyroid  scan  are  obtained
routinely   before  surgical  excision  of  the  cyst  and  remaining  tract.
BRANCHIAL CLEFT CYSTS AND FISTULAS: They  develop  in patients of any age and
are found with equal frequencies on both sides of the neck.   More  than  95%
are located on the surface of the carotid sheath, deep to the anterior border
of  the  sternocleidomastoid  muscle.   They  are  usually  small,  but  with
enlargement  may  extend  toward the base of the skull or the tonsillar fossa
and  pass  between  the  internal  and  external  carotid  arteries.  Gradual
enlargement is typical, but they may fluctuate in size.   They  often  appear
after  an  infection  of  the  upper  respiratory  tract.  A single painless,
moveable, nontender cystic lesion that is located in the upper half or 2/3 of
the sternocleidomastoid muscle and increases  gradually in size is probably a
branchial cleft cyst.  The external sinus of a first branchial cleft cyst  is
characterized  by  an  opening  into  the  external auditory canal.  A second
branchail cleft cyst presents  at  the  anterior  border of the sternomastoid
muscle and opens internally  into  the  tonsillar  fossa.   Disorders  to  be
differentiated  from branchial cleft cysts include cystic hygromas, which can
be transilluminated, and more lobular  and  diffuse; lipomas, which are solid
but spongy; thyroglossal duct cysts, which are in the  midline,  and  carotid
body  tumors,  which  may produce a bruit and can be moved from side to side,
but not up and down.  LYMPHANGIOMAS  AND CYSTIC HYGROMAS: Of these cysts, 80%
are found in the posterior cervical triangle or in the supraclavicular  area.
However, they may extend into the cheek, mouth, tongue, parotid gland and ear
canal.   Diagnosis  is  made by physical exsam.  They are diffuse, irregular,
soft, compressible and painless and  can  be transilluminated.  Two thirds of
cystic hygromas are noted at birth, and 90% are found before  the  age  of  2
years.   Cystic  hygromas are symptomatic primarily because of their size and
appearance.  As the size increases, stridor may result because of compression
of the trachea in the  neck  or  mediastinum or both.  Treatment is surgical.
DERMOID CYSTS: Dermoid cysts often contains cheesy material, hair,  sebaceous
glands and sweat glands.  They may be congenital or acquired.  Of all midline
cysts,  28%  are  dermoid.   Dermoid  cysts  typically  present as a painless
midline swelling in the submental area  beneath  and attached to the skin and
free of the underlying tissue.  Infections may cause progressive enlargement,
which may result in obstructive symptoms.  Treatment  is  surgical  excision.
HEMANGIOMAS: These typically occur within the substance of the parotid gland,
but  may  occur  in  the  skin  or  deep  tissues  of the neck.  They are the
commonest benign tumors found in  infancy.   A hemangioma is present at birth
or appears in the first year as a diffuse, soft, nonpulsatile, bluish mass in
the area of the parotid gland that pushes the pinna out,  and  often  narrows
the  external  auditory  canal.   The  hemangioma  may  increase in size with
straining  or  crying.   Treatment  is   usually  not  necessary  since  most
hemangiomas regress spontaneously.  LARYNGOCELES: Laryngocelses occur with  a
male  to  female  ratio  of 5:1 with a peak incidence between ages 50-60.  Of
these tumors, 85% are  unilateral  and  15  %  are bilateral.  An association
exists between a laryngocele and the presence of carcinoma, or a papilloma of
the larynx which acts as a one way valve allowing air into, but  not  out  of
the  cyst.  Therefore laryngoscopy should be performed on all patients with a
laryngocele to search  for  an  underlying  lesion.  The external laryngocele
should be differentiated from the more  common  branchial  cleft  cyst  since
either  may present anterior to the sternocleidomastoid muscle.  Treatment is
surgical  revoval.   CERVICAL  LYMPHADENITIS:  Acute  inflammatory adenopathy
usually presents as multiple firm tender masses in the neck, often associated
with  tonsillitis  and  pharyngitis.   Dental  infections  account  for  30%.
TUBERCULOSIS LYMPHADENITIS: TB produces conglomerate masses of  lymph  nodes,
and  occasionally  a  chronic  draining  sinus  in the neck.  Of all cases of
pulmonary TB in the USA  5%  are  accompanied  by cervical TB.  A positive TB
test skin test, demonstration of acid fast bacilli in an excisional biopsy or
aspirate, or growth of Mycobacterium tuberculosis in culture establishes  the
diagnosis.   Atypical  TB usually presents with unilateral, painless discrete
lymph  nodes  in  the  submental,  submandibular,  or  carotid  triangles.  A
draining fistula may be present.  They  have  no  fever  or  other  signs  of
infection.   PPD  testing  is  negative whereas testing with antigen from the
atypical strains is positive.  Pulmonary  involvement may not be present with
atypical TB.  Excision or treatment with antituberculous drugs is  indicated.
CAT  SCRATCH  DISEASE:  There  is unilateral tender cervical adenopathy.  The
overlying skin may be erythematous  and  suppuration may occur.  Most are due
to intracutaneous inoculation by a cat scratch, although another  animal  may
be  implicated.   Diagnosis  is made by means of a skin test with cat scratch
antigen.  Treatment is symptomatic.   INFECTION  IN  THE  NECK SPACES: 90% of
abcesses occur  in  only  three  spaces:  The  retropharyngeal,  the  lateral
pharyngeal  and  the  submandibular.   The  retropharyngeal  space abscess in
infants and children usually results from lymphadenitis secondary to an upper
respiratory tract  infection.   The  child  typically  presents  with  a sore
throat, swelling behind a normal  tonsil,  and  sometimes  a  temperature  of
101-102  F.  Lateral  neck  x-rays  show  a  large  retropharyngeal swelling.
Treaatment is I&D.  In  adults,  a  retropharyngeal  abscess amy signify a TB
infection of the cervical spine There is an insidious onset with a low  grade
fever.   Pus may be aspirated from the retropharyngeal space and treatment is
with anti TB drugs.  The  lateral  pharyngeal  abscess  is seen more often in
adults  than  children.   They  are  a  complication  of   tonsillectomy   or
tonsillitis  in  60%  and  of  extraction  of  the  lower third molar in 30%.
Typically the  patient  has  had  an  upper  respiratory  tract  infection or
tonsillitis for 5-10 days before presentation and  have  septicemia,  chills,
and  spiking  fevers.  Unilateral or bilateral cervical fullness is felt deep
to the sternomadtoid muscle.  The tonsil and soft palate are displaced to the
midline on the affected  side.   The  neck  is diffusely tender and voluntary
motion of the neck is minimal to avoid pain.  Dysphagia is  present  and  the
patient  drools  to  avoid  swallowing.   If  left  untreated a peritonsilalr
abscess may extend  through  the  superior  constrictor  muscle laterally and
enter the parapharyngeal space.  Airway obstruction  is  a  life  threatening
complication  of  a  parapharyngeal  abscess.   Late signs include hoarsness,
cough and dyspnea.  Other complciations include septicemia and erosion of the
carotid artery.   Treatment  is  with  IV  antibiotics  and  drainage  of the
abscess.  The sumandibular infection, Ludwigs angina, is a  rapidly  swelling
cellulits  of the floor of the mouth secondary to infection of a submaxillary
gland or tooth.  OF patients  with  Ludwigs  angina, 80% have dental disease.
The tongue is elevated superiorly and posteriorly and the airway  may  be  in
danger.   Pain,  trismus  and  salivation  may  be  present.  Treatment is IV
antibiotics.  I&D is usually not necessary, since pus is seldom found in this
cellulitis.  INFECTIOUS MONONUCLEOSIS: Is  caused  by the Epstein Barr virus.
Atypical mononuclear cells derived from lymphcytes constitute 10-20%  of  the
leukocytes  in  the  peripheral  blood and invade the spleen and lymph nodes.
The  peripheral  Heterophile  antibody  titer  is  greater  than  1:256.  The
cervical nodes are enlarged and rubbery, and the  tonsils  are  covered  with
exudate.   High  fever,  anorexia  and  malaise  are usually presen,t and the
patient is usually young.   Infectious  monnuceleosis  should be suspected if
there is no response to antibiotics and the lymph nodes are larger than 3 cm.
It may resemble lymphoma.  However,  the  nodes  in  lymphoma  are  typically
asymptomatic   and   unilateral.    SYPHYLIS:   Syphylis  may  present  as  a
progressively enlarging, mildly painful cervical node.  The intraoral chancre
may not be found if treatment has  been  given or if the time interval is not
appropriate.  Lymphadenopathy may occur in the secondary stage  of  syphilis,
2-10  weeks  after  infection.  The onset of the secondary stage is marked by
malaise, chills,  headache,  myalgias  and  sore  throat.  Maculopapular skin
lesions involve the palms and soles, and mucous patches or focal  superficial
ulcers  may  be  seen on the mucous membranes.  A mildly tender cervical node
may be found.  Spirochetes in ulcerated nodes may be identified by dark field
microscopy.  An FTA-ABS is obtained  to  identify  a false positive result on
the VDRL test or to confirm clinical suspicion in the presence of a  negative
result  on  the  VDRL.   Treatment  is  surgical  excision  of  the node if a
diagnostic specimen is needed, but primary treatment is penicillin.  CERVICAL
METASTASIS: A firm nontender enlarging  mass  in  the neck, particularly in a
person over 40 should be considered to be metastatic cancer  from  a  primary
lesion in the head and neck until proved otherwise.  The tumor most likely to
metastasize  to  the  cervical  nodes  is  squamous cell carcinoma, which may
originate anywhere in  the  mucosa  of  the  upper respiratory and alimentary
tracts or in the  skin  of  the  face  or  the  scalp.   Metastatic  cervical
adenocarcinoma  may  originate  from  a primary tumor in the lung, breast, GI
tract, or pancreas.  If metastasis is to the bone, possible locations for the
primary tumor are  the  kidney,  breast,  and  prostate gland.  Postauricular
nodes drain the scalp and external ear.  Midjugular (mid sternocleidomastoid)
drains the hypopharynx, larynx, and  thyroid  gland.   Supraclavicular  nodes
drain  the  hypopharynx (pyriform sinuses), lung, breast, cervical esophagus,
and abdomen.  Posterior triangle nodes (posterior to the sternocleidomastoid)
drains the naso pharynx, and posterior part of the scalp.  Preauricular nodes
drain the anterior part of  the  scalp,  lateral part of the orbit, forehead,
ear canal and parotid gland.  Angle of the jaw nodes drain  the  nasopharynx,
supraglottic  larynx,  tonsil  fossa,  hypopharynx,  tongue base, and parotid
gland.  The submaxillary nodes drain  the face, nose, maxillary sinus, buccal
mucosa, floor of the mouth, and submaxillary  glands.   The  submental  nodes
drain  the  anterior  part  of  the  mouth  and  lip.   The  low jugular (low
sternocleidomastoid)  nodes  drain  the  subglottic  larynx,  esophagus,  and
thyroid gland.  OCCULT PRIMARY LESIONS: In  about 2/3 of patients in whom the
primary tiumor is not located, the primary lesion eventually is found in  the
nasopharynx,  thyroid  gland, tonsil, base of the tongue or hypopharynx.  The
remaining 1/3 of primary lesions are  found below the caivicle, most often in
the lung, GI, pancreas,  prostate  gland,  or  breast.   Radiography  of  the
sinuses  should be done to rule out silent carcinoma.  Adenocarcinoma is more
likely to present without a  suspicious  primary lesion than is squamous cell
carcinoma.  HISTIOCYTIC LYMPHOMA AND HODGKIN'S DISEASE: These 2  account  for
55%  of  all cancer in children.  Hodgkin's disease is rare in children under
the age of 5 and peaks  in  children  between  ages  5-9 , with a 3:1 male to
female ratio.  Histiocytic  lymphoma  may  occur  in  patients  of  any  age.
Children  with  a  neck mass greater than 3 cm in diameter should be examined
for  involvement  of  other  lymphoid  tissue  in  the  groin,  axillae,  and
Waldeyer's ring.  Check for  hepatosplenomdegaly  or enlarged mediastinal and
hilar nodes.  RHABDOMYOSARCOMA: Is the commonest solid  tumor  found  in  the
head  and  neck  of  children  between  ages  1-4,  in contrast to peripheral
rhabdomhyosarcoma  which  is  commonly  found  in  the  40-60  year  old  age
group.Rhabdomyosarcoma is uncommon in  the  black  patient.  The orbit is the
most frequent site of involvement in the head and  neck.   It  is  associated
with  the  best  prognosis  in this site.  Other sites of involvement are the
soft tissues of the neck, nasopharynx, face, ear, mastoid, and the tongue.  A
nontender  firm  cervical  mass  may  be  the  first  indication.   Signs  of
nasopharyngeal obstruction, such as adenoid facies, mouth breathing, snoring,
and hearing loss secondary to  serous  otitis  media may be present.  THYROID
DISEASE: Special attention should be directed to the thyroid gland  in  young
persons  and  female  patients.   A  child  10 years of age or younger with a
solitary nodule has more than  a  70%  chance of having thyroid cancer.  This
probability is increased with a history of radiation to the  head  and  neck.
Hoarseness and dysphagia may accompany.  Serum measurements of calcitonin are
useful  for  medullary  cancer.   Thyroid  scan shows a cold nodule.  Diffuse
enlargement of the  thyroid  may  be  caused  by  simple  goiter, but this is
unusual because of the routine addition of  iodine  table  salt.   Autoimmune
thyroiditis  may cause acute painful swelling of the thyroid.  SALIVARY GLAND
TUMORS: 	In adults 25% of solid tumors of the parotid gland are malignant.
In children 50% are malignant.  An 8  fold increase in breast cancer has been
associated with cancer of the salivary glands.  Cancer of the salivary glands
usually presents as a painful,  firm  fixed  mass.   Facial  nerve  paralysis
accompanies   advanced   disease  and  almost  always  indicates  malignancy.
Radionuclide scanning which may show a cold lesion in the presence of cancer.
The exception is mucoepidermoid carcinoma, which  may appear as a hot spot on
the scan.  Technetium scan is  a  specific  test  for  papillary  cystadenoma
lymphomatosum  (Warthins  tumor).   Sialography  may show a filling defect or
splaying of the ducts around  a  tumor.  Computed tomography with sialography
is helpful in defining the lcoation and extension of  the  tumor  beyond  the
gland  into  the  neck.  Overall, fine needle aspiration cytology is the most
useful study.

                        -NEPHROTIC SYNDROME-
Nephrotic  syndrome affects children from ages 1.5 to 6 years.  Adults can be
affected at any age and males  equal  females in incidence.  The basic lesion
is increased glomerular permeability that allows protein  to  leak  into  the
urine  with  proteinuria  that  is  greater  than  3.5  grams/24  hours  or >
2gm/day/square meter.  There also  is  hypoalbuminemia  of less than 3 gm/dL,
generalized edema, lipiduria and hyperlipidemia.   SIGNS  AND  SYMPTOMS:  The
clinical  findings  of nephrotic syndrome stem from the hypoalbuminemia which
lowers the oncotic pressure which  results in movement of intravascular fluid
to the extravascular compartment.  With the  decreased  volume,  compensatory
measures are activated with an increase of the renin-angiotensin- aldosterone
system,   increased   antidiuretic   hormone  release  and  decreased  atrial
natriuretic peptide.   This  causes  an  increase  in  the  sodium  and water
retention in an effort to offset the  decreased  intravascular  volume.   The
patient  may  have  edema, abdominal pain and distention, hypertension, puffy
eyelids, scrotal swelling,  and  dyspnea.  LABORATORY: Hyperlipidemia results
from an increase in hepatic cholesterol and lipoprotein  synthesis,  decrease
in peripheral and liver catabolism of lipoproteins and an increase in urinary
excretion  of HDL.  There is an increase of the following in the serum: total
cholesterol, LDL,  VLDL  and  triglycerides.   The  HDL  is  decreased.  This
profile  is  important  because  the  lipoprotein  alteration  can  cause  an
accelerated coronary atherosclerosis and progression of renal  disease.   The
serum  calcium  is  often  decreased  also.   The  BUN  and creatinine may be
elevated and the urine usually will  show  fat bodies ( macrophages and renal
tubular epithelial cells that are filled with fat  droplets).   The  24  hour
total  protein  should  exceed 3.5 g/day or the protein/creatinine ratio on a
random urine  is  approximately  3.5  or  greater  in  the nephrotic patient.
(normal is < .2).  These two tests will yield very accurate  results.   There
may   also   be   aminoaciduria.   There  may  be  an  increased  serum  IgM,
beta-globulin and IgG.   Biopsy  results  of  the  kidney  may show thickened
glomerular basement membrane, fused foot processes, focal sclerosis and renal
tubular atrophy.  SPECIAL LABORATORY TESTS: Antinuclear antibody,  rheumatoid
factor,  C3,  C4,  CH50, venereal disease serology including HIV, hepatitis B
surface antigen, protein  and  urine  electrophoresis, sedimentation rate and
cryoglobulins.  EVALUATION: The most important aspect in evaluation is a good
history and physical.  If the history and physical is largely  negative  then
the  patient  has  one  of  the primary forms, whereas if a secondary form is
present then there may  be  symptoms  of  connective tissue disease, sexually
transmitted disease,  hepatitis,  malignancy,  HIV  infection,  ingestion  of
prescription  or over the counter medicines and diabetes mellitus.  Nephrotic
syndrome can be divided into  a  primary  group  which  have no know cause or
secondary  forms.   PRIMARY  DISEASES:  Minimal  change  disease,  membranous
glomerulonephritis,  focal  glomerulonephritis,   focal   glomerulosclerosis,
membranoproliferative    glomerulonephritis,   IgA   nephropathy,   mesangial
proliferative glomerulonephritis and  rapidly progressive glomerulonephritis.
SECONDARY  DISEASES:  Diabetes  mellitus,   Systemic   lupus   erythematosus,
Allergens   (snake   venoms,  insect  stings,  poison  ivy  and  antitoxins),
Amyloidosis,  Erythema  multiforme,  Henoch-  Schonlein  purpura,  Toxemia of
pregnancy,  Malignancy   (lung,   breast,   stomach,   kidney   and   colon),
Heredofamilial    (Alport's   syndrome   and   fabry's   disease),   Familial
mediterranean  fever,  Hodgkin's   disease,   Infections  (bacterial,  viral,
helminthic  and  protozoal),  Lymphomas  and  leukemias,  Multiple   myeloma,
Melanoma,  Drugs and toxins (mercury, gold, penicillamine, captopril, heroin,
Sarcoidosis, Serum  sickness,  Polyarteritis  nodosa  and Sjogren's syndrome.
RENAL BIOPSY: Minimal change disease  is  likely  in  patients  in  whom  the
nephrotic  syndrome develops rapidly and there is massive proteinuria of > 10
g/day.  Most clinicians would  probably  not  obtain  a  renal biopsy in this
disease.  Renal biopsy is probably not necessary in  long  standing  diabetes
mellitus.   If  the  patient has small shrunken kidneys, a bleeding diathesis
and   uncontrolled   hypertension,   then   renal   biopsy   is   a  relative
contraindication.  However, SLE has several subsets of renal histology and it
is important to have this information to  afford  the  best  treatment  plan.
COMPLICATIONS:  If  the  patient  develops  hyperlipidemia there is premature
atherosclerosis and all  of  its attendant complications.  Hypercoagulability
due to protein S deficiency is present and can cause pulmonary embolism,  DVT
and  renal  vein  thrombosis.   Dehydration can cause acute renal failure and
hypotension.  The potential of  infection  is  always  present because of the
decreased protective immunoglobulin decrease.  The patient may  also  develop
anasarca, pleural effusion and ascites.  There may be development of a factor
IX  deficiency.   HISTOLOGY AND DISEASE: Hodgkin's disease is associated with
minimal  change  disease.   Solid  tumors  and  hepatitis  B  infection  with
membranous glomerulonephritis, and  vesicoureteral  reflux, HIV infection and
heroin abuse are often associated with  focal  segmental  glomerulosclerosis.
SLE    can    be    associated    with   several   types   of   proliferative
glomerulonephropathies.  TREATMENT (NON-SPECIFIC) Aggressive diuretic therapy
should be tempered because of the decreased volume that may precipitate renal
failure and initiate a hypercoagulable state.  The patient's weight should be
followed carefully.  Lasix should  be  given  initially  and  if the edema is
resistant then metolazone can be added.  The hypoalbuminemia  is  managed  by
using  a  high  biologic  value protein restriction daily diet of 0.8 g/kg of
ideal body weight.  Protein loading has  been shown to increase urine protein
excretion.   Some  patients,  particularly  in  diabetes  may  benefit   from
angiotensin  converting  enzyme  inhibitors  or  calcium  channel blockers by
decreasing proteinuria.  The hyperlipidemia may  be  managed with a bile acid
resin or one of the HMG CoA reductase inhibitors.  These should be used  with
caution  however  as  the  inhibitors may cause rhabdomyolysis and worsen the
renal failure.  SPECIFIC THERAPY:  Minimal  change  disease  in adults can be
treated with prednisone at 2 mg/kg of body weight  daily  for  1  week,  then
every  other day for 7 weeks.  This will bring about a remission in about 80%
of adults.  Up to  16  weeks  of  therapy  may  be  required.  If the patient
doesn't  respond  then  a  second  biopsy  may  reveal  a   focal   segmental
glomerulosclerosis that was not seen on the first specimen.  Another schedule
in adults would be to use prednisone at 1-1.5 mg/kg/day for 4-6 weeks.  After
response,  continue  the  prednisone  for  another  2  weeks  then  change to
maintenance of 2-3 mg/kg on  alternate  days  for  4  weeks and taper to zero
during the next 4 months.  For children use prednisone 60 mg/square meter  or
2 mg/kg/day orally for 4 weeks.  After response, continue for another 2 weeks
then  change  to  maintenance  of 2-3 mg/kg on alternate days for 4 weeks and
taper to zero during the next 4 months.  Membranous glomerulonephritis can be
treated with month long  prednisone  alternating  with  month long courses of
chlorambucil for 6 months.

                         -NEUROFIBROMATOSIS-
Neurofibromatosis occurs as two types.   Type I neurofibromatosis, also known
as von  Recklinghausen  disease  affects  about  1/4000  individuals  and  is
transmitted  as  an autosomal dominant trait.  About 50% are familial and the
remainder occur sporadically due  to  new  mutations.  It is characterized by
multiple neurofibromas, and multiple hyperpigmented  macules  (cafe  au  lait
spots).   Type  II  is  characterized  by  bilateral acoustic neuromas of the
eighth nerve.  Type II is  much  less  common, affecting only about 1/50,000.
It is also transmitted as an  autosomal  dominant  trait.   Neurofibromatosis
type  I  can  be  diagnosed if 2 of the following are present: 1..two or more
neurofibromas  of  any  type,  or  one  plexiform  neurofibroma.  2..multiple
freckles in the axillary or inguinal regions.  3..six  or  more  cafe-au-lait
macules.   In  prepubertal  patients  these  should  be  greater than 5 mm in
diameter; those that are postpubertal  should  have diameters greater than 15
mm.  4..optic glioma.  5..two or more Lisch nodules (iris hamartomas).   6..a
first   degree  relative  such  as  a  parent,  sibling  or  offspirng,  with
neurofibromatosis.  7..a bony  lesion  such  as  sphenoid  dysplasia, that is
typical for neurofibromatosis.   Type  II  is  diagnosed  by  fulfilling  the
following  criteria:  1..bilateral eighth nerve tumors that can be visualized
with CT or MRI.  2..a  first  degree relative with neurofibromatosis type II,
and either a unilateral eighth nerve tumor, or 2 of the  following;(plexiform
neurofibroma,   neurofibroma  of  another  type,  glioma,  meningioma,  or  a
presenile  posterior  cataract).   Neurofibromatosis  usually  presents  with
cafe-au-lait spots during the first year of life.  The cafe au lait spots are
usually distributed over the trunk, pelvis,  and flexor creases of the elbows
and knees.  However, they can occur anywhere with the exception of the palms,
soles and scalp.  They can vary between a  few  millimeters  to  centimeters.
Rarely,  children  may  be  born with bowing or pseudoarthrosis of the tibia,
large  plexiform  neurofibroma,  or  absence   of  the  sphenoid  wing.   The
neurofibromas usually do not appear  until  late  childhood  or  adolescence.
There  may  be  only  a  few or thousands.  They may be distributed along any
peripheral  nerve  producing  symptoms  secondary  to  nerve  or  spinal cord
compression.   Patients  may  also   develop   Lisch   nodules   (melanocytic
hamartomas) that appear as round elevations that project from the iris.  They
tend  to be age dependent and bilateral, found in 10% of patients less than 6
years old, 50% of patients less  than  30,  and in almost all patients by the
age of 50.  They may be clear, yellow or brown.  They are  visible  with  the
naked  eye,  but  will require slit lamp examination to distinguish them from
nevi of  the  iris.   Patients  may  also  have  patchy  or  diffuse areas of
hyperpigmentation, hypopigmented spots and  angiomnas.   Intracranial  tumors
may  also be present.  These usually consists of astrocytomas that can affect
the cerebrum or cerebellum.  There  is  also  an increased incidence of optic
nerve gliomas.  The incidence of  optic  gliomas  ranges  from  15-20%  Optic
gliomas usually present with decreased visual acuity or visual field defects.
The  glioma  mass  may involve the optic chiasm or hypothalamus.  Meningiomas
can be seen in Type I or II,  but  are more common in type II.  There also is
an increased  incidence  of  ependymomas,  medulloblastomas  and  hamartomas.
Patients  may  also  have  tumors  of  the  spine  that  can  be  intradural,
extradural,  single  or  multiple.   These  tumors can be dumbbell shaped and
extend through the intervertebral foramen  with enlargement of the foramen or
create  a  defect  of  the  adjacent  bone.   Accompaning  syringomyelia  may
co-exist.   Congenital  glaucoma  may  also  be  present,  caused  by   angle
obstruction  from  neurofibromas,  angle  synechiae,  and  thickening  of the
ciliary body and choroid.  Osseous  changes consist of pseudoarthrosis of the
distal tibia, scoliosis (10-40%), kyphosis, bowing of the tibia  and  fibula,
anterior  meningocoeles,  enlarged  intervertebral  foramina,  enlarged sella
turcica, J-shaped sella,  sphenoid  wing  abnormalities,  bony defects of the
orbit, absence of the greater wing of the sphenoid bone,  subperiosteal  bone
cysts,  and  vertebral  scalloping.   Other  lesions include macrocephaly and
short stature which occur in  10-40%  of patients.  Precocious puberty may be
seen in patients with hypothalamic gliomas and hamartoma.  Mental retardation
and  seizures  may  occur  in  10%.   Less   than   1%   of   patients   with
neurofibromatosis will have pheochromocytomas, whereas 4-23% of patients with
pheochromocytomas  will  have  neurofibromatosis.  There also is an increased
frequency of Wilm's  tumor,  multiple  endocrine neoplasia, medullary thyroid
carcinoma, leukemia and neuroblastoma  in  patients  with  neurofibromatosis.
The  prognosis  for  types  I  and  II  is usually normal unless they develop
malignant tumors.  TREATMENT: There is  no specific treatment for either form
of neurofibromatosis.  Local excision may  be  carried  out  for  symptomatic
lesions.

                  -NEUROLEPTIC MALIGNANT SYNDROME-
The  neuroleptic  malignant  syndrome  (NMS) is a potentially fatal syndrome,
characterized  by  fever,  muscle  rigidity,  autonomic  instability,  and an
altered  sensorium   caused   by   neuroleptic   drugs   as   phenothiazines,
thioxanthenes,  butyrophenones, loxapine and clozapine.  There is no relation
to the duration or  dose  of  the  medications,  but  there  appears to be an
increased incidence of the syndrome when the  dosage  is  suddenly  increased
from  a  previously  stable level.  The incidence of the syndrome in patients
taking neuroleptic drugs is .5  -  1%.   Many  of these neuroleptic drugs are
used to treated conditions such as Tourette's syndrome, Huntington's  chorea,
Sydenham's  chorea,  emesis  and  in  managing  dissociative anesthesia.  The
syndrome appears to  be  more  common  in  young  men  who  have disorders as
depression, mania and schizoaffective  disorders.   At  particular  risk  are
those  taking  lithium  along with neuroleptic medications.  Also, any person
taking the  very  potent  drugs,  haloperidol  (Haldol),  and trifluoperazine
(Stelazine) and fluphenazine (Permitil,  Prolixin)  are  at  increased  risk.
There seems to be an increased incidence of neuroleptic malignant syndrome in
those  in  whom  the  dose of neuroleptic has recently been increased, and in
patients that are  using  the  depot  preparations  of fluphenazine decanoate
(Prolixin).  The major criteria of NMS includes fever, rigidity and  elevated
creatine  phosphokinase.   The  minor  criteria consist of tachycardia, blood
pressure alteration,  diaphoresis,  tachypnea,  leukocytosis  and  an altered
state of consciousness as excitement, coma and stupor.  To make  a  diagnosis
of  NMS  requires  3  major  criteria  or  two  major criteria and four minor
criteria.  The temperature  usually  is  between  101  and  104 F, but higher
temperatures have been seen.  The rigidity may be associated with dysarthria,
dysphagia, tremors, opisthotonos, blinking eyes and a positive Babinski.  The
tempo of the evolution of the disease may be characterized  as  being  fairly
swift,  usually  developing  over 24-72 hours unless treatment is instituted.
Once treated, the syndrome slowly  subsides  over about 10 days, unless there
is intervening  complications.   Those  patients  that  have  received  depot
medications as Prolixin may take 10-30 days to recover.  COMPLICATIONS: There
may  be  20-30%  mortality over a 3-30 day period.  Complications that may be
life threatening include acute  renal  failure  developing from myolytic heme
pigment  tubular  necrosis,  dehydration,  decreased  renal  perfusion   from
autonomic instability.  There may be cardiovascular collapse which can be due
to   rhythm   disturbances   and   electrolyte   alterations.    Disseminated
intravascular  coagulation  may  develop  as  well  as  thromboembolism.  The
decreased level of consciousness may result in dysphagia and aspiration.  The
rigidity  may   cause   decreased   chest   compliance   with  its  attendant
complications.  LABORATORY: The creatine phosphokinase levels  are  extremely
high,  being reported up to 100,000 IU/L, but more typically between 2000 and
15000.  The aldolase may be elevated.  There is a leukocytosis usually in the
range of 15,000 to 30,000 with a leftward shift.  UA may reveal hematuria due
rhabdomyolysis.  Liver function tests  may  be elevated.  CSF sometimes shows
increased protein but otherwise is benign.  At  autopsy  there  has  been  no
specific   findings.    The   EEG   may  reveal  only  non-specific  changes.
DIFFERENTIAL DIAGNOSIS: Several other diseases  may be simulated, but usually
can be distinguished by subtle differences.  For example, patients  that  are
taking  MAO inhibitors may develop hypertension if exposed to tyramine, which
can cause rigidity and hyperthermia.  The distinction between NMS and the MAO
syndrome is  extremely  important,  because  treating  the  MAO syndrome with
levodopa and bromocriptine (drugs used in  treating  NMS),  may  augment  the
hypertensive  hyperthermic  crisis  of  the  MAO syndrome.  Infections of the
central  nervous  system   are   differentiated   by   changes  in  the  CSF.
Phenothiazine induced heat stroke may be  confusing,  but  in  this  disorder
there  is no diaphoresis or rigidity.  Malignant hyperthermia is an autosomal
dominant condition which  is  associated  with  anesthetic  exposure.  In the
so-called  anticholinergic  crisis  there  is  dry  skin,  no   rigidity   or
diaphoresis,  but  there  are dilated pupils.  In lethal catatonia there is a
history of  schizophrenia  and  an  absence  of  neuroleptic medication.  Any
hypertonic state as tetany, strychnine poisoning and stiffman  syndrome  must
be  ruled out.  CNS AIDS, viral encephalitis and Wilson's disease may also be
considered in the  differential.   TREATMENT:  Treatment starts with stopping
the offending neuroleptic.  Dialysis is of no help because  of  high  protein
binding and lipid solubility.  The patient should be hydrated to help prevent
and  control  myoglobinuric  renal  failure.   Control  of fever with cooling
blankets  and  adequate  nutrition  is  essential.   Prevention  therapy with
subcutaneous Heparin  should  be  given  to  avert  pulmonary  thromboembolic
disease.   Measures  should  be  taken to keep the lungs clear of secretions,
prevent pulmonary aspiration, use  antibiotic  therapy as needed, and provide
ventilatory support as needed.  Bromocriptine 2.5-10 mg po tid and amantadine
100-200 mg po bid have been used.  Dantrolene can be given as 50  mg  IV,  as
needed  to  help  the  rigidity,  but  10  mg/kg/day  should not be exceeded.
Dantrolene may also be  given  orally  50-200  mg qd.  Monitor liver function
tests when using Dantrolene.  l-DOPA and electroshock therapy have been  used
as  well  as  Nitroprusside  IV  and  minoxidil  when Dantrolene failed.  Any
patient  after  recovering  from  NMS,  must  be  evaluated  individually for
re-institution of neuroleptics in order to control their underlying  disease.
Several  points should be mentioned.  It is critical that informed consent be
obtained, and that from 10-30 days  elapse after remission from the syndrome.
The dopamine agonist used in treatment should be continued for  at  least  10
days  following  remission  of  NMS,  and  even  longer,  if depot drugs were
involved.  Try to use low  potency  neuroleptics  at low dosages, and titrate
very slowly.  Creatine phosphokinase levels should be  monitored  frequently.
It  is estimated that about 25% of patients will re-develop the NMS after the
original episode and another 25 %  will  develop  at least one feature of the
neuroleptic malignant syndrome.  The other 50% of patients  must  be  watched
indefinitely, because re-development is always a possibility.

                       -NEUTROPENIA AND FEVER-
Neutropenia  is an absolute granulocyte count of < 1500 granulocytes/mm3.  It
is calculated as the neutrophils  plus  bands  x  total white cell count.  If
there is no fever present the patient may be asymptomatic.  However,  as  the
neutropenia  declines,  fever  and  infection  intervene.   Usually,  if  the
neutrophil  count is > 1000 there are normal host defenses against infection.
For neutrophils counts between 500-1000, the  patient  is at some risk and is
capable of showing signs of  infections.   However,  with  neutrophil  counts
between  200-500  the patient is at great risk for infection and may not show
signs of infection.  For neutrophil counts  < 200, the patient is susceptible
to life threatening infections and must  be  hospitilized  and  treated  with
antibiotics.   The  risk  of  a  neutropenic  patient developing infection is
related to  the  severity  and  duration  of  the  neutropenia.  Chemotherapy
induced neutropenia secondary to cancer is a very  common  cause  of  febrile
neutropenia.   Most of these infections can be found in the lungs, alimentary
canal, skin and sinuses.  Fever, is not necessarily associated with infection
in cancer patients.  It may  be  caused  by  the tumor itself, transfusion of
blood products, inflammation, antimicrobial drugs and chemotherapeutic drugs.
Patients  that  have  had  bone  marrow  transplantation  are  at  risk   for
interstitial  pneumonia,  particularly  from  cytomegalovirus.  Patients with
Hodgkin's disease are at risk  for  herpes zoster and cryptococcal pneumonia.
Patients on high  dose  steroids  are  at  risk  for  fungal  infections  and
pneumocystis  pneumonia.   Also,  patients  that are taking steroids and have
severe neutropenia are  not  capable  of  displaying  any signs of infection.
Common bacterial causes of fever in neutropenic patients include  Pseudomonas
aeruginosa,  Escherichia coli, Klebsiella, Streptococcus pneumoniae, viridans
and  pyogenes,  Enterococcus  faecalis,  Corynebacterium,  and Staphylococcus
aureus  and  epidermidis.   Aerobic  gram  negative   bacilli,   particularly
Escherichia coli and Klebsiella and Pseudomonas aeruginosa, account for up to
50%  of all culture infections.  However, the incidence of coagulase negative
staphylococci  and  other  gram  positive  bacteria  is  becoming  much  more
frequent,  and  may  represent  30-50%  in  some  hospitals.   Common  fungal
infections which may emerge  during  treatment with broad spectrum antibiotic
therapy include candidiasis and  aspergillosis.   For  example,  any  patient
complaining  of  mild  pain  in  the  central face may be developing a fungal
infection secondary  to  Aspergillus  or  Mucor.   Since  the  granulocyte is
responsible for the inflammatory response, the presence  of  neutropenia  may
obscure  this  inflammatory  response  and the classic signs and symptpoms of
infection  may  not  be  present.    All   IV  catheters,  biopsy  sites  and
venipuncture sites should be examined.  With the best of cultures only  about
30-50%  of  pathogens  are usually identified, and if the absolute neutrophil
count is less than  100  cell/ul,  bacteremias  are  only documented in about
20-30%.  The mouth, oral pharynx, sinus, lungs, and anus should	be  examined.
Tenderness  in  the  perianal  area  can indicate an anaerobic infection, and
diffuse abdominal  pain  is  suggestive  of  typhlitis.   Prior  to beginning
antibiotic therapy, cultures should be obtained from the blood, urine and any
other suspicous sites, along from blood in the lumen  of  catheters.   Lumbar
puncture  and  cultures  of  the  CSF may be indicated also.  Chest x-ray and
sinus x-rays  are  routinely  done.   TREATMENT:  Broad  spectrum antibiotics
should  be  started  immediately   after   cultures   have   been   obtained.
Traditionally,  in  the  past  the  patient  has  been started on combination
therapy with an aminoglycoside and either a beta lactam penicillin or a third
genration cephalosporin to cover gram  negative pathogens.  However, to avoid
the  nephrotoxicity  with  aminoglycosides,  or  in   patients   with   renal
impairment,  the  combination  of  a  third  generation cephalosporin such as
ceftazidime or cefoperazone 30-50 mg/kg  every  8 hours + a ureido-penicillin
such as piperacillin or mezlocillin  350-500  mg/kg  every  4  hours  may  be
started.   In  patients without renal dysfunction, the patient may be started
on   an   aminoglycoside   (gentamicin,   tobramycin   or   amikacin)   +  an
antipseudomonal carboxy or ureido-penicillin (piperacillin, ticarcillin  with
or  without clavulanic acid, azlocillin or mezlocillin OR an aminoglycoside +
a   third   generation    antipseudomonal   cephalosporin   (ceftazidime   or
cefoperazone) OR monotherapy with  either  ceftazidime  or  imipenen.   Serum
levels  of  the  aminoglycoside  should  be done and adjusted to achieve peak
levels of 5-8 ug/ml  and  trough  levels  of  2  ug/ml or less.  If coagulase
negative  staphylococci,   methicillin   resistant   staphylococcus   aureus,
corynebacterium,  or  alpha  hemolytic streptococci are suspected, vancomycin
can be added at day  four  if  there  has  been  no response from the initial
antibiotics.  If, at the end of one  week,  there  is  persistent  fever  and
neutropenia,  amphotericin  B should be started, after a test dose of 1 mg of
amphotericin is given over  1  hour.   If  the  patient becomes afebrile, all
sites of infection have cleared and the neutrophil count  is  >  500/ul,  the
antibiotic  therapy  can  be  discontinued  after 7 days.  Colony stimulating
factors (CSF) such as G-CSF, have  been  used to hasten recovery of the white
count and reduce infectious complications in a variety  of  malignancies  who
have  received  high  dose  chemotherapy  with or without bone marrow rescue.
G-CSF is given at a dose  of 5 ug/kg/day subcutaneously.  Therapy with growth
factors has not,  however,  demonstrated  a  decrease  in  the  incidence  of
infections  or  improved survival.  G-CSF may also be given IV.  Side effects
of G-CSF include rare cases  of  vasculitis  and  bone pain.  Side effects of
GM-CSF include pleural and pericardial effusions,  fluid  retention,  cardiac
arrhythmias, renal and hepatic

                   -NICARDIPINE AND HYPERTENSION-
5-10  mg/hr  IV.   Side  effects:  tachycardia,  flushing,  headache,   local
phlebitis.

                          -NIPPLE DISCHARGE-
Patients with nipple discharge that are non-lactating or non-pregnant  should
be   questioned  about  the  medications  that  they  are  currently  taking.
Estrogen,  reserpine,  opiates,   diazepam,   phenothiazines,  and  tricyclic
antidepressants can cause galactorrhea.  Any cause of an  elevated  prolactin
can  cause  galactorrhea  such  as  throacotomy scars, stress, herpes zoster,
cervical spinal lesions, nipple  stimulation  (clothing and sexual foreplay).
A differentiation between galactorrhea and non-galactorrheal discharge should
be made by obtaining a fat stain such as  an  oil  red  O  stain  which  will
identify  fat  droplets  seen  in  galactorrhea.   Galactorrhea  implies that
underlying  breast  disease  is  not  present.   If,  indeed  galactorrhea is
present, TSH, and prolactin should be done.  If the prolactin  is  normal  or
elevated  and  the TSH is elevated, check patient for hypothyroidism.  If the
prolactin is  elevated  with  normal  TSH,  evaluation for hyperprolactinemia
should be carried out.  If the prolactin  is  >  100  evauate  for  pituitary
adenoma  with  CT  or  MRI.   If prolactin is < 100 check for other causes as
drugs, nipple stimulation, and repeat prolactin in the fasting state.  If the
repeat  prolactin  in  the  fasting  state  is  normal,  follow  the  patient
clinically and repeat exam in  3-6  months.   If  the patient presents with a
discharge that is non-galactorrhea, palpate breast carefully for masses.   If
no mass is palpable do cytology on the specimen, followed by a mammogram.  If
mammogram  is normal and no physical findings are present, recheck patient in
6-12 months if the discharge persists.

                           -NITROGLYCERIN-
5-100 ug/min as IV infusion.  Start at 5 ug and increase by 5-10 ug/min after
5 min until desired effect.  (Add  25  ug of nitroglycerin (Tridil) to 250 ml
D5W and drip at 5 ug/min or 3 ml/hr to start.  Use glass IV  bottle  and  non
PVC    IV   tubing.    Side   effects:   flushing,   tachycardia,   headache,
methemoglobinemia, vomiting.

                          -NITROGLYCERIN IV-
INDICATIONS:  Is  used  for   myocardial   infarction  associated  with  CHF,
perioperative hypertension, unstable angina, refractory angina pectoris,  and
operative    control    of    hypertension.     CONTRAINDICATIONS:    Include
hypersensitivity  to  nitrates, hypotension, increased intracranial pressure,
constrictive pericarditis,  uncorrected  hypovolemia,  closed angle glaucoma,
pericardial tamponade, head trauma and cerebral hemorrhage.  ADVERSE EFFECTS:
Headache, restlessness, apprehension, nausea, vomiting,  tachycardia,  muscle
twitching,  palpitations, dizziness, abdominal pain, retrosternal discomfort,
and hypotension.  DOSE: For adults start at 5 mcg/minute IV and increase by 5
mcg/min every 3-5  minutes  until  the  desired  response.   The mean dose to
relieve angina is 75-100 ug/min, but may increase  up  to  400  ug/min.   The
limiting  factor  is  hypotension  and  is  usually  seen at greater than 150
ug/min.  Add 50 ug of IV nitroglycerin to 250 or 500 ml of D5W.  TRADE NAMES:
Nitro-Bid IV, Nitrostat  IV,  Tridil.   DRUG INTERACTIONS: Antihypertensives,
opioid  analgesics,  ethanol,  beta  blockers,  calcium   channel   blockers,
tricyclic   antidepressants   will   potentiate   nitroglycerin   and   cause
hypotension.   The effects of acetylcholine, histamine, norepinephrine may be
decreased.   Ergot  alkaloids   may   reverse   the  antianginal  effects  of
nitroglycerin and cause angina.   Nitroglycerin  potentiates  nondepolarizing
muscle  relaxants  such  as  tubocurarine and cause apnea.  Nitroglycerin may
antagonize the effects of heparin.  ACTIONS: Nitroglycerin is a smooth muscle
relaxant  that  dilates   arterial   and   venous  beds.   Myocardial  oxygen
consumption, preload and afterload are reduced, along with central venous and
pulmonary and systemic vascular resistance.

                  -NITROPRUSSIDE AND HYPERTENSION-
(Nipride, Nitropress) 0.25 ug/kg/min.   Start  at  .25  ug and increase by .5
ug/kg/min q 3-5 min until desired effect.  (Add 50 mg nitroprusside to 250 ml
D5W).  Formula = 0.3 ug (.25) x kg (70) = 5 ml/hr.   Formula  only  valid  if
above  concentration  is  used.   Side  effects: nausea, vomiting, swearting,
twitching, thiocyanate intoxication.

                            -NOCARDIOSIS-
Nocardiosis  is a rare disease in the USA and even large medical centers will
only see  about  3  cases  per  year  and  about  85%  of  the  cases  are in
immunocompromised patients.  Nocardia are  aerobic  gram  positive  branching
rods  that  can  also  occur  in  the  coccoid form.  The branching filaments
measure .5 to 1 um and have a beaded appearance on gram or modified acid fast
stains.   Most  of  Nocardia   asteroides,  Nocardia  caviae,  and  Norcardia
brasilensis are weakly acid fast if stained by  the  Kinyoun  modified  Ziehl
Neelsen  method.   The  organisms are best seen in tissue specimens using the
Brown-Brenn variation of the gram stain, modified Ziehl Neelsen stain, or the
Gomori methenamine silver stain.  Cultures  for  Norcardia should be kept for
at least 4  weeks.   Nocardia  is  an  opportunistic  organism  that  affects
immunocompromised patients who have received organ transplants with intensive
immunosuppression,  and  in  cancer  patients who have received chemotherapy.
The risk of norcardiosis  is  greatest  in  recipients of cardiac allografts,
with a prevalence rate of 1-5%.  Transplantation of kidney,  lung  and  liver
will  have  a 1-4% norcardia infection rate.  It is rare to see the infection
sooner than  6  weeks  after  transplantation.   Nocardia  may  rarely affect
patients who have been on long term steroid immunosuppression,  or  in  those
who  have  collagen  vascular  disease,  Cushing's  disease, hemochromatosis,
cirrhosis,  bronchiectasis,  sarcoidosis,  lymphoma,  leukemia,  inflammatory
bowel  disease,  pemphigus,  chronic   obstructive  pulmonary  disease,  SLE,
diabetes mellitus, chronic  granulomatous  disease  of  childhood,  pulmonary
alveolar  proteinosis,  dysgammaglobulinemias  and tuberculosis.  Surprising,
norcardia infection is infrequent in AIDS patients, with a reported incidence
of about .3%.  Norcardia has a predilection for the lung, but also may affect
the  CNS,  subcutaneous  tissues,  and  distant  sites.   About  90%  of lung
infections are caused by N. asteroides and about 33% of localized soft tissue
or skin infections are caused by N. brasiliensis.  Nocardia caviae is usually
only seen in very severe immunocompromised patients and represents only about
.5-3% of Norcardia infections.  Norcardia asteroides is  usually  transmitted
by  inhalation.   Nocardia  brasilensis is acquired by local inoculation from
breaks in  the  skin  as  abrasions  and  puncture  wounds.  CLINICAL: LUNGS:
Nocardia sets up an infection  in  the  lung  in  about  65-85%  of  patients
although  it  can  also  involve  the  CNS,  skin,  subcutaneous  tissue  and
disseminated   disease.    About  1/3  of  patients  with  lung  disease  are
asymptomatic despite the  characteristic  subacute  or chronic pneumonitis or
nodular infiltrates of the lung.  Others have weight loss, fatigue, and  high
fever  with  rigors.   The lung lesions may be seen on chest x-ray as nodular
densities,  segmental  or  lobar   infiltrates   with  air  bronchograms,  or
cavitation which occurs  in  about  25%  of  patients.   Rarely,  miliary  or
reticulonodular  infiltrates  may  be seen.  Adenopathy may be seen in 10-40%
and pleural effusions can be seen  in  about 33%.  CNS: Patients will present
with headaches, seizures and focal neurologic defects.  The head CT will show
single or  multiple  brain  abscesses.   The  abscess  has  an  area  of  low
attenuation  in  the  center  that  represents necrosis.  There is an area of
increased density  around  the  lesion  that  represents  the  capsule and is
enhanced with contrast material.  This ring enhancement is seen in more  than
80%  with  a  mature  lesion.   Early cerebritis will not reveal the capsule.
Norcardia occasionally will involve the spinal cord, epidural space, meninges
and eyes.   SKIN:  The  skin  is  infected  in  about  9-20%  of cases.  Skin
involvement may present  as  pustules,  skin  or  subcutaneous  nodules  with
possible  draining  sinus tracts and surrounding cellulitis.  Madura foot may
occur which is a chronic indurated granulomatous tumor or mycetoma.  There is
usually multiple  sinus  fistulae  and  the  mycetomas  can invade contiguous
muscle and bone.  In about 15-20% of Nocardiosis caused  by  N.  brasiliensis
there  is  an ascending lymphangitis and regional lymphadenopathy that is not
unlike that of sporotrichosis.  OTHER SITES OF INVOLVEMENT: Dissemination may
occur to bone, joints, peritoneum,  spleen, kidney, liver, lymph nodes, heart
valves and great vessels.  LABORATORY: Smears and cultures should be obtained
from all sites of involvement including the respiratory tract, pleura,  sinus
tracts,  skin or any draining cutaneous sites.  They will be positive in only
about  10-30%  of  cases.    False   positive   cultures  are  rare  and  any
immunocompromised patient in whom the culture is positive should be  treated.
The  characteristic  filamentous beaded coccobacillary structures may be seen
on modified Ziehl Neelsen or  Gram  stain.   Blood cultures are almost always
negative, even in disseminated cases.  Fiberoptic  bronchoscopy  and  biopsy,
open  lung  biopsy,  bronchoalveolar lavage or percutaneous needle aspiration
are usually required for diagnosis.  A  positive diagnosis can be obtained in
about 70-90% when percutaneous needle aspiration can be done.  TREATMENT: The
treatment    of    choice    is    sulfadiazine    or    sulfisoxazole,    or
trimethoprim-sulfamethoxazole.  If the patient is  unable  to  tolerate  this
first    line   of   treatment,   or   there   is   resistance,   minocycline
imipenem-cilastatin, cefuroxime or amikacin  may  be  given.  In general, all
patients should be treated at least for 6-12 months, and in some patients  at
particular  risk  prophylactic  therapy should be instituted with 1 tablet of
TMP 80 mg-SMX 400  mg  three  times  per week.  SULFADIAZINE: Sulfadiazine is
given at 6-8 grams/day either IV or PO in 4  divided  doses.   SULFISOXAZOLE:
Sulfisoxazole    is    given   at   4-12   grams/day   either   IV   or   PO.
TRIMETHOPRIM-SULFAMETHOXAZOLE: Trimethoprim-sulfamethoxazole is  given at 160
mg of trimethoprim/800 mg of sulfamethoxazole either 3 or 4 times  daily,  IV
or  PO.  MINOCYCLINE: Minocycline is given at 300 mg bid.  Minocycline may be
used in pulmonary and  systemic  nocardiosis.   The patient should be treated
for at least 6 months or more.  It is not a good choice for  CNS  nocardiosis
because  of  the  low  concentrations  in  the  brain  tissue  and CNS fluid.
IMIPENEM-CILASTATIN: Imipenem-cilastatin	is given  at  500-1000 mg every 8
hours IV.  Imipenem-cilastatin achieves very good concentrations in  the  CNS
and  in  serum.   Because of this it is useful in combination with TMP-SMX in
disseminated and cerebral  nocardiosis.   Imipenem-cilastatin  at 500-1000 mg
every 8 hours IV plus TMP (480 mg)-SMX (2400 mg) given  daily  in  3  divided
doses  PO or IV is given for 10-14 days and followed with only the TMP-SMX at
the same dose either IV  or  PO.   Imipenem-cilastatin  should not be used in
mild to moderate nocardiosis, because most of  these  cases  can  be  treated
appropriately with TMP-SMX, minocycline or cefuroxime without the expense and
seizures  associated  with  Imipenem-cilastatin.   CEFUROXIME:  Cefuroxime is
given at 750-1500 mg every  8  hours  IV  until there is a clinical response,
then 500 mg bid PO.  Cefuroxime should be given orally for 6-12 months  after
the initial IV dose is given.  AMIKACIN: Amikacin is given at 5 mg/kg every 8
hours IV.  Because amikacin must be given IV and the toxic risk for renal and
vestibular  abnormalities are present, amikacin is not a good primary choice.
Amikacin does not give good  lung  and CNS concentrations.  Amikacin has been
used with good results in disseminated disease when given in conjunction with
cefuroxime and sulfonamides.

                       -NON-HODGKIN'S LYMPHOMA-
Non-Hodgkin's  lymphomas  (NHL)  represent   a  neoplastic  proliferation  of
lymphocytes that compose a morphologically and immunologically diverse  group
of  lymphoproliferative  diseases.   The  incidence in the USA increases from
less than 1/100,000 before the age  of  10  to about 80/100,000 by the age of
80.  The mean age of presentation is about 50.  There is  an  increased  risk
for  NHL  in  inherited  disorders as Chediak-Higashi syndrome , Bequez Cesar
disease and Klinefelter's syndrome.   Others  at increased risk include those
with  congenital  immunodeficiency   (ataxia   telangiecgtasia,   Louis-Bar's
syndrome,  Wiscott-Aldrich  syndrome)  and  acquired immunodeficiency (AIDS).
Other diseases  considered  at  increased  risk  for  NHL  include Swiss-type
agammaglobulinemia,   acquired   hypogammaglobulinemia,    common    variable
immunodeficiency,  sarcoid,  celiac  disease  and collagen vascular diseases.
Infections with Epstein-Barr  and  human  T  cell leukemia/lymphoma virus has
been associated with African Burkitt's lymphoma and Japanese endemic adult  T
cell  lymphoma,  respectively.   Cyclophosphamide  and azathioprine have also
been associated with an increased risk for NHL.  Phenytoin is associated with
a lymphoma-like syndrome.  In  order  to  appropriately treat these malignant
lymphomas it is important to identify  the  specific  histologic  subtype  of
lymphoma   present,  and  determine  the  stage  of  the  disease.   This  is
accomplished by  obtaining  a  good  amount  of  tissue,  preferably  from an
involved lymph node, and then analyzing the sample by  various  standard  and
immunohistochemical   stains  using  cytogenetic,  cytometric  and  molecular
genetic techniques as required in order  to arrive at a diagnosis.  About 80%
of patients will present with superficial  lymphadenopathy.   Cervical  lymph
node  biopsy  is  usually carried out, but occasionally axillary and inguinal
node biopsy may be necessary.  The  Histologic classification used in the USA
is the working formulation which has been modified to include the subtypes as
follows: LOW GRADE which  includes  follicular  small  cleaved  cells,  small
lymphocytic, follicular mixed small and large cells.  Low grade lymphomas are
indolent,  treatable,  but  rarely cured.  They are usually widespread at the
time of presentation involving  the  bone  marrow  in  about 50% of the time.
They usually present as stage IIIA  and  IVA,  have  a  long  survival  time,
respond  readily  to  initial  treatment,  but are not curable.  INTERMEDIATE
GRADES include	follicular large cells,  diffuse small cleaved cells, diffuse
mixed  small  and  large  cells,  diffuse  large  cells,  and  immunoblastic.
Intermediate grade lymphomas are curable, but  if  they  do  not  respond  to
initial therapy, survival is short.  Complete remissions will occur in 53-86%
with  cure  rates of about 30-65%.  The prognosis is worse if the patient has
stage III or IV disease, is older than 60 years, has more than one extranodal
site, or has an elevated  serum  LDH.  HIGH GRADE MALIGNANT LYMPHOMAS include
lymphoblastic, small non-cleaved cell of the Burkitt type and the non-Burkitt
type.  High grade lymphomas have a tendency to grow rapidly  and  invade  the
bone  marrow  and  the CNS.  They are more common in children than in adults.
STAGING: Staging is carried out  with  a history including any constitutional
symptoms.  The patient should  be  checked  for  lymph  nodes  and  abdominal
masses.   CBC,  serum  creatinine, LDH, calcium, protein electrophoresis, and
liver function testing should be  done.   CT  of the abdomen and pelvis, bone
marrow  biopsy  and  aspiration  and   chest   x-ray   are   all   indicated.
Thromnbocytopenia  may be secondary to hypersplenism, bone marrow involvement
or autoimmunity.  Anemia may result from  bone marrow involvement or a Coombs
positive autoimmune hemolytic anemia.  BUN and  creatinine  may  be  elevated
from  direct  tumor  infiltration  or  ureteral obstruction.  Chest x-ray may
detect mediastinal and hilar adenopathy in 5-25%, pleural effusions in 8-10%,
and lung infiltration which is  uncommon.   Abdominal  CT is 83% accurate for
detection of abdominal adenopathy, especially in the upper  abdomen,  but  it
will  underestimate  splenic involvement because the tumor nodules may be < 1
cm in diameter.  CT is  very  good  for  detection of adenopathy in the upper
abdomen.  Bipedal lymphangiography is inaccurate in the  upper  abdomen,  but
has   a   90-95%   positive   and   60-80%   negative  predictive  value  for
retroperitoneal adenopathy.  Bilateral  bone  marrow aspirations and biopsies
of the iliac crests are done using a Jamshidi needle.  In general,  there  is
bone  marrow  involvement  in  39-45% of patients, but 50-70% with small cell
lymphocytic cells.  It is important  to  know  that only 33% of patients with
bone marrow involvement have abnormalities of the peripheral blood.  The  LDH
correlates  with  the tumor burden and can also be used to follow response to
treatment.  Uric acid may  be  elevated  in advanced disease, particularly in
the rapid lysis syndrome, which can cause renal insufficiency.  An  upper  GI
and small bowel series may be needed if there are GI symptoms and lymphoma of
Waldeyer's  ring.   Barium enema is ordered for those with lower GI symptoms.
Ultrasound is used to detect  obstructive  uropathy from enlarged para aortic
nodes.  Percutaneous liver biopsy can detect lymphoma of the liver in 20%  of
blind  needle liver biopsies with a 35% false negative rate.  Lumbar puncture
with CSF analysis will reveal  meningeal  involvement  in 8% of patients with
lymphoblastic lymphoma and may  also  be  indicated  in  diffuse  histiocytic
lymphoma   involving   the   bone   marrow   and   in   testicular  lymphoma.
Mediastinoscopy  and  anterior  parasternal   mediastinotomy  may  rarely  be
indicated.  STAGING SYSTEM CLASSIFICATION: A practical  system  for  dividing
malignant  lymphomas  into limited disease or advanced disease is as follows:
LIMITED: Ann Arbor stage I or II  and no B symnptoms (fever, night sweats, or
more than 10% weight loss) and no tumor > 10  cm  in  the  largest  diameter.
ADVANCED:  Ann  Arbor  stage  III or IV or B symptoms, or any tumor > than or
equal to 10 cm in the  largest diameter.  TREATMENT: Treatment can be planned
by taking into consideration the histologic subtype, stage and the age of the
patient.  LOW GRADE LYMPHOMAS: About 90% of low grade lymphomas will  present
in  the  advanced stage with widespread nodal or extranodal involvement.  The
extranodal disease is usually found  in  the  GI tract, bone marrow, liver or
soft tissue of the upper aerodigestive tract, but occasionally  is  found  in
the  lungs  and  conjunctiva  and  rarely in bone, muscle, skin, and visceral
organs other than the liver, gonadal  and  CNS.  The treatment will depend on
the extent of the disease.  The 90% that have advanced staging usually have a
good short term prognosis of about 8-10 years, depending on the age.  Most of
these patients will ultimately die however.  Because of this, most  of  these
patients  who  are  asymptomatic  can  be  followed with observation.  Slowly
progressive  disease  may  be  treated  with  irradiation  (if  localized) or
cyclophosphamide if widespread.  One can add steroid therapy which may  treat
autoimme  hemolytic anemia.  Ultimately, the disease will progress, and these
patients can be treated  as  an  intermediate grade lymphomna.  The remaining
10% that present with limited localized disease  have  a  good  prognosis  if
treated  with  irradiation  to  the  involved area.  If, however, the patient
relapses after radiation therapy, they  are  treated as if they have advanced
disease.  INTERMEDIATE GRADE LYMPHOMA: About 30% of  the  intermediate  grade
lymphomas  will  present  with  limited  disease  and about 70% with advanced
disease.  However,  the  limited  disease  is  usually  not  limited as these
patients will relapse in 50-75% of cases if treated  with  radiation  to  the
localized  area  of involvement.  This is due to micrometastasis.  Therefore,
these patients  should  be  treated  with  chemotherapy  consisting  of CHOP,
M-BACOD, ProMACE-CytaBOM, MACOP-B or  VACOP-B  for  6-12  weeks  followed  by
involved field radiation.  Most elderly patients will tolerate this treatment
plan which can result in a relapse free and disease specific survival of 90%.
Patients  that have disease at salivary sites which would result in radiation
therapy to these areas and subsequent xerostomia are not given radiation, but
treated with extended chemotherapy  only.   Also,  patients that have had all
local diseased tissue removed surgically, may be spared radiation therapy and
treated with only short term chemotherapy.  Treatment for the  other  70%  in
the  advanced  stage  are treated with multiagent chemotherapy using regimens
such as CHOP, M-BACOD, ProMACE-CytaBOM, MACOP-B, or VACOP-B.  About 70-80% of
younger patients with low tumor burden  can  be cured by using this approach.
Some  of  these  younger  patients  who  relapse  can  be  given  high   dose
chemoradiotherapy  and  stem  cell  transplantation which may cure as many as
30%.  Patients that have a high  tumor burden and poor prognostic factors are
not likely to be cured and should be  entered  into  experimental  protocols.
HIGH GRADE LYMPHOMAS: This group includes lymphoblastic and small non cleaved
cell  Burkitt  lymphomas  usually seen in children and young adjults, and are
rare.  Lymphoblastic lymphomas  are  T  cell  lymphomas often associated with
mediastinal tumors, bone marrow and CNS involvement, and are usually seen  in
males.   They  a re aggressive, with early spread and frequent involvement of
the CNS and bone  marrow,  and  are  very  sensitive to chemotherapy.  All of
these patients should be started on therapy immediately.  They are all  prone
to  rapid  tumor  lysis  and  metabolic  overload, and renal dysfunction, and
should be followed  closely  with  creatinine,  elecrtrolytes,  uric acid and
phosphate determinations.  They should be treated with  allopurinol,  urinary
alkalinization,  IV  fluids  and  may  need  hemodialysis.  All patients with
Burkiit's and  lymphoblastic  lymphoma  should  be  treated  with intrathecal
chemotherapy since there is a high risk for CNS involvement.   Patients  that
are  <  60  years old are treated with intensive chemotherapy with or without
bone marrow transplantation  plus  CNS  treatment.   Those  patients that are
greater than 60, are usually  treated  with  palliative  chemotherapy.   CHOP
therapy consists of cyclophosphamide 750 mg/m2 IV day 1, doxorubicin 50 mg/m2
IV day 1, vincristine 1.4 mg/m2 IV (max dose 2 mg), and prednisone 60 mg/d po
days  1-5.   This  is  cycled  every  3-4  weeks for 6 cycles.  BACOP therapy
consists of bleomycin 5 units/m2 IV  on  days 15, 22, doxorubicin 25 mg/m2 IV
days 1,8, cyclophosphamide 650/m2 IV days 1,8, vincristine 1.4 mg/m2 IV  days
1,8, and prednisone 60 mg/m2 po days 15-28.  This is cycled every 4 weeks for
6 or more cycles.  COMLA therapy consists of cyclophosphamide 1.5 g/m2 IV day
1,  vincristine  1.4  mg/m2/d  IV days 1,8,15, cytarabine 300 mg/m2/d IV days
22,29,36, 43, 50, 57, 64, 71,  methotrexate  120  mg/m2/d IV days 22, 29, 36,
43, 50, 57, 64, 71, leucovorin 25 mg/m2 po q6h times  4,  starting  24  hours
after methotrexate.  This is cycled every 12 weeks for 3 cycles.  COP therapy
consists  of  cyclophosphamide 800-1000 mg/m2 IV day 1, vincristine 1.4 mg/m2
IV day 1 (max dose 2  mg),  and  prednisone  60 mg/m2/d po days 1-5.  This is
cycled  every  3  weeks  for  6  cycles.   COP-BLAM   therapy   consists   of
cyclophosphamide 400 mg/m2 IV day 1, vincristine 1 mg/m2 IV day 1, prednisone
40  mg/m2/d  PO days 1-10, bleomycin 15 mg IV day 14, doxorubicin 40 mg/m2 IV
day 1, procarbazine 100 mg/m2/d po  days  1-10.  This is cycled every 3 weeks
for 8 cycles.  COPP or CMOPP consists of cyclophosphamide 650 mg/m2/d IV days
1, 8, vincristine 1.4 mg/m2/d po days 1, 8 max dose 2 mg),  procarbazine  100
mg/m2/d  po  days  1-14,  prednisone 40 mg/m2/d po days 1-14.  This is cycled
every 4 weeks for  6  cycles.   CVP  therapy consists of cyclophosphamide 400
mg/m2/d po on days 2-6, vincristine 1.4 mg/m2 IV  day  1  (max  dose  2  mg),
prednisone  100  mg/m2/d  po on days 2-6.  This is cycled every 3 weeks for 6
cycles.  COP, COPP or C  MOPP,  and  CVP  are used for favorable histologies.
BACOP, CHOP, COMLA, and COPP OR C MOPP are used for unfavorable  histologies.
COP-BLAM  is used for non hodgkin's lymphoma with advanced histiocytic, stage
III or IV.

                   -OBSESSIVE-COMPULSIVE DISORDER-
Obsessive-Compulsive disorder (OCD) is  a  common  disorder in which patients
have disturbing, repetitive thoughts that necessitate certain behaviors as  a
response  to the obsessive thoughts.  About 80% will have obsessions followed
by compulsions, but in 15% of  cases there are only obsessions.  The symptoms
begin in childhood in about 50% of all cases.  Compulsive washing is  present
in  more  than  85%  of  children,  and about 50% of adults .  About 15% will
appear before the age of 10, and  in most cases, the fully developed syndrome
will be apparent by the age of 25.  Celebrities  that  are  renown  for  this
disorder  have included Howard Huges who had a terrible fear of germs, Samuel
Johnson, who would meticulously count the number  of steps to a door in order
to figure out which foot would move first, and Lady  Macbeth  who  constantly
rubbed  her  hands  together to wipe the imagined blood of King Malcolm away.
It once was considered a rare  disorder,  but now is recognized as an anxiety
disorder that affects 2-3% of the population.  This is an incidence  that  is
higher  than  asthma  or diabetes.  These patients have unending, relentless,
irrational thoughts that can  produce  severe  anxiety.  The patient is fully
aware that the formulated ideas are untrue and nonsensical,  and  will  spend
much  time  and energy in an attempt to resist them.  This may be temporarily
successful, but eventually, the  ideas,  words and images return incessantly.
In response to these ideas the patient has an overwhelming  need  to  satisfy
these  desires  by  aggressive,  obscene  and  disgraceful  behaviors.   Most
childhood  cases  occur  in  males,  but in adults the sexual distribution is
fairly even.  Examples that are  typical  of this disorder include repetitive
washing of the hands to the point of bleeding,  checking  foods  for  poison,
various  counting  rituals,  the  need  for  symmetry  and  order, repeatedly
checking for breast cancer, sexual  obsessions  such as fear of homosexuality
and child molesation, repeated impulses to kill a religious person or a loved
child, irrational hoarding of expired calendars and garbage,  rechecking  the
doors  to  see  if  they are locked, arranging items in a particular pattern,
showering for hours in  an  attempt  to  remove  imagined dirt from the body,
constantly examining parts of the body for imperfections,  various  religious
obsessions,  cleaning the house repeatedly, and repetitive checking to see if
the stove has been turned off.  Many  of these patients, since they are aware
of their absurd behavior, will resort to performing the compulsions in secret
when no one is around, or fabricate stories in an attempt to cover  up  their
behavior.   DIAGNOSIS: Many of these patients will not mention their symptoms
if they are not  specifically  questioned.   The  patient should be asked the
following questions: Do you have thoughts  which  bother  you,  or  make  you
anxious  that  you can't get rid of, regardless how hard you try, even though
you know the  act  is  irrational?   TREATMENT: PHARMACOTHERAPY: Clomipramine
hydrochloride (Anafranil) is a tricyclic antidepressant  which  inhibits  the
reuptake  of  serotonin.   It  has  been  most  effective  in controlling the
obsessional thinking, which in  turn  leads  to decreased rituals.  It should
not be used within 14 days of  an  MAOI  or  in  combination  with  an  MAOI.
Seizures  may  occur  if  the daily dose exceeds 250 mg.  It is started as 25
mg/day with food.   It  is  gradually  increased  up  to  100 mg/day given in
divided doses during the first 2 weeks, and then gradually increased over the
ensuing weeks up to a maximum of 250 mg/day in divided  doses.   The  patient
should  be  advised that the full effects of the drug may not become apparent
for 6-12 weeks or in some  cases  18 weeks.  The serotonin selective reuptake
inhibitors (SSRI) such  as  fluoxetine  (Prozac),  sertraline  (Zoloft),  and
paroxetine  (Paxil)  also  have  been  useful  in  treating  OCD.  Fluoxetine
(Prozac) is started as 20  mg/day  in  the morning.  After several weeks, the
dose may be increased to 80 mg/day in equally divided BID doses.   It  should
not  be  used  in  conjunction with or within 5 weeks of an MAOI.  Sertraline
(Zoloft) is started as 50 mg/day  in  the  AM  or PM.  It may be increased at
weekly intervals up to 200 mg/day.  It should not be used in combination with
or within 14 days of an MAOI.  Paroxetine (Paxil) is started as 20 mg/day  in
the  morning.   In  general  the  side effect and safety effects of SSRIs are
minimal, and they are usually  well  tolerated.  Occasionally, they may cause
headache, insomnia, nausea, diarrhea, drowsiness,  weight  loss  and  delayed
orgasm.  The sexual problems may be helped by taking bethanechol (Urecholine)
10-50  mg  1  hour prior to sexual activity.  Other medications that may help
the  sexual  problems   include   cyprohepatadine  (Periactin)  or  yohimbine
(Yohimex).  Combination drug therapy is beneficial in those patients that are
only partially helped with monotherapy.  The other drugs that may be used  in
combination with clomipramine, fluoxetine, paroxetine, and sertraline include
buspirone  (Buspar),  clonazepam  (Klonopin),  lithium  carbonate (Eskalith),
clonidine (Catapres), and fenfluramine  (Pondimin).  This combination therapy
is used in patients that do not completely respond to  monotherapy  with  the
primary drugs.  Buspirone (Buspar) enhances the antidepressive effects of the
SSRIs and also reduces the associated anxiety.  If given with fluoxetine, 25%
of patients will further improve.  It is started as 5 mg TID and is increased
as  needed by 5 mg every 3 days up to 60 mg/day in divided doses.  Clonazepam
(Klonopin) may be started as 1.5  mg/day in divided doses.  This is increased
every 3 days by .5-1 mg up  to  a  total  of  20  mg/day  in  divided  doses.
Clonidine  is  started  as  .1  mg  BID, and increased by .1 mg/day up to 2.4
mg/day.  Lithium has been  shown  to  increase  response rates when used with
clomipramine.  It is started as 600-900 mg/day in BID  or  TID  doses  up  to
1,800  mg/day.   Lithium levels are always required.  BEHAVIOR MODIFICATIONS:
In order to combat the  obsessive  phase,  patients are exposed to the feared
object or situation that has precipitated his anxiety.  In the second part of
therapy, aimed at the compulsive component, the  patient  is  prevented  from
performing  the  ritualistic behavior that has followed the initial exposure.
This combination therapy may be exemplifed by the following example.  Suppose
a patient has an adversity for contamination.   He is then asked to touch the
imagined contaminated object (such as a door knob) for a prolonged amount  of
time, and then resist from washing the hands.

                         -OLIGURIA (Sudden)-
PRERENAL AZOTEMIA: BUN:creatinine > 20:1; urine osmolality > 500; urine  spot
urine sodium < 20; FEna < 1%; urine sediment may show hyaline casts; Signs of
intravascular  volume  depletion  include  low  cardiac output states as CHF,
tamponade, arrhythmias,  cardiogenic  shock,  massive  pulmonary embolism, OR
intravascular volume depletions secondary to hemorrhage,  renal  losses  with
diuretics,  osmotic diuresis, sequestration of fluid in a third space such as
diarrhea,  pancreatitis,  peritonitis,  skin  looses  from  burns,  excessive
sweating OR increased renal/systemic vascular resistance such as vasodilation
from antihypertensive drugs, anaphylaxis,  anesthesia, sepsis, drug overdose,
OR renal  vasoconstriction  from  alpha  adrenergic  agonists  or  high  dose
dopamine,  surgery,  anesthesia,  hepatorenal  syndrome,  OR  impaired  renal
autoregulation  from prostaglandin synthesis inhibitors such as NSAIDs in the
presence of CHF,  nephrotic  syndrome,  cirrhosis, hypovolemia or preexisting
liver disease, ACE inhibition in  the  presence  of  bilateral  renal  artery
stenosis or CHF.  POSTRENAL AZOTEMIA: (Obstructive uropathy) BUN:creatinine >
20:1;  urine osmolality variable; urine spot sodium is variable, may be < 20;
FEna variable; may be <  1%;  urine  sediment  is normal or may contain RBCs,
WBCs,  or  crystals;  urine  volumes  fluctuate   day   to   day;   bilateral
hydronephrosis  or  hydroureter  on sonography; enlarged bladder or prostate.
Ureteral obstruction  may  be  caused  by  papillary  necrosis,  blood clots,
sulfonamide or uric acid  crystals,  fungus  balls,  stones,  retroperitoneal
hemorrhage  and fibrosis, ureteral ligation during pelvic surgery, and tumors
of the prostate, cervix and uterus.  Bladder outlet obstruction can be caused
by bladder carcinoma, stones, clots, functional impairment from neuropathy or
ganglionic blocking  agent,  prostatic  hypertrophy  or malignancy.  Urethral
obstruction  is  caused  by  congenital  valves,  strictures,  and  phimosis.
INTRINSIC RENAL DISEASE: acute tubular necrosis will produce a BUN:creatinine
< 20:1; urine osmolalirty < 350; urine spot sodium > 20;  FEna  >  1%;  urine
sediment  shows  granular casts, renal tubular epithelial cells, and cellular
debris, pigment,  and  crystals.   There  may  be  a  history  of significant
hypotension  and  renal  hypoperfusion,   and   exposure   to   nephrotoxins.
Nephrotoxins  include  aminoglycosides,  ampotericin B, radiographic contrast
media,  immunosupprdessive  drugs  as  cyclosporin,  heavy  metals  as  lead,
arsenic, chemotherapeutic agents as cisplatin, methotrexate, organic solvents
as ethylene glycol, myoglobin,  hemoglobin,  calcium, uric acid and oxalates.
Acute glomerulnephritis and vasculitis will produce a BUN:creatinine >  20:1;
urine osmolality > 500; urine spot sodium < 20; FEna <1%.  The urine sediment
shows  RBCs  and RBC casts.  There may be systemic evidence of vasculkitis as
SLE or other collagen  vascular  disease.   There  may  be  a history of sore
throat and strep infections.  The causes include glomerulonephritis,  toxemia
of  pregnancy,  hemolytic  uremic  syndrome, DIC, malignant hypertension, and
radiation injury.  Acute interstitial  nephritis  shows a BUN:creatinine less
than 20:1; urine osmolality is variable; urine spot sodium is variable;  FEna
variable;  urine sediment shows WBC and WBC casts and eosinophils.  There may
be a history of allergic reaction, drugs, infections, peripheral eosinophilia
and   thrombocytopenia.    Causes   include   fungal   infections,  bacterial
infections, viral infections, drugs as beta lactam antibiotics, sulfonamides,
rifampin,  NSAIDs,  cimetidine,  and  phenindione.   Renovascular   occlusion
(Arterial) shows a BUN:creatinine < 20:1; urine osmolality is variable; urine
spot  sodium is variable; FEna is variable; urine sediment is variable; renal
vein thrombosis is associated with  nephrotic syndrome or with compression or
invasion of the renal  vein  by  tumor.   The  causes  include  renal  artery
embolism,  thrombosis,  dissection  (postangiopalsty  or  traumatic),  aortic
aneurysm,  and  thrombotic  microangiopathy.  Renovascular occlusion (Venous)
shows a BUN/creatinine < 20:1;  urine  osmolality variable; urine spot sodium
variable; FEna variable; urine sediment variable.  Renal vein  thrombosis  is
associated  with  nephrotic syndrome or with compression or invasion of renal
vein  by  tumor.   Causes  include  renal  vein  thrombosis  and compression,
Individuals with sudden occlusion of one or both of their main renal arteries
may have acute flank pain, fever, livedo reticularis, marked elevation of LDH
(found in large quantities in renal cells), increased  ESR,  decreased  serum
complement   levels,   thrombocytopenia,   eosinophilia  and/or  evidence  of
thrombotic  thrombocytopenic  purpura.    There   may  be  abdominal  bruits,
aneursyms, reduced or  absent  femoral  pulses,  or  peripheral  or  cerebral
vascular   diseases.    There  may  be  atrial  fibrillation,  recent  MI  or
endocarditis that embolizes.  A  history  of aortic catheterization may point
to cholesterol embolization.  The FEna (fractional excretion of sodium) = Una
x Pcr/Pna x Ucr x 100 where the Una=urine sodium (mEq/L),  Pna=plasma  sodium
(mEq/L),  Pcr=plasma  creatinine  (mg/dL),  and the Ucr=spot urine creatinine
(mg/dL).

                      -ORTHOSTATIC HYPOTENSION-
Orthostatic hypotension is characterized by a reduction of greater than 20 mm
Hg in the systolic BP upon standing upright with production of symptoms  such
as light-headedness, faintness, dizziness, visual blurring and confusion.  In
more  severe  cases  there  may  be  seizures  if  there  is  severe cerebral
hypoperfusion.  The most common causes of orthostatic hypotension are related
to drugs, volume  depletion,  peripheral  and autonomic neuropathies, central
nervous sytem diseases, idiopathic orthostatic  hypotension  and  physiologic
causes.   Physiologic  orthostatic  hypotension is fairly common in the aging
population.  In  the  aged,  there  is  an  exaggerated plasma norepinephrine
response when a  change  in  posture  occurs.   Clinically,  the  orthostatic
hypotension  is  unmasked  when  certain  conditions intervene such as volume
depletion, prolonged bed rest, and hypotensive drugs.  Idiopathic orthostatic
hypotension characteristically has a  lower basal plasma norepinephrine level
in the  supine  position,  lack  of  increase  in  norepinephrine  levels  on
standing,   a   lowered   threshold  for  a  pressor  response  with  infused
norepinephrine, and a greater pressor response to tyramine at the sympathetic
nerve endings, despite release of  less norepinephrine.  DRUGS: Several drugs
may be associated with orthostatic hypotension such as clonidine, methyldopa,
reserpine,   ganglionic   blocking   agents,   calcium   channel    blockers,
vasodilators,   quinidine,   barbiturates,  alcohol,  vincristine,  levodopa,
monoamine   oxidase    inhibitors    (tranylcypromine,   isocarboxazid,   and
phenelzine),  tricyclic  antidepressants  (   amitriptyline,   nortriptyline,
imipramine,  desipramine,  and  protriptyline),  phenothiazine  antipsychotic
medications  (chlorpromazine,  thioridazine,  and promazine), and tetracyclic
antidepressants.   NEUROLOGIC  CAUSES:   This   category  comprises  diabetic
neuropathy,  pophyria,  tabes  dorsalis,  amyloidosis,   pernicious   anemia,
alcoholic  neuropathy,  syringomyelia,  spinal  cord  transection,  Riley-Day
syndrome,  Guillain-Barre  syndrome,  Shy-Drager syndrome, brainstem lesions,
multiple cerebral  infarcts,  myelopathy,  paraneoplastic syndromes, surgical
sympathectomy,  varicose  veins,  vasospastic  disordders,  pheochromocytoma,
primary   hyperaldosteronism,   and   Parkinson's   disease.     HYPOVOLEMIA:
Hypovolemic  causes  of  orthostatic  hypotension include diarrhea, excessive
sweating, vomiting, hemorrhage, osmotic  diuresis from diabetes mellitus, and
Addison's  disease.   TREATMENT:  All  patients  should  be   hydrated.    An
investigation  of all over-the-counter, as well as prescription drugs, should
be undertaken.  Patients should be  encouraged  to dorsiflex their feet while
recumbent in order to promote venous return to the heart and  accelerate  the
heart.   They  should  sit  on  the  side  of  the bed for a while after long
episodes of recumbency.  An increase of  the salt intake may also augment the
volume.  This usually consists of an increase of 5-10 grams above  the  usual
level.   Elastic  hose  worn  on  the legs and the thighs may increase venous
return.  Another effective measure may be  elevating the head of the bed 5-20
degrees.  This will  prevent  nocturnal  diuresis.   Anemia  and  electrolyte
imbalance  should be corrected.  Patients should be cautioned about prolonged
standing.  Mild orthostatic hypotension may  be improved with the addition of
ephedrine 25-50 mg PO q4h while awake.  Fludrocortisone .1-.5  mg/day  PO  is
often  effective, and is usually given until there is mild edema of the legs.
This will sensitize  the  blood  vessels  to  the  vasoconstrictive effect of
norepinephrine.  Fludrocortisone is contraindicated  in  CHF-prone  patients.
Propranolol  may  also  augment  the  beneficial effects of mineralocorticoid
(fludrocortisone)  and  sodium  therapy.   Beta  blockers  will  block  Beta2
vasodilator receptors.  Indomethacin can  increase renal sodium retention and
inhibit prostaglandin-induced vasodilation.  It is given  as  25-50  mg  TID.
Side   effects,   however,  are  common,  consisting  of  GI  irritation  and
inappropriate pressor reactions if the patient is also taking sympathomimetic
drugs along with  the  indomethacin.   Morning  caffeine may also be
beneficial. 

                            -OSMOLAR GAP-
The   osmolar   gap   =   Osmolality(measured)-Osmolality(calculated).    The
Osmolality(calculated)=2(Na)+(glucose/18)+(BUN/2.8).  The normal osmolar  gap
is  <10  mOsm/kg.   An OG >10 with a normal Posm(measured)s suggest decreased
water    content,    dysproteinemia    or    extreme    hyperlipidemia.    An
Osmolality(measured) < Osmolality(calculated) suggests a lab  or  calculation
error.  An OG >10 with a normal Posm(calculated) indicates unmeasured osmols.
Common  causes  include  methanol,  ethanol,  ethylene  glycol,  isopropanol,
mannitol,  diatrizoate  (Hypaque).   Uncommon  causes include acetone, ether,
INH, sorbitol, trichloroethane, and glycerin.

                           -OSTEONECROSIS-
Osteonecrosis is also  known  as  avascular  necrosis, Kienbock's disease, or
subchondral fracture.  CAUSES: Causes are trauma, sepsis, stress  or  fatigue
fractures, alcohol abuse, Gaucher's disease, Dysbarism, rheumatoid arthritis,
SLE,  vasculitis,  hemoglobinopathy,  coagulopathy,  radiation, steroids (may
occur in high  short  term  doses,  long  term or intra-articular injections.
Onset of symptoms is usually greater than 6 months, but may be  more  than  3
years),  pregnancy,  gout,  aging, pancreatitis, Legg-Calve-Perthes, Sever's,
Kohlers,  Larsen's,  Blount's,  Panner's   disease,  Diabetes  mellitus,  and
hyperlipidemia type 2 & 4. CLINICAL: Presentation is pain, decreased range of
motion, possible tenderness, and limp.  May affect the shoulders,  hips,  and
knees.   LABORATORY: Bone scan shows a photon deficient area or doughnut sign
early.  Later, there is increased uptake.   MRI shows a decreased signal with
T1 & T2 weighting.  Signal may vary over time.   X-ray  varies  from  mottled
increased  density  in  the  femoral head to intense subchondral radiolucency
(Crescent  sign).   TREATMENT:  In  the  Alcoholic:  (abstinence), Transplant
patients: (regulate the calcium & phosphorus  &  decrease  steroids),  Sickle
cell: (hydration, exchange transfusion, oxygenation).  Limit weight bearing &
use crutches, NSAID's, and prosthetic joint replacement.

                           -OSTEOMYELITIS-
Osteomyelitis  can  occur  in  an  acute  or  chronic  form,  involve adults,
pediatric patients, diabetic and immunocompromised patients, drug addicts and
sickle cell patients.   It  may  be  caused  by  trauma,  contiguous  spread,
hematogenous  spread,  and peripheral vascular disease.  Traditionally, it is
divided into acute hematogenous  osteomyelitis, osteomyelitis associated with
a contiguous site and osteomyelitis associated with a  contiguous  site  with
vascular  insufficiency.   Osteomyelitis  is  primarily  a  disease caused by
pyogenic  bacteria,  but  can   be   secondary  to  mycobacteria  and  fungi.
GENERALITIES: Patients under the age of 20 and those over the age of 60  have
the  highest  incidence  of  osteomyelitis.  Males are involved slightly more
than females.  Staphylococcus aureus  is  the  most common hematogenous cause
and Hemophilus influenze is a common offender in children.  Diabetics have  a
higher  incidence  of  osteomyelitis  involving  the  feet  than  the  normal
population, and there is a higher incidence of osteomyelitis in patients that
are  IV  drug  abusers  and  patients  undergoing  hemodialysis.  Sickle cell
disease is associated with Salmonella osteomyelitis.  The most common site of
osteomyelitis  is  the   tibia.    ACUTE  HEMATOGENOUS  OSTEOMYELITIS:  Acute
hematogenous osteomyelitis (AHO) is usually seen in children and  those  over
the  age of 50.  Those over 50 will also have a higher incidence of vertebral
osteomyelitis.  The tibia, femur and humerus are predominantly involved.  The
most  common  cause  of  AHO  is  Staph  aureus  and  gram  negative bacilli.
Hemophilus influenzae is a common organism in young infants and Salmonella in
sickle cell anemic patients.  In the infant, Staphylococuus aureus,  group  B
streptococcus, and Escerichia coli are the most frequent causes.  In children
1-4  years  of  age,  Staph  aureus,  Streptococcus pyogenes, and Haemophilus
influenzae are the most common.   After  the  age  of  4, the incidence of H.
influenzae decreases.  In the adult,  Staph  aureus,  Staph  epidermidis  and
aerobic  gram  negative  organisms  account for most cases.  In children, the
onset is usually abrupt  with  high  fever,  systemic toxicity and local pain
around the involved site.  In adults, the onset  is  more  subacute,  from  a
contiguous  source  or  previous  trauma,  often  with  swelling, redness and
localized pain.  The patient usually gives  a history of previous fracture or
soft tissue infection.  As the condition progresses, the symptoms may  become
less  impressive, with intermittent drainage from a sinus tract indicating an
acute  episode  of  chronic  osteomyelitis.   OSTEOMYELITIS  SECONDARY  TO  A
CONTIGUOUS INFECTION: The  most  common  cause  is  a postoperative infection
(such  as  open  fractures,  surgical  reduction  and  internal  fixation  of
fractures, but in the nonsurgical patient the infection may start in infected
teeth, sinuses, following animal or human bites (secondary to P. multocida or
E. corrodens) chronic soft tissue infections and radiation therapy..  Most of
these patients will be older than 50.  Other infections  may  originate  from
decubital  ulcers,  infected  sternums secondary to median sternotomies (from
cardiac surgery), postoperative  neurosurgery,  and  oral  surgery.  The most
common organism involved is Staph aureus, but there may be  mixed  infections
when  decubitus  ulcers  and  diabetic  foot  ulcers  develop.  OSTEOMYELITIS
ASSOCIATED WITH  A  CONTIGUOUS  INFECTION  AND  VASCULAR INSUFFICIENCY: These
patients are usually diabetic or have advanced atherosclerosis and peripheral
vascular disease.  Most of these patients are older than 50.   The  feet  are
the  most  commonly  involved.   The  infection commonly develops after minor
trauma to the feet,  cellulitis,  infected  nails or trophic skin ulceration.
Most infections are mixed with Staphylococci, gram negative aerobic  bacilli,
anaerobes, Enterococcus spp.  and Staph epidermidis being the most common.  A
common  situation in diabetic patients with extensive destruction of the foot
bones  is  distinguishing  between  chronic  osteomyelitis  or  noninfectious
neuropathic disease.  VERTEBRAL  OSTEOMYELITIS:  The  vertebrae are the third
most  common  bones  involved  in  hematogenous  osteomyelitis.   The  lumbar
vertebrae are involved in  about  50%  of  cases  of  hematogenous  vertebral
osteomyelitis with the lower lumbar vertebrae more commonly involved than the
upper lumbar vertebrae.  In about 33% of cases the thoracic area is involved.
Cervical  involvement  is uncommon.  If TB is the cause, the thoracic area is
the most commonly involved in over  50% of cases.  Vertebral osteomyelitis is
usually hematogenous in adults, but may occur secondary to  trauma.   It  may
also  be  a  complication  of  back  surgery,  drug  abuse  or  urinary tract
infection.  Gram negative  bacteria  may  seed  the  vertebral  body from the
urinary tract  by  the  posterior  venous  system  of  the  vertebral  column
(Batson's   plexus).    Other   sources  of  infection  include  soft  tissue
infections, infected vascular sites, pulmonary infections, dental infections,
infective endocarditis and surgery of the spine or disc.  About 33% will have
no obvious source  of  infection.   Clinically,  these  patients  have a dull
constant back pain and spasm.  There is usually pinpoint tenderness over  the
involved  vertebral body.  There may be a low grade fever, or the patient may
remain  afebrile.   About  50%   of   patients  with  hematogenous  vertebral
osteomyelitis  will  have  symptoms  for  about  3  months  before  seeing  a
physician.  About 15% will have a neurologic sensory or motor deficit.  If  a
patient  presents  with  back  pain  and progressing weakness or paralysis, a
spinal epidural abscess  should  be  entertained.   The  infection is usually
monomicrobic if hematogenous in origin.  The most  common  is  Staphylococcus
aureus.   However,  in  about 30% of cases, aerobic gram negative rods may be
found.  Pseudomonas aeruginosa and Serratia  marcescens are common in IV drug
abusers.  Mycobacteria and fungi  have  also  been  implicated  in  vertebral
osteomyelitis,     including    Mycobacterium    tuberculosis,    Blastomyces
dermatitidis, Coccidioides immitis and Candida.  Anaerobes are extremely rare
in contiguous  osteomyelitis  secondary  to  infected  ducubital ulcers.  The
earliest x-ray change is a  rarefaction  of  the  vertebral  end  plate.   In
advanced  disease there is narrowing of the adjacent joint and involvement of
the vertebral body.  The technetium  99M  bone scan is usally positive, while
the indium and gallium scans are difficult  to  interpret  due  to  the  high
amounts  of  hematopoietic  tissue  in  the vertebral bodies.  CT and MRI are
helpful  in  assessing   the   degree   of   involvement  of  the  vertebral,
paravertebral and  soft  tissue.   A  diagnosis  of  vertebral  osteomyelitis
requires  isolation  of  the  organism  from  the vertebral body, disk space,
paravertebral abscess or blood.  This may  be accomplished by a closed biopsy
for culture and histology performed with fluoroscopy or CT guidance.  An open
biopsy is done if there is a high risk for complications.  Make sure you send
the biopsy for  culture  as  well  as  histology,  because  the  differential
involves  mycoses,  TB,  primary  and  metastatic  neoplasms.   DIAGNOSIS  OF
OSTEOMYELITIS:  About  50%  of  patients  will  have positive blood cultures.
Chronic osteomyelitis  is  rarely  associated  with  bacteremia.   The WBC is
usually elevated in acute osteomyelitis, but in  chronic  osteomyelitis,  the
leukocyte  count  may  be  normal.   The sedimentation rate is usually always
elevated in  acute  or  chronic  osteomyelitis.   The  most  efficient way of
diagnosing acute osteomyelitis, in the absence  of  bacteremia,  is  by  bone
biopsy.   However,  in  diabetic  foot patients, the yield may be low because
bone lesions may  be  due  to  neuropathic  or  vascular  changes rather than
infection.  Furthermore, there is poor healing.  Culturing  sinus  tracts  is
not  reliable.  Typical x-ray changes of osteomyelitis do not occur for about
2 weeks after the onset of  infection, with the earliest changes being subtle
soft tissue  swelling,  periosteal  thickening  or  elevation  and  localized
osteopenia.   The  typcial  lytic  changes may not appear for several months.
Successful  antibiotic  treatment  may  lead  to  a  radiographic  lag behind
clinical improvement.  Technetium 99M bone scans are typically positive after
a few days of infection.  In adult patients with  normal  x-rays,  the  three
phase  bone  scan  has  a high sensitivty and specificity for bone infection.
This is not true in infants  with osteomyelitis who will have false postitive
bone scans in 20-70% of  cases.   The  uptake  is  related  to  the  skeletal
vascularity  as  well  as  the osteoblastic activity.  A triple phase scan is
usually done.  The first phase (flow  phase)  is done while the Technetium is
being injected.  The second phase is known as the blood  pool  image  and  is
obtained  within 5 minutes following injection.  There will be increased flow
and blood pool activity in  areas  where  inflammation is present.  The third
phase  (bone  phase)  is  obtained  about  3   hours   following   injection.
Osteomyelitis  is  associated with increased activity in the first two phases
and increased third phase  focal  bone  activity,  while cellulitis alone has
increased activity in the first two phases, but  no  focal  increase  in  the
third  phase.  Indium-111 leukocyte scans have a sensitivity of 80-100% and a
specificity of 50-100%.  MRI scanning  is helpful for differentiating between
bone and soft tissue infection.  The typical MRI findings of osteomyelitis is
a localized area of abnormal marrow with decreased  signal  intensity  on  T1
weighted  images  and  an  increased  signal intensity on T2 weighted images.
Separating infection from neoplasm is  difficult  by MRI.  CT scans will show
increased marrow density  early  in  osteomyelitis.   CT  may  also  identify
necrotic  bone.   EMPIRIC  TREATMENT:  In general, in settings in which Staph
aureus is the suspected pathogen, use  nafcillin or oxacillin with or without
an  aminoglycoside,  vancomycin  with  or  without  an   aminoglycoside,   OR
clindamycin   with   or   without   an   aminoglycoside.    Patients  with  a
hemoglobinopathy  are  treated  empirically  with  nafcillin  or  oxacillin +
ampicillin.  Alternatively, the patient can  be  treated  with  nafcillin  or
oxacillin   +   cefotaxime   or  cefriaxone,  OR  nafcillin  or  oxacillin  +
chloramphenicol, OR cefazolin, cephalothin,  or cephapirin + chloramphenicol.
For patients with vascular  insufficiency,  decubitus  ulcer,  diabetic  foot
ulcer, use aminoglycoside + clindamycin, cefoxitin, imipenem, betalactam-beta
lactamase inhibitor or anti-pseudomonad penicillin.  Alternatively, aztreonam
+  clindamycin,  imipenem  (alone),  OR  a  quinolone  +  metronidazole  OR a
quinolone + clindamycin.  SPECIFIC THERAPY FOR ADULTS: Staphylococcus aureus:
(Nafcillin 2 gm q6h or clindamycin  900  mg q8h OR vancomycin, or cefazolin),
Methicillin  resistant  Staphylococcus  aureus:  (Vancomycin  1  gm  q12h  OR
sulfamethoxazole-trimethoprim   +    rifampin,    or    imipenem-cilastatin),
Staphylococcus  epidermidis: (Vancomycin 1 gm q12h, OR nafcillin 2 gm q6h, OR
cefazolin, or clindamycin), Pseudomonas aeruginosa: (Piperacillin 3 gm q4h or
ceftazidime 2 gm  q8h  +  tobramycin  5  mg/kg/day  q8h  OR ciprofloxacin, or
amikacin), Bacteroides fragilis: (Clindamycin 900 mg q8h OR metronidazole, or
ampicillin-sulbactam),  Serratia  marcescens:  (Cefotaxime  2  gm   q6h   +/-
gentamicin  5  mg/kg/day  q8h OR ciprofloxacin, or mezlocillin + gentamicin),
Enterococcus species: (Ampicillin 2 gm q6h  +/- gentamicin 5 mg/kg/day q8h OR
vancomycin, or ampicillin-sulbactam), Group A streptococcus: (Penicillin G  2
million   U   q4h  OR  clindamycin,  or  cefazolin),  Group  B  sreptococcus:
(Penicillin G 2  million  U  q4h  OR  clindamycin, or cefazolin), Escherichia
coli: (Ampicillin 2 gm q6h OR cefazolin, or tobramycin),  Proteus  mirabilis:
(Ampicillin  2  gm  q6h  OR  cefazolin,  or gentamicin), Morganella morganii,
Proteus vulgaris, proteus rettgeri:  (Cefotaxime  2  gm  q6h +/- gentamicin 5
mg/kg/day q8h  OR  mezlocillin  +  gentamicin),  Peptostreptococcus  species:
(Penicillin   G  2  million  U  q4h  OR  clindamycin,  or  metronidazole,  or
ampicillin-sulbactam.   In  children,  acute  hematogenous  osteomyelitis  is
usually treated  with  antibiotics  alone,  but  in  the  adult, debridement,
incision and drainage of soft tissue abscesses are usually required if  there
has  been  no  response  to antibiotics after about 48 hours.  The patient is
treated  for  4-6  weeks  with  IV  therapy.   In  children  it  is sometimes
permissible to treat the patient with appropriate IV antibiotics for 2  weeks
followed  by  oral  therapy.   A  peak  bactericidal dilution of at least 1:8
should be maintained.  Remember,  however,  that pediatric patients under the
age of 16 cannot be treated  with  quinolones.   Vertebral  osteomyelitis  is
treated  for  4-6  weeks.   In  patients  with  osteomyelitis  and  secondary
contiguous  foci,  the  patient is started on an appropriate antibiotic for a
few days, followed by debridement.  This approach will decrease the incidence
of bacteremia following surgery.  Debridement  may  need to be done every 2-3
days until all necrotic  tissue  has  been  removed.   Patients  are  usually
treated  with antibiotics for 4-6 weeks using outpatient Hickman, Broviac, or
Groshong  catheters.    Patients   with   chronic   osteomyelitis  cannot  be
successfully treated with antibiotics alone, and  surgery  is  necessary  for
eradication.   For  superficial  bone infections secondary to diabetic ulcers
and  open  fractures,  repeated  debridement   should  be  carried  out  with
subsequent coverage of soft tissue with skin grafts, muscle flaps or allowing
the ulcer to granulate.  For more advanced disease, the dead  space  must  be
managed  with  antibiotic  beads,  muscle  flaps and bone grafts.  Hyperbaric
oxygen may be helpful in some cases of chronic osteomyelitis.

                           -OSTEOPOROSIS-
Causes:    Cushing's    syndrome,    hyperparathyroidism,    hyperthyroidism,
hypercalciuria,   hypogonadism,   alcoholoism   malabsorption,  osteomalacia,
malabsorption, anorexia nervosa,  furosemide, tetracyclines, glucocorticoids,
anticonvulsants, excessive  thyroid  hormone,  severe  liver  disease,  renal
failure, primary biliary cirrhosis, multiple myeloma, carcinoma metastatic to
bone,  female  sex,  advancing  age, nulliparity, early menopause, fair skin,
short stature, slender body  build,  intercurrent illness, cigarette smoking,
sedentary lifesytle, low calcium  intake  and  genetic  factors.   Treatment:
Calcium 1000-1500 mg daily at hs.  Exercise walking 20-30 minutes three times
a  week  and  carrying  light  weights  of 2-3 lb.  Vitamin D 400-800 U daily
should be ensured in patients  with  osteoporosis.  Vitamin D supplements are
not recommendeded for  general  use.   Estrogen-either  transdermal  or  oral
should  be  initiated  at  time  of  menopause  to  prevent bone loss, if not
contraindicated.  Even after osteoporosis has developed estrogen will cause a
modest increase in  bone  density.   Estrogen  will  also  reduce the risk of
myocardial infarction and possibly stroke.  Calcitonin probably  reduces  the
risk of new vertebral fractures and also is analgesic which makes it suitable
for  those  with  acute or chronic pain from osteoporosis.  Salmon calcitonin
(Calcimar, Miacalcin) given subcutaneously daily 100 U produces improved bone
density in 6-12 months followed by  a  plateau.   If given every other day it
appears to prevent bone loss.  Etidronate (Didronel) and pamidronate (Aredia)
have not been approved as of this writing for osteoporosis by the FDA in  the
USA.   It  is  approved  in  other countries.  Intermittent cyclic etidronate
giving 400 mg (5-10 mg/kg)/day  for  2  weeks  and  repeated every 3 months +
calcium 500 mg daily for 2 years or more has increased  spinal  bone  mineral
density and reduced the rate of new vertebral fractures.  This regimen may be
useful  for  women  who  cannot  take  estrogen  and  for  whom calcitonin is
ineffective or unacceptible because of  cost,  side effects, or problems with
injections.   Fluoride  therapy  will  increase  trabecular  bone  mass,  but
possibly at the expense of cortical bone.  The  quality  of  trabecular  bone
formed  has  been questionable.  However, fluoride may be considered in those
unresponsive to other  treatments  and  those  whose  osteoporosis  is due to
glucocorticoid treatment or  liver  disease  where  osteoblast  formation  is
defective.

                    -PAGETS DISEASE OF THE BONE-
Paget's  disease  (PD)  is  a  bone disease that has no known cause, is often
asymptomatic, but does cause bone  pain,  and is characterized by an increase
of the alkaline phosphatase.  About 3% of persons greater than 40  will  have
Paget's'  disease,  and males are more affected than females.  The disease is
more common in England, Australia,  New  Zealand, Eastern and Western Europe.
There may be a family history in about  10-20%  of  patients.   There  is  an
increase in osteoclastic bone resorption and then remodeling with an increase
in  osteoblastic  activity.   The  abnormal bone that is formed has increased
numbers of arterioles and venous sinuses which causes arteriovenous shunting.
CLINICAL: The most common complaint, in  about  50% of patients, is pain that
is usually in the back, lower extremities, pelvis and hips.  About 75% of all
patients with Paget's disease have pelvic and sacral involvement.  About  50%
have  some  vertebral  and/or  femoral  involvement, and about 1/3 have skull
involvement.  Disease in isolated long  bones outside of joints responds best
to treatment, whereas disease in the vertebrae or joint spaces never responds
completely to treatment.  About 45% have neuromuscular  signs  and  symptoms,
and  cardiovascular  findings occur in about 35%.  Cardiac calcifications are
not uncommon and have been reported  to  involve the aortic and mitral valves
or the interventricular septum.  There  may  be  complete  heart  block  with
calcification in the bundle of His.  Defective hearing, headaches and urinary
tract  complaints  occur  in  14%.   Deafness  is  the most common neurologic
complication and may be secondary to  damage  of the middle ear or the eighth
nerve, and does not improve with treatment.  Approximately 20-40% have  skull
or  jaw  enlargement  and  bowing  of  the  lower  extremities.   Dyspnea and
increasing head size may occur.  There may be cranial nerve palsies involving
the V and VII and VIII cranial  nerves.  Also, there may be hydrocephalus due
to basilar invagination with obstruction of the CSF flow.  Vertebral or brain
stem  involvement  causes  the  greatest  morbidity,  but  fortunately  often
reverses with therapy.  Fractures, compression, and radicular  symptomatology
may  be present.  Physical examination reveals increased warmth overlying the
involved bone, dilated scalp veins,  and angioid streaks on funduscopy.  High
output heart failure may occur if there is more  than  35%  of  the  skeleton
involved.   Osteosarcomas  may develop in long standing disease.  LABORATORY:
There is an elevated alkaline phosphatase.  It is important to rule out other
causes of elevated of  alkaline  phosphatase,  such as liver disease, healing
fracture, metastatic  cancer,  osteomalacia,  and  hyperparathyroidism.   The
serum  calcium and phosphorus are usually normal.  There is an increase in 24
hour urinary hydroxyproline.  The bone scan is the most sensitive for picking
up the early areas of Paget's  disease.   On  x-ray, there may be cortical or
trabecular coarsening, with or without enlargement of bone.   The  x-ray  may
also  show  areas  of  lysis, and osteoporosis circumscripta (the lytic phase
that precedes sclerotic overgrowth) in  the skull.  In an occasional patient,
bone biopsy may be needed to make the diagnosis, but  in  the  majority,  the
entire  picture  is clear enough to make a diagnosis.  TREATMENT: CALCITONIN:
For routine maintenance, 50 MRCU  of  calcitonin  three times per week may be
given.  Many patients, however, will require higher doses of 100  MRCU  three
times  per  week.   As  preparation  for  orthopedic surgery, OR treatment of
immobilization hypercalcemia, OR as initial  treatment of patients with lytic
disease in a weight bearing bone,  100  MRCU  should  be  given  daily.   For
neurologic  complications, 100 MRCU bid will maximize the treatment response.
Calcitonin is expensive and ranges  from  about  $27.00  per week for 50 MRCU
taken three times per week to $252.00 per month for 100 MRCU  taken  twice  a
day.   Because  this treatment is expensive and requires repeated injections,
Didronel is often prescribed  for  most  indications.  Calcitonin is safe and
effective with a rapid onset of action.  About 80-90% of patients develop  an
acute  clinical  remission,  and most patients demonstrate a 50% reduction in
biochemical indicators of disease.  Although sustained biochemical remissions
are  rare  after  12  months,  many  patients  experience  prolonged clinical
remissions.   DIDRONEL  (EHDP):  Oral  didronel  is  about  as  effective  as
calcitonin, but has a slower onset of action and may predispose  to  fracture
in  patients  with  lytic bone lesions.  It can be administered at doses of 5
mg/kg/day po for no more than 6  months  OR  20 mg/kg/day po for no more than
one month.  With either one of these  regimens  it  is  possible  to  achieve
50-70%  suppression  of  biochemical  indicators of disease, and to achieve a
clinical  response  in  up  to  90%  of  patients.   Since  Didronel produces
hypocellular bone, it should be  avoided  in  patients  requiring  orthopedic
surgery,  or  those  with  lytic  disease  in  a  weight  bearing  bone.  For
emergencies such as  neurologic  complications  of  Paget's disease, Didronel
should be given at doses of 4.3 mg/kg/d IV for seven  days.   Since  Didronel
frequently produces long term remissions, it is reasonable to follow patients
after  one  treatment  cycle,  and  repeat  treatment  only  when biochemical
indicators rise or the patient again becomes symptomatic.  Remissions lasting
up  to  24  months  are  fairly  common.   Didronel  should  be  discontinued
intermittently, even if long term remission is not achieved.  It is common to
treat with Didronel for 6 months and  then  follow with a six month drug free
holiday.  If symptoms become troublesome during the drug holiday,  calcitonin
can  be  used.  Combination therapy with Didronel is not significantly better
than maximal therapy with either agent alone.  Didronel is safe and non-toxic
if used properly, but onset of  action  is slow.  Didronel is inexpensive and
not  associated  with  drug  resistance.   Almost  90%  of  patients  improve
clinically.  Biochemical indicators of disease decrease by 50-70%.  Long term
biochemical and clinical remissions are common.  Osteomalacia and possibly an
increased  risk  of  fracture  are  significant  disadvantages.   SUMMARY  OF
SPECIFIC TREATMENT: 1...For bone pain  prescribe  calcitonin  50-100  MRCU  3
times per week or Didronel 5 mg/kg/d po for 6 months.  2...For bone pain with
a  lytic lesion prescribe calcitonin 100 MRCU/day until the lesion is healed.
Then,  use  either  calcitonin  or  didronel  as  described  above.   3...For
congestive heart  failure  find  and  treat  the  underlying  cause.  4...For
neurologic complications prescribe calcitonin 100 MRCU  bid  and/or  Didronel
4.3 mg/kg/d IV times 7 days.  5...For orthopedic surgery prescribe calcitonin
100  MRCU  qd for 3 months before and 6 months after surgery.  6...For active
disease in a young patient prescribe  calcitonin 50-100 MRCU 3 times per week
or Didronel 20 mg/kg/day po for one month.  Follow patient until relapse.

                           -PANCREATITIS-
POOR  PROGNOSTIC  FACTORS  IN  PANCREATITIS:  1..CARDIAC  (BP  <  90  mm Hg),
2..PULMONARY (Tachycardia >  130),  3..RENAL  (Urinary  output < 50 ml/hour),
4..METABOLIC (Calcium < 8 mg/dl, Albumin < 3.2 g/dl).  MANAGEMENT: 1..MILD TO
MODERATE  -  Treatment  involves  volume  repletion  and  pain  control  with
nasogastric suction as needed for vomiting.   The  patient  should  be  given
sufficient  medication  to  relieve  pain.  Demerol is preferable to morphine
because it has less tendency to cause  spasm of the sphincter of Oddi.  Fluid
sequestration can be considerable, even in mild pancreatitis; up  to  30%  of
the  circulating  plasma  volume  may  form  a  peripancreatic exudate.  Some
physicians suggest that a unit (12.5  g)  of albumin should be given for each
liter of fluid for deficits greater than 2 or 3 L. Symptoms will  resolve  in
about  4-7  days.   Persistence  of  symptoms  or recurrent symptoms when the
patient begins eating again may suggest development of a complication such as
a pseudocyst or  abscess,  although  it  only  occurs  in 10-20% of patients.
Amylase elevations may persist up to two weeks in about 10% of patients,  but
should  prompt  a  search  for  pseudocyst formation.  Routine treatment with
antibiotics should not  be  necessary.   Many  patients  will  have low grade
temperature  elevations  and  leukocytosis   without   bacterial   infection.
2....SEVERE  PANCREATITIS - is less common than mild to moderate pancreatitis
and has a high morbidity and mortality.   Hospital stays of up to 60 days are
common with about  half  this  time  spent  in  ICU.   Patients  with  severe
pancreatitis  generally  are hypotensive and need large volume resuscitation.
If this is not  sufficient  to  stabilize  blood pressure then pressor agents
should be added in as low a dose as possible with dopamine as a first  choice
to  protect  renal blood flow.  Oxygen by nasal cannula is routinely required
and many eventually require ventilator  support.  In addition modalities such
as antibiotic and lavage with or without added protease inhibitors are  often
tried.   Peritoneal  lavage has not been clearly shown to affect mortality in
well designed trials.  In general,  surgery  for acute pancreatitis is rarely
needed.  Indications are  pancreatic  sepsis  with  infected  pseudocysts  or
abscesses, rare GI perforations, unresolved mature pancreatic pseudocysts and
very  rarely  protracted pancreatitis with necrosis, or when the diagnosis is
unclear  and  the  patient  is  deteriorating.   BILIARY  PANCREATITIS  -  If
underlying gallbladder or common  duct  stones  are not dealt with reasonably
soon, the incidence of recurrent pancreatitis in the next 6 weeks to 6 months
is quite high.  In severe cases of  biliary  pancreatitis,  ERCP  to  extract
stones within three days resulted in fewer complications and shorter hospital
stays than when patients were treated with conventional therapy.  In contrast
early  surgery  (less  than  48 hrs) results in increased mortality in severe
pancreatitis and should be  delayed.   IMAGING STUDIES IN ACUTE PANCREATITIS:
Imaging studies in acute pancreatitis are not as important for  diagnosis  as
for  detection  of  complications  and to look for treatable problems such as
gallstones.  The chest radiograph is  important  to assess baseline status of
the heart and lung.  Some patients develop pleural effusions.  Atelectasis is
common.  1....PLAIN FILM OF THE ABDOMEN -  All  patients  should  have  plain
films  of  the  abdomen  with both an AP view and either an upright film or a
left lateral decubitus.  You may  see  ileus or gastric dilatation.  Rarely a
mass will be seen in patients with pseudocyst or abscess.  In  patients  with
suspected  alcoholic pancreatitis, calcifications of the pancreas support the
diagnosis of chronic pancreatitis  with  an  acute episode superimposed.  You
may detect free air from a perforated viscus.  2....ABDOMINAL SONOGRAM  -  is
used  to detect gallstones with or without ductal dilatation and later in the
course identifying  and  following  pseudocysts.   In  mild pancreatitis, the
sonogram may be normal, but in more advanced cases the  pancreas  will  often
appear  enlarged  and  hypoechogenic.   Hemorrhage in and around the pancreas
causes increased echoes.   Sonography  is  limited  by  the presence of small
bowel dilatation.  3....ABDOMINAL CT - is  best  reserved  for  complications
such  as  abscesses  which  may  occur late.  In early pancreatitis, like the
sonogram the abdominal CT will  show  either  no abnormalities or a diffusely
enlarged gland.  The head of the gland  is  sometimes  particularly  enlarged
which may raise the question of pancreatic cancer.  Follow up generally shows
resolution   after  several  weeks  or  months.   In  more  severe  cases  of
pancreatitis, the peripancreatic fat often  develops a streaky appearance due
to fat necrosis.  When intravenous contrast material is given,  the  necrotic
areas  of  the  pancreas  will  not  perfuse  well, allowing visualization of
phlegmons (exudates), pseudocysts or hemorrhage.  A very important use of the
CT scan is to allow direct  visualization and aspiration of these collections
when sepsis is suspected.  Occasionally pseudocysts can be drained by placing
drainage catheters under CT guidance.  COMPLICATIONS OF  ACUTE  PANCREATITIS:
1....SYSTEMIC  COMPLICATIONS  The  most  common  of these are hypovolemia and
shock,    hypocalcemia,     hyperlipidemia,     hyperglycemia,    coagulation
abnormalities, respiratory  complications,  renal  problems  and  less  often
arthritis,  bone  and  skin lesions.  A....Hypovolemia and shock with cardiac
decompensation  is  the  cause  of  the   majority  of  deaths  in  in  acute
pancreatitis.  As in sepsis, the cardiac index  increases  and  the  systemic
vascular  resistance  increases.  B....Hypocalcemia less than 8 mg/dl is seen
in a  large  proportion  of  patients  with  acute  pancreatitis (30-60%) and
denotes a poorer prognosis.  Hypocalcemia is generally  worst  in  the  first
several  days  of  the illness.  Hypokalemia, hypomagnesemia, and hypokalemia
must be corrected to prevent cardiac arrhythmias.  C....Hyperlipidemia may be
either the cause or consequence of acute pancreatitis.  About 20% of patients
have hyperlipidemia.  High triglycerides  may  occur with normal cholesterol.
It is important to recognize hyperlipidemia for  several  reasons:  1.  In  a
minority  of patients hyperlipidemia may be the primary cause of pancreatitis
so they should be treated appropriately  when the patient recovers to prevent
recurrences.  2. Patients who develop acute respiratory distress syndrome are
more likely to have hypertriglyceridemia.  3. Hyperlipidemia can lead to  fat
embolizations in the brain and other organs.  4. Serum amylase may be falsely
depressed  in  patients with hyperlipidemia, confusing the diagnosis of acute
pancreatitis.  D....Hyperglycemia is  another  poor  prognostic sign in acute
pancreatitis.  As many as 2-10% may develop  diabetes  after  an  episode  of
severe  acute  pancreatitis.   During  the  acute illness it is generally not
necessary to treat hyperglycemia unless  it  is severe, since patients may be
quite  sensitive  to  insulin  and  develop  hypoglycemia.   E....Coagulation
abnormalities  in   pancreatitis   can   cause   disseminated   intravascular
coagulopathy  (DIC),  bleeding  and  intravascular  thrombosis.   They do not
respond well to heparin therapy.   Although  5-10%  of patients may have some
upper  GI  hemorrhage  from  inflammation  of  the  stomach   and   duodenum,
transfusion  is rarely necessary.  More rarely pancreatic inflammation causes
erosion  of  a   major   intraabdominal   vessel  with  internal  hemorrhage.
Angiography is the best method for diagnosing this, and in  centers  equipped
to  do  so,  embolization may obviate the need for surgery.  F....Respiratory
complications are organized into 3 categories:  1. About 60% of patients have
mild respiratory insufficiency with arterial hypoxemia  but  no  clinical  or
radiographic  abnormalities in the first few days of illness.  These patients
need  to  be  given  oxygen  and   monitored  for  response  with  blood  gas
determinations but rarely need other treatment.  2. About 1/3 have  not  only
hypoxia,   but   demonstrable   abnormalities   such   as  pleural  effusion,
atelectasis, elevation of the diaphragm,  or pulmonary infiltrates.  3. About
10-15% develop  respiratory  distress  syndrome,  with  ventilation/perfusion
mismatch, severe hypoxia, and fluffy pulmonary infiltrates.  Patients require
close  attention  to  fluid balance and intubation and ventilatory assistance
with PEEP.   Steroids  are  often  given,  but  probably  are not beneficial.
G....Renal complications are serious and  are  due  primarily  to  shock  and
tubular  necrosis.   These  patients  may also develop deposits of fibrin and
fibrinogen in the glomerular capillaries.  Acute renal failure in conjunction
with acute pancreatitis  carries  a  mortality  rate of 80%.  H....Arthritis,
bone and skin lesions are generally  due  to  metastatic  fat  necrosis  from
circulating  pancreatic  lipase.   Skin lesions appear like erythema nodosum,
but are found on the thorax, buttocks  and thighs as well as on the pretibial
and  malleolar  areas.   2....LOCAL  COMPLICATIONS   Local   pancreatic   and
peripancreatic  fluid collections can be divided into Pseudocysts, Phlegmons,
and Abscesses.  Sonography and abdominal  CT  scanning are essential for good
diagnosis and management  of  these  problems.   A....The  pseudocyst  is  an
encapsulated  collection of fluid arising initially from the pancreas.  There
is no true wall composed of  cells, thus the name pseudocyst.  The pseudocyst
contains pancreatic enzymes and debris.  Although most pseudocysts are in  or
near  the  pancreas, frequently in the lesser sac, they may track through the
retroperitoneal  tissues  into  distant  locations  such  as  the  pelvis  or
mediastinum.   Frequent  use  of   the   sonogram   in  patients  with  acute
pancreatitis has shown that pseudocysts  are  exceedingly  common;  most  are
small  and resolve without sequelae and require no specific treatment.  Up to
50% of patients with severe pancreatitis may develop pseudocysts.  Continuing
abdominal pain in a patient with  acute  pancreatitis after a week of therapy
may  indicate  pseudocyst  formation.   In  patients  with  elevated  amylase
concentrations after  three  weeks  of  observation,  50%  have  pseudocysts.
However,  it  should  be  noted  that  half of patients with pseudocysts have
normal  amylase  concentrations.   Pseudocysts  larger  than  5  cm generally
require surgical treatment.  Generally the patient  should  be  observed  for
four  -  six  weeks  to  allow the wall, composed of fibrous tissue, to form.
Then the patient should have either excision of the cyst (usually technically
not feasible) or internal  drainage  into  the  stomach, duodenum or jejunum.
External drainage should be avoided except in critically ill patients,  since
about  30%  will  develop  pancreatic fistulae.  In some centers percutaneous
drainage with CT placed catheters  is  tried initially, and surgery performed
only if the procedure is unsuccessful.  B....Pancreatic phlegmons are  poorly
localized  collections  of  necrotic  material, fluid and pancreatic enzymes.
Phlegmons  do  not  need  particular  treatment,  but  clinically  are  quite
difficult  to   distinguish   from   pancreatic  abscesses.   C....Pancreatic
abscesses occur when pseudocysts or more commonly phlegmons become  infected.
Eventually frank pus will form.  This complication is more frequent by far in
patients  with  necrotic,  hemorrhagic  pancreatitis.  As many as 9% of these
patients develop an abscess.   Sonography  and  CT cannot distinguish between
sterile and infected fluid collections.  Abscesses occur relatively  late  in
the  course  of pancreatitis, often two to three weeks after diagnosis.  Most
common clinical findings are  fever, leukocytosis and clinical deterioration.
These  symptoms  occur  very  frequently  in  patients  with  severe  sterile
pancreatitis as well.  Early diagnosis and surgical treatment of abscesses is
essential for the patients survival, but surgery itself has a high  morbidity
and  mortality in these critically ill patients, and should be avoided unless
necessary.  When abscess  is  suspected  on  clinical  grounds,  CT scan with
aspiration of any fluid collections should be performed  to  obtain  material
for  culture  and to make the correct decision regarding surgical management.
This aspiration is done  with  a  20  gauge  needle  and in experienced hands
appears to be quite  safe.   A  wide  variety  of  organisms  can  be  found.
ETIOLOGY  OF  PANCREATITIS:  In  the  USA  excessive  alcohol consumption and
gallstones cause about 65% of cases  of acute pancreatitis, while no cause is
found in another 20% and  referred  to  as  idiopathic  pancreatitis.   Other
causes  are  rare but include drugs, infections, trauma including surgery and
endoscopic  retrograde  cholangiopancreatiography  (ERCP),  renal transplant,
hyperlipidemia, hypercalcemia, penetrating ulcer, cancer,  hereditary  causes
and  perhaps rarely, anatomic or functional problems such as pancreas divisum
and  sphincter  of  Oddi  dysfunction.   A....Alcoholic  Pancreatitis  -These
patients are generally men and 30-45  years  of age.  In general, the initial
episode of alcoholic pancreatitis will be the most severe.   Technically  all
patients  with acute alcoholic pancreatitis already have chronic pancreatitis
histologically and although the patient may return to normal clinically after
the episode has resolved, permanent pancreatic damage exists.  B....Gallstone
pancreatitis occurs in patients  most  likely to have cholesterol gallstones.
Thus it is more common in women than men and occurs in a somewhat  older  age
group peaking between ages 50-70.  Again, the initial episode of pancreatitis
is  most  likely  to be the worst.  50% with gallstone pancreatitis will have
repeated attacks if left  untreated  while cholecystectomy prevents recurrent
episodes in virtually all patients.  Small gallstones are more dangerous than
large one, which generally cannot pass into the cystic duct but remain in the
gall bladder.  C....Idiopathic pancreatitis  clinically  resembles  gallstone
pancreatitis   in   its  patient  population  and  mortality.   However,  the
recurrence rate is less  than  half  of  that seen in gallstone pancreatitis.
D....Drug induced pancreatitis  is  quite  uncommon.   AZATHIOPRINE  and  its
metabolite 6-MERCAPTOPURINE cause a generally mild pancreatitis in about 3-6%
of  patients who take these drugs; most commonly given for inflammatory bowel
disease or after organ  transplant.   This  is  felt to be a hypersensitivity
reaction.   THIAZIDE  DIURETICS   Thiazide   diuretics   occasionally   cause
pancreatitis,  which  can  be fatal.  The risk of pancreatitis increases with
dose and duration  of  treatment.   SULFONAMIDES  produce  pancreatitis by an
allergic mechanism since symptoms  of  vasculitis  occur  in  most  patients.
TETRACYCLINE  like  thiazide  diuretics, cause pancreatitis in relation to an
increasing dose and  duration  of  use.   The  pancreatitis is complicated by
simultaneous liver disease and  prognosis  is  quite  serious,  with  a  high
mortality   rate.    ESTROGENS   produce   pancreatitis  by  elevating  serum
triglycerides, usually to greater than  3,500 mg/dl.  In patients with normal
triglycerides, estrogens are not associated with pancreatitis.  VALPROIC ACID
and SULINDAC have both been associated with  cases  of  pancreatitis.   Drugs
which  probably  cause  pancreatitis include CHLORTHALIDONE, ETHACRYNIC ACID,
L-ASPARAGINASE,  PHENFORMIN,  METHYLDOPA   AND   RARELY  STEROIDS.   CLINICAL
PRESENTATION OF ACUTE PANCREATITIS: SYMPTOMS AND SIGNS - There is  epigastric
pain  often  radiating  to  the  back,  nausea,  vomiting,  fever, and volume
depletion.  Jaundice may occur,  but  hematemesis  is  much more unusual.  In
some slow GI bleeding occurs in about 10%  of  patients  due  to  gastric  or
duodenal  inflammation secondary to the contiguous inflammed pancreas.  These
patients rarely require transfusion.   The  most  simple pathological form of
pancreatitis is edematous pancreatitis.   Symptoms  and  pancreatic  swelling
resolve  without sequelae.  The pancreas is pale and boggy with fluid between
the pancreatic  lobules.   Acinar  cell  necrosis  does  not  occur,  but fat
necrosis may be present.  More severe pancreatic injury results  in  necrosis
and  or  hemorrhage  of the pancreas, leading to severe systemic symptoms and
local complications such  as  phlegmons,  pseudocysts, abscess, fistulae, and
pancreatic ascites.  After an acute attack of pancreatitis is over, it  takes
weeks  or  months  for  endocrine  and exocrine pancreatic function to return
entirely to normal.  SERUM AMYLASE -  False negative and positives may occur.
When amylase is normal, serum lipase will usually be elevated, but  about  5%
of patients with clinical symptoms and CT findings of acute pancreatitis will
have  normal  serum  concentrations of both amylase and lipase.  DIFFERENTIAL
DIAGNOSIS: Differential  diagnosis  includes  perforated  peptic ulcer, acute
cholangitis, and mesenteric infarction.  Perforated  peptic  ulcer  generally
has  a  very  abrupt  onset  of  severe pain and is associated with prominent
peritoneal signs such as abdominal rigidity.   In at least 75% of cases, free
air in the abdomen is apparent on chest  radiograph  or  plain  film  of  the
abdomen.   Perforations into the lesser sac or retroperitoneal tissues may be
more difficult to detect.  Acute CHOLANGITIS, like pancreatitis, has an onset
over minutes  to  a  few  hours.   Temperature  elevations  may  be higher in
cholangitis, and pain is more likely to  be  localized  to  the  right  upper
quadrant.   MESENTERIC INFARCTION is almost always difficult to diagnose, but
should be considered in older  patients  or  those with a history of vascular
disease.  The pain of mesenteric infarction  is  generally  more  gradual  in
onset  than  that  of  pancreatitis.   An important clinical clue is that the
patient's pain is often out of  proportion to the relatively normal abdominal
exam.  CAUSES OF HYPERAMYLASEMIA: Chronic pancreatitis Pancreatic  pseudocyst
Carcinoma  of  pancreas Common bile duct obstruction Peptic ulcer penetrating
into  pancreas  Peptic  ulcer   perforation  Mesenteric  infarction  Salivary
adenitis  Acute  alcoholism  Hepatocellular  disease  Opiate   administration
Ovarian neoplasm Macroamylasemia Acute pancreatitis Postoperative state Burns
Diabetic  ketoacidosis  Chronic  renal  insufficiency Pancreatic duct rupture
Acute cholecystitis Afferent  loop  obstruction  Salpingitis Ruptured ectopic
pregnancy Post ERCP.

                       -PANCREATITIS (Causes)-
OBSTRUCTION:   Choledocholithiasis,  pancreas  divisum  with  accessory  duct
obstruction, ampullary  or  pancreatic  neoplasms,  worms  or  foreign bodies
obstructing the  papilla, periampullary  duodenal  diverticula,  hypertensive
sphincter   of   Oddi,   and   choledochocele.    INFECTION:   Parasitic,  as
clonorchiasis,  ascariasis.   Viral  such  as rubella, hepatitis A, B, non-A,
non-B,   mumps,   adenovirus,   echo   virus,   varicella,   cytomegalovirus,
Epstein-Barr virus, HIV.  Bacterial such as Campylobacter jejuni, mycoplasma,
Mycobacterium  TB,  Mycobacterium  avium  complex,  leptospirosis, legionell.
TOXINS AND DRUGS: Toxins such as methyl and ethyl  alcohol,  organophospnorus
insecticides,  and scorpion venom.  Drugs such as valproic acid, azathioprine
and  mercaptopurine,   estrogen,  metronidazole,  tetracycline,  pentamidine,
nitrofurantoin,    furosemide,    salicylates,    sulfonamides,   cimetidine,
ranitidine,   methyldopa,    didanosine,    sulindac,    erythromycin,    and
acetaminophen.   VASCULAR: Atheroscerotic emboli, hypoperfusion such as after
cardiac  surgery,  vasculitis  secondary   to  SLE,  malignant  hypertension,
polyarteritis  nodosa.    METABOLIC:   Hypertriglyceridemia,   hypercalcemia.
TRAUMA:  Iatrogenic  such  as  ERCP,  endoscopic sphincterotomy, manometry of
sphincter of  Oddi,  and  postoperative  trauma.   IDIOPATHIC  AND INHERITED.
OTHER:  Crohn's  disease,  Reye's  syndrome  and  cystic  fibrosis  (only  in
children), hypothermia, and penetrating peptic ulcer.

                    -PANCREATITIS COMPLICATIONS-
Shock: is due to sequestration of retroperitoneal  fluid  or  hemorrhage  and
kinin  activation.   Treat with volume replacement and dopamine.  RESPIRATORY
FAILURE:  is  due  to   surfactant   degradation   secondary  to  release  of
phospholipase A2.  Treatment is mechanical ventilation.  HYPOCALCEMIA: is due
to peripancreatic fat necrosis and  hypoalbuminemia.   Treatment  is  calcium
replacement.   ACUTE  RENAL FAILURE: is due to acute tubular necrosis.  Treat
with dialysis.   HYPERGLYCEMIA:  is  due  to  excessive  glucagon release and
decreased insulin levels.  Treat with insulin.  SUBCUTANEOUS NODULES: is  due
to  metastatic  fat necrosis.  COAGULOPATHY: is due to circulating proteases.
Treat with fresh frozen  plasma.   RETINOPATHY:  is due to retinal arteriolar
obstruction.  PSYCHOSIS: is due to demyelination and cerebral  hypoperfusion.
NECROSIS:  may  be  sterile due to microvascular hypoperfusion and is treated
with debridement or observation,  OR  may  be infected secondary to bacterial
infection which is treated with debridement and antibiotics.  PSEUDOCYSTS: is
due to extravasation of fluid and inflammatory debris in  the  peripancreatic
spaces.   Suspect if there is persistent pain and persistent hyperamylasemia.
In 50-80% the pseudocyst  will  resolve  within 6 weeks without intervention.
Treat by drainage or observation.  ABSCESSES: due to bacterial infection  and
is  treated  with  drainage.   Usually  develop  2-4  weeks after the initial
episode and presents as fever > 101, persistent abdominal pain and persistent
hyperamylasemia.  If not drained, the  mortality is 100%.  Antibiotics should
be directed against gram negative and anaerobic organisms.  COLON OBSTRUCTION
OR FISTULA: due to necrosis and is treated by  surgery  or  observation.   GI
HEMORRHAGE:   due   to   ulceration,   gastric   varices   and   rupture   of
pseudoaneyurysm.   Ulceration  is  due  to stress and ischemia and is treated
with transufions, and H2 blockers.   Gastric  varices are due to splenic vein
obstruction and is treated with sclerotherapy  and  surgery.   Pseudoaneurysm
rupture  is  treated  with  embolization  and  surgery.   SPLENIC  RUPTURE OR
HEMATOMA: is due to extensiion of  the inflammation.  Treatment is by surgery
or  observation.   RIGHT  SIDED  HYDRONEPHROSIS:   is   due   to   peri-renal
inflammation  and is treated by observation.  PLEURAL EFFUSIONS: usually left
sided, occurring in 20% and  have  a  high  content of amylase in the pleural
effusion.  PANCREATIC ASCITES: results from disruption of the pancreatic duct
or a leaking pseudocyst.  JAUNDICE: is due to common bile duct obstruction.

                             -PAP SMEAR-
A low grade squamous intraepithelial lesion (SIL) or atypical squamous  cells
of  undetermined  significance (ASQUS) requires no further evaluation until a
repeat pap in 4-6 months  because  progression  to a higher grade takes place
after 8 months.  If the repeat pap is normal, do another at 6-12 months.   If
this  again shows ASQUS or low grade SIL colposcopy or cervicography is done.
If the cervix  stains  uniformly  with  Lugol's  solution  with  no sign of a
detectable  lesion  biopsy  is  not  needed.   Any  tissue  that  appears  as
metaplasia, cervical intraepithelial neoplasia or  high  grade  SIL  requires
biopsy.

                     -PARANEOPLASTIC SYNDROMES-
Paraneoplastic syndromes consist of a group of clinical findings secondary to
various endocrine, metabolic, hematologic  or neuromuscular symptoms, that is
not  attributed  to  direct  neoplastic  invasion   or   metastatic   causes.
Paraneoplastic syndromes are important as they may be the first indication of
a  cancer,  may  be  life  threatening as hypercalcemia, and treatment of the
underlying neoplasm usually causes resolution of the paraneoplastic symptoms.
The best known syndromes  are  associated  with ectopic production of altered
hormones or  prohormones  that  differ  in  molecular  weight  from  hormones
secreted  by  normal  endocrine cells.  The following are examples of various
cancers and  their  corresponding  paraneoplastic  presentations.   These are
listed  in  descending   order   of   frequency.    BRONCHOGENIC   CARCINOMA:
Bronchogenic  carcinoma  may  cause  Cushing's  syndrome,  inappropriate  ADH
secretion,  hypercalcemia,  dermatomyositis,  neuromyopathies, coagulopathies
and production of gonadotropins.   BREAST  CARCINOMA: Breast cancer can cause
hypercalcemia, coagulopathies, neuromyopathies  and  dermatomyositis.   RENAL
CARCINOMA:  Renal  cancer  can  cause  polycythemia, fever, hypercalcemia and
Cushing's syndrome.  ADRENAL  CARCINOMA:  Adrenal  carcinoma causes Cushing's
syndrome, hypercalcemia, hypoglycemia and polycythemia.  HEPATOMA:  Hepatomas
can  cause  hypoglycemia,  polycythemia, fever, hypercalcemia, coagulopathies
and  increased  gonadotropins.   MULTIPLE  MYELOMA:  Multiple  myeloma causes
hypercalcemia,  humoral  immune  deficits  and   coagulopathies.    LYMPHOMA:
Lymphomas  cause fever, humoral immune deficits, hypercalcemia, inappropriate
ADH secretion,  and  hypoglycemia.   THYMOMA:  Thymomas  cause humoral immune
deficits, Cushing's syndrome, erythroid aplasia, fever,  neuromyopathies  and
hypercalcemia.   PROSTATIC CARCINOMA: Prostatic cancer causes coagulopathies,
hypercalcemia,  Cushing's  syndrome,  neuromyopathies,  and thrombophlebitis.
PANCREATIC   CARCINOMA:   Pancreatic    cancer    causes    thrombophlebitis,
coagulopathies,   Cushing's   syndrome,   hypercalcemia,   inappropriate  ADH
secretion,  fever,  neuromyopathies,  and  dermatomyositis.  CHORIOCARCINOMA:
Choriocarcinoma  causes  an  increase  in  gonadotropins  and   thyrotropins.
SARCOMA:  Sarcomas  cause  hypoglycemia, hypercalcemia and fever.  PERIPHERAL
NEUROPATHY:   Peripheral   neuropathy   is   the   most   common   neurologic
manifestation.  It can be symmetrical,  pure sensory or a rapidly progressive
sensorimotor neuropathy.  Sensorimotor neuropathy causes distal sensory  loss
and  muscle  weakness.   Cancers  of  the  lung, breast and GI tract are most
associated with  sensorimotor  neuropathies.   Neurologic syndromes involving
the neuromuscular junction  include  dermatomyositis,  polymyositis  and  the
Eaton-Lambert  syndrome.   Serum aldolase, serum creatinine phosphokinase and
sedimentation rates are  increased.   Muscles  biopsy  will show inflammatory
changes and myonecrosis.  Dermatomyositis and polymyositis is seen  in  lung,
breast, gastric and ovarian cancer.  Steroids can be used for treatment.  The
Eaton-Lambert  syndrome  is  usually  seen  in  small cell lung cancer and is
characterized by  increased  muscle  strength  after  repetitive  exercise as
opposed to myasthenia gravis.  There  is  no  response  to  Tensilon  in  the
Eaton-Lambert  syndrome.   There  is usually sparing of the ocular and bulbar
muscles,  but  there  may  be  dysphagia,  dysarthria,  diplopia,  ptosis and
proximal muscle weakness.  Deep tendon reflexes  are  usually  reduced.   The
diagnosis  is  usually  made  by  demonstrating  an  incremental  response to
repetitive nerve stimulation with the amplitude of the compound muscle action
potential  increasing  greater  then  200%  at  rates  greater  than  10  Hz.
Chemotherapy  treatment  of  the   lung   cancer  will  usually  resolve  the
Eaton-Lambert syndrome.  If this doesn't help, then guanidine 125 mg  qid  po
daily  may  be  used.  The dose may be increased up to 35 mg/kg.  The patient
should  be  monitored  because  there  can  be  altered  liver  function  and
depression of the bone  marrow.   Steroids  and plasmapheresis have also been
used  with  some  success.   SUBACUTE   CEREBELLAR   DEGENERATION:   Subacute
cerebellar   degeneration   symptoms   consisting  of  arm  and  leg  ataxia,
dysarthria,  vertigo,  diplopia,  dementia,  ophthalmoplegia,  nystagmus  and
extensor plantar reflexes  may  antedate  the  associated  cancer by weeks to
years.  The CSF may demonstrate a mild lymphocytic pleocytosis.  The  CT  may
show  cerebellar  atrophy.   Treatment  is not satisfactory, but treating the
underlying tumor may help somewhat.   ECTOPIC  ACTH: The diagnosis of ectopic
ACTH producing tumors should be entertained if the ACTH level is greater than
200 pg/mL and there is failure to suppress  plasma  cortisol  or  urinary  17
hydroxycorticosteroids  with  dexamethasone 2 mg po every 6 hours for 2 days.
If  there  is  failure   to   suppress   plasma  cortisol  with  higher  dose
dexamethasone, then ectopic production by a tumor is  fairly  secure.   Also,
hypokalemic  alkalosis  and  hyperglycemia  are  usually  the  most prominent
findings in neoplastic ectopic ACTH  production.  Other symptoms of Cushing's
syndrome would include hirsutism, obesity,  striae,  weakness,  hypertension,
and  moon  face.   Cushing's  syndrome  is  most  frequently  associated with
carcinoma of the lung with a frequency  of  about 1%.  If there is small cell
lung cancer then the frequency increases to 5.5%.  Other  cancers  associated
with  ectopic  ACTH  include  thymomas,  carcinoids, islet cell cancer of the
pancreas, medullary  thyroid  cancer,  neuroblastomas  and pheochromocytomas.
Treatment should be aimed at the underlying tumor, which  will  result  in  a
slow  resolution  of  the features of Cushing's syndrome.  If this fails then
you can treat with  aminoglutethimide,  metapyrone  or o'p'DDD in conjunction
with replacement corticosteroid as 37.5 -  40  mg  of  hydrocortisone  daily.
INAPPROPRIATE  SECRETION  OF ANTIDIURETIC HORMONE: To diagnose SIADH you must
satisfy the criteria  of  hyponatremia,  hypo-osmolality  of  the serum and a
hyperosmolar urine.  The patient must  not  have  volume  depletion,  adrenal
insufficiency   or  hypothyroidism.   Symptoms  of  SIADH  include  weakness,
lethargy, somnolence and  behavioral  changes.   Some  patients  may not have
symptoms.  SIADH is usually associated with small cell carcinoma of the lung.
Treatment of SIADH  is  restriction  of  water,  hypertonic  saline  with  IV
furosemide  and  treatment of the underlying tumor.  Lithium carbonate 300 mg
tid or demeclocycline  900-1200  mg  bid  may  both  be used.  GONADOTROPINS:
Elevations  of  FSH,  LH  and  human   chorionic   gonadotropin   occurs   in
trophoblastic  tumors,  germ  cell  cancers  of  the  ovary,  testis,  or  in
extragonadal  sites.   Elevations  of  the beta chain of hCG has been seen in
patients with lung, breast,  colorectal,  hepatocellular and pancreatic islet
cell tumors.  Elevations of the alpha chain of hCG is  seen  with  colorectal
and  islet  cell  cancers.  Symptoms of ectopic gonadotropin syndrome include
gynecomastia, oligomenorrhea, amenorrhea,  hirsutism  and irregular bleeding.
ERYTHROCYTOSIS: Erythrocytosis is  associated  with  renal  cell  carcinomas,
hepatomas,  cerebellar  hemangioblastomas,  uterine  fibroids,  Wilms' tumor,
sarcomas, pheochromocytomas, thymomas,  cancers  of  the  ovary, and lung and
adrenal adenomas.  There is elevation  of  erythropoietin  in  about  50%  of
cases.   The  erythrocytosis  will disappear if the primary tumor is treated.
LEUKEMOID REACTIONS: Leukemoid  reactions  are  seen  with  carcinomas of the
lung,  pancreas,  and  stomach,  lymphomas,  melanomas  and   brain   tumors.
HYPERCOAGUABLE  STATES:  Cancer  is  associated with a hypercoagulable state.
There  may  be  DIC,   nonbacterial  thrombotic  endocarditis  and  migratory
thrombophlebitis (Trousseau's syndrome).  Trousseau's syndrome occurs  mainly
with pancreatic cancer.  Treatment is with heparin, warfarin and treatment of
the  underlying  cancer,  but  patients  may  not respond optimally.  GASTRIN
SECRETING TUMORS:  Gastrin  secreting  tumors  produce  the Zollinger-Ellison
syndrome with peptic ulcerations even distal to the duodenal bulb.   This  is
caused  by  a  pancreatic  islet  cell  tumor  which  is  usually very small.
Diagnosis is made by gastrin elevations greater than 150 pg/mL.  Treatment is
with Cimetidine  and  total  gastrectomy.   VASOACTIVE INTESTINAL POLYPEPTIDE
SECRETING  TUMORS:  Islet  cell  carcinomas  of  the  pancreas  produce   the
Verner-Morrison  syndrome consisting of inordinate amounts of watery diarrhea
with  concomitant  hypokalemia  and   volume  depletion.   The  treatment  is
resection, if the  tumor  can  be  located.   If  not,  then  treatment  with
streptozocin  may  help.  There have been variable blood levels of vasoactive
intestinal polypeptide.  GLOMERULOPATHIES: Patients  that have minimal change
nephrotic  syndrome  may  have  an  underlying  Hodgkins's  disease.   If   a
membranous  glomerulopathy is found, then seek out carcinomas of the stomach,
colon and  pancreas.   INSULIN  SECRETING  TUMORS:  Insulin  secreting tumors
produce  hypoglycemia  which  typically  occur  after  fasting  or  exertion.
Cancers    associated    with     hypoglycemia     include     fibrosarcomas,
neurofibrosarcomas,  mesotheliomas,  hepatomas  and  islet  cell  carcinomas.
Again,  treatment  is  therapy  of  the  primary tumor.  AUTOIMMUNE HEMOLYTIC
ANEMIA: Patients with  autoimmune  hemolytic  anemia  may  have an underlying
lymphoma,  chronic  lymphocytic  leukemia,  Waldenstrom's  macroglobulinemia,
carcinoma of the ovary, breast, kidney, stomach, colon, cervix  or  seminoma.
Treatment is with steroids, surgical resection of the tumor, chemotherapy and
radiation   of   the   tumor   and   splenectomy,  if  other  measures  fail.
MICROANGIOPATHIC HEMOLYTIC  ANEMIA:  Microangiopathic  hemolytic  anemias are
associated with mucin producing adenocarcinomas as breast, lung and  stomach.
Diagnosis is by finding the typical schistocytes on peripheral smears.

                         -PARASITIC TESTING-
GIARDIASIS AND CRYPTOSPORIDIOSIS: These  two  parasites  account for the most
common causes of diarrhea in the USA and are best diagnosed by ELISA  testing
of  the  stool,  which  detects  antigens of Giardia and Cryptosporidium.  If
watery diarrhea develops in patients  with AIDS, municipal water outbreaks or
in patients who have had contact with farm animals, ELISA testing  should  be
done for Crytosporidium.  In patients that develop watery diarrhea and are in
day  care  centers,  or  are  backpackers,  ELISA  testing should be done for
Giardia.  If the  tests  are  negative  and  the  diarrhea continues, ova and
parasite stool examination should be carried out.  OVA AND PARASITE  TESTING:
Ova  &  parasite  (O&P)  testing  is  the best testing for patients that have
traveled or reside in endemic areas  outside the USA.  O&A testing can detect
all forms of intestinal parasites such  as  the  larvae,  ova  or  adults  of
helminths,  and  cysts  and trophozoites of protozoa.  It is best to obtain 3
specimens collected on different days.  In some cases, more specimens will be
needed  as  in  Giardiasis.    Fresh   specimens  are  preferred  for  direct
visualization of live amebae and larvae.   Many  parasites  will  deteriorate
outside  the bowel lumen and should be submitted in preservatives of formalin
and polyvinyl alcohol.  O&P testing should not be done if the patient has had
recent barium studies, is  taking nonabsorbable antidiarrheal agents, mineral
oil or tetracycline.  If the patient is constipated and a stool  specimen  is
difficult  to  obtain, Epsom salts may be used.  Cryptosporidium, Giardia and
the larvae of Strongyloides may be difficult to detect and examination of the
duodenal contents may help.   This  can  be  accomplished  by the string test
(Entero-Test), endoscopy or by examining the contents from an  enteric  tube.
In  the  string  test,  the  patient  swallows a string enclosed in a gelatin
capsule.  After 4 hours the  string  is retrieved, the duodenal fluid removed
and examined within one hour.  Patients  that  have  Schistosoma  haematobium
urinary  bladder  infections  are  diagnosed  by  passing the urine through a
Nucleopore filter  and  examining  for  ova.   Pinworms  (Enterobius) ova are
detected by pressing scotch tape or a Swube paddle against the perianal  skin
in  the  early  AM.   Cryptosporidium,  Cyclospora and Microsporidium require
special stains for their identification.   SEROLOGY: ELISA testing is carried
out  for  amebiasis,   echinococcosis,   cysticercosis,   and   toxocariasis.
Toxoplasmosis is diagnosed by an indirect fluorescent antibody test that will
detect  IgM and IgG.  Trichinosis is diagnosed by a latex agglutination test.
All parasitic serologic tests,  with  the  exception of toxoplasmosis, detect
only total antibody and do not detect IgG and IgM by themselves.   Therefore,
positive  tests are not specific for recent infections, and could represent a
recent or past infection.  However, the higher the titer, the more likely the
infection is recent.  BLOOD SMEARS:  Giemsa-stained thick and thin smears are
used to diagnose malaria, the lymphatic filariases, babesiosis,  African  and
American (Chagas' disease) trypanosomiasis.  Finger sticks should be used for
blood  rather than anticoagulated blood obtained via venipuncture.  The films
are prepared by placing a small and  large  drop of blood on two slides.  The
thin film is made by spreading from the small drop of blood as in preparing a
slide for a differential leukocyte count.  The thin smear is  helpful  for  a
detailed  identification  of the species of Plasmodium and Babesia within the
red blood cells.  The thick smear  is  prepared by smearing the large drop of
blood onto a slide and dried.  The thick smear is  more  sensitive  than  the
thin  slide but is not as effective in identifying the species of Plasmodium.
Microfilaremia caused by Wuchereria and Brugia  can be visualized on the thin
or the thick slide that is obtained between 10 PM and 2 AM (some microfilaria
are nocturnal).  By using the Knott concentration technique (concentrating  5
ml   of   anticoagulated   ethylenediaminetetraacetic   acid-blood  and  then
centrifuging), the sensitivity of  detection  can be increased.  Trypanosomes
of African and American trypanosomiasis are detected by wet preparations  and
stained  smears  of  the  buffy  coats of 5 ml of centrifuged citrated blood.
Kala-azar (visceral leishmaniasis is diagnosed by staining smears with Giemsa
stain, and  checking  for  intracellular  parasites (amastigotes).  Cutaneous
leishmaniasis is diagnosed by obtaining smears that  are  obtained  from  the
base  of  the  skin  ulcer  and  culturing  for Leishmania.  ACANTHAMOEBA AND
NAEGLERIA:  These  free  living   protozoa   are  diagnosed  by  culture  and
microscopic scrutiny of centrifuged CSF and corneal  scrapings  with  stained
smears   and   wet   mounts.   Naegleria  is  the  cause  of  primary  abebic
meningoencephalitis.  Acanthamoeba  causes  granulomatous amebic encephalitis
and a keratitis in people that wear contact lenses.

                        -PARKINSON'S DISEASE-
MILD  DISEASE:  All  newly diagnosed patients with Parkinson's disease should
probably be started on selegiline  (Eldepryl)  which may slow the progression
of the disease.  The dose is 5 mg in the morning  and  midday.   About  5-10%
will  have  nausea  and  insomnia.   Tridhexyphenidyl  (Artane)  2-6  mg/day,
benztropine  (Cogentin)  1-4  mg/day or amantadine (Symmetrel) 100-300 mg/day
all may be used for tremor,  decreased dexterity, salivation and slowed motor
function.  MODERATE DISEASE: Start with a half tablet of Sinemet  25/100  BID
or  half  a  Sinemet  CD.   In order to keep the levodopa in the low range of
300-500 mg/day,  some  physicians  would  add  bromocriptine (Parlodel) 10-15
mg/day or pergolide (Permax) 1-1.5 mg/day.  The use  of  these  with  Sinemet
gives  a smoother response, but there may be greater toxicity.  The key is to
start all medications at a  low  dose  and  gradually increase the dose.  For
example, bromocriptine may be started at 1.25 mg/day  and  pergolide  at  .05
mg/day  and  increase  over a 2-3 week period.  After the patient has been on
Sinemet for about 5-6 years,  deterioration sets in and response fluctuations
intervene as the patients  enter  into  the  advanced  stage  of  Parkinson's
disease.   ADVANCED  DISEASE:  Strategies  must  be  developed  to extend the
actions of levodopa.  This may be  obtained  by using Sinemet CD BID to start
with, but may need to increase the frequency.  Adding Selegiline  will  block
the  breakdown of dopamine in the brain and extend the levodopa.  The dose is
5 mg BID.   Amantadine  100-300  mg  will  also  extend the levodopa effects.
Paradoxically, the benefit afforded by these ancillary  drugs,  may  increase
the  involuntary  dyskinetic  movements.  Adding pergolide or bromocritine to
Sinemet is also helpful in advance Parkinson's disease, in reducing the motor
fluctuations.   They  are  useful   in  freezing,  hesitancy  and  immobility
episodes.  By adding these drugs, the dose of Sinemet can be reduced in order
to decrease the dyskinetic movements.  Postural  hypotension  may  be  helped
with fludrocortisone (Florinef) or Indocin.

           -PARKINSON'S DISEASE (Levodopa complications)-
DYSKINESIAS: Levodopa induced dyskinesias are dose  related  and  will  abate
when  the  dosage  is  reduced,  but  reduction  may  increase  the Parkinson
symptoms.  The  prevalence  increases  with  the  duration  of  treatment and
usually first begin on the  side  of  the  symptoms.   The  most  common  and
earliest dyskinesia to appear is usually related to the peak dose and consist
of  non  repetitive  choreatic, non purposeful movements affecting the limbs,
face and neck.  Dystonias  consist  of  blepharospasm,  dystonic foot and leg
postures, muscular spasms and dystonic postures of the upper extremity.  Foot
dystonia consists of a downward turning of the toes or inward turning of  the
foot, may be painful, and usually occur early in the morning before the first
dose of levodopa (off-period dystonia), and usually disappear after the first
dose of levodopa.  Akathisia, which is a restless feeling and a need to move,
occurs  in  25%  of  patients  treated  with  chronic  levodopa.   Multifocal
myoclonic  jerks  are rare and may occur at rest.  Nocutrnal myoclonus may be
increased with levodopa.  Severe  dyskinesias can affect swallowing, balance,
respiration  and  speech.   MOTOR  COMPLICATIONS:  Initially,  the   clinical
response is constant throughout the day, but after about 3-5 years of chornic
levodopa  most  patients  will  notice  fluctuations  in  their response.  On
periods represent levodopa efficacy  in  reducing the symptoms of Parkinson's
disease.  Off periods represent return of symptoms.  PEAK DOSE DYSKINESIA  OR
DYSTONIA: These symptoms are worse at the peak effect of levodopa.  Treatment
is  reducing  the  amount  of  each  dose of levodopa, or using a long acting
levodopa preparation.  OFF PERIOD DYSKINESIAS: Is most common in the morning,
but  can  occur  at  any  time  when  levodopa  levels  are  reduced.   These
dyskinesias are usually  dystonic  and  will  disappear  when the levodopa is
discontinued.  Improvement will occur if a sustained release levodopa is used
as Sinemet-CR, or by adding Eldepryl (selegiline) or  by  adding  a  dopamine
agonist  as  pergolide  or bromocriptine.  Selegiline increases the effect of
levodopa by inhibiting  the  catabolism  of  dopamine.  WEARING OFF RESPONSE:
This occurs about 2-4 hours after each dose and is treated by giving levodopa
closer together, or  using  Sinemet-CR,  or  adding  a  dopamine  agonist  as
pergolide, bromocriptine, or a MAO-B inhibitor as selegiline.  Also by taking
the  levodopa  a  half  hour  before  or  1 hour after meals, the levodopa is
enhanced.  ON-OFF RESPONSE: This is a sudden unpredictable immobility that is
unrelated to the levodopa  schedule.   Treatment is with dietary manipulation
or by changing these unpredictable responses to predictable ones,  by  giving
4-5  large doses of levodopa.  Of course, there will be still be off periods.
DRUG FAILURE RESPONSE: This is  usually  related to poor absorption and tends
to occur in the afternoon.  Avoiding protein or adding a dopamine agonist  as
pergolide  or  bromocriptine  may  help.  DIPHASIC DYSKINESA: The patient has
dyskinesias at the  beginning  and  the  end  of  one  dosing interval, which
relates to the rising and falling of ldevodopa levels.  Raising the dose  may
temporarily  help  or  using  a  sustained  release levodopa also is helpful.
BEGINNING OF DOSE  DETERIORATION:  These  patients  experience a worsening of
symptoms which lasts for about 20 minutes after taking  levodopa.   Treatment
is  usually  not  necessary.  POSTURAL HYPOTENSION: Blood pressure is reduced
and dizziness on standing can  occur.   Treatament  is with high sodium diet,
elevation  of  the  head  at  night  and  fluorocortisone  acetate.   NAUSEA:
Carbidopa, which is usually given with levodopa will dramatically reduce  the
nausea.   About  75-100 mg of carbidopa is needed to suppress the nausea, but
occasionally 200 mg is needed.   Carbidopa  (Lodsyn)  can be added if needed.
If increasing the dose of carbidopa is ineffective, domperidone can  be  used
(not  available in the USA, but can be obtained in Canada).  PSYCHIATRIC SIDE
EFFECTS: Psychiatric complications  usually  start  after  3 years of chronic
therapy.  Therapy is difficult because the patient may need  an  increase  of
levodopa  to control symptoms of Parkinson's disease, but increasing the dose
increases mental side effects.   Initial  symptoms include nightmares, visual
illusions, vivid dreams, and visual hallucinations which  consist  of  formed
objects  as people or animals.  Auditory hallucinations are rare.  Amantadine
and  bromocriptine  can  also  cause  these  mental  changes.   Confusion and
paranoid psychotic states can be due to Parkinsons or due to levodopa.   Drug
induced  behavioral  alterations  will  disappear if the dose is decreased or
discontinued.  Thioridazine and molindone  are  the  drugs of choice, because
they will not increase Parkinson symptoms.  Clozapine  will  reduce  levodopa
induced   psychosis   and   is  free  of  extrapyramidal  side  effects,  but
agranulocytosis is a  rare  side  effect  mandating  weekly CBCs.  Start with
25-50 mg/day.

                             -PAROTITIS-
CAUSES: dehydration, malnutrition, calculi in the salivary glands, dry  mouth
due   to   medications,   surgery,  mouth  breathing,  guanethidine,  chronic
inflammation  associated  with   TB,   actinomycosis,  leukemia,  alcoholism,
diabetes,  Hodgkin's  disease,  Laennecs   cirrhosis,   hypertriglyceridemia,
connective  tissue  disorders  as SLE, Sarcoidosis, Sjogren's syndrome, mixed
parotid tumor, lymphoma, phenylbutazone,  iodides and thiouracil.  TREATMENT:
Treat with vancomycin, as many of these  are  due  to  methicillin  resistant
Staph  aureus.  Also can use nafcillin, and hydration.  Also may be caused by
Klebsiella pneumoniae,  Streptococcus  pneumoniae,  beta  hemolytic Strep and
gram negative organisms.   SYMPTOMS:  include  erythema  of  Stenson's  duct,
fever,  chills  and  leukocytosis.   The parotid gland should be massaged and
cultured.  After patient is  cured  start  non  sugar  hard candy, good mouth
hygiene and hydration.

              -PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA-
CLASSIFICATION:  PSVT  can  be  divided  into  4  types  as follows: AV nodal
reentrant tachycardias are the most common  and represent about 60% of PSVTs.
AV reciprocating tachycardias (25%), intraatrial  and  sinus  node  reentrant
tachycardia (10%), and automatic atrial tachycardia (5%).  AV NODAL REENTRANT
TACHYCARDIA:  The rate of this tachycardia is usually between 150-250.  It is
common in young to older females  that  have no structural heart disease.  It
is usually initiated by a premature atrial beat that blocks  conduction  over
the  fast  AV  pathway,  allowing  antegrade conduction over the slow pathway
followed  by  retrograde  conduction  over  the  fast  pathway  which  is now
non-refractory.   This  circuit  conduction   then   repeats	itself.    The
reentrant retrograde beat is usually concealed in the terminal portion of the
QRS interval due to the rapid rate of the tachycardia and will not be seen on
the  surface  ECG.  The tachycardia can be precipitated by caffeine, alcohol,
exercise and sympathomimetic drugs.  It may be terminated by vagal maneuvers,
valsalva,  iced  water,  carotid  stimulation  and  coughing.   If  these are
unsuccessful, adenosine 6  mg  given  as  an  IV  bolus  is  very  effective.
Radiofrequency ablation in a young healthy patient with recurrent episodes of
AV  nodal reentrant tachycardia is the treatment of choice.  The area of slow
conduction is ablated with a success  rate >90%.  Complications are rare with
complete heart block necessitating permanent pacing occurring in < 5%.  Drugs
such as verapamil 240-360 mg/day, diltiazem 240-300 mg/day, digoxin  .125-.25
mg/day  or  beta  blockers  can  also  be  used  for  long  term therapy.  If
refractory to these drugs, flecainide and propafenone may be used effectively
in patients without structural  heart disease.  AUTOMATIC ATRIAL TACHYCARDIA:
Is usually  seen  in  those  with  heart  disease,  metabolic  disorders  and
digitalis  toxic  patients.   The  rate  is  usually  100-250  and the P wave
morphology depends on the  site  of  atrial  origin, but is usually different
than the sinus beat.  Atrial tachycardia with block may be due  to  digitalis
excess  and  usually  occurs with a 2:1 AV block.  Vagal maneuvers may reduce
the ventricular rate by  increasing  the  block,  but  will not terminate the
rhythm and should not be used  if  digitalis  is  the  cause.   Treatment  is
discontinuing the digitalis and maintaining a normal serum potassium.  If not
caused  by  digitalis,  digoxin  or  a  beta  blocker may be used to slow the
ventricular  rate.   RECIPROCATING  TACHYCARDIAS:  Tachycardias  that involve
accessory pathways are called reciprocating or  reentry  tachycardias.   They
usually  involve  conduction  down  the  AV  node and returning by way of the
accessory pathway to the atria.   This  results  in  a narrow QRS complex, in
which the P wave occurs after the QRS  on  orthodromic  conduction.   Rarely,
conduction  occurs in the opposite direction producing an antedromic wide QRS
reciprocating  tachycardia.   In   the   WPW   syndrome  there  is  antegrade
propogation over the accessory pathway which produces a short PR interval and
a delta wave.  If the antegrade conduction down the accessory bundle of  Kent
is  followed  by  retrograde  conduction  up  the  AV  node,  a reciprocating
tachycardia  is  established.    In   the  Lown-Ganong-Levine  syndrome,  the
accessory pathway is from the atrium to the His bundle.  Antegrade conduction
down this accessory pathway produces a short  PR  itnerval  but  the  QRS  is
normal,   and   not   widened   as   in  the  WPW  syndrome.   Paitnets  with
Lown-Ganong-Levine syndrome are  also  subject to reciprocating tachycardias.
CLINICAL: Patients with reciprocating tachycardias typically present  at  one
of  three ages, such as during the first year of life, in the teens, and 20s,
or in middle age.  Children in the  first hyear of life can present with CHF,
lethargy, feeding problems and dyspnea.  Symptoms in the teens are frequently
precipitated by exercise and occur suddenly.  These  episodes  may  last  for
seconds  to several hours and usually are well tolerated.  TREATMENT: Various
maneuvers may be utilized to  terminate the reciprocating tachycardia such as
the Valsalva maneuver, ice water  facial  immersion  and  unilateral  carotid
artery pressure in the young.  In children, atrial fibrillation is rare under
the  age  of  10  and  digoxin  may  be used for prophylaxis during this time
period.  Digoxin, verapamil and  calcium  antagonists are contraindicated for
acute termination  of  atrial  fibrillation  that  produces  a  wide  complex
irregular  ventricular  tachycardia, as this is produced by conduction of the
atrial  fibrillation   through   the   accessory   bundle.    Narrow  complex
reciprocating tachycardias occur down the AV node and can be terminated  with
adenosine.  Class 1A and 1C agents block the accessory pathway.

                      -PATENT DUCTUS ARTERIOSUS-
The  ductus  arteriosus is a vascular channel connecting the descending aorta
with  the  pulmonary  artery  that   is   kept   open  prior  to  birth  with
prostaglandins.  If normal closing at birth  doesn't  occur,  there  will  be
persistent  systolic  and  diastolic  continuous  flow  from the aorta to the
pulmonary artery which  will  cause  volume  overload  of the left ventricle.
Pulmonary hypetension can occur if there  are  obliterative  changes  in  the
pulmonary arterioles which can then produce a reversal, or bidirectional flow
through  the  ductus.  Patent ductus arteriosus (PDA) only accounts for about
2% of congenital heart disease  defects  in  adults, but is common in infants
and children.  PDA is more common in females, premature infants, infants born
at high altitude, infants with respiratory distress and can occur as a result
of maternal rubella during the first trimester of pregnancy.  Most low  birth
premature  infants with PDA will need to be closed.  This can be done with IV
indomethacin, or if  this  fails  ligation.   Sometimes,  the  PDA will close
spontaneously in many children within 3 months.  A PDA in  premature  infants
is  more  likely  to close spontaneously or with indomethacin.  If the mother
had a PDA, there is a 4% chance  of having a child with PDA.  However, if the
father has a PDA, the chance is only 2%.  DIAGNOSIS: Usually an  older  child
is  asymptomatic  unless  there  is  left  ventricular  failure  or pulmonary
hypertension.  There may be a  hyperdynamic apex, widened pulse pressure with
a low diastolic pressure.  The heart  is  usually  normal  size  or  possibly
slightly enlarged.  There is a rough continuous machinery murmur, accentuated
in  late  systole,  best  heard  in  the  left infraclavicular area.  This is
usually accompanied by a thrill.  On  chest  x-ray there may be prominence of
the pulmonary artery,  left  atrium,  aorta,  and  left  ventricle.   Cardiac
catheterization  will  define  the  presence  and  severity  of the shunt and
ascertain if pulmonary  hypertension  is  presnet.   Echo-doppler may also be
helpful.  TREATMENT: Only a few patients will develop pulmonary  hypertension
and  Eisenmenger's syndrome.  Even small shunts may be compatible with a long
life.  Endocarditis prophylaxis  is  necessary.   Closure  should  be done in
large shunts or those children with symptoms.  Closure may be accomplished by
an umbrella device, surgical ligation, or  indomethacin.   PDA  closure  with
pulmonary hypertension is controversial.

                     -PATENT DUCTUS ARTERIOSUS-
Congenital lesion that is  often  heard  at  birth,  especially  in  pre-term
infants.  Bounding pulses, precordial hyperactivity and murmur intensifies on
supination.   Murmur  is  continuous  along  the  ULSB  (seldom continuous in
neonates), thrill, machinery like and grade  1-4.  May be transmitted to left
axillary region.  An apical diastolic rumble may be present due to high  flow
across  the  mitral  valve.   Can  be  confused  with an innocent venous hum,
although the diastolic component  of  venous  hum  is louder thanits systolic
murmur. This is opposite to patent ductus arteriosus.

                    -PELVIC INFLAMMATORY DISEASE-
Pelvic inflammatory  disease  (PID)  is  usually  a  polymicrobial  infection
affecting the female pelvic organs.  It is an ascending infection starting in
the vagina and endocervix and proceeding to the endometrium, fallopian tubes,
ovaries  and  surrounding  organs.   There  may  be  salpingitis, pyosalpinx,
tubo-ovarian abscess, salpingo-oophoritis,  adnexitis  or pelvic peritonitis.
Sometimes, a perihepatitis will develop due to Chlamydia or gonococci.   This
is known as the Curtis-Fitz-Hugh syndrome.  The predominant age is from 16-40
and the annual incidence in the USA is about 100-200 per 100,000.  Blacks and
non-white women have a high incidence.  Those at risk are the sexually active
during  the  reproductive years.  There are usually multiple sexual partners.
If a patient has an IUD she is  at increased risk during the first few months
after insertion.  IUD patients often times have actinomyces infection.  If  a
patient  has  had PID in the past, then she will have a reoccurrence in about
25% of  the  cases.   If  a  patient  is  diagnosed  as  having Chlamydial or
gonococcal cervicitis, she has a 10% chance of  developing  PID.   Gonococcal
salpingitis usually develops around the time of the menses.  Any patient that
uses  illicit  drugs as crack cocaine, alcohol, come from a low socioeconomic
status  or  have  substance  abuse  are  at  increased  risk  for  PID.  Oral
contraceptives, vaginal spermicides and condoms all help to  protect  against
PID.   CAUSES:  Common  infections  involve  Neisseria gonorrhoeae, Chlamydia
trachomatis, aerobic  and  anaerobic  bacteria.   The  anaerobic bacteria are
usually  Bacteroides,  Peptococcus,  and  Peptostreptococcus.    Occasionally
Mycoplasma  will  be  the  cause.   Most  of  the  infections involve several
bacteria.  It has been  estimated  that  approximately  6% of sexually active
women in the reproductive age range will have positive cultures of the cervix
for Neisseria  gonorrhoeae  and  25%  of  these  will  also  have  Chlamydia.
However,  surprisingly, only about 22% will have N. gonorrhoeae isolated from
the peritoneum in patients  with  cervical  positive gonococci.  About 85% of
infections will be spontaneous, but in 15% of cases there  is  a  history  of
instrumentation  of  the  uterus  as  dilatation  and  curettage, endometrial
biopsy, IUD  placement,  or  hysterosalpingography.   CLINICAL: Most patients
with PID will have localized bilateral pain with fever.  There may be rebound
tenderness and bilateral  adnexal  tenderness.   The  liver  area  should  be
checked to rule out Fitz-Hugh-Curtis syndrome.  This syndrome occurs in about
5%  of  PID.   There  may  be  continuous  diaphragm  inflammation with right
shoulder pain.  Usually this pain  starts  within  7 days of the menses.  The
patient may have a vaginal discharge, bleeding, nausea, vomiting and dysuria.
The pain of Chlamydia may be  less  than  that  of  Gonococcal  PID.   Pelvic
examination  may  reveal  purulent  cervical  discharge and tenderness of the
cervix when moved.  There may be  fullness  of the cul-de-sac.  Masses may or
may not be felt.  The patient may have a characteristic gait characterized by
a bent over, shuffling gait with the patient holding her pelvis.  The patient
should be asked specific questions regarding whether she is  sexually  active
with  multiple  partners,  when her last menses occurred, whether she douches
excessively, whether she has been  taking  any medication, whether she or her
partners have ever had PID before, and whether she  has  substance  abuse  or
HIV.   Also,  inquire if the patient has an IUD.  LABORATORY: Pregnancy tests
should be done in all patients  of reproductive age to rule out complications
of uterine pregnancies and ectopic pregnancy.  All patients that have PID may
be at increased risk for syphilis and should have routine syphilis  serology.
The  peripheral  WBC is usually greater than 10,000 per mm3.  Gram stains and
cultures should be done  from  the  endocervix  looking for the gram-negative
intracellular diplococci of Gonococci.  Obtain an antigen test for  chlamydia
of  chlamydial  culture.  The ESR is usually elevated.  Pelvic ultrasound may
be useful.  A culture  of  the  aspirate  from  the  cul-de-sac may yield the
diagnosis.  A laparoscopic exam can be done if still in doubt.   DIFFERENTIAL
DIAGNOSIS:  All  of  the  following  should be considered in the differential
diagnosis:  ectopic  pregnancy,  ovarian  torsion,  cystitis, diverticulitis,
inflammatory colitis, cholecystitis, appendicitis,  hemorrhagic  or  ruptured
ovarian  cyst,  endometriosis,  and  irritable bowel syndrome.  Patients with
ovarian cyst rupture have unilateral pain  and tenderness and no fever.  They
often feel faint.  Appendicitis usually starts in the mid  abdomen  and  then
localizes  to the lower right quadrant.  Adnexal torsion is poorly localized,
but the pain is definite and  may  be  either unilateral or bilateral plus it
may be referred to the perineum, thigh or flank.  Usually they have no fever.
TREATMENT:  OUTPATIENT: Cefoxitin 2 grams IM plus probenecid (Benemid) 1 gram
po or Ceftriaxone (Rocephin) 250 mg IM PLUS Doxycycline 100  mg  po  bid  for
10-14  days  or Tetracycline 500 mg qid for 10-14 days.  If patient is unable
to take doxycycline or  tetracycline,  give  erythromycin  500  mg po qid for
10-14 days.  As  of  this  writing  Azithromycin  (Zithromax)  has  not  been
approved for treatment of C. Trachomatis, but studies in progress are looking
good.   Advantages  are that the patient may be given the entire treatment in
one dose which would help compliance.   INPATIENT: For the inpatient you have
a choice of two regimes: Cefoxitin (Mefoxin) 2  grams  IV  q6h  or  Cefotetan
(Cefotan)  2 grams IV every 12 hours PLUS Doxycycline hyclate 100 mg po or IV
every 12 hours.   Give  this  combination  for  at  least  48 hours after the
patient has improved.  After discharge from the hospital give doxycycline 100
mg po bid for a total of 10-14 days.  OR Clindamycin (Cleocin phosphate)  900
mg  IV  every  8  hours PLUS Gentamicin sulfate Garamycin, Jenamicin) using a
loading dose of 2 mg/kg IV or IM  followed by a maintenance dose of 1.5 mg/kg
every 8 hours.  This combination should be continued for at  least  48  hours
after  clinical  improvement.   After  discharge  the  patient  will continue
doxycycline 100 mg po  bid  or  clindamycin  450  mg  po  qid for 10-14 days.
COMPLICATIONS: Patients that have had PID will have  recurrent  infection  in
about 20-25% of cases.  A tubo-ovarian abscess will develop in about 7-16% of
patients.   Tubal  infertility  increases with the number of episodes of PID.
With 1, 2, and 3 episodes there will  be tubal infertility of 15, 35, and 55%
respectively.  Following infection, patients may have chronic pelvic pain  in
about 20%, due to adhesions and chronic infection.  Patients who have had PID
have a 7-10 fold increased risk for ectopic pregnancy.

             -PELVIC INFLAMMATORY DISEASE (Outpatient)-
Cefoxitin 2  g  IM  once  +  probenecid  (Benemid)  1  g  PO  concurrently or
ceftriaxone 250 mg IM once.  Each of above is given with doxycycline  100  mg
PO  bid  for  14  d.  Alternatives: Ofloxacin 400 mg PO bid for 14 d + either
clindamycin (Cleocin) 450 mg PO  qid or metronidazole (Flagyl, Protostat) 500
mg PO bid for 14 days.

                            -PELVIC PAIN-
Chronic  pelvic  pain  may  be  due  to  psychiatric causes with a history of
psychosexual  trauma,  physical   abuse   and  sexual  abuse,  endometriosis,
malignancy, sexually transmitted diseases, salpingitis,  adhesions  or  nerve
entrapment,  irritable  bowel  syndrome.   Check  for  trigonal  or  urethral
tenderness.   Abdominal trigger points account for most patients with chronic
pelvic pain.  Do CBC  and  UA  and  check  for STD, especially chlamydia.  Do
guaiac stool and cervical  cytology.   A  lactose  intolerance  test  may  be
useful.   Laparoscopic  exam can show endometriosis and pelvic adhesions, but
about 1/3 to 50% show  no  abnormality.   A pelvic ultrasound, endoscopy, and
barium enema may be done.  Some patients may benefit from  cycle  suppression
with  a  monophasic  oral  contraceptive.   Tricyclic antidepressants such as
amitriptyline, imipramine, and doxepin may help  even in low doses, which may
also help sleep disorders.  For tricyclic failure, fluoxetine (Prozac)  might
be helpful.  Give fiber supplement for IBS such as fiberall, metamucil.  Oral
analgesics  should start with ibuprofen.  Trigger points may be injected with
marcaine biweekly or monthly, using 5-10 mL.  May have a 90% success rate.

                        -PEMPHIGUS VULGARIS-
CLINICAL:  Pemphigus  vulgaris  usually  arises  during  the fourth and fifth
decades.  It is uncommon,  but  can  be  a  potentially fatal or debilitating
disease.  Before steroids were available more than 90% of patients died after
months or years of the disease.  Now, with  steroid  therapy,  there  can  be
expected  recovery  of  some  patients  and  control of others with sustained
steroid therapy.  However, about 10%  will  succumb from complications of the
therapy.  Complications from sustained and large dose  immunotherapy  include
osteoporosis, diabetes, hypertension, devastating infections, reactivation of
tuberculosis,  gastric  or  duodenal  ulceration,  myocardial infarctions and
psychiatric disease.  Most deaths  are  attributed  to infections of the lung
and pulmonary emboli.  There is no sex predilection, and there  is  a  higher
incidence  in  Jewish or Mediterranean descent.  Microscopic examination will
reveal  splitting  among  the   keratinocytes,  accumulation  of  fluid,  and
formation of thin walled bullae.  The bullae that develop are  flaccid,  just
the  reverse  of  bullous  pemphigus,  which  tend  to be tense.  The initial
lesions  in  pemphigus  may  involve   the  oral  mucous  membrane  surfaces,
particularly  the  posterior  mouth,  for  several  weeks  or  months  before
spreading to a more generalized eruption.  Mucosal lesions  are  involved  in
greater  than 90% of patients and in greater than 50% the initial lesions are
in the mouth.  If lesions are  not  seen  in the mouth consider a superficial
variety of pemphigus known as pemphigus foliaceus.  The bullae  of  pemphigus
vulgaris  predominate  on  the  head  and  neck,  flexural  areas and mucosa.
Nikolski's sign is positive.  This  sign  is performed by applying a twisting
pressure to normal appearing skin.  Upon doing this there is avulsion of  the
epidermal layers from the basal layer.  There is also a positive Asboe-Hansen
sign.   The  is  produced  by  applying  pressure over the surface of a newly
developed blister.  When this is done  there is enlargement of the blister by
peripheral  extravasation  of  the  fluid  into  the  surrounding  epidermis.
Pemphigus vulgaris is a non-scarring disease when healing takes  place.   The
differential  diagnosis  of  pemphigus  includes  bullous  pemphigoid, benign
mucosal pemphigoid,  toxic  epidermal  necrolysis,  dermatitis herpetiformis,
erythema  multiforme,  drug  eruptions,  varicella-zoster,  herpes,   bullous
impetigo,  and  eczematous  disorders.  TREATMENT: Pemphigus vulgaris must be
treated with very  large  doses  of  prednisone,  must  be continued for long
durations, and must cautiously be reduced.  If these  3  rules  are  violated
there  may  be  failure  to  control  the  blistering.   Suppression  of  the
blistering  is  usually  seen  after  about  2-4  weeks  using  high doses of
prednisone.  For mild  or  moderate  disease  start  with  about  60-80 mg of
prednisone.  For more extensive disease, daily doses of 160 mg may be  needed
initially.  It is important to use very high doses at first in order to bring
the  disease  under  control  and  then  slowly reduced.  When about 40 mg of
prednisone daily is reached, alternate  day  therapy can be tried.  From this
point on, slowly reduce by about  5  mg  every  2-3  weeks.   Adding  steroid
sparing  drugs  may be needed because of the massive doses of prednisone that
are needed.  Start with Azathioprine using  between 50 and 250 mg daily.  The
average starting dose may be around 175  mg.   Monitor  for  leukopenia,  and
liver  enzyme  changes.  Cyclophosphamide may be started at 100-200 mg/day in
conjunction with the  prednisone.   Watch  for  side  effects, as hemorrhagic
cystitis,  neutropenia,  and  alopecia.   In   order   to   prevent   bladder
inflammation  encourage  fluid  intake  during therapy.  Cyclophosphamide can
lead to tumors of the  urinary bladder after prolonged therapy.  Methotrexate
can be used, but can cause cirrhosis of the liver  with  long  term  therapy.
Because  of this, methotrexate is not considered first line therapy among the
immunosuppressive agents.  It may be given as  a 25 mg oral dose once a week.
Liver biopsy is usually recommend after the patient has received a  total  of
1.5  grams  of methotrexate.  CBC and liver enzymes must be monitored	and all
hepatotoxic drugs and alcohol are interdicted.  Gold has also been effective.
If it is given alone  about  50%  of  patients  will respond, but it may take
months to control the eruptions with gold alone.  Since  gold  can  cause  an
initial  flare of the disease, prednisone should be started first in order to
get the disease under control and  then add the gold therapy.  Myochrysine is
given IM in incremental doses weekly.  Start with 10 mg, then  25  mg  during
the  second week and then 50 mg weekly thereafter.  Once the disease has been
under control for at least 2 months,  the  dose may be reduced to every other
week for 2 months, then every third week and  ultimately  to  once  a  month.
From  this  point, an attempt is made to wean the patient off the gold.  Oral
gold (Ridaura) therapy  may  also  be  used.   Side  effects  of gold include
exfoliative dermatitis, agranulocytosis, nephrotic  syndrome,  pruritus,  and
lichenoid dermatitis.  Follow the patient with CBC, platelets, and urinalysis
before  each  dose  of  injectable  gold and frequently with oral gold.  Most
reactions to gold will not occur until  more  than  a total dose of 250 mg of
gold has been given.  Plasmapheresis used in conjunction with prednisone  and
immunosuppressives can also lead to improvement of the disease.

                          -PENILE LESIONS-
Warts (condyloma acuminatum) are  caused  by  human papillomavirus and may be
dry or wet.  There is no cure.  Condylox may be used  for  treatment.   Since
human  papillomavirus is associated with precancderous lesions of the uterine
cervix, female partners  with  this  virus  should  be  checked for warts and
undergo a Pap smear twice a  year.   Molluscum  contagiosum  are  umbilicated
papules  and  can  be  treated  with  freezing  with  liquid nitrogen, and by
curettage.  Check sexual partners.  Herpes simplex may present as vesicles or
pustules typically or atypically as ulcers and erosions.  Check for syphilis.
Therapy is with acyclovir 200 mg 5  times a day for 5-7 days.  Moniliasis can
be  confirmed  with  20%  KOH  wet  mount  which  shows  budding  yeast   and
pseudohyphae.  Scabies of the penis is common.  Always check the trunk, wrist
and  fingers also for papules, pustules and excoriations.  Raised lesions may
represent psoriasis presenting as  well  demarcated red patches with scaling,
lichen planus, as polygonal, shiny  flat  topped  papules  or  benign  pearly
penile  papules  on  the  coronal rim.  Always check the rest of the body for
lichen planus and psoriasis as they may have more of the same lesions.  Other
lesions found are seborrheic dermatitis, contact dermatitis, Reiter's disease
and early fixed drug  eruption.   Cancer  of  the penis is rare.  Superficial
intraepidermal squamous cell  is  the  most  common,  presenting  as  a  well
demarcated  moist  nonhealing  red patch called erythroplasia of Queyrat.  It
becomes invasive if not  treated.   Invasive  squamous  cell ca presents as a
slow growing nonhealing ulcer that may metastasize early  to  regional  lymph
nodes.    Kaposi's  sarcoma  in  AIDS  presents  as  a  violaceous  patch  or
infiltrated plaque and is treated  with either localized radiation therapy or
intralesional injections of 0.2% vinblastine solution.  Syphylis may  present
as  an  ulcer  or  erosion,  or  masquerade  as  a  papule,  scab or patch of
dermatitis.  Do dark field  exam  and  serologic  test  for syphilis.  One of
these should give a diagnosis.   If  doubt,  biopsy  lesion.   Treatment  for
primary  and  secondary syphilis is penicillin G benzathine 2.4 million units
(1.2 MU  IM  in  each  buttock)  given  on  two  occasions  1-2  weeks apart.
Chancroid presents as an ulcer or ulcers  that  are  soft  and  very  tender.
There  may  be  a history of travel to Southeast Asia or Third World country.
Gonorrhea usually  presents  as  gonococcal  urethrits,  but  may  present as
erosive balantitis or produce pustules and even ulcers.

                            -PERICARDITIS-
COMMON  CAUSES  OF PERICARDITIS: Most causes are idiopathic or due to a viral
infection.  Most cases can readily be diagnosed in the clinical setting.  For
instance, if a patient has a malignancy and develops pericarditis, there is a
possibility of metastatic disease  to  the  pericardium.   In a young healthy
person, viral or idiopathic would be suspected.  Pericarditis that develops a
few weeks after cardiac surgery could be due to post-pericardiotomy syndrome.
Pericarditis in a uremic patient cound be due  to  advanced  kidney  disease.
VIRAL:  Viral pericarditis can be caused by echovirus, coxsackie, adenovirus,
mumps, varicella, mononucleosis, hepatitis and  AIDS.  Males under the age of
50 are the  most  susceptible  to  viral  etiologies.   Confirmation  may  be
obtained  by  rising  viral  titers  in  paired sera.  Cardiac enzymes may be
slightly elevated.  Pericarditis  usually  starts  after an upper respiratory
infection.  Indomethacin 100-150 mg/day in divided doses or ASA 650 mg QID is
usually effective, but if not, prednisone may  be  added.   Most  cases  will
resolve  after  a  few  days to weeks.  However, there may be recurrences and
rarely this may cause  contrictive  pericarditis.   Tamponade occurs in < 5%.
TUBERCULOUS:  Tuberculous  pericarditis  is  rare  in  the  USA.   Associated
clinical involvement of the lungs may be absent, but  pleural  effusions  are
common.   The  patients may have fever, fatigue, night sweats with a subacute
presentation  for  days  to  months.   Spread  is  usually  by  lymphatics or
hemagtogenous.  The effusions are usually  small  or  moderate.   Pericardial
biopsy  has a higher yield than pericardiocentesis fluid and diagnosis may be
made at another site  of  involvement.   Patients usually respond to standard
anti-tuberculous pharmacologic therapy, but constrictive pericarditis may  be
a  sequela.   MALIGNANT:  Common  causes  of  neoplastic pericarditis include
carcinoma of the  breast  and  lungs,  renal  carcinoma, leukemia, lymphomas,
Hodgkin's disease and melanoma.  Neoplastic pericarditis is a common cause of
pericardial  tamponade  and  frequently  is  painless,  but  presenting  with
hemodynamic consequences.  Diagnosis is by cytologic exam of the  pericardial
effusion and/or pericardial biopsy, which may be difficult if the patient has
had  mediastinal  radiation  within the last year.  CT and MRI may be of some
benefit in  visualizing  proximal  tumor.   Once  the  patient  has malignant
invasion of the pericardium, the prognosis is  very  poor  with  only  a  few
surviving  for  a  year.  Palliation can be achieved by drainage, followed by
instillation of  chemotherapeutic  agents  or  tetracycline  in  an effort to
reduce recurrence of fluid accumulation.  Partial pericardiectomy may  be  of
some benefit while pericardial windows are rarely helpful.  Be careful not to
assume  that  the  cause  is  neoplastic  in  a  patient  that has cancer, as
radiation, infection and autoimmune  disorders  may be instrumental.  Rarely,
mesotheliomas are causative.  RADIATION: Radiation for neoplastic disease may
present months or years after radiation.  The patients may present as  acute,
or  subacute  pericarditis  or constrictive pericarditis due to fibrinous and
scar formation of  the  pericardium  as  well  as  the myocardium, conducting
system and coronary arteries.  Radiation  pericarditis  usually  develops  if
there is more than 4000 cGy delivered to ports including more than 30% of the
heart.   POST  MI AND DRESSLER'S SYNDROME: Dressler's syndrome is probably an
autoimmune disease.  It occurs weeks  to  months  after open heart surgery or
MI, and can be recurrent.  The  sedimentation  rate  is  elevated,  there  is
leukocytosis,   pain,   malaise,  and  fever,  and  pleural  effusions.   The
pericardial effusions tend to be  large  and  tamponade is rare after MI, but
not  so  in  postcardiotomy  pericarditis.   Treatment  is  with  NSAIDs  and
corticosteroids.  Pericarditis accompaning MI usually occurs  2-5  days  post
MI.   Large  effusions  are  rare.   Differential  from  progressive ischemic
changes may  be  difficult  as  evolutionary  repolarization  changes  of the
pericarditis  may  simulate  ischemic  changes.   There  is  usually  a  rub.
Spontaneous resolution usually occurs after a few days.  NSAIDs or  ASA  will
help  the  pain.   ACUTE  BACTERIAL  INFECTION:  Staphylococcus, pneumococci,
streptococci,  Legionella,  Neisseria  gonorrhoeae,  Neisseria  meningitidis.
INFLAMMATORY DISEASE: SLE,  rheumatoid  arthritis, scleroderma, polyarteritis
nodosa, amyloidosis, sarcoidosis, acute  rheumatic  fever,  and  inflammatory
bowel  disease.   DRUGS:  Procainamide,  hydralazine,  isoniazid,  phenytoin,
dantrolene, phenylbutazone, methysergide and cyclophosphamide.

                    -PERICARDITIS (Constrictive)-
Constrictive pericarditis can  result  from  any  disease  that is capable of
causing acute pericarditis with subsequent chronic scarring,  thickening  and
fibrosis.   Common  causes  include  carcinoma of the breast, lung, lymphoma,
chest  trauma  and  mediastinal  radiation.   Less  frequent  causes  include
rheumatoid arthritis, systemic  lupus  erythematosus, dialysis, chronic renal
failure, and bacterial pericarditis.  The principal  problem  in  contrictive
pericarditis  (CP)  is  a  reduction  in late diastolic filling caused by the
non-distensible pericardium.  This  produces  a  decrease  in cardiac output,
hypotension and systemic and pulmonary congestion.  CLINICAL: Patients  often
complain  of  fatigue,  weight  loss,  exertional dyspnea, and weakness.  The
cervical veins are distended.  About 33%  of patients will have a paradoxical
pulse.  Hepatomegaly and ascites may be present.  Cardiomegaly is present  in
about  50%  of  patients.   There may be a third heart sound, the pericardial
knock, which occurs .06-.12  seconds  following  aortic valve closure.  Heart
sounds are diminished and the  apical  pulse  retracts  during  systole,  and
protrudes  in  diastole.   The  spleen  may  be  palpable.  The ECG shows low
voltage of the QRS  complexes  and  flattening  or  inversion of the T waves.
Atrial fibrillation occurs in a third of patients.  P mitrale may be present.
Echocardiography may  show  increased  pericardial  thickening  and  abnormal
ventricular  diastolic  function,  but normal systolic function.  Doppler may
show impaired late  diastolic  flow  across  the  mitral or tricuspid valves.
MRI, and ultrafast CT can measure the thickness of the pericardium.   Cardiac
catheterization  documents  elevation  and  equalization  of  right  and left
ventricular diastolic  pressures.   Early  diastolic  filling  is normal, but
falls abruptly in late diastole producing the square root sign or the dip and
plateau signs on right and left ventricular  diastolic  pressure  recordings.
Tachycardia  may  obscrue  these findings.  Right atrial tracings will show a
prominent y descent  and  preservation  of  the  x  descent  and right atrial
pressure may not decrease with  inspiration.   Many  of  these  patients  are
misdiagnosed  as  having  cirrhosis  of  the liver, because of a normal sized
heart, lack of cardiac murmur, and  the presence of hepatomegaly and ascites.
To avoid this erroneous diagnosis, the neck  veins  should  be  examined  for
fullness  and  calcification  of  the  pericardium  should be sought by chest
x-ray, fluoroscopy, and  echocardiography.   Calcification  occurs  in 50% of
patients.  Tricuspid stenosis may also be  confused  with  CP.   However,  in
tricus[pid stenosis, there is a characteristic murmur, absence of a paradoxic
pulse  and  absence  of  the  y  descent  followed by a rapid ascent.  Mitral
stenosis  usually  co-exists  with  tricuspid  stenosis  which  helps  in the
differential.  Patients with chronic constrictive pericarditis  usually  will
have  left  atrial  or  pulmonary  arterial  wedge pressures that equal right
atrial pressures.  The  right  atrial  pressure  often  is  >  15 mm Hg.  The
pulmonary artery systolic pressure is usually < 50 mm  Hg,  while  the  right
ventricular   end-diastolic  pressure  often  reaches  1/3  of  the  systolic
pressure.  In patients with cardiomyopathy,  the left atrial pressure usually
is > than the right atrial pressure by more  than  5  mm  Hg,  the  pulmonary
artery  systolic  pressure  is  often  >  50  mm  Hg,  the  right ventricular
end-diastolic pressure is usually less than 1/3 of the systolic pressure, and
the mean right atrial pressure  is  often  <  15 mm Hg.  The left ventricular
end-diastolic volume may be  elevated  in  some  cardiomyopathies,  while  in
constrictive  pericarditis,  the  volumes  of  both ventricles are reduced or
normal and the ejection fractions are near normal.  Ohter disease to be ruled
out include right ventricular  infarction, cardiac tamponade, and restrictive
cardiomyopathy.  In cardiac tamponade,  Kussmaul's  sign  is  usually  absent
while  pulsus  paradoxus is usually present.  The dip and plateau square root
sign is absent in tamponade as is  the  rapid y descent of the jugular venous
pulse.   Restrictive   cardiomyopathy   may   be   extremely   difficult   to
differentiate  from  contrictive pericarditis.  Restrictive cardiomyopathy is
due  to   infiltration   by   hemochromatosis,   amyloidosis,  endomyocardial
fibroelastosis,  and  mediastinal  radiation.    Both   diseases   can   show
equilibration of the right and left ventricular diastolic pressure and square
root  sign.  Endomyocardial biopsy may be helpful as is ultrafast cine-CT and
MRI in differentiating the  two  diseases.   TREATMENT: Treatment is surgical
resection of the pericardium.  Operative mortality  is  about  5%.   In  some
patients,  the  results  are  immediate, while others may slowly improve over
several days to weeks.  In some,  surgery  affords no benefit, usually due to
incomplete resection or underlying myocardial disease.  A few cases of CP may
be due to TB, and anti-tuberculous therapy should be initiated  early  during
the effusion stage.

                      -PERIPHERAL ALIMENTATION-
For peripheal alimentation use 500 ml D10W + 500 ml amino acids of 7% or 8.5%
every  12 hours.  This will provide 2000 ml/day, 1320 Cal/day and 675 mOsm/L.
500 ml fat emulsion as Intralipid 20%  is  given over 8 hrs during each 24 hr
period which provides 1000 Cal and  165  mOsm.   Supplements  may  be  needed
depending upon ability to take enterally.

                      -PERIPHERAL NEUROPATHIES-
Peripheral  neuropathies  can  be  categorized in a number of different ways.
EMG and nerve conduction  studies  can  classify  the neuropathy into 2 major
categories: axonal and demyelinating.  Axonal neuropathies are  characterized
by  decreased  amplitude  and  some  slowing  on  nerve  conduction  studies.
Demyelinating  neuropathies  show  a  marked  slowing of the nerve conduction
velocity.  ACUTE AXONAL NEUROPATHIES: Acute axonal neuropathies can be caused
by  porphyria,  toxins  and  tick  paralysis.   Toxins  causing  acute axonal
neuropathies include  thallium  and  triorthocresylphosphate.   Porphyria  is
precipitated  by  barbiturates  and  alcohol.  A urine should be obtained for
porphobilinogen.  The attacks  consist  of  abdominal pain, seizures, bizarre
behavior, sympathetic overactivity and weakness of the  arms.   SUBACUTE  AND
CHRONIC  AXONAL  NEUROPATHIES:  In  this category there are TOXIC causes from
alcohol, organophosphates, heavy metals  (thallium, mercury and arsenic), and
industrial  solvents.   METABOLIC  causes  consist  of   diabetes   mellitus,
hypothyroidism,   and   renal   failure.    DRUGS   consist  of  hydralazine,
vincristine,  isoniazid,  nitrofurantoin,   disulfiram,  cisplatin,  suramin,
dapsone and amiodarone.  NUTRITIONAL causes  are  deficiencies  of  B6,  B12,
thiamine  and  vitamin  E.  VASCULITIC  causes  include polyarteritis nodosa,
rheumatoid  arthritis,  Wegener's   granulomatosis,  and  allergic  angiitis.
INFECTIOUS causes include Lyme disease  and  AIDS.   DYSPROTEINEMIAS  include
multiple  myeloma,  cryoglobulinemia,  amyloidosis, macroglobulinemia, benign
monoclonal gammopathy, and ataxia telangiectasia.  CARCINOMATOUS neuropathies
are  paraneoplastic  and  may   present   months  prior  to  the  malignancy.
DEMYELINATING NEUROPATHIES:  Demyelinating  neuropathies  can  be  caused  by
hereditary  diseases  as  Charcot-Marie-Tooth  disease  or  peroneal muscular
atrophy,    Refsum's     disease,     metachromatic     leukodystrophy    and
abetalipoproteinemia.  Acute  segmental  demyelinating  neuropathies  include
diphtheria, and Guillain-Barre.  Chronic or relapsing segmental demyelinating
neuropathies  include  dysproteinemias,  lead,  osteosclerotic  myeloma,  and
chronic  inflammatory demyelinating polyradiculoneuropathy.  The latter often
begins clinically as Guillain-  Barre  does,  but  has a longer and relapsing
course.  The diagnosis is made by nerve conduction  studies  and  EMG,  nerve
biopsy  and  lumbar  puncture.   MULTIFOCAL  MONONEUROPATHIES:  Most of these
neuropathies are axonal and nerve biopsy  is important in the diagnosis.  The
causes are as follows: Diabetes mellitus, rheumatoid arthritis, SLE, allergic
angiitis, Wegener's granulomatosis, polyarteritis nodosa,  sarcoidosis,  Lyme
disease,  AIDS,  Leprosy  and a variant of chronic inflammatory demyelinating
polyradiculoneuropathy  which  may  be   associated  with  multiple  myeloma,
malignancy, dysproteinemias or  idiopathic.   DIABETIC  NEUROPATHY:  Diabetic
neuropathy  is somewhat uncommon under the age of 30 and affects about 15% of
adults with diabetes mellitus.   In  general,  there  are 4 types of diabetic
neuropathies: distal  symmetric,  proximal  asymmetric  multiple  neuropathy,
mononeuropathies,  and  autonomic  neuropathies.  The most common type is the
distal symmetric neuropathy which  initially  causes  a sensory neuropathy of
the feet and progresses to cause  motor  neuropathies.   Other  diseases  and
drugs that may cause a distal symmetric neuropathy include uremia, phenytoin,
vincristine,  cisplatin,  nitrofurantoin  and  isoniazid.   There is impaired
appreciation  of  vibration  in  the  legs  and  decreased  DTRs.   Pain  and
paresthesias may be  present.   Sequels  to  this  type of neuropathy include
chronic foot ulcerations and neuropathic arthropathy (Charcot joint).   There
is  no  specific treatment for diabetic neuropathies.  Tight diabetic control
may help as  well  as  amitriptyline  (Elavil)  25-150  mg  at his or doxepin
(Sinequan) 25-150 mg at hs.)  If  anticholinergic  side  effects  from  these
tricyclic antidepressants occur, substitute trazodone (Desyrel), 50-150 mg at
hs.   If  unable  to tolerate trazodone, try nortriptyline (Pamelor) 25 mg at
hs.   Always  start  at  low  doses  for  elderly  patients.   If  the  above
therapeutic  measures  fail  or   there   is  a  suboptimal  response,  start
carbamazepine (Tegretol) 100 bid to 400 mg tid.  Failure of carbamazepine  to
help may be followed by a trial of phenytoin (Dilantin) at 300 mg/day.  Blood
levels  for  these  two  drugs  should be done as well as CBCs.  The last two
drugs to be  tried  are  clonazepam  and  baclofen.  Clonazepam (Klonopin) is
given at .5 mg tid-2 mg tid.  Baclofen (lioresal) is given from 10 mg  tid-20
mg  qid.   Capsaicin cream (Zostrix .025%) applied to the painful area tid or
qid  has  been  found  to   be   useful.   In  proximal  asymmetric  multiple
neuropathies (diabetic amyotrophy),  there  is  sudden  onset  of  hip  pain,
weakness  and  wasting  of  the  hip  girdle muscles and loss of the patellar
reflex.  It tends to occur  in  poorly controlled older diabetic patients and
those diabetics who have lost weight.  The condition is often bilateral.  The
onset is usually subacute and is caused by ischemic infarction of  the  upper
lumbar  plexus.  The neuropathy causes a long term disability, but eventually
does improve after several  months  or  up  to  a  year  or  so.  In order to
differentiate this neuropathy from disc  herniation,  CT  scans  and  EMG/NCS
should  be  done.   Thoracoabdominal radiculopathy produces pain in the chest
and abdomen.  Oculomotor  neuropathy  (3rd  nerve)  is usually unilateral and
causes ptosis and diplopia.  It is due to ischemia of the central portion  of
the  nerve.  The pupillary reflex is preserved because the constrictor fibers
are located in the periphery of  the nerve.  Compressive aneurysms and tumors
of the oculomotor nerve usually will produce pupillary dilatation, but CT and
MRI may be needed for differentiation.  There may be pain in the orbit.   The
neuropathy  resolves  spontaneously  over  weeks  to months and recurrence is
rare.  Trochlear  neuropathy  (4th  nerve)  can  occur,  but  is  uncommon in
diabetics.   Autonomic  diabetic  neuropathy  can  cause  impaired  sweating,
constipation,  diarrhea,  flatulence,  impotence,   retrograde   ejaculation,
esophageal  dysmotility,  urinary  incontinence,  urinary retention, postural
hypotension, nausea and  vomiting.   Orthostatic  hypotension  may be treated
with volume expansion and elastic stocking.   Fludrocortisone  (Florinef)  at
100  ug/day  is  helpful).   Gastrointestinal dysmotility may be treated with
metoclopramide (Reglan) 10 mg QID, ac  and hs.  Diabetic impotence is treated
with penile prosthesis  or  cavernous  injections.   NUTRITIONAL  NEUROPATHY:
Nutritional  neuropathies are easy to diagnose.  Nutritional neuropathies are
associated with deficiencies of thiamine, B complex, pyridoxine (vitamin B6),
folate and B12, and vitamin E.  They  generally occur in patients with weight
loss, malnutrition and alcoholic patients.  Anorexia nervosa, fad  diets  and
patients  with malignancy can also develop nutritional neuropathies.  Most of
these are sensory  initially,  presenting  as  a distal symmetric neuropathy.
There may be some difficulty in diagnosis in patients that have a malignancy,
as  several  of  the  drugs  used  in  treating  the  malignancy  can   cause
neuropathies.   Pyridoxine  deficiency  can  occur  secondary  to  isoniazid,
hydralazine  and  penicillamine.   Treatment  is with pyridoxine 50 mg daily.
Avoid megadoses of  pyridoxine  as  this  can  produce  a sensory neuropathy.
Folic acid deficiency is treated with folic acid 1 mg daily, vitamins  and  a
healthy  diet.   B12  deficiency,  usually  secondary to Pernicious anemia or
post-gastrectomy, is treated with IM vitamin  B12  1000 ug daily for 2 weeks,
weekly for 3 months and then monthly.  Vitamin E deficiency, which is usually
secondary to fat malabsorption (cystic fibrosis, cholestatic liver  disease),
abetalipoproteinemia  and resection of long segments of intestine, is treated
with vitamin E if blood  levels  are  less  than 5 ug/ml.  UREMIC NEUROPATHY:
Uremic neuropathy causes a symmetric sensorimotor polyneuropathy in  patients
that  have  advanced  uremia  with  a  creatinine clearance < 10 mg/min.  The
distal lower  extremities  are  affected  more  than  the  upper extremities.
Muscle weakness involves the distal feet.  Peripheral neuropathy develops  in
about  50%  of  those in renal failure who need hemodialysis.  If the patient
has  renal  transplantation  or  chronic  dialysis,  the  neuropathy  usually
improves.  If the neuropathy worsens  during dialysis, increase the frequency
and duration of dialysis.  Slow improvement of  the  neuropathy  after  renal
transplantation   usually   is   takes  place  in  1-6  months.   SARCOIDOSIS
NEUROPATHY: The most frequent neuropathies in sarcoidosis are cranial, mainly
facial nerve  palsies.   Most  of  these  cranial  neuropathies  will resolve
spontaneously.   Other  neuropathies  that  may  develop   include   multiple
mononeuropathies,  symmetrical  sensorimotor,  and truncal neuropathies.  For
diagnosis, a sural nerve biopsy may be needed.  Prednisone at 40 mg daily may
or may not be helpful.  LYME  NEUROPATHY:  In  stage  2 and 3 of Lyme disease
neurologic symptoms may develop.  These  include  cranial  neuritis  such  as
Bell's palsy, acute polyradiculoneuropathy resembling Guillain-Barre syndrome
and  meningoradiculitis.  Treatment is penicillin 24 million units/day for 14
days, or if allergic to penicillin tetracycline 500 mg q6h for 30 days.  AIDS
NEUROPATHY: The most common neuropathy  in  AIDS is a chronic painful, distal
sensory polyneuropathy which is usually seen in about 50% of advanced disease
associated with opportunistic infections.  There is  no  treatment  for  this
particular   neuropathy.    Other   types  of  neuropathy  in  AIDS  includes
Guillain-Barre syndrome which follows the typical course of GBS without AIDS.
There is  spontaneous  recovery  and  it  will  respond  to plasma exchanges.
Chronic idiopathic demyelinating polyradiculoneuropathy also occurs.  LEPROSY
NEUROPATHY: In the USA leprosy is seen in Louisiana and Texas and  new  cases
are  usually  from  immigrants  into  the  USA  from  Asia  and  Mexico.  The
neuropathy is sensory with loss  of  sensation which then leads to undetected
trauma, deformity and amputation.  Nerves affected are the  common  peroneal,
ulnar,  median  and facial.  Diagnosis depends on sural nerve biopsy and skin
punch biopsy.  Therapy includes  dapsone  100  mg  daily plus rifampin 600 mg
once a month for 6 months.   For  multibacillary  infections  (borderline  or
lepromatous  leprosy)  use  dapsone  100  mg/day, plus rifampin 600 mg once a
month plus clofazimine 50 mg daily, all for 2 years.  HYPOTHYROID NEUROPATHY:
Neuropathy in hypothyroidism  usually  is  a  unilateral  or bilateral carpal
tunnel median neuropathy.  However, sensorimotor  polyneuropathies  may  also
occur.   These  neuropathies  are  treated  with  thyroid replacement and are
responsive to treatment.   MALIGNANT  NEUROPATHIES: Neuropathies occurring in
malignancy may be caused by direct invasion from the tumor or  remotely  from
paraneoplastic  syndromes  in about 2-3% of cancer patients.  Direct invasion
may  affect  the  lumbosacral  or   brachial  plexus,  or  by  leptomeningeal
metastases of the spinal roots.  These can  be  treated  with  radiation  and
chemotherapy.  Sensorimotor neuropathies of the axonal or demyelinating types
are  the  most  common  and  are secondary to lung, stomach, pancreas, colon,
breast   and   testicular   malignancies.    Treatment   is   with  steroids,
plasmapheresis and removal of the primary tumor.  Paraneoplastic pure sensory
neuropathies may develop prior to the recognition of malignancy.   There  may
be  aching  of  the  extremities,  dysesthesia,  loss of reflexes, ataxia and
pseudoathetosis.   Treatment  is  poor   for   this  type  of  neuropathy  as
plasmapheresis and steroids usually do not help.   DRUG  NEUROPATHIES:  MOTOR
NEUROPATHIES  are  produced  by  dapsone,  vincristine  and Cimetidine.  PURE
SENSORY NEUROPATHIES may be caused by metronidazole, dapsone, dideoxyinosine,
ethambutol,   cisplatin,   nitrous   oxide   and   pyridoxine.   SENSORIMOTOR
NEUROPATHIES can be produced by  amiodarone,  phenytoin,  disulfiram,  taxol,
penicillamine,  hydralazine,  gold  salts,  chloramphenicol,  nitrofurantoin,
vincristine,   vinblastine,   and  lithium.   HEAVY  METAL  NEUROPATHY:  LEAD
neuropathy produces  a  motor  neuropathy  that  involves  the radial nerves.
There is wrist drop with weakness of the wrist extensors and extensors of the
digits.  Sensory findings are minimal.  With lead  levels  greater  than  100
ul/dl   the  patient  should  be  treated  with  a  combined  course  of  BAL
(dimercaprol) IM at 3 mg/kg/day given in divided doses IM q 4 hours plus EDTA
(ethylenediamine tetra-acetic acid) given at  12.5 mg/kg/day in divided doses
every 4 hours IM starting 4 hours after the initial BAL dose, both given  for
5  days.   Penicillamine  is not approved for lead intoxication, but for less
severe cases, is given at 600 mg/M2/day  as  a single po dose for 3-6 months.
MERCURY neuropathy produces a stocking-glove sensory neuropathy.   There  may
be  perioral  paresthesias,  cerebellar ataxia, diminished hearing and visual
field constrictions.  ARSENIC  neuropathy  produces  paresthesias in the feet
and weakness in a stocking glove fashion.  The neuropathy is painful  and  is
associated   with  hyperkeratosis  of  the  palms  and  soles.   Mee's  lines
(transverse white lines on  the  nails)  develop  about 1 month after chronic
ingestion of arsenic.  There may be GI symptoms and  skin  changes.   Arsenic
neuropathy  may  be  caused  by  pesticide ingestion producing a sensorimotor
neuropathy.  Treatment is  suboptimal  with  full  blown neuropathies, but is
treated with either penicillamine or BAL.  THALLIUM poisoning will produce  a
predominantly  sensory polyneuropathy, but there may be some mild weakness of
the distal  legs.   Alopecia,  seizures,  coma  and  psychosis are associated
features  of  thallium  poisoning,  which  can  occur   with   ingestion   of
rodenticides.   Treatment  includes a single po dose of 250 mg/kg of Prussian
blue, forced diuresis  and  hemoperfusion.  ENVIRONMENTAL TOXIC NEUROPATHIES:
ACRYLAMIDE produces a distal sensorimotor polyneuropathy which begins in  the
leg.  Ataxia may be marked.  There is profuse sweating of the extremities and
red,  exfoliating skin.  Acrylamide is used in plastic and mining industries.
CARBON DISULFIDE produces a sensorimotor  polyneuropathy  and is found in the
viscose rayon industry.  HEXACARBONS are solvents  that  are  used  in  shoe,
furniture,   and   printing  industries.   N-Hexane  produces  glue  sniffing
neuropathies which  is  a  slowly  progressing  sensorimotor neuropathy which
starts in the legs and is associated with foot  and  wrist  drop  and  absent
reflexes.   BUCKTHORN  TOXINS  can  cause  a flaccid quadriparesis and bulbar
symptoms.  PARAPROTEINEMIA NEUROPATHIES: Multiple myeloma without amyloidosis
can  cause  a  sensorimotor  polyneuropathy,  sensory  neuropathy  and  motor
polyneuropathies.  Multiple  myeloma  with  amyloidosis produces sensorimotor
polyneuropathy and median nerve mononeuropathy.   Sclerotic  myeloma  without
amyloidosis  causes a sensorimotor polyneuropathy which is not unlike that of
a  chronic  inflammatory  polyneuropathy  and  is  severe  and  debilitating.
Osteosclerotic  myeloma  produces  osseous  plasmacytomas,  has  a smoldering
course and usually occurs in younger patients than typical multiple  myeloma.
Some  of  the  patients have features of the POEMS syndrome which consists of
polyneuropathy, organomegaly,  endocrinopathy,  M  protein  and skin changes.
Treatment  of  the  neuropathy  associated  with  osteosclerotic  myeloma  is
radiation and/or resection of the sclerotic lesions.   Benign  or  monoclonal
gammopathy  of  undetermined  significance  (MGUS)  can  cause a sensorimotor
polyneuropathy.  Waldenstrom's macroglobulinemia  will produce a sensorimotor
polyneuropathy with or without amyloidosis, median nerve  mononeuropathy  and
multiple  mononeuropathies.   Any  patient  in which the diagnosis is obscure
should have serum and urine protein electrophoresis and immunoelectrophoresis
seeking out abnormal monoclonal  protein  of  IgG,  IgM  or IgA.  If abnormal
spikes are found, order bone marrow aspiration and biopsy and skeletal x-rays
and nerve biopsies.  Patients that have  MGUS  neuropathies  may  respond  to
plasma  exchanges.  Those that have IgG and IgA MGUS will respond better than
IgM MGUS.  Plasmaphoresis may be carried out using two exchanges per week for
3 weeks.  The neuropathy of multiple myeloma is poorly responsive to therapy,
but fortunately the incidence is only about 3-5% in classic multiple myeloma.
PRIMARY AMYLOID NEUROPATHY: Primary  acquired  amyloid  neuropathy has a high
association with carpal tunnel syndrome with an incidence of about 50%.  Also
these  patients  have   autonomic   symptoms   manifesting   as   orthostatic
hypotension,  impotence and pupillary abnormalities.  The neuropathy produces
lower limb pain, weakness and  paresthesias.   The diagnosis is made by sural
nerve biopsy.  Treatment is not effective and pain  is  controlled  with  the
usually  neuropathic drugs.  PORPHYRIA NEUROPATHY: Motor neuropathic symptoms
predominate with  acute  episodes  of  either  variegate  porphyria  or acute
intermittent porphyria.  Weakness tends to affect the upper extremities  more
than  the  lower,  and  the  weakness is proximal.  There may be mild sensory
symptoms and sometimes marked  autonomic  symptoms.  The neuropathy is axonal
and is treated with Hematin 4 mg/kg intravenously over a 15 minute  period  q
12   hours   for   6  doses.   This  will  suppress  hepatic  ALA-synthetase.
Barbiturates, sulfonamides, anticonvulsants, estrogen, alcohol and sun should
be avoided.  Beta blockers as propranolol  up  to 100 mg q4h may help control
the tachycardias and hypertension.  High carbohydrate  diet,  IV  glucose  or
levulose  may help in severe cases.  Psychotic symptomatology is treated with
chlorpromazine 25 mg or more,  IM.   IV  diazepam  is  the drug of choice for
seizures, because most anticonvulsants will  precipitate  or  exacerbate  the
disease.   CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY: CIDP is
an acquired immunologically  mediated  disease  that  may clinically simulate
Guillain-Barre syndrome, but differs  in  that  it  is  relapsing  (33%),  or
progressive  (50%)  over  months  to  years.   Eventually,  there  is  severe
functional  disability  with  either  type.   Nerve  biopsies  may  help  but
sometimes the biopsy is normal or nonspecific.  On the other hand, the biopsy
may  show  perivascular  inflammatory  infiltrates  in  the  endoneurium  and
epineurium  without  any evidence of vasculitis.  CIDP must be differentiated
from hereditary demyelinating neuropathies.   Treatment  is with steroids and
plasmapheresis.  Start with prednisone 60 mg daily for  2-3  months.   If  no
response  increase  the dose until there is a response or there is no effect.
Once the neuropathy remits, slowly  taper the prednisone.  Most patients will
need some prednisone, perhaps maintenance with 20 mg every  other  day.   For
patients  that do not respond to steroids, try plasmapheresis for a series of
6-12 exchanges.  Azathioprine (Imuran) may  be  used  to help reduce the side
effects of prednisone.   Start  at  2  mg/kg/day  up  to  3  mg/kg/day.   The
beneficial  results  from azathioprine may take at least 3-6 months, so don't
prematurely  stop  the  drug.    If   azathioprine   is  not  successful  try
cyclophosphamide 2 mg/kg/day (Use is not listed in  manufacture's  pamphlet).
VASCULITIC  NEUROPATHIES:  Polyarteritis  nodosa,  Wegener's  granulomatosis,
primary mixed cryoglobulinemia, Churg-Strauss syndrome, rheumatoid arthritis,
SLE   and   Sjogren's   syndrome  are  the  diseases  responsible  for  these
neuropathies.  A diagnosis  depends  on  tissue  transmural inflammatory cell
infiltrates plus fibrinoid necrosis of blood vessels.  Biopsy  of  the  sural
nerve,  and  superficial peroneal nerve may help establish the diagnosis.  In
general, mild to moderate neuropathies  caused  by vasculitis is treated with
prednisone at 1.5 mg/kg/day plus oral cyclophosphamide at 2  mg/kg/day.   The
prednisone  is  continued as a single dose for a month.  At that time one may
switch to every other day  therapy  contingent upon the response.  For severe
case of vasculitic neuropathy treat with methylprednisolone pulse therapy  of
1   gram  every  other  day  for  7  treatments  followed  by  oral  therapy.
Cyclophosphamide at 2 mg-4 mg/kg may  be  given  IV for 3 days followed by po
administration  at  2  mg/kg/day  if  the  neuropathy  is  extremely  severe.
Combination prednisone and cyclophosphamide therapy will  create  a  complete
remission  in  about  90%  of cases.  Multiple mononeuropathies (mononeuritis
multiplex) is  the  most  common  type  of  neuropathy  produced  by systemic
vasculitis.  There may also be a distal symmetrical  sensorimotor  neuropathy
that  has  an  acute  or  subacute  onset.  About 10% of rheumatoid arthritis
patients will have  a  peripheral  neuropathy.   These neuropathies can range
from   compressive   to   distal   symmetrical   sensory    polyneuropathies,
mononeuropathy  or  mononeuritis multiplex.  Treatment is with prednisone and
cyclophosphamide.  In  SLE,  the  most  common  neuropathy  is  a symmetrical
subacute or chronic axonal sensorimotor polyneuropathy.  Cranial  nerves  may
be  affected.   Rarely,  there  may  be  CIDP  or  GBS types of neuropathies.
Prednisone may be given  at  80  mg  QOD  plus  azathioprine 2-3 mg/kg/day or
cyclophosphamide 1.5 mg to 2 mg/kg/day depending on  the  severity.   WORKUP:
The  patient  should  have a work up for diabetes mellitus, deficiency states
for vitamin B12, folate,  vitamin  E  and  thyroid  hormone.   A CBC may show
megaloblasts of pernicious anemia  or  RBC  stippling  from  lead  poisoning.
Abnormal  hepatic  tests  may  suggest  malignancy.   Abnormal creatinine may
indicate  uremic  neuropathy.   Connective  tissue  disease  workup  includes
sedimentation rate, ANA, rheumatoid factor.  Workup for paraprotein disorders
include serum and urine protein electrophoresis and immunoelectrophoresis and
cryoglobulin.  Selective lab use  for  more  exotic disease would include CSF
fluid examination (CSF  protein  is  elevated  in  Guillain-Barre,  diabetes,
carcinoma,  amyloidosis  and Refsum's disease.  The usual elevation is 50-200
mg/dl,  but  higher  values  can  occur),  heavy  metal  screening, hepatitis
profile, Cranial or MRI imaging, porphyria screen, cancer workup, sural nerve
biopsy.   Remember  that  several  diseases  such  as  carcinoma,   diabetes,
alcoholism,  amyloidosis  and  dysproteinemias  may  be  preceded  by various
neuropathies before the  disease  is  clinically  apparent.  Nerve conduction
studies  and  electromyography  (EMG)  are  useful  to  differentiate  axonal
involvement from demyelinating lesions.   Axonal  lesions  cause  spontaneous
activity  on  the  EMG  with  low  amplitude  evoked responses and a relative
preservation  of  conduction  velocities  on  the  nerve  conduction studies.
Demyelinating lesions will slow nerve  conduction  and  there  may  be  focal
blocks  seen.   Furthermore,  the  type of fiber involved, such as sensory or
motor can be documented.  Muscle biopsy  may also be helpful in patients with
polyarteritis, and sarcoidosis.

                    -PERIPHERAL VASCULAR DISEASE-
ACUTE  ISCHEMIA  OF  THE  LOWER   EXTREMITY:  Acute  ischemia  of  the  lower
extremities usually presents with pain, paresthesia,  pallor,  pulselessness,
paralysis, and poikilothermia.  If the patient has motor and sensory changes,
impending limb loss should be addressed.  Intact sensation and motor strength
indicate that limb loss is not imminently threatening.  Alternatively, if the
limb  is  numb  with  motor  weakness,  profound  ischemia  is present and an
emergency exists.  In general, these patients  must be treated within 6 hours
in  order  to  avert  limb  loss.   However,  if  the  ischemia  is   severe,
intervention  must  be  accomplished  within  3 hours to prevent irreversible
damage.   The  most  common  cause  is  embolization,  but  thrombosis  of  a
pre-exisiting stenotic lesion can  also  cause  acute ischemia.  A history of
intermittent  claudication  in  the  past  that  has  worsened,  and  finally
culminating in a pale, cool, painful extremity, is suggestive of a thrombotic
lesion.  Any patient that has a hypercoagulable  state  is  a  candidate  for
thrombosis.   If  the  patient  has  atrial  fibrillation  or  other  cardiac
dysrhythmias,  embolization  should  be  considered.   Physical exam may also
suggest whether the cause is  thrombotic  or  embolic.  If examination of the
non-critical leg reveals normal pulses, this again would suggest  an  embolic
phenomonen.   TREATMENT:  As  a temporizing measure, until a vascular surgeon
can be summoned, the patient should be  treated with heparin, if there are no
contraindications.  The leg should be protected from trauma  and  temperature
changes by wrapping the affected leg in a blanket.  For the patient that does
not  present  as  an  emergency,  angiography will be needed to ascertain the
level and site of the lesion.  Angiography is contraindicated if limb loss is
threatening.  Intraarterial infusion of  urokinase  into the affected leg may
be the treatment of choice.  CHRONIC ISCHEMIA OF THE LOWER  EXTREMITIES:  The
patient  with  chronic  ischemic  changes  of  the  lower  extremity commonly
presents with intermittent  claudication.  Atherosclerotic occlusive arterial
disease is the usual cause.  The atherosclerosis can affect  the  aortoiliac,
femoral  or  popliteal  segments.  The location of the pain can determine the
level of involvement.  If the patient experiences ambulatory pain of the hip,
buttocks  and  thigh,  aortoiliac  occlusive  disease  should  be  suspected.
Patients with involvement of  the  femoral-popliteal areas usually present as
cramping and heaviness of the calf.  The pain is reproducible and  occurs  at
about  the same walking distance on each occurrence, if the patient walks the
same degree of incline.  Patients that  walk up hills usually have pain after
a shorter  distance.   Characteristically,  the  pain  disappears  after  2-3
minutes  of rest.  If pain occurs at less than 600 feet, the patient probably
has severe ischemia.  Patients that can walk greater than 1800 feet have mild
ischemia, while those  acquiring  pain  between  600-1800  feet have moderate
disease.  In  general,  the  rate  of  limb  loss  occurs  at  1%/year.   The
progression  of  the  atherosclerotic disease is perpetuated by nicotine use.
The differential of  atherosclerotic  occlusive  disease  is usually straight
forward in the elderly.  However, in the younger patient, popliteal aneurysm,
popliteal entrapment syndrome and adventitial cystic disease of the popliteal
artery  should  be  ruled  out.   Lumbar  stenosis  may  mimic   intermittent
claudication,  but  resting  usually  does  not  alleviate the pain of lumbar
stenosis.  Also, lumbar stenosis  is  not  consistently reproducible with the
same walking distance as in ischemia, and the pulses may be normal in  lumbar
stenosis.  Patients that have dependent rubor, ulcers of the feet or gangrene
indicate  severe  ischemic  disease.   Patients should have an ankle-brachial
index obtained.  This is done  by  obtaining  the blood pressure in both arms
while supine.  The systolic blood pressure is also obtained at the  ankle  by
placing a BP cuff around the calf and registering the pedal arterial systolic
blood  pressure  by a doppler ultrasound device.  The ankle/brachial index is
obtained by dividing the  systolic  pedal  pressure  by the systolic brachial
blood pressure.  The normal ratio is 1.0.  Most  patients  with  intermittent
claudication will have ankle/brachial indices between 0.5-0.8.  If there is a
strong  suspicion  for  peripheral  vascular  disease  in  the face of normal
ankle/brachial indices, the ankle pressure  should  be done after the patient
has walked to the point of pain, and then calculating  the  index.   Patients
that  have  a decrease in the ankle/brachial index greater than 15%, or those
that have disappearance of the  pedal pulses following exercise have ischemic
atherosclerotic occlusive disease.  TREATMENT  OF  CHRONIC  ISCHEMIA  OF  THE
LOWER  EXTREMTITES:  After  it  has  been  determined  that  the  patient has
peripheral vascular disease, segmental  Doppler ultrasound examination should
be done.  Patients should terminate their smoking, lose weight, and  start  a
daily  exercise  training  program.  Exercise should include ambulating up to
75% of the claudication distance  several times daily.  Smoking cessation can
increase walking distances by at least 40%.  THE BLUE TOE SYNDROME: The  blue
toe syndrome is characterized by a blue painful digit that is due to an acute
embolic event.  Rarely, more than one digit may be involved.  with petechiae,
and mottling.  The emboli can arise from an atheromatous plaque in the aorta,
an intracardiac  thrombus  or  an  intraarterial  thrombus  from a peripheral
artery.  In most cases, palpation of  the  arteries  is  unrewarding  as  the
pulses  are  usually  normal.   The  main  differential is with warfarin skin
necrosis.  These patients may develop necrosis secondary to thrombosis in the
microvasculature after warfarin is started,  if  the patient has protein C or
protein S deficiency.  The patient should be worked up for a  source  of  the
embolus.   An ECG and echocardiogram should be done, along with ultrasound of
the  abdominal  aorta.   BUERGER'S  DISEASE:  Buerger's  disease  is  a rare,
non-atherosclerotic disease affecting the arteries and veins of male  smokers
between  the  ages of 20-60.  However, most of these will present between the
ages of 20-40.  Most cases are seen in Asia and Israel.  It is rarely seen in
the USA.   The  patient  presents  with  intermittent claudication, migratory
superficial vein thrombophlebitis and Raynaud's phenomenon.  It  may  involve
the upper and the lower limbs, with involvement of the lower extremities more
common.

                      -PHENOTHIAZINE OVERDOSE-
Chlorpromazine,   promazine,   haloperidol,   prochlorperazine   may    cause
drowsiness,  orthostatic  hypotension,  miosis,  tachycardia,  covulsions and
coma.  EKG may show prolongation  of  the  QRS or QT interval and ventricular
arrhythmias.  Therapeutic  doses  may  cause  extrapyramidal  reactions  with
spasmodic contractions of the face and neck muscles, extensor rigidity of the
back  muscles, and motor restlessness.  Severe rigidity with hyperthermia and
metabolic acidosis is known as the  neuroleptic malignant syndrome and may be
life-threatening.   Treatment:  treat   hypotension,   cardiac   arrhythmias,
prolonged QT and QRS with IV sodium bicarbonate.  For extrapyramidal symptoms
give benztropine mesylate 1-2 mg IM or diphenhydramine .5-1 mg/kg, and follow
with  PO  for 48 hours.  Bromocriptine 2.5-7.5 mg PO may help the neuroleptic
malignant syndrome.  Emesis, gastric  lavage followed with activated charcoal
is initially used.  Convulsions are treated with diazepam 5-10 mg IV.  Fluids
and pressor agents may be needed for hypotension.

                         -PHEOCHROMOCYTOMA-
Can be ruled out by measuring metanephrines in a spot urine (expressed per mg
creatinine.   Remember  that  all  blood and urine catechol tests are falsely
elevated by  metabolites  of  labetalol.   The  labetalol  metabolites do not
interfere with measurement of urine VMA or plasma catechols by radioenzymatic
assay.

                         -PHEOCHROMOCYTOMA-
Pheochromocytoma  (PC)  is  a  neoplasm composed of chromaffin cells which is
usually  located  in  the   adrenal   medulla   in  about  80%  and  secretes
catecholamines.  It is a rare disease with an incidence of .01% to .1% of the
hypertensive population.  It can occur at any age, but peaks  out  at  around
30-60  years  of  age.   There  is  no  sexual predilection.  If the tumor is
malignant the 5 year  survival  rate  is  less than 50%.  Otherwise, patients
usually have a normal survival following removal  of  a  benign  tumor.   Ten
percent  of  the  tumors  are  extra-adrenal, multiple or bilateral, occur in
children, are familial, recur after  surgical removal, and are malignant (the
rule of 10s).  The average size of the tumor  is  5-6  centimeters.   If  the
tumor  has  not  invaded  the capsule then it is benign.  The tumor itself is
well encapsulated.  Besides the adrenals, the tumor may be found in the organ
of Zuckerkandl at  the  aortic  bifurcation,  paraganglia  of the sympathetic
chain, brain, the wall of the  urinary  bladder,  sympathetic  chain  in  the
mediastinum  or  neck,  and  even  in  dermoid cysts.  Pheochromocytomas have
interesting associations with  other  diseases  such  as: Tuberous sclerosis,
Sturge-Weber syndrome, Neurofibromatosis, Von Hippel-Lindau syndrome (retinal
angiomatosis and cerebellar hemangioblastoma,  Multiple  endocrine  neoplasia
type  IIA  (  medullary  thyroid  carcinoma and primary hyperparathyroidism),
Multiple endocrine neoplasia type IIB (mucosal neuromas and medullary thyroid
carcinoma), Cholelithiasis, Ataxia-telangiectasia  and renal artery stenosis.
CLINICAL: Hypertension is a common feature and may  be  paroxysmal  (45%)  or
sustained  (50%).   These paroxysms may last from minutes to hours.  It would
be rare not to have hypertension  as  part of the symptoms.  The symptoms are
due  to  episodic  secretion  of   catecholamine   hormones   or   precursors
(epinephrine,  norepinephrine,  dopa  or  dopamine).   The  paroxysmal spells
consist of headache,  pain  in  the  abdomen  or chest, perspiration, pallor,
flushing, palpitations and a sudden  increase  of  the  blood  pressure.   In
addition,  the  patient  may have tremor, weight loss, cardiomegaly, anxiety,
nausea   ,   fever   constipation,   dyspnea,   paresthesiae,  hyperglycemia,
hypercalcemia, and erythrocytosis.  There may  be  postural  hypotension  and
postural  tachycardia  with a change of more than 20 beats per minute.  There
may be a retinopathy  grade  II  to  IV  consisting  of retinal hemorrhage or
papilledema.  Induction of the symptoms  may  occur  if  there  is  abdominal
compression  or  massage,  palpation  of  the tumor, change in position, beta
adrenergic   blocking   agents,   anesthesia   induction   and   micturition.
LABORATORY: A 24  hour  urinary  collection  for metanephrines, vanilmandelic
acid (VMA), catecholamines and creatinine should be done.  All of  these  may
be  collected in the same 24 hour urinary sample.  These tests may especially
be positive when  an  attack  has  just  occurred  or  is ongoing.  Values of
urinary metanephrines greater than 1.8 mg/24 hours or  VMA  greater  than  11
mg/24  hours  are  abnormal.   The  24  hour urinary VMA may have a 60% false
negative rate, and  metanephrines  a  20%  false  negative.  Beware that many
drugs and foods can alter these tests and it is recommended that all  of  the
following    drugs   be   discontinued   1   week   prior   to   the   tests.
1....Metanephrines, VMA, and catecholamines  can  be  FALSELY ELEVATED if the
patient has ingested bananas, ephedrine, theophylline,  nasal  decongestants,
bronchodilators,   amphetamines,   levodopa,   nitroprusside,  nitroglycerin,
quinidine,  tetracyclines,   methenamine,   methocarbamol,   nicotinic  acid,
bretylium, phenosulfophthalein, chloral hydrate, methenamine, nicotinic acid,
quinine, or riboflavin.  Withdrawal from clonidine and  several  diseases  as
Guillain-Barre syndrome, lead poisoning, acute porphyria, amyotrophic lateral
sclerosis,  intracranial  lesions can all elevated these.  Common causes such
as exercise, undue  emotions,  and  pain  may  all  be  associated with false
elevations.   2....Metanephrines,  VMA  and  catecholamines  can  be  FALSELY
DECREASED with reserpine, guanethidine, malnutrition, dysautonomia and  renal
insufficiency.   3....Catecholamines by themselves can be FALSELY ELEVATED by
methyldopa,     phenothiazines,     labetalol,     and     MAO    inhibitors.
4....Metanephrines by themselves can be FALSELY ELEVATED by  MAO  inhibitors,
ethanol,  methyldopa, phenothiazines and benzodiazepines.  5....Metanephrines
by themselves can be FALSELY DECREASED by several different radiopaque media.
6....VMA by itself can be FALSELY ELEVATED with sulfonamides, nalidixic acid,
lithium, methocarbamol, glycerol guaiacolate,  and mephenesin.  Foods such as
citrus, tea, chocolate,  vanilla  and  coffee  can  also  elevated  the  VMA.
7....VMA  by  itself  can  be  FALSELY  DECREASED by MAO inhibitors, ethanol,
disulfiram, mandelamine and clofibrate.  CT and MRI and aortograms are useful
for localization and diagnosis.  MRI may be better to differentiate malignant
from benign tumors.  CT is 92%  sensitive  and  has a 80% specificity.  CT is
able  visualize  the  tumors  if  they  are  greater  than  1  cm3.    Plasma
catecholamines  greater  than  2000  pg/mL with the patient supine 30 minutes
after the needle is placed can  be  used for diagnosis.  Apparently there are
no false positives, but there may be  5-10%  false  negatives.   DIFFERENTIAL
DIAGNOSIS: Several conditions can simulate an attack of Pheochromocytoma such
as   thyrotoxicosis,   anxiety   ,   panic,  labile  essential  hypertension,
hypoglycemia, mastocytosis, hyperventilation,  angina,  migraines, cocaine or
amphetamines,  menopausal  syndrome  or  ingestion  of  any   sympathomimetic
medications.   TREATMENT:  About  90% of these tumors are benign and surgical
removal is curative.  The  patient  should  be  prepared  for surgery with an
alpha blocker as phenoxybenzamine (Dibenzyline) given first at  10  mg  daily
and  then  increased  by  about 10 mg every 2-3 days as needed to control the
symptoms.  An average dose  for  doing  this  would  be  .5 to 1.0 mg/kg/day.
After the symptoms are controlled with Dibenzyline then the patient should be
started on a beta blocker as propranolol (Inderal) at 10 mg  every  6  hours.
This  may  be  increased  to  control the tachycardia.  Always give the alpha
blocker first and  then  follow  with  the  beta  blocker.  Acute episodes of
Pheochromocytoma may be controlled with phentolamine (Regitine) 5 mg IV,  but
this  drug  has a short half life and a drip may be required.  If the patient
has a  hypertensive  episode  during  surgery,  nitroprusside or trimethaphan
camsylate  may  be  used.   Tachycardias  occurring  during  surgery  can  be
controlled with propranolol .5 to 2 mg IV and  if  frequent  PVCs  develop  a
lidocaine bolus followed by drip can be used for control.  If the patient has
an inoperable or malignant tumor, medical management with metyrosine (Demser)
may be used at an initial dosage of 250 mg qid with increases daily of 250 mg
until  a  maximum  of  4  grams per day is achieved.  Dibenzyline may also be
used.  These patients have huge  volume  deficits and these must be replaced.
Some can be 10 Liters  deficient.   During  surgery  the  patient  should  be
continuously  monitored  with  an  intra  arterial  catheter  and  Swan  Ganz
catheter.   Induction  of  anesthesia  should  be  done  with  a drug such as
thiobarbiturate and then sustained with  enflurane.   If a muscle relaxant is
required, pancuronium may be used as this drug will  not  release  histamine.
Atropine  should  not be used preoperatively.  If hypotension develops during
surgery use a levarterenol infusion  of  4-12 mg/liter and hydrocortisone 100
mg IV.  Following surgery another  collection  of  catecholamines,  VMA,  and
metanephrines  should be done since these tumors may be multiple and may have
been missed during  surgery.   If  the  patient  happens  to be pregnant then
surgical resection of the tumor could be done during  the  first  and  second
trimester.   If  the  patient  is  in  the  third  trimester,  C-section  and
extirpation of the tumor both can be done.

                   -PHENTOLAMINE AND HYPERTENSION-
(Regitine). 5-15 mg IV. Side effects: tachycardia, flushing.

                          -PITUITARY TUMORS-
Any patient that presents with headaches and visual disturbance  may  have  a
pituitary  tumor with excessive hormone production and/or compressive changes
of  the   surrounding   area.    Most   pituitary   tumors   do  not  produce
hypopituitarism.  Any female with infertility should be suspect for pituitary
disease.  PROLACTIN excess can produce amenorrhea/galactorrhea in the  female
and  impotence  in  the  male.   GROWTH HORMONE can produce acromegaly in the
adult and gigantism  in  the  child.   Acromegaly  can  be  confirmed with an
elevated serum growth hormone that doesn't suppress after an  oral  100  gram
glucose  load, or an elevated serum insulin like growth factor level (IGF-I).
THYROID STIMUALTING HORMONE  (TSH)  can  produce  hyperthyroidism with a high
TSH.   ACTH  excess  can  produce  Cushing's  disease.   Pituitary  dependent
Cushing's disease is indicated if there is an elevated 24 hour  urinary  free
cortisol  and non suppression after dexamethasone along with a normal to high
ACTH level.  The dexamethasone suppression  test  is  done  by giving 1 mg of
dexamethasone at bedtime which should then suppress the AM cortisol  to  <  5
ug/dl.   Patients  who fail to suppress will need further testing with higher
doses of dexamethasone and imaging.  Petrosal  sinus drainage for ACTH may be
used to rule out an ACTH ectopic syndrome  such  as  a  bronchial  carcinoid.
Depression,  stress  and  other  illnesses  may  alter  this  screening test.
Pituitary adenomas that are < 1 cm and are contained within the sella turcica
are microadenomas and usually present with hormone excess.  Macroadenomas can
expand  to   the   suprasellar   area   producing   headache,  cranial  nerve
abnormalities, bitermporal hemianopsia, and CSF rhinorrhea.   Visual  testing
should   be  done  in  these  patients.   Prolactinomas  usually  present  as
microadenomas in women and  produce  such symptoms as galactorrhea, menstrual
irregularities, and infertility.  However, men usually  present  with  larger
prolactinomas with impotence and mass-effect symptoms.  Hyperprolactimona has
a  large  differential including drugs (narcotics, estrogens, phenothiazines,
reserpine), renal disease,  hypothyroidism,  cirrhosis, pregnancy, chest wall
or breast disease, and hypothalamic disease affecting  the  pituitary  stalk.
Other  diseases  that may be associated with normal or low pituitary hormones
include  craniopharyngioma,   meningioma,   hamartoma,  chromophobe  adenoma,
aneurysm, sarcoidosis, empty sella and eosinophilic granuloma.

                         -PLEURAL EFFUSION-
LABORATORY:  All  pleural  effusions  should  be  subjected   to   laboratory
examination  and inspection.  Between the two an appropriate diagnosis can be
ascertained in conjunction with the history and physical.  The following will
address the laboratory findings in various diseases.  GRAM STAIN AND CULTURE:
This should be done to rule out infection and empyema.  Also acid fast smears
and cultures should be done.  WBC  AND DIFFERENTIAL: If there is greater than
1000 WBC/mm3 then you should suspect an exudate.  If there  is  greater  than
25,000  WBC/mm3  then  an  empyema  should  be  suspected.   An  increase  of
polymorphonuclear  cells  would  indicate empyema, parapneumonic effusion and
pulmonary embolus.  When mononuclear  cells  are  found in predominance, this
would suggest a transudate  and  a  chronic  inflammation.   An  increase  of
eosinophils would be compatible with drug reaction, pneumothorax, hemothorax,
sarcoidosis,  asbestosis,  parasitic,  fungal or autoimmune origin.  GLUCOSE:
Low glucose of the pleural fluid  when  compared with the serum glucose would
suggest rheumatoid arthritis, tuberculosis, empyema and  esophageal  rupture.
AMYLASE:  If the amylase is elevated suspect esophageal rupture or pancreatic
disease.  FAT STAIN: If there appears to  be chylous effusion then do a Sudan
fat stain.  AUTOIMMUNE DISEASE STUDIES: Examine  the  fluid  for  antinuclear
antibodies,  complement  and  immune  complexes.   PH:  To obtain accurate pH
studies, the specimen must  be  handled  anaerobically  as you would handle a
blood gas.  pH studies  should  be  done  for  diagnosis,  and  also  can  be
important  in  indicating  if a tube thoracostomy is needed.  A pH lower than
7.30 would suggest an exudate as  empyema or rheumatoid arthritis.  If the pH
is lower than 7.0 then empyema is likely.  A  pH  of  less  than  7.3  and  a
glucose  of  < 60 with a normal plasma glucose would narrow the possibilities
of  an  exudate  to   empyema,  malignancy,  esophageal  rupture,  rheumatoid
effusion, lupus and tuberculosis.  CYTOLOGY: Cytology may yield a  diagnosis,
but  the  yield is only about 50% if the pleura is involved.  The most common
causes of metastatic pleural effusions  would include lung, breast, ovary and
stomach.  LDH AND PROTEIN RATIOS: A pleural fluid LDH/serum LDH ratio greater
than 0.6 would indicate an exudate.  A pleural  fluid  Protein/serum  Protein
greater  than  0.5  would  indicate  an  exudate.  In general, if the pleural
protein is  greater  than  3  g/dl  then  an  exudate  is  probable.   If the
cholesterol level in the fluid is less than 60 the  effusion  is  probably  a
transudate,  whereas  if > than 60 it is an exudate.  BLOODY EFFUSION: If the
fluid is  bloody,  you  should  suspect  a  hemothorax  secondary  to trauma,
dissecting aneurysm, pneumothorax, pulmonary embolism, or malignancy.  If the
pleural/serum hematocrit is greater than 50% then consider  placing  a  large
thoracostomy  tube.   If  the  tube  output  is  greater  than  100  ml/hr, a
thoracotomy is indicated as the patient likely has complications from trauma,
dissecting aneurysm  or  pneumothorax.   If  the  RBC  count  is greater than
100,000/mm3, asbestos pleural effusion and thoracic endometriosis would  also
have  to  be  ruled  out.   CHYLOTHORAX:  Chylothorax  can  be  identified by
measuring the pleural triglyceride.  A  level greater than 110 is diagnostic.
If below 50, this would rule it out.  Levels in  between  are  non-diagnostic
and would require a lipoprotein electrophoresis.  If chylomicrons are present
then  there  is  a  chylothorax.   Chylothorax  usually  arises when there is
disruption of the thoracic duct in the chest, but the disruption can be below
the diaphragm where there is a  chylous ascites and then transgression to the
chest.  Lymphomas are commonly  associated  with  chylothorax  as  can  other
malignancies.    Trauma   can   also   cause  chylothorax.   EXUDATES  VERSUS
TRANSUDATES: It is convenient to  divide  diseases that produce exudates from
diseases associated with transudates.  By far, exudates are more difficult to
diagnose.  The following shows the diseases of each  category.   TRANSUDATES:
Transudates  are  commonly  due  to  congestive heart failure, Cirrhosis with
ascites,  nephrotic   syndrome,   hypoalbuminemia,   myxedema  and  pulmonary
embolism.  Less common causes  would  be  peritoneal  dialysis,  constrictive
pericarditis,   superior   vena   cava  obstruction,  glomerulonephritis  and
urothorax  from  an  obstructive  uropathy.   The  pH  in  urothorax  is low.
EXUDATES:  Multiple  diseases  are   capable   of   producing   exudates   as
parapneumonic  effusion,  empyema,  tuberculosis,  connective tissue disease,
infections as viral, fungal,  rickettsial  and parasitic, pulmonary embolism,
neoplasm, Meig's syndrome, pancreatic disease, asbestos, atelectasis, uremia,
chylothorax, sarcoidosis, post-myocardial infarction  syndrome  of  Dressler,
drug  reactions,  and  trapped  lung.   More  than  40% of exudates are blood
tinged.   DISEASES:   TUBERCULOSIS:  In  TB  effusions  the  WBC  is  between
5000-10,000 with a mononuclear  predominance.   The  glucose  is equal to the
serum levels but occasionally less than 60 mg/dl.  The protein  may  be  >  5
g/dl.   The  appearance may be serosanguinous with positive acid fast bacilli
seen.  MALIGNANCY: The WBC can range  from  1000  to less than 100,000 with a
predominance of mononuclear cells.  The glucose is equal to the serum  levels
and  less  than  60  mg/dl  in 15% of patients.  Cytology can be positive and
eosinophilia would be uncommon.   The  fluid  can be serosanguinous.  Pleural
metastasis is caused mostly by lung and breast  cancer  and  these  represent
about  75%  of  all  malignant  effusions.   Lymphomas account for about 10%.
PARAPNEUMONIC EFFUSION: The fluid is clear  to  turbid and the WBC is between
5000 to 25,000 with a  predominance  of  polymorphonuclear  leukocytes.   The
glucose is equal to serum levels but may be low.  If the pH < 7.0 or there is
a  positive  gram's  stain  or low glucose or LDH > 1000, then a thoracostomy
tube should be placed along with  antibiotics.   If the pH is between 7.0 and
7.2 with a negative gram's stain and a glucose greater than 40 and the LDH is
less than 1000 without loculations antibiotics should be given.   Follow  the
patient  with a short period of observation and repeat the thoracentesis.  If
there now is an increase of the LDH >  1000 or the pH is less than 7.0, place
a thoracostomy tube.  For parapneumonic effusions with a pH >  7.2,  negative
gram  stain,  LDH  less  than  1000,  and  glucose > 40, antibiotics only are
indicated.  EMPYEMA: The fluid would be turbid to purulent with a WBC between
25,000 and 100,000.   Polymorphonuclear  leukocytes predominate.  The glucose
is low and may be extremely low.  If  there  is  a  putrid  odor  this  would
suggest  an anaerobic infection.  The gram stain may be positive.  RHEUMATOID
ARTHRITIS: The fluid color  may  be  greenish-yellow  to  cloudy.  The WBC is
usually   between   1000-20,000.    The   cells   may   be   mononuclear   or
polymorphonuclear leukocytes.  The glucose is usually < 40 ng/dl.  There  may
be  a  high  LDH,  low  complement,  high cholesterol crystals and rheumatoid
factor.   Gram  stain  is  negative  unless  there  is  a  secondary empyema.
PANCREATITIS:  The  fluid  is  cloudy  to  serosanguinous  with  WBC  between
1000-50,000 and there is a predominance of polymorphonuclear leukocytes.  The
glucose is equal to serum.  The amylase is elevated and the pleural  effusion
is  usually  on  the  left  chest.   Pancreatic pseudocysts can cause pleural
effusions and are usually  seen  in  chronic alcoholics.  PULMONARY EMBOLISM:
The fluid is serous to bloody and the WBC is between  1000  and  50,000  with
either  mononuclear  of  polys  present.   The glucose is equal to the serum.
ESOPHAGEAL RUPTURE: The effusion fluid is  reddish brown and can be cloudy to
purulent.   The  WBC  is  less  than  5000  to  greater  than   50,000   with
polymorphonuclear  leukocytes  predominating.   The  glucose  is usually low.
There may be a pneumothorax and  a  left  sided effusion.  A pH less than 6.0
would be compatible with esophageal rupture.  There may be  a  high  salivary
amylase.   TRAPPED  LUNG:  Trapped lung usually denotes prior inflammation of
the pleura from  pneumonia  or  tuberculosis.   There are recurrent effusions
following paracentesis.  YELLOW NAIL SYNDROME: In this disease, which  has  a
median  age  of  onset  of  40,  there  is a decrease of the lymphatics.  The
syndrome is  very  rare.   There  are  yellow  nails,  lymphedema and pleural
effusion, bronchiectasis, bronchitis,  sinusitis  and  recurrent  pneumonias.
The  effusions  never  increase  in volume after thoracentesis.  The fluid is
usually yellow with a protein  greater  than  4  and an LDH greater than 200.
The glucose is equal to blood and the pH is usually around 7.4.  There  is  a
predominance  of  lymphocytes.   MEIGS  SYNDROME:  There  is  usually a right
pleural effusion with large  ovarian  or  uterine  masses.  These are usually
associated with  ascites.   DRUGS:  Several  drugs  are  capable  of  causing
effusions  as  nitrofurantoin, bromocriptine, methysergide, drug induced SLE,
dantrolene, chemotherapeutic agents,  amiodarone,  sclerosing agents used for
esophageal varices and l-tryptophan.   ASBESTOSIS:  Asbestosis  may  be  very
difficult  to  diagnose  because  of  the  time  elapse  between exposure and
symptoms.  Usually, symptoms don't develop  for  15-30 years and this history
may have been forgotten.  Chest x-ray 15 years later may only  show  a  small
effusion.   Of  course,  if  there  is pleural calcification or diaphragmatic
pleural calcification then this would help.

                   -PNEUMOCYSTIS CARINII AND AIDS-
Trimethoprim  (15 mg/kg/day) + sulfamethoxazole (75-100 mg/kg/day) PO or IV x
21 days in 3-4 daily doses or Pentamidine (4 mg/kg/day) IV or IM x 21 days or
Dapsone (100 mg/day) PO + trimethoprim (5 mg/kg)  PO  or IV q 8h x 21 days or
Clindamycin (600-900 mg) IV q th x 10 days, then 450 mg PO q6h x  11  days  +
primaquine  (15  mg  base)  PO  qd or Atovaquone (Mepron), 750 mg PO tid with
food.   Maintenance   therapy:   Trimethoprim-sulfamethoxazole,   one  double
strength tablet PO qd for 7 days/wk  or  2  double  strength  tabs  PO  three
times/wk  or  Dapsone 100 mg PO three times/wk or Aerosol pentamidine, 300 mg
monthly by nebulizer or Pyrimethamine  + sulfadoxine (25 mg/500 mg, Fansidar)
PO each week.

                        -PNEUMONIA (Atypical)-
The most common atypical pneumonias are  due  to  Mycoplasma,  Chlamydia  and
Legionella.   The  key  features  of  these  infections  will  be  discussed.
MYCOPLASMA   PNEUMONIA:   Mycoplasma   pneumonia   is  caused  by  Mycoplasma
pneumoniae, and is spread by infected droplets.  It accounts for about 20% of
all cases of community acquired pneumonia, and is usually seen in children or
young adults, but may also  occur  in  the elderly.  The incubation period is
about 21 days with the highest incidence during the fall and winter, but  can
occur  in epidemics at any time.  CLINICAL: Most of these patients start with
upper respiratory symptoms such as  sore  throat, low grade fever, chills and
possibly ear pain.  They may also  have  headache,  myalgias,  and  diarrhea.
Sinusitis  and  otitis are commmon.  Eventually a cough develops that is only
productive of small amounts of  mucoid  sputum,  and is associated with rales
and rhonchi.  Any patient that has a non-productive cough, diarrhea,  otitis,
and a unilateral interstitial infiltrate on chest x-ray should be suspect for
Mycoplasma  pneumoniae.   Hoarseness  and  pulse  temperature deficit are not
features of  Mycoplasma.   Complications  include  myocarditis, pericarditis,
meningoencephalitis, mononeuritis multiplex, transverse myelitis,  cerebellar
ataxia,    Guillain-Barre    syndrome,    autoimmune    hemmolytic    anemia,
thrombocytopenia,   disseminated   intravascular  coagulation,  splenomegaly,
lymphadenopathy,	glomerulonephritis,    interstitial     nephritis,    and
pancreatitis.  LABORATORY: The patient may have a mild leukocytosis,  usually
less  than  15,000  cell/mm3.   Cold  agglutinins may be present in 50-75% of
cases.  A presumptive daignosis can be made  if the titer is 1:64 or greater.
Obtaining  the  IgM  antibody  is  more  specific.   Acute  and  convalescent
complement fixation titers can confirm the  diagnosis.   Gram  stain  of  the
sputum  will  only  show  a  few  polymorphonuclear leukocytes or mononuclear
cells.  Chest x-ray usually shows  a  lower lung patchy alveolar or reticular
infiltrate.  Rarely, there may be  small  pleural  effusions.   There  is  no
cavitation  or  consolidation.   TREATMENT:  Treatment  is with erythromycin,
tetracycline, or doxycycline for 2-3 weeks.  Antibiotic therapy will decrease
the severity and duration of symptoms,  but  does not influence the course of
the disease or the  possible  development  of  extrapulmonary  complications.
Patients  tend  to  be infectious for weeks after antibiotic therapy has been
started.  Most patients will have  symptoms  for  about 2 weeks if untreated,
and in some cases, may last for up to 6 weeks.  However, the  x-ray  findings
may  persist  for weeks.  CHLAMYDIAL PNEUMONIA: Chlamydial pneumoniae is also
known as the TWAR agent.   It  was given this nomenclature because Chlamydial
pneumonae was origianlly isolated from the conjunctiva of a Taiwan child, and
from the pharynx of a student at the University of Washington.  The  mode  of
transmission  is  probably  through  respiratory  secretions.   Infection  is
uncommon  in  children,  but  usually  occurs as endemic infections througout
life.   CLINICAL:  Most   patients   present  with  hoarseness,  pharyngitis,
non-productive cough and fever.  Some patients will have sinusitis,  rhinitis
and  pleuritic  chest  pain.   About  33%  will  have  sinus tenderness.  The
development of  cough  may  be  delayed  for  several  days  to weeks.  Chest
examination will reveal rales and rhonchi.  LABORATORY: The WBC may be normal
or elevated.  Chest x-ray findings usually consist of a  single  subsegmental
infiltrate  that  often has a conical or funnel configuration.  Small pleural
effusions may  be  seen  in  the  elderly,  but  usually  not  in  the young.
Diagnosis may be obtained with a single high antibody  titer  or  a  fourfold
increase  in  acute  and  convalescent  serum  titers.  The IgM titer becomes
elevated in 2-4 weeks with  primary  infections  from C. pneumoniae.  The IgG
does not become elevated until the 6-8th week.   However,  with  reinfection,
there  may  be no IgM response.  TREATMENT: Treatment with erythromycin often
fails.  The treatment of choice  is  tetracycline or doxycycline for 14 days.
Clarithromycin (Biaxin) and azithromycin (Zithromax) may also  be  effective.
Treatment at best may be slow and incomplete, and the cough and tiredness may
persist.  Sometimes an additonal course of tetracycline or doxycycline may be
helpful.    LEGIONELLA   PNEUMONIA:   Legionella   pneumophila  is  the  most
common	organism encountered, and  may  be  responsible  for Pontiac fever as
well as legionnaires's disease.  The incubation period is usually 2-10  days.
Legionella  may  account  for  about  15%  of  community  acquired pneumonia.
Legionella species  is  typically  found  in  humidifiers,  water heaters and
freshwater habitats.   Spread  is  by  inhalation  of  infected  aerosols  or
aspiration  of  infected liquids.  Risk factors include smoking, chronic lung
disease, steroid use  and  old  age.   CLINICAL:  Patients  present with high
fevers (102-105 F), chills and flu like symptoms, such as headache, myalgias,
and dry cough.  Occasionally, there may be hemoptysis, pleuritic  chest  pain
and  dyspnea.   Auscultation  of  the  lungs  reveals rales and rhonchi.  The
patient may also have a relative bradycardia  in  spite of a temp of 102 F or
greater (If not on beta blockers).  Extrapulmonic symptoms are frequent,  and
include   watery  diarrhea,  abdominal  pain,  nausea,  vomiting,  confusion,
cerebellar ataxia, peripheral neuropathy, proteinuria, microscopic hematuria,
renal   insufficiency,    pericarditis,    myocarditis,   and   pancreatitis.
LABORATORY: Mild elevation of the liver transaminases, hypophosphatemia, mild
leukocytosis, and hyponatremia are relatively common.  Gram stain  of  sputum
usually  only  shows a few polymorphonuclear cells or monocytes.  The initial
chest  radiograph  shows  a  patchy  unilateral  infiltrate  which progresses
rapidly.  Cavitation is rare, but can occur  in  immunocompromised  patients.
CSF  may  reveal  pleocytosis  and  increased  protein.  Diagnosis is made by
culture on buffered charcoal-yeast extract agar.  The growth may take up to 5
days as Legionella organisms grow  slowly.  Direct fluorescent antibody (DFA)
stains of fluid or tissue is specific, but the sensitivity is dependent  upon
the  number  of  organisms  present  in  the  sample.   There  also  is cross
reactivity  with  some  gram   negative   species  such  as  Pseudomonas  and
Bacteroides fragilis, and the DFA rapidly becomes  negative  with  treatment.
The  urinary  Legionella  antigen  may  be  positive  after  several  days of
infection, and can remain positive for months.  A single indirect fluorescent
antibody titer of  1:256  or  greater  is  presumptive evidence of Legionella
infection, as is a 4 fold increase of acute to convalescent serum  specimens.
However,  it may take 4-6 weeks for a positive antibody response.  TREATMENT:
The  treatment  of  choice   is   with   erythromycin  using  2-4  grams/day.
Doxycycline has also been successful.  Clarithromycin  and  azithromycin  may
also  prove  to be effective.  Rifamipin (Rimactane, Rifadin), quinolones and
trimethoprimn/sulfamethoxazole may also be effective.  Initial therapy should
be with IV  antibiotics  for  the  first  week  of  therapy, followed by oral
antibiotics if there are no complications.  The chest infiltrates are slow to
resolve even after therapy, and may take months for complete resolution.

                     -PNEUMONIA IN THE ELDERLY-
It is estimated that by the year 2030, 17% of the population will be over the
age of 65.  There is  an  increasing  population  in  nursing  homes  and  in
intensive  care  units.   This  subject  will address the clinical aspects of
bacterial pneumonia  in  the  elderly  as  well  as  the treatment.  Atypical
pneumonia will not be addressed.  CLINICAL: Pneumonia in  the  elderly,  more
frequently  presents  with  dyspnea.   Most of the patients will have chills,
cough, fever, chest pain  and  increased  sputum  production, but to a lesser
extent than the young.  Some may not even have a cough, sputum or chest pain.
Tachycardia isn't common in  the  elderly  and  fever  may  not  be  present.
Confusion  is  common  in  the  elderly  and  this  may  be the only symptom.
LABORATORY: There may be  a  leukocytosis,  leukopenia  or even a normal WBC.
However, there is usually a consistent shift to increased numbers of band and
polymorphonuclear leukocytes.  On chest X-ray there is an increase of pleural
effusions, incomplete consolidation and involvement of greater than one  lobe
in the elderly.  Resolution typically takes greater than 14 weeks, as opposed
to  about  6  weeks  for  younger patients.  In the elderly, there is greater
progression of the infiltrates after  appropriate antibiotic therapy has been
started.  TYPES OF PNEUMONIA IN THE AGED: Streptococcus pneumoniae  is  still
prevalent  in  the aged and constitutes about 40-60% of community pneumonias.
However, bacteremia is more  common  in  the elderly.  Haemophilus influenzae
pneumonia occurs in about  15%  of  community  acquired  pneumonia.   If  the
patient  has  chronic  obstructive  lung  disease,  Haemophilus influenzae is
common, as the oropharynx is colonized in about 60%.  The type B encapsulated
strain is the one that usually causes bacteremia.  In community pneumonia due
to  Haemophilus  influenzae   the   organism   are  frequently  non-typeable,
unencapsulated Beta lactamase  producers.   Staphylococcus  aureus  pneumonia
commonly  occurs  during  influenza  epidemics  and  constitutes about 10% of
community pneumonia.  Gram  negative,  community  acquired pneumonia accounts
for only a small percentage.  Klebsiella pneumoniae is the most common.  Next
common would be Proteus mirabilis, Escherichia coli  and  Enterobacter  which
account  for  about  8%.   Pseudomonas,  Serratia marcescens, Citrobacter and
Acinetobacter are  rare.   In  hospital  pneumonia,  there  is  a decrease in
Pneumococcal pneumonia with an increase of Haemophilus influenzae and a large
increase  in  gram  negative  pneumonia.   TREATMENT  OF  COMMUNITY  ACQUIRED
PNEUMONIA: Trimethoprim sulfamethoxazole has a good spectrum of coverage that
would  encompass  the  pneumococcus,  beta  lactamase  producing  Haemophilus
influenzae  and  the  gram  negative  organisms  as  Klebsiella   pneumoniae,
Escherichia   coli   and  Enterobacter  aerogenes.   If  the  patient  has  a
Staphylococcal pneumonia, then Nafcillin should be added, particularly during
periods   of   influenza.     Community    acquired   methicillin   resistant
staphylococcal pneumonia in the aged apparently has not been reported in  the
elderly.   TMP/SMX  can  be  given IV or taken orally, and is fairly cheap as
compared to other antibiotics.   What  if  the  patient is allergic to sulfa?
Then, the patient should be treated with  a  third  generation  cephalosporin
which  has good activity against beta lactamase producers.  Either cefotaxime
or ceftriaxone may be used as  they provide good coverage similar to TMP/SMX.
Cefixime would be an alternative oral 3rd generation drug that could be used.
Two other antibiotics, Ampicillin/sulbactam, and Ticarcillin/clavulanate have
a spectrum similar to the third  generation  cephalosporins  and  will  treat
Streptococcus  pneumoniae,  beta  lactamase producing Haemophilus influenzae,
Staphylococcus aureus (non methicillin resistant) and the usual gram negative
pneumonia.  Ticarcillin/clavulanate could  be  used  if  there is Pseudomonas
aeruginosa or Serratia marcescens.  TREATMENT OF HOSPITAL  AND  NURSING  HOME
ACQUIRED  PNEUMONIA:  Pseudomonas aeruginosa pneumonia may be increased up to
10% in this group.   There  also  is  an  increase of gram negative bacillary
pneumonia.   Good  choices  would  be  an   antipseudomonal   penicillin   as
mezlocillin  plus  Gentamicin, or Ceftazidime plus Gentamicin.  Gentamicin is
usually preferred over Tobramycin  as  most strains of Pseudomonas aeruginosa
are sensitive to gentamicin and the cost is usually better.  (It is important
to remember that in the elderly there is a reduction in the  lean  body  mass
and  and total body water, and an increase in body fat.  Therefore, blood and
tissue concentrations of antibiotics may be higher than usual.  The decreased
muscle mass also means there would  be  a  lower serum creatinine, and if the
serum creatinine is used to calculate the  dose  of  an  aminoglycoside,  you
might  get a higher than expected peak aminoglycoside level, which could lead
to  nephrotoxicity).    If   the   patient   has   non-methicillin  resistant
Staphylococcal pneumonia, these two combinations will  be  effective.   If  a
methicillin  resistant  Staphylococcal  pneumonia is present, use vancomycin.
SPECIFIC PNEUMONIAS IN  THE  AGED:  Legionella  pneumophilia pneumonia is not
common, but occurs occasionally,  particularly  in  smokers.   The  frequency
varies  geographically.   Only about 2% of nursing home residents will have a
significant antibody titer that is  greater  than  1:64.  The onset is abrupt
with headache, myalgias, weakness,  fever,  hemoptysis,  bradycardia,  watery
diarrhea,  abdominal pain and encephalopathy.  Gram stain of the sputum shows
leukocytes, but no organisms.  The  patient  has alteration of liver function
tests and hyponatremia is common.  A direct fluorescent antibody test of  the
sputum  should be done.  This test has a high specificity of about 90%, but a
low sensitivity  varying  between  25-80%.   Legionella  pneumophilia  can be
treated  with  erythromycin,  rifampin  or   Trimethoprim   sulfamethoxazole.
Branhamella catarrhalis pneumonia occurs mainly in adults over the age of 65.
Many  of these patients have chronic obstructive pulmonary disease.  Symptoms
are usually uncommon.  About  50%  will  be  afebrile  and have a normal WBC.
Chest x-ray shows an incomplete consolidation.  Positive blood  cultures  are
rare,  and  pleural  effusion and cavitation have not been reported.  Most of
the organisms are beta  lactamase  producers.   Sputum exam would reveal gram
negative diplococci in the WBCs.  Acute and convalescent serology  should  be
done.   Treatment  is  with  the  same  antibiotics  that  are  used to treat
community acquired pneumonia.

                             -POISONING-
[Initial  management]  Provide  airway, ventilation and vital signs.  Protect
yourself from organophosphate &  carbamate  insecticides and cyanide.  If the
patient is unconscious and convulsing, give Dextrose, and naloxone (2  mg  in
child  or  adult.   If  there  is  ingestion  of propoxyphene, pentazocine or
butorphanol then more than 2 mg may be required), and Oxygen.  If the patient
is alcoholic, give Thiamine 100 mg  IV  or  IM before dextrose.  If unable to
give drug IV then may give  atropine,  epinephrine,  lidocaine  and  naloxone
through  an endotracheal tube.  Diazepam can be given rectally.  SEIZURES: If
the seizures are due to  theophylline  then  they  may be refractory to usual
therapeutic  medications,  and  the  patient  may  need  general  anesthesia.
Seizures due to  hypoglycemia  must  be  treated  immediately  with  glucose.
Seizures  due  to  isoniazid will respond to pyridoxine.  Seizures related to
anticholinergic  agents  may   respond   to   physostigmine,   if  the  usual
anticonvulsants are not effective.  Hemodialysis may be needed  for  seizures
due  to salicylates or lithium.  Be aware that alcoholic withdrawal may cause
seizures.  Tricyclic seizures may need bicarbonate.  INVESTIGATIONS: EKG (for
dysrhythmias  or  conduction  defects  from  tricyclics).   Chest  x-ray (for
aspirations & non cardiogenic pulmonary edema).  Measure the  anion  gap  and
electrolytes   (salicylates,  methanol,  ethylene  glycol,  carbon  monoxide,
toluene, cyanide, and hydrogen  sulfide).   Get  serum osmolality & calculate
the osmolality (2x  sodium)  +  (glucose/18)  +  (BUN/2.8).   The  difference
between  these two is the osmolar gap.  If more than 10 mOsm/liter then think
methanol, ethylene glycol,  or  isopropanol  poisoning.   UA (for crystals of
ethylene glycol) Qualitative  drug  screening  of  urine,  serum  &  possibly
gastric  contents).   Specific  drug  levels  are  useful  in  acetaminophen,
anticonvulsants,  digoxin, aspirin, ethanol, methanol, ethylene glycol, iron,
isopropyl alcohol,  lithium  &  theophylline  overdoses.   Contact the poison
center.   For  salicylates  &  ethanol  treat  with  urine  alkalinization  &
hemodialysis.  For  methanol  &  ethylene  glycol  treat  with  hemodialysis.
Breath   analysis   will   reveal   clues.    Petroleum  distillates  have  a
characteristic odor,  fruity  odor  (ketoacidosis  &  ketones  of ethanol and
isopropyl  alcohol),  almond  odor  (cyanide),  garlic   odor   (arsenic   or
organophosphates),  glue  odor  (chronic  toluene  abuse) and rotten egg odor
(hydrogen sulfide or  disulfiram).   Do  a  physical  exam  to look for focal
neurological signs (CVA, subdural hematoma),  nuchal  rigidity  (meningitis),
needle  tracts  (arms, feet, groin, under the tongue, neck, supraclavicular),
drugs in the rectum,  vagina  &  swallowed  drug  packets, and cardiac arrest
(cocaine).  Get family members to bring in prescription bottles and call  the
pharmacy  to get a list of drugs.  Search the clothing, home & garbage.  Look
for drug paraphernalia.  ANTIDOTES:  1....Benzodiazepines [Flumazenil] 0.2 mg
over 30 seconds.  If ineffective after 30 seconds give .3 mg over 30 seconds.
If no response after 30 seconds give .5  mg  over  30  seconds  at  1  minute
intervals  up  to  a  total  dose of 3 mg.  Flumazenil should not be given if
benzodiazepines are being  given  for  convulsions  or  there is simultaneous
ingestion  of  tricyclics.   2....Tricyclics  antidepressants   [Bicarbonate]
3....Digitalis  [Digoxin  specific antibody fragments] If the amount ingested
and the serum digoxin concentration  are  both unknown then given 10-20 vials
IV if there is a life threatening dysrhythmia.  If the number  of  milligrams
is  known then divide that by 0.6 to ascertain the number of vials to give OR
if the serum  digoxin  concentration  is  known,  the  number  of vials = the
digoxin concentration in ng/ml  x  5.6  x  weight  in  kg/600.   4....Opiates
[Naloxone]  Start  at  2  mg  IV.   Less  may be needed to prevent withdrawal
symptoms.  More may  be  needed  if  synthetic  narcotics  have been taken as
propoxyphene,  pentazocine  &   butorphanol.    5....Anticholinergic   agents
[Physostigmine]   1-2  mg  IV  over  5  minutes.   May  be  useful  to  treat
tachydysrhythmias or seizures.   Should  only  be  used  for severe delirium.
6....Methanol, ethylene glycol [Ethanol] Give loading dose of 10  ml  of  10%
solution /kg of body weight.  Maintenance dose 0.15 ml/kg/hr.  If the patient
is  on dialysis, double the maintenance dose.  Titrate to blood ethanol level
of  100  mg/dl.   7....Calcium   channel  blockers,  hydrofluoric  acid,  and
fluorides [Calcium] 1 g calcium chloride given over 5 min by IV infusion with
cardiac monitoring.  Monitor  the  calcium  level.   8....Organophosphate  or
carbamate  insecticides  [Atropine]  Give  an  initial  test dose of 2 mg IV.
Repeat in  larger  doses  until  there  is  drying  of  pulmonary secretions.
9....Isoniazid, hydrazine, monomethylhydrazine in gyromitra species mushrooms
[Pyridoxine].  If the amount of ingestion is unknown,  start  with  5  g  IV.
Overdose  can  cause neuropathy.  If amount ingested is known then given gram
per gram equivalent of pyridoxine.  10....Beta blockers [Glucagon] Start with
5-10 mg IV.  Titrate to

                       -POLYARTERITIS NODOSA-
Any young male between the ages of 40-50 years of age presenting with  weight
loss,  fever  and  mononeuritis  multiplex  should  be  suspected  of  having
Polyarteritis  nodosa  (PN).   PN  is  a necrotizing vasculitis affecting the
small and medium sized  arteries  in  multiple  organs.   There is a 3:1 male
predominance and a large share of the patients are  between  40-50  years  of
age.   In general, the pulmonary arteries are not affected.  However, if they
are and there is a history of asthma, the diagnosis of Churg-Strauss syndrome
or allergic  granulomatosis  may  be  made.   Churg-Strauss  syndrome  may be
considered a subset of Polyarteritis nodosa.  PN is a progressive  and  fatal
disease  if  not  treated.   Many  will  die  from  GI  infarction  and renal
insufficiency.  Renal failure accounts for about  65% of the causes of death.
If the patient is not treated only 33% will be alive at the end of  one  year
and  88%  will  be  dead  by  5  years.  PATHOLOGY: The pathological features
consist of segmental, necrotizing  inflammation  of  the the small and medium
arteries involving the media and adventitia.  Biopsy may reveal a spectrum of
active  and  healing  lesions.   Fresh  lesions  may  show  polymorphonuclear
leukocytes and eosinophils, whereas older lesions may demonstrate lymphocytes
and plasma cells.  There also may be deposition of complement, immunoglobulin
and  fibrinogen.    The   pathology   commonly   involves   arteries   around
bifurcations.   There  is  intimal  proliferation  with subsequent thrombosis
leading to aneurysms and infarction.   If  the lesions heal there is fibrosis
of the adventitia.  CLINICAL: Around 70%  of  patients  will  develop  fever,
malaise  and  weight  loss  and  about the same percentage will have these as
initial findings.  These findings  must  then  be coupled with involvement of
other organs in order to help facilitate a  diagnosis.   The  following  will
report on the other systems involved.  SKIN: There may be a multitude of skin
changes  including  petechiae,  ulcers,  urticaria, purpura and maculopapular
rash.  Purpura has an incidence of about 33% whereas urticaria has only about
3% incidence.  Subcutaneous  nodules  may  be  present  in about 16%.  Livedo
reticularis is commonly seen.  There may be digital  ulcers,  infarction  and
gangrene.   NEUROLOGIC:  Neurologic involvement may be central or peripheral.
Peripheral neuropathy involving the  distal  sensory  or sensorimotor type is
more common than mononeuritis multiplex, but the latter is more specific  for
PN.   The  overall  incidence  of  neuropathy  is  about 50%.  The CNS may be
involved with development  of  visual  loss, aphasia, subarachnoid hemorrhage
and confusion in about 11%.   CARDIOVASCULAR:  Cardiovascular  symptoms  will
occur  in  up  to  50%  of  cases.   EKG findings may include non-specific ST
segment changes, arrhythmias and heart  block and even myocardial infarction.
If myocardial infarction occurs in a young person, consider PN.  There may be
an enlarged heart  with  CHF  and  myocarditis.   Pericarditis  may  also  be
present.   GASTROINTESTINAL:  Gastrointestinal  findings  usually  consist of
abdominal pain in about 65%  of  cases.   This  may occur with diarrhea.  The
liver may be enlarged and there may be GI  bleeding.   Mesenteric  infarction
may  occur which can be catastrophic.  There may be hemorrhagic infarction of
the pancreas as well as the  liver.   If there is a positive HBsAg associated
with PN, there are usually abnormal liver function  tests  with  hepatomegaly
and  jaundice.   For  some  reason  there is a higher incidence of rheumatoid
factor and cryoglobulinemia  in  patients  with mesenteric arteritis.  RENAL:
Renal involvement consisting of proteinuria  and  hematuria  are  present  in
about  60-70 percent of patients during the course of PN.  There may be renal
infarction  and  glomerulonephritis.   Hypertension  and  renal  failure  are
usually late sequelae of the disease.   Hypertension as an initial finding in
the disease is only about 25%.  MUSCULOSKELETAL: About 60% will  complain  of
transient  and  migratory myalgias and arthralgias.  Arthritis only occurs in
up to 27% affecting any joint  but commonly the knees and wrists.  PULMONARY:
Pulmonary findings are not common in classic PN, but eosinophilia and  asthma
may  suggest Churg-Strauss syndrome, a subset of PN.  LABORATORY: The average
elevation of the sed rate is around  75 mm/hour, and this will occur in about
90% of patients.  The HBsAg will be elevated in about 20-50% of patients with
PN.  The vasculitis may antedate or postdate the development  of  a  positive
HBsAg.   The perinuclear antineutrophil cytoplasmic antibody (P-ANCA) is very
useful in helping to  diagnose  patients with renal microscopic polyarteritis
consisting of vasculitis and crescentic glomerulonephritis.  There is usually
a leukocytosis in the range of 20,000 to 40,000/uL in about 80%  of  patient.
Anemia  is  common  and as mentioned occasionally there is eosinophilia.  The
BUN and creatinine  may  be  elevated  along  with proteinuria and hematuria.
Autoantibodies as the ANA and rheumatoid factor may occasionally be  present.
Immune  complexes may be seen in up to 93% of patients.  DIAGNOSIS: Diagnosis
depends on biopsy of  a  symptomatic  area  as  muscle,  sural nerve, skin or
testes.  It is important to biopsy an area that is clinically active as  only
13-32%  of biopsies done blindly will be positive.  For example, if a patient
has myalgia or neuropathy then a muscle biopsy or sural nerve biopsy would be
indicated.  If these biopsies are negative  or  the patient has no myalgia or
neuropathy, mesenteric or renal angiography should be performed, looking  for
aneurysms.   Renal,  hepatic  and  mesenteric angiography will yield multiple
aneurysms in about 60% of biopsied proven cases.  The aneurysms alone are not
diagnostic as they may also be  seen in SLE, hypernephroma, atrial myxoma and
thrombotic  thrombocytopenic  purpura.   TREATMENT:  Treatment  consists   of
prednisone  in  doses  of 40 to 60 mg per day.  Many patients will respond to
prednisone alone.  However, if the course  of the disease is not modified and
there is rapid and systemic involvement, cyclophosphamide 100-150 mg/day  po,
OR  500-1000  mg IV via pulse therapy every 3-4 weeks may be started.  It has
been shown that the highest mortality usually occurs in the first year of the
disease with GI and  renal  insufficiency  causing  a large proportion of the
deaths.  Other causes as drug side effects, cardiovascular and infection also
will contribute to the mortality.  Most recent studies indicate  that  the  5
year  survival  is  now  around 75% as compared with a mortality of about 88%
within 5 years in those who are not treated.

                           -POLYARTHRITIS-
Polyarthritis   is   characterized   by   pain   and  inflammation  occurring
simultaneously in 2 or more joints.   The most common causes of polyarthritis
are rheumatoid arthritis, SLE, ankylosing spondylitis,  psoriatic  arthritis,
Crystal  induced  arthritis (gout, pseudogout), and Reiter's syndrome.  Other
causes  include  systemic  sclerosis,  inflammatory  bowel disease-associated
arthritis, rheumatic fever, mixed connective  tissue  disease,  hepatitis  B,
HIV,  rubella,  polyarteritis  nodosa, gonococcal arthritis, hemochromatosis,
sarcoidosis, and osteoarthritis.   HISTORY  AND  PHYSICAL: Every patient that
you see with polyarthritis should be asked about inflammatory bowel  disease,
morning stiffness, pleuritis, mucocutaneous changes, and eye problems such as
iritis.   Physical  exam  should  include a search for tophi, psoriasis, nail
pitting, malar rash, oral  ulcers,  vasculitis,  Raynauds's disease, dry eyes
and  mouth,  urethritis,  aortic  regurgitation,  discoid  lupus,   alopecia,
circinate  balantis,  keratoderma  blennorhagica,  subcutaneous  nodules, and
carpal tunnel syndrome.  LABORATORY: A  rheumatoid  factor of 1:80 or greater
is suggestive of RA.   However,  it  may  be  negative  in  early  rheumatoid
arthritis  and  is  not  sensitive  or specific for rheumatoid arthritis.  An
antinuclear antibody (ANA) that  is  1:80  or  greater  is suggestive of SLE.
However,  mixed  connective  tissue  disease  (MCTD)  and  primary  Sjogren's
syndrome may be associated with a positive ANA.  Some healthy individuals may
have  positive  ANAs.   Double  stranded  DNA  antibodies  are  specific  and
diagnostic for SLE, but the sensitivity is very low.  The sedimentation  rate
can  be  elevated  in  all types of polyarthritis.  Sacroiliac x-rays will be
positive in patients  with  ankylosing  spondylitis,  psoriatic arthritis and
Reiter's syndrome.   X-rays  of  the  hands  can  demonstrate  characteristic
features for rheumatoid arthritis, gout, and the spondyloarthropathies.  Bone
scans  are  not  specific,  but  can  define increased uptake in the affected
joints before x-ray  findings  become  positive.  Arthrocentesis and synovial
fluid  analysis  can  identify  crystal  disease  of  gout  (uric  acid),  or
pseudogout (calcium pyrophosphate).  All joint fluid should  be  cultured  as
infection  is more common in diseased joints, and external signs of infection
may be minimal.  Marked turbidity  is  suggestive of infection.  Viscosity is
inversely related to inflammation.  PROFILES:  RHEUMATOID  ARTHRITIS:  RA  is
more  common  in  females  by 3:1.  The prevalence rate is 10-30/1000.  Other
high risk groups include those  with  HLA-DR4.  There is no particular racial
predilection.  The onset is gradual and symmetric in about 80% of cases.  The
most commonly affected joints include the metacarpophalangeal joints,  wrist,
knee,  elbow,  hip  and  shoulder.   Morning stiffness is present in 90-100%.
Systemic complaints  consist  of  weight  loss,  fatigue  and sicca symptoms.
Extraarticular signs include vasculitis, carpal tunnel syndrome, subcutaneous
nodules on the extensor surfaces, and pulmonary fibrosis.  Physical  exam  of
the  joints  may  reveal  swan  neck  and  buttoniere  deformities, and ulnar
deviation at the MCP and wrist.   The  rheumatoid factor by latex fixation is
usually positive in a titer of 1:80 or greater, particularly after the  first
year  of the disease.  There may be a false positive low titer ANA of 15-20%.
The anti double  stranded  DNA  is  negative.   The  ESR is usually elevated.
X-rays of the joints  may  reveal  periarticular  osteopenia,  and  symmetirc
erosion  without  new bone formation.  The HLA-B27 may be positive.  SYSTEMIC
LUPUS ERYTHREMATOSIS: SLE affects females in a ratio of 9:1 with a prevalence
rate of .1-1/1000.  There is  a  peaking  of  the disease in the 2-4 decades.
There is a higher incidence in Blacks.  The onset  is  usually  gradual  with
symmetrical  involvement  in greater than 80% of cases.  SLE tends to involve
the MCP,  PIP,  wrist,  knee,  ankle  and  elbows.   Morning  stifness is not
typical, but can occur in 20%.  Other symptoms may include Raynaud's disease,
pleuritis, sicca symptoms, photosensitivity, renal disease, and CNS symptoms.
Physical findings can include malar rash, alopeica, discoid lupus and mucosal
ulcers.  The rheumatoid factor may be falsely elevated in 20-40%.  The ANA is
positive in greater than 90%, usually in a titer of  1:80  or  greater.   The
anti  double  stranded  DNA  can  be  positive in 80-90%.  The ESR is usually
elevated.  X-ray findings may reveal periarticualr osteopenia and soft tissue
swelling.  PSORIATIC ARTHRITIS: Psoriatic arthritis  has a prevalence rate of
.2-1.4/1000 with out any sex preference.  The disease peaks between the  ages
of  15-45.   Patients  may  be  HLA-B27  positive.  The onset can be acute or
subacute.  It is asymmetric in  80%  of  cases.  Commonly affected joints are
the hands and feet, sacroiliacs, and the axial skeleton.   Morning  stiffness
is  common.  Psoriatic skin lesions may be gross or occult.  Typical physical
presentation is  a  sausage  digit.   There  can  be  deformities  as seen in
rheumatoid	arthritis.   Nail  pitting  is  characteristic.   The  rheumatoid
factor, ANA, anti double stranded DNA  are  all  negative.   About  20%%  are
positive   for  HLA-B27.   Typical  x-ray  findings  include  pencil  in  cup
deformities, distal phalangeal tuft  resorption,  erosion with sclerosis, and
spondyloarthropathies.  REITER'S  SYNDROME:  Reiter's  syndrome  has  a  male
predominance  with  a  prevalence rate of 1/1000.  The disease usually occurs
between the ages of 15-45.   HLA-B27  may  be positive.  The onset is usually
acute with an asymmetric presentation in 95% of  cases.   The  most  commonly
involved  joints  include  the  sacroiliac,  knees  ankle  and feet.  Morning
stiffness is comnmon.  Other  symptoms  may  include urethritis, iritis, back
pain, and enthesopathy.  Deformaties are  rare.   Physical  exam  may  reveal
circinate  balanitis, urethritis, keratoderma blennorhagica, and oral ulcers.
The rheumatoid factor, ANA and  anti  double  stranded DNA are negative.  The
HLA-B27  is  positive  in  75-80%.   X-rays  may  show  a  plantar  spur   or
sacroiliitis.   ANKYLOSING  SPONDYLITIS:  Ankylosing  spondylitis  has a male
preference of  3:1.   The  prevalence  rate  is  1-10/1000.   It  has  a peak
incidence of between 15-30 years of age.  There is a 4  fold  increased  risk
for  whites.   The onset is usually gradual, affecting the spine, sacroiliac,
hips,  knees,  shoulder  and  costovertebral  joints.   Morning  stiffness is
present in 15%.  Patients may develop iritis and aortic  regurgitation.   The
sed  rate  is  usually  elevated.  The rheumatoid factor, ANA and anti double
stranded DNA are  negative.   HLA-B27  is  positive  in 90-95%.  X-Rrays will
reveal sacroiliitis, and vertebral ankylosis.  GOUT: Gouty  arhtritis  has  a
strong  male  predominance  and  a  prevalence  rate  of  1-3/1000.  The peak
incidence is between 40-60 years  of  age.   It is commonly seen in alcoholic
and obese patients.  The onset is acute and asymmetric.  Gout attacks the MTP
joint, ankle, arch of the foot, knee, wrist and hand.  Morning  stiffness  is
absent.   There may be associated tophi.  The rheumatoid, ANA and anti double
stranded DNA are negative.  The sed  rate is elevated during the acute phase.
X-rays may reveal joint erosion with an overhanging margin, ankylosis, tophi,
and joint destruction.

                      -POLYARTHRITIS AND FEVER-
Infectious: septic, bacterial endocarditis,  Lyme  disease,  Mycobacterial  &
fungal  arthritis  &  viral.  Reactive or post-infectious: enteric infection,
urogenital  infection,  inflammatory  bowel   disease  and  rheumatic  fever.
Rheumatoid  arthritis  and  Still's   disease:   Crystal-induced   arthritis:
pseudogout and gout.  Systemic rheumatic diseases: SLE & systemic vasculitis.

                         -POLYCYTHEMIA VERA-
Polycythemia vera (Vaquez-Osler disease is a myeloproliferative disease  with
monoclonal  stem  cell  proliferation  of  all three hematopoietic cell lines
(erythroid, myeloid and megakaryocytic  elements  of the bone marrow).  There
is no known genetic transmission and the incidence  in  the  USA  is  .5  per
100,000.   Males  are  affected slightly more than females.  The usual age of
presentation is around 60 years  of  age,  but can range from 15-90.  CAUSES:
Polycythemia vera always has to be differentiated from spurious  polycythemia
(increased  Hb  with  a  normal  or  high  normal RBC mass and reduced plasma
volume).  This can be  due  to  diuretic  therapy and hypertension.  Spurious
polycythemia can result in thrombotic events.  Treatment would be to decrease
the diuretics and find out why the plasma  volume  is  decreased.   Secondary
polycythemia  would  also have to be ruled out.  This results in an increased
RBC mass and Oxygen  saturations  of  <90%.   The  hypoxia leads to increased
erythropoietin levels and subsequent secondary polycythemia.   Patients  with
this  pattern  should  have  renal  ultrasonography  or  CT  scan to rule out
hepatoma, cerebellar hemangiomas,  uterine  fibromas,  renal cysts and tumors
which  cause  compression  of   intrarenal   vessels   and   local   hypoxia.
Arteriography  may  be  needed.   In  some patients with chronic lung disease
there is a diurnal  pattern  and  hypoxia  only  occurs at night.  Therefore,
night time oximeter studies or blood gases should be done.  Pulmonary disease
and right to left shunts would have to be ruled out, but the  latter  usually
occurs   during   childhood.    Hemoglobinopathies   can  also  present  with
polycythemia because there is increased oxygen affinity and reduced unloading
of oxygen.  This results in  a  shift in the oxyhemoglobin dissociation curve
and  an  increased  O2  concentration  at  which  50%  O2  delivery   occurs.
Hemoglobin electrophoresis should be done to rule out abnormal hemoglobins as
Ranier,  Chesapeake, Kempsey, and Yakima.  Increased carboxyhemoglobin levels
due to CO2 in  cigarette  smokers  with  a  level  greater  than 6% can cause
polycythemia.  LABORATORY: The following findings may be present Polycythemia
vera.  Increased RBC mass in females > 32 mL/kg and  in  males  >  36  mL/kg,
Normal   arterial   oxygen   saturation   greater   than  92%,  Splenomegaly,
Thrombocytosis with platelets  >  400,000,  Leukocytosis  > 12,000, Leukocyte
alkaline phosphatase, Increased serum B12 and increased  unsaturated  vitamin
B12  binding  capacity  (transcobalamin),  Elevated  uric  acid, cholesterol,
histamine and basophils (greater than  40/mm3), Erythropoietin levels are low
to normal (3-5 U/d in 24 hour urine.   (In  secondary  anemic  and  secondary
polycythemia  these  will  increase to 30 U/d), Plasma volume is increased in
60% of polycythemia vera cases and reduced in stress polycythemia, Hemoglobin
electrophoresis   is   normal   in   polycythemia   vera   but   abnormal  in
hemoglobinopathies.  CarboxyHgb levels are increased in smoking, Bone  marrow
biopsy  will show RBC hyperplasia, absent iron stores and fibrosis during the
spent phase of polycythemia  vera.   There  is panmyelosis.  There are larger
megakaryocytes unlike chronic myeloblastic leukemia and secondary  causes  of
elevated platelets.  DIAGNOSIS: Increased RBC mass + normal oxygen saturation
+  splenomegaly OR Increased RBC mass + normal oxygen saturation + any two of
the following: thrombocytosis,  leukocytosis, leukocyte alkaline phosphatase,
B12 or vitamin B12 binding  capacity.   SYMPTOMS  AND  SIGNS:  There  may  be
headaches,  fatigue,  dizziness,  pruritus  after warm baths, conjunctivitis,
plethora,  tinnitus,   blurred   vision,   epistaxis,  spontaneous  bruising,
sweating, arterial  and  venous  occlusive  events,  weight  loss,  upper  GI
bleeding with peptic ulcer disease, splenomegaly, hepatomegaly, bone pain and
tenderness  of  ribs and sternum.  COMPLICATIONS: Budd-Chiari syndrome due to
hepatic  venous  occlusion,  mesenteric  artery  thrombosis,  gout,  vascular
thrombosis as stroke  and  myocardial  infarction,  hemorrhage, peptic ulcer,
leukemic transformation and increased risk for  complications  and  mortality
form surgery.  Patients should not undergo surgery until the polycythemia has
been  corrected.   TREATMENT: Polycythemia vera is managed by phlebotomy, but
when done alone there may be  an  increased incidence of thrombotic events in
the early stages.  Adding alkylating agents to  phlebotomy  will  reduce  the
thrombotic   events  but  there  be  increased  transformation  to  leukemia.
Hydroxyurea may not cause this increased rate of transformation.  Allopurinol
300 mg/day is used for  uric  acid  reduction,  Cyproheptadine 4-16 mg can be
used for pruritus and H2 receptor blockers for  GI  hyperacidity.   Low  dose
aspirin  to treat the potential proclivity toward thrombosis is controversial
because of the associated bleeding.  The  goal of phlebotomy is to reduce the
hematocrit to about 45%.  Phlebotomy can be performed as often as  every  2-3
days  with  250-  500  cc  removed  unless  the  patient  is  elderly and has
cardiovascular disease then reduce.

                   -POLYCYTHEMIA VERA AND SURGERY-
High surgical mortality is associated with poorly controlled polycythemia due
to  thromboembolic  events.   Phlebotomy  should  be  done  to  decrease  the
hematocrit  to < 45% prior to elective surgery.  Platelet counts < 50,000/mm3
or > 1,000,000 should be  evaluated  with bleeding times and corrected before
surgery.  A platelet count of 50,000 usually gives sufficient hemostasis  for
most  types  of  surgery.   If the count is < 20,000, spontaneous bleeding is
common.

                       -POLYMYALGIA RHEUMATICA-
Polymyalgia rheumatica (PR)	is a disease  of  the  elderly  characterized  by
proximal  muscle  aching  and stiffness of the shoulder, neck and hip girdle.
Polymyalgia can coexist with giant  cell  arteritis  in 15% of cases.  On the
other hand, about 50%  of  patients  with  giant  cell  arteritis  will  have
polymyalgia  rheumatica.   Patients  with  polymyalgia rheumatica do not need
temporal artery biopsy routinely,  unless  there  are  symptoms of giant cell
arteritis.  The age at onset is usually in patients that are 60 or older, and
the incidence increases with age.  Females are more  commonly  affected  than
men  in  a ratio of 2:1.  The incidence is about 50/100,000 patients over the
age of 50.  The cause  is  unknown,  but  is  has  been reported in twins and
families,  and  has  been  associated  with  human  leukocyte  antigen  (HLA)
determinants.  The disease has not been  found  to  be  due  to  myositis  or
vasculitis.   CLINICAL: The patients may present abruptly or insidiously with
pain  and  stiffness  of  the   proximal   muscle  girdles  that  is  usually
symmetrical.  The symptoms are particularly common  in  the  morning  due  to
prolonged  inactivity.   The  patient typically complains of the inability to
get out of bed in the morning.  Physical examination reveals no weakness, but
there may be tenderness of  the  muscles on palpation.  The temporal arteries
should  be  examined  in  every  patient  to  rule  out  concurrent  temporal
arteritis.  There  may  be  mild  inflammation  of  the  joints.   Associated
findings  may  include weight loss, fatigue, low grade fever, depression, and
carpal tunnel syndrome.  LABORATORY:  The  Westergren ESR is usually elevated
to greater than 50.  A normochromic  anemia  is  common,  and  there  may  be
increased platelets.  The creatine phosphokinase is normal and the rheumatoid
factor is negative.  However, remember that about 5% of patients over the age
of 60 will have a positive rheumatoid factor without disease.  ANA is usually
negative.   There  has been a slight association with HLA-DR4/DR/CW3.  Immune
complexes may be seen.   Liver  enzymes, especially the alkaline phosphatase,
can be elevated in 30%.  Bone scans may show increased  uptake  around  large
joints.  X-rays are negative.  Synovial fluid is negative.  The EMG is normal
as  are  muscle  biopsies.   Biopsy of the temporal muscle may be positive if
there  is  coexisting   temporal   arteritis.   DIFFERENTIAL  DIAGNOSIS:  The
differential diagnosis includes fibromyalgia,  hypothyroidism,  polymyositis,
depression,  rheumatoid arthritis, and other connective tissue disease, viral
myalgia, and occult  infection  or  malignancy.   TREATMENT: The treatment of
choice is prednisone.  The average  starting  dose  of  prednisone  is  10-15
mg/day.   With  this  minimal  dose,  the patient should improve dramatically
within a few days.  After about  1  month,  the prednisone is tapered by 1 mg
every 1-4 weeks, aiming at a goal of  5-7.5  mg/day.   This  dose  should  be
continued  for  about  18 months to 2 years, if there is no exacerbation.  At
this point, the prednisone is further decreased by 1 mg every 2-4 weeks until
the prednisone is discontinued.  While the patient is taking prednisone watch
for drug complications such  as  infection, avascular necrosis, osteoporosis,
cataracts,  hypokalemia,  infection,  water  retention,  worsening  of   CHF,
gastritis  and  peptic  ulcer.  Polymyalgia usually lasts from 1-4 years, but
the prognosis is good.  However, relapses are common.

                    -POLYMYOSITIS/DERMATOMYOSITIS-
Polymyositis and dermatomyositis (PM/DM)  occur  at  two different periods in
life.  The first peak occurs in childhood below the age of 15 and the  second
peak is in adulthood between 45 and 55 years of age.  It has a preference for
females  in  a  ratio  of  2:1  and belongs to a class of diseases called the
inflammatory myopathies.  The disease is  not  rare,  and is less common than
SLE or  PSS  (progressive  systemic  sclerosis),  but  is  more  common  than
polyarteritis  nodosa.   The  cause is unknown and is characterized by muscle
weakness.  Other  diseases  can  mimic  PM  such  as  drug induced myopathies
(gembirozil,     lovastatin,     steroids,     tryptophan,     penicillamine,
hydroxychloroquine, colchicine), alcoholic  myopathy,  metabolic  myopathies,
viral  myositis, hypothyroidism, and inclusion body myositis.  Inclusion body
myositis usually occurs in patients  over  the  age of 50, affects the distal
muscles, does not respond to prednisone,  and  has  characteristic  inclusion
bodies  on  muscle  biopsies  identified by electron microscopy.  Polymyalgia
rheumatica usually causes more pain than weakness and occurs in patients over
the age of 50.  HIV  and  zidovudine  therapy  can also cause a polymyositis.
Other diseases that can produce weakness  would  include  myasthenia  gravis,
multiple sclerosis, amyotrophic lateral sclerosis and Eaton-Lambert syndrome.
These  can  usually  be  identified by EMG and clinical symptomatology.  If a
patient  with   polymyositis   has   skin   manifestations,   it   is  called
dermatomyositis.  There is an increased risk for  malignancy,  especially  in
patients  with  dermatomyositis.   The frequency varies from 8-30% in DM.  In
patients older than 40 years,  about  10%  of those with polymyositis and 30%
with dermatomyositis have an associated malignancy.  In most  patients  there
should be a routine chest x-ray, pelvic examination and ultrasound, mammogram
and  stool  occult  blood.   It  is  usually  not  worthwhile to search for a
malignancy if there are no  symptoms  suggestive of such.  The malignancy may
be present from the start or may develop months following the  onset  of  the
disease.  CLINICAL: The onset of the disease can be sudden or insidious.  The
onset  is more acute in children and more insidious in adulthood.  Otherwise,
the symptoms tend to be the same.   The patient may report an infection prior
to the onset.  The onset is characterized by proximal muscle weakness, muscle
tenderness, polyarthralgias, Raynaud's phenomenon, rash, dysphagia, dysphonia
fatigue, fever and weight loss.  Neck flexor weakness is common and occurs in
about 66%.  The muscle weakness usually  progresses  over  weeks  to  months.
They  have weakness of the shoulder and pelvic girdle, and have difficulty in
climbing steps, getting out  a  chair,  raising  the arms above the shoulder,
(combing the hair) and raising the head from  a  pillow.   Dysphonia  may  be
present secondary to weakness of the laryngeal muscles.  Patients may develop
dysphagia  and regurgitation secondary to involvement of the striated muscles
of the pharynx and esophagus.   The  characteristic  rash is a dusky red rash
that can be seen over the malar area of the face, neck, shoulders,  forearms,
lower   legs,   elbows,  knees,  medial  malleoli,  dorsum  of  the  proximal
interphalangeal and metacarpophalangeal  joints,  and  upper  chest and back.
The  scaly  patches  that  develop  over   the   dorsum   of   the   proximal
interphalangeal  and  metacarpophalangeal  joints is known as Gottron's sign,
and is fairly specific.  There may also  be hyperemia of the base and lateral
aspects of the fingernails.  Typically there may be a periorbital edema  with
a  purplish  suffusion  over  the upper eyelids.  This latter rash is usually
pathognomonic of DM.  Some patients,  particularly in childhood, will develop
subcutaneous calcification which is similar to that of PSS,  but  is  usually
more  extensive  (calcinosis  universalis).  Polymyositis can also develop in
association with Sjogren's  syndrome,  SLE  or  scleroderma.  In these latter
patients there may be a high incidence of Raynaud's phenomenon.  Patients may
also  develop  dyspnea  and  cough  secondary  to  interstitial  pneumonitis.
Cardiac involvement  can  lead  to  conduction  disorders,  arrhythmias,  and
abnormal  systolic time interals.  Abdominal symptoms, such as hematemesis or
melena from GI ulcerations, are more  common in children than adults, and may
cause perforations.  There have been some cases of acute renal failure  as  a
consequence of rhabdomyolysis with myoglobinuria.  LABORATORY:	The best test
is  the  creatine  kinase  (CK) which is elevated in 95% of cases.  Also, the
aldolase and transaminases may be  eleveated.   The sedimentation rate may be
elevated in about 50% of patients.  Antinuclear  antibodies  are  present  in
many  patients  and  about  2/3  of patients will have antibodies to a thymic
nuclear antigen PM-1  or  whole  thymus  and  thymic nuclear extracts (Jo-1).
These are particularly elevated  in  patients  that  have  interstitial  lung
disease.   Anemia  is not common.  Electromyographic abnormalities consist of
spontaneous  fibrillations  and  positive  sharp  potentials  with  increased
insertional  irritablity,  polyphasic   short   potentials  during  voluntary
contraction, and repetitive, high  freqjuency  discharges  during  mechanical
stimulation.   Muscle  biopsy of the deltoid and quadriceps is diagnostic and
consists of necrosis  of  muscle  fibers  associated  with inflammatory cells
(predominantly T lymphocytes and monocytes).  There  is  variation  in  fiber
size  with  degenerating and regenerating muscle fibers.  Electron microscopy
should be done to exclude  inclusion body mhyositis.  PROGNOSIS: The survival
is approximately 95% at 1 year, 85% at 2 years and 80% at 5  years,  although
patients  with  malignancy  have a poor prognosis.  Complete remission of the
disease is uncommon.  Mortality  is  usually related to aspiration pneumonia,
respiratory failure + infection, malnutrition, and dysphagia.   Mortality  in
children  is  usually related to vasculitis of the bowel.  Patients that have
pulmonary and cardiac involvement have  a more resistant disease.  TREATMENT:
Prednisone is started at 1 mg/kg or about 40-60 mg/day.  While being  treated
with  prednisone  the  CK  should  be  monitored.  CK usually starts to reach
normal around 4-6 weeks with  concomitant  increase in muscle strength.  Once
the levels have reached normal, the dose should be decreased gradually to  20
mg/day  which  should  be maintained for about 1 year, and then tapered again
over 1-2 years.   Any  time  the  CK  rises,  the  prednisone  may have to be
temporarily increased.  Long term prednisone will be needed  to  control  the
disease.   Children  can  be  treated  with  30-60 mg/m2/day.  Be aware, that
increasing weakness may be  due  to  steroid  myopathy,  and not secondary to
progression  of  PM/DM.   If  this  is  the  case  the  steroids  should   be
discontinued    and    the    patient    started    on    immunosuppressants.
Immunosuppressants  consist  of  methotrexate, cyclophosphamide, azathioprine
and chlorambucil.   Immunosuppressants  are  effective  in  patients that are
resistant to prednisone.  NSAIDs are usually not effective.

                   -PORPHYRIA (Acute intermittent)-
Acute  intermittent porphyria (AIP) is due to a deficiency of porphobilinogen
deaminase (PBG) that is transmitted as  an autosomal dominant pattern.  It is
the  most  common  of  the  genetic  porphyrias.   It  has  an  incidence  of
5-10/100,000, although many cases will  have  a  latent  form.   The  highest
incidence  occurs  in  Scandinavia,  the  United  Kingdom and in the Lapland.
Patients that are  clinically  affected  involve  more  women  than men.  The
deficient enzyme activity of PBG is usually about 50% of normal, and is found
in  all  tissues  including  the   liver,   erythrocytes,   fibroblasts   and
lymphocytes.   The  cardinal  features  of  the disease include abdominal and
neurological disturbances  without  skin  lesions.   CLINICAL:  About  90% of
heterozygotes  with  PBG  deaminase  deficiency  will   not   have   abnormal
concentrations  of  heme  pathway  intermediates,  and will not have clinical
manifestations.  However, those patients  that  have the clinically expressed
form, or those with latency will have clinical symptoms that are  induced  by
various  precipitating  factors.  These include drugs, starvation, female sex
hormones,  infections   and   excessive   dieting.    Common  drugs  include,
barbiturates,  griseofulvin,   sulfonamides,   chlordiazepoxide,   phenytoin,
meprobamate,      isopropylmeprobamate,      methsuximide,      glutethimide,
dichloralphenazone, imipramine, methprylon, danazol, methyldopa, tolbutamide,
chloramphenicol,  pentazocine,  chlorpropamide,  and  eucalyptol.   The acute
attack  is  characterized  by  abdominal  pain  which  may  be  localzied  or
generalized.  The acute  attacks  of  AIP  usually  begin after puberty.  The
abdominal pain may be cramping or steady.  There may  be  associated  nausea,
vomiting, constipation, diarrhea, ileus, and abdominal distention.  About 40%
of   patients   will   experience  autonomic  manifestations  such  as  sinus
tachycardia, labile hypertension, sweating, postural hypotension and vascular
spasm of the skin and retina.   If neuropathy occurs during the acute attack,
it is usually preceded by abdominal pain.  The neuropathy can be  sensory  or
motor.  It usually begins proximally in the legs, but can involve the arms or
the  distal extremities.  It may be symmetric, asymmetric or focal.  Patients
will complain  of  pain  in  the  back  and  legs,  and  paresthesias.  Motor
involvement can also affect the cranial nerves.  When it does,  the  7th  and
10th  nerves  are  commonly  involved.   This  can  lead to bulbar paralysis,
pulmonary insufficiency and death.  In severe attacks, patients are unable to
breathe, speak or swallow.  Motor involvement  of the extremities can lead to
a flaccid paralysis over a few days.  Patients may also have central  nervous
systems  such  as  hallucinations,  acute  and  chronic  psychoses, seizures,
cerebellar  and  basal  ganglion   symptoms,  and  depression.   Hyponatremia
develops in some patients that  may  be  due  to  vomiting  or  inappropriate
release  of  antidiuretic  hormone.   LABORATORY:  Patients  with  clinically
expressed  AIP  will  have  have varying amounts of alpha aminolevulinic acid
(ALA) and PBG in the  urine  between  attacks.  Some patients with the latent
form will also have ALA and PBG	in  the  urine.   However,  during  an  acute
attack, there is a substantial increase in the amount of ALA and PBG found in
the  urine.   Patients with hereditary coproporphyria and variegate porphyria
will also have  ALA  and  PBG  in  the  urine.   The  distinction  is made by
measuring stool prophyrins, which are negative in  AIP.   If  the  attack  is
severe,  the  urine  takes  on  a  port  wine color due to the high cntent of
prophobilin.  Suspect AIP if  the  urine  darkens  when  left standing in the
light.  Stool porphyrins are usually normal  in  AIP,  but  may  be  slightly
elevated   in   some   cases.    Patients  are  screened  by  performing  the
Watson-Schwartz  urinary   test   which   detects   urinary   PBG.    If  the
Watson-Schwartz test is positive it should be confirmed by  the  quantitative
column  method  of  Mauzerall and Granick.  A diagnosis of AIP may be made in
greater  than  85%  of  patients  by  demonstrating  decreased  PBG deaminase
activity in the erythrocytes.  TREATMENT: Treatment, for the  most  part,  is
supportive.   All  infections should be treated promptly.  All drugs known to
induce AIP should be avoided, and a good nutritional diet should be employed.
The acute attacks may  be  helped  with  a  high  carbohydreate intake of 400
grams/day or more.  This causes a decrease of prophyrin  precursor  excretion
and  will produce a clinical improvement in some patients.  If the patient is
unable to tolerate an oral intake, IV 10% dextrose should be given to provide
a minimum of 300 grams of carbohydrate/day.  Hematin given IV at 4 mg/kg over
a 30 minute period  q  12-24  hours  is  also  helpful  in aborting the acute
attack.  The response to hematin is usually noted within 48  hours.   Hematin
has  also  been  given prophylactically at 200 mg/week to interrupt recurrent
perimenstrual attacks.  Luteinizing hormone releasing hormone (LHRH) agonists
have also been used to prevent  repeated premenstrual AIP crisis.  Drugs that
may be safely given to patients  with  AIP  include  acetaminophen,  aspirin,
morphine,   steroids,   phenothiazines,  vitamin  K,  nifedipine,  clonidine,
bromides, vancomycin and penicillin.

                   -POST CORONARY BYPASS ISCHEMIA-
After about 7-10 years post-coronary artery bypass surgery, approximately 50%
of  patients  will  have  recurrent angina which is often due to occlusion or
stenosis of bypass grafts.  About 25% of patient will have this difficulty in
the first few  days  following  surgery  due  to  technically difficult graft
placement, poor distal runoff and pericarditis, even in the face of  adequate
antiplatelet  therapy.   During  the  first  year  post  bypass there will be
further stenosis secondary  to  fibrous  intimal  hyperplasia  of the grafts.
From year 1-6 following bypass surgery, atheroswclerotic graft closure occurs
at a frequency of 2% per year.  At the same time that vein graft attrition is
occurring, there is evidence of new native coronary artery stenosis in 33% of
patients by 5-7 years and 50% by 10 years post bypass  surgery.   MANAGEMENT:
If  angina  recurs during the first 6 years following bypass surgery, cardiac
catheterization should be carried out,  and  if  the angina occurs during the
first 3 years post-bypass surgery, PTCA should be performed for focal disease
in by pass grafts or native arteries.   The  ideal  patient  for  PTCA  after
bypass  has focal narrowing at the distal anastomosis of a saphenous vein, or
an internal  mammary  artery  graft.   These  areas  are  very susceptible to
dilation and the restenosis rate is low.  Stenosis in the main  body  of  the
vein  graft will dilate well, but in some patients the restenosis rate may be
as high as 50%.  Patients that  have  PTCA within the first 3 years following
bypass surgery have the lowest complication rates  and  the  highest  success
rate.  Obsolescent grafts that have become diffusely diseased and degenerated
are  not good candidates for PTCA because of the risk for distal embolization
by vein-graft debris.  Therefore,  patients  that  are 3-6 years post bypass,
are only considered for PTCVA if there are focal lesions in  grafts  free  of
diffuse  atherosclerosis.   Patients that have diffuse atherosclerosis should
be treated medically as should  patients  presenting  later than 6 years post
bypass surgery unless they are refractory to medical treatment, in which case
repeat bypass surgery may be considered.  Repeat bypass surgery carries  with
it  an  increased  risk  for myocardial infarction,  mediastinal bleeding and
peri-operative death as well as  stroke.   The patient must have large distal
vessels and adequate veins or mammary arteries along with diffusely  occluded
or degenerated grafts in order to be a suitable candidate for repeat coronary
artery bypass surgery.

                           -POST PTCA CARE-
EXERCISE  TESTING:  The  patient  should have a Thallium exercise stress test
performed following  PTCA  in  order  to  assess  for restenosis.  Restenosis
usually occurs during the first  3  months  following  PTCA.   Early  testing
should be avoided unless there is some particular reason, such as determining
if  the  patient is a candidate for returning to work or is going to enter an
exercise training program.  Otherwise,  the  testing should be deferred until
between months 1 and 3 and again between months 3 and  6.  In  about  1/3  of
patients  the thallium image doesn't revert to normal until about 1 month and
therefore performing the thallium imaging before this might indicate that the
PTCA was unsuccessful.  Restenosis is  asymptomatic in about 10% of patients.
If restenosis is detected, catheterization should be carried out  again.   In
preparation  for this the patient should be taking a calcium channel blocking
agent and ASA.  Many patients  that  have recurrent chest pain following PTCA
do not have restenosis found on maximal thallium exercise stress testing.  In
these patients the prognosis  is  excellent  and  they  can  return  to  full
activity.   A  second  PTCA  usually  is more successful and accompanied by a
lower complication rate than the first  PTCA and most patients do not develop
a restenosis after the second PTCA.  After PTCA involving  a  single  vessel,
the  closure rate is about 20-30%.  PROCEDURE COMPLICATIONS: In general, most
patients, following PTCA  have  no  major  complications  from the procedure.
However, some patients will develop a hematoma at the femoral area.  Most  of
these  will  not  require  evacuation  of  the  hematomaq  and  will  resolve
spontaneously.   Sometimes  a  pseudoaneurysm  will  develop  which  has  the
potenital  to  hemorrhage  into  the thigh and lead to arterial insufficiency
from femoral thrombosis or embolization.  The pseudoaneurysm is characterized
by a pulsatile swelling associated with  a systolic bruit which is present in
about 50% of cases.  If  there  is  a  continuous  bruit  present,  this  may
indicate  the  development  of an arteriovenous fistula which usually develop
from arterial and venous femoral punctures.   If  the fistula is large it can
result in CHF and necessitate surgical closure.  If the arteriovenous fistula
is small, it may close spontaneously.  Diagnosis and follow-up of the fistula
is with color flow Doppler imaging.  Anemia may develop following PTCA due to
blood loss but usually is not  sufficient  to  warrant  transfusion  or  iron
replacement.   A  third  complication  of  PTCA  is  nephropathy secondary to
contrast media.  The nephropathy  may  not  become  apparent for several days
following the  procedure.   The  nephropathy  is  usually  non-oliguric,  but
occasionally  is  oliguric  and  will  require  dialysis.   Risk  factors for
contrast renal failure include  pre-exisiting azotemia and diabetes mellitus.
PROGNOSIS: Studies have shown that for single vessel PTCA, the survival at  5
years is about 98% and at 10 years is 92%.  A second PTCA during the 10 years
was  required  in  about  27%  and 18% required bypass surgery.  For multiple
vessel PTCA the survival rate  at  5  years  was  88% and 16% required bypass
grafting.  MEDICATIONS: Most patients will be discharged  from  the  hospital
after PTCA with prescriptions for daily ASA, calcium channel blocking agents,
and  sublingual  nitroglycerin  as  Nitrostat.   If  the patient is unable to
tolerate ASA, persantine may be  substituted.   ASA  has been shown to reduce
the risk of acute vessel closure in  the  hospital.   Warfarin  has  not  had
favorable  effects  on the closure rate, but could be used for about 3 months
in patients that have arterial dissection or large coronary arterial thrombi.
Patients that do not demonstrate restenosis  on exercise imaging studies at 6
months may  be  considered  for  discontinuing  antianginal  therapy  and  be
continued  only on daily ASA and sublingual nitroglycerin.  It is recommended
however that all patients have  annual  maximal treadmill testing in order to
detect new coronary lesions and those few that might develop restenosis late.
Lipid lowering drugs should be continued as studies have shown that they  may
reduce closure rate.

               -PREGNANCY AND CONGENITAL HEART DISEASE-
The incidence of congenital heart disease among all live births in the USA is
.8% or 15% in those with one parent having congenital heart disease.  Persons
with autosomal dominant  conditions  as  Marfan's  syndrome  or  hypertrophic
cardiomyopathy  have  a  50%  chance  of  transmitting them to the offspring.
AORTIC STENOSIS: Congenital aortic stenosis usually affects males.  Pregnancy
is not recommended for those  with  severe  aortic stenosis prior to surgical
correction because of the high maternal  (17%)  and  fetal  (32%)  mortality.
Medical  treatment  includes  bed rest in the left lateral decubitus position
starting early in the  second  trimester,  digitalization, and an increase in
preload.  Vasodilators, beta blockers and verapamil should not  be  given  in
critical  aortic  stenosis.   Fetal  mortality  is  high  with valve surgery.
Therefore,  corrective  valvular  surgery   is  indicated  before  pregnancy.
EISENMENGER'S CYANOTIC HEART DISEASE: Those lesions  causing  cyanotic  heart
disease  include hypoplastic left heart syndrome, single ventricle, tetralogy
of  Fallot,  transposition  of  the  great  vessels,  tricuspid  atresia  and
Eisenmenger's syndrome.  Some of  these  patients will reach childbearing age
with a maternal  mortality  of  4%  and  fetal  mortlaity  of  about  50%  in
uncorrected  tetralogy  and  even  higher  in  Eisenmenger's  syndrome.   All
patients  should  be  strongly  advised  against  pregnancy  without surgical
correction.  Should pregnancy occur,  therapeutic abortion should be advised,
but if refused, treat as for aortic stenosis maintaining venous return.  Poor
prognostic  signs  include  a  hematocrit  >60%,  recurrent  syncope,   right
ventricular  systolic  pressures  >  120  mm Hg, and oxygen saturation < 80%.
PULMONIC STENOSIS: Mild  to  moderate  pulmonic  stenosis is tolerated fairly
well during pregnancy.  Inferior vena  cava  compression  should  be  avoided
particularly  in  the  third trimester and during labor and delivery.  Severe
pulmonic stenosis  should  be  corrected  prior  to  pregnancy.  HYPERTROPHIC
CARDIOMYOPATHY: HCM is well tolerated during pregnancy, but  hypotension  and
hypovolemia  should  be avoided.  Beta blockers may be used if indicated, but
their  use  during  labor   and   delivery  is  controversial.   Prophylactic
antibiotics should be used at delivery.  COARCTATION OF THDE AORTA:  Patients
with coarctation of the aorta may have several complications such as cerebral
hemorrhage   from   associated  intracranial  berry  aneurysms,  aortic  root
dissection and rupture, CHF and endocarditis.   Coarctation of the oarta is a
relative contraindication  to  pregnancy  as  there  can  be  a  3%  maternal
mortality.   Blood  pressure must be well controlled throughout pregnancy and
antibiotic prophylaxis must  be  given  at  delivery.   VSD AND APTENT DUCTUS
ARTERIOSUS: Both of these conditions  are  tolerated  well  during  pregnancy
unless there is significant shunting.  Ideally these defects should be closed
during  childhood.  Antibiotic prophylaxis is indicated for both at delivery.
ATRIAL SEPTAL DEFECTS: Patients that have  >  2:1 left to right shunts do not
tolerate  pregnancy  well  because  they  may  develop   pulmonary   vascular
congestion,  particuloarly  after  the  3rd  month  of  gestation.  Treatment
includes  diuretics.   Ideally  these   defects  should  be  repaired  during
childhood.  Prophylactic antibiotics are not  required  at  deliver.   MITRAL
REGURGITATION  AND  PROLAPSE:	Both  of these conditions are usually tolerated
well during pregnancy if  the  symptoms  are mild or asymptomatic.  Diuretics
may be needed if pulmonary congestion develops.  Endocarditis prophhylaxis is
needed for both.  MARFAN'S SYNDROME: Marfan's syndrome carries a  significant
maternal  risk  for  aortic  dissection  and  rupture  and patients should be
counseled against pregnancy,  or  if  pregnant,  advised  to have therapeutic
abortion.  If she elects to continue pregnancy, the  hypertension  should  be
controlled  and  beta  blocker  therapy  considered.   Since  there is a high
incidence of aortic regurgitation  and  mitral valve prolapse associated with
Marfans, antibiotic prophylaxis is indicated at delivery.   MITRAL  STENOSIS:
About  25%  with MS will have their initial symptoms during pregnancy, mostly
during  the  latter  portion  of   gestation.   Digitalis  is  usually  given
prophylactically for atrial fibrillation, since AF and  pulmonary  edema  are
assoicated  with  a  15%  mortality.   Cardioversion  is  indicated for AF if
refractory AF develops.  Chronic AF  and  a history of thromboembolism should
be anticoagulated with heparin.  Mitral valvotomy is indicated for  resistent
failure.  Epidural anesthesia is preferred in labor.

            -PREGNANCY AND CONTRACEPTION (NEWER METHODS)-
NORPLANT: The Norplant subcutaneous implant was approved in December of 1990.
Because there are menstrual irregularities associated with its use, about 50%
will have the  implant  removed  after  about  3  years.   About a third will
complete the 5 year treatment, and of these, about 3/4 will request a renewal
with the implant.  In spite of this, it is convenient, and compliance is  not
an  issue,  and it is rapidly reversible, with immediate return to fertility.
Six non-biodegradable silicone rubber capsules containing a total of 36 mg of
levonorgestrel are buried in  the  subcutaneous  tissue  of the arm and these
release about 30 ug per day.  This will prevent contraception by  suppressing
ovulation  and  also  by  producing a thick cervical mucus which inhibits the
sperm entry.  The failure rate in the  first year is 0.04% and 1.1 percent in
the fifth year.  If the patient is obese there has been shown to be a  higher
failure  rate.   In  about  one  third  of  patients  there will be irregular
bleeding and prolonged bleeding  and  in  some, particularly later, will have
amenorrhea.  The irregular bleeding improves with time and after about 1 year
there may be regular bleeding that is timely.  (at 2  years  about  60%  will
have regular bleeding).  If the patient does experience troublesome bleeding,
and  wants  to  remain with the system, then they may be treated with ethinyl
estradiol .05 mg for 20  days  (best  for controlling irregular bleeding), OR
conjugated estrogen 1.25 mg for 1-3 weeks, OR levonorgestrel, .03 mg bid  for
20  days OR Ibuprofen 800 tid for five days.  (Ibuprofen is best for reducing
the length of bleeding).  These are all  started on the 8th day of the cycle.
Of these, Levonorgestrel is the least effective.  The best candidates for the
Norplant system are those patients who have a contraindication  to  estrogen,
women  who  can't  comply  with  daily  doses  of  oral contraceptives, those
patients who smoke and are  older  than  35 and want contraception, and those
that  may  want   an   immediate   return   to   fertility.    The   absolute
contraindications  are  undiagnosed  vaginal  bleeding, active liver disease,
benign or malignant liver  tumors,  known  or suspected breast cancer, active
thrombophlebitis or thromboembolic disease, and pregnancy.  If  patients  are
concurrently  taking  drugs  such  as  phenobarbital,  anti-seizure drugs and
rifampin, the serum levels of the levonorgestrel may dip to below therapeutic
and protective levels with pregnancy resulting.  The average cost for 5 years
of treatment varies, but at  the  current  time  is  $ 450.00 - 750.00.  Some
insurance  carriers  cover  this  type  of   contraceptive.    DEPTO-PROVERA:
Depo-Provera (medroxyprogesterone acetate or DMPA) was approved in the USA in
the  late  part  of  1992.   It  is  estimated that more than 9 million women
world-wide are  using  this  form  of  contraceptive.   Its  use equates with
sterilization as far as efficacy.  Of course, if the patient  doesn't  return
to  the doctors office at 3 month intervals, then the efficacy is diminished.
This is the critical factor, for  the  patient  will have to return 4 times a
year to the physician's office for injection.  The typical pregnancy rate for
the first year is estimated to be .3% and, 0.9% for the five year  cumulative
rate.  The cost varies, but in general at the current writing, is about 25-50
dollars  for  a  3  month  period.   DMPA will reduce the risk of ovarian and
endometrial cancers and  helps  endometriosis.   The  overall risk for breast
cancer is not increased.  There may be a minor increase  in  cervical  cancer
and  patients  should  be  monitored with PAP smears.  DMPA has a tendency to
reduce sickle cell crises  and  seizures.  Protection is afforded immediately
after the 150 mg intramuscular dose is given.  Patients should be told not to
rub the injection site as this has been shown to shorten the efficacy.   Like
the  Norplant  system,  DMPA  works  by  thickening  the  cervical mucous and
preventing ovulation.  The dose is usually  given  during the first 5 days of
menses so that pregnancy will be averted and no back up method of  protection
is required because of the instant protection.  Menstrual cycles are going to
change,  just  as with the Norplant.  There will be spotting and bleeding and
most will  eventuate  with  amenorrhea  which  is  different  course than the
Norplant.  One cannot  predict  the  menstrual  irregularities.   Minor  side
effects  may occur as weight gain, nausea, headaches, dizziness mood changes,
hair loss, depression and decreased libido.  The lipids may change with minor
decreases  of  the  HDL  and  increase  of  the  LDL.   If  the  patient  has
hyperlipidemia, this may  be  a  relative  contraindication.  For post partum
protection, the drug should  be  given  within  five  days  of  delivery  for
non-lactating  women,  and  at six weeks for lactating women.  It is probably
safe for women who breast feed.   DMPA is also useful for post-abortion.  The
usual absolute contraindications are essentially those  associated  with  the
Norplant  system  (see Norplant).  One major drawback for the injectable DMPA
is that the median period for return to fertility is about 9-10 months.  This
may not be agreeable for some  women  who may want to become pregnant sooner.
About 70% of women will become pregnant within 1 year  after  stopping  DMPA,
and  85%  will  return  to  fertility  by 2 years.  POST OOITAL MORNING AFTER
PROTECTION: Even though this is not a new method of treatment it is presented
so that it can be compared with Mifepristone, which will probably be approved
soon.  Norgestrel .5 mg and  ethinyl  estradiol  50 ug (Ovral) has been used,
giving two tablets within 72 hours after coitus when barrier methods fail, or
there is unplanned intercourse.  With this, the  endometrium  sloughs,  which
makes  nidation unfavorable.  Difficulties with this therapy is that the high
dose may cause vomiting with poor  absorption.  Giving the medication with an
anti-emetic will help.  A better morning after drug that will  probably  soon
be  available  will  be  Mifepristone  (RU 486).  This has been used in Great
Britain for some time.  The advantage  to  RU 486 is that this medication may
be given past the 72 hour period.

                 -PREGNANCY AND DRUGS TO BE AVOIDED-
Coumarin  compounds,   colchicine,   doxycycline,   ergotamine,  erythromycin
estolate, ethacrynic acid, griseofulvin,  lindane,  lisinopril,  mebendazole,
metolazone,    metronidazole,   misoprostol,   norfloxacin,   phenylbutazone,
piroxicam, tetracyclines, tolazamide, tolbutamide, valproic acid.

             -PREGNANCY AND DRUGS THAT MAY BE INDICATED-
The following drugs  are  indicated  for  some  conditions, but may adversely
affect the fetus or  other  medication  may  be  preferable.   Acetazolamide,
acyclovir,   albumin,   albuterol,   amikacin,   amiloride,  aminoglycosides,
amitriptyline, aspirin (avoid  in  3rd trimester), atenolol, benzodiazepines,
beta  blockers,  benztropine  mesylate,  betamethasone,  bumetanide,  calcium
channel   blockers,    carbamazepine,    chlorpheniramine,    chlorthalidone,
cholestyramine,  clonazepam,  clonidine,  codeine  (avoid  in  1st  and third
trimester),    crotamiton,     cyclic    antidepressants,    cyclobenzaprine,
cyproheptadine,  dextromethorphan,  diazepam,  diazoxide,  didanosine  (DDI),
digoxin,  diltiazem,  dipyridamole,  disulfiram,   ephedrine,   ethosuximide,
fentanyl (avoid in 1st and 3rd trimester), furazolidone, furosemide (avoid in
1st    trimester),    gentamicin,    glipizide,   haloperidol,   hydralazine,
hydrochlorothiazide (avoid  in  first  trimester),  ibuprofen  (avoid  in 3rd
trimester), indapamide, indomethacin (avoid in 3rd trimester),  ketoconazole,
labetalol,  lithium  (avoid  in 1st and 3rd trimester), lorazepam, meperidine
(avoid in  1st  and  3rd  trimester),  meclizine, metaproterenol, methyldopa,
metoprolol, minoxidil, morphine (avoid in 1st and  3rd  trimester),  nadolol,
naproxen  (avoid in 3rd trimester), narcotic analgesics (avoid in 1st and 3rd
trimester),  nifedipine,   nitrates,   NSAIDs   (avoid   in  3rd  trimester),
omeprazole,   oxybutynin,   pentamidine,    phenobarbital,    phenothiazines,
phenytoin,  prazosin, primidone, procainamide, prochlorperazine (avoid in 3rd
trimester),  propoxyphene,  propranolol,  pseudoephedrine,  pyrantel pamoate,
pyrazinamide, pyrilamine, quinacrine,  quinidine,  rifampin,  spironolactone,
oral   steroids,   streptokinase,  sulfonamides  (avoid  in  3rd  trimester),
thiazides (avoid in 1st trimester), tissue plasminogen activator, tobramycin,
triamterene,  tricyclic   antidepressants,   trimethobenzamide,  trimethoprim
(avoid in  3rd  trimester),  trimethoprim/sulfa  (avoid  in  3rd  trimester),
vancomycin, verapamil, zidovudine (AZT).

                    -PREGNANCY AND HEART DISEASE-
PERIPARTUM CARDIOMYOPATHY:  Peripartum  cardiomyopathy  has  an  incidence of
about 1 in 15,000  deliveries  in  the  USA.   Predisposing  factors  include
toxemia,  twinning  and hypertension, with a high prevalence in Afro-American
women and older women.  Peripartum cardiomyopathy (PC) begins near term or in
the postpartum period, and may  have  a  50%  mortality within 5 years with a
high incidence in subsequent pregnancies.  Active myocarditis may be  present
in  about  33%.   Any  patient  that develops CHF and dyspnea during the last
month of pregnancy and the six  month's post-partum should be suspect.  About
7-50% will develop symptoms in the month prior to delivery and the  remainder
post-partum.   Symptoms  include chest pain, hemoptysis, paroxysmal nocturnal
dyspnea, palpitations and arrhythmias which consist of atrial and ventricular
ectopy, along with  atrial  fibfrillation.   Ventricular tachycardia is rare.
Mural thrombi in the left ventricle are common and embolism occurs  in  about
33%.   The  echocardiogram demonstrates LV and possibly left and right atrial
dilatation.  Pericardial effusion may be  seen.  Doppler will show mitral and
tricuspid   regurgitation.    Therapy    includes,    digitalis,    diuretic,
vasodilators, bed rest and anticoagulation with subcutaneous heparin.  MITRAL
REGURGITATION:  MR  may  be  caused  by  floppy valve syndrome, endocarditis,
hypertrophic cardiomyopathy,  rheumatic  heart  disease  and ruptured chordae
tendineae.  MR is usally well tolerated during pregnancy, but if symptomatic,
after load reduction with hydralazine, preload reduction  with  nitrates  and
diuretics  may be used.  Atrial fibrillation is treated with digoxin.  AORTIC
REGURGITATION: Chronic aortic regurgitation  is  well tolerated with possible
reduction  of  the  regurgitant  volume  as  peripheral  vascular  resistance
decreases.  Causes include congential  bicuspid  valves,  rheumatic  disease,
endocarditis,   and  floppy  valve  syndrome.   HYPERTROPHIC  CARDIOMYOPATHY:
Obstructive hypertrophic  cardiomyopathy  is  usually  well  tolerated during
pregnancy, but hypovolemia must be avoided.   Cardioselective  beta  blockers
and calcium channel antagonists may be used to improve LV diastolic function.
High  risk  patients  as identified by Holter with severe complex vetnricular
arrhythmias should be treated with procainamide, quinidine and beta blockers.
Spinal  and  epidurals  should  be  avoided.   C-section  anesthesia  may use
halothane.  Avoid inferior vena cava pressure.

                      -PREGNANCY AND THE HEART-
In  order  to  understand  some  of  the changes in the diseased heart, it is
necessary  to	understand  the  normal  physiologic  changes  in pregnancy.
NORMAL CARDIOVASCULAR  CHANGES  DURING  PREGNANCY:  CARDIAC  OUTPUT:  Cardiac
output shows a modest increase by the end of the first trimester.  However by
the  10th  week  of  pregnancy  the  cardiac  output will increase by 30-50%.
Maximal peaks are  usually  achieved  by  the  20-24  week followed by slight
decrease near term possibly due to compression of  the  inferior  vena  cava.
Early first trimester cardiac output is accomplished mainly by an increase in
stroke  volume.   As  the  pregnancy  progresses,  the heart rate contributes
mostly to the cardiac output increase,  with  falling of the stroke volume to
pre-pregnancy levels.  HEART RATE: Heart rate shows  a  progressive  increase
during  pregnancy  so  that  there is a 10-25% increase.  There is peaking at
term to about 15 beats per  minute above pre-pregnancy levels.  BLOOD VOLUME:
Most of the increase in blood volume is by an increase in the plasma  volume.
The  red  blood  cell  mass  increases by about 24% and usually later.  Blood
volume will increase by about 40-50%  starting  at about the 6th week.  There
are larger increases in multigravid and multiparous women.  The blood  volume
shows a progressive rise during pregnancy.  Since the plasma volume increases
disproportionately  to  the  increase  in  red  blood  cell  mass, there is a
relative hemodilution with  the  hematocrit  ranging  between  33-38% and the
hemoglobin between 11-12 gm/dl.  STROKE VOLUME: The  stroke  volume  shows  a
small increase during the first trimester, a large increase during the second
trimester  and then a reduction in the 3rd trimester, eventually returning to
pre-pregnancy  levels.   SYSTEMIC  AND  PULMONARY  VASCULAR  RESISTANCE:  The
systemic and pulmonary vascular resistance  are decreased slightly during the
first trimester and then plummet during the second trimester, with a moderate
decrease during the 3rd  trimester.   SYSTOLIC  BP:  The  systolic  BP  shows
essentially  no  change  during the first and third trimester, but during the
second trimester there is a small decrease in the systolic BP.  DIASTOLIC BP:
The diastolic BP shows  a  small  decrease  during  the first trimester and a
moderate decrease in the second trimester.  In the 3rd trimester there  is  a
return  to baseline essentially.  PHYSICAL EXAMINATION: Physical findings and
symptoms are  present  during  pregnancy  that  can  easily  be confused with
diseased states as the following will demonstrate.  During pregnancy there is
accentuation  of  the  1st  heart  sound,  and  its  splitting   may   become
exaggerated.   Most  pregnant women will have an early or mid-systolic murmur
at the lower left sternal border  or  the 2nd right intercostal space.  These
systolic  murmurs  may  imitate  pulmonic  stenosis  and   aortic   stenosis,
respectively.  There may also be a diastolic murmur at the lower left sternal
border  that  may  mimic  mitral or tricuspid stenosis, or aortic or pulmonic
insufficiency.  Right  ventricular  and  pulmonic  arterial  pulses are often
palpable because of the increased blood volume.  An S3 sound may  occur  late
in pregnancy in 90% of patients.  S4 gallops are rare.  Continuous murmurs of
cervical  venous  hum  and mammary souffle are common and may be difficult to
differentiate  from  patent  ductus   arteriosus  or  arteriovenous  fistula.
Persistent splitting of S2 may imitate atrial septal defect.   There  may  be
basilar  crepitant  rales  secondary  to  mechanical  compression.   Late  in
pregnancy there is a laterally displaced ventricular apex.  Late in pregnancy
peripheral   edema  and  jugular  vein  distention  may  occur  which  mimics
congestive heart  failure.   Patients  may  complain  of  dyspnea, orthopnea,
paroxysmal nocturnal dyspnea, syncope and dizziness due to compression of the
inferior vena cava.  Chest pain may occur that is not unlike that  of  angina
pectoris.  ATRIAL SEPTAL DEFECT: Many women become pregnant during the second
and  third  decade  and at this time in there lives they are able to tolerate
the extra burden of ASD.   In  the absence of pulmonary hypertension pregnant
women will usually tolerate pregnancy well.   If  pulmonary  hypertension  is
present,  dyspnea  and  right  heart  failure  will intervene.  Atrial septal
defect is one of  the  most  common congenital heart lesions appearing	during
the child bearing years, and usually is the ostium secundum variety.  Many of
the physical findings in ASD are those found in normal pregnancy.  There is a
systolic ejection murmur in the second left  intercostal  area,  a  diastolic
rumble at the lower left sternal border, wide fixed splitting of S2, slightly
increased P2 and right ventricular enlargement.  Echocardiography in ASD will
show  right  ventricular  enlargement,  left  to right shunt with Doppler and
abnormal or paradoxical septal movement.  Injection of agitated saline during
Echocardiography will demonstrate the  bubbles  passing  through to the right
atrium.  The EKG may show right intraventricular conduction delay  and  right
axis  deviation  if  of  the secundum type.  In the primum type there is left
axis deviation.  Supraventricular  arrhythmias  may appear.  Complications of
ASD may include paradoxical embolization, congestive heart failure, pulmonary
hypertension,  shunt  reversal,  supraventricular  arrhythmias,  edema,   and
thromboembolism.   In  Eisenmenger's  syndrome  (pulmonary  hypertension  and
reversal  of  shunt)  mortality  of  the  mother may range from 36-56%.  This
complication is usually not seen  in  females  who  are less than 30 years of
age.  Bacterial endocarditis is rare in association with an  ostium  secundum
defect  and prophylaxis is not indicated.  This does not apply if the patient
has an ostium primum  defect.   VENTRICULAR SEPTAL DEFECT: Ventricular septal
defects are not usually seen in adults because they  spontaneously  close  or
are  repaired during childhood.  Patients that have uncomplicated VSD usually
tolerate pregnancy  well  because  the  peripheral  and pulmonary resistances
usually fall, with no change in the left to right shunt.  If there is a  huge
defect,   CHF   can   develop.    Complications   of  VSD  include  pulmonary
hypertension.  If this is  suspected,  cardiac catheterization should be done
to evaluate the pulmonary pressure.  The BP should not be allowed to fall  in
order  to  prevent  shunt reversal.  Bacterial endocarditis is a complication
and antibiotic prophylaxis is indicated.   Physical examination will reveal a
harsh holosystolic murmur at the left sternal border which may be  associated
with  a thrill.  If the defect is large, there may be diastolic rumble at the
apex.  If pulmonary  hypertension  develops,  the  left  to  right shunt will
decrease and also the murmur.  Chest  x-ray  will  show  increased  pulmonary
markings  in  large  VSD  defects.   The left atrium and and ventricle may be
enlarged.  Echocardiography will demonstrate  the  size  and place of the VSD
along with left atrial and ventricular dilatation.  EKG  will  show  LVH  and
left  atrial  abnormality  if  the  defect  is large.  If there is right axis
deviation with bi-ventricular  enlargement,  pulmonary hypertension should be
suspected.  COARCTATION OF THE AORTA: Coarctation of the aorta is more common
in men by a ratio of 3:1.  Coarctation is often associated  with  a  bicuspid
aortic  valve.   Ideally,  coarctation  of  the  aorta  should  be surgically
repaired in childhood prior to  pregnancy.   Fetal mortality may approach 15%
with intrauterine growth retardation occurring secondary to an  insufficiency
of  placental  blood flow.  There is no increase in the incidence of toxemia.
Echocardiography will  demonstrate  left  ventricular  enlargement.  EKG also
shows left ventricular hypertrophy and left atrial abnormality.  Chest  x-ray
may  show rib notching.  Complications of coarctation include cerebrovascular
events, aneurysm rupture,  arterial  hypertension,  congestive heart failure,
bacterial endocarditis, and aortic dissection  and  rupture.   PATENT  DUCTUS
ARTERIOSUS:  PDA  is rare in pregnancy because it has usually been identified
and corrected  during  childhood.   The  degree  of  shunting usually doesn't
change during pregnancy.  Reversal of flow can occur  if  there  is  arterial
hypotension  or  increased  pulmonary  pressure  which  can cause dyspnea and
fatigue.  If the ductus is large,  left ventricular volume overload and heart
failure may develop.  However, most women that have a small or moderate sized
ductus have no problems during pregnancy.  Surgical closure during  pregnancy
is  usually  not  necessary.   Antibiotic  prophylaxis  is given at delivery.
Physical findings include a hyperdynamic left ventricle, continuous murmur in
the  second  left  intercostal  space,   and  an  apical  S3.   If  pulmonary
hypertension  develops  there  may  be  cyanosis,   and   a   prominent   P2.
Echocardiography will show left ventricular and left atrial enlargement.  Ekg
may  show either left ventricular or biventricular hypertrophy.  TETRALOGY OF
FALLOT: Most  of  these  patients  will  have  had  corrective surgery during
childhood.   If  pregnancy  occurs  without  surgical  correction  there   is
increased  mortality.   The  increased  cardiac output and decreased systemic
resistance will worsen  the  right  to  left interventricular shunt.  Because
there is decreased arterial oxygen saturation due to the shunt,  there  is  a
rise  in  the  hematocrit  and  cyanosis.   Poor  prognostic  markers  are  a
hematocrit  >  than  60%, right sided overload, syncope and oxygen saturation
less  than  80%.   Antibiotic  prophylaxis  is  indicated.   Hypovolemia, and
hypotension should be avoided and oxygen  supplementation  should  be  given.
EKG  may  show right ventricular enlargement, RBBB, and right axis deviation.
Physical exam will reveal a  left  parasternal lift, systolic thrill and loud
ejection murmur along the upper left sternal border.  The  patient  may  have
cyanosis,  dyspnea and syncope.  Squatting is typical.  Echocardiography will
reveal the ventricular septal defect, anterior displacement of the aorta, and
the aortic septal discontinuity.   Doppler  will  pick  up  the right to left
shunt and pulmonary outflow obstruction.  Chest x-ray shows the typical  boot
shaped  heart, small pulmonary artery with reduced vascular markings, and the
right  aortic  arch.   EISENMENGER  COMPLEX:  Most  of  these  patients  have
unrepaired atrial or  ventricular  septal  defects  with  large left to right
shunts, and have developed  pulmonary  hypertension  and  pulmonary  vascular
disease  with  reversal of the shunt.  When these features develop, pregnancy
is not tolerated well.  The maternal mortality  is  > 50% and there is a high
incidence of fetal death.  Termination of pregnancy  should  be  recommended.
However,  if  the patient refuses, she should be hospitalized at 20 weeks and
started on anticoagulation with  heparin  supplemented  with oxygen, red rest
and hemodynamic  monitoring.   Premature  delivery  should  be  expected  and
vaginal  delivery  is preferred over C-section.  Epidural anesthesia is used.
Clinical findings include  right  ventricular hypertrophy, cyanosis, dyspnea,
syncope and chest pain.  Chest x-ray will show enlargement of  the  pulmonary
artery.    EKG   shows   right   ventricular  hypertrophy  and  right  atrial
abnormality.  Echocardiography  will  again  document  the  right ventricular
enlargement and Doppler will show the tricuspid and pulmonary  regurgitation.
MARFAN'S  SYNDROME:  Marfans's  syndrome,  is due to an inherited disorder of
connective tissue, and predisposes  the  patient to aortic dilatation, aortic
dissection, rupture and aortic regurgitation.  Pregnancy  will  worsen  these
potential threats.  For most patients, pregnancy should be avoided.  However,
if  the aortic root diameter is less than 4 cm	and the aortic regurgitation
is not  severe,  pregnancy  prognosis  is  improved.   Beta  blockers  may be
indicated,  as  in  aortic  dissection,  to  decrease  the  shearing   force.
Antibiotic  prophylaxis  is indicated.  MITRAL STENOSIS: Most of the problems
in mitral stenosis occur during  the  3rd  trimester when the cardiac output,
heart rate and blood volume are at  their  peak.   Congestive  heart  failure
usually  develops during the last trimester and early puerperium in about 75%
of cases, and after the 36th week in 40%.  The mortality is about 4-5% if the
patient is classified as New York  Heart  Association class III or IV, and if
they have pre-existing atrial fibrillation the mortality increases to 14-17%.
The risk of congestive heart failure is  about  72%  if  atrial  fibrillation
develops  during  pregnancy.   The  over-all  mortality  for mild to moderate
mitral  stenosis  is  1%.   Mitral   stenosis  with  atrial  fibrillation  is
associated with thromboembolism.  Patients are given heparin 5,000 to  10,000
units  subcutaneously  every  8 hours during pregnancy, as warfarin can cause
fetal  anomalies  and   fetal   bleeding.    Atrial  fibrillation  with  fast
ventricular rates and congestive heart  failure  are  treated  with  digoxin.
Cardioselective  beta blockers may be used to slow the ventricular rate so as
to improve diastolic filling.  Thiazide  diuretics should not be used because
of  liver  damage,  thrombocytopenia,  and  fetal  and  neonatal  electrolyte
imbalance.  Atrial fibrillation may need to be converted with procainamide or
DC cardioversion if the loss  of  the  atrial  kick  causes  refractory  CHF.
Physical  activity  should  be  curtailed  and  the patient	placed on a low
sodium  diet.   Symptoms  of  mitral  stenosis  include,  dyspnea, orthopnea,
paroxysmal nocturnal dyspnea, fatigue, and cough.  There is an increased  S1,
and  opening  snap.  Hemoptysis may occur if pulmonary hypertension develops.
Echocardiography will show mitral  valve  calcification, thickening, and poor
opening excursion.  MITRAL REGURGITATION: Mitral regurgitation can be  caused
from  a variety of diseases as floppy valve syndrome, bacterial endocarditis,
hypertrophic cardiomyopathy,  rheumatic  heart  disease  and ruptured chordae
tendineae.  For the most  part,  the  patient  is  able  to  tolerate  mitral
regurgitation  throughout  the  pregnancy, partly because peripheral vascular
resistance falls with a reduction of afterload.  Severe regurgitation coupled
with the increased blood volume  can  result  in congestive failure.  If this
does  occur,  treat  with  digoxin,  diuretics,  an  afterload   reducer   as
hydralazine,  low  salt  diet and rest.  If there is a sudden onset of mitral
regurgitation  secondary  to  rupture  of   a  valvular  leaflet  or  chordae
tendineae, surgery is needed promptly.  This usually occurs in the setting of
bacterial endocarditis.  Antibiotic prophylaxis is  needed  at  the  time  of
delivery.   Echocardiography  will  demonstrate a dilated left ventricle with
increased wall motion,  left  atrial  enlargement  and  Doppler will show the
mitral  regurgitant  jet.   EKG  may  show  atrial  fibrillation   and   left
ventricular  hypertrophy.   Examination  of  the patient will reveal the left
ventricular impulse to be  displaced  to  the  left,  increased P2, an apical
holosystolic murmur with a possible diastolic rumble and S3  sound.   Basilar
rales  may  be  present.   The  patient  will complain of increasing dyspnea,
orthopnea, paroxysmal nocturnal dyspnea and fatigue.  Atrial fibrillation may
develop with the potential for embolism.  MITRAL VALVE PROLAPSE: Mitral valve
prolapse usually poses no problem during  pregnancy.  There is no increase in
the incidence of spontaneous abortion  or  preterm  delivery.   Uncomplicated
mitral valve prolapse does not increase the risk for maternal or fetal death.
The  incidence  of  mitral  valve  prolapse is about 6% and usually in women.
Prophylaxis at the time  of  delivery  and  labor is controversial.  Patients
with mitral valve prolapse complain of  chest  pain,  palpitations,  dyspnea,
anxiety,  fatigue,  dizziness, depression and panic attacks.  Systolic clicks
may be heard and may be  associated with a systolic murmur.  Echocardiography
will reveal the mitral leaflets prolapsing back into the left atrium.  AORTIC
STENOSIS: If the aortic valvular stenosis is mild to moderate, most  pregnant
females  will  tolerate  the pregnancy.  Rheumatic aortic stenosis is usually
combined with mitral  valvular  disease.   Most  cases  are  due to rheumatic
disease and congenital bicuspid valves.  The limiting factor in severe aortic
stenosis is reduction of cardiac output which leads to decreased cerebral and
uterine blood flow.  Severe aortic stenosis is rare in pregnancy, but  has  a
maternal  mortality  of  17% and a fetal mortality of up to 32%.  Hypotension
should be avoided as this will  intensify the effects of the aortic stenosis.
Hypotension may result from blood loss, postural hypotension and  anesthesia.
Bed  rest  is  recommended  if  the  patient  is  able  to  continue with the
pregnancy.  If not, and the  patient  develops  heart failure, chest pain and
syncope, aortic valve replacement may be needed during pregnancy.  Antibiotic
prophylaxis is recommended.  Exam of the patient will reveal  an  absent  S2,
delayed  and  weak  carotid  upstroke  and  a  thrill  in  the  second  right
intercostal  space.   Echocardiography  will  show  thickening  of the aortic
valve, reduced opening, and concentric  left ventricular hypertrophy.  If the
Doppler shows a mean trans-aortic gradient of 50 mm Hg or  more,  the  aortic
stenosis  is  considered  to be severe.  However, the gradient may be falsely
elevated due to the high flow  state  imparted by the pregnancy.  The patient
will complain of  increasing  dyspnea,  fatigue,  syncope,  and  chest  pain.
AORTIC  REGURGITATION:  Aortic  regurgitation  may  be  caused  by  rheumatic
valvular  disease,  endocarditis, congenital bicuspid aortic valve and floppy
leaflets.  The fall in peripheral  systemic  resistance tends to palliate the
disease.  Most women will tolerate the  chronic  aortic  regurgitation  well.
However,  if  acute  aortic  regurgitation  develops  secondary  to bacterial
endocarditis, congestive heart failure  may ensue.  Antibiotic prophylaxis is
recommended.   Physical  examination  in  chronic  aortic  regurgitation  may
demonstrate Corrigan's pulse and Musset's sign.  The apex  may  be  displaced
laterally and there is a high pitched, decrescendo diastolic murmur beginning
after S2 and continuing through part or all of diastole.  This murmur is best
heard  in  the  sitting  position in full expiration.  This murmur is usually
accompanied by a mid-systolic  murmur  along  the  left sternal border due to
forward flow across the valve.  There may be a diastolic rumble (Austin Flint
murmur) heard at the apex and there may be a S3  gallop.   Chest  x-ray  will
show enlargement of the left ventricle and left atrium.  EKG will demonstrate
LVH.   PULMONIC  STENOSIS:  Pulmonic  stenosis  which  is mild to moderate is
tolerated well  during  surgery.   With  severe  pulmonic  stenosis  there is
decreased cardiac output and  right  sided  heart  failure  which  can  cause
dyspnea    and    fatigue.    If   the   patient   has   severe   symptomatic
pulmonic	stenosis, treatment  with  preload  reduction  and  diuretics are
started.  If this  doesn't  improve  the  failure,  surgical  valvulotomy  is
indicated.   Examination  of  the  patient  with  pulmonic stenosis reveals a
systolic thrill and harsh midsystolic  murmur  in the second left intercostal
space, a right ventricular lift and a pulmonic ejection click.  The  Ekg  may
show  right  ventricular  hypertrophy  if  the  stenosis is severe.  Symptoms
include dyspnea, syncope and  fatigue.  PERIPARTUM CARDIOMYOPATHY: Peripartum
cardiomyopathy  develops  in  the  last  month  of  pregnancy  to  6   months
post-partum.  Cardiac symptoms develop in the month prior to deliver in about
7-50% of patient and the remainder develop after delivery.  It is most common
in  multiparous  black women over the age of 30.  Other risk factors are twin
gestation,  postpartum  hypertension,  and  pre-eclampsia.   The differential
would  include  myocarditis   hypertrophic,   and   dilated   cardiomyopathy.
Treatment  includes  digoxin,  diuretics,  bed  rest,  sodium restriction and
vasodilators.  Anticoagulation is  needed  after  thromboembolic events.  The
risk for future  pregnancies  depends  on  the  response  of  the  idiopathic
cardiomyopathy  to therapy.  If severe left ventricular dysfunction persists,
future  pregnancies  are  not  recommended.   There  is  a  tendency  for the
cardiomyopathy to recur in subsequent  pregnancies.   Prognosis  is  best  if
there  is  resolution  of  the  symptoms  and cardiomegaly within the first 6
months.  Some patients with  peripartum cardiomyopathy will have inflammatory
infiltrates on endomyocardial biopsy.   A  previous  history  of  a  flu-like
illness should be elicited.  Echocardiography will demonstrate a dilated left
ventricle  and  usually  global  hypokinesis,  enlarged atria, and mitral and
tricuspid  regurgitation  via  Doppler.    EKG  will  show  left  ventricular
hypertrophy, left bundle  branch  block,  atrial  and  ventricular  premature
contractions, deep Q waves, atrial fibrillation and nonspecific ST and T wave
changes.   Chest  x-ray  will  show  an  enlarged  heart.   There is a mitral
systolic regurgitant murmur, S3 gallop  and possibly hemoptysis.  The patient
will complain of dyspnea, chest pain, palpitations and  supine  dyspnea.   If
the  patient  has  myocarditis there may be elevated SGOT, LDH and CPK during
the acute portion of  the  disease.  HYPERTROPHIC CARDIOMYOPATHY: Obstructive
hypertrophic cardiomyopathy is usually well tolerated during pregnancy unless
hypovolemia or  increased  left  ventricular  contractility  supervene.   The
hypervolemia  of  pregnancy  will  reduce  the left ventricular outflow tract
obstruction by increasing the size  of  the left ventricle and decreasing the
excursion of the mitral valve.  Two other factors may,  however,  worsen  the
obstruction.    These  are  compression  of  the  inferior  vena  cava  which
diminishes the venous return to the  heart,  and  the second is a decrease in
the  systemic  vascular  resistance  which   can   adversely   increase   the
obstruction.    Hypotension,  digoxin,  nitrates,  and  diuretics  should  be
avoided.  Antibiotic prophylaxis is recommended at delivery.  Cardioselective
beta blockers and calcium channel  blockers are used to reduce contractility.
Exercise should be interdicted because of the increased risk of sudden  death
inherent  in this disease.  Ventricular dysrhythmias may predispose to sudden
death and may  be  treated  with  procainamide,  beta blockers and quinidine.
Holter monitoring should be done.  During delivery  the  inferior  vena  cava
should  not  be  compressed.   Paracervical,  pudendal  blocks,  and  inhaled
anesthesia  should  be  used.   Epidural  and  spinal  anesthesia can produce
hypotension and should be avoided.   If  C-section is needed halothane may be
used.  Physical exam  will  reveal  a  hyperkinetic  left  ventricular  apex,
prominent  A  waves  in  the  jugular  vein  pulse, brisk carotid pulses, S4,
midsystolic left sternal border  murmurs  which  are augmented if the patient
performs the Valsalva maneuver or stands.   The  Echocardiogram  demonstrates
asymmetric  septal  hypertrophy,  with  a  septal/posterior wall ratio > 1.5.
There  is  anterior  systolic  motion   of   the  mitral  valve  against  the
interventricular  septum.   Mitral  regurgitation  is  present  on   Doppler.
The	EKG  will  show left ventricular hypertrophy, Q waves in the inferior and
lateral leads and possible complex ventricular arrhythmias.  The patient will
complain  of  dyspnea,  chest  pain,  dizziness,  syncope,  palpitations, and
orthopnea.

                -PREGNANCY AND HEMATOLOGIC DISORDERS-
IDIOPATHIC THROMBOCYTOPENIC PURPURA: ITP is characterized by a platelet count
< 100,000/mm3 and  a  normal  CBC.   ITP  is  an immunologic thrombocytopenic
purpura with  development  of  IgG  immunoglobulin  antibodies  that  have  a
propensity   for   adhering   to   the   platelets,  and  subsequently  cause
sequestration in the  reticuloendothelial  system with destruction.  Platelet
survival ranges from a few minutes to 2-3 days.  The  bone  marrow  shows  an
increase  of  megakaryocytes  which  is  a response to the destruction of the
peripheral  platelets.   There  is  a  prolonged  bleeding  time.   Excessive
surgical  bleeding  is  rare  unless   the  platelet  count  is  <	50,000.
Spontaneous bleeding starts at < 20,000/mm3 platelets.   Medical  therapy  is
started  when  the platelet count is below 100,000 with prednisone being used
at a dose of 1-1.5  mg/kg  of  prednisone  daily in divided doses.  This will
result in a 60% response.  If the dose  in  increased  to  2  mg/kg  then  an
additional  10%  will  respond.   An  attempt  is  made  to taper the dose to
maintain the platelets at 50,000.  If  the  patient is going to respond there
will be a decrease of purpura usually within 2-3 days and and increase of the
platelets in 7-10 days.  If the platelet count hasn't,t increased  to  50,000
by  3  weeks  then  the treatment is unsuccessful.  Splenectomy is the second
line of therapy with a  significant  response in about 70-90%.  The platelets
rise  immediately  following  surgery  and  are  normal   with   2-4   weeks.
Splenectomy  should  be considered during the second trimester if the patient
doesn't respond to drugs.  The  surgery  may  be technically difficult due to
the enlarged uterus and there may be excessive blood loss.  If the  pregnancy
is  advanced  into  the  third  trimester  then  a C-section may be required.
Circulating antiplatelet antibodies remain elevated following splenectomy and
there is  a  danger  of  neonatal  thrombocytopenia  with  fetal intracranial
hemorrhage during vaginal delivery.  There is no maternal platelet count that
would indicate danger to the fetus.  A  fetal  scalp  blood  sampling  during
labor  or  by percutaneous umbilical cord just prior to labor should be done.
If the fetal platelets  are  <  50,000  then C-section is recommended.  Gamma
globulin given at a dose of .4 gm/kg over 6-8 hours  daily  for  5  days  may
result  in a rapid increase in platelets but unfortunately is transient.  The
therapy  may  have  to  be  repeated  weekly.   Immunosuppressive  agents  as
azathioprine appears to be  relatively  safe, but cyclophosphamide should not
be used as it is teratogenic.  VON WILLEBRAND'S  DISEASE:  Von  Willebrands's
disease  is  an  inherited  disease  affecting  both males and females and is
caused by  a  deficiency  of  factor  VIII-related  von  Willebrands's factor
(VIII:vWF).   It  is  usually  an  autosomal  dominant  trait  but  a  severe
phenotypically recessive form is  seen.   The  homozygous  recessive  patient
generally has severe bleeding.  The heterozygous forms have varying levels of
factor  VIII  and  the  patient  can be asymptomatic or have severe bleeding.
Pregnancy may increase the factor VIII  in  the heterozygous form and cause a
reduction of bleeding.  Some patients may hemorrhage  at  delivery.   If  the
patient  has  type  I  disease  which  is  the  most  most  common form, then
desmopressin may be used at a dose of  0.3-.4 ug/kg in 50 cc of normal saline
infused over 30 minutes.  The bleeding time, factor VIII C, factor VWF:Ag and
ristocetin  cofactor  should  be  done  30  minutes  and  3-4   hours   after
desmopressin  infusion  is  stopped.   If  the  patient doesn't normalize the
bleeding time or factor VIII C levels are < 50% by term, then cryoprecipitate
may be given at 10 bags before  delivery  and 10 bags every 8-12 hours with a
reduction in dose to daily for about 4-5 days.  If the patient should need  a
C-section  the  factor  VIII C should be 80% or greater and the bleeding time
normal.  If the patient is hemorrhaging, then cryoprecipitate should be given
at 20 bags initially  and  then  followed  by  10-15  packs  q 12 hours until
stable.  Factor VIII concentrates have less VIII:vWF than cryoprecipitate and
are less effective in controlling  hemorrhage.   LUPUS  ANTICOAGULANT:  Lupus
anticoagulant  (LA)  is  an  antibody  that  is directed against phospholipid
surfaces such  as  blood  cells,  platelets  and  vascular endothelium.  This
immunoglobulin on the phospholipid prevents the phospholipid from interacting
with the coagulation factors to form fibrin.  This leads to a prolonged  PTT.
LA   causes   thrombosis   and   not  bleeding.   Pregnant  patients  have  a
hypercoagulable state and LA augments  this.   If  a pregnant patient has the
lupus  anticoagulant  there  is  fetal  growth  retardation  and  death  with
recurrent abortion, placental infarction and decidual vasculopathy.   Aspirin
at  80  mg  per  day  may  be  tried.  ANTITHROMBIN III DEFICIENCY: This is a
disease that produces venous  thrombosis  that  is  inherited as an autosomal
dominant trait.  The patient should be told that 50% of  the  offspring  will
inherit  the  disease.   It is estimated that it occurs as 1 in 2000.  Again,
pregnant patients are at  higher  risk  because  of the hypercoagulability of
pregnancy.  The highest risk is in the immediate postpartum  period  when  AT
III  levels fall to their lowest level.  Patients with AT III deficiency have
plasma levels 25-50% of normal.  Low AT  III levels can also be seen in fatty
liver of pregnancy, DIC, heparin therapy and pre-eclampsia.  The level of  AT
III in normal term infants is 50% of the adult and most affected infants have
25-30%  activity.   Diagnosis  is made clinically with a history of recurrent
thrombosis in family members as well  as the patient, thrombosis resistant to
heparin, and thrombosis in unusual places as cerebral and  mesenteric  veins.
Therapy   includes   anticoagulation   with   heparin   that   may  be  given
subcutaneously  during  pregnancy  and  IV  or  subcutaneously  post  partum.
Heparin is required  during  the  first  trimester  because of the associated
embryopathy with warfarin during the first trimester.   Following  the  first
trimester  warfarin may be used because heparin will further lower the AT III
levels.  Coumadin is used until 2  weeks  prior to delivery when the warfarin
should be stopped in order to prevent bleeding in the fetus and  mother.   AT
III concentrates can be given at this point to maintain adequate levels of AT
III.   Following  delivery,  heparin  should  be  resumed as the mother is at
particular risk during this  period.   Coumadin  can  be  started at the same
time.  The coumadin should be continued for at least 4 months, and  for  life
if  there is a history of thrombotic events.  The heparin can be discontinued
when the PT is in  a  satisfactory  range.   Also,  AT III concentrate can be
given at the time of highest risk around the delivery  period.   DISSEMINATED
INTRAVASCULAR  COAGULATION:  DIC  can  be  triggered  by  abruptio placentae,
amniotic fluid embolus,  dead-fetus  syndrome,  sepsis,  and preeclampsia and
eclampsia.  Liberation of thromboplastin  from  injured  or  necrotic  tissue
activates  the  extrinsic system.  Endothelial cell injury will also activate
the Hageman factor and  the  intrinsic  clotting  system.  The last mechanism
producing DIC is injury to red cells or platelets  which  will  then  release
phospholipid   and   this   starts   the   intrinsic  and  extrinsic  system.
Thromboplastin activation  causes  release  of  tissue  plasminogen activator
which converts fibrin bound plasminogen to plasmin which in  turn  will  lyse
fibrin  and  fibrinogen  with  subsequent  production  of  fibrin degradation
products.   These   fibrin   degradation   products   interfere  with  fibrin
polymerization, and  they  also  coat  platelet  membranes  which  makes  the
platelets  unable  to  function.   DIC is diagnosed with decreased platelets,
prolongation of  the  PT,  PTT,  decreased  fibrinogen  and  increased fibrin
degradation products, shortened euglobulin  clot  lysis  time  and  decreased
antithrombin III.  There is oozing at venipuncture sites, purpura, petechiae,
thrombotic  or  embolic events, and minor or generalized bleeding.  Treatment
of DIC is directed at the  underlying  cause.  This means treatment of sepsis
and delivery of the infant.  Fibrinogen should be kept at more than 100 mg/dL
with fresh frozen plasma or cryoprecipitate.  The platelet  count  should  be
kept  >  50,000/ml  and  the  hematocrit > 30%.  Packed RBCs are deficient in
several coagulation factors and fresh frozen  plasma should be used to supply
these factors in a ratio of 1 unit of fresh frozen plasma for every  4  units
of  packed  RBCs given.  Antithrombin III concentrates or fresh frozen plasma
which  contains  some  antithrombin  III   may  be  given  for  the  depleted
antithrombin III.  ABRUPTIO PLACENTAE: Abruptio placentae is the most  common
cause  of  DIC  in  pregnancy.   Approximately 10% of abruptio placentae will
develop DIC.  If cesarean section  is  needed then fresh frozen plasma should
be given prior to surgery to raise the fibrinogen above 100 mg/mL.   However,
vaginal  delivery  is  better  if there is no fetal distress and the fetus is
dead  as  happens  in   about   38%   of  abruptio.   FETAL  DEATH  SYNDROME:
Thromboplastin from the dead fetus is released very slowly  and  causes  DIC.
The  defibrinogenation is much slower than in abruptio placenta.  A decreased
fibrinogen level is seen  2-5  weeks  following the intrauterine fetal death.
Treatment should consist of induction of labor or  D  &  C  as  soon  as  the
diagnosis  of  fetal  death  is  made.  Within twin gestation, the release of
thromboplastin may jeopardize  the  viable  infant  causing thrombotic events
that could lead to renal or neurological damage  and  death.   Therefore,  if
fetal  maturity  is  present,  then  the  viable  twin  should  be  delivered
immediately.   If  there  is  still immaturity then the viable twin should be
monitored with ultrasound  for  growth  and  any  changes  in the brain.  The
mother should also be followed closely for development of DIC.   Heparin  may
be given if patient is not in labor giving 5000 units as an IV bolus followed
by  1000  units  per hours in order to keep the PTT between 1.5 and 2.5 times
control.   Induction  of  labor  can  start  6  hours  after  the  heparin is
discontinued.  If patient is in  labor  given  cryoprecipitate  to  keep  the
fibrinogen  between  200-  300 mg/dL.  AMNIOTIC FLUID EMBOLUS: Amniotic fluid
embolus is a rare disease but  can  be  fatal  to the mother in 80% of cases.
The incidence is 1 per 8000 to 80,000  live  births.   Presentation  is  with
shock,  chest  pain  and dyspnea.  It is more common in multigravid patients,
tumultuous labor, first  stage  of  labor  and  rupture  of membranes.  Death
occurs in the first hour in 25%.  Therapy includes cryoprecipitate and volume
replacement with support by positive end expiratory pressure, pressor  agents
and  possibly  aminophylline  and  digoxin.   SEPSIS:  Can  occur with septic
abortion, pyelonephritis,  infected  amniotic  fluid  and  endometritis.  The
bacterial endotoxins  will  decrease  platelets  and  fibrinogen.   Treatment
consists  of  antibiotics,  removal  of  infected  material,  restoration  of
platelets,  volume  and  factors.   Shock  is  monitored  with  Swan-Ganz and
arterial lines.  PREECLAMPSIA AND ECLAMPSIA:  There  can  be a low grade DIC,
but thrombocytopenia is the principal  defect.   The  fibrinogen  is  usually
normal, but fibrin degradation products are elevated and there is a reduction
of  antithrombin  III.   Treatment  is  delivery and replacement of deficient
coagulation factors.

                     -PREGNANCY AND SAFE DRUGS-
All  of  the  following  drugs  are   safe  in  pregnancy  for  all  accepted
indications:        Acetaminophen,        aminophylline,         amoxicillin,
amoxicillin/clavulanate,   amphotercin,   ampicillin,   ampicillin/sulbactam,
antacids   (avoid   in   1st   trimester),   carbenicillin   indanyl  sodium,
cephalosporins (1st,  2nd,  3rd  generation),  chloramphenicol  (avoid in 3rd
trimester),  cimetidine,  clindamycin,  clotrimazole,  cloxacillin,  cromolyn
sodium,   dicloxacillin,   diphenhydramine   (avoid   in   1st    trimester),
diphenoxylate,  erythromycin,  ethambutol,  famotidine,  ferrous  sulfate and
gluconate, fluconazole, folic  acid,  glyburide,  heparin, hepatitis B immune
globulin, hydroxyzine (avoid in 1st trimester), isoniazid,  lactulose,  local
anesthetics,  metoclopramide,  miconazole,  moxalactam,  naloxone,  nystatin,
oxacillin,   permethrin,   probenicid,  ranitidine,  spectinomycin,  steroids
(topical), sucralfate, terbutaline, tetanus/diphtheria toxoid, tetanus immune
globulin, theophylline, ticarcillin.

                 -PREMENSTRUAL SYNDROME (Treatment)-
VITAMIN B6: can give up to 100 mg qd for affective symptoms.   ALDACTONE:  25
mg QID is given during the luteal phase for water retention, and weight gain.
PARLODEL:   is  given  for  breast  discomfort  beginning  at  ovulation  and
continuing until menses at 2.5 mg qd  or bid.  DANOCRINE: is given for breast
discomfort and may be used continuously or during the luteal  phase.   At  200
mg/day  it  does not inhibit ovulation and barrier or IUD should be used.  It
can  masculinize  the  patient  or  female  fetus.   PONSTEL:  is  given  for
dysmenorrhea, headaches and  affective  symptoms  at  500  mg  tid.  LOW DOSE
MONOPHASIC OR MULTIPHASIC ORAL CONTRACEPTIVES: can be given for  dysmenorrhea
at  1/day for 21 days each month.  PROGESTERONE can be used for affective and
behavioral symptoms given just after  ovulation and continued to menstruation
at 200 mg bid vaginal suppository or 100 mg tid in micronized  form.   LUPRON
is given for somatic, affective, behavioral and other symptoms at 3.75-7.5 mg
IM  monthly.   Do not use for more than 6 months without addition of estrogen
and progesterone.  SYNAREL NASAL SPRAY has the same indications as Lupron and
is given at 200 mg bid.  XANAX  is  given for affective symptoms at .25-.5 mg
tid.

                       -PRIMARY ALDOSTERONISM-
Often  presents  as  a  resistant  hypertension  but  can  be  ruled  out  by
simultaneous measurement of plasma aldosterone and renin levels.  A  ratio  >
30:1 is strongly suggestive of primary aldosteronism.

                  -PRIMARY BILIARY CIRRHOSIS (pbc)-
PBC should be suspected in any middle aged woman that complains  of  pruritus
and has an elevated serum alkaline phosphatase.  The disease is considered by
some  to be an immune mediated disease and perhaps an immune complex disease.
The disease can  recur  in  patients  that  have  had liver transplants.  The
female:male ratio is about 10/1.  All races can be involved and the incidence
is about 10/1 million/year.   CLINICAL:  Patients  present  insidiously  with
pruritus  and  fatigue.   There  may  be  diarrhea  due to fat malabsorption,
xanthomata(40%,  hepatomegaly  initially,  and  later  a  small  liver.   The
bilirubin has been used as  an  estimate  of  the progression of the disease.
The disease has a range between 20-80 years, but mainly affects  middle  aged
females.   The  cholesterol  is  elevated.  Bone pain and osteomalacia may be
present.  Splenomegaly may even be  detected in an asymptomatic patient early
in the disease.  Occasionally corneal Kayser Fleishcher rings are  found  due
to  accumulation  of  copper  secondary to impaired copper excretion in bile.
There may be wrist drop and foot drop due to an accumulation of lipids around
the nerves.  Late portal  hypertension,  ascites and bleeding esophagogastric
varices may  be  seen.   COMPLICATIONS:  Patients  may  develop  scleroderma,
Sjogren's  syndrome  and  CREST.  Primary hypothyroidism has been reported at
25%.    Other   associations   have   been   made   including   polymyositis,
polyarthritis,  renal  tubular   acidosis,  Hashimoto's  thyroiditis,  celiac
disease,  primary  pulmonary  hypertension,   vasculitis   and   interstitial
pneumonitis.   It has been noted that non Hodgkin's lymphomas and even breast
cancer are more frequent with  PBC.  LABORATORY: The diagnosis is established
by finding a positive antimitochondrial antibody (AMA) in association with  a
compatible  liver biopsy which shows a non-suppurative cholangitis associated
with  granulomas.   The  liver  is   enlarged   and  has  a  smooth  surface.
Lymphocytes and plasma cells predominate in the portal  areas.   Similarities
between  the lesions of PBC and graft versus host disease have been observed.
The identification of granulomas on initial liver biopsy is associated with a
more favorable prognosis.  High titers of AMA  > 1:160 are rarely seen in any
other condition and are found in about 95% of patients.  Make sure  there  is
no  evidence  of  any  extrahepatic  bile  duct  obstruction such as stone or
stricture, carcinoma of the bile  ducts, cholestatic liver disease associated
with sarcoidosis, or inflammatory bowel disease.  Ultrasonography  should  be
done   to   exclude   bile   duct   obstruction   and  endoscopic  retrograde
cholangiography may be indicated.   Transhepatic cholangiography is used less
often because the bile ducts are very  small  and  few  in  number.   A  drug
induced   cholestasis  has  to  be  ruled  out,  especially  that  caused  by
phenothiazines as well  as  sclerosing  cholangitis, chronic active hepatitis
and bile duct carcinoma.  Sarcoidosis may be  clinically  and  histologically
difficult  to  differentiate  from  PBC.   The 5' nucleotidase and GGT can be
increased to similar extents as  the  alkaline phosphatase.  The bilirubin is
normal or slightly elevated in early asymptomatic  patients.   A  progressive
rise in bilirubin is ominous.  The cholesterol may get as high as 1000 mg/dl.
There is an increase of HDL in mild to moderate cases.  This tends to fall in
the  later stages of the disease.  The IgG, IgA, and IgM may all be elevated,
but the IgM is usually always elevated more  than the IgG or the IgA, and the
IgM is elevated in about 75% of the cases.  The Antimitochondrial  antibodies
are  usually  performed  using  the ELISA analysis.  AMAs are rarely found in
patients with mechanical obstruction of the biliary tract, primary sclerosing
cholangitis or in any other  chronic  forms of cholestatic liver disease such
as drug induced disease and sarcoidosis.  AMAs may be found in about 5-15% of
patients with idiopathic chronic active hepatitis, but in general the  titers
are  lower  (1:40  to  1:80).   The  anticentromere  antibody may be found in
patients with primary biliary cirrhosis with the CREST variant.  (calcinosis,
raynauds, esophageal motility  disorders,  sclerodactyly and telangiectasia).
This variant has been estimated to occur in about 3-17% of patients with PBC.
Evidence of Raynauds or scleroderma may precede evidence  of  liver  disease.
The  calcinosis is the least common part of the CREST syndrome when it occurs
with PBC.  Chronic  destructive  intrahepatic  cholangitis  would be a better
descriptive name for the disease, as cirrhosis is usually not seen  when  the
diagnosis  is first made.  There is progressive destruction and disappearance
of the small  interlobular  hepatic  bile  ducts.  TREATMENT: Cholestyramine,
4-24 grams per day is useful for  the  pruritus  if  the  bilirubin  is  only
moderately  increased.   Cholestyramine may also help improve the serum lipid
levels.  Give the drug a few days to work.  There may be mild constipation or
diarrhea as side  effects.   The  drug  may  be  given  with  food, but other
medications should be given 2 hours later to allow absorption.  Colestipol is
probably just as effective.  Antihistamines and phenobarbital  may  help  the
pruritus.   Rifampicin 10 mg/kg/day and phenobarbital 3 mg/kg/day given for 2
weeks with an interval of 30  days  between treatments is often times useful.
Plasmapheresis can help  but  is  expensive  and  must  be  done  frequently.
Vitamin  D replacement therapy can be given to prevent or treat osteomalacia.
Give 1 gram of calcium/day  to  prevent osteoporosis, as fractures are common
later in the disease.  Azathioprine hasn't helped much.   D-penicillamine  is
ineffective  in  improving survival or decreasing complications.  Colchicine,
0.6 mg bid may  be  helpful,  but  dose  related  diarrhea may develop.  With
colchicine, the bilirubin, alkaline phosphatase and  aminotransferase  levels
all  decrease  and  survival  might be improved.  Ursodeoxycholic acid may be
helpful using 13-15 mg/kg/day.  There is usually an improvement in bilirubin,
aminotransferases, alkaline phosphatase and  GGT.   The pruritus improves and
the liver biopsies improve.   Chlorambucil  has  not  been  used  because  of
toxicities,  and  Cyclosporine  A  is  of limited benefit because of its side
effects of hypertension and  increased  creatinine.  Liver transplantation in
primary biliary cirrhosis is done as as a last resort.

                   -PRIMARY SCLEROSING CHOLANGITIS-
Primary sclerosing cholangitis (PSC) is a rare chronic obliterative  fibrotic
and  inflammatory  process  affecting  the  extrahepatic bile  ducts with  or
without involvement of the intrahepatic bile  ducts.  It occurs mainly in the
3rd-4th decade, affecting males in  about  60-70%  of  cases.   It  has  been
associated  with  inflammatory  bowel disease (primarily ulcerative colitis).
in about 70% of cases, as  well as retroperitoneal fibrosis, Reidel's struma,
mediastinal fibrosis, histiocytosis X and vasculitis.  The natural history of
PSC is a slow progression to biliary cirrhosis and death.   There  is  a  33%
mortality rate for patients over a 5-108 month follow-up period.  The patient
may  first  present as an asymptomatic elevation of the alkaline phosphatase,
pruritus, jaundice, abdominal pain, fever  or  weight  loss.  In about 50% of
cases  the  physical  exam  will  be  negative.   Otherwise,  there  may   be
hepatomegaly,  splenomegaly and jaundice.  LABORATORY: There may be elevation
of the alkaline phosphatase,  GTT,  and 5-nucleotidase, aminotransferases and
hypergammaglobulinemia (30%).  The alkaline phosphatase  is  usally  elevated
3-10  times normal while there is only modest elevation of the transaminases.
The total lipids are elevated,  while  the  chlesterol  is elevated in 50% of
PBC.  It is also important to realize that the following lab tests are normal
in PBC: Antimitochondrial antibodies  (AMA),  antinuclear  antibodies  (ANA),
anti-smooth  muscle  antibodies  (ASMA),  and  hepatitis  B  surface antigen.
Rarely, there may be  low  titers  of  ANA, AMA, ASMA.  Endoscopic retrograde
cholangiopancreatography  usually  is  able  to  make  the  diagnosis  early.
TREATMENT: The pruritus may be treated with  cholestyramine  4-16  grams/day,
with  or without phenobarbital.  Vitamin supplementation should be given with
A, D, and K. Suppurative  cholangitis  is  treated with antibiotics and major
strictures may  be  dialted  by  endoscopic  or  percutaneous  means.   Liver
transplanation is the only definitive treatment.

                        -PRINZMETAL'S ANGINA- 
CLINICAL:  Prinzmetal's  angina  (PMA),  otherwise known as variant angina is
characterized by its propensity to occur at rest and by ST segment elevation,
as opposed to typical angina pectoris,  that usually occurs with exercise and
ST depression.  It was described by Myron Prinzmetal in the late  1950's  and
early 1960's.  The ECG changes are due to transient epicardial coronary spasm
and are often accompanied by arrhythmias and conduction disturbances.  The ST
segment  elevations  are most commonly seen in the inferior leads, reflecting
involvement of the right coronary artery.   It  is more often seen in younger
patients and in women  and  may  be  accompanied  by  Raynaud's  syndrome  or
migraine headaches.  Cigarette smoking may aggravate the disorder.  Oliva, in
1973,  demonstrated  coronary  artery  spasm  associated with the pain and ST
segment elevation.  The spasm  amy  be  seen  in normal coronary arteries and
those with fixed obstructions.  Between  attacks,  the  ECG  may  be  normal.
Myocardial  infarction  may  occur  in  about  25%  of  patients  and  may be
associated with ventricular  fibrillation  or  high  grade  heart block.  The
episodes of chest pain may be  precipitated  by  emotional  upsets  at  rest,
exposure  to  cold  weather,  during  or after a meal, and have a tendency to
occur mainly during the night  or  early AM hours.  Ergonovine stimulation in
the lab using 0.5-0.4 mg IV, is the most sensitive useful test for  provoking
an  episode.   A positive test is indicated by focal spasm using low doses of
ergonovine.  This may in turn produce electromechanical dissociation and life
threatening  arrhythmias  that   is   unresponsive  to  sublingual  nitrates.
Coronary artery arteriography should be done in variant angina  to  determine
if  fixed  stenotic lesions are present in association with the spasm.  These
patients will need  medical  therapy  as  well as possible revascularization.
MANAGEMENT: Nitrates are usually effective in reversing the spasm and respond
to sublingual, oral or topical nitrates.  Sudden withdrawal may provoke spasm
and this may be a problem in nitrate tolerance.  Calcium  blockers  are  very
effective  in  preventing  vasospasm  and  decreasing  the  frequency  of the
episodes  and  the  need  for   nitroglycerin.   Beta  blockers  are  usually
ineffective in patients with normal arteries and spasm and have been known to
exacerbated  coronary  spasm.   Fixed  stenotic  lesions  +  spasm  may  need
revascularization.

                   -PROGRESSIVE SUPRANUCLEAR PALSY-
Progressive   supranuclear   palsy   (PSP)   is    also    known    as    the
Steele-Richardson-Olszewski  syndrome.   Its  major  feature is a progressive
supranuclear ophthalmoplegia involving vertical  gaze,  which is a paresis of
voluntary  vertical  movement  without  loss  of  the  vertical  doll's  eyes
maneuver.  Impairment of downward gaze is more prominent  than  upward  gaze.
Due  to  this,  there  may  be  a history of frequent falls as the patient is
unable to see the  floor.   The  patient  may  also  have blurring of vision,
diplopia, tearing and burning of the eyes, photophobia and retraction of  the
upper  lids  which  causes  a  mask-like  facies.  Other pseudobulbar palsies
include dysarthria, dysphagia,  and  hyperactive  jaw  jerk.  The patient may
also have difficulty with gait, rigidity, bradykinesia and tonic contractions
of  the  facial  muscles.   As  you  can  see,  patients  with  PSP  have   a
pseudo-Parkinsonism.   (They  do  not  have  a  tremor  and  do not walk bent
forward, but do have mask facies, and  tend to fall backwards).  There may be
insomnia, irritability, agitation and retarded thinking.  Axial  dystonia  of
the neck (the neck stiffens in extension), and upper trunk are common.  Later
in  the  course  of  the  disease  there  may  be  subcortical  dementia  and
depression.   The  onset of PSP is usually around the 6th decade of life, but
it can begin in the 40s.  The  cause is unknown, but degenerative changes are
found in the cerebellar nuclei, brainstem, and  diencephalon.   About  4%  of
patients with Parkinson's disease may actually have PSP.  The disease is more
common  in men, and there is no racial or ethnic preferences.  The disease is
relentless,  leading  to  incapacity  within  2-3  years  with  death usually
occurring within 10 years.   LABORATORY:  CSF  studies  may  reveal  only  an
increase  in  protein.   CT  and  MRI  imaging may demonstrate atrophy of the
cerebellum, midbrain and the  cerebral  hemispheres.   Later in the course of
the disease,  the  EEG  may  show  bifrontal  non-rhythmic  bursts  of  delta
activity.   TREATMENT: There is no definitive treatment.  Dopaminergic agents
may help the parkinsonian  symptoms,  but  they  have  no  affect on the gaze
palsies.

                   -PROPRANOLOL AND HYPERTENSION-
(Inderal).   1-10 mg loading dose; then 3 mg/hr.  Side effects: bronchospasm,
decreased cardiac output.

                    -PROSTHETIC VALVE DYSFUNCTION-
OBSTRUCTION AND  INCOMPETENCY:  Mechanical  prosthetic  valves  such  as  the
Starr-Edwards  valve, a ball cage valve, may function for more than 30 years,
but thrombus due to suboptimal anticoagulation may lead to obstruction and/or
regurgitation.  Ingrowth  of  tissue  tends  to  cause prosthetic dysfunction
also.  On a single leaflet valve, sudden death can be  caused  by  the  valve
sticking  in  a closed position.  The St.  Jude valve is bileaflet and causes
stenosis  and  regurgitation.   The  Bjork-Shiley  has  suffered  from  strut
fracture while the older  Starr-Edwards  valves have developed poppet failure
due to ball variance and fractures.   Bioprosthetic  valves  will  eventually
calcify and become incompetent and stenotic.  Many of these are sudden events
which can be catastrophic unless recognized and treated.  Tissue degeneration
of  bioprosthetic  valves will occur with time.  After about 10 years, 20% of
bio-prostheses will have  degenerated  and  require  replacement.  The tissue
degeneration is especially high in younger persons.   CHOICE  OF  PROSTHESIS:
There  are  two  choices  of  prosthetic valves being used in the USA; either
mechanical or bioprosthetic.  Of the mechanical  type, there are 3 main types
such as the St.  Jude which is a bileaflet, the  Starr-Edwards,  which  is  a
ball  and  cage  and  the  Medtronic  Hall valve.  The Bjork-Shiley spherical
occluder valve isn't used any  longer  in  the USA.  The bioprosthetic valves
are porcine heterografts such as the Carpentier-Edwards and the Hancock.  The
main disadvantage of mechanical  valves  is  the  need  for  anticoagulation.
Bioprosthetic  valves do not require anticoagulation, but their durability is
limited.  The thromboembolic rate is  similar  between  the two types.  At 15
years, heterograft failure due to degeneration  and  obstruction  is  between
40-65%.   Antibiotic sterilized homograft valves have a very low complication
rate such as endocarditis, but the failure rate is about 19% at 10 years, 54%
at 14 years and  88%  at  20  years,  and  in  addition they are difficult to
insert.  Bioprosthetic valves should be chosen in those who  cannot  tolerate
anticoagulation,  women  of  childbearing  age  who  desire pregnancy and for
patients that only have a life  expectancy of between 7-10 years.  Mechanical
valves are indicated in those with atrial fibrillation, long life expectancy,
and those who require smaller valves.   IDENTIFICATION  OF  DYSFUNCTION:  The
patients may show evidence of CHF and murmurs that are usually present may be
fainter  than  usual  due  to  low  cardiac output or high filling pressures.
Those   patients   that   have   a   bioprosthesis   should   have  immediate
transesopohageal echocardiography with Doppler  evaluation  to  assess  valve
areas  and  transprosthetic  valve  gradients.   Clots and reduced prosthetic
leaflets may be  seen.   If  there  are  large  pressure gradients across the
valve, thrombosis is suggested.  The patient will probably need urgent  valve
replacement  with  heparinization and hemodynamic monitoring.  Although there
is some risk of embolization of  lysed clots and CNS hemorrhage, thrombolytic
therapy  can  markedly  improve   the   situation.    Alteplase   (t-PA)   or
Streptokinase  has  been  used  if  the  patient  is in cardiogenic shock and
immediate valve replacement  is  too  risky.   Alteplase can produce clinical
improvement in about 1.5 hours, and heparinization should continue after  the
thrombolytic  therapy.  PARAVALVULAR LEAKS AND DEHISCENCE: Paravalvular leaks
can be due to  intra-operative  technical  problems  or endocarditis, and can
occur in mechanical as well as bioprosthetic valves.   Endocarditis  produced
dehiscence is usually progressive with ultimate failure along with mechanical
hemolysis.   In  this  setting  a surgical emergency is produced which if not
corrected will eventuate  with  sepsis,  intractable  CHF  and death.  On the
other  hand,  minor  technical  imperfections  may  not  be   hemodynamically
significant   and   may   be  tolerated  for  years.   Even  with  long  term
anticoagulation of  mechanical  prostheses,  there  is  a  1-2%  or less/year
embolic rate for aortic  prostheses  and  a  3-4%  or  less/year  for  mitral
prostheses.   If  in  spite  of anticoagulation, emboli develop, dipyridamole
must be given with the  warfarin.   Heterografts  in the aortic position have
similar  embolic  rates  without  anticoagulation.    Mitral   valve   tissue
prostheses must have anticoagulation when atrial fibrillation is present.  If
anticoagulation is stopped in those patients with mechanical valves, there is
a  20-25%  incidence  of  systemic embolism in the first year.  Patients with
cerebral emboli may convert  a  bland  stroke  into a hemorrhagic stroke with
anticoagulation.  Waiting 2-3 days may avoid this.  Limb vessel emboli may be
removed by surgical means.

                            -PROTEINURIA-
A 24 hour urine collection for  protein  and creatinine should be done as the
initial step in work-up for proteinuria.  IF THE 24 HR TOTAL PROTEIN IS  <  3
GM/DAY, do a urine protein electrophoresis.  (MONOCLONAL LIGHT CHAINS, either
kappa  or  lambda  are seen in multiple myeloma.  Amyloidosis occurs in about
10% of patients with multiple myeloma  and can cause proteinuria, but usually
in excess of 3 g/24h.  If urine ALBUMIN  is  found,  minimal  change  disease
could be present or the proteinuria may be due to exercise or fever.  If BETA
MICROGLOBULIN  (tubular proteinuria) is found check for hereditary disease as
Wilson's disease, oxalosis,  and  medullary  cystic  disease.  Also check for
congenital disease such as Fanconi syndrome and renal tubular  acidosis,  and
acquired  tubular  disease  as  heavy metal toxicity, interstitial nephritis,
obstructive uropathy, pyelonephritis,  vitamin  D  intoxication and radiation
nephritis.  IF THE 24 HOUR PROTEIN ELECTROPHERESIS IS > 3  G/24H,  check  for
INFECTIONS    such   as   poststreptococcal   glomerulonephritis,   bacterial
endocarditis, shunt nephritis and  syphilis,  DRUGS as NSAIDs, penicillamine,
probenecid and mesantoin, FAMILIAL disease as sickle  cell  disease,  Fabry's
disease,  nail-patella  syndrome  and  Alport'syndrome and NEOPLASTIC disease
secondary  to   Wilm's   tumor,   lymphomas,   leukemias  and  	membranous
nephropathy secondary to carcinoma of the  breast,  lung  and  colon.   RENAL
BIOPSY   may   be   needed   to  diagnose  focal  sclerosis,  membranous  and
proliferative glomerulonephritis, minimal change disease, SLE, polyarteritis,
diabetes,  hypertension,  myxedema,  Goodpasture's  syndrome, Henoch-Shonlein
purpura, sarcoidosis, Takayasu's syndrome and dermatitis herpetiformis.

                      -PRURITUS (Generalized)-
This discussion will deal with generalized  pruritus and will not address the
various skin lesions that are capable of causing pruritus.  DRUGS: A  history
of  all  the  drugs  that the patient has, or is taking, should be assembled.
These should include  prescription  and  over-the-counter  drugs.  Drugs that
most   commonly   causes   rashes    include    sulfonamides,    allopurinol,
phenylbutazone,  streptomycin, nitrofurantoin, penicillins and carbamazepine.
Drugs causing histamine release  from  mast  cells include morphine, codeine,
merperidine, vancomycin, aspirin, and estrogens.  Amphetamines can also cause
pruritus.  ONCOLOGIC DISORDERSl Approximately  6  percent  of  patients  with
Hodgkin's  lymphoma  may  present with generalized pruritus without any other
symptom.  The itching usually  starts  on  the  legs  and  some complain of a
burning sensation.  Itching may  be  associated  with  dome-shaped  keratotic
papules  on  the  arms  and legs (nodular prurigo) in patients with Hodgkin's
disease.  Carcinoma of the  stomach  and  pancreas (glucagonoma syndrome) may
also cause pruritus.  NEUROLOGIC DISORDERS: Notalgia paresthetica is  a  form
of  pruritus  that is localized to an area of the back and just medial to the
left scapula.  This may  be  a  variant of peripheral neuropathy.  Paroxysmal
pruritus has been noted in multiple sclerosis and nostril pruritus  has  been
associated  with  frontal  brain  neoplasms.   CARCINOID  SYNDROME: Carcinoid
syndrome occasionally will be associated  with  itching, but should not cause
any particular problem in diagnosis.  LIVER DISEASE: Various  liver  diseases
may  be  associated  with  pruritus.   Primary  biliary  cirrhosis  should be
suspected in any  middle  aged  female  in  whom  the alkaline phosphatase is
elevated.   Itching  may  be  the  first  symptom.   It  causes   progressive
destruction  of  the  small  intrahepatic bile ducts probably secondary to an
immunologic process.  Cholestasis  of  pregnancy  may  also produce pruritus.
This pruritus is most severe in the third trimester and will disappear  after
delivery.   The  patient  should  be  worked  up for any type of extrahepatic
biliary  obstruction  syndromes.   Drugs  such  as  oral  contraceptives  and
chlorpropamide  may  produce  obstructive   biliary  disease  with  pruritus.
HEMATOLOGIC DISORDERS: Polycythemia vera is the most notable disease in  this
category.   Pruritus of 15-30% has been noted in polycythemia vera.  Patients
complain  of  itching  after  bathing.   Multiple  myeloma  may  also produce
pruritus.  Check for lymphadenopathy  as  Hodgkin's  and  non-Hodgkins's  and
mycosis  fungoides  and the Sezary syndrome may be present.  Leukemia also is
capable of causing itching, as is iron deficiency anemia.  After therapy with
iron the itching usually  resolves.   ENDOCRINE DISORDERS: Thyrotoxicosis may
produce generalized pruritus in about 8% of patients that will  improve  when
the  patient  is treated.  Hypothyroidism also can cause pruritus and most of
these are secondary to  xerosis.   Diabetes  mellitus may produce pruritus in
less than 5% of patient and does not correlate  with  the  disease  severity.
RENAL  DISORDERS:  Uremic  pruritus  is associated with chronic renal failure
when the BUN is  greater  than  50  mg/dl.  Dialysis may produce intermittent
bouts of intense itching.  Causes of uremic pruritus has been  attributed  to
increased  mast  cells, increased plasma histamine, increased serum magnesium
and vitamin A with xerosis  and  decreased  sweating.  There may be secondary
hyperparathyroidism with metastatic calcifications and peripheral neuropathy.
WORKUP: Physical  exam  should  search  for  lymph  nodes,  hepatomegaly  and
splenomegaly.   Laboratory  investigations  should include CBC, BUN, alkaline
phosphatase, BIlirubin, T4 and TSH,  glucose,  Chest x-ray and stool exam for
blood.  TREATMENT: Treatment is for the underlying disease  and  conservative
symptomatic  measures may be employed as menthol lotions, and cyproheptadine,
hydroxyzine or doxepin can be given before bedtime.  Treat dry skin with luke
warm bath water and mild soaps,  patting  the  skin dry instead of rubbing it
with a towel.  Immediately apply a moisturizing lotion.   Bathing  should  be
limited.  Cholestyramine can be helpful in uremia and cholestasis.

                      -PSEUDOMEMBRANOUS COLITIS-
Pseudomembranous colits is a toxin mediated colitis  secondary  to  antibotic
therapy  that  occurs  in  about 10% of patients taking antibiotics.  The two
toxins responsible for  the  injury  are  toxin  A  (enterotoxin) and toxin B
(cytotoxin).  Toxin A stimulates neutrophil chemotaxis and toxin B interferes
with mucosal protein synthesis.  Both toxins are  capable  of  attacking  the
membranes, however.  It is usually caused by Clostridium difficile which is a
spore  forming gram positive obligate anaerobe.  C. difficile occurs in about
5% of normal persons, but can reach as high as 50% in those patients that are
hospitilized.   Almost   every   antibiotic   except   vancomycin   has  been
incriminated in the production of pseudomembranous colitis.  The most  common
offending    antibiotics    include    ampicillin,   clindamycin,   and   the
cephalosporins.    Other   causative    antibiotics   include   erythromycin,
penicillins, sulfamethoxazole/trimethoprim, tetracycline and chloramphenicol.
Even metronidazole has been incriminated.  Diarrhea is more common with  oral
antibiotics,  but  parenteral antibiotics can also cause.  The major route of
transmission  is   person-to-person   cross   infection   secondary  to  hand
transmission, due to the fact  that  infective  spores  can  persist  in  the
environment  for  months.  CLINICAL: The patient will present, in most cases,
with a nonbloody diarrhea  that  can  be  characterized as a watery, greenish
diarrhea that is associated with abdominal pain.  The symptoms usually  occur
during  the  course  of  the  antibiotic  administration, but in about 33% of
patients the symptoms  begin  1-10  days  following  treatment.  In fact, the
diagnosis should be considered in anyone up to 6 weeks  following  antibiotic
therapy.   The  patient  may have bloody stools, fever, leukocytosis, protein
losing enteropathy,  hypotension,  dehydration,  electrolyte imbalance, toxic
megacolon and even colonic perforation.  The patient may give  a  history  of
AIDS,  malignancy,  uremia,  recent  bowel surgery, intestinal ischemia, bone
marrow  transplantation,  chemotherapy,  or  cystic  fibrosis  which  can  be
predisposing factors.  Physical exam may reveal tachycardia, fever, abdominal
distention, absent bowel sounds or peritoneal signs.  LABORATORY: Examination
of the stool should be done  for  stool  leukocytes  which are seen in 50% of
cases.  There may be leukocytosis, hypoalbuminemia, azotemia and elevation of
the sedimentation rate.  KUB films may show a dilated colon and thumbprinting
with bowel wall edema.  CT of the abdomen may show thick  colon  walls.   The
diagnosis  is  usually  established,  in  part,  by  a  positive  Clostridium
difficile stool culture or toxin assay.  The standard toxin assay is a tissue
culture based analysis which is 95-100% sensitive and specific.  However, the
frequency  of  a  positive  toxin  assay  increases  with the severity of the
colitis, ranging from 20%  in  mild  cases without sigmoidoscopically visible
lesions, to > 90% in cases of full blown cases.  Endoscopic examination  will
show  dirty  white to yellow plaques that are usually seen in the left colon.
In mild cases the colonic  mucosa  may  just show edema or mild inflammation.
As the colitis becomes more severe, diffuse friable ulcerations  may  develop
that are not unlike those of ulcerative colitis.  The mucosal involvement can
pregress  to  transmural involvement, and about 10-20% of patients with toxin
positive  stools  will   fail   to   develop   the  classic  pseudomembranes.
Histologically,  the  membranes  consist  of   fibrin,   sloughed,   necrotic
epithelial  cells and WBCs.  TREATMENT: The first step should be cessation of
all  antibiotics.   If  an  antibiotic  is  needed,  substitute  one  that is
infreuently associated with pseudomembranous  colitis..   Antimotility  drugs
should  be  discontinued  and avoided, since they may cause the disease to be
protracted.  Most mild cases will respond to these simple measures.  Patients
in  the  hospital  should   be   placed  on  enteric  isolation  precautions.
Cholestyramine given at 4 grams PO TID for 5-10 days is used  in  mild  cases
who have discontinued antibiotic therapy.  It may also be used in combination
with  metronidazole  or  vancomycin.  Should the patient not improve with the
above measures, oral metronidazole 250  mg  TID  for  7-10 days may be given.
The use of IV metronidazole should only be given to those unable to take oral
medications.  Oral vancomycin is a second choice, because  it  is  much  more
expensive.   It  is  given as 125-500 mg PO QID for 7-14 days.  Vancomycin is
reserved for those who  fail  to  respond  to  metronidazole or are unable to
tolerate metronidazole.   For  patients  that  have  multiple  relapses,  the
addition  of Lactobacillus preparations given at 1 gram QID for 7-14 days may
be of benefit.  Relapses can occur in 5-50% of cases and of these, 10-15% may
be multiple.  They are usually less  severe and are treated by observation or
by repeat antibiotic therapy for 7-10 days.

                      -PSEUDOMONAS AERUGINOSA-
Purulent material that is green suggests P. aeruginosa.  P. aeruginosa mostly
causes  nosocomial  infections  from   water   supplies.    Pseudomonas   and
Staphylococcus  aureus  are the most common infections of massive burns.  Hot
tub  folliculitis,  osteomyelitis,  particularly   in  IV  drug  abusers,  or
osteomyelitis secondary to nail puncture wound, and malignant otitis  externa
in  patients  with  diabetes  mellitus  are  all  caused  by  P.  aeruginosa.
Nosocomial  pneumonia  and complicated urinary tract infections can be caused
by Pseudomonas.  Pseudomonas meningitis  following  neurosurgery is common as
well as  lung  infections  in  cystic  fibrosis  patients.   Neutropenia  may
predispose  to Pseudomonas bacteremia and ecthyma gangrenosum.  Ceftazidime +
an  aminoglycoside  is   an   effective   combination  for  life  threatening
infections.   Extended  spectrum  penicillins   +   an   aminoglycoside   are
synergistic  against  most  Pseudomonas species.  Imipenem, ciprofloxacin and
aztreonam are also effective against most strains.

                        -PSEUDOTUMOR CEREBRI-
Pseudotumor  cerebri  has undergone numerous changes in its name since it was
first described in  1897  by  Quincke.   It  also  has  been  known as benign
intracranial hypertension and  idiopathic  intracranial  hypertension,  among
others.  Certain criteria must be met before you can make a diagnosis of this
disease.   There  must  be normal results on CT and MRI or at the very most a
reduction in the size of the  ventricles.   There must be an elevation of the
CSF greater than 250 mm H2O and cytology and chemistry of  the  CSF  must  be
normal.   Pseudotumor cerebri has been reported in all ages, from 4 months of
age to the elderly.  A large number of the pediatric cases are due to steroid
withdrawal, post-traumatic or toxic causes.   There  seems to be a propensity
for obese females in the childbearing ages.  There is about an 8:1  ratio  of
females  to  males.   The  incidence  in the general population is about 1 in
100,000, but rises to 19 in 100,000 in obese women in the childbearing years.
CAUSES: The cause is  essentially  unknown,  but  it has been associated with
several conditions as:  the  use  of  oral  contraceptives,  pregnancy,  iron
deficiency  anemia,  renal  failure,  hypoparathyroidism,  SLE,  heavy  metal
poisoning,  occlusion of an intracranial venous sinus, chronic CO2 retention,
Addison's disease,  vitamin  A  toxicity,  tetracycline  usage, withdrawal of
corticosteroids, prolonged use of steroids, nalidixic acid, lithium,  danazol
and  isotretinoin  therapy.   CLINICAL:  Symptoms can range from headaches to
nausea and vomiting, double vision, visual loss, sixth cranial nerve paresis,
and papilledema.  There may be  subretinal or splinter hemorrhages around the
optic disc.  The double vision occurs in about one third of patients  and  is
usually  horizontal.  The cranial nerve palsy is almost always the sixth.  If
there is involvement of another  cranial nerve, re-evaluation for a different
cause should entertained.  The patients may have loss of color vision, visual
fields and visual acuity.  Monocular and binocular visual  obscurations  will
occur  in  about  two  thirds  of  patients,  many  of these occurring during
postural changes.  These transient obscurations  also can occur in myopia and
in optic nerve head drusen.  Enlarged blind spots are found in patients  with
papilledema.   The  enlarged blind spot may persist after the papilledema has
resolved.  Visual field loss may occur in 10 - 27% with the most common being
loss of the inferonasal portions of  the visual field.  There may be central,
paracentral and cecocentral scotomas, and altitudinal loss.  This visual loss
may lead to blindness which can occur in 11 - 24%.  Headaches  are  the  most
common, occurring in over 75% of the patients.  There may be a bruit over the
head  with the patient reporting noise in the ears.  If this is the case, the
you  should  rule  out   venous   occlusion  or  arteriovenous  malformation.
TREATMENT: About 10% of patients will  recover  spontaneously  and  80%  will
recover  after  treatment  with  medicine  or  surgery within 4 months of the
onset.  About 10% will continue to have  a more chronic course.  There may be
a 10-30% recurrence rate, usually within 2.5 years.  An average  attack  will
last  about  1-3  months.   Treatment either consists of medical, surgical or
both.  Acetazolamide 250 mg po tid  will  reduce the formation of the CSF and
should be used initially.  Steroids, as prednisone  60-80  mg  daily  may  be
needed.   If  the  patient is obese, and many are, then weight loss should be
advised.  The course of the disease  should be followed with visual field and
visual acuity checks, funduscopic  exam  and  CSF  pressure  monitoring.   If
medical  treatment is not effective, as demonstrated by persistent headaches,
diplopia, optic disc elevation > 5 diopters, engorgement of retinal veins and
characteristic visual evoked potential changes,  then surgical insertion of a
lumboperitoneal shunt may be placed.  Optic  nerve  sheath  decompression  in
some  cases  is  used as a first line surgical approach for correction of the
disorder.  Most patients will  have  a  reduction  of the headache after this
procedure in spite of continued elevation of the CSF pressure.  Complications
of the procedure have been an occasional case of  transient  ocular  motility
disturbance, atonic pupil and sudden visual loss.

                            -PSITTACOSIS-
Psittacosis  is  also  known as parrot fever, or ornithosis.  It is caused by
Chlamydia psittaci which is a ubiquitous obligate intracellular parasite.  It
is usually  transmitted  by  parrots  or  parakeets,  but  ducks, cockatiels,
pigeons and canaries can also transmit  the  disease  to  humans.   When  the
animals  are  sick  they  may  have  sneezing,  diarrhea or ruffled feathers.
Direct contact with feces, feathers,  or aerosolized excreta can transmit the
disease.  Even after the bird  recovers,  it  can  still  be  infectious  for
several  months.  Humans become ill about 1-2 weeks after contact with a dry,
nonproductive cough, headache, abnormal  liver tests and splenomegaly.  Chest
x-ray may reveal a characteristic wedge shaped infiltrate.  There may also be
a rash  that  is  similar  to  the  rash  seen  in  typhoid  fever,  myagias,
arthralgias,  and sore throat.  The diagnosis requires acute and convalescent
complement fixation titers, since  serologic conversion usually doesn't occur
until the fourth or fifth week of the disease.  Presumtive  evidence  of  the
disease  may  be inferred if a single titer is > 1:32.  The drug of choice is
tetracycline for 2-3 weeks or eythromycin in children and pregnant women.

                             -PSORIASIS-
Psoriasis is  a  chronic  inflammatory,  benign,  recurrent  disease  that is
characterized by epidermal hyperproliferation producing  well  circumscribed,
silvery,  and  scaling plaques.  It is estimated that about 2-4% of the white
population is involved.  It is less  common  in Blacks.  The cause is unknown
and a family history of psoriasis is common.  The onset  is  usually  between
the  ages  of  10 and 40 years of age.  The sites of predilection include the
extensor surfaces of the knees, elbows, nails, scalp, umbilicus, intergluteal
cleft, the back, glans penis,  vulva, eyebrows, anogenital area, and axillae.
Nail involvement  is  characterized  by  pitting  or  stippling,  thickening,
discoloration and separation of the distal margin.  In psoriasis of the scalp
there  are  large silvery scales that are dry, well marginated and heaped up,
which  distinguish  it  from  the  diffuse,  yellowish,  greasy,  scaling  of
seborrheic  dermatitis.   The   lesions   are   well  circumscribed,  usually
nonpruritic, papules or plaques that are covered with  silvery  scales.   The
most  common  sites are the elbows, knees and the scalp.  Several factors are
known to  exacerbate  the  lesions  such  as  chloroquine antimalarial drugs,
lithium, beta blockers, group A beta hemolytic  streptococci,  local  trauma,
sunburn,  topical  drugs, interferon-alpha and withdrawal of steroids.  There
are several variants of the disease.   The  most common variant is the plaque
type.  The plaque type or erythrodermic psoriasis may be  seen  in  AIDS  and
usually  has  an abrupt onset.  Guttate (eruptive) psoriasis occurs following
streptococcal pharyngitis or stress, and  may  be  pruritic.  There also is a
generalized pustular type that may be severe.  Pustular psoriasis is typified
by sterile pustules that can be generalized or localized  to  the  palms  and
soles.   Psoriasis  may  be  associated with arthritis which may present as a
peripheral  type  and/or  a  spondylitic   type,  that  is  seronegative  for
rheumatoid factor.  DIFFERENTIAL DIAGNOSIS: Differential  diagnosis  includes
seborrheic  dermatitis,  squamous  cell  carcinoma in situ, fungal infection,
eczema, lichen planus, cutaneous  LE,  secondary  syphilis, and the cutaneous
findings of Reiter's syndrome.  TREATMENT: Since psoriasis is  a  non-curable
disease,  simple  measures  should be used for the limited form of psoriasis.
This  consists  of  keratolytics,  lubricants  and  topical  corticosteroids.
Lubricating agents such  as  hydrogenated  vegetable  cooking  oil, and white
petrolatum may be used in conjunction with topical steroids, crude coal  tar,
anthralin, and salicylic acid.  The lubricating agents should be applied when
the  skin  is  wet,  such  as  following a bath or shower.  Systemic steroids
should not be used, because pustular lesions may develop during the course of
treatment.  Sunlight is usually beneficial,  but in some cases may exacerbate
the disease.  TOPICAL STEROIDS: In general, the ointments  are  more  potent,
but  creams  are  more  cosmetically  acceptable.   Increased efficacy of the
topical steroids can be enhanced  by  using  a plastic occlusive dressing for
1-8 hours.  Occlusive dressings should not be used for  extended  periods  of
time.   Patients  may  be  started  with  0.1%  triamcinolone (Aristocort and
Kenalog) cream or ointment  BID-TID  for non-intertriginous, non hair bearing
areas of the skin.  If this is  ineffective,  then  the  preparation  may  be
changed  to  a  more  potent  topical  steroid  such  as desoximetasone 0.25%
(Topicort), or  fluocinonide  0.05%  (Lidex),  applied  BID.   For refractory
cases,   clobetasol   (Temovate)   or   betamethasone   dipropionate    0.05%
(Diprolene)	may be used for short periods of time.  These latter preparations
should  not  be  used longer than 2 weeks at a time because they produce skin
atropy.  Patients with intertriginous  areas  or facial involvement should be
treated  with  low  potency  steroid  creams  such  as  desonide   (DesOwen),
alclometasone  dipropionate  (Aclovate),  or  2.5%  hydrocortisone.  By using
these low  potency  preparations,  you  can  reduce  the  risk  of striae and
telangietctasias.  Scalp psoriasis is treated with topical steroid  solutions
such as triamcinolone 0.1% (Kenalog), fluocinolone (Synalar), or fluocinonide
0.05%  (Lidex) BID + tar shampoos.  For resistant scalp patches triamcinolone
acetonide suspension 2.5 mg/mL may  be  used.  SALICYLIC ACID: Salicylic acid
(Keralyt Gel) is a keratolytic agent that can be used to treat patients  that
have  very  thick  scales.   It is usually employed in conjunction with other
agents.  By loosening the scales, topical steroids are able to penetrate much
better.  Baker's P and S is a phenol and saline preparation that is available
as an over-the-counter solution or  shampoo.   This may be applied at bedtime
to the scalp and left overnight.  This  is  then  washed  out  the  following
morning  and followed by a tar shampoo.  A shower cap may be used to minimize
the  mess  and  increase  the  penetration.   ANHTHRALIN:  Anthralin  is very
irritating and should not be used in intertriginous areas.  It also  is  very
messy  and will stain the clothing and the sheets.  It is available in 0.1-1%
forms as Anthra-Derm or Dithrocreame, which is applied for only 30 minutes to
1 hour/day, and is then removed with  soap and water.  TARS: Tar shampoos are
considered the treatment of choice for scalp psoriasis.  Tars are  effective,
but  work slower than topical steroids, are messy, but have few side effects.
For the scalp, a tar shampoo, such  as  Neutrogena T/Gel, or Ionil T Plus may
be used daily.  Ionil T Plus shampoo is applied to  wet  hair,  and  massaged
into  the  scalp.  Let the lather stand one minute and then rinse.  It should
be used at least twice a week, or  more often if needed.  It is supplied as 8
oz plastic bottles.  There is a chance of sunburn for  24  hours  after  each
application.   Other  tar  preparations  include Carbonis Detergens 5%, Estar
gel, Fototar, PsoriGel, Balnetar bath, and Zetar emulsion (bath) and shampoo.
Zetar bath is used as  15-25  ml  added  to  lukewarm bath, immerse for 15-20
minutes, and then rinse off.  It may be used 3-7 times weekly.  Zetar shampoo
is massaged into a wet scalp, rinsed, repeated, wait  5  minutes  and  rinsed
again.   Zetar  emulsion  and  shampoo both are supplied as 6 oz.  In general
these are applied overnight.   ETRETINATE  (tegison)  is a synthetic retinoid
that can be used in psoriasis.  It is most effective in  pustular  psoriasis,
erythrodermic  psoriasis,  and the plaque varieties.  It has significant side
effects such as elevation of  liver  enzymes  and serum lipids, chapped lips,
dry  nose,  dry   scaly   skin,   hair   loss,   itching,   eye   irritation,
hypertriglyceridemia,  headache, pseudotumor cerebri, hepatitis, fatigue, and
musculoskeletal pains.  Diffuse  idiopathic  skeletal  hyperostosis  has been
reported in those using this in high doses for a prolonged  amount  of  time.
It  is  not  recommended  during  childbearing years, except for very unusual
situations, as the drug is teratogenic.  The  drug is stored in the body, and
drug levels can be detectable 2-3 years after it is discontinued.   Women  of
childbearing  age must use effective contraception while taking the drug, and
probably for 2-3 years following  its termination.  METHOTREXATE: can be used
in patients that are  refractory  to  other  treatments.   It  is  especially
helpful in widespread pustular psoriasis, exfoliative psoriasis and psoriatic
arthritis.   Close  supervision  is  necessary, and monitoring of hepatic and
renal function is  necessary.   It  is  used  in  doses similar to rheumatoid
arthritis, such  as  5-20  mg/week.   ULTRAVIOLET  PHOTOTHERAPY:  Ultraviolet
phototherapy  may be used alone or with tars.  If used with topical tars, the
therapy  is  more  effective.   The   phototherapy  is  usually  given  three
times/week, increasing the dose by about 10-15% each treatment.   It  may  be
combined with Estar gel, Balnetar bath, or Carbonis Detergens 30 minutes to 2
hours prior to the ultraviolet phototherapy.  PUVA: Psoralen plus ultraviolet
A can be very effective in treating extensive psoriasis.  The skin is exposed
to  long  wave  ultravilet  light  (330-360  nm),  plus  the photosensitizing
compound 8-methoxypsoralen (methoxsalen)  (Oxsoralen-Ultra).  This is usually
initiated at .5 mg/kg given 1.5 hours prior to the treatment in a ultraviolet
light block.   Treatments  are  started  at  three  times/week.   Maintenance
therapy  is  usually  required.  The relapse rate is about 63% in 1-6 months.
There are side effects to this  therapy.   Epidermal dystrophy can be seen in
50% of patients, atypical lentigines are common, and there  is  an  increased
incidence of cutaneous cancer in patients with fair skin or who have recieved
previous  x-ray  radiation.   There  is  a  potential  for the development of
cataracts, scrotal cancer,  and  cutaneous  discoid lupus.  During treatment,
patients are required to wear eye goggles and athletic supporters.

                        -PSORIATIC ARTHRITIS-
About 15-20% of  patients  with  psoriasis  will  have  psoriatic  arthritis.
Psoriasis  usually  antedates the onset of arthritis in about 80% of cases by
months to years.  Arthritis is  about  5  times more common in those patients
that have severe skin disease.   A  hidden  source  of  psoriasis  should  be
sought, such as a small patch in the umbilicus, scalp or gluteal cleft.  Nail
pitting  may  be  the  only  clue  present  in  some cases.  The nail pitting
frequently overlies the involved distal  interphalangeal joint.  About 33% of
patients will have conjunctivitis, episcleritis,  and  iritis  at  some  time
during  the  course  of  their  disease.   Aortic regurgitation and pulmonary
interstitial fibrosis has  been  associated  with psoriasis.  HLA-B27 antigen
will  be  present  in  some  patients,  particularly  those  with   psoriatic
spondylitis.   HLA-B27  is less associated with the nonaxial skeleton.  There
is a  40  fold  increase  of  psoriatic  arthritis  in  family  members.  The
male:female ratio is about 1:1.  The most common age of onset is 35-45  years
of age.  Psoriatic arthritis can present in different manners and evolve into
different  patterns  during  the  course of the disease..  However, about 50%
will develop spondylitis,  and  most  have  peripheral articular involvement.
The most  common  presenting  type  is  mono  and  asymmetric  pauciarticular
arthritis.  In this form the distal and proximal interphalngeal joints of the
hands  ,  feet,  wrist, ankles, elbows and knees can be involved.  Typically,
there is a sausage like swelling  of  a  single digit.  The digit is painful,
red, cool to touch, and diffusely swollen.   Inflammatory  arthritis  of  the
distal  interphalangeal  joints  occurs  in  about  5-10%.   As  the  disease
advances,  phalangeal  bone  resorption  and  osteolysis  occurs,  leading to
arthritis mutilans.  About  25%  of  patients  will  present with a symmetric
polyarthritis, which is similar to  rheumatoid  arthritis,  except  that  the
distal  interphalangeal  joints  may  be  involved.  Usually fewer joints are
involved than  in  rhematoid  arthritis,  and  rheumatoid  factor  is absent.
Spondylitis and sacroiliitis frequently co-exists with all of the  peripheral
types.    In   the  absence  of  peripheral  involvement,  the  incidence  of
spondylitis and sacroiliitis is only about 10%.  Spondylitis, overall, occurs
in a greater than 40% of patients,  and can involve any portion of the spine,
but  more  frequently  the  cervical  spine.   Syndesmophgtes   are   common.
Sacroiliitis  is usually asymmetric, and occrus in more than 20% of patients.
Radiographic studies may reveal osteolysis, bony ankylosis, marginal erosions
of bone  and  irregular  destruction  of  joints  and  bone  (penicil  in cup
deformities), fluffy periosteal new bone formation,  particularly  marked  at
the  insertion  of  muscles and ligaments into bone.  Asymmetric sacroiliitis
and atypical syndesmophtes  may  also  be  seen.   There may be paravertebral
ossification, which is  distinguished  from  ankylosing  spondylitis  by  the
absence  of  ossification  in the anterior portions of the spine.  Laboratory
shows an elevation of  the  sedimentation  rate  and  possibly the uric acid,
which represents the active turnover of skin by  psoriasis.   The  rheumatoid
factor   is  negative.   Anemia  of  chronic  inflammation  may  be  present.
Immunoglobulin levels are usually normal.  Synovial  fluid may show a mild to
moderate inflammatory reactive effusion with mostly neutrophils.   TREATMENT:
Treatment  is essentially the same as that for rheumatoid arthritis, with the
exception of antimalarials.  Antimalarials  can cause exfoliative dermatitis,
and  can  exacerbate  the  psoriasis.   The  mainstay  of  therapy  is   with
nonsteroidal  anti-inflammatory  agents.  Steroid injections may be useful in
the  mono  and  oligoarticular  forms.   Intramuscular  gold  is  often  very
effective.  Oral gold is not  as  effective  as  IM gold.  Methotrexate is an
effective agent for cutaneous psoriasis and also is  effective  in  psoriatic
arthritis.   Sulfasalazine has also been useful, starting with 500 mg/day and
increasing  at  weekly  intervals  by   500   mg   up  to  1-1.5  grams  BID.
Photochemotherapy with oral methoxsalen and long  wave  ultraviolet  A  light
(PUVA)   is  effective  for  both  cutaneous  psoriasis  and  the  peripheral
arthritis, but is not beneficial  for  spine involvement.  Most patients will
have  exacerbations  and  remissions  of  their   disease.    Patients   with
pauciarticular  disease  usually  do  not  progress to the mutilating form of
arthritis as do the other forms.

                     -PTCA VS THROMBOLYSIS IN MI-
There is evidence now accumulating that primary PTCA may be just as effective
as IV thrombolytic therapy in  the  treatment of acute myocardial infarction.
In addition PTCA is less costly and associated with less major morbidity.  It
can  be  particularly  useful  in   those   patients   with   advanced   age,
hemodynamiclly   compromised   infarctions   and  very  large  anterior  wall
myocardial infarctions.  Thrombolysis has been  shown to give poor results in
those patients with previous CABG and consideration should be given  to  PTCA
in  these  patients.   Also,  in those patients where thrombolytic therapy is
contraindicated and where the diagnosis of MI is in doubt, direct PTCA may be
used.  In patients  that  have  had  CABG  surgery  and subsequently suffer a
myocardial infarction, about 76% will have the  occlusion  in  the  saphenous
vein  graft.   Thrombolytic  therapy has only been effective in opening about
25% of these occlusions, whereas  PTCA  has  a reported success rate of about
85%.  Thrombolytic  therapy  in  those  acute  MI  patients  with  associated
cardiogenic  shock has not improved survival.  Conventional medical treatment
yields a 20% survival, whereas  aggressive  therapy  with PTCA and/or CABG in
conjunction with intraaortic balloon pump has  been  around  60%.   The  PAMI
trial  (Multicenter  Priamry  Angioplasty  and  Acute  Myocardial Infarction)
compared t-PA followed by  heparin  with  PTCA.   In  this study of about 400
patients, patients with symptoms of less than 12 hours were  enrolled.   Even
though  the mean time to onset of therapy with PTCA was 30 minutes later than
with  thrombolytic  therapy,  angioplasty  more  swiftly  established  vessel
patency so that the  mean  time  of  pain  resolution  was reduced by 1 hour.
Angioplasty was effective in 97% of  the  attempts.   Bleeding  complications
were  similar in those treated with thrombolysis and those treated with PTCA.
However, hemorrhagic strokes occurred  in  2%  of  the t-PA group while there
were no strokes in  the  PTCA  group.   Moreover,  there  was  more  residual
ischemia  in  the  t-PA  group  versus  the  PTCA  group.   Hospital  related
reinfarction  or  death  was  12%  in  the t-PA group versus 5.1% in the PTCA
group.  With PTCA there  also  was  reduced  mortality  with  > 70 y/o and in
anterior wall MIs.

                         -PULMONARY EMBOLISM-
TREATMENT:  Many patients with pulmonary emboli (PE) will have no venographic
or ultrasonographic evidence  of  deep  vein  thrombosis  (DVT).  If clinical
suspicion remains high, ventilation-perfusion lung scanning should  be  done.
Low  or  intermediate  probability  scans  in  the face of clinical suspicion
should  prompt  pulmonary  angiography.   Patients  that  are hemodynamically
unstable may benefit from bedside echocardiography.  Suggestive findings  for
PE   include   normal  LV  function,  with  RV  dilatation  and  hypokinesis,
interventricular  septal  bowing  into  the  left  ventricle,  and  tricuspid
regurgitation.  Echo is important in  critical  patients, for it can rule out
aortic dissection, pericardial tamponade,  and  ventricular  septal  rupture.
When  PE is strongly suspected, treatment should be started immediately while
the diagnostic evaluation is carried  out.   Screening  for PE may be done by
obtaining  a  blood  sample  for  plasma  D-dimer  level  by  enzyme   linked
immunosorbent  assay.   Levels  <  500  ng/ml  are against a diagnosis of PE.
ANTICOAGULATION: Heparin is  currently  the  initial  treatment of choice for
both PE and DVT.  Therapy should start by  giving  a  bolus  of  5,000-10,000
Units   of   heparin   sodium.   Some  would  give  even  higher  boluses  of
15,000-20,000 Units.  This is followed by a continuous IV infusion of heparin
giving about 30,000 U/24 hours or  1,250  U/hour.  The PTT should be targeted
to reach a goal  of  1.5-2.5  times  control.   Some  would  advocate  higher
infusions  of  20 U/kg/hour or 1400 units/hr in a 70 kg person or 40,000 U/24
hours, if there is no  increased  risk  of  bleeding.   The APTT is checked 6
hours after the loading dose is given and the maintenance infusion begun  and
followed  at 24 hour intervals.  The half life of heparin is about 1.5 hours,
so that by 4-6 hours  after  the  loading  dose  the  APTT is very close to a
steady state level.  If there is any interruption in the heparin infusion for
more than 2 hours, the APTT will be greatly reduced.   If  the  APTT  returns
less  than  1.5  x  control at 6 hours, a 3,000-4000 U rebolus is given along
with an increased maintenance  infusion  rate.   If IV heparin is impossible,
subcutaneous heparin can be given using 7,500-8,000 units every 8 hours.   As
a general rule large amounts of heparin are usually required during the first
24  hours,  which  may be reduced after that.  Hemoglobin and platelet counts
should be done QOD  with  UA  and  stool  spot  checks for occult blood.  The
effects of heparin may be reversed by using protamine sulfate  1  mg  IV  for
every  100  units  of heparin, which may be repeated in 15 minutes if needed.
Never exceed 50 mg in any 10 minute  period or 100 mg in 2 hours.  Heparin is
usually given for about 7 days.  Warfarin should be started on day 1 or 2 and
the heparin is usually discontinued when the PT has been in  the  therapeutic
range of 1.3-1.5 seconds or INR 2-3 for 3 days.  Warfarin is usually given in
the  evening starting with 10 mg daily for 2-3 days and adjusted according to
daily   PT   values.    The    major   complications   of   heparin   include
thrombocytopenia,    hypersensitivity     reactions     and     osteoporosis.
Thrombocytopenia  usually  occurs after 5-6 days of heparin therapy.  Heparin
should be discontinued if  the  platelet  count falls below 75,000.  Warfarin
therapy should be continued for 3-6 months depending  on  risk  and  previous
history  of PE.  Reversal of warfarin therapy is with fresh frozen plasma and
vitamin K  subcutaneously.   Patients  that  have  baseline  elevation of PTT
because of lupus anticoagulant or for the  patient  that  is  thought  to  be
heparin  resistant  (low PTT in spite of high doses of heparin), measurements
of plasma  heparin  levels  may  be  substituted  for  the PTT.  THROMBOLYTIC
THERAPY:  For  the  hemodynamically  unstable  patient  with  PE   who   have
echocardiographic evidence of RV dysfunction, extensive deep vein thrombosis,
or   for  anatomically  large  pulmonary  emboli  with  hypotension,  tPA  or
streptokinase may be  given.   Rt-PA  is  given  at  50  mg  over 2 hours x2.
Maintenance  IV  heparin  is  started  simjultaneously  at  a  rate  of  1000
units/hour.  A front loading dose of t-PA may be given starting with a  bolus
of  15  mg followed by 50 mg over 30 minutes and then 35 mg over 30 minutes a
an alternative.  Streptokinase is given  at  a  dose of 250,000 units IV over
20-30 minutes followed by 100,000  U/hr  x  24  hours.   Following  this  the
infusion  is  discontinued  for  about 2-3 hours before starting heparin as a
maintenance infusion.  Thrombin times should be > 1.5 x control 4 hours after
the loading dose and at  24  hours  (no  adjustment is made based on thrombin
times).  Fibrinogen levels < 150 mg/dl or fibrin degradation products  <  400
mg/dl  can  be associated with an increased risk for bleeding.  Reversal from
thrombolytic  therapy  is  with  fresh  frozen  plasma,  cryoprecipitate,  or
epsilon-aminocaproic acid.   Embolectomy  is  reserved  for  life threatening
situation and is associated with a high mortality, requiring  cardiopulmonary
bypass and an IVC filter.

                 -PULMONARY FLOW MURMUR (Innocent)-
Is present in infants or adolescents.  The murmur dissipates  on  supination.
The murmur is systolic at the ULSB and is transmitted to the axillae and back.

                  -PULMONARY HYPERTENSION (Primary)-
Primary pulmonary hypertension (PPH) is a disease characterized  by  elevated
pulmonary  hypetension  and increased vascular resistance of unknown etiology
that occurs predominantly in females  (3:1).   It has a 7% autosomal dominant
familial incidence with variable expression.  The mean age of presentation is
around 35 years, with  a  second  peak  in  males  at  50-60  years  of  age.
Pathologically,  it  is  characterized  by intimal thickening and fibrosis in
small  pulmonary  arteries,  increased  medial  thickness  of  small muscular
pulmonary arteries, necrotizing arteritis and fibrinoid necrosis in the walls
of the muscular pulmonary arteries, and dilated thin walled side branches  of
muscular  pulmonary  arteries  known  as  plexiform  lesions.   It  has  been
postulated that unrecognized recurrent pulmonary emboli or in situ thrombosis
may be causative in some cases.  At any rate, PPH must be differentiated from
other  causes  as  COPD,  pulmonary  fibrosis, granulomatous disease, asthma,
malignancy, pulmonary thromboembolism,  collagen  vascular disease, pulmonary
arteritis, schistosomiasis, sickle cell  disease,  congenital  heart  disease
with  Eisenmenger  reaction, mitral stenosis, cor triatriatum, cardiomyopathy
and pulmonary venous obstruction.   This  can  be done with echocardiography,
lung scanning,  pulmonary  arteriography,  and  cardiac  catheterization  and
pulmonary  function testing.  CLINICAL: PPH symptomatology is similar to that
of pulmonary hypetension from other causes.  They present with right cardicac
failure that is progressive, eventually leading  to death in 2-8 years.  Most
cases are in women, and in advanced  cases  will  have  ascites,  edema,  low
cardiac  output  with  weakness  and  fatigue.   In addition they have effort
syncope,  anginal  chest  pain  and  exertional  dyspnea  without  orthopnea.
Palpitations are frequent and  can  cause sudden death.  Physical examination
findings are consistent with  pulmonary  hypetension  and  right  ventricular
pressure  overload.  There is a left parasternal right ventricular heave that
is present in about 80% of cases.   A  large A wave is present in the jugular
venous  pulse.   Pulmonary  ejection   clicks   and   murmurs   of   pulmonic
insufficiency are present in less tha 50%.  There is a loud P2 heard in > 80%
of  cases along with a right ventricular fourth heart sound in 50-80%, murmur
of  tricuspid  insufficiency  in   50-80%,   right   ventricular  S3  <  50%,
hepatomegaly, and Raynaud's phenomenon in less than 50%.  LABORATORY: The ECG
will demonstrate right ventricular hypertrophy, right axis  deviation,  right
atrial enlargement manifested as P pulmonale.  Chest x-ray will show enlarged
prominent  central  pulmonary  arteries  and  its  major branches with severe
tapering of the peripheral arteries.  The  lung fields will be lucent and the
right atrium and right ventricle are enlarged.  Echocardiography will  reveal
an enlarged right ventricle, thickened interventricular septum, and normal to
small  left  ventricular dimensions.  Doppler may show pulmonic and tricuspid
regurgitation.  Perfusion lung imaging may show small non-specific defects or
be entirely normal.  Arterial  blood  gas  determinations will show decreased
PCO2 secondary to hyperventilation, elevated pH, with the PO2 being normal or
decreased.  Right heart catheterization will be needed  for  confirmation  of
PPH.   Findings  include  severely  elevated  pulmonary  arterial  and  right
ventricular  pressures.   If right ventricular failure is present, there will
be increased right atrial  pressures  as  well.  Left atrial, ventricular and
pulmonary capillary wedge pressures are low or normal.  Pulmonary angiography
should be performed if segmental or large defects are seen  on  VQ  scanning.
Sudden  deaths  have  occurred  with  pulmonary  angiography  and  should  be
undertaken  with caution using low osmolar agents and subselective injections
rather than injections  into  the  main  pulmonary artery.  Determinations of
antinuclear antibodies (ANA) should be done as about  33%  of  patients  will
have   positive  ANAs.   Pathologic  findings  include  plexogenic  pulmonary
arteriopathy  found  in  30-70%   of   cases;   laminar  onion  skin  intimal
proliferation, focal medial disruption, aneurysmal dilation,  veno  occlusive
disease in 10-15%, and microthromboemboli in 20-50%.  TREATMENT:	Long term
oral   warfarin  therapy  is  usually  employed  empirically  because  silent
recurrent emboli or in situ thrombosis  may  be  the  cause of PPH or lead to
pulmonary hypertension.  Some patients  will  dramatically  reduce  pulmonary
artery  pressures  when hydralazine, nifedipine or diltiazem are used.  These
should be tried in the cardiac lab prior to chronic utilization because there
have been some fatalities or  worsening  of PPH with these drugs.  Heart-lung
transplantation is being used more and more because of cyclosporine's success
in averting rejection.

                      -PULMONARY REGURGITATION-
There is a short early diastolic murmur and secondary midsystolic murmur  due
to increased flow along LSB. Is usually a congenital lesion.

                         -PULMONIC STENOSIS-
CLINICAL: Pulmonic stenosis can  be  valvular, subvalvular, or supravalvular.
The most common type is valvular stenosis with thickening of the leaflets and
commissural  fusion.   Subvalvular  is  usually  secondary  to   infundibular
hypertrophy  and  valvular  pulmonic stenosis.  Supravalvular stenosis may be
caused by congenital rubella,  and  is  due  to pulmonary artery narrowing at
various levels.  Pulmonic stenosis may also co-exist with other defects  such
as tetralogy of Fallot.  It is convenient to divide PS into mild, moderate or
severe, based on the right ventricular-pulmonary artery gradient.  Mild cases
have  a  gradient  < 30 mm Hg, moderate to severe, 50 to > 80 mm HG.  Mild PS
rarely progresses after the first  few  months  of life.  There is a systolic
ejection click followed by a systolic ejection murmur heard best at the upper
left sternal border.  The  ECG  may  be  normal  or  show  right  ventricular
hypertrophy  and incomplete RBBB.  Most patients are asymptomatic.  The heart
is usually not enlarged.  The  right  atrial  and jugular venous pressure are
normal.  Moderate PS usually has a palpable thrill in the left upper  sternal
area,  along  with  a  right  ventricular heave, plus the murmur and ejection
click.  Rarely there may be cyanosis due  to a right to left shunt across the
interatrial septum which is usually seen in neonates and patients with severe
PS.  The ECG in most cases will reveal RVH.  Most of these moderate PS  cases
will  progress  to  exercise  intolerance with right ventricular dysfunction.
Severe PS patients have  a  thrill,  harsh systolic murmur, right ventricular
hypertrophy on ECG, and most  are  exercise  intolerant.   If  the  valve  is
dysplastic  there  may  not  be an ejection click.  The murmur peaks later in
systole and radiates widely.   The  second  heart  sound may be split.  Chest
x-ray will show enlargement of the right heart and poststenotic  dilation  of
the  main  pulmonary  artery.   Echocardiography  can  usually  differentiate
valvular  from subvalvular obstruction, but may not show peripheral pulmonary
artery stenosis.  However, CT or MRI  may be able to visualize the peripheral
stenosis.  Doppler  quantifies  the  pressure  gradient  and  determines  any
assoicated  pulmonic  insufficiency.   Cardiac catheterization will elucidate
the level and severity of  obstruction or associated lesions, while selective
angiography can assess the pulmonary artery anatomy.  TREATMENT: Treatment of
the critically ill neonate requires maintenance or restoration of patency  of
the  ductus  arteriosus  with  IV  PGE1  given  by  continuous infusion at .1
ug/kg/min initially followed by .075 or .05 ug/kg/min if hypotension develops
and cannot be corrected with volume.  Patients have 2D echo and Doppler exams
plus cardiac catheterization in  order  to  evaluate the RV cavity dimensions
and the tricuspid and pulmonary  annular  sizes.   If  balloon  valvuloplasty
cannot  be  achieved, surgical valvulotomy or valvectomy is carried out.  For
infants and children beyond the  neonatal period, with commissural fusion and
severe  obstruction  balloon  valvuloplasty  is  the  procedure  of   choice.
Initially  most  gradients  can  be  reduced  to  <  50  mm Hg, followed by a
progressive decrease to below  30  mm  Hg  in  the year following the balloon
valvuloplasty due to resolution of the subvalvular muscular obstruction.  The
mortality associated with valvuloplasty approaches zero, but is usually  less
than 1% with surgical valvectomy.  Severe valve dysplasia may be treated with
balloon  valvuloplasty.   There  are  certain  features  that  may be used to
differentiate commissural  fusion  from  leaflet  dysplasia.   In commissural
fusion, the QRS axis may be normal or demonstrate right axis deviation on the
ECG.  The chest x-ray will show the  main  pulmonary  artery  segment  to  be
prominent,  while  the  echocardiogram  will  show  mildly  thickened  mobile
leaflets  with  a  normal  annulus  and  post-stenotic dilatation of the main
pulmonary artery.  Fusion is usually  not  familial  and there will be normal
growth and facies.  The angiogram will demonstrate  doming  of  the  leaflets
with  systole  and  a central jet.  Dysplastic leaflets are associated with a
short stature, Noonan's syndrome and  dysmorphic facial features and there is
a familial tendency.  The ECG may show a  superior  QRS  axis  and  the  main
pulmonary  artery  segment  is usually normal on chest x-ray.  Echo will show
very thick, immobile  leaflets  with  a  hypoplastic  annulus  and usually no
post-stenotic dilation.  Angiograms do not show  doming  during  systole  and
there  is  no jet.  The ong term outlook is very good.  Valvular obstruction,
once corrected, rarely returns.

                        -PULMONARY STENOSIS-
Congential   lesion.    Inspiration   intensifies   the   murmur,  expiration
intensifies the click.  There is an ejection murmur at ULSB with a thrill and
ejection click.  Murmur can be loud and grating and widespread.  The best way
to localize is to move slowly across and down the chest to the  mitral  valve
area using the bell headpiece in infants and the diaphragm in older children.

                         -PURPURA (Palpable)-
Palpable purpura can be  a  vesicle,  papule  or  pustule  and  are  strongly
associated with a vasculitis.  The lesions may be associated with sepsis such
as   staphylococcal   sepsis,   streptococcal   infection,  viral  infection,
rickettsial disease, gonococcemia and meningococcemia.  In gonococcmeia there
are a few purpuric lesions  and  vesicles  seen  on the acral portions of the
extremities that develop into pustules.  Patients with  meningococcemia  have
many   hemorrhagic   papules  over  the  entire  body  that  usually  develop
explosively.   Rocky  mountain  spotted  fever  produces  pink  macules  that
progress to red papules  and  purpuric  papules, starting on the extremities.
Patients that have systemic signs, sepsis and palpable purpura should  arouse
suspicion  for  Henoch-Schonlein  purpura,  polyarteritis  nodosa, urticarial
vasculitis, inflammatory  bowel  disease,  cancer,  giant  cell arteritis and
granulomatous  vasculitis.   Henoch-Schonlein  purpura  occurs  in  children,
involves the joints, GI tract, kidneys and skin and, usually follows an upper
respiratory infection.  It  will  last  for  1-2  weeks,  but  there  may  be
recurrences.  Wegener's disease involves the upper respiratory tract, kidneys
and  skin.   Polyarteritis nodosa affects small and medium sized arteries and
involves the kidneys,  lungs,  nervous  system,  joints  and  skin.  The skin
lesions can be purpuric papules, cutaneous ulcerations,  livedo  reticularis,
or  subcutaneous  nodules.   Allergic granulomatosis (Churg-Strauss syndrome)
occurs in asthmatics  and  can  develop  chronic  pneumonitis, neuropathy and
hypertension.  Urticarial vasculitis manifests as recurrent  purpuric  wheals
which last several days associated with hypocomnplementemia in some patients.
The  workup  in  these patients include CBC, UA, ESR, ANA, rheumatoid factor,
serum protein electrophoresis, serum complement, chest x-ray, skin biopsy and
stool for blood.   In  patients  without  any  other  symptoms except for the
palpable purpura,  consider  hypersensitivity  vasculitis,  hyperglobulinemic
purpura,   erythema   elevatum   diutinum,  essential  cryoblobulinemia,  and
idiopathic  cutaneous  vasculitis.   Hypersensitivity  vasculitis  occurs  in
patients > 16 years of age, that have palpable purpura, blanching red papules
and macules usually occurring on  the  lower extremities.  Medications may be
causative.  Skin biopsy should be done to rule out immune complex disease  as
essential  mixed  cryoglobulinemia and hyperglobulinemic purpura and erythrma
elevatum diutinum.  Other tests  that  should  be  done in patients that have
only palpable purpura include a CBC, serum  cryoglobulins,  serum  complement
and chemistry panel.

                               -RABIES-
Rabies is primarily a disease of animals and is caused by  several  different
strains  of  neurotropic  viruses.   The virus gains entry into the body by a
bite or an open wound from  infected saliva.  The incubation period period is
usually 3-7 weeks, but varies widely from 10 days to several years  depending
on  the  distance  of the wound from the CNS.  The virus then travels through
the nerves to the brain where it  multiplies and then travels along nerves to
the salivary glands.  Rabies has almost a 100% mortality.  Most wild  animals
are capable of being infected, but coyotes, foxes, wolves and jackals are the
most  susceptible with raccoons, bats, skunks, bobcats, monkeys and mongooses
also susceptible.  In general  bats,  foxes,  skunks, and raccoons are widely
infected along with dogs and  cats  in  developing  countries.   Rodents  and
rabbits  are seldom infected.  Most cases of rabies are due to the bite of an
animal.  However, it can  also  be  transmitted  by  contamination of an open
wound or mucous membrane with saliva, Cases  of  rabies  occurring  following
abrasions,  scratches  or licking of open wounds or mucous membranes are very
rare.  Rabies has also  occurred  after  after inhaling aerosolized saliva in
caves that are infested with bats.  Exposure to the feces, urine or blood  of
rabid  animals  does not require any prophylaxis.  There have been 6 cases of
transmission from infected corneas that were transplanted.  Usually there are
paresthesias and pain at the  bite  site with the skin exhibiting sensitivity
to air currents and temperature changes.  The patient  becomes  restless  and
develops  convulsions,  laryngospasm,  and paralysis.  There is production of
large amounts of thick saliva and  any attempt at drinking will cause painful
laryngeal spasm which precludes any further drinking.   Any  domestic  animal
that  is  healthy  appearing  after  biting  a  person  should  be kept under
observation for 7-10 days.  Any wild  animal  should be sacrificed, if it can
be captured, and examined for rabies.  If  the  animal  cannot  be  captured,
bats,  skunks,  foxes, coyotes and raccoons should all be considered infected
and rabid.  The diagnosis can be made rapidly by fluorescent antibody testing
of the brain.  Also  sick  or  dead  animals  should likewise be examined for
rabies.  TREATMENT: Treatment  is  based  on  the  type  of  exposure  (bite,
contamination  of  open  wounds),  the  location and extent of the wound, the
regional types of rabies, and  the  type  of animal responsible for the bite.
Treatment consists of a combination of local wound care, passive immunization
and vaccination.  This combination of treatment is given  regardless  of  the
interval  between  exposure  and  the  beginning  of  treatment.  The average
interval between exposure and  start  of  prophylaxis  in  the USA is about 5
days.  All bites and scratches should be cleaned with soap and water as  this
has  shown  to markedly reduce the rate of rabies.  Rabies immune globulin is
given at 40 IU/kg.  Half of this dose is used to infiltrate around the wound.
The remaining amount is given IM  in  the gluteal area.  The syringe that has
been used to administer vaccine should never be used  for  administration  of
the rabies immune globulin, and two different anatomical sites should be used
for  the  vaccine  and  the  immune  globulin.  Never mix the vaccine and the
immune globulin in  the  same  syringe.   In  the  USA  there  are two rabies
vaccines  that  are  available;  the  human  diploid  cell   rabies   vaccine
(HDCV;Imovax  Rabies)  and  rabies vaccine adsorbed (RVA).  Both of these are
equally effective as far as efficacy  and safety.  The dose of either vaccine
is 1 ml of HDCV or RVA given IM in the deltoid area on days 0, 3, 7, 14,  and
28  (The  deltoid  area  is the preferred area for adults and older children.
For younger children the  outer  aspect  of  the  thigh is used.  The vaccine
should never be given  in  the  gluteal  area).   If  the  patient  has  been
previously  vaccinated  with  HDCV or RVA or any other type of rabies vaccine
with a documented antibody response, should  be treated with vaccine only, by
giving 1 ml of HDCV or RVA IM in the deltoid area on days  0  and  3.  Rabies
immune globulin is not indicated.  Persons that are at high risk for exposure
to  the virus as veterinarians, animal handlers, and laboratory workers where
live rabies  virus  is  handled,  or  persons  spending  a  month  or more in
countries where rabies is common and medical care is scarce, may  be  treated
prophylactically  before  exposure  to  Rabies.   It  is  not recommended for
hunters.  The dose is 1 ml of HDCV  or  RVA IM in the deltoid area on days 0,
7, and 21 or 28.  Boosters may be given depending on the amount of  continued
risk  that  may be present.  The booster dose is 1 ml of HDCV or RVA given IM
in the deltoid area.  Allergic reactions  to  the vaccine are rare, but there
may be local tenderness, pruritus and erythema  which  occur  in  about  25%.
Systemic reactions such as myalgias, headaches and nausea occur in about 20%.
The vaccine is usually obtained at the local health department.

                        -RADIATION PROCTITIS-
Radiation  proctitis  is  a  consequence  of  radiation  therapy  for  pelvic
malignancies such as cancer of the prostate and cervix.  The patient may have
chronic intermittant bleeding from  the  rectum  secondary  to  ischemic  and
fibrotic  changes.   The bleeding usually begins 6-24 months after completion
of  the  radiation  therapy.   Endoscopic  examination  will  reveal  friable
telangiectatic lesions  in  up  to  60%  of  cases.   In  the past, radiation
proctitis  was  treated  with  steroid  retention   enemas,   cholestyramine,
sulfasalazine  and  antibiotics.   These treatments have been suboptimal, and
some patients have required rectosigmoid  resection or a diverting colostomy.
Diverting colostomy may not control the bleeding, and rectosigmoid  resection
is  associated  with  a  great  deal  of  morbidity such as wound dehiscence,
infection, and poor healing.   Recently,  there  has  been success with laser
cauterization using neodymium:yttrium-aluminum-garnet laser photocoagulation.
This has controlled the bleeding, and transfusion dependent patients have not
needed transfusions.  More than 90% have been  helped  with  this  treatment.
The   remaining   patients  have  not  been  helped,  apparently  because  of
inaccessible vascular lesions.  The  best  candidates for laser treatment are
patients that have vascular lesions located  mainly  in  the  rectum.   Laser
treatment  is usually well tolerated and usually can be done as an outpatient
with  sedation.   In  most   cases   two   sessions  are  necessary.   Rarely
rectovaginal  fistulae  have  developed  as   a   complication   from   laser
photocoagulation.

                      -RASH PLUS FEVER TESTING-
SEROLOGIC  TESTING:  syphilis,  rickettsial,  streptococcal,   leptospirosis,
typhoid  fever,  Lyme  disease,  coccidioidomycosis, Mycoplasma, hepatitis B,
cytomegalovirus,   Epstein-Barr   virus,   atypical   and   typical  measles,
trichinosis, SLE, enterovirus, adenovirus.  ASPIRATION  OF  LESION  AND  GRAM
STAIN  AND CULTURE: Positive in up to 60% of meningococcemia.  Most useful in
pustular  and  petechial  lesions.   BIOPSY:  vasculitis,  fungal infections,
granulomatous disease.   Do  immunofluorescence  for  RMSF  and  SLE.   BLOOD
CULTURES:  for bacteremia, fungemia.  URETHRAL, CERVIX, JOINT, RECTUM, THROAT
CULTURE:  disseminated  gonococcal  infection.   WRIGHT  OR  GIEMSA  STAIN OF
VESICULAR  FLUID:  Herpesvirus  will  show  multinucleated  giant  cells   or
cytoplasmic inclusion bodies in up to 70%.

                        -RAYNAUD'S SYNDROME-
CLINICAL: Raynaud's syndrome may  be  divided  into  those patients that have
idiopathic Raynauds phenomenon  (Raynaud's  disease)  and  those  that  occur
secondary  to another disease.  Raynaud's phenomenon (RP) is characterized by
episodic digital ischemia which causes  blanching, cyanosis and rubor changes
of the fingers and toes when exposed  to  cold.   The  blanching  is  due  to
ischemia,  the  cyanosis secondary to deoxygenated blood that is present, and
the rubor is secondary to  rewarming  with reactive hyperemia.  Most patients
with Raynaud's syndrome (RS) are women between the ages of 25-40 years.   The
episodes  are  more  common  and  severe  in the northern climates during the
winter.  Emotion may also induce the digital vasospasm.  The fingers and toes
are usually involved  but  occasionally  the  nose,  cheeks  and  ears may be
affected.  RAYNAUD'S DISEASE is  present when no secondary  diseases  can  be
found.   Over 50% of RP is due to RD.  Initially, only the tips of one or two
fingertips may be involved,  but  later  in  the  course  of the disease, the
entire finger, or all of the fingers may be involved.  The toes are  affected
in  about 40% of cases.  RP is somewhat common in patients that have migraine
headaches and  variant  angina.   Between  attacks,  the  hands  and toes are
normal, with normal radial, ulnar and pedal pulses.  In about 10% of patients
with RD there is tightening of the  digital  subcutaneous  tissue.   Patients
that  have  RD  usually  have  a  milder  form of the disease than those with
secondary causes.  Less than 1%  of  RD  will  lose  a digit.  RD improves in
about 15% of  patients  and  worsens  in  about  30%.   SECONDARY  RAYNAUD'S:
Systemic  sclerosis  (Scleroderma) is the most common cause of RP.  RP occurs
in about 80-90% of patients with scleroderma and is the presenting symptom in
about 30%.  In fact RP may precede scleroderma by years.  Ischemic ulcers may
progress to  necrosis,  gangrene  and  autoamputation.   Approximately 20% of
patients with SLE will develop RP with occasional gangrene.  RP  develops  in
about  30% of patients with polymhyositis or dermatomyositis.  It may also be
seen  in  rheumatoid  arthritis.   Some  drugs  such  as  ergot preparations,
beta-adrenergic  blockers,   methysergide,   vinblastine,   bleomycin,   oral
contraceptives, nicotine, caffeine, sympathomimetics and cisplatin may induce
vasospasm.   Other immunologic and collagen vascular diseases associated with
RP  include   hepatitis   B   associated   vasculitis,   Sjogren's  syndrome,
polyarteritis nodosa,  hypersensitivity  vasculitis,  CREST  syndrome,  mixed
connective  tissue  disease,  Henoch-Schonlein purpura and Reiter's syndrome.
Neurologic diseases associated with  RP include syringomyelia, intervertebral
disk disease, spinal cord tumors,  carpal  tunnel  syndrome,  stroke,  reflex
sympathetic  dystrophy,  carpal  tunnel  syndrome  and peripheral neuropathy.
Blood   dyscrasias    associated    with    RP    include   cryoglobulinemia,
cryofibrinogenemia,   Waldenstrom's   macroglobulinemia,   myeloproliferative
disorders,   cold   agglutinins,    hyperviscosity    states,    disseminated
intravascular  coagulation,  and paroxysmal hemoglobinuria.  Endocrine causes
include myxedema, Graves's disease, Cushing's disease, and Addison's disease.
Trauma and occupational causes include cold injury, forstbite, vibratory tool
exposure, hypothenar-hammer syndrome,  piano  playing, typing, electric shock
and vibration injury.  Obstructive arteriopathies include Takayasu's disease,
thoracic outlet compression, arteriosclerosis obliterans,  Buerger's  disease
and  thromboembolic  obstruction.   TREATMENT: Tobacco should be interdicted.
All patients should dress warmly  with  mittens and gloves.  Nifedipine 10-30
mg TID and diltiazem 30-90 mg TID are drugs  of  choice.   Reserpine  may  be
helpful  in  doses  of  .25-.5  mg  daily,  but  side  effects  such as nasal
stuffiness,  depression,  lethargy   and   hypotension  may  be  troublesome.
Prazosin 1-5  mg  TID  may  give  favorable  results.   Also,  terazosin  and
dosazosin  have also been used with good responses.  Guanethidine 10 mg daily
in combination with prazosin 1-3  mg  daily  may  also  be used in cases that
respond poorly to the above.  LABORATORY: Initial testing should include CBC,
chemistry profile, sedimentation rate, UA, and  antinuclear  antibody  (ANA).
Other  tests  that  may  be  indicated include serum protein electrophoresis,
serum immunoglobulins, complement levels, double stranded DNA, anticentromere
antibodies, cryoglobulins and cryofibrinogen levels, anti-extractable nuclear
antigens, hepatitis B surface antigen and antibody, nerve conduction and EMG,
cine esophagography, chest x-ray, and pulmonary function tests.

                         -REITER'S SYNDROME-
Reiter's Syndrome (RS) is classified as a  seronegative  spondyloarthropathic
disease   characterized   by   the   triad   of   non-bacterial   urethritis,
conjunctivitis  and mucocutaneous lesions.  It may be sexually transmitted or
be secondary to dysentery.  The sexually transmitted form usually occurs 7-14
days after exposure.   The  predominant  age  is  between  20-40  with a male
preponderance of 9:1.  RS may follow infection with Campylobacter, Chlamydia,
Salmonella or Yersinia.  CLINICAL:  Usually  the  urethritis  develops  first
about   7-14   days   following   sexual   exposure   and  then  followed  by
conjunctivitis, arthritis and fever over  the next few weeks.  The urethritis
in men is  not  as  painful  as  that  in  gonorrhea  and  the  discharge  is
mucopurulent  or  mucoid  and  in  fact  may  be asymptomatic.  A hemorrhagic
cystitis or prostatitis may develop in 80% of the cases.  In women, there may
be a cervicitis or vaginitis  with  a  mild discharge.  The conjunctivitis is
usually mild and affects both eyes, but keratitis and  anterior  uveitis  may
develop.   The  arthritis  may  run  the  spectrum  of  severity.   The joint
involvement has a predilection  for  the  lower extremity joints particularly
the knees and ankles.  The onset is usually sudden and may last  for  several
months.   About 1/3 will have recurring attacks over years and about 1/5 will
develop chronic arthritis.  In some, the  disease  will only last for a short
time	and  then  not  reoccur.   The  patient  may  develop   enthesopathic
involvement  with  plantar  fasciitis, and achilles tendinitis and chest wall
pain.  Pain may develop  in  the  buttocks  and  back  area due to unilateral
sacroiliitis.  However, unlike ankylosing spondylitis cephalad involvement of
the axial skeleton  would  be  rare.   The  patient  may  develop  a  sausage
appearing  dactylitis  of  the  digits which is caused by inflammation of the
joints and tendon  sheath  fascia.   Very  rarely,  the  patient  may have an
aortitis with regurgitation and conduction abnormalities.  The  mucocutaneous
lesions  are painless small ulcers seen on the tongue, oral mucosa, and glans
of the  penis.   The  latter  is  known  as  balanitis  circinata.  Circinate
balanitis may antedate RS.  Hyperkeratotic skin  lesions  of  the  palms  and
soles  and  nails  may  develop  and  is known as keratoderma blennorrhagica.
Lesions may also appear on the scalp, palms, scrotum and trunk.  Prior to the
development of the hyperkeratotic  lesions,  vesicles appear which then leads
to papules  and  ultimately  to  the  hyperkeratotic  state.   There  may  be
periungual erythema and nail involvement with a brownish orange discoloration
of  the  nail.   The syndrome may last for 3-4 months, but may not completely
resolve and there may be exacerbations  of  any component of the disease over
many years.  LABORATORY: HLA-B27 is present in about 60-75% of cases and  the
sedimentation rate is elevated.  There may be a mild anemia, leukocytosis and
hypergammaglobulinemia.   X-rays  of  peripheral joints are usually normal at
the start of the disease.  There may  be  spurs and new bone formation at the
calcaneous.  Sacroiliac  x-rays  show  sclerosis  and  erosion  unilaterally.
Syndesmophytes  of  the  spine  may  be  seen.   DIFFERENTIAL  DIAGNOSIS: The
differential  diagnosis  would  include  ankylosing  spondylitis,  gonococcal
arthritis, psoriasis, rheumatoid arthritis, psoriatic arthritis and bacterial
arthritis.  Synovial fluid analysis in Reiter's syndrome would typically show
leukocytes counts from 5000 to 50,000/mm3 with a predominance of neutrophils.
Reiter's syndrome appears to be  increasing in HIV disease.  TREATMENT: Since
sexual exposure is considered a route of infection,  the  patient  should  be
treated  with tetracycline or erythromycin 500 mg qid for 10 days in order to
eradicate Chlamydia trachomatis.  Otherwise,  symptomatic  care is given with
NSAIDs.  In particular, indomethacin and  phenylbutazone  may  be  used.   No
treatment  is  given for the conjunctivitis unless there is co-existence with
keratitis and iritis,  and  then  topical  ophthalmic  steroids  may be used.
Systemic steroids are not useful.  Local steroids may control flairs.

                           -RENAL CALCULI-
Renal calculi (urolithiasis, nephrolithiasis, kidney  stones)  affects  about
4-8% of the people in the USA.  It has an incidence of 7-21 cases/10,000 with
a  lifetime  prevalence  of  12%  for men, and 5% for women by the age of 75.
Eighty percent of patients are  men  with  a  peak onset between 20-30 years.
The incidence is greatest in the southeastern USA and in the summer.   Stones
are  typically  located in the renal calicies or pelvis, but may become lodge
in the ureter or  bladder.   Calculi  can  vary  in  size from microscopic to
stones that are several centimeters in diameter.  Most stones are less than 5
mm in diameter and will pass spontaneously, usually within 2-3 days.   Stones
larger  than  5 mm are reluctant to pass.  About 80% of stones in the USA are
composed of calcium (mainly calcium oxalate),  5% are uric acid stones and 2%
are  cystine.   The  rest  are  composed  of  magnesium  ammonium   phosphate
(infection  or  struvite  stones).  Of the patients who have a urinary stone,
about 50% will have a recurrent  stone within 10 years.  White adult patients
with a first stone require only a measurement of SMA 25 and determination  of
urinary  acidification.   Black  patients  have a low incidence of idiopathic
stone formation, and an  etiology  should  be determined.  Children require a
complete workup.  CLINICAL: If there is obstruction  of  the  calyces,  renal
pelvis  or  the  ureter, there may be back pain and renal colic (intermittent
excruciating pain starting in the flank and radiating along the course of the
ureter into the genitalia and  inner  thigh).  Calculi in the bladder usually
cause  suprapubic  pain.   Patients  may  have  nausea,  vomiting   abdominal
distention,  and  ileus.  There may be fever, chills, hematuria and frequency
of urination.  Patients with  staghorn  calculi  often  have chronic flank or
back pain.  Anterior abdominal pain is a rare  finding.   Physical  exam  may
reveal  tachycardia,  diaphoresis and tachypnea.  Patients with stones at the
ureterovesical junction have  irritative  urinary  symptoms  such as urgency,
frequency and dysuria.  Stones in the renal pelvis may  be  asymptomatic,  as
may small caliceal stones.  LABORATORY: 	There may be gross or microscopic
hematuria.   Absence  of  hematuria  does not rule out a stone.  There may be
mild  proteinuria  and   glycosuria   reflecting   tubular  dysfunction  from
obstruction.  If an acid pH is  found  on  examination  of  the  urine,  this
virtually  excludes  renal  tubular  acidosis  as a cause.  An alkaline pH is
suggestive of urea-splitting bacterial  struvite  stones.  Calcium stones are
usually associated with an alkaline urine (pH >7), urate or purine stones are
associated with an acidic urine (pH <7), and  cystine  stones  are  variable.
All  patients  should  have  a  blood  CBC,  serum calcium, sodium, chloride,
potassium, bicarbonate, uric acid and creatinine.  Hypercalcemia will require
a serum parathyroid hormone assay.  If the composition of a stone is unknown,
a qualitative urine screen should  be performed for cystinuria (nitroprusside
test).  All urine should be strained,  as  80%  of  first  stones  will  pass
spontaneously.   The  stone  should  then  be  sent  for  chemical  structure
analysis.   A  spot  urine  should  be  done for urine calcium and creatinine
(milligrams).  From  this  calculate  the  calcium/creatinine  ratio which is
normally less than 0.1.  If the ratio is greater than 0.3, hypercalciuria  is
usually  present.   Also,  a  magnesium/calcium  (milligrams) ratio should be
done.  If the ratio is  less  than 33, this indicates hypomagnesiumuria.  The
IVP is the study of choice, which  may  reveal  a  dense  nephrogram  on  the
affected  side,  or  the  contrast  column may be "cut off", or demonstrate a
stone shadow.  A delay in visualization is suggestive of complete or subtotal
ureteral obstruction.  An IVP done  during  an  acute  episode may be of poor
quality and a repeat high resolution  IVP  with  tomograms  may  be  done  to
exclude  medullary  sponge kidney.  For patients that are allergic to the IVP
dye, renal ultrasound can be  done.   False  positives  may occur in renal US
with lower ureteral stones.  Most calculi  can  be  seen  on  KUB,  with  the
exception  of  uric  acid  stones, xanthine calculi, and some stones composed
mainly of protein matrix.  These  are radiolucent.  Calcium that is deposited
in the pyramids is diagnostic of nephrocalcinosis and should lead to a search
for sarcoidosis,  renal  tubular  acidosis,  hyperparathyrodism,  milk-alkali
syndrome  and  Cushing's  disease.   All patients should have a 24 hour urine
collection  for  analysis  of  volume,  pH  and  calcium,  phosphate, sodium,
oxalate, uric acid, citrate and creatinine.  Urine cultures should be done if
indicated.   DIFFERENTIAL  DIAGNOSIS  includes  irritable   bowel   syndrome,
intestinal  obstruction,  appendicitis,  peptic  ulcer,  mesenteric adenitis,
inflammatory   bowel    disase,    gastroenteritis,   acute   diverticulitis,
cholecystitis,   pancreatitis,   ectopic   pregnancy,   salpingitis,   aortic
dissection and mesenteric infarction.  CALCIUM STONES: Calcium stones are the
most common and may be divided into two types; calcium oxalate,  and  calcium
phosphate  oxalate  stones.   All  of  these are radiopaque.  Ultimately, all
cases are due to  increased  levels  of  calcium  in  the urine and different
mechanisms may be responsible for the increase in urinary levels.  In men,  a
24  urinary  calcium  greater than 300 mg, or greater than 250 mg in women is
abnormal.  Secondary  causes  of  hypercalciuria include hyperparathyroidism,
Cushing's syndrome,  sarcoidosis,  TB,  disseminated  candidiasis,  leukemia,
lymphoma,  myxedema,  adrenal insufficiency, milk-alkali syndrome, idiopathic
infantile   hypercalcemia,   leprosy,   hyperthyroidism,   multiple  myeloma,
metastatic cancer, vitamin D intoxication, immobilization,  Paget's  disease,
renal  tubular  acidosis  and hypomagnesemia.  Primary hyperparathyroidism is
caused  by  a  parathyroid  adenoma  or  parathyroid  hyperplasia  causing an
elevated PTH which leads to a secondary  hypecalciuria.   This  is  the  most
common  hypercalcemic  cause  of  urinary  calculi.   About  15%  of  primary
hyperparathyroidism  patients will have stones, and many of these are calcium
phosphate.   Hyperuricemia   and   hyperuricosuria   may   coexist  with  the
hypercalcemia.  Primary Hyperparathyroidism	is responsible for about 5-15% of
all  stones.   IDIOPATHIC  HYPERCALCIURIA  may  be  divided  into  absorptive
hypercalciuria and renal hypercalciuria, and renal phosphate leak.  It  is  a
hereditary  condition that is present in 50% of men and 75% of women who form
calcium stones.  Absorptive hypercalciuria is due to increased absorptiopn of
intestinal calcium with increased GI loads.  In renal hypercalciuria there is
impaired renal tubular  reabsorption  of  calcium.   In  renal phosphate leak
there is impaired renal tubular  reabsorption  of  phosphate  which  in  turn
stimulates  synthesis of 1,25-(OH)2-vitamin D. Calcium stones may be promoted
by  hyperuricosuria,  hyperoxaluria,   hypocitraturia,  and  hypomagnesiuria.
HYPERURICOSURIA  occurs  in  20%  of  calcium  oxalate  stone  formers.   The
monosodium urate or uric acid crystals form the nidus  for  calcium  oxalate.
The  hyperuricosuria  may  be due to increased intake of purine from poultry,
fish, and meat, or primary  uric acid overproduction.  Hyperuricosuria should
be suspected when the 24 hour uric acid in men is  greater  than  800  mg  or
greater  than  750  mg in women.  HYPEROXALURIA can be due to enteric causes,
excess dietary  oxalate,  hereditary,  hypervitaminosis  C  (ascorbic acid is
metabolized to  oxalate),  methoxyflurane  anesthesia,  and  ethylene  glycol
intoxication.   Enteric  causes  are  due  to  small  bowel  disease  and fat
malabsorption.  Unabsorbed bile  salts  and  fatty  acids increase intestinal
permeability to oxalate.  Unabsorbed  fatty  acids  will  complex  with  free
calcium  which leaves less calcium to complex dietary oxalate.  This leads to
more free oxalate available for  absorption.   HYPOCITRATURIA can cause up to
30% of stones.  A 24 hr urinary citrate less than 320 mg can lead to  calcium
stones.  Plentiful urinary citrate will complex with calcium and reduce ionic
calcium  concentrations.   Citrate also can directly impede crystal formation
of calcium oxalate and  calcium  phosphate.   Causes of hypocitraturia may be
metabolic acidosis due to thiazide induced hypokalemia, high  sodium  intake,
distal  renal tubular acidosis, chronic diarrhea and excessive dietary animal
protein, OR the hypocitraturia  may  be idiopathic.  HYPOMAGNESIURIA can also
cause calcium stones.  Urinary magnesium complexes with oxalate and decreases
the free oxalate available.  Magnesium depletion may  be  due  to  inadequate
dietary  intake  or  malabsorption.  ALKALINE URINE has a tendency to calcium
phosphate crystallization.  TYPE I DISTAL  RENAL TUBULAR ACIDOSIS is uncommon
and is due to tubular dysfunction  which  causes  an  inappropriate  loss  of
calcium  in  the  urine  with  a  concurrent decrease in the normal amount of
citrate in  the  urine.   Citrate  normally  complexes  calcium  in the urine
decreasing the risk of stone formation.  URIC ACID STONES: Uric  acid  stones
are uncommon.  Uric acid stones make up about 5-10% of all calculi.  They are
radiolucent  and  therefore  are  invisible  on x-rays.  Causes may be due to
hyperuricosuria, acidic urine (acidic urine causes a shift from urate to less
water soluble uric acid), and low  urine volume.  In tophaceous gout there is
an increased hyperuricosuria.  Tophaceous gout is another cause of uric  acid
stones.   Tophaceous  gout  occurs  in  patients  who  have a long history of
recurrent gouty arthritis.  The total  body  stores of uric acid are elevated
which leads to  deposition  in  the  soft  tissues  (tophi).   DEFICIENCY  OF
HYPOXANTHINE-GUANINE   PHOSPHORIBOSYL   TRANSFERASE   (HGPT)  results  in  an
inability   to   catabolize    purines,    leading   to   hyperuricemia   and
hyperuricosuria.  If the deficiency is complete, the patient  has  the  Lesch
Nyhan  syndrome.   MYELOPROLIFERATIVE  DISORDERS  may be associated with high
uric acid levels.  HIGH DOSE SALICYLATES AND PROBENICID can lead to increased
tubular excretion of  uric  acid  and  uric  acid stones.  MAGNESIUM AMMONIUM
PHOSPHATE (STRUVITE STONES, STAGHORN CALCULI): These  stones  are  associated
with chronic urinary tract infections with urease-splitting organisms such as
Pseudomonas,  Proteus,  Morganell  spp,  and  Klebsiella).   These  organisms
contain  the  enzyme  urease,  which breaks down urea, and causes an alkaline
urine with NH4 in the urine, which promotes the formation of triple phosphate
crystals.  Struvite stones account for about 5-10% of all urinary stones, and
are more common in women  than  men.   These calculi are radiopaque.  CYSTINE
STONES: Cystine stones are rare and usually are congenital.  About .5% of all
stones are cystine stones.  They are radiopaque.  It appears as an  autosomal
recessive  trait  which results in defective proximal tubular reabsorption of
cystine.  MISCELLANEOUS CAUSES OF STONES: Triamterene can precipitate in some
patients that are taking this diuretic.  Xanthine stones are due to excessive
production of xanthine  in  patients  with  high  purine  metabolism that are
treated with allopurinol.  TREATMENT OF STONES: GENERAL: All patients  should
be  hydrated.   The  average normal person has a 24 urinary output of about 1
liter.  Increasing the urinary  output  to  about  2  L/day will decrease the
chance of recurrence by about 66%.  Increasing the urine output  to  3  L/day
will  reduce  the  chance  of recurrence by 90%.  The greatest risk for stone
formation is nocturnally, and 2-3  hours following meals.  Thus, fluid should
particularly be encouraged  during  these  times.   For  obstructed  ureteral
stones,  ESWL  is  the preferred treatment for calculi in the proximal 2/3 of
the ureter.  For calculi in the distal 1/3 of the ureter, either ureteroscopy
or WSWL may be used.  Renal colic  can  be treated with morphine 10 -15 mg or
meperidine 100 mg IM q3-4 hours.  CALCIUM STONES: Thiazides are effective for
patients with hypercalciuria greater than 250 mg/24 hours, and in those  with
normal  levels  of  calcium  in  the urine.  Thiazides function by increasing
distal calcium reabsorption.  The dose  is  usually 25-50 mg daily.  The mean
reduction in urinary calcium is about 150 mg/day which is usually maximal  at
about  1-2 weeks.  For absorptive hypercalciuria the calcium intake should be
reduced, and  treated  with  sodium  cellulose  phosphate, or orthophosphate.
Sodium cellulose phosphate can be used to bind calcium in the GI tract.   The
average adult dose is 10-15 g qd.  It is contraindicated in urinary infection
or  poor  renal  function.   Diarrhea  is a side effect.  Orthophosphate will
inhibit  1,25-(OH)2-vitamin  D  synthesis,  decrease  saturation  of  calcium
oxalate by  increasing  urinary  pyrophosphate  and  bind intestinal calcium.
Orthophosphates are supplied as acidic,  neutral  or  alkaline  preparations.
The  patient is usually placed on a neutral preparation.  The dose for men is
1500 mg or more of phosphorus  given  as  500  mg every 8 hours.  For women a
total dose of 1250 mg, given every 8 hours may  be  used.   Side  effects  of
orthoposphate  are  usually diarrhea.  It is contraindicated in patients with
poor renal  function  or  urinary  infection.   Patients  with hypocitraturia
(usually occurs in patients with renal tubular acidosis  and  in  those  with
hypercalciuria and hyperuricosuria, or in those with chronic diarrhea) can be
treated  with  potasssium  citrate  tablets.  This causes an elevation of the
urinary pH which will  in  turn  increase  the  excretion of urinary citrate.
Potassium citrate tablets are given as 20 mEq TID PO initially, and  titrated
until  the  24  urinary citrate is greater than 320 mg.  Potassium citrate is
contraindicated in renal insufficiency.  The side effect is sodium retention.
Allopurinol may be useful in  those  patients with calcium oxalate stones and
hyperuricosuria.  It is usually given as 300 mg daily.   The  patient  should
also  be  on a decreased purine diet.  Patients that have a magnesium deficit
may be treated with magnesium oxide  or  gluconate  150 mg qid or 500 mg bid.
This will increase urinary magnesium and decrease urinary calcium.  The  side
effect  is  diarrhea.   In  summary,  those  patients  with hypercalcemia and
hypercalciuria with  elevated  parathyroid  hormone  should  be  treated with
surgical removal of the parathyroid glands.  Those  who  have  hypercalciuria
and  hyperabsorption  may  be  treated  with neutral or cellulose phosphates.
Those patients that have hypercalciuria due to a renal leak, are treated with
thiazides.  Those patients that have  normocalciuria and low urinary citrate,
are  treated  with  oral  citrates.    Those   patients   with   a   relative
hypercalciuria  and  a  low  magnesium can be treated with magnesium oxide or
gluconate.  Those patients that  have  hyperuricemia and hyperuricosuria with
calcium stones, can be treated with allopruinol.  Patients with hyperoxaluria
and intestinal  hyperabsorption  are  treated  with  low  oxalate  diet  plus
citrate,  and  magnesium  gluconate.   URIC  ACID  CALCULI  are  treated with
allopurinol 300 mg daily if  the  24  urinary  uric acid excretion is greater
than 750 mg/day.  Alkalinzation of the urine may also help decrease the  uric
acid  stones.  Sodium bicarbonate or potassium citrate is usually given every
6 hours to achieve  a  urinary  pH  of  6.7-7.   Most  uric acid calculi will
dissolve with this therapy.  Most uric acid stone formers have low volumes of
urine less than 1200 ml/day.  Patients should increase their fluid intake  to
keep  the urinary output to at least 2 liters or more/day.  STRUVITE CALCULI:
The initial treatment  should  be  surgical  removal  of  the stones and then
control of  chronic  urinary  infections.   Surgery  may  be  a  percutaneous
nephrolithotomy,  open  lithotomy,  or  extracorporeal shock wave lithotripsy
(ESWL), depending on the size of  the  stone.   More than 90% of renal stones
can be treated with ESWL.  ESWL is the best treatment for renal  stones  less
than  2  cm.  Lithotripsy may be used for stones in the calyces, renal pelvis
and the ureter.  Struvite calculi are usually large and branched which form a
cast of the  collecting  system,  the  renal  pelvis  and  one  or all of the
calyces.  These large calculi are usually first debulked with a  percutaneous
nephrolithotomy.   The  residual  stones  are then fragmented with ESWL.  The
fragments are allowed to pass for  about 2 weeks before the collecting system
is visualized through the  original  nephrostomy  tract.   If  any  fragments
remain,  these  are  removed.   This  second visualization may be bypassed by
irrigating the  collecting  system  with  hemiacidrin  (Renacidin), which can
dissolve  the  stones.   Prior  to  surgery  the  patient  is  treated   with
appropriate  antibiotics  for  1  week, and for 2-3 weeks post surgery.  Long
term prevention of struvite stones  may require prophylactic antibiotics such
as amxoicillin 250 mg daily.  Furthermore, patients should avoid  medications
that contain magnesium such as Mylanta, Maalox and milk of magnesia.  CYSTINE
STONES  are  treated  with  hydration  which may require more than 4 L/day of
fluids.  Potassium citrate or  sodium  bicarbonate  may be used to alkalinize
the urine to a pH of 7-7.5.

                       -RENAL FAILURE (Acute)-
Acute renal failure  represents  a  sudden  decrease  in renal function.  The
history  should  rule  out   infection,   volume   disturbances,   allergies,
medications,  systemic  disease,  malignancy,  prostatism,  and  stones.  The
urinalysis becomes important  in  identifying  the  different etiologies.  If
pyruia,  WBC  casts  and  a  positive  culture  are  present  consider  acute
pyelomephritis.  If pyuria, WBC  casts  and  negative  culture  are  present,
consider   allergic   interstitial  nephritis.   The  most  common  cause  of
interstitial nephritis is a drug induced allergic reaction from such drugs as
pemnicillin,  NSAIDs,  methicillin,   cephalothin,  sulfonamides,  thiazides,
furosemide, and cimetidine.  In  general,  there  will  be  partial  to  full
recovery  following  withdrawal of the offending drugs.  Patients with severe
interstitial nephritis characterized by a  creatinine > 2.5-3, may respond to
prednisone at 60 mg/day.  If the UA  discloses  RBC  casts,  proteinuria  and
dysmorphic  RBCs,  a  rapidly  progressing glomerulonepritis (RPGN) should be
considered, and  should  prompt  an  array  of  serologic  tests.  Such tests
include, antineutrophil cytoplasmic antibodies (Wegner's granulomatosis or  a
necrotizing   systemic   vascultis),  low  C3,  C4  (SLE  glomerulonephritis,
postinfectious glomerulonephritis, cryoglobulinemia or membrano-proliferative
glomerulonephritis),  positive  anti-glomerular  basement  membrane  antibody
(Goodpasutre's disease), positive hepatitis  B  or HIV antigenemia (hepatitis
or  AIDS-related  nephropathy),  and  ANA  (lupus  glomerulonephritis).    If
serology  is  negative,  focal  sclerosis,  minimal  change disease and drugs
should be considered.  If the UA  discloses tubular cell casts or muddy brown
casts consider acute tubular necrosis (ATN) resulting from toxic or  ischemic
damage  to  the  renal  tubular  epithelium.   Common  causes of toxic damage
include drugs as aminoglycosides, cisplatin  and amphotericin B, heavy metals
as mercury and lead, radiocontrast material, myoglobin and multiple  myeloma.
In  ATN  the BUN/Pcr is usually normal at 10-20:1.  Also, a urine sodium > 20
mEq/L or fractional excretion of sodium (FeNa)  > 1 % supports a diagnosis of
ATN, but lower values for both of these tests may  be  present,  particularly
early  in  ATN.   To  calculate  the  FeNa%  obtain a random urine sample for
analysis of sodium and creatinine and  a  sample of plasma for creatinine and
sodium, and then use the following formula: FeNa%=Una x Pcr/Ucr x Pna x  100.
Rhabdomyolysis  can  be  confirmed  by elevation of plasma creatine kinase, a
positive urine  dipstick  for  heme  without  RBCs  see  on  microscopy and a
positive test for myoglobinuria.  Also, there usually is a low BUN/Pcr ratio,
and  high  serum  concentrations   of   potassium,   urate   nad   phosphate.
Rhabdomylosis  is  made  worse  by  dehydration  and  hypotension.  Causes of
rhabdomyolysis include alcohol, cocaine,  heat  stroke, and trauma.  Prerenal
acute renal failure is characterized by an elevated BUN/Pcr  ratio,  Una  <10
mEq/L  or FeNa <1%.  Prerenal causes for azotemia include hypotension, volume
depletion, CHF, NSAIDs, cirrhosis and severe bilateral renal artery stenosis.

                      -RENAL FAILURE (Chronic)-
Chronic  renal failure is an irreversible loss of nephrons that occurs slowly
over years.  Common  causes  include chronic glomerulonephritis, hypertensive
arterionephrosclerosis, diabetes mellitus, interstitial nephritis,  analgesic
abuse,  adult  polycystic kidney disease, chronic pyelonephritis, and various
hereditary disorders.  Diabetes mellitus accounts  for about 33% of end stage
renal disease (ESRD),  hypertension  29%,  glomerulonephritis  (15%),  cystic
kidney disease 4%, and interstitial nephritis 3%.  Overall, males account for
55%  of  ESRD and females 45%.  Glomerulonephritis is usually associated with
proteinuria > 3.5  g/dl,  hypertension,  and  an  active  urine consisting of
hematuria and red cell casts.  The  kidneys  are  small  on  ultrasound  with
increased  echogenicity.   Patients  with  neprosclerosis  have a proteinuria
between .5 and 1  g/day,  decreased  urinary  volume, hypertension, and small
echogenic kidneys on ultrasound.  Patients with interstitial nephritis have a
proteinuria < 1.5 g/dl.  The urine may show white  cell  casts,  and  pyuria.
The  kidneys  are  small and echogenic by ultrasound with an irregular cortex
due  to  scarring.   Hypertension  is  uncommon  in  interstitial  nephritis.
Patients with CRF may  be  asymptomatic  until the glomerular filtration rate
decreases to less than 25% of normal.  Most patients will  need  dialysis  or
renal  transplant  when the nephrons decrease to below 5%.  During the course
of development  of  chronic  renal  failure,  several  changes  take place as
follows: The serum creatinine will rise and  once  it  has  reached  a  level
greater  than  1.5  g/dl,  progression  to  end stage renal disease (ESRD) is
common.  There is a fall in renal function in a linear fashion as seen by the
formula  1/serum  creatinine.   As  the  renal  failure  advances  the  serum
creatinine will double for every  50% reduction in glomerular filtration rate
(GFR).  The PO4 will rise and the serum calcium will fall.  Hypocalcemia will
stimulate PTH which will cause phosphaturia and mobilization of calcium  from
the  bones.   This  leads  to  metabolic  bone  disease  as renal rickets and
osteomalacia (deficiency of  vitamin  D),  osteitis  fibrosa (secondary to an
increase in PTH)  and  metastatic  calcification.   Metastatic  calcification
occurs when the PO4 x Ca product is > 70.  The calcification can be vascular,
visceral   or  periarticular.   Vascular  calcification  can  cause  ischemic
ulcerations of the skin and GI  tract.  Organ calcification can cause cardiac
conduction and arrhythmic disorders, restrictive lung  diease,  and  skeletal
calcifications.   Periarticular  calcification can cause arthritis.  Osteitis
fibrosa cystica is characterized  by  an  elevated parathyroid hormone level,
increased alkaline phosphatase and subperiosteal reabsorption noted on x-rays
(particularly  the  phalanges  and  the  distal  third  of  the   clavicles).
Osteomalacia  is  characterized  by  decreased vitamin D levels, decreased or
normal parathyroid hormone  levels,  normal  alkaline  phosphatase levels and
normal or increased calcium levels.  As the  renal  failure  progresses,  the
hemoglobin  will  drop.   This  leads  to  a  compensatory shift of the O2-Hb
dissociation curve to the  right  which  unloads  oxygen at the tissue level.
However, as the hemoglobin decreases to less than 7-8 g/dl, the patient  will
become  symptomatic.   The  anemia  is  normocytic  and  normochromic  due to
decreased RBC survival, erythropoietin deficiency and a decreased response to
erythropoietin due to uremic toxins.  Transfusions may be necessary, but this
brings with it an increased  risk  for  viral infections such as hepatitis C,
HIV infections, and hemochromatosis.   Anabolic  steroids  are  effective  in
about  1/2  of  the  patients  treated.  Howver, the effect is very slow (> 6
months).  These  function  by  stimulating  erythropoietin.   Side effects of
anabolic   steroids   include   virilization   in   women,    hepatotoxicity,
hepatocellular   cancer   and   peliosis   hepatitis.    Recombination  human
erytropoietin (EPO) may also  be  used  to  raise  the hemoglobin.  It can be
given intravenously or subcutaneously.  It is probably  more  effective  when
given subcutaneously, and when given by this mode, the dose is usually 1/2 to
1/3  that  of  the  IV  dose.   It should be given to maintain the hematocrit
between 30-36%.  Complications of EPO include the development of hypertension
in about 35-40%  of  patients,  seizures  (is  a relative contraindication in
patients with seizures), hyperkalemia, hyperphosphatemia and  increased  BUN,
and  iron deficiency (patients should be started on iron therapy when the EPO
is started).  Failure  to  respond  to  EPO  can  be  due to iron deficiency,
infections, febrile illness, malignancy, and aluminum intoxication.  Patients
may be monitored by hematocrits, iron saturation and  ferritin  levels.   The
goal is to keep the ferritin level > 100 ng/ml and the iron saturation > 20%.
CLINICAL:  Early  symptoms  of  chronic  renal failure consist of GI symptoms
(nausea, anorexia, vomiting  and  weight  loss),  CNS symptoms (nocturnal leg
cramps, poor concentration, and fatigue).  Late symptoms consist  of  cardiac
symptoms   (  uremic  pericarditis,  and  cardiac  tamponade),  CNS  symptoms
(neuropathy  and  encephalopathy),  and  metabolic  symptoms  as  itching and
metabolic bone disease.  TREATMENT: It has  been  shown  that  diets  low  in
protein  and phosphorus will retard the progression of chronic renal disease,
and diets  high  in  lipids  may  accelerate  it.   ACE  inhibitors  are also
important in slowing the progression by reducing intraglomerular pressure  in
the  remaining hyperfunctioning glomeruli.  ACE inhibitors are also important
in controlling  systolic  and  diastolic  hypertension.   Volume overload can
aggravate the blood pressure and may require the use  of  diuretics  such  as
furosemide.   Thiazides  are  usually  not  effective  in  severe  CRF.   All
secondary  factors  should  be  controlled as correcting volume depletion and
hypotension.  Drugs such as  NSAIDs,  aminoglycosides, and radiocontrast dyes
should be avoided.  Metabolic acidosis is common in patients with CRF because
of increased renal loss of  bicarbonate  and  impaired  excretion  of  acidic
metabolites.   If  the acidosis is mild, NaHCO3 can be given as 600 mg bid or
tid or CaCO3 500-1000 mg bid or  tid,  in order to keep the serum HCO3 around
20 mEq/l and an arterial pH less than 7.35.  Anemia is treated  with  EPO  at
40-100  IU/kg  SC  3  times/week.   Packed  RBC  should only be used in those
patients with angina or  CHF.   When  given  for these situations, furosemide
should be given concomitantly.  Hyperkalemia is usually not a problem  unless
the  patient  has  oliguria.   However, nonselective beta blockers, potassium
sparing  diuretics,   ACE   inhibitors,   NSAIDs,   metabolic   acidosis  and
hyporeninemic hypoaldosteronism can  all  increase  the  potassium.   If  the
potassium  needs  to  be  restricted,  the  diet  should  be  restricted to 1
mEq/kg/day (50-70 mEq/day).  The sodium is usually restricted to 1-3 g/day (1
gram of sodium is equal to 43 mEq  of sodium) OR 2-6 g/day of sodium chloride
(1 gram of NaCl is equal to 17 mEq of sodium).  Patients should have  dietary
restriction  of  PO4  to  300-700  mg/day.   Patients  should avoid very high
phosphorus containg foods such as eggs, cheese, milk and cream.  If a further
reduction is needed, CaCO3 .5-1 gram tid  will bind PO4 and decrease the PO4.
Protein should be restricted to .6-1 g/kg.  Patients  that  have  proteinuria
will  need  added  protein of 1 gram/day for every 1 gram/day of proteinuria.
Patients on peritoneal diaylsis  will  also  need  an  increase in protein of
1.2-1.5 g/kg/day due to peritoneal loss of protein into the  dialysate  which
can  be  up  to  10-20  grams/day.   Patients  on hemodialysis require .8-1.2
g/kg/day of protein.  Approximately  1/3  of  the  protein should be given as
high biological protein rich in essential amino acids as milk eggs, meat  and
fish.   Patients  will need about 35-40 kcal/kg/day to avoid malnutrition and
catabolism.  Patients on  peritoneal  dialysis  will  add calories.  About 71
kcal are added with 2 liters of 1.5% dextrose, and up to 214 kcal with  4.25%
dextrose.   Fluid  management  is  also  important  in chronic renal failure,
especially in those that  are  receiving peritoneal dialysis or hemodialysis.
Patients  on  hemodialysis  are  usually  restricted  to  1000-1500   ml/day.
Peritoneal  dialysis  will remove more fluid from the patient with hypertonic
dialysate solutions, so  they  may  be  given  more  fluids than hemodilaysis
patients.  In general 2 liters of 1.5% dextrose will remove 200  ml/exchange.
Two  liters  of  4.25%  dextrose  will  remove  400-600 ml of fluid/exchange.
Magnesium should be avoided in  CRF  because of decreased excretion.  Several
antacids contain antacids and should be  avoided.   Iron  supplementation  is
needed,  due  to blood loss in hemodialysis, blood loss from uremic gastritis
and EPO use.  Water soluble vitamins  must  also be replaced, due to dialysis
loss and poor intake.  Patients should receive  vitamin  C,  folic  acid  and
pyridoxine.  At some point during the course of CRF, drugs and diet will fail
to  control  the  patient's  uremia  and  hyperkalemia, and dialysis or renal
transplant will  be  needed.   Dialysis  should  be  considered  when the BUN
reaches  between  80-100  mg/dl  and  the  creatinine  reaches  8-10   mg/dl.
Hemodialysis can be accomplished in two manners.  For short term hemodialysis
a  subclavian catheter can be inserted.  For long term dialysis, the patients
will need an AV fistula  or graft.  Continuous ambulatory peritoneal dialysis
(CAPD) is used in those who have diabetes, cardiovascular  problems,  elderly
patients, and in those who have difficult vascular access.  CAPD is easier to
manage,  but  does  have  complications  such as protein loss, hyperglycemia,
peritonitis, and dyspnea in COPD patients.  Renal transplantation can be more
economical than chronic dialysis on a long term basis.

                    -RENAL FAILURE (reversible)-
Check for  a  change  in  mental  status,  family  history  of renal disease,
nephrotoxic medications, iodine contrast use, and decreased  urinary  volume.
There  may  be  worsening  of CHF or hypertension.  Check BUN and creatinine.
The bladder should be catheterized.  A  residual > 100 ml suggests incomplete
emptying.   A  fresh  urine  prior  to  diuretics  is  checked  for  UA,  Na,
creatinine,  Ucr/Pcr,  renal  failure  index  (100  x   (UNa)/(Ucr/Pcr)   and
Fractional  excretion  of  sodium,  (FENa)=(100  x  (UNa  x PNa)/(Ucr x Pcr).
PRERENAL PROFILE:UNa IS <20  (is  also  found  in acute obstructive uropathy.
UNa <10 is found in hepatorenal syndrome), Ucr/Pcr > 20, renal failure  index
<1,  and  FENa  <1.  ACUTE TUBULAR NECROSIS PROFILE: UNa >40 (may be found in
chronic obstructive uropathy), Ucr/Pcr < 20, renal failure index >2, FENa >2.
UNa and Ucr/Pcr are about 70% specific while the renal failure index and FENa
are >90% specific for acute tubular necrosis.  RENAL CAUSES: aminoglycosides,
iodine  contrast  media,  nonsteroidal  anti-inflammatory  agents, Captopril,
enalapril  in  presence  of  renovascular  disease,  sepsis,  accelerated  or
malignant hypertension,  severe  increase  in  serum  calcium  or  potassium,
rhabdomyolysis  and  myoglobinuria,  multiple myeloma, athero-embolic disease
(may masquerade as autoimmune  disease),  urate nephropathy from neoplasm and
chemotherapy, adult hemolytic uremic  syndrome,  thrombotic  thrombocytopenic
purpufa, and lead or other heavy metal toxicity.  POSTRENAL: carcinoma of the
prostate,   bladder,   or   cervix,  papillary  necrosis  from  diabetes  and
analgesics, and benign prostatic hyperplasia.

                       -RENAL TRANSPLANTATION- 
All patients with end stage renal disease  should  be  considered  for  renal
transplantation,  but  there  are  many  obstacles  to  overcome.  There is a
problem  with  donor   availability   and   selection,  transplant  procedure
complications  and  rejection,   transplantation   costs   (about   $40,000),
infection, post transplantation hypertension, dyslipidemia, acute and chronic
rejection,  recurrence  of  the  original  disease, high incidence of cancer,
hepatic disease, osteopenia, and renal  rejection drug complications.  On the
other hand, there has been increasing recipient survival over the years.  The
patient survival 1 year after a transplant from a  living  related  donor  is
greater  than  95%  with  approximately  90%  of  the  allografts maintaining
function.  After the first year,  there  is  an annual attrition rate of 3-5%
for graft loss and death.  The 1 year survival rate after a tranplant from  a
cadaver is approximately 90% with graft survival rates between 70-90%.  After
the  first  year  following  a  cadaver  transplant,  5-8% of grafts are lost
yearly.  The waiting list for kidney donors has increased over the years.  In
the USA, there were approximately 18,000 patients waiting for a transplant in
1990, and this increased to  about  25,000  in  December of 1993.  Only about
30-50 cadaveric kidneys/million population are available in the USA.  Most of
the recipients that have had cadaveric tranplants had end stage renal disease
secondary to  insulin  dependent  diabetes  mellitus  (31%).   The  remaining
consist of chronic glomerulonephritis (28%), polycystic kidney disease (12%),
nephrosclerosis  (9%), SLE (3%), interstitial nephritis (3%), IgA nephropathy
(2%), and Alport's syndrme (1%).   Greater  than  66% of kidneys obtained for
transplant are obtained from cadavers that have sustained  brain  death,  but
have  had  stable  renal  and  cardiovascular  function.   Other  kidneys are
obtained from living relatives.  Donors are excluded if there is a history of
diabetes,  hypertension   or   malignancy.    The   best   donor   for  renal
transplantation  is  an  HLA-identical  sibling,  because  of  the  excellent
survival.  The second choice is a sibling who has a  lesser  match,  and  the
last  choice  would  be  the cadaver.  Special cooling solutions that contain
mannitol  or  hetastarch,  and  electrolytes,  such  as  the  Euro-Collins or
University of Wisconsin solutions, are used to flush the  kidney  immediately
following brain death.  The kidneys are then stored in an iced solution.  The
kidney  should  be  transplanted  within  48-72 hours.  They are transplanted
retroperitoneally  in  the  iliac  fossa  using  an  oblique  lower abdominal
incision in adults and a midline abdominal incision in small  children.   The
renal artery is anastomosed end-to-end to the recipient's hypogastric artery,
or  end-to-side  to  the common iliac artery.  There is a higher incidence of
renal artery thrombosis when using  the end-to-end anastomosis.  Renal artery
thrombosis presents with accelerated hypertension and renal dysfunction.  The
diagnosis may be made  by  angiography.   If  present,  it  is  treated  with
angioplasty or surgical repair.  The renal vein is attached to the iliac vein
in  adults  and to the inferior vena cava in children.  Both renal artery and
vein stenosis are rare.  The donor ureter is then attached to the recipient's
bladder using a submucosal tunnel.  Rarely (2%), a urinary leak will develop.
Lymphoceles (leakage of lymph from  the  recipient's lymphatic ducts or renal
hilum occurs in 2-5%.  Lymphoceles can become quite large  and  can  lead  to
ureteral  obstruction  or a mass effect.  Treatmetn is with drainage into the
peritoneal cavity.  The transplanted kidney may produce urine immediately, or
may fail  to  make  urine  in  the  first  24  hours  of  transplantation.  A
significant decrease in hourly urine output may be the earliest  sign  of  an
endangered  transplant.   The  initial  production of urine is dependent upon
many factors.  Patients with polycystic  renal disese may produce near normal
amounts of urine.  Patients receiving  kidneys  from  living  donors,  either
related  or  unrelated,  also  tend  to  have  high initial outputs of urine,
because of minimal acute  tubular  necrosis.  Almost all transplanted kidneys
will have some acute tubular necrosis, but the degree is less in those living
related transplants because the preservation time  is  very  short,  and  the
donor  has  normal  circulation.   Cadaver kidneys have increasing amounts of
acute tubular necrosis after  24-36  hours  of preservation.  If both kidneys
are oliguric, acute tubular necrosis is a  likely  diagnosis.   If  there  is
oliguira  only  from  one kidney, other complications may be the problem.  In
evaluating the cause of the  oliguria,  prerenal, renal, and postrenal causes
should be ruled out.  Post renal causes commonly are  due  to  clots  in  the
bladder.   Another postrenal cause is obstruction or leak of the transplanted
ureter at the site of attachment  to  the bladder.  If obstruction is found a
percutaneous stent can be placed with nephrostomy drainage.   A  radionuclide
scan  or  ultrasound  study  can  usually  demonstrate  fluid collections and
extravasations from a leak.  Volume depletion  as a cause of the oliguria can
be  treated  by  measuring  central  venous  pressure  or  pulmonary   artery
pressures.   If  the readings are normal or high, diuretics may be tried.  If
the measurements are low,  fluid  challenge  is given.  Cardiac output should
also be maintained in order to perfuse the kidneys.  The most common cause of
intrarenal dysfunction is acute tubular necrosis.  The most common  cause  of
renal  dysfunction from days 5-30 post transplant is cyclosporine toxicity or
rejection.  Cyclosporine may be used  immediatly  in recipients of live donor
kidneys.   In  patients  that  have  received  cadaveric   transplants,   the
cyclosporine  may  be  delayed  due  to the higher incidence of acute tubular
necrosis of the transplanted kidney in these cases.  Despite prophylaxis with
immunosuppressants given just  before  or  at  the  time  of transplant, most
patients will suffer 1 or more acute rejections in the  early  posttransplant
period.   Most  rejections  occur  within  3-4  months  following transplant.
Symptoms and signs  of  rejection  include  deterioration  of renal function,
weight gain, hypertension, fever, tenderness and swelling of the  graft,  and
protein,  renal  tubular  cells,  and lymphocytes appearing in the urine.  At
times, it  may  be  difficult  to  differentiate  cyclosporine  toxicity from
rejection, and a percutaneous needle biopsy may be needed.  Even  the  biopsy
may  not  clearly differentiate the cause.  Cyclosporine toxicity is infereed
if the cyclosporine level is very  high.  If the cyclosporine level is normal
or low the patient may have rejection.  Usually intensified immunosuppression
will reverse rejection.  A trial of steroids is  usually  started.   If  this
fails  to  improve  renal  function,  an  antilymphocyte  preparation  may be
started.  If it is  unsuccessful,  the  immunosuppression  is tapered and the
patient is placed on hemodialysis  again  to  wait  for  another  transplant.
COMPLICATIONS:  INFECTION: Antibiotic therapy has decreased the morbidity and
mortality following transplantation.  By giving trimethoprim/sulfamethoxazole
there has been a reduction  in  pulmonic Pneumocystis carinii.  Patients that
are cytomegalovirus (CMV) negative, but have received  positive  CMV  kidneys
are  now  given  routine  antiviral  therapy.   Ganciclovir  can  be used for
treatment and prevention of clinical  CMV  disease.  CMV disease is also more
common in CMV positive recipients  treated  with  antilymphocyte  antibodies.
HYPERTENSION:  About  60-80%  of patients receiving renal grafts will develop
hypertension  which  is  due  to  cyclosporine,  steroids  and  dysfunctional
allografts.  Renal artery stenosis as a cause is a rare cause (2%).  The clue
is a sudden development  of  hypertension,  or  sudden worsening in a patient
with hypertension.  Treatment with surgery usually has a  better  record  for
long  lasting  benefits  than treatment with angioplasty (81.5% versus 40.8%,
respectively).   ACE  inhibitors  may  also  cause  impaired  function  of an
allograft that will lead to hypertension.  Calcium blockers and diuretics are
good choices for treating hypertension.  CANCER:  There  is  an  increase  of
malignancy   in   renal  allograft  recipients.   There  is  an  increase  of
Epstein-Barr  virus  associated   B   cell   lymphomas  in  renal  transplant
recipients.  There is an increase of Kaposi's sarcoma, basal cell  carcinoma,
hepatobiliary carcinoma, vulva and perineal carinoma, non Hodgkin's lymphoma,
and  carcinoma in situ of the uterine cervix in graft recipients.  There is a
40 fold increase of lymphoma and a 10-15 fold increase of epithelial cancers.
Most of these squamous cell epitheliomas do not require discontinuance of the
immunosuppressive therapy, but  it  is  usually  necessary  for lymphomas and
aggressive tumors.  There is no increase in the incidence  of  carcinomas  of
the prostate, colon, lung or breast.  LIVER DISEASE: There is an incidence of
hepatitis  B  of  15%  in  renal  graft  recipients, whereas the incidence of
hepatitis C is  5%.   This  is  a  higher  incidence  than  that occurring in
patients receiving dialysis.  The  reason  for  the  high  incidence  is  the
immunosuppressive  therapy.   RECURRENCE  OF THE ORIGINAL DISEASE: There is a
recurrence of the original disease in 10-20% of renal grafts, but loss of the
graft is a rare event occurring  in  less than 2% of patients.  DYSLIPIDEMIA:
Renal graft recipients have a high incidence of cardiovascular  disase  which
is  the  most  common  cause of long term mortality.  The reason for the high
incidence is an atherogenic lipid  profile, caused by cyclosporine, steroids,
nonselective beta blockers, and loop diuretics.

                     -RENOVASCULAR HYPERTENSION-
If there is a moderate index of suspicion, non  invasive  testing  should  be
done such as the captopril test or the captopril renogram or stimulated renal
vein  renins  or  duplex  ultrasound.   Moderate suspicion includes diastolic
blood pressure >  120  mm  Hg,  hypertension  refractory to standard therapy,
abrupt onset of sustained moderate to severe hypertension at age < 20 or > 50
years, hypertension with a long  high  pitched,  localized  abdominal  bruit,
moderate  hypertension  (diastolic >105) in a smoker, a patient with evidence
of cerebrovascular, coronary, and  peripheral  vascular disease, or a patient
with  unexplained,  but  stable  elevation  of  the  serum   creatinine,   or
normalization  of  blood  pressure  by  an  ACE  inhibitor  in a patient with
moderate or  severe  hypertension.   If  clinical  suspicion  is high proceed
directly to arteriography + renal vein renins.  Renal arteriograms should  be
done in all black hypertensives in whom renovascular hypertension needs to be
excluded,  because blacks have more severe hypertension associated with renal
insufficiency.

                    -REVASCULARIZATION APPROACHES-
Revascularization indications include patients with 3 vessel disease  and  an
ejection  fraction < 50% OR privious MI, patients with refractory symptoms in
spite of intensive medical therapy,  patients  with left main coronary artery
stenosis > 50% with or without symmptomatolgy, patients with >  90%  proximal
stenosis  of the left anterior descending artery, post MI progressive angina,
and patients with unstable angina  who have controlled symptomatic angina but
continue to have exercise induced ischemic changes, particularly early in the
exercise.  PERCUTANEOUS CORONARY  ANGIOPLASTY:  PTCA  now  enjoys  ubiquitous
application  in multivessel disease associated with multiple stenoses, except
for left  main  involvement.   Ideal  lesions  for  correction  would include
non-eccentric, proximal, and plaque-free lesions, but its use has  even  been
expanded  to  include  stenosis  of  bypass grafts.  Success rate, in general
approaches 90%.   Complications  include  intimal  dissection  with occlusion
which will require emergency CABG in about 3-5% of cases.  In about 25-35% of
cases restenosis will occur in the first 6 months, which can successfully  be
retreated  with  another  PTCA.   The mortality rates of PTCA versus CABG are
similar in stable angina.   CORONARY  ARTERY BYPASS GRAFTING: Saphenous graft
patency rates average about 85-90% during the first 6 months after CABG,  and
even higher with internal mammary grafts.  After 6 months the closure rate is
4%  per  year.   Early  graft  failure is primarily due to poor distal runoff
flow, while late closure is  related  to continued smoking and poorly treated
hyperlipidemia.  Target cholesterol levels should be  <  130  mg/dL  for  LDL
cholesterol,  and  >  45  mg/dL  HDL cholesterol.  Long term ASA therapy will
improve graft  patency  rates.   Should  the  patient  need  repeat CABG, the
results are usually less than satisfactory and  technical  complications  are
more of a problem.  In healthy patients, the mortality is 1-3%, but increases
to  4-8% with high risk elderly patients, patients with LV ejection fractions
< 35%, and those patients that  require multiple surgical procedures as valve
replacement + CABG.  Internal mammary artery  grafts,  usually  to  the  left
anterior  descending  artery  and  branches, enjoy the most favorable results
with better long term patency and flow as opposed to saphenous grafts between
the aorta and  the  coronary  artery  distal  to  the obstruction.  Following
successful  CABG  surgery,  the  patient's  pain  usually   disappears,   and
anti-anginal medications may cautiously be withdrawn.  

                          -REYE'S SYNDROME-
Reye's  syndrome was first identified as a clinical and pathologic disease in
1963.  To this date no  etiology  has  been  firmly established.  It has been
associated with outbreaks of varicella, and influenza A and B. Epidemics have
been seen during influenza B outbreaks.   Other  associations  have  included
coxsackie   virus   A,   echovirus   2,  Epstein-Barr  and  reovirus.   Toxic
associations include  aflatoxins,  salicylates,  insecticides, herbicides and
defects in the urea cycle.  The  underlying  mechanism  responsible  for  the
disease   is   thought  to  be  mitochondrial  damage  caused  by  salicylate
metabolites or other agents, that leads  to elevated short chain fatty acids,
hyperammonemia and cerebral edema.  The syndrome is usually seen in  children
less  than  18 years of age, but occasionally has affected older individuals.
Most causes in the  USA  occur  in  the  late  fall  and winter.  There is an
increased incidence in siblings.  The use of salicylate during an  influenzal
illness can materially increase the risk for developing Reye's syndrome by as
much  as  35  fold.   CLINICAL:  Most  of the patients will give a history of
varicella or upper respiratory  disease.   Following this, usually around day
6, there is severe nausea and vomiting, followed by  changes  in  the  mental
status,  such  as  stupor,  delirium,  coma  and seizures.  The delirium is a
hyperexcitable state that is  associated  with fever, tachycardia, tachypnea,
sweating  and  pupillary  dilation.   Coma   is   manifested   by   advancing
unresponsiveness,  decerebrate  and  decorticate posturing, flaccidity, fixed
dilated pupils and respiratory arrest.  Jaundice is not prominent.  The liver
may be minimally enlarged or normal.  There is no splenomegaly.  In the later
stages there is  a  positive  Babinski  and  hyperreflexia.  Complications of
Reye's syndrome consist of inappropriate ADH secretion, cardiac  arrhythmias,
hypotension,  GI  bleeding,  diabetes  insipidus,  electrolyte  disturbances,
hepatic  failure,  renal  failure,  pancreatitis,  aspiration  pneumonia  and
pulmonary  insufficiency.  Reye's syndrome has been dividded into 5 stages as
follows: Stage I:  Stage  I  is  typified  by lethargy, drowsiness, vomiting,
normal posturing and response to painful stimuli, normal pupillary reactions,
normal Doll's eyes and normal or hypeventilation.  Stage 2  is  characterized
by delirium, combative behavior, inappropriate verbalization, disorientation,
unresponsive  to command, normal posturing, pupillary sluggishness, conjugate
deviation of the eyes,  dilated  responsive pupils, purposeful pain responses
and hyperventilation.  Stage 3 consists of obtundation and coma,  decorticate
posturing,  sluggish pupillary reaction, dilated pupils, conjugate deviation,
and hyperventilation or Cheyne-Stokes  respiration.  Stage 4 is characterized
by coma, decorticate posturing, decerebrate pain responses, dilated, sluggish
pupillary reactions, inconsistent or absent Doll's eyes, and hyperventilation
that may be irregular or absent.  Stage 5  is  characterized  by  a  comatose
condition,  flaccid  posturing,  no response to painful stimuli, no pupillary
reaction and absence of Doll's eyes.  The  stage of the illness on arrival at
the hospital tends to correlate with the degree of recovery.  Patients have <
2% mortality in stage I to > 80%  in  patients  with  Stage  4  and  5.  Most
patients  will  progress  from  Stage 1 to higher stages if the initial blood
ammonia is greater than 100 ug/dL and  the PT is greater than 3 seconds above
the control.  If the disease does  not  progress  beyond  stage  3,  complete
recovery  can  be expected.  In those that survive, there is mormalization of
the histologic  findings  by  8-12  weeks  after  the  onset  of the disease.
Recurrences  are  uncommon.   LABORATORY:  There  is  an  increase  of  liver
transaminases, AST and ALT, greater than three times normal.   The  bilirubin
is usually normal.  There is a prolonged prothrombin time and increased blood
ammonia.   EEG  will  show  diffuse slow wave activity.  LDH may be elevated.
The alkaline phosphatase is usually normal or minimally elevated.  There is a
mixed respiratory alkalosis and metabolic acidosis.  Cerebrospinal fluid will
show increased pressure, normal protein  and  less than 8-10 WBC/uL.  The CSF
glutamine  may  be  elevated.   In  about  15%  of  cases  hypoglycemia   and
hypoglycorrhachia  are  seen.   There  may  be hypokalemia, hypophosphatemia,
hypernatremia,  and  changes  in  the  osmolality.   DIFFERENTIAL  DIAGNOSIS:
Differential diagnosis includes hepatic  coma, fulminant hepatitis, and acute
toxic encephalopathy.  Inborn abnormalites of urea synthesis  or  fatty  acid
oxidation  such as medium chain acyl-CoA dehydrogenase and systemic carnitine
deficiency  (causes  hypoglycemia  and   hyperammonemia),  inborn  errors  of
carbohydrate  metabolism  ,  aminoacidurias   such   as   lysinuric   protein
intolerance,  phosphorus  or  carbon  tetrachloride  intoxication, salicylate
intoxication, viral encephalitis, and  meningoencephalitis  must all be ruled
out.  Liver biopsy and electron microscopy are diagnostic and may be required
in atyical cases.  PATHOLOGY: Findings in the brain include perineuronal  and
perivascular  clear  spaces,  edematous  astrocytes,  cerebral  edema,  gyral
flattening,  swollen  white  matter and compression of the ventricles.  There
may be fatty  infiltration  of  the  liver,  pancreas,  kidneys, heart, lymph
nodes,  and  spleen.   Electron  microscopy  reveals  mitochondrial   injury.
TREATMENT:  Treatment  includes IV 5-10% glucose and electrolyte solutions to
keep the urinary output  at  1-1.5  mL/kg/hour, or about 1600-1800 mL/M2/day,
with careful attention to central venous or pulmonary wedge pressures.  Serum
glucose, serum electrolytes and osmolarity  should  be  measured  every  four
hours.   CBC,  coagulation  profile, ammonia, osmolarities and liver function
tests should be done every 24 hours.   Vitamin  K1 3-5 mg IM daily PRN may be
needed to help corect the PT.  Hyperventilation, and  mannitol  infusions  of
.5-1  gram/kg  every  4  hours, dexamethasone .5 mg/kg/day IV or glycerol 3-6
grams/kg/day via gastric tube will be  needed to decrease the cerebral edema.
Patients in advanced states will need endotracheal intubation with controlled
ventilation, arterial  catheter  blood  pressure  monitoring  and  Swan  Ganz
catherization.   Arterial  blood  gas  and  pH  should  be  done  frequently.
Intracranial pressure should be monitored and kept below 15-20 mm Hg, and the
systemic  blood  pressure  should be elevated to maintain cerebral perfusion.
Hypothermia at  30-33  degrees  C.  and  pentobarbital  10-50  mg/kg/day (1-2
mg/kg/every 1-2 hours) may be used to decrease body metabolism.

               -RHEUMATIC DISEASES AND DRUG TREATMENT-
CORTICOSTEROIDS: Rheumatoid arthritis (1-10  mg/day);  SLE and vasculitis (60
mg/day  initially);  Polymyositis  (60-80  mg/day  initially);   Giant   cell
arteritis    (60-80    mg/day   initially);   life   threatening   situations
(methylprednisolone  (Solu-Medrol)  1  gm  in   divided  doses  daily  x  3.)
Prednisone  is  prepared  as  1,  2.5,  5.0,   10,   20,   50   mg   tablets.
Methylprednisolone  sodium  acetate (Solu-Medrol) IV comes as 40, 125, 500 mg
or 1 grams/vial.  Triamcinolone  hexacetonide  (Aristospan  20 mg/ml) is used
for intra articular injections, because there is less chemical synovitis, but
is not recommended for injection of trigger points  because  it  may  produce
lipoatrophy.   All  medication  should be taken in the early AM so that there
will be a normal PM fall in  cortisol which will help facilitate the recovery
of the hypothalamic-pituitary axis.  Every other day  regimens  will  produce
less  adrenal  suppression,  but  may not reduce the risk of osteoporosis and
usually are not very effective in  controlling  daily symptoms of RA and SLE.
Death has been reported following high doses  of  methylprednisolone  due  to
rapid   electrolyte   changes   or  progression  of  occult  infections  with
dessimination.  The risk  of  opportunistic  infections  is  increased if the
maintenance dose is > 20 mg/day.  The estimated cost is about $15.00/month at
7.5 mg/day.  METHOTREXATE: Is indicated in  Rheumatoid  arthritis,  Psoriatic
arthritis and spondyloarthritis.  It is prepared as 2.5 mg tabs (Rheumatrex).
Assuming  that  the  patient will be taking 10 mg/wk, the cost for 16 tablets
would be about  $38.00/month.   Methotrexate  also  comes  as 250 mg/vial (25
mg/ml) for IM use.  Use .1 cc in a tuberculin syringe to obtain  2.5  mg  for
the  IM  dose.   For  home use, you must order the protected multi-dose vial.
The estimated cost is $25.00 for a  multi  dose vial or 65 cents/dose for one
month assuming the patient is taking 10 mg/wk.  The oral and IM  preparations
are  started  as  2.5 mg one day/week, then 5 mg/second week, then 7.5 mg one
day of each subsequent week.  It is  permissable to give the total daily dose
in divided doses q12h, but all meds must be given within 24  hours  to  avoid
toxicity  and  cytopenias.   Methotrexate is usually given in this fashion to
avoid nausea and vomiting.  If  the  patient  fails to obtain a good response
after about 2 months, increase each month by 2.5 mg/wk to a maximum of  15-25
mg/week.   Toxicity  is related to the duration of treatment rather than peak
concentrations.   Methotrexate  is  contraindicated  in  patients  that drink
ethanol regularly  with  preexisting  liver  disease,  or  are  at  risk  for
pregnancy   as   this   drug   is  teratogenic  and  abortogenic.   Transient
oligospermia is seen in men.  Pregnancy  should be avoided in either mate who
has received  methotrexate  within  4  months.   There  also  is  a  probable
increased risk of hepatic fibrosis and tramsaminemia in diabetic patients and
in  those  with  previous  liver disease.  The patient should have a baseline
chest x-ray, CBC,  hepatitis  B  and  C  serology  and chemistry panel.  Then
monitor CBC and liver panel every two weeks x 4; then monthly.  If  the  dose
is  increased,  monitor  weekly  x  4.  If patient is on a stable dose and is
tolerating well, monitor q 1-2 months.  Do not obtain LFTs within 48 hours of
administration of  methotrexate  because  the  ALT  and  AST  can  be falsely
elevated.  Creatinines and albumin should be done every 3 months.  About  33%
of  patients will have adverse effects.  Eleven percent will have GI symptoms
as diarrhea, abdominal pain and melena), 15% will have elevated LFTs, 5% will
have cytopenias, with leucopenia more common than anemia or thrombocytopenia,
6% will have stomatitis, < 1%  will have interstitial lung disease.  A rising
MCV  may  be  indicative  of  hematologic  toxicity.   ASA,  probenecid,  and
phenylbutazone  can  release  methotrexate  from  binding  sites,  increasing
toxicity.  NSAIDs can cause an increase of LFTs.  Mucocutaneous  lesions  and
hematologic changes may be reversed with daily folic acid at 1 mg/day without
affecting  the  efficacy  of  methotrexate.  Sulfa drugs should be avoided as
these drugs may increase  methotrexate  toxicity,  since they are anti-folic.
There is no consensus as to when liver biopsy should be done, providing there
are no risk factors for hepatocellular disease and  there  is  no  persistent
abnormal elevation of LFTs.  The risk for serious liver disease after 5 years
of methotrexate treatment is estimated to be < 1:1,000.  Methotrexate induced
lung  disease  can present as idiopathic pulmonary fibrosis, granuloma, hilar
adenopathy, bronchiolitis  obliterans,  and  pleural  effusion.   It  is rare
however, and is not dose related.  It has been reported with < 90 mg on a low
dose regimen.  Most patients will respond  within  the  first  6  weeks,  but
maximum  effect  is  seen  at 6 months.  Patients who fail to respond to oral
doses or have GI side effects may respond  to  IM doses up to a maximum of 25
mg/week.  The cost of IM doses may be 1/10th the  cost  of  PO  methotrexate.
Patients  can be taught to self administer the methotrexate in the thigh with
a  27  gauge  1/2  inch  tuberculin  syringe.   GOLD:  Gold  is  indicated in
rheumatoid  arthritis,  juvenile  rheumatoid  arthritis,   Still's   disease,
palindromic  rheumatoid  arthritis  and  psoriatic  arthritis.   Preparations
include  PO  auranofin  (Ridaura)  3  mg  bid and IM Myochrysine (gold sodium
thiomalate) and IM  Solganal  (aurothioglucose).   IM administration is given
weekly at 10 mg, 25 mg, then 50 mg weekly x 5 months  or  until  the  disease
process  is  under  control.   Then  reassess  the response by increasing the
interval between injections, such as every  2  weeks x4, then every 3 or four
weeks.  The maintenance dose is usually 50 mg IM every 3-4 weeks.  If a flare
is noticed, return to weekly doses for 8 weeks.  Gold should  be  avoided  in
women  that are planning pregnancy.  Baseline chest-ray, CBC UA and chemistry
panel should be done.   Prior  to  each  injection  obtain  a CBC and UA.  If
proteinuria, mucosal ulcerations, cytopenias, dyspnea, or rales (gold induced
interstitial pneumonitis), develop, discontinue the gold.   Gold  rashes  may
respond  by  reducing the dose, and/or using a hydrocortisone cream.  Also be
aware that MYochrysine may cause a  vasovagal reaction which is not seen with
Solganal.  About 66% of patients will respond well, about 33%  will  need  to
discontinue  because of side effects.  Rash may occur in 60% and > stomatitis
> proteinuria > blood dyscrasias.  Symptom  relief is rare before 2 months of
therapy.  Ridaura is given as 3 mg BID PO, but  is  less  effective  than  IM
gold.   However, serious side effects (hematologic and renal) are less common
than  IM  gold,  while   mild   symptoms   such  as  cramping,  diarrhea  and
mucocutaneous lesion are more common.  The cost for Ridaura, giving 3 mg  bid
for one month, is about $72.00.  IM gold is about $10.00/injection for 50 mg.
The   cost   for   a   10  ml  vial  (50  mg/ml)  is  approximately  $118.00.
SULFASALAZINE: is used in rheumatoid arthritis, Reiter's syndrome, ankylosing
spondylitis and inflammatory bowel arthropathies.   It  is prepared as 500 mg
tablets  which  can  be   obtained   as   enteric   coated	(sulphapyridne   +
5-aminosalicylic  acid)  given  BID,  with the final dose of 2-3 grams daily.
Most patients will tolerate 1  gm  BID  if  started  slow at 500 mg daily and
increased by one tablet every week.  Can be increased to 3 gm/day for maximum
efficacy.   Sulfasalasine  should  not  be  used  if  allergic  to  sulfa  or
salicylate.  CBCs should be done periodically.  About 20%  of  patients  will
not  take  the  drug because of nausea, vomiting and dyspepsia.  You can give
the drug TID or QID  to  reduce  the  GI  toxicity.  Rashes only occur in 2%.
There may be pancytopenia and transient falls in  the  sperm  count,  all  of
which  are rare.  Macrocytosis, hepatitis and hemolysis are more common.  The
cost using 2 grams/day  is  $16.00/month.  HYDROXYCHOLROQUINE (Plaquenil) AND
CHLOROQUINE PHOSPHATE: These drugs may be used for rheumatoid  arthritis  and
SLE.   Plaquenil  comes  as  200  mg  with a dose of 400 mg hs or 200 mg bid.
Chloroquine is given as 250 mg PO  daily.  A baseline eye exam should be done
and then every 6-12 months by an ophthalmologist.  Ocular  toxicity  is  very
rare  with  Plaquenil.   Other  side effects are headaches, diarrhea, nausea,
blood dyscrasias, neuropathies, myopathies,  and hemolytic anemia.  The onset
of action is very slow and most will not have benefit  until  4-6  months  on
full  doses.   Generally  speaking,  it  is  not  as  effective  as  gold  or
methotrexate,  but  is  the least toxic.  It can used very effectively in SLE
for articular complaints and cutaneous  lesions,  and can be steroid sparing.
AZATHIOPRINE (IMURAN): Azathioprine is indicated in rheumatoid arthritis, SLE
and systemic vasculitis that is non life threatening.  Azithioprine comes  in
50  mg  tablets and is is usually given in a daily dose of 100 mg, but ranges
from 50-200 mg.  Elderly patients  may  be more sensitive.  If allopurinol is
given concomitantly, the azathioprine should be reduced by 1/5 to 1/10th  the
usual  dose.   A  CBC  should  be  done weekly x 4 then q 2-4 weeks x 4, then
monthly.  Occasionally,  a  chemistry  panel  should  be  done.   Bone marrow
suppression is the most frequent side  effect  which  would  limit  its  use.
Leukopenia  may  develop  at  any  time, even in the first week.  Nausea is a
common side effect that would limit  its used.  Other side effects that occur
less frequently include alopeica, hepatitis and rash.  It  is  not  known  if
there is an increased incidence of lymphoproliferative malignancies when used
in  patients  with  rheumatic  disease.  The onset is delayed until about 4-6
weeks.  It is also used to reduce  the total prednisone dose and is useful in
some patients with lupus nephritis.  Azathioprine is expensive costing  about
$76.00/month when used at 100 mg/day.  CYCLOPHOSPHAMIDE (CYTOXIN): Cytoxin is
indicated  in  lupus  nephritis,  CNS  vasculitis  or mononeuritis multiplex,
Wegener's, severe vasculitis, severe interstitial lung disease and transverse
myelitis.  It comes in 50 mg tablets and is used in a daily dose of 50-150 mg
(.7-3 mg/kg/day).  The monthly IV  bolus  that is used for glomerulonephritis
is 0.5-1 gram/M2.  For lupus nephritis  an  IV  bolus  of  Cytoxan  is  given
monthly x 6, then every 2 months x 6. The lowest WBC is reached in about 7-10
days  after  cytoxan is given.  To prevent nausea, dexamethasone may be given
at 10-20 mg PO or IV, and/or Zorfran 8 mg PO q4h x3, and prn, or Compazine SR
15 mg PO initially prior to therapy,  and then every 12 hours post treatment.
Oral and IV therapy  requires  large  amounts  of  fluid  volume  to  prevent
hemorrhagic  cystitis.  1000 ml of normal saline should be given prior to the
administration of cytoxan, during and  following cytoxan therapy.  As the WBC
falls, the drug will need to be titrated downward.  Caution must be used with
cytoxan as it is the most immunosuppressive of all agents with death from  an
opportunistic infection a real possibility.  The highest risk of infection is
when the patient is taking high dose steroids with cytoxan.  There also is an
increased  incidence  of  lymphoprofliferative  malignancies  associated with
cytoxan.  There is an  increased  incidence  of hemorrhagic cystitis, bladder
cancer, and bladder fibrosis which can be reduced with high fluid intake  and
by  giving  cytoxan IV.  Cytoxan is contraindicated in women of child bearing
years at risk  for  pregnancy  because  it  can  result  in sterilization and
premature menopause.  There is a  greater  risk  of  sterilization  in  older
women.    Rarely,   there  may  be  pulmonary  fibrosis,  hepatotoxicity  and
dermatitis.  CBCs are obtained monthly  and  if  it  it  seen that the WBC is
dropping, the CBCs are done more frequently.  Cytoxan is the  most  effective
of  all of the immunosuppressive agents.  The cost is high and averages about
$164.00/month assuming  the  patient  is  taking  100 mg/day.  PENICILLAMINE:
Because of its toxicity, penicillamine is rarely used in rheumatoid arthritis
anymore.  It may, however, be useful in systemic sclerosis.

                          -RHEUMATIC FEVER-
Rheumatic  fever  (RF)  is  an  immune  sequelae  to  hemolytic streptococcal
infections that has a peak incidence from ages 5-15.  It is rare  before  the
age  of  4,  and after the age of 40.  Recently there has been reports of new
outbreaks in several area of the USA.  There was a resurgence in 1985 in Salt
Lake City, Pennsylvania and  Ohio.   These  cases, were associated with white
middle class children, and the mucoid M type 18 Group A  streptococci.   This
type  has been a rare etiologic type in the past.  There was also an outbreak
in a military camp in  1989.   Otherwise,  it  has become uncommon in the USA
except  for  immigrants.   It  is  characterized  principally  by  arthritis,
carditis and chorea, that may appear in combination, or alone.   There  is  a
predisposition  in  those  with  malnutrition,  low  income  and  in areas of
overcrowding.  The diagnosis is based on the Jones criteria which consists of
two major or one  major  and  two  minor  manifestations.  The major criteria
consist of carditis, polyarthritis, chorea, subcutaneous nodules and erythema
marginatum.  The  minor  criteria  consist  of  fever,  arthralgia,  elevated
sedimentation  or  C-reactive protein, and a prolonged PR interval.  Patients
must also have positive throat  culture  for group A Streptococcal infection,
or elevated or rising antistreptococcal antibody  serum  titers.   The  joint
pain and fever usually subside within 2 weeks, and usually do not last longer
than  1  month.   Howver,  about 5% of rheumatic patients will have prolonged
episodes of 8 months or  longer.   The  ESR,  in the absence of carditis will
retun to normal within 3  months.   CARDITIS:  The  most  characteristic  and
damaging  lesion  in  RF  is  on  the  cardiac valves.  The most common valve
involved is the mitral valve.  The next  most common is the aortic valve with
involvement of the tricuspid infrequently.  Involvement of the pulmonic valve
is rare.  There is edema, thickening, fusion and retraction of  the  leaflets
and  cusps  which  can  lead  to regurgitation or stenosis.  There is similar
involvment of the chordae tendineae which adds to the regurgitation.  Further
regurgitation can also be caused by dilation of the valve rings.  In children
and adults, carditis is mainly manifested by mitral regurgitation.  Thus, the
diagnosis  in  children  will  depend  on  hearing  a  new  murmur  of mitral
regurgitation, which is a high frequency systolic murmur that is heard at the
apex with radiation to the left axilla.  In older patients that are  >  30  ,
the  predominant  hemodynamic  alteration  is  due to mitral stenosis, due to
repeated attacks of inflammatory injury to the valves, resulting in fusion of
the chordae and mitral leaflets.   Therefore,  if  there has been a change in
the murmur from mitral regurgitation to mitral stenosis, this  would  support
the  diagnosis.   This subtle change may be difficult to appreciate, and will
require an echocardiogram  with  doppler interrogation.  Aortic regurgitation
can also be present, usually with involvement of the  mitral  valve.   Aortic
regurgitation is a blowing soft diastolic murmur that is best heard along the
lower  left  sternal  border.   The  mitral  stenosis murmur is a presystolic
murmur that is heard above  or  medially  to  the apex.  The patient may also
have pericarditis, although it is uncommon in adults.  It can be detected  by
auscultation  of  a  friction  rub  or  evidence of a pericardial effusion on
echocardiogram.  Patients with  a  first  attack  of rheumatic fever, usually
have about 50% involvement of carditis  and  arthritis.   Children  that  are
acutely  ill  may  develop  cardiac  decompensation characterized by dyspnea,
upper  quadrant  or  epigastric  pain  (liver  engorgement  due  to tricuspid
regurgitation), nausea, vomiting and a cough.  ECG manifestations consist  of
PR  prolongation  greater than .04 seconds above the patient's normal.  There
may also be nonspecific T  wave  inversion  and  a  changing contour of the P
wave.  Sinus tachycardia usually persists  during  the  sleeping  hours,  and
there  may  be  various ectopic beats and shifting pacemakers.  ARTHRITIS: In
children, the arthritis is a  migratory polyarthritis that involves the large
joints (ankles, knees, elbows and wrists.   The  shoulders,  hips  and  small
joints  of  the  hands and feet can be involved, but usually not alone).  The
joints become painful  and  tender  and  can  be  hot,  red  and swollen with
effusions.  The arthritis usually lasts about 1-5 weeks and  then  disappears
without    residual    deformity.    SYDENHAM'S   CHOREA:   are   involuntary
choreoathetoid movements of the  face,  tongue  and upper extremities.  Girls
are more freqeuntly involved, and chorea is rare in adults.  It has a  latent
period  of  6  weeks  to  several  months  after  the preceding streptococcal
infection.  Chorea is rarely seen (3% of  cases), but when manifest it is the
most diagnostic.  ERYTHEMA MARGINATUM: Erythema marginatum occurs as  a  flat
serpiginous  rash  that  is fleeting (lasts less than 1 day).  They appear as
macular  rings  or  crescents  with  clear  centers.   SUBCUTANEOUS  NODULES:
Subcutaneous nodules are uncommon in  adults,  but may be common in children.
They are usually less than 2 cm, nontender and attached to tendon  or  fascia
over  bony  prominences.   They  may  be  present  for days to weeks, and are
recurrent.  They occur most frequently on  the extensor surfaces of the large
joints.  They rarely  occur  alone,  but  in  combination  with  carditis  or
arthritis.   LABORATORY: The sedimentation rate is high.  About 90% will have
elevated   or    increasing    titers    of    antistreptococcal   antibodies
(antistreptolysin O and anti-DNAse B).  Ten percent will not  have  serologic
evidence  of recent streptococcal infection.  Throat cultures are freaquently
negative at the time of the initial presentation.  The serologic tests should
be repeated over a 2-4 week period to detect any rise in the serologic titer.
The WBC may be elevated  to  between  12,000-20,000/uL.  If the patient is on
steroids, the WBC may be even higher.  Prolongation of the PR interval is the
most common ECG finding, but is nonspecific.  DIFFERENTIAL  DIAGNOSIS:  Gout,
rheumatoid  arthritis,  osteomyelitis, endocarditis, SLE, sickle cell anemia,
serum sickness,  drug  reactions,  subendocardial  fibroelastosis, gonococcal
arthritis, chronic meningococcemia, and Lyme disease.  The main  differential
is  with  juvenile  arthritis,  which  may  occasionally  begin suddenly, and
occasionally involve the heart.  TREATMENT: ASPIRIN: Aspirin (ASA) is used to
control the arthritis, fever and  help  suppress the carditis.  It is usually
started at 60 mg/kg divided into 4 equal doses QID.  The  absorption  may  be
variable,  and  serum salicylate levels should be measured about 5 days after
treatment to achieve a therapeutic  serum  level  of 20-25 mg/dL.  Adults may
require 600-900 mg every 4 hours to control the symptoms.  The ASA should  be
continued  until  the  sedimentation level returns to normal.  If the patient
develops influenza or varicella,  the  ASA  should be discontinued.  Systemic
salicylate toxicity  is  manifested  by  tinnitus,  tachypnea,  vomiting,  GI
bleeding, and headache.  CORTICOSTEROIDS: Steroids may be started if there is
no  response  to  ASA  after  about 4 days of therapy with ASA.  Steroids are
given for moderate and  severe  carditis.   Prednisone  is usually started at
40-60 mg (1-2 mg/kg) daily with tapering over a 2 week  period.   PENICILLIN:
Penicillin  (benzathine penicillin, 1.2 units IM once, or procaine penicillin
600,000 units IM  daily  for  10  days  is  used  to  treat the streptococcal
infection.  Alternatively, the patient may be treated with oral penicillin V,
125-250 mg QID for 10 days.   If  the  patient  is  allergic  to  penicillin,
erythromycin  can be used at 50 mg/kg up to a maximum of 1 gram in 2-4 doses.
Clindamycin is another alternative in  those patients allergic to penicillin.
Recurrences of rheumatic  fever  are  prevented  by  prophylactic  benzathine
penicillin  G, 1.2 million units IM monthly.  Oral penicillin V 250 mg BID is
an alternate method,  but  less  reliable.   If  the  patient  is allergic to
penicillin, sulfadiazine or sulfisoxazole, 1 gram  daily  may  be  given,  OR
erythromycin  250 mg bid.  The length of prophylaxis is variable.  Some would
recommend prophylaxis for life, while others would continue prophylaxis until
the age of 45.  At any  rate,  those  at high risk should continue treatment.
Those considered at high risk include military recruits, nurses, and those in
crowded living conditions as prisions, schools,  and  teachers.   Recurrences
are  most  common  in those patients who have had carditis during the initial
episode and in children, 20% of  whom  will  have a second attack in 5 years.
Congestive heart failure is treated with digoxin, diuretics and  oxygen.   If
patients  fail  to respond to treatment, surgical valve repair or replacement
may be needed.  Sydenham's chorea is usually short lived, lasting for several
months.  The only treatment needed in  most mild cases is mild sedation.  The
child may need to be  removed  from  school  for  a  short  period  of  time.
Carbamazepine,  valproate, prednisone and haloperidol have all been used with
some success.

                 -RHEUMATOID ARTHRITIS AND THE LUNG-
Pleuritis with or without effusion is  the most common respiratory finding in
Rheumatoid arthritis (RA).  The incidence of pleuritis is about 21%,  pleural
effusion  3%.  Subcutaneous nodules may be present in 80%, indicating disease
activity.  Pleural effusions are more common in men and those over the age of
50.  About 50% of  patients  with  rheumatoid  peluritis are asymptomatic and
about 1/3 will have pleuritic pain, with 1/4 having dyspnea.  Only  about  8%
will  have  a  temperature > 38 C. As compared with SLE pleuritis, rheumatoid
pleuritis is much less  symptomatic.   The  patients  may have right, left or
bilateral effusions with bilateral effusions occurring in only 5%..   Pleural
fluid  may be turbid, milky, serous, yellow green or rarely hemorrhagic.  The
pH of rheumatoid  effusions  is  usually  <  7.2  which  usually decreases as
glucose  end  products  accumulate.   Protein  varies  from  3.5-5.5   gm/dl,
compatible  with  an  exudate.   Pleural  fluid LDH is > 1000 IU/L.  The cell
count ranges from about  100-7000/mm3  with  a lymphocytic predominance.  The
effusion glucose is < 50 mg/dl  in  about  82%.   However,  the  decrease  in
pleural fluid glucose is associated with the duration of the effusion and may
not  be present in acute effusions.  Rheumatoid arthritis cells (granulocytes
containing rheumatoid factor) may  be  found,  but are not diagnostic because
they may also occur in malignancy, TB and pneumonia.   Rheumatoid  factor  is
usually  at  least  1:320 or greater and is usually higher than serum values,
but not always.  There may  be  increased  amounts  of IgG and IgM and immune
complex formation.  C3, C4, and  total  complement  may  be  decreased.   The
finding  of  elongated  macrophages  with or without a background of granular
debris, and giant multinucleated  macrophages  may  be specific of rheumatoid
effusion.  Milky effusions may contain cholesterol and  cholesterol  crystals
which  causes  a pseudochylous effusion.  It is present only in patients that
have had  rheumatoid  arthritis  for  some  time.   Thorascopy  may  reveal a
characteristic frozen or gritty appearance of the  parietal  pleura,  whereas
the  visceral pleura will show nonspecific inflammation.  Rarely the parietal
layer will  show  rheumatoid  granuloma.   Rheumatoid  effusions  stay around
longer than those caused by SLE, but  about  75%  will  clear  in  6  months,
usually  with  residual  pleural  thickening.   Most effusions are small, but
occasionally they are large.  No treatment is needed for the small effusions,
but the large ones will  respond  to systemic steroids.  NODULES: Nodules are
more common in males and occur mainly in patients with  subcutaneous  nodules
and seropositive arthritis.  Most patients are asymptomatic, but there may be
dyspnea, hemoptysis and cough.  The nodules are frequently subpleural and can
therefore  cause  pleural  effusion,  bronchopleural fistula or pneumothorax.
The nodules seem to parallel  the  presence  of the subcutaneous nodules with
waxing and waning.  A majority of these involve the periphery  of  the  upper
and  mid  lung fields without calcification.  Cavitation is reported to occur
in 50%.  All of these features make it difficult to differentiate from cancer
of the lung.  Patients that smoke, and have lung nodules that are increasing,
should have thoracotomy or  thoracoscopy  as fiberoptic bronchoscopy and fine
needle aspiration are  usually  not  helpful.   CAPLAN'S  SYNDROME:  Caplan's
syndrome was first recognized in 1953 and consisted of nodules in coal miners
with  rheumatoid  arthritis.   These  nodules are usually .5-5 cm in diameter
distributed  mainly  in  the  periphery.    These  nodules  may  precede  the
development of RA.  These nodules  have  also  been  seen  in  pneumoconioses
associated   with   foundry  workers,  roof  tile  manufactures,  silica  and
asbestosis related  workers,  dolomite  quarry  workers  and  aluminum powder
exposure.  INTERSTITIAL LUNG DISEASE: Typically the x-ray will  show  basilar
interstitial  infiltrates  in  about  4% of patients.  Early findings include
bilateral soft alveolar  infiltrates  in  the  bases,  followed by incomplete
clearing and fibrosis.  As the lung disease advances a honey comb  appearance
will surface.  In about 20% of cases there will be concurrent nodules.  These
changes  can occur before, during or after overt Rheumatoid arthritis occurs,
just as in pleural and nodular  forms  of  RA.  The diffusion capacity may be
decreased in 40% and open lung biopsy of the  lung  will  show  fibrosis  and
interstitial  inflammation  in  up to 60%.  Interstitial lung disease is more
common in males (2:1)  and  in  those  older  than  60.   About 50% will have
subcutaneous nodules.  Clinically, the patient will present with dyspnea, and
rales.  Clubbing, pleuritic  chest  pain  and  Sjogren's  syndrome  also  may
appear.   Rheumatoid  arthritis  patients with lung fibrosis will have higher
rheumatoid factor titers  and  lower  C4  levels  than  patients without lung
findings.  Also, patients with RA lung fibrosis have a 50% incidence  of  non
MM  (MZ or MS) phenotypes of alpha 1 antitrypsin when compared to RA patients
without  lung  involvement  (12-14%  incidence).   TREATMENT:  Treatment with
prednisone gives  rather  unpredicatble  results.   In  general,  it  is  not
unreasonable  to  start  therapy  with  high dose corticosteroids followed by
immunosuppressive drugs such as azathioprine and methotrexate.  BRONCHIOLITIS
OBLITERANS (BO): In BO there is a sudden onset of dyspnea which is associated
with bilateral  rales.   The  chest  x-ray  will  show hyperinflation without
infiltration, but CT will delineate irregular  patchy  infiltrates  that  are
either  peripheral or central in location.  Spirometry will demonstrate small
and large airways obstruction with  a  normal  DLCO.  Blood gases show a mild
hypoxemia, hypocapnia and respiratory alkalosis.   Lung  biopsies  will  show
mononuclear  cell  infiltration  of  peribronchiolar  tissue.   Later, as the
disease progresses, there is  complete  luminal obliteration with replacement
by fibrous tissue.  There is immunoglobulin deposition consisting of IgM  and
IgG  in  bronchiolar  and  alveolar  walls.   BO occurs almost exclusively in
females with RA (10:1).  Almost all  patients will be RF seropositive and 50%
ANA positive.  The mean age of  involvement  is  around  50.   About  50%  of
patients  will  have Sjogren's syndrome and about 50% will have received gold
or penicillamine during the course of the RA.  BO + RA has a rapidly downhill
course with death  occurring  in  about  18  months  after  the  onset of the
symptoms.   BRONCHIOLITIS  OBLITERANS  WITH  ORGANIZING   PENUMONIA   (BOOP):
Patients  are  almost  alway  females  (10:1)  with  a mean age of 58.  These
patients  have  80%  RA  seropositivity  with  high  titers.   The  articular
involvement is erosive, without  nodules.  Clinically, these patients develop
a rapid dyspnea with normal findings usually  found  on  examination  of  the
chest.   Chest  x-ray will show a lower lobe predilection for patchy alveolar
ground glass infiltrates, and the lungs  volumes  may be reduced.  CT is used
to confirm these findings and find a suitable site  for  biopsy.   Spirometry
will  show  a  restrictive  pattern  with a reduction of the DLCO.  Open lung
biopsy is usually used for diagnosis.  The distinguishing histologic features
consist of plugs of  fibrin  and  granulation  tissue that fills the alveolar
ducts and alveoli with  less  involvement  of  the  bronchioles.   The  plugs
consist  of  collagen,  elastin  and  chronic inflammatory cells.  Honey comb
lungs are  only  rarely  reported,  fibrosis  is  initially  minimal  and the
underlying lung architecture is preserved.  BOOP + RA has a better  prognosis
than  idiopathic BOOP, and will respond to prednisone 40-80 mg/day with usual
complete resolution of the chest radiograph.  However, relapse may occur with
termination of the prednisone.

                 -RHEUMATOID ARTHRITIS (TREATMENT)-
Treatment of rheumatoid arthritis has been changing over the last  few  years
and  it  is  now permissible to treat moderate or severe rheumatoid arthritis
with remittive agents as  methotrexate,  gold, azathioprine or penicillamine.
For mild disease which occurs in about 80% of cases,  many  physicians  would
start  with hydroxychloroquine, sulfasalazine or prednisone in low doses.  In
the past a common approach was  to  treat rheumatoid arthritis with high dose
aspirin or NSAIDs.  Early studies have suggested that starting patients  with
remittive  therapy  early  can  delay  the  crippling  portion  of rheumatoid
arthritis.  When to intervene with the remittive drugs has been varied.  Some
physicians would start early after  a  few  weeks  after it is known that the
patient is not responding to standard therapy.  Others may wait  for  several
months  to  see  if  the  patient  may  remit.   One  of the problems is that
rheumatoid arthritis may be  atypical  early  in  the disease with a negative
rheumatoid factor  and  the  disease  may  present  with  asymmetrical  joint
involvement.  Early in the disease there may not be any radiographic features
typical  of  rheumatoid  arthritis  such  as  periarticular  osteopenia,  and
erosions.   The lack of concrete findings of rheumatoid arthritis early would
stall some physicians in using  more  toxic agents such as methotrexate early
in the course.  However, with a judicious approach, these remittive drugs can
be used safely either as monotherapy  or  as  combination  therapy.   Because
rheumatoid  factor  may  only  be  present  in  about  50%  of cases of early
rheumatoid  arthritis,   rheumatoid   factor   false   positives  occur,  and
radiographic features are lacking, it is important to rely on  early  morning
stiffness,  fatigue  and  mild  anemia  as important constitutional symptoms.
Rheumatoid arthritis can attack  the  hands, wrists, elbows, shoulder, knees,
ankles, and feet.  METHOTREXATE THERAPY: If the patient has  symmetric  joint
involvement  and  a  positive rheumatoid factor and has been diagnosed as new
rheumatoid arthritis,  the  drug  of  choice  currently  may  be methotrexate
(Rheumatrex).  It is usually started at 7.5 mg as a once  a  week  dose.   If
there  is  no  response  after  several  months  of  therapy, the dose may be
escalated to 10-15 mg once  a  week  therapy.   Even though methotrexate is a
fast acting drug, in contrast to some of the others, responses usually  don't
occur  for about 1 month.  At that time there may be decreased joint pain and
a  decrease  of  the  constitutional  symptoms.   Other  remittive  drugs  as
hydroxychloroquine and gold may  take  2-3  months  for  a response to occur.
During this interval, the patient should  be  maintained  on  NSAIDs.   After
several  years  of  treatment  with  methotrexate  liver  biopsy is sometimes
recommended to check for  development  of  hepatic  fibrosis that can develop
even with normal LFTs.  Serious side effects of methotrexate therapy  consist
of  hepatic dysfunction, leukopenia, thrombocytopenia and pulmonary fibrosis.
Methotrexate is contraindicated in pregnancy.   Knowing what course of action
to take if these do develop is important and the following will address  this
problem.   HEPATIC:  Hepatic side effects will develop in about 15% of cases.
If the liver function  tests  are  increased  to  more than twice normal, the
methotrexate  should  be  temporarily  discontinued   and   then   cautiously
re-introduced  after  one month if the LFTs have returned to normal.  Careful
monitoring of these tests should  then  be followed.  All patients should not
consume any form of alcohol.  HEMATOLOGIC: Hematologic side effects occur  in
about  1-10%.   Methotrexate  should be discontinued if a leukopenia develops
with the leukocyte count below  1000.   If thrombocytopenia develops at below
3000, the methotrexate should be  discontinued.   Macrocytosis  may  develop.
This  may  be  followed  if  in  the  range of 110-115, and folic acid may be
started.  PULMONARY FIBROSIS: Pulmonary fibrosis  is  a rare side effect only
occurring in about 2-5.5%, but steroids should be started if this occurs, and
the methotrexate should be discontinued.   INFECTION:  Infection  is  another
rare  side effect occurring in about 3.8%.  If this happens, the methotrexate
should be stopped and the  infection  treated.  Minor side effects occur such
as nausea (10-23%),  diarrhea  (8%),and  vomiting  (4%).   If  any  of  these
gastrointestinal  side effects occur, give the methotrexate in divided doses,
with the drug given with meals over  a 12 hour period once a week.  Dizziness
occurs in 2%, headache (9%), and hair loss (1-5%).  If any of  these  develop
treat  by  reducing  the dose of methotrexate.  If stomatitis occurs (3-10%),
reduce the dose  and/or  start  folic  acid  therapy.   GOLD  THERAPY: If the
patient doesn't respond to methotrexate therapy, gold therapy is an option if
the patient has severe rheumatoid arthritis.  Gold is given initially as a 50
mg injection once a week until a total of 1 gram has been given (Myochrysine,
Solganal).   This  normally  takes  about  5  months.   Following  this,  the
injection may be given every 2 weeks or monthly depending  on  the  response.
Oral  gold  (Ridaura) is less effective than IM gold and has a high incidence
of diarrhea.  Ridaura is started at  3  mg bid.  Gold is usually discontinued
during pregnancy since it is  excreted  in  breast  milk.   Side  effects  of
injectable  gold are as follows: CYTOPENIAS: Cytopenias develop in about 1-5%
and should be treated  by  discontinuing  the gold.  PROTEINURIA: Proteinuria
develops  in  about  10-20%  of  patients  treated  with  gold  but  is  only
significant in about 1-3%.  If it does develop,  discontinue  the  gold,  and
restart after one month if the proteinuria clears and continue to monitor the
urine.   PRURITUS AND RASH: Because development of exfoliative dermatitis can
be devastating, gold should be discontinued at  the first sign of a rash.  If
the rash disappears, the gold may be restarted at a  lower  dose.   PULMONARY
FIBROSIS,  HEPATITIS,  ENCEPHALOPATHY:  All of these are rare, but if they do
develop discontinue the gold.   ANAPHYLACTOID  REACTIONS:  This may happen in
about 5% of cases.  Changing from aurothioglucose to sodium aurothiomalate or
visa versa may be appropriate.  AZATHIOPRINE: If the patient doesn't  respond
to  methotrexate or gold, azathioprine (Imuran) may be used, but has a fairly
high  incidence  of  cytopenias  which   are   usually  mild.   The  dose  of
azathioprine is  50-150  mg  daily.   In  transplant  patients  there  is  an
increased  incidence  of  malignancy,  but  this  is  controversial  in other
populations.   Early  studies   have   shown   no   increase  in  hematologic
malignancies while treating rheumatoid arthritis patients.   Azathioprine  is
contraindicated in pregnancy.  Side effects are as follows: CYTOPENIAS: These
will  develop  in  about  28%,  and  if  they  do  occur,  reduce the dose of
azathioprine and monitor the counts.  If  there  is a continued trend for the
count to decrease  or  the  leukopenia  persists  after  reducing  the  dose,
discontinue  the  azathioprine.  HEPATIC: Hepatic involvement is rare, but if
it does develop, discontinue the  drug.   INFECTION: Infection is a rare side
effect in only  about  1-3%  and  should  be  treated  by  discontinuing  the
azathioprine.    PANCREATITIS:   Again,  this  is  rare  and  is  treated  by
discontinuing the drug.  NAUSEA  AND  VOMITING,  DIARRHEA: This will occur in
about 12-16% of cases  and  is  treated  by  dividing  the  dose  and  taking
azathioprine  with  meals.   RASH, STOMATITIS, HAIR LOSS: These are also rare
presentations and may be  treated  by reducing or discontinuing azathioprine.
PENICILLAMINE: Penicillamine (Cuprimine) can used as an alternative drug  for
azathioprine.   It  is  started  at  250  mg daily and gradually increased at
monthly intervals to a total of 750-1000 mg.  Side effects of this drug limit
its usefullness.  About 40% will discontinue  the drug at one year because of
side effects.  However, if the patient is fortunate enough  to  tolerate  it,
penicillamine  is  effective.   Side  effects  of penicillamine include rash,
pruritus, loss of taste,  cytopenias,  nephrotoxicity, autoimmune disease and
GI side effects.  If the patient  appears  to  have  a  mild  form  of  early
rheumatoid  arthritis,  treatment  with  hydroxychloroquine  sulfasalazine or
prednisone may be used initially.  About 20% of patients will not develop the
classic  course  of   rheumatoid   arthritis   and   have   a  mild  disease.
HYDROXYCHOLOROQUINE: Hydroxychloroquine (Plaquenil) therapy must be  preceded
by  an  eye  examination from an ophthalmologist because of the potential for
toxic effects on the retina.  It  is  also  advised to follow up with 6 month
interval exams as long as the patient is taking  the  drug.   It  is  usually
prescribed  at  200  mg bid and at this dose retinal damage is extremely low.
The most common side effects of hydroxychloroquine are nausea, abdominal pain
and rash.  If patient is pregnant  there  is  a risk of retinal damage to the
newborn  if  hydroxychloroquine  is  given.    SULFASALAZINE:   Sulfasalazine
(Azulfidine)  is started at a dose of 500-1000 mg/day and slowly increased to
2-3 grams/day over a 4-6 week period.  Side effects include blood dyscrasias,
hepatic and  renal  toxicity,  fibrosing  alveolitis, severe hypersensitivity
reactions, peripheral neuropathy, convulsions,  nausea,  vomiting,  anorexia,
headache,  depression,  drowsiness,  male  infertility  and  skin  and  urine
discoloration.   The  urine and blood should be monitored.  To circumvent the
GI side effects  use  Azulfidine  En-Tabs.   PREDNISONE:  Low dose prednisone
therapy is being used for mild rheumatoid arthritis  with  the  dose  ranging
from  5-7.5  mg given in the AM.  PM doses should be avoided.  This dose will
probably have to be supplemented with  NSAIDs to produced the desired effect.
With this combination there may be increased GI complaints.  It is  extremely
important  that  the 7.5 mg daily dose is not exceeded for long term therapy.
Prednisone is relatively safe in  pregnancy  if  prednisone is not given at a
dose greater than  20  mg/day.   If  NSAIDs  are  given  with  prednisone  in
pregnancy  expect a possible delay in labor and NSAIDs are excreted in breast
milk.

                      -RHEUMATOLOGY LAB TESTING-
Laboratory testing for rheumatologic disorders can be useful in arriving at a
diagnosis, if you are aware of the pitfalls.  The value of a particular blood
test  is  contingent upon the known false positives and negatives for a given
test, and also the sensitivity  and  specificity for that particular test.  A
particular test should only  be  ordered  in  the  context  of  the  probable
disease.   A  particular  test  may  be  positive  in  several  rheumatologic
diseases.   On  the other hand, a particular test may be virtually diagnostic
of a single disease.  For example, the  ANA  is not specific for SLE, but the
presence of high titers of anti-double stranded DNA  and  anti-Sm  antibodies
are  usually diagnostic for SLE.  The following discussion will center on the
usefullness of the ESR, ANA, rheumatoid factor assay, complement level assay,
antineutrophil cytoplasmic  antibody  assay,  HLA  B27,  and Lyme antibodies.
ERYTHROCYTIC  SEDIMENTATION  RATE  (ESR):	Elevation  of   the   ESR   is   a
non-specific  indicator of inflammation, whether it be malignancy, infection,
vasculitis or autoimmune disease.   The  Westergren method is recommended, as
it has less influence from the hematocrit.  An elevated ESR is  a  reflection
of  acute  phase  reactants  as haptoglobin, fibrinogen, alpha-1 proteins and
polyclonal  or  monoclonal  hypergammaglobulinemia.   It  is  very  useful in
diagnosing and following polymyalgia rheumatica and giant cell arteritis.   A
low  ESR  is  suggestive  of cryoglobulinemia, and is also seen in congestive
heart failure.   ANTINUCLEAR  ANTIBODY  (ANA):  The  ANA  is  a  non specific
indirect immunofluorescent screening test for autoimmune  disease.   The  ANA
reflects  the  presence  of  specific  antinuclear  antibodies  which include
antihistone  antibodies,  anti-double  stranded  DNA  antibodies,  antibodies
directed against  acid  extractable  nuclear  antigen (anti-RNP, anti-Scl-70,
anti-Sm, anti-SS-A, anti-SS-B, and anti PM1).  The ANA is positive in greater
than 95% in patients with SLE, but it  is  also  positive  in  several  other
autoimmune  disease  including  Sjogren's  syndrome,  mixed connective tissue
disease, progressive  systemic  sclerosis,  CREST  syndrome, dermatomyositis,
acute bacterial endocarditis, acute and  chronic  liver  disease,  rheumatoid
arthritis,  autoimmune  thyroiditis,  and  Raynaud's disease.  Drugs can also
produce a positive  ANA.   These  include  procainamide and hydralazine which
produce antihistone or anti-single stranded DNA antibodies.  To make  matters
more  complicated, positive ANAs occur in healthy individuals in about 3%.  A
positive anti-double stranded DNA or  anti-Sm is virtually diagnostic of SLE,
but suffers from insensitivity.  RHEUMATOID  FACTOR:  A  positive  rheumatoid
factor  reflects  the  presence  of antibodies against the Fc portion of IgG.
Most  assays  detect  only  IgM  rheumatoid  factors.   Rheumatoid  factor is
important in helping to establish a diagnosis of  rheumatoid  arthritis,  but
has  several drawbacks.  It is only positive in about 75% of patients with RA
and like ANA, is positive in a number of other diseases.  Positive rheumatoid
factor may be seen  in  Sjogren's  syndrome  (90%),  and  in  type II and III
cryoglobulinmeia (100%), SLE, mixed connective  tissue  disease,  progressive
systemic  sclerosis, bacterial endocarditis, acute and chronic liver disease,
and in malignancy (especially  in  lung  cancer).  Therefore, is it important
that the clinical findings support a positive rheumatoid factor.  COMPLEMENT:
The most common complement components include C3, C4 and CH50.  Decreases  of
complement  are  useful  in  following  SLE  disease  activity (The lower the
complement,  the  more   active   the   disease,   which  reflects  the  high
concentration of circulating immune complexes).   ANTINEUTROPHIL  CYTOPLASMIC
ANTIBODIES  (ANCA):  These  antibodies  are  important,  because  they can be
helpful in diagnosing Wegener's granulomatosis and microscopic polyarteritis.
There are 2 immunofluorescent patterns  seen, depending upon which antibodies
are present.  The first is  known  as  c-ANCA  (antibodies  directed  against
proteinase  3)  which  produces  a  characeristic  cytoplasmic pattern.  This
pattern  is  found  in   about   90%   of  patients  with  classic  Wegener's
granulomagtosis, 75% in limited  Wegener's,  and  about  40%  in  those  with
microscopic polyarteritis.  The second type of immunofluorescense is known as
the p-ANCA assay (antibodies directed against various cytoplasmic substances)
which  produces  a characteristic perinuclear pattern.  If the antibodies are
directed  against   cytoplasmic   myeloperoxidase,   Churg-Strauss  syndrome,
systemic necrotizing vasculitis, and cresenteric glomerulonephritis should be
ruled out.  Patients with a positive  p-ANCA  directed  against  lactoferrin,
should be studied for ulcerative colitis, Crohn's disease, primary sclerosing
cholangitis,  and  RA.   About  5%  of healthy individuals will have positive
p-ANCA.  HLA-B27: The HLA-B27 assay is  a  non specific test that can be used
to help verify spondylopathies.  However, it is present in about 7& of normal
healthy whites in the USA, which dilutes it specificity.  It is found in more
than 95% of patients with ankylosing spondylitis, 80% of  Reiter's  syndrome,
50%  of psoriatic spondylitis, and in 25% of spondylitic chronic inflammatory
bowel disease.  ANTIPHOSPHOLIPID ANTIBODIES:  The  lupus anticoagulant is one
of the antiphospholipid antibodies.  It has the ability to prolong  the  PTT,
and  is associated with an increased risk for arterial and venous thrombosis,
an  increased  incidence  of   spontaneous  abortion,  and  thrombocytopenia.
Anticardiolipin  antibody  is  another  antiphospholipid  antibody  that   is
detected  by ELISA.  It also is associated with increased arterial and venous
thrombosis.  LYME ANTIBODIES: Non-specific tests for Lyme disease include the
indirect immunofluorescnce  and  enzyme  linked  immunosorbent assays.  These
tests are sensitive, but are not specific.  There may be cross reactions with
other Borrelia infections, SLE and syphilis.  The Western blot	test is  more
specific, but less sensitive.

                   -RIGHT VENTRICULAR INFARCTION-
Patients usually have  hypotension,  clear  lung  fields and elevated jugular
venous pressure in the face  of  an  inferior  infarction.   Kussmaul's  sign
(distention of the jugular vein on inspiration), also present in constrictive
pericarditis,  is  a  sensitive  and  specific  indicator  for rt ventricular
infarction.   There  may  be   atrioventricular  dissociation  and  tricuspid
regurgitation.  EKG: ST segment elevation in lead V4R is the most predictive,
but may be transient.  Right bundle branch block and complete heart block are
the  most  frequent   conduction   disturbances.    ECHOCARDIOGRAPHY:   Right
ventricular   dilatation,   right  ventricular  wall  asynergy  and  abnormal
interventricular  septal  motion.   The  short  axis  view  has  the  highest
sensitivity.  There may be interatrial  septal bowing toward the left atrium.
Doppler may show tricuspid  regurgitation  and  VSD,  as  well  as  premature
opening  of  the pulmonic valve indicative of a noncompliant right ventricle.
NUCLEAR  IMAGING:   Radionuclide   ventriculography   will   show  low  right
ventricular ejection fraction and wall motion abnormality with a  sensitivity
of  92%  and  82%  specificity.   HEMODYNAMIC:  The  right atrial pressure is
elevated and exceeds  the  capillary  wedge  pressure.  The right ventricular
pressure tracing is broad and bifid.  A dip  and  plateau  in  the  diastolic
pressure curve may be seen.  COMPLICATIONS: High degree AV block may occur in
48%   of   right   ventricular   infarctions.   Shock  is  uncommon.   Atrial
fibrillation may occur in 33%  of  patients.  There is an increased incidence
of ventricular arrhythmias with and without right heart catheterization.  VSD
may   occur.    Other   complications   include   tricuspid    regurgitation,
pericarditis,  right  to left shunt through a patent foramen ovale, and rignt
ventricular thrombus with embolization.

              -RIGHT VENTRICULAR INFARCTION TREATMENT-
Patients should have maintenance of right  ventricular  preload  with  volume
loading  using  IV  normal  saline.   Nitrates, diuretic and morphine sulfate
should be avoided  as  they  may  reduce  cardiac  output  and produce severe
hypotension.  If complete heart block is present atrioventricular  sequential
pacing  may be needed and cardioversion may be needed for atrial fibrillation
in order  to  maintain  atrioventricular  synchrony.   Inotropic support with
dobutamine is helpful if volume loading fails.  Nitroprusside or  intraaortic
counterpulsation  may  reduce  right  ventricular afterload and improve right
ventricular function.  Thrombolytic agents and angioplasty have also improved
hemodynamic function.

         -RISK STRATIFICATION IN ACUTE MYOCARDIAL INFARCTION-
INITIAL STRATIFICATION: The risk of non-reperfusion from thrombolytic therapy
during the first 24 hours of hospitilization should be the initial appraisal.
Reperfusion  success  is  usually heralded by immediate relief of chest pain,
onset of  reperfusion  arrhythmias  and  return  of  elevated  ST segments to
normal.   The  reperfusion  arrhythmias  consist  of  bradycardia,  PVCs  and
accelerated idioventricular rhythms.  If none of these appear and the patient
has continued pain, evidence of a large infarction on ECG and echocardiogram,
left ventricular dysfunction, and failure to  improve  hemodynamically,  then
perhaps  the patient is a candidate for catheterization to assess the anatomy
of the lesions(s).   PTCA  of  an  occluded  artery  that  has failed to open
following thrombolytic therapy may be beneficial, but  early  PTCA  has  been
shown   to   be   associated  with  increased  procedure  related  morbidity.
INTERMEDIATE PHASE: The intermediate  phase  encompasses  the period from the
2-5th day of hospitilization.  During  this  period,  one  should  watch  for
complications  of  MI, such as septal and free wall rupture, papillary muscle
rupture and evidence  of  any  ongoing  ischemia  as  manifested by recurrent
angina, hypotension and CHF.  PREDISCHARGE  PHASE:  A  low  level  submaximal
stress  test  with  thallium  should be done prior to discharge to assess any
ischemia.  If the  patient  is  unable  to  exercise, persantine or adenosine
thallium scanning can be substituted  as  these  are  just  as  effective  in
identifying  those  at  risk.  At 6-8 weeks post discharge the patient should
have a maximal stress test  done  in  order  to  ascertain if the patient can
resume normal activities and rehabilitation.  If during the course  of  these
tests  exercise  induced  ischemia  is  discovered,  angiography  followed by
revascularization should be carried out.  The  signal averaged ECG is used to
ascertain if the patient is vulnerable to electrical instability  and  sudden
death  following  acute  myocardial  infarction.   If  late potentials or low
amplitude depolarizations are seen following  the  QRS complex, there is a 10
fold increased chance in those patients with  ejection  fractions  less  than
0.40 for significant future arrhythmic events.  Unfortunately, however, there
is currently no good pharmacologic therapy for complex ventricular ectopy and
electrophysiologic studies are not routine.

                   -ROCKY MOUNTAIN SPOTTED FEVER-
Rocky mountain spotted fever (RMSF)  can  be a deadly disease.  Even patients
that are treated may have a  mortality  of  3-6%.   The  diagnosis  often  is
evasive as the classic retro-orbital headache, fever and rash, and history of
tick  bite  are not always present.  Only about 70% of patients will report a
tick bite.  Always  consider  RMSF  if  typical  symptoms  are present in the
spring, summer or early fall when the ticks are active.  RMSF  is  caused  by
Rickettsia rickettsii and is transmitted mostly by Dermacentor andersoni (the
wood tick) and Dermacentor variabilis (the dog tick).  In the past, North and
South  Carolina,  Virginia and Oklahoma have had a very high incidence of the
disease.  The disease apparently has  not  been reported in Alaska or Hawaii.
CLINICAL: The incubation period for RMSF is about 2-14 days  after  the  tick
bite  occurs.  Following this a very severe headache occurs (60%) with nausea
and vomiting (30-50%),  myalgia  (45%),  conjunctivitis (30%), abdominal pain
(50%), and fever (100%).  The fever may reach 103-104 F. In severe cases  the
temperature  may stay elevated for 2-3 weeks.  The rash occurs about 3-4 days
after  the  onset  of  the  fever  and  typically  occurs  in  a  centripetal
distribution affecting the wrists,  ankles,  hands  and feet.  The peripheral
rash typically spreads  rapidly  to  the  neck,  face,  trunk,  buttocks  and
axillary  areas.  About 90% will develop a rash.  The first signs of the rash
are irregular red macules that measure about 3-4 mm.  The macules evolve over
the next few days  into  papules  which  are  a  darker  shade of red.  These
eventually develop into petechiae and purpura which may  go  on  to  necrosis
involving  the  digits  and  scrotum.   As the rash heals it usually causes a
brownish discoloration.   The  rash  may  be  difficult  to  detect  in Black
patients.  Other symptoms that may occur but less frequently than  the  above
include:  hypotension, pulmonary edema and myocarditis, peripheral edema, and
pleural effusion.  Neurologic symptoms that may be present at sometime during
the course of the  disease  include  seizures, deafness, meningismus, ataxia,
coma and paralysis.  LABORATORY: A useful hint that may point  you  toward  a
diagnosis  of  RMSF is hyponatremia.  This is not specific for RMSF, but will
usually occur in up to 90% of cases.  The sodium may dip as low as 110 mEq/L.
Platelets may also be  as  low  as  2000  to  3000  which  is in the range of
bleeding.  The hemoglobin may drop as low as 7 gm/dl while the hematocrit may
reach a nadir of around 20%.  The WBC is not useful in the  diagnosis  as  it
may  range from 4,000 to 35,000.  Always check the LDH as this may be as high
as 5000 U/L.  Serum creatine kinase may  rise to 40,000 U/L.  Jaundice may be
present with the total bilirubin rising to as high as 16 mg/dl.  If a  spinal
tap  is  done,  which  may  be  done  because  the patient develops seizures,
meningismus and coma, the CSF  culture  and  Gram stain will be negative, but
there will be lymphocytes or polymorphonuclear cells depending on  the  stage
of  evolution  of  the disease.  The CSF glucose may be reduced with elevated
protein.  Antibody titers are worthless  because  it  takes more than 10 days
for these to return.  Direct fluorescent antibody testing from a skin  biopsy
may  be useful as the results are available in some centers in 4-6 hours.  If
the indirect fluorescent antibody assay  is  greater  than 1:64, then this is
considered a positive test  for  RMSF.   The  Weil-Felix  test  is  not  very
reliable.  DIFFERENTIAL DIAGNOSIS: The differential would include enteroviral
infections,  gonococcemia,  measles  and  meningococcemia.   Meningococcemia,
however,  tends  to  occur  in the late winter and early spring as opposed to
RMSF which occurs during  the  summer  months.   TREATMENT: Treatment is with
either tetracycline, doxycycline or chloramphenicol.  The patient usually  is
treated  with tetracycline or doxycycline except when the patient is pregnant
or less than 8 years of age,  or  when the patient is extremely sick.  In the
latter case, chloramphenicol is used.   However,  chloramphenicol  may  cause
bone  marrow  depression  and  aplastic  anemia  which  fortunately  is rare.
Tetracyclines may stain the teeth  if  given during pregnancy and to patients
less than 8  years  of  age.   Both  tetracyclines  and  chloramphenicol  are
rickettsiostatic.   Treatment  must be started early because of the potential
for mortality.  Tetracycline may be given  orally  at 25-50 mg/kg/day up to 1
gram/day divided into 4 doses for 7-14 days.  Alternatively, doxycycline  100
mg  (2-2.5  mg/kg po) bid for 7-14 days may be used.  Intravenous doxycycline
is given at 4.4 mg/kg IV  initially  then  2.2 mg/kg every 12 hours.  Both of
these antibiotics may be  discontinued  3  days  after  the  patient  becomes
afebrile.   Chloramphenicol  may  be  given  orally or IV at a dose of 75-100
mg/kg/day up to 3 grams/day in  4  divided doses.  After one day of treatment
at this dose, the chloramphenicol may be reduced to 50 mg/kg/day, unless  the
patient  is  very  ill.   Ancillary treatment of complications of the disease
would  include  fluid  support   if   hypotension  develops  and  saline  for
hyponatremia.  Myocarditis may intervene and  the  patient  may  need  to  be
monitored.  Prophylaxis for tick bites should include deet application to the
skin  plus  permethrin  on  clothing for tick repellent.  All ticks should be
removed from the skin by gentle traction on the head of the tick.

                   -ROCKY MOUNTAIN SPOTTED FEVER-
Symptom triad includes fever,  retrobulbar  headache and initial ankle, wrist
macular coalesing, blanching pink rash which  usually  begins  4  days  after
symptoms.  Rash then spreads to arms, legs and trunk.  Palms and soles may be
involved.   LDH,  bilirubin,  creatine  kinase  and  PT  may  be  high.  Hgb,
platelets and sodium may be low.   CSF shows sterile leukocytosis with either
polymorphonuclear  or  lymphocytes  predominating.   Ten  days  required  for
immunofluorescence antibodies to becme positive, but high titers may be found
as early as 3-4 days.  A 4 fold increase over 2 weeks is diagnostic.   Direct
fluorescent  antibody  staining of biopsy from active skin lesion can confirm
diagnosis in  4-6  hours.   Treatment  is  oral  tetracycline 25-50 mg/kg/day
divided into 4 doses for 7-14 days or doxycycline 100 mg bid.  Children  less
than  8 years of age will stain their teeth with tetracycline and are usually
given  a  limited  dose  of   tetracycline   in  order  to  spare  them  from
chloramphenicol   which   can   cause    idiosyncratic    aplastic    anemia.
Chloramphenicol  is  usually  used only in severe infection, giving 100 mg/kg
divided into 4 doses for the first 24 hrs, then 50 mg/kg/day.

                        -SALICYLATE POISONING-
Salicylates are  widely  available  in  multiple  forms.   They  are not only
available as aspirin preparations, but many  over  the  ocunter  preparations
contain   salicylates.    Aspirin   is  available  in  tablet,  capsule,  and
suppository    forms,    often    in    combination    with   antihistamines,
anticholinergics, narcotics, and muscle relaxing and neuroleptic agents.  Oil
of  wintergreen  contains  concentrations  up  to  7  grams/teaspoon.   Other
non-aspirin sources of salicylates  include  bismuth  subsalicylate,  choline
salicylate,    choline   magnesium   trisalicylate,   magnesium   salicylate,
homomenthyl  salicylate  (sunscreen),   sodium   salicylate,  salsalate,  and
salicylic acid (topical keratolytics).  The recommended dose  of  aspirin  is
10-15  mg/kg  every  4-6  hours, and should not exceed 80 mg/kg/day.  Aspirin
inhibits   platelet   aggregation,   while    other   salicylates   do   not.
Therapeutic	serum concentrations range from 10-30 mg/dL.  Peak  blood  levels
of  10-20  mg/dL  usually occurs 1-2 hours after ingestion.  Salicylates that
are given in therapeutic doses for the treatment of inflammatory disorders in
doses  of  4-6  grams/day   result  in  a  half  life  of  about  6-12 hours.
Salicylates used in lower doses, such as for relief of fever,  results  in  a
half  life  of  2-3 hours.  However, in toxic ingestions, the effective serum
half life can increase to more than 20 (18-36) hours due to saturation of the
metabolic  pathways.   The  major  pathway  of  excretion  of  the  unchanged
salicylagte is thorugh the kidney  in  an overdose.  Aspirin is a significant
toxin to cells.  It uncouples oxidative phosphorylation, interferes with  the
Krebs   cyle  and  carbohydrate  metabolism,  and  stimulates  the  medullary
respiratoy  center.   This   causes   an   early   hyperglycemia  that  later
deteroriates into hypoglycemia, hyperventilation and alkalosis, and metabolic
acidosis.   Salicylates  also  cause  decreased   platelet   aggregation   by
interfering    with   prostaglandins   and   platelet   associated   enzymes.
Furthermore, aspirin causes irritation of the gastric mucosa, abodominal pain
and bleeding.  There has been a decrease of salicylism in recent years due to
the use of  child  resistant  containers,  and  decreased  use  of aspirin in
pediatric  patients  because  of  an  association   with   Reye's   syndrome.
Salicylate  poisoning  can  conveniently  be  divided  into acute and chronic
intoxications.  Acute toxicity can occur  from accidental administration of a
toxic dose, intentional overdose, or associated with the use of normal  doses
in  a patient that is dehydrated.  Symptoms of salicylate poisoning depend on
the the weight of the  child,  the  dose  taken,  and whether the overdose is
acute or chronic.  Doses less than 150 mg/kg usually do not produce symptoms,
or symptoms that are very mild.  Doses between 150-300 mg/kg, cause  mild  to
moderate  symptoms,  and  doses  between  300-500  mg/kg  cause  life  severe
symptoms.   The  Done  nomogram may also be utilized for an estimation of the
toxicity.  This is done  by  obtaining  a  salicylate  level  at 6 hours post
ingestion.  Levels of 40 mg/dl  are  typically  seen  in  patients  who  have
ingested  less  than  150  mg/kg, and are not associated with any significant
symptoms.  Six hour levels between  60-95  mg/dl are associated with moderate
intoxication, and most  will  have  hyperpnea  and  CNS  symptoms  of  either
somnolence or excitability.  Six hour levels greater than 110-120 on the Done
nomogram  indicate  severe  toxicity.  CLINICAL: ACUTE INTOXICATION: Patients
usually  develop  vomiting  early  after  ingestion.   This  is  followed  by
hyperpnea, tinnitus and lethargy. There may be fever, asterixis, diaphoresis,
slurred  speech,  disorientation,  hallucinations,  tachycardia, hypotension,
leukocytosis, thrombocytopenia,  hypokalemia,  increased  BUN,  creatine  and
ketones.   There  may  be mixed respiratory alkalosis and metabolic acidosis.
If  the  intoxication   is   severe,  seizures,  hypoglycemia,  hyperthermia,
pulmonary edema and coma may ensue.  Death is usually due  to  cardiovascular
collapse  and  CNS  failure.   CHRONIC  INTOXICATION:  These  individuals are
usually elderly patients or are  very  young children.  They may present with
dehydration, confusion, and metaboic  acidosis.   These  patients  are  often
misdiagnosed  as  gastroenteritis,  sepsis  and  pneumonia.  The diagnosis is
frequently missed.   The  symptoms  may  be  similar  to acute intoxications.
Pulmonary edema is  common  in  the  elderly,  and  hyperventilation  may  be
prominent.   The Done nomogram should not be used to predict the morbidity in
chronic  intoxication.    In   chronic   intoxication,   chronic  therapeutic
concentrations in  arthritis  patients  range  between  100-300  mg/L  (10-30
mg/dL).  Levels greater than 600 mg/L (60 mg/dL) associated with acidosis and
altered  mental  status  should  be  considered  as potentially very serious.
LABORATORY: All patients  should  have  electrolytes, anion gap calculations,
prothrombin time determinations, BUN, creatinine, arterial blood gases, chest
x-ray and salicylate  levels  drawn.   A  urine  Phenistix  test  is  usually
positive  as  is  the ferric chloride test.  The ferric acid chloride test is
performed by adding 5-10 drops of 10% ferric chloride solution to urine which
has been boiled for 1-2 minutes.  If  positive the urine will turn a burgundy
color.  Chest x-ray may reveal pulmonary edema with a normal sized heart.  CT
of the head may reveal cerebral edema and hemorrhage.  Stool samples  may  be
positive  for  blood.  UA can show proteinuria, and liver enzymes and amylase
may be elevated, if hepatic  toxicity and pancreatitis occur.  TREATMENT: The
urine should be alkalinized.  If the patient is considered to be dehydrated a
bolus of 10-20 mL/kg of 5% dextrose in 1/4 strenth saline is  infused.   This
is followed by adding 100 meq of sodium bicarbonate to 1 Liter of 5% dextrose
in  1/4  strength saline and infusing at 200 mL/h (3-4 mL/kg/hour.  Add 30-40
meq of KCL to each liter also,  if  there is no renal failure.  Be careful in
patients that are elderly and at risk for pulmonary edema, and in those  with
chronic  salicylate  intoxication.   Alkalemia  is  not a contraindication to
bicarbonate therapy, because patients often have  a base deficit, even in the
face of an elevated serum pH.  Hemodialysis is indicated  for  patients  with
acute  ingestion and serum levels higher than 1200 mg/L (120 mg/dL), or those
with  severe  acidosis.   Indications  for  chronic  toxicity  include  those
patients  with  salicylate  levels  higher   than  600  mg/L  (60  mg/dL)  in
association  with  confusion,  acidosis,  and  lethargy.    Hemodialysis   is
preferred over hemoperfusion because hemoperfusion does not correct acid base
or   fluid   abnormalities,   as  does  hemodialysis.   If  the  patient  has
hyperpyrexia, sponge baths with tepid water  or cooling blankets may be used.
Seizures are treated with diazepam given IV.  Prolonged prothrombin times are
corrected with vitamn K. Cerebral  edema  can  be  treated  with  mannitol  1
gram/kg  of  a  20%  solution  IV  and/or dexamethasone.  Pulmonary edema may
require intubation and  mechanical  ventilation  with positive end-expiratory
pressure (PEEP).  Hypotension is treated  with  fluids  and/or  vasopressors.
General  decontamination  measures  are  carried  out  with gastric lavage in
patients with an ingestion of greater than  100 mg/kg within 4 hours prior to
presentation, and  those  who  have  ingested  enteric  coated  preparations.
Activated charcoal is given to all patients and repeated as needed.

                        -SALMONELLA AND AIDS-
Ampicillin 8-12 gm/day IV x 2wk followed by amoxicillin 500 mg PO tid  x  2wk
or  Ciprofloxacin  750  mg PO bid x 2-4 wk or Trimethoprim (5-10 mg/kg/day) +
sulfamethoxazole IV or PO x 4 wk.  Maintenance therapy: Amoxicillin 250 mg PO
bid or Ciprofloxacin 500  mg  PO  qd  or  bid  or  Trimethoprim (2.5 mg/kg) +
sulfamethoxazole PO bid.

                           -SALMONELLOSIS-
Salmonellae  are gram negative bacilli that are capable of causing food borne
gastroenteritis,  and  a   bacteremic   infection   of   bone  and  meninges.
Salmonellae can be found  almost  anywhere  in  nature,  affecting  wild  and
domestic  animals.   Reptiles and fowl have high carriage rates.  The disease
may occur by direct  or  indirect  contact  with  infected poultry, raw milk,
eggs, egg products, and contaminated  water.   Contaminated  egg  powder  and
frozen  whole  egg  preparations have been used to make mayonnaise, custards,
and ice cream, causing sporadic  outbreaks.   Infected beef and pork products
account for approxiamtely 13% of outbreaks.  One large outbreak in  the  past
affected  over 16,000 individuals, and was due to Salmonella typhimurium that
contaminated pasteurized milk.  In that particular outbreak, the organism was
resistant to multiple  antibiotics.   Other  rare  sources  of infection have
included contaminated marijuana,  infected  pet  turtles,  lizards,  platelet
transfusions,  mouth  to  mouth  resuscitation, fomites, and carmine red dye.
Hospital  workers  may  carry  the   organisms  on  the  hands  or  clothing.
Salmonella have been to shown to survive on the hands for at least  3  hours.
They  also  can  survive  refrigeration  and  egg  boiling  for  2-3 minutes.
Patients  that  have  sickle  cell  anemia,  diabetes  mellitus, splenectomy,
achlorhydria, gastrectomy, renal transplant  patients,  cirrhosis,  leukemia,
lymphoma,  HIV,  malaria,  bartonellosis, and louse borne relapsing fever are
more predisposed to  infection  with  Salmonella.   Newborns and infants less
than 1 year of age are particulary  at  risk  for  infection.   There  are  3
species  of  salmonella:  (Salmonella  typhi,  Salmonella  choleraesiuis  and
Salmonella enteritidis) and about 1800 serotypes.  Salmonellae	penetrate the
small  bowel  epithelial cells and multiply in the submucosa.  Salmonella can
produce  a  variety   of   illnesses.    These   are   usually  divided  into
gastroenteritis,  enteric  fever  and  bacteremia.    The   most   frequently
encountered  syndrome  is  gastroenteritis.   SALMONELLA GASTROENTERITIS: The
incubation period varies between 8-48  hours.  The patient initially develops
nausea and vomiting which is then followed by abdominal cramps and  diarrhea.
The  stools  may  have a rotten egg odor.  The diarrhea can be mild to bloody
stools with mucus.   Fifty  percent  of  patients  will develop a temperature
greater than 38.9 C which usually only lasts for  24-48  hours.   The  entire
episode  usually  lasts from 1-4 days.  However, about 33% will have positive
stool cultures up to 3 weeks following  the onset of the illness, in spite of
being asymptomatic.  Most will have cleared the stools by 6  months.   Smears
of  the  stool  may show WBCs when stained with methylene blue.  Diagnosis is
made by culture.  Loperamide and diphenoxylate are contraindicated since they
can prolong the infection.  Ciprofloxacin,  ofloxacin and norfloxacin are the
antibiotics of choice.  Quinolone antibiotics are not indicated in  children.
Antibiotics  are  recommended  for  high  risk  individuals which include the
elderly, patients who are immunocompromised (lymphoproliferative disease, and
AIDS), neonates less than 3 months old, patients with cardiovascular disease,
patients with sickle cell disease and other hemolytic syndromes, and patients
that have bone  and  joint  disease.   ENTERIC  FEVER:  The prototype of this
disease is typhoid fever which is caused by Salmonella typhi, but can also be
associated  with  Salmoneallae  paratyphi  A  and  B  (S.    schottmuelleri),
Salmonella paratyphi C (Salmonella hirschfeldii), and Salmonella sendai.  The
incubation  period is from 1-3 weeks.  A few patients (10%) will present with
diarrhea  initially  followed   by   fever,  anorexia,  myalgia,  arthralgia,
headache, cough and sore throat.  In the second week of illness, the  patient
usually  develops  abdominal  tenderness  and constipation.  Rose spots (pink
macules) 2-4 mm develop  in  crops  of  5-15,  last  about 3-4 days, and then
disappear.   They   characteristically   blanch   upon   pressure.    If   no
complications develop, the untreated patient will improve sponataneously from
the  2-4th  week  of  illness.   If the patient does not improve by the 4-5th
week, metastatic  infection  and  relapse  can  occur (3-15%).  Complications
include intestinal perforation and hemorrhage, pneumonia, cholecystitis,  and
myocarditis.   Unusual  complicatons  include  prostatitis, epididymitis, and
pyelonephritis.  Diagnosis may be difficult in the early stages.  The patient
may give a history of recent travel  in an endemic area.  Blood cultures will
be positive in about 80% of patients for about 2 weeks.  Cultures of the bone
marrow are an excellent source during  the  acute  phase.   Urine  and  stool
cultures  become positive following the septicemia.  Biopsy of the rose spots
can reveal the bacilli when  cultured.   The Widal reaction detects increases
in O and H agglutinating antibodies.  Treatment of enteric fever  classically
is  treated with chloramphenicol 50 mg/kg/day up to a maximum of 4 grams/day,
given in 4 divided doses.  Ampicillin 150-200 mg/kg/day up to a maximum of 12
grams/day is given in 4-6 divided doses.  TMP-SMX is given as 5 mg/kg/dose of
trimethoprim and 25 mg/kg/dose of  sulfamethoxazole every 12 hours.  Patients
should be treated for at least 2 weeks, or 10 days beyond defervescence.   If
the  organism is resistant to the above antibiotics, ceftriaxone, cefotaxime,
or ciprofloxacin may be used.  Ciprofloxacin  is given as 10 mg/kg/dose every
12 hours.  Ceftriaxone is given  as  100  mg/kg/day  in  two  divided  doses.
Cefotaxime  is  given  as 200 mg/kg/day in 4 divided doses.  Choloramphenicol
and  TMP/SMX   are   contraindicated   in   pregnant   women   and  neonates.
Ciprofloxacin is contraindicated in pregnancy and children less than 18 years
of age.  Patients with AIDS should  be  placed  on  prophylactic  maintenance
doses  of  ciprofloxacin  or  norfloxacin.  SALMONELLA BACTEREMIA: Salmonella
choleraesuis, Salmonella typhimurium, and  Salmonella heidelberg are the most
common causes of bactermia causing an intermittent  prolonged  fever  lasting
for  days  to  weeks.  Diarrhea is not present and stool cultures are usually
negative.  The bacteremia can  cause endocarditis, meningitis, brain abscess,
infected  aneurysms,  pneumonia,  empyema,  lung  abscesses,   osteomyelitis,
splenic  abscesses,  hepatic  abscesses, orchitis, septic arthritis, and soft
tissue abscesses.  Salmonella osteomyelitis  is  seen in sickle cell disease.
It  can  also  be  a  complication  of  total  hip  replacement.   Salmonella
meningitis is usually seen in neonates and infants  from  a  complication  of
gastroenteritis.    Hepatic   abscesses   may   occur  with  amebic  abscess,
echinococcal cysts and hematomas.   Splenic  abscesses may be superimposed on
subcapsular hematomas or splenic cysts.  Pulmonary abscesses and empyema  are
seen  in  the  immunocompromised and the elderly.  Salmonella endocarditis is
treated  with  bactericidal  drugs  such  as  cefotaxime  or  ceftriaxone IV.
Meningitis is treated with cefotaxime 50 mg/kg every 6 hours for at  least  3
weeks.    Infected  aneurysms  will  usually  need  surgical  excision,  plus
antibiotics (Ciprofloxacin or TMP-SMX).  Bactermias  are treated for 2 weeks,
but osteomyelitis and  endocarditis  need  treatment  for  4-6  weeks.   AIDS
patients  will  need  prophylaxis  with  ciprofloxacin  or  TMP-SMX.  CARRIER
STATES: About 3% of patients  with  typhoid fever will develop carrier states
while about .2-.6% of nontyphoidal salmonellosis will develop chronic carrier
states.  The chronic carrier state is defined as postive stool cultures  that
persist   for   1  year  or  longer.   Patients  with  obstructive  uropathy,
individuals  over  50  years   of   age,   biliary   tract  disease,  TB  and
shistosomiasis are risk factors for the carrier states.  Carrier  states  are
especially  important  in  food  handlers.   Cholecystectomy may be needed in
those who do not  respond  to  antibiotic  therapy.   The drugs of choice are
ampicillin or amoxicillin 4-6 grams/day in four divided doses for  4-6  weeks
if  there is no biliary disease, TMP-SMX	160 mg of tremethoprim and 800 mg of
sulfamethoxazole BID, ciprofloxacin 750 mg BID for 28 days, and ceftriaxone 2
grams/day IM or IV for 3 days.

                            -SARCOIDOSIS-
Sarcoidosis  is  a  multisystem granulomatous disease that has a predilection
for the lungs, but can  affect  other  systems  such as the following seen in
descending frequency: lungs, mediastinal lymph nodes, peripheral lymph nodes,
skin, eyes, liver, spleen, bone, salivary and lacrimal glands, joints, heart,
skeletal muscle,  central  nervous  system,  and  kidneys.   Since  it  is  a
noncaseating  granulomatous  disease  that  can  proceed to hyalinization and
fibrosis, other causes of non-caseous granulomata  would have to be ruled out
as: fungal,  mycobacterial,  infections,  berylliosis,  syphilis,  Hodgkins's
disease,  brucellosis,  Q fever, histiocytosis, tularemia, biliary cirrhosis,
drug  reactions  as  sulfonamides   and  phenylbutazone,  leprosy,  Wegener's
granulomatosis and focal sarcoidal reactions in lymph  nodes  which  drain  a
solid  tumor.   The  cause  of  Sarcoidosis  is unknown.  Sarcoidosis is more
common in blacks between the ages of 20 and 40 and they typically have a more
aggressive prolonged course.  The pulmonary disease is typically divided into
3 stages which also can serve as a prognostic guide.  Stage I shows symmetric
bilateral hilar adenopathy along with possible right paratracheal adenopathy.
Prognosis for stage  I  is  excellent  especially  if  it  is associated with
erythema nodosum.  Since this stage is usually associated with no symptoms it
can sometimes be found on routine  chest  x-ray  that  is  done  for  another
reason.   Stage  II  is  bilateral  hilar  lymphadenopathy  plus  parenchymal
infiltration  and  stage  III  is  parenchymal infiltration in the absence of
hilar lymphadenopathy.   CLINICAL:  Symptoms  would  depend  on  the  site of
involvement. If the lung is involved  there  may be cough, dyspnea,  fatigue,
fever  and  weight loss.  If there are pulmonary fibrosis and cystic changes,
there may be  symptoms  and  signs  compatible  with  cor pulmonale.  Uveitis
occurs in about 15% of patient.  It is  bilateral  usually,  and  has  to  be
treated  as  there  may  be loss of vision from the secondary glaucoma.  Skin
disease  usually  presents  as  subcutaneous  nodules,  papules  and plaques.
Myocardial involvement can cause conduction abnormalities, heart failure, and
angina.   CNS  involvement  occasionally  shows  cranial  nerve  palsies,  in
particular 7th nerve palsies.  Diabetes insipidus can occur with  involvement
of  the  pituitary  or  hypothalamus.   Polyarthritis may cause periarticular
swelling and tenderness associated with  changes in the phalanges.  The knees
and ankles are  commonly  involved.   Hypercalcemia  is  caused  by  alveolar
macrophage  production of 1,25 dihydroxyvitamin D. The hypercalcemia may then
cause damage to  the  kidneys  by  nephrocalcinosis,  renal calculi and renal
failure.  Sometimes, Erythema nodosum occurs in conjunction with Stage I lung
disease, and when this combination occurs, the diagnosis  of  sarcoidosis  is
secure, and the prognosis is good.  Hepatic granulomas are found in 70%, even
when  the  liver function tests are normal and the patient has no symptoms of
liver  disease.   Hepatomegaly  is  only   present  in  about  10%  or  less.
LABORATORY: There is hypergammaglobulinemia, cutaneous anergy, positive Kveim
test (the Kveim test is not used much because there is a lack of the antigen,
a waiting period of 6 weeks until the test area can be  biopsied,  and  false
negative reactions that increase with the duration of the disease.  There may
also  be  hyperuricemia,  hypercalcemia  and  hypercalciuria, low parathyroid
hormone levels and  elevated  rheumatoid  factor.  The angiotensin converting
enzyme (ACE) can be used to follow the activity of  the  disease,  but  isn't
good  for diagnosis as a false positive test may occur with other diseases as
histoplasmosis, acute  miliary  TB,  lymphoma  and  hepatitis.   The alkaline
phosphatase  is  elevated  in  liver  disease.   Biopsy  sites  include   the
mediastinal  nodes  via  mediastinotomy  or mediastinoscopy, intercostal lung
biopsy, and liver biopsy.  The  most common procedure performed for diagnosis
is transbronchial biopsy.  The biopsies will show  non-caseating  granulomas.
Bronchoalveolar  lavage  and  whole  body  gallium  scans can also be done if
diagnosis is obscure.  The gallium  scan  will show symmetrical uptake in the
hilar and mediastinal nodes, parotid, lacrimal and  salivary  glands.   These
areas  may  then  be  used  for  biopsy sites.  A second use of gallium is to
differentiate pulmonary  fibrosis  from  reversible  inflammation.  Pulmonary
function should be done which usually shows restrictive changes in  Stage  II
and  III.   With  advanced  pulmonary disease there are obstructive findings.
There is decreased diffusion  capacity.   Chest  x-rays in advanced pulmonary
sarcoidosis may show cystic, or bullous disease and cavities with aspergillus
(fungus balls).  TREATMENT: If the patient has stage  I  lung  disease,  then
baseline  studies  should  be done as CBC, creatinine, calcium and serum ACE.
The fundus should be examined as  uveitis may be subclinical and asymtomatic.
If there is painful erythema nodosum, this can be treated with  NSAID's.   No
other  treatment  is needed as the prognosis is excellent.  Stage one usually
resolves in 1-2 years but is  not  predictable.  Some have resolved after one
month and as late as 15 years.  The chest x-ray should be repeated in about 6
months.  Once the chest x-ray does resolve there is very  little  chance  for
recurrence.  Stage II or III should be followed for about 6 months.  If there
is  no spontaneous resolution or there is progression, then probably steroids
are indicated  to  suppress  the  inflammation  with  an  attempt  to prevent
progression to fibrosis.  Patients can be started on  alternate  day  therapy
with  prednisone  40-60  mg  per  day.   When  there is evidence of decreased
activity of the angiotensin converting enzyme, and the patient's clinical and
laboratory  parameters  parallel  this  improvement,  the  prednisone  can be
tapered by about 10  mg  every  3  months.   If  there  is  hypercalcemia  or
involvement  of critical organs as heart, CNS, and eyes, prednisone should be
used.  Minor  hemoptysis  usually  subsides  depending  on  the etiology.  In
advanced sarcoid lung disease there may be massive  hemoptysis  and  this  is
treated  with  gel  foam  bronchial  artery embolization or resection of lung
tissue.   Fungous  balls  may  require   resection  if  not  controlled  with
embolization, but the morbidity and mortality are high.  Chloroquine has been
effective in controlling cutaneous disease.

                     -SARCOIDOSIS HEART DISEASE-
Cardiac sarcoidosis can  present  as  ventricular  arrhythmias, sudden death,
complete  heart  block,  congestive  heart  failure,  bundle  branch   block,
supraventricular    tachycardia,   pericarditis,   chest   pain,   tamponade,
ventricular aneurysms, and valvular lesions.  However, diagnosis is only made
in less than 50%  prior  to  autopsy.   The  most common ECG findings include
arrhythmias,   conduction   disturbances    and    repolarization    changes.
Pseudo-infarction  Q  waves  may  be  seen secondary to infiltrative changes.
Combination gallium and  thallium  scintigraphy  with  single photon emission
computed  tomography  (SPECT)  will  show  gallium  depositing  in  areas  of
decreased thallium uptake.  Thallium scanning alone may  demonstrate  resting
thallium defects that disappear on 4 hour delayed studies or decrease in size
on  exercise  or IV dipyridamole infusion.  Endomyocardial biopsy is hampered
because of the spotty nature  of myocardial sarcoid infiltration.  CONDUCTION
PROBLEMS: Conduction disturbances are the most common clinical  manifestation
of  sarcoid  heart  disease.   The  bundle  of  His  is particularly at risk.
Complete heart block has been  demonstrated  in  up  to 30% of patients, with
about 68% experiencing syncope.  Bundle branch blocks are also fairly  common
with  RBBB more common than LBBB.  CONGESTIVE HEART FAILURE: Left sided heart
failure is due to myocardial  involvement by inflammatory and fibrotic tissue
causing systolic and diastolic dysfunction.  Right  sided  heart  failure  is
usually  due  to  extensive  fibrotic pulmonary disease.  ARRHYTHMIAS: Sudden
death may be caused by ventricular arrhythmias.  When ventricular tachycardia
occurs,  there  usually  is  extensive  scarring  or  granulomata formations.
Ventricular aneurysms may also contribute  to  the  ventricular  arrhythmias.
Atrial  arrhythmias  are  less  common  and  are  probably  caused  by atrial
dilatation  rather  than  infiltrative  disease.   VENTRICULAR  ANEURYSM: The
incidence of left ventricular aneurysms is approximately 10%.   They  may  be
small  or  diffuse  and may involve the right or left ventricular walls which
microscopically will show sarcoid granulomas  and scar tissue.  The aneurysms
are considered non-ischemic and steroids may contribute to  their  formation.
CHEST  PAIN: Patients may present with typical or atypical chest pain.  Chest
pain has been attributed to coronary artery spasm and vasculitis.  There have
been reports of  intramural  coronary  artery  involvement  by granulomas and
fibrosis.  VALVULAR PROBLEMS: Valvular dysfunction may be  caused  indirectly
by involvement of the papillary muscles which occurs in about 68% of patients
with  cardiac  sarcoidosis,  producing  mitral regurgitation.  Direct sarcoid
valvular invasion is uncommon and  occurs  in  less than 3% of patients.  The
aortic, pulmonic and tricuspid  valves  may  all  be  involved  with  sarcoid
granulomas.  PERICARDIAL DISEASE: Recurrent pericardial effusion secondary to
sarcoid involvement has been reported.  Small pericardial effusions have been
reported to occur in about 19% of patients when examined by echocardiography.
Constrictive   pericarditis   and   pericardial   tamponade  are  both  rare.
TREATMENT: Steroids have been  very  useful  in resolving sarcoid granulomas.
They may  even  reverse  clinical  and  laboratory  abnormalities.   This  is
reflected  by  improvement  of electrocardiographic conduction abnormalities,
ventricular arrhythmias, disappearance  of  Q  waves,  improvement  in R wave
progression and improvement of T  wave  contours.   Thallium  perfusion  scan
defects  have  improved  or  disappeared and there has been improvement in LV
systolic and diastolic  function  following  steroid  treatment.  It would be
prudent to initiate steroid treatment early when  myocardial  sarcoidosis  is
diagnosed,  in  order  to  obviate  fibrotic changes.  Steroids, on the other
hand,  may  be  instrumental  in   fostering  the  formation  of  ventricular
aneurysms.   Cardiiac  transplantation  may  be  considered   when   systemic
involvement  is  excluded  with  gallium  scans  of  the  chest  and abdomen,
pulmonary function tests, sedimentation  rates,  lymph  node biopsy and serum
ACE levels.  The prognosis of myocardial sarcoidosis is grim and is dependent
upon  the  extent  of  cardiac  involvement.   The  average  survival   after
symptomatic involvement of the heart is 1-2 years.

                              -SCABIES-
Scabies  is  caused by a small female itch mite Sarcoptes var.  hominis.  The
adult female measures about 400  microns  and  is extremely difficult to see.
It causes a significant amount of morbidity in the family and also in nursing
homes.  The most fequent location of the rash is  on  the  wrists  and  hands
followed  by  the  extensor elbows, feet, ankles, penis, scrotum buttocks and
axillae.  Scabies is  usually  acquired  by  sleeping  with  a  person who is
infested, or in the bed of an infested person.   The  entire  family  can  be
affected.  The mite is incapable of jumping or flying but can cover about 2.5
cm  of  warm skin per minute.  The mite seems to be attaracted to the skin by
host odor and body heat.   The  mite  is  transferred between hosts by direct
contact, infested clothing and linens.  Live mites can be found from the dust
of bedroom floors, mattresses, chairs, floors, curtains and dirty laundry  of
nursing  homes.   CLINICAL:  The  eruption  consists  of  burrows,  pustules,
papules,  nodules and occasionally urticaria.  Itching is extreme and usually
occurs at night.  The onset of symptoms usually are delayed for several weeks
after the first infestation.  The pruritis  is caused by sensitization to the
mite.  Usually only a few mites are present with most patients having  around
10.   There  are epidemics of scabies which occur in cycles.  The lesions are
typically  seen  on  the  volar  aspect  of  the  wrists,  breasts,  axillae,
interdigital webs of  the  hands  and  genitalia.   Females  may have lesions
around the areolae of the nipples and male patients may have the  lesions  on
the  penis.   In  young  children,  the  palms and soles may be involved with
vesicular and pustular lesions.  In immunosuppressed patients the lesions may
occur on the face  and  scalp  which  are  usually  spared except possibly in
infants.  The burrow is a 2-3 mm track, but may be difficult to see in  about
a  quarter  of  the  patients.  The mite, eggs and stool reside in this track
which is formed  by  the  female  mite  tunneling  under  the stratum corneum
epidermidis.  The female mite in the burrow lays eggs at about  2-3  per  day
for  up  to  2 months.  The egg hatches in about 3-4 days.  Only about 10% of
the eggs will eventually become  adults.   As  the  larvae emerge after a few
days from the burrow, papules are formed around hair follicles  which  become
pruritic.   The  larvae  become adults in about 10-14 days.  The adult female
burrows into the skin and is  eventually fertilized starting the entire cycle
again.  Continuous scratching can lead to thickening of the skin  and  nodule
formation.   with  hyperpigmentation.   Some of these lesions become infected
with group  A  beta-hemolytic  Streptococcus  pyogenes  or coagulase positive
Staphylococcus aureus.  Atypical presentations may  occur  in  two  different
froms:  Scabies  incognito and Norwegian scabies.  Scabies incognito causes a
widespread non-inflammatory distribution	due  to  previous  use of topical
corticosteroid preparations.  Norwegian scabies or crusted scabies is a  rare
presentation  seen  in immunocompromised or neurologically impaired patients.
Typical  patient  populations   would   include  the  malnourished,  mentally
retarded, AIDS patients,  leukemia,  diabetes  mellitus  or  those  receiving
immunosuppressive  therapy.   In  this  form  there  is crusting of the face,
scalp, hands, feet and pressure bearing areas.  Generalized body distribution
may occur affecting even  the  nails.   The  pruritus is minimal.  DIAGNOSIS:
Diagnosis is made from the history of contact with an infested  person  along
with  the  typical  presentation  of  lesions in the interdigital web spaces,
axillae and genitalia.  The patient  should  be  asked  if anyone else in the
household  or  nursing  home  is  itching  and  scratching.   The  definitive
diagnosis depends on microscopic identification of  the  mite.   Several  non
excoriated  lesions  should  be  chosen  and  scraped with an #15 mineral oil
impregnated	scalpel.  This debris is then  transferred  to a slide with cover
and viewed under the microscope.  The mite, larvae, eggs  and  excrement  all
may  be  seen.   TREATMENT:  LINDANE:  Lindane should not be used in pregnant
patients, infants and those  that  have  excoriations.  It is relatively safe
when used appropriately.  In older patients lindane is no  longer  considered
the  first  line treatment.  Rare cases of seizures in neonates has occurred.
Lindane (1% gamma benzene  hexachloride)  is  available  as Kwell, G-well and
Scabene.  It should not be applied to  damp  skin  which  will  increase  the
absorption.  Typically, 1 oz of lotion or cream is applied from the chin down
to  the  toes  and  is  then  showered  off 8-12 hours later.  This should be
repeated in one week  in  order  to  eliminate late hatching larvae.  Lindane
does not kill the eggs.  PERMETHRIN: Permethrin 5% cream  is  now  considered
the  treatment  of  choice.   It  is  available  as  a 5% cream base known as
Elimite.  It was originally marketed as Nix, a 1% cream rinse.  Permethrin is
often times effective  when  lindane  fails.   It  is  poorly absorbed and is
rapidly metabolized and excreted making it safer than lindane.  It may safely
be used in infants aged 2 months to 5 years of age.  Permethrin 5%  cream  is
probably the drug of choice if the patent is pregnant.  The cream is massaged
into the skin from head to toe and left on the body for 8-12 hours.  A repeat
application  is  given in one week.  CROTAMITON: Crotamiton (Eurax) 10% cream
or lotion is applied from chin to  toes  for  8-12 hours for 5 nights.  It is
far less effective than the above two.  The cure rate is  only  about  50-66%
that  of  lindane.   It may used in children and pregnant or lactating women.
For itching, topical  .1%  fluorinated  corticosteroid  ointment  may be used
bid.The pruritis often takes about 2 weeks to subside after  the  patient  is
treated  with  lindane  or  permethrin.   In  severe  cases a short course of
prednisone, 40 mg daily,  and  tapered  over  2-3  weeks may be necessary for
refractory pruritis.  All clothes that have been  worn  within  48  hours  of
treatment  along  with  bedclothes  and towels must be machined-washed in hot
water or dry cleaned.  Shoes  should  be  placed  in  plastic bags for 1 week
before these are worn again.  Floors should be swept, chairs  and  mattresses
should also be cleansed, as it has been shown that the mite can live for more
than  2 days on floors and furniture.  There should be simultaneous treatment
of all members of the  household,  sexual  contacts and household guests that
frequent the domicile.

                        -SCOMBROID POISONING-
Scombroid  poisoning  usually  occurs  after  eating tainted tuna, mahi mahi,
bonita, mackerel, wahoo, skipjack or kingfish.  The poisoning may also affect
bluefish,  amberjack,  dolphin,  black  marlin,  bluefish,  and  herring.  It
basically  occurs  in  decomposing  or  rotting  fish.   Unfortuantely,   the
definition of fresh fish is that which is caught within 14 days and never has
been  frozen.  During this 14 days of "freshness", the histidine can ungdergo
bacterial decomposition, resulting in the formation of histamine which causes
the symptoms.  Only small amounts of histamine (less than 1 mg/100 grams) are
usually present in  fresh  or  well  refrigerated  fish.  Histamine levels in
toxic fish are normally greater than 50 mg/100 grams  of  flesh.   Scrombroid
toxins are heat stable and not inactivated by cooking.  CLINICAL: About 15-90
minutes  following  ingestion  of the toxic fish, allergic like symptoms will
develop such as skin flushing (especially of the head, neck and upper chest),
itching,  palpitations,  tachycardia,   angioedema,  urticaria,  hypotension,
abdominal pain, vomiting, diarrhea, and  bronchospasm.   You  must  rule  out
other  conditions  that  can  produce  flushing  such  as  niacin,  rifampin,
monosodium  glutamate,  vancomycin,  and  disulfiram  ethanol reactions.  The
first indication that "bad fish" may have been eaten is a metallic or peppery
taste which may or may  not  be  present.   However,  if the fish has a cajun
flavor,  this  will  not  be  appreciated.   TREATMENT:  Treatment  is   with
antihistmaines  such  as  diphenhydramine 25-50 mg IV and H2 blockers such as
cimetidine 300 mg IV.  Severe reactions  may also be treated with epinephrine
.3-.5 mL of a 1:1000 solution subcutaneously.

                  -SEDIMENTATION RATE (Westergren)-
If sed rate is >  100  the  following  may be present: autoimmune vasculitis,
polymyalgia  rheumatic,  malignant  lymphoma,  leukemia,  sarcoma,   multiple
myeloma,  Waldenstrom's  macroglobulinemia, carcinoma, acute severe bacterial
infection, early viral  pneumonitis,  ulcerative  colitis,  biliary or portal
cirrhosis, and severe anemia or renal disease.  If the  sed  rate  is  30-100
consider  the following: TB, rheumatic fever, acute hepatitis, abscess, acute
or chronic  infectious  disease,  acute  glomerulonephritis, malignant tumors
with  necrosis,  nephrosis,  autoimmune  disease  as  SLE,   RA,   hyper   or
hypothyroidism,     polymyalgia     rheumatica,     myocardial    infarction,
Henoch-Schonlein purpura,  postcommissurotomy  syndrome, internal hemorrhage,
lead  and  arsenic  intoxication,  oral  contraceptives,   ruptured   ectopic
pregnancy, old age, menstruation, and high molecular IV dextran.  If sed rate
is  normal  the  following  diseases  may  be  present: Rickettsial, typhoid,
pertussis,  brucellosis,  uncomplicated  infectious  mononucleosis  and viral
diseases, peptic ulcer, cirrhosis of the liver, rheumatic carditis with  CHF,
osteoarthritis,  acute  allergies,  early unruptured ectopic pregnancy, early
acute appendicitis, malaria and toxoplasmosis.  If  the sed rate is near zero
consider the following: sickle cell anemia, polycythemia vera, and hemoglobin
C disease.

                             -SEIZURES-
GRAND  MAL:  Is  prefaced  by an aura.  There is sudden loss of consciousness
followed by tonic, then  clonic  muscle  contractions  of the head and limbs.
Urinary and fecal incontinence are usually present.  The attacks last several
minutes followed by postictal disorientation.  Seizures may occur at any age.
EEG will show 25-30/sec high volgtage spikes over any  area  of  the  cortex.
PETIT  MAL:  Sudden  loss  of awareness (absence) that lasts at most about 30
seconds, and may occur many times  during  each  day.  The most common age of
occurrence is 4-8 years.  EEG  shows  3/sec  spike  and  wave  (generalized).
TEMPORAL  LOBE:  There  may  be  an  aura consisting of a sensory illusion or
hallucination.  Patients will then lose  contact  with the environment and an
automatic activity is  initiated  such  as  trying  to  speak,  inappropriate
movements, etc.  They will not respond to questions and can become violent if
restrained.  The attack usually lasts several minutes.

                       -SEIZURES (TREATMENT)-
In  all  patients  with  seizures  a finger stick should be done for glucose.
Hypoglycemia can  be  a  cause  of  seizures  as  well  as  a complication of
seizures, particularly in alcoholic patients.   If  the  patient  has  status
epilepticus brain glucose levels are usually lower than blood levels.  If the
seizures  last  longer  than 45 minutes another bolus of the original glucose
concentration may be delivered IV.  If  the patient does have hypoglycemia or
you don't have time to obtain a glucose give 50 ml  of  50%  glucose  in  the
adult  and  2 ml/kg of 25% glucose	in a child.  This should be followed by
100 mg of thiamine  delivered  IV for Wernicke's encephalopathy.  LABORATORY:
The patient should have a calcium, BUN, sodium, electrolytes, CBC, and  blood
levels  for  the  anticonvulsant  that  the  patient is currently taking.  In
certain subsets of patients you  will  want  to order a toxicologic screen of
the  blood  and  urine.   Be  aware   that   certain   drugs   as   tricyclic
antidepressants, theophylline and isoniazid can cause seizures.  Seizures may
also  occur with drug withdrawal.  If you are suspicious that the patient may
have an infectious cause,  as  meningitis,  obtain  blood cultures.  A lumbar
puncture may be done if there is a consideration for meningitis.  First  make
sure  there  are  no  contraindications  as  a space occupying brain tumor or
hydrocephalus.  If any doubt,  obtain  a  CT  of  the head, but remember that
meningitis is an emergency  and  treatment  should  be  started  immediately.
Examine  the  head  CT  for  dilated  ventricles, hemorrhage, depressed skull
fracture and herniation.  CT is  usually done initially during the emergency,
followed later possibly with  an  MRI  if  there  is  recalcitrant  seizures.
DIAZEPAM:  Usually, the first drug given to abort a seizure is diazepam.  The
adult dose is 5 mg given IV at  a  rate of 5 mg/minute.  If diazepam is going
to be effective the seizure  will  stop  in  2-5  minutes.   Protection  from
another  seizure  is  only  for 15-30 minutes as the half life of diazepam is
short.  If 5 mg of  diazepam  is  ineffective  increase  to  10 mg IV.  It is
usually safe to give a total of 20 mg of diazepam.  The interval  between  IV
boluses  should  not  be  less than every 2 minutes.  In a child the starting
dose of diazepam is .1-1 mg/kg.   If  for  some reason you are unable to give
diazepam IV the drug may be given rectally.  The dose  is  .5  mg/kg  of  the
parenteral diazepam solution given rectally.  The maximum amount given should
not  exceed  20  mg.   The  diazepam takes about 10 minutes to be absorbed so
don't expect immediate results.   LORAZEPAM:  Lorazepam  may  also be used to
terminate a seizure.  The starting dose is 2 mg IV given over  a  one  minute
period.  The seizure should stop in 2-5 minutes.  The anti-seizure properties
of  lorazepam will last about 12 hours.  Additional 2 mg boluses may be given
IV for a total of 12-16 mg  in  an  adult if the initial dose is ineffective.
The starting dose in children is .05-.1 mg/kg.  PHENYTOIN: If  maximal  doses
of  diazepam  and  lorazepam  have been given and the patient is still having
seizures start phenytoin, sodium.   Phenytoin  is  most effective in seizures
that are idiopathic.   If  the  seizure  is  caused  by  metabolic  or  toxic
etiologies,  phenytoin  may not be beneficial.  The advantage of phenytoin is
that there is  no  sedation  as  with  lorazepam, diazepam and phenobarbital.
Before giving phenytoin make sure the patient has not been taking  this  drug
or  you  know  the blood concentration so that the dose may be titrated.  The
total dose of dilantin is 10-15 mg/kg  given at 50 mg/minute in the adult and
in children given at 1-3 mg/kg/minute.  Do not give phenytoin through a  line
that has D5W running as phenytoin is incompatible with glucose.  Always flush
the  line  with normal saline before administering phenytoin.  While the drug
is being given monitor  the  heart  and  blood pressure.  PARALDEHYDE: Rectal
paraldehyde may be useful if there is no access to a vein such as in  infants
and small children.  The dose is .3-.5 mL/kg diluted 1:1 in vegetable oil and
given  rectally.   If  the  seizures  do  not  abate give the same dose in 20
minutes.   PHENOBARBITAL:  If  seizures  are  not  controlled  with diazepam,
lorazepam or  phenytoin,  phenobarbital  may  be  effective,  but  the  doses
required  may  necessitate  that  the  patient  be  intubated  and  placed on
mechanical assisted ventilation.  The  starting  dose  of phenobarbital is 20
mg/kg given at 100 mg/minute.  The seizure will stop in about 20  minutes  if
effective and the duration of effectiveness is about 2 days.

                      -SELECTIVE IgA DEFICIENCY-
Selective IgA deficiency is the most common and the mildest immunodeficiency.
It has an incidence of 1:400, and usually occurs sporadically, although there
has been a familial occurrence.  It  is  characterized by serum IgA levels of
less than 10 mg/100 ml and normal or elevated levels of IgG or IgM.  Many  of
these  patients  stay  healthy  during  their  lifetime,  whereas others have
recurrent infections, diarrhea, autoimmune disease and allergy.  It can occur
from phenytoin treatment  and  as  a  result  of chromosome 18 abnormalities.
Most of the IgA found in bone marrow plasma cells and serum  is  IgA1  (90%),
whereas  intestinal  plasma cells and secretions contain equal amount of IgA1
and IgA2.  In some patients with serum IgA deficiency, the gut IgA2 producing
plasma cells are present in sufficient  numbers, but the serum IgA deficiency
is due to a decrease of serum IgA1.  Most of the patients with IgA deficiency
will have a deficiency of both serum and secretory IgA1 and IgA2.  About  50%
of patients with selective IgA deficiency will also have a deficiency of IgE.
IgG2 and IgG4 deficiencies sometimes are also associated with IgA dificiency.
Therefore, selective IgA may be a misnomer, as several other deficiencies may
be  present.  CLINICAL: About 50% with selective IgA deficiency have frequent
infections, while about  25%  have  autoimmune  or collagen vascular disease.
There are several autoimmune diseases that occur with a greater frequency  in
patients  with  IgA  deficiency.   These  include  SLE, rheumatoid arthritis,
pernicious  anemia,  dermatomyositis,   Sjogren  syndrome,  Addison  disease,
dermatomyositis,   thyroiditis,   chronic   active    hepatitis,    pulmonary
hemosiderosis,  and autoimmune hemolytic anemia.  Patients with selective IgA
deficiency  have  increased   autoantibodies  against  human  immunoglobulins
(antihuman IgG, IgA, and IgM), DNA,  gastric  parietal  cells,  mitochondria,
basement  membranes,  thyroid  antigens,  and  muscle  tissue.   About 50% of
patients with selective  IGA  deficiency  will  have  anti-IgA antibodies and
therefore are at risk for anaphylactoid reactions following administration of
plasma or immune serum globulin that contain IgA.  The patient should wear  a
Medic  Alert bracelet to prevent administration of plasma or immune globulin.
Any patient that is suspected of  having IgA deficiency should have serum IgA
determinations,  quantitation  of  IgG  and  IgA  subclasses,  secretory  IgA
determinations, and B and T cell  function.   TREATMENT:  Treatment  in  most
cases is not needed.  Continuous antibiotic therapy may be indicated in those
with recurrent infections.  IgA free gamma globulin may be indicated in those
with  severe  recurrent  infections, or in those who also have associated IgG
subclass deficiences.

                              -SEPSIS-
CLINICAL:Sepsis may be suspected if  there  is  fever,  diaphoresis,  chills,
confusion,,  obtundation  or  delirium.   Hypotension  with  septic shock may
develop.  Urinary output  may  diminish  and  the  patient may have vomiting,
diarrhea, abdominal pain, and jaundice.  Examination of the skin  may  reveal
pustules, ecthyma gangrenosum, petechiae, ecchymosis, Osler nodes and Janeway
lesions.   In  the elderly hypothermia may be present.  About 40% of patients
with bacteremia will continue on  to septic shock with acidosis, hypotension,
azotemia, hypoxemia and coagulation disorders.  History is very important  in
sepsis.   For  example,  the  patient  should  be  questioned  about previous
splenectomy.  Asplenic patients  may  develop fulminant bacteremia associated
with  infection  secondary  to  Streptococcus  pneumoniae.    Occupation   is
important.   Those  patients  that have worked around saltwater may develop a
rapidly spreading cellulitis infection secondary to Vibrio.  Physical exam is
important in detecting  cardiac  murmurs  secondary  to endocarditis.  Rectal
examinations should  be  done  for  perirectal  abscesses  or  extensions  of
intraabdominal   abscesses.    The   skin  should  be  examined  for  ecthyma
gangrenosum which is  associated  with  Pseudomonas  aeruginosa septicemia in
granulocytopenic patients.   Purpura  may  indicate  meningococcemia.   About
40-60% of patients with septic shock will develop ARDS with diffuse pulmonary
infiltrates,   resistant   hypoxemia,   and  normal  pulmonary  artery  wedge
pressures.  Most of the  patients  that  succumb  from septic shock will have
multiple organ failure secondary to hypoperfusion, microvascular  injury  and
toxic  products.  The main organs involved in failure include the lung, liver
and kidneys.  The  mortality  is  80-100%  with  failure  of  these 3 organs.
Bacteremia is very common and is associated with  teeth-brushing  and  during
other  diagnostic  and  therapeutic  procedures.  In immunocompetent patients
there are usually  no  sequelae.   However,  in immunocompromised patients or
asplenic patients, infections may readily  develop  producing  septic  shock.
LABORATORY:  Patients may have either a leukocytosis or neutropenia with left
shifts.  Dohle bodies may be  seen,  and there may be vacuolated neutrophils.
Lactic acidosis, thrombocytopenia, anemia, coagulation abnormalities from DIC
as  hypoprothrombinemia,  hypofibrinogenemia,   and   increased   titers   of
fibrinogen  degradation  products  may be seen.  Liver changes may consist of
elevations of alkaline phosphatase and transaminases.  Hyperbilirubinemia may
be present  and  microangiopathic  changes  in  the  erythrocytes  may occur.
Azotemia, hypoxemia and hypophosphatemia may develop.   Hypoglycemia  may  be
present in liver failure.  BLOOD CULTURE: Bacteremia is usually classified as
transient,  intermittent  or  continuous.   Transient  bacteremia  occurs  in
localized   infections   early,   as   pneumonia  and  pyelonephritis,  after
manipulation of infected or  colonized  tissue,  as  in tooth extractions and
endoscopy.  Intermittent bacteremia occurs with abscesses that have not  been
treated.   Continuous  bacteremia occurs with IV catheters, endocarditis, and
septic thrombophlebitis.  One blood culture  is almost never sufficient.  Two
blood cultures may be sufficient if the probability of bacteremia is  low  to
moderate  as in pneumonia or GI bacteremia.  Three cultures should be done in
continuous bacteremia  as  with  endocarditis.   Four  blood  cultures may be
required if there is a good chance for contamination-associated organisms  as
in  prosthetic  valve  endocarditis,  or  if  there  is a high probability of
bacteremia, or if patients  have  received antibiotics recently.  In patients
with genuine sepsis almost 100% will be detected with 3 cultures using 10  ml
of  blood  each  time at different sites.  False positive cultures may occur.
The most common are organisms from skin and mouth which are contaminates.  In
immunocompetent hosts, diphtheroids,  Bacillus  species and Staph epidermidis
are  usually  not  important.   About  50%   of   Clostridium   species   and
Streptococcus   viridans   may   be  insignificant  in  healthy  individuals.
Klebsiella  pneumoniae,  E.  coli,  Streptococcus  pyogenes,  Bacteroides and
Streptococcus pneumoniae are almost always pathogenetic.  Contaminants  often
are slow growers with positive cultures only after 48-72 hours of incubation.
Skin  organisms  that  are  found in only one of several cultures are usually
insignificant.  PRINCIPLES OF THERAPY: Bactericidal  agents should be used in
bacteremic patients such as those that are immunocompetent, have  meningitis,
endocarditis or neutropenia.  First and second generation cephalosporins will
not  cross  the  blood  brain  barrier  and  should  not  be used in treating
meningitis with the exception of  cefuroxime.   Try to use an antibiotic that
doesn't cause hepatic or renal  toxicity  as  these  organs  may  already  be
affected  from  the  bacteremia.   Multiple antibiotics should be used in the
appropriate  clinical  setting.    Intra-abdominal   infections  are  usually
polymicrobial and may be treated with gentamicin, clindamycin and ampicillin.
On the other hand, imipenem may be effective as solo treatment because of its
broad spectrum.  Dual antibiotic therapy may also be more  effective  because
one  antibiotic  at  certain  times  may  fall  below  the minimum inhibitory
concentration while the other is still in the therapeutic range.  Antibiotics
that are synergistic should be  used in Pseudomonas aeruginosa infections and
endocarditis.  In enterococcal endocarditis ampicillin should  be  used  with
gentamicin.   Ampicillin  alters  the  cell  wall  of the bacteria permitting
gentamicin to  penetrate  the  bacteria  and  inhibit  its protein synthesis.
Using either of these antibiotics as solo therapy is not effective.  Treating
with a single drug can lead  to  development  of  resistant  bacteria.   This
occurs  with  pseudomonas  aeruginosa,  Enterobacter  and  Serratia  species.
Therefore,   in   Pseudomonas   aeruginosa   infections   treatment  with  an
antipseudomonal penicillin  and  aminoglycoside  is  effective.   The  use of
empiric antibiotics must be used before the  causative  organisms  have  been
determined.   Selection  of  the  appropriate  antibiotics depends on several
factors as whether the infection  is  nosocomial, community acquired, site of
infection, IV drug use, etc.  Broad spectrum  antibiotics  should  be  chosen
with  coverage  for  staphylococci, streptococci, and gram negative bacteria.
If there is suspected urinary  tract infection, enterococci and gram negative
bacilli should be covered.  Intra-abdominal infections must include  coverage
for  anaerobes.   Lung  infections  should  cover gram negative organisms and
pneumococci.  Neutropenic patients  must  always  be covered for Pseudomonas.
Cardiovascular infections must have coverage  for  staphylococci.   Once  the
organisms  have  been  isolated  empiric  broad  coverage  may be narrowed to
obviate development of  superinfections  and  resistance.  After a sufficient
amount of IV therapy the patient should be converted to an oral  preparation.
Staphylococcus  aureus  bacteremia  should be treated with IV antibiotics for
about 1-2 weeks.   Intravenous  therapy  should  always  be used initially in
sepsis because oral preparations may not be absorbed in malabsorption states,
and patients that develop a paralytic  ileus.   Intramuscular  administration
has  erratic  absorption  because of the hypoperfusion associated with septic
shock.  Once the  patient  has  been  started  on antibiotics, monitoring for
response and side effects of the antibiotics must be initiated.  If there  is
no clinical response after about 3 days of therapy, the blood cultures should
be  repeated.   If  there is persistence of positive blood cultures, consider
that there may be an abscess,  or the antibiotic therapy is inadequate.  Peak
and trough levels of vancomycin and aminoglycosides  should  be  done.   Most
antibiotics  have  the  potential of causing rashes and diarrhea.  Persistent
diarrhea may not  be  due  to  the  antibiotics  themselves, but secondary to
Clostridium difficile.  Aminoglycosides can lead to renal tubular damage  and
impaired  hearing  and  tinnitus.   Beta  lactams  or  sulfonamides can cause
interstitial nephritis.  Beta  lactams  and  vancomycin  can cause reversible
leukopenia.   Imipenem-cilastatin  has  been  associated  with  seizures   in
patients  with  a history of seizures, or in whom there is renal dysfunction.
Cephalosporin antibiotics such cefoperazone  and  cefotetan can be associated
with bleeding  due  to  interference  of  conversion  of  active  vitamin  K.
Metronidazole  can  cause  disulfiram  like reactions.  Nosocomial infections
within the hospital have  organisms  that  are  more resistant than community
acquired infections.  Each hospital's  resistance  and  sensitivity  patterns
should  be  reviewed.   Patients that have Staphylococcus aureus endocarditis
should  be  treated   with   combination   therapy,   as  nafcillin  plus  an
aminoglycoside, in order to accelerate the rate  of  sterilization.   If  the
patient has a culture negative endocarditis caused by nutritionally deficient
alpha  streptococci, response will be better with a combination of penicillin
G and gentamicin.  EMPIRIC THERPAY  BASED  ON SITE OF INFECTION: BOWEL: Bowel
perforation, diverticulitis, appendicitis, hepatobiliary  tract  obstruction,
biliary  surgery,  biliary  stents  and  bowel surgery may be associated with
Enterococcus faecalis, gram  negative  and anaerobic infections.  Peritonitis
may occur from cirrhosis and infected ascites, nephrotic syndrome, peritoneal
dialysis, and  peritoneovenous  shunts.   Typical  pathogens  in  peritonitis
include E. coli, K. pneumoniae, S. aureus and S. pneumoniae.  Empiric therapy
for  these may include ampicillin/sulbactam (Unasyn), ticarcillin/clavulanate
(Timentin), imipenem (Primaxin) or a combination of ampicillin + gentamicin +
clindamycin or metronidazole.  MENINGITIS: Adult  meningitis may be caused by
meningococci or pneumococci.   Treatment  is  with  ceftriaxone,  cefotaxime,
ceftizoxime,  penicillin  or  chloramphenicol.   Meningitis  associated  with
neurologic  surgery  may  be  caused  by  gram  negative  rods, S. aureus and
Staphylococcus epidermidis.  Treatment is  with  vancomycin, or nafcillin and
gentamicin.  Meningitis in the  aged  or  immunosuppressed  patients  may  be
caused by Listeria monocytogenes.  Ampicillin + gentamicin OR TMP/SMX are the
treatments  of  choice.   ENDOCARDITIS:  Endocarditis  associated with native
valve IV drug abusers may commonly be infected with Staphylococcus aureus and
Enterobacteriaceae.  Treatment in these cases is with Nafcillin or vancomycin
+ gentamicin.  Acute  Endocarditis  of  native  valves associated with non-IV
drug  abuse  is  caused   by   Staphylococcus   aureus,   enterococcus,   and
Streptococcus  pneumoniae.   Treatment  is  with  Nafcillin  or  vancomycin +
gentamicin.  Subacute endocarditis of a  native  valve in non-IV drug abusers
may have Streptococcus bovis, Streptococcus viridans and enterococcus as  the
cause.   Treatment for these pathogens would include Ampicillin or Penicillin
G + gentamicin.  Endocarditis  of  prosthetic  valves  may include S. aureus,
Gram negative rods or coagulase negative staphylococci.   Treatment  is  with
nafcillin, vancomycin and gentamicin.  INTRAVASCULAR CATHETERS: Intravascular
catheter  infections  are  commonly  caused by S. aureus, S. epidermidis, and
gram  negative  rods.   Treatment   is   with  vancomycin.   NEUTROPENIC  AND
IMMUNOSUPPRESSED PATIENTS: Neutropenia  is  associated  with  S.  aureus,  S.
epidermidis,   enterobacteriaceae   and   Pseudomonas.    Treatment  is  with
Ticarcillin  +  tobramycin  OR  imipenem  OR  ceftazidime  or  ticarcillin  +
aminoglycoside.   SPLENECTOMIZED  PATIENTS:  In  patients  without  a  spleen
Pneumococci, meningococci, Hemophilus  influenzae  and Salmonella are common.
Treatment is with penicillin or, ampicillin.  RAW  SHELLFISH  INGESTION:  Raw
shellfish  may  cause  Salmonella, Vibrio and Listeria infections.  Treatment
for Vibrio is tetracycline and  aminoglycoside.  Listeria can be treated with
ampicillin + gentamicin.   Salmonella  will  respond  to  chloramphenicol  or
ampicillin.   SKIN  AND  SOFT TISSUE INFECTIONS: Typical pathogens include S.
aureus, gram negative rods, S.  pyogenes  and B. fragilis.  Treatment is with
nafcillin, vancomycin, ceftazidime and  aminoglycoside.   RESPIRATORY  TRACT:
Community  acquired  pneumonias  may  be  caused by aspiration from a seizure
disorder, IV drug abuse,  or  alcoholic  stupor,  and are commonly associated
with anaerobes.  Treatment is with penicillin, metronidazole or  clindamycin.
Pneumococcus  is treated with Penicillin G. Haemophilus influenzae is treated
with  ampicillin.   Legionella  and  atypical  pneumonias  are  treated  with
erythromycin.  Nosocomial pneumonias may  be  caused by S. aureus, Legionella
and gram negative rods.  Legionella is treated with erythromycin,  S.  aureus
is  treated with nafcillin or vancomycin.  Gram negative rod pneumonia may be
treated with ceftazidime,  gentamicin,  or  piperacillin.  UROSEPSIS: Urinary
tract infections  may  be  caused  by  gram  negative  rods  or  enterococci.
Enterococci   are  treated  with  ampicillin  +  gentamicin.   Gram  negative
enterobacteriaceae  may  be  treated  with  ceftriaxone,  aminoglycosides  or
ceftazidime.  GYNECOLOGIC INFECTIONS: Gynecologic post-surgical or postpartum
endometritis is caused by Bacteroides  fragilis and other anaerobes, and gram
negative rods.  Treatment for gram negative rods may be with ceftazidime,  or
aminoglycosides   and   anaerobic   therapy   is  treated  with  clindamycin,
piperacillin, metronidazole and chloramphenicol.

             -SEXUALLY TRANSMITTED DISEASES (Treatment)-
GONORRHEA: The treatment of uncomplicated gonorrhea according to the 1993 CDC
recommendations  is  as  follows: Ceftriaxone 125 IM, or Ciprofloxacin 500 mg
PO, or Ofloxacin 400 mg PO, or  Cefixime  400  mg PO.  All of these should be
given with doxycycline 100 mg PO bid x 7 days.  If  patient  is  allergic  to
penicillin  use quinolones unless the patient is less than 16 years of age or
pregnant in which case spectinomycin, 2 gm IM should be used.  For pharyngeal
GC use ceftriaxone 125  mg  IM  once,  or  ciprofloxacin  500  mg PO once, or
TMP/SMX (720/3600 mg qd x 5 days.  For conjunctival GC use ceftrizxone 1g IM.
For disseminated GC use ceftriaxone 1g IM or IV q  24  hours.   Alternatively
Cefotaxime  1  g  IV  every 8h or ceftizoxime 1 g IV every 8h or for patients
allergic  to  beta  lactam  drugs  spectinomhycin  2  g  IM  every  12 hours.
CHLAMYDIA: The recommended treatment of Chlamydia is Doxycycline  100  mg  PO
bid  x 7 days or Azithromycin 1 gm PO.  Alternatives include Ofloxacin 300 mg
PO bid x 7 days or Erythromycin base  500 mg PO qid x 7 days or Sulfisoxazole
500 mg PO qid x 10 days.  If pregnant use erythromycin (1/2 dose x 2 weeks if
GI intolerance), or amoxicillin 500 mg PO tid  x  7  days.   SYPHYLIS:  Early
syphilis  (Primary,  secondary,  Early  latent)  is  treated  with Benzathine
penicillin 2.4 million units IM.  If  allergic to PCN used doxycycline 100 mg
bid x 14 days or erythromycin 500 mg qid x 14 days.  For late syphilis  (Late
disease  except Neurosyphilis) use Benzathine penicillin 2.4 million units IM
once a week for 3 consecutive weeks (total dosage of 7.2 million units).  For
PCN allergic patients use doxycycline  100  mg  bid x 28 days or erythromycin
500 mg qid x 28 days.  For Neurosyphilis give aqueous crystalline  penicillin
G  12-24  million  units daily (2-4 million units every 4 hours IV) for 10-14
days.  Alternatively Procaine penicillin IM,  2.4  million units IM daily and
probenecid, 500 mg PO QID, both for 10-14 days.  CHANCROID:  Can  be  treated
with azithromyicn 1 g PO in a single dose or erythromycin 500 mg PO QID for 7
days  or  ceftriaxone  250  mg  IM  in  a single dose.  GENITAL HERPES: FIRST
EPISODE: Patients with  symptoms  <  7  days,  continued  new lesions, and no
history of oral herpes give acyclovir 200 mg PO 5x/day or 400 mg tid  x  7-10
days.   For the first clinical episode of herpes proctitis give ACV 400 mg PO
5x a day for 10 days.  For  patients with severe disease or complications ACV
is given IV at 5 mg/kg  every  8h  for  5-7  days.   RECURRENT  EPISODES:  If
symptoms  have  been  present for less than 2 days may use ACV 200 mg PO 5x a
day for 5 days or 800 mg PO  BID for 5 days.  SUPPRESSION THERAPY: ACV 400 mg
PO BID or 200 mg PO 2-5x a day.

                            -SHIGELLOSIS-
Shigellosis is caused by various  species  of  Shigella, and is spread by the
excreta from infected individuals (fecal-oral route), convalescent  carriers,
and  contaminated  food.   Transmission  by water is unusual.  Flies are also
important carriers and vectors.  Epidemics can  occur in day care centers and
overcrowed areas with inadequate sanitation.  The major casue in the  USA  is
Shigella  sonnei, followed by Shigella flexneri.  Shigella dysenteriae is the
most  virulent  species.    Shigella   can   survive   alcohol  and  freezing
temperatures.  It is capable of causing seizures in children.  As few  as  10
organisms   can   cause   a   dysentery  syndrome.   Shigella  are  nonmotile
gram-negative rods that are classified  into  four groups (S.  dysenteriae, S
flexneri, S. sonnei, and S. boydii) and 39  serotypes.   These  bacilli  have
cell  wall  (O)  antigens, but do not have the flagellar antigens found in E.
coli and Salmonella.  The virulence of the bacillus is determined by the side
chain sugars of the O antigen. Shigella replicates on the intestinal wall and
penetrate the mucosa of  the  lower intestine causing leukocyte infiltration,
edema, mucus secretion, and superficial mucosal  ulcerations.   Severe  cases
can  result  in involvement of the entire colon and the distal ileum.  Adults
usually have less severe  cases  that  involve  the  lower half of the colon.
Children 1-4 yeasrs of age are  most  susceptible.   About  50%  of  Shigella
infections  will affect children under the age of 9. CLINICAL: The incubation
period is usually about  2-7  days  with  an  acute  onset of fever, cramping
abdominal pain, tenesmus, which is folowed by watery or pasty stools that may
contain blood and mucous.  The number of  stools  usually  progresses  up  to
about  20/day.   In  young  children  weight  loss and dehydration can appear
rapidly, and if untreated can result  in  death.  Adults may not present with
the typical symptoms initially as found in younger  children.   Instead  they
may have no fever, no blood or mucous in the stool, and may even present with
formed  stool  initially.   Patients  have  an  urge  to  defecate  which can
temporarily alleviate  the  abdominal  cramping.   Later,  diarrhea ensues in
adults, and may become marked with blood and mucous.  The disease is  usually
self limiting in adults in 4-8 days in mild cases, but in severe cases it may
take 3-6 weeks.  LABORATORY: The peripheral WBC may be low or high.  There is
usually  a  marked left shift in the differential.  Wrights or methylene blue
stain of the stool will  reveal  sheets of polys that differentiate bacillary
from amebic dysentery.  Stool culture  is  positive  for  shigellae  in  most
cases,  but  blood  cultures  are  positive  in  less  than 5% of cases.  The
differential diagnosis for  blood  and  mucous  diarrhea includes Salmonella,
Yersinia, Campylobacer, amebiasis, invasive E.  coli,  viral  diarrheas,  and
ulcerative  colitis  in  the  adolescent patient.  Sigmoidoscopic examination
will show  diffuse  erythema  and  several  small ulcerations.  Complications
include  arthritis,  disaccharidase   deficiency,   intestinal   perforation,
myocarditis,  hemolytic  uremic  syndrome  in  children,  secondary bacterial
infections,  and  Reiter's  syndrome.   TREATMENT:  All  patients  should  be
hydrated.  Trimethoprim-sulfamethoxazole double strength BID or ciprofloxacin
750 mg BID are the treatments of choice in adults.  Norfloxacin 400 mg PO BID
may  be  given  instead   of   ciprofloxacin  in  adults.   Ciprofloxacin  is
contraindicated in children and pregnant  women.   The  dose  of  TMP/SMX  in
children  is  2.5 mg/kg PO every 6 hours of the TMP component.  Children that
cannot take TMP/SMX may be  given  furazolidone  5  mg/kg/day PO in 4 divided
doses for 5 days.  Many Shigellae are resistant to  ampicillin.   Amoxicillin
should  not be used as it is usually ineffective.  Antidiarrheal drugs should
be avoided as they can lead  to complicatons.  Oral electrolyte solutions can
be used to maintain hydration.

                        -SHORT BOWEL SYNDROME-
Short bowel syndrome (SBS) may be present when more than  75%  of  the  small
bowel  has  been  removed.   Up  to  40%  of  the  small intestine is usually
tolerated well.   Conditions  that  may  predispose  to  SBS  include Crohn's
disease, neoplasm, volvulus of the small intestine, superior mesenteric  vein
thromboses,   thrombosis   or  emboli  of  the  superior  mesenteric  artery,
jejunoileal bypass for obesity, and trauma.   The  ileum is able to adapt and
carry out the functions of the jejunum if the jejunem is  removed.   However,
the jejunum cannot absorb vitamin B12 or conjugated bile salts.  If more than
100  cm  of  ileum  is  resected  there  will  be  bile  salt  malabsorption,
steatorrhea, and diarrhea.  Removal of 60-100 cm of terminal ileum will cause
bile  acid induced fluid loss.  If the ileoceccal valve is removed, there may
be bacterial overgrowth of the  small  bowel.   The fluid losses may exceed 5
liter/day in the immediate  postoperative  period.   There  is  reduction  of
absorption  of  electolytes, fat, protein, carbohydrates, vitamins, water and
trace elements.  Patients may  also  develop gastric hypersecretion early on,
which predisposes them to peptic ulcer.  Duodenal resections or bypasses will
result in in iron and folate deficiency anemia, and osteopenia due to calcium
malabsorption.  DIFFERENTIAL DIAGNOSIS: Other diseases that  can  affect  the
small  bowel  such  as  sprue,  Whipple's  disease,  lymphoma, giardiasis and
radiation enteritis must be ruled out.  CLINICAL: Patients may present with a
history of small bowel  resection  along  with diarrhea, fatigue, weight loss
and symptoms of vitamin deficiency  as  neuropathy,  osteopenia,  anemia  and
bleeding.   They  may  be  dehydrated  and  have symptoms of hypocalcemia and
hypomagnesemia.   LABORATORY:  There  may  be  hypocalcemia,  hypomagnesemia,
hypokalemia, and hyponatremia.   There  will  be  elevated quantitative fecal
fat, decreased prothrombin time, carotene, albumin, carotene and zinc levels.
There  may  also  will  be  be  decreased  vitamin  B12,  iron,  and  folate.
TREATMENT: Antimotility drugs may be given to increase luminal contact  time.
Cholestyramine  Questran)  is  beneficial  for  the  bile  acid malabsorption
associated with  limited  ileal  resections  of  less  than  100  cm.  In the
immediate postsurgical resection patient, acid suppression is indicated  with
H2  blockers  or  omeprazole.   Bacterial  overgrowth in patients with bypass
loops  or  ileocecal  valve   resection   is  treated  with  broad  sprectrum
antibiotics.  Large resections with excessive diarrhea may need to be treated
with total parenteral nutrition.  Early oral feedings  with  elemental  diets
and  medium  chain  triglycerides  is essential to stimulate adaptive mucosal
hyperplasia of the  remaining  small  intestine.   Low  oxalate  diets may be
useful in ileal resections, in order to avert the formation of renal  stones.
Patients  with chronic malabsorption should be started on a high carbohydrate
diet with about  30  grams  of  fat/day.   They  will  also  need fat soluble
vitamins, including calcium, vitamin  D,  folic  acid,  iron  and  parenteral
vitamin B12.  Calcium should be given as 1500 mg per day.

                        -SHY-DRAGER SYNDROME-
Shy-Drager syndrome is  a  degenerative  disease  that  affects  CNS  neurons
including cerebellar, basal ganglia, corticospinal, extrapyramidal, autonomic
and  the  intermediolateral  colums  of the spinal cord.  These patients have
normal levels  of  circualting  norepinephrine,  normal  response  to infused
norepinephrine and tyramine with increased levels  of  plasma  norepinephrine
upon  standing.   It  has  been  estimated  that  about  11% of patients with
orthostatic hypotension will  have  the  Shy-Drager  syndrome.  Most patients
will present between the ages of 37-75, with a mean age of 55  years.   Males
are  affected  more  than  females in a ratio of 3:1, and there is no genetic
predisposition.   The  main  feature   of   the   disease  is  the  autonomic
insufficiency which presents as dizziness, syncope, and  light-headedness  on
standing.  There are wide swings of the blood pressure.  There may be reduced
sweating,  urinary  incontinence, stool incontinence, diarrhea, constipation,
sexual impotence,  nocturnal  diuresis,  nystagmus,  impaired  eye movements,
Horner's syndrome and abnormal convergence.  Patients may have symptoms  that
are  suggestive  of Parkinson's disease such as intention tremor, dysarthria,
and ataxia.  There may  be  fasciculation  and  wasting of the distal muscles
secondary to anterior horn cell degeneration.  The disease is progressive and
patients usually die after 7-10  years  of  the  disease.   Common  modes  of
expiration  include  cardiac  arrhythmias,  pulmonary emboli and sleep apnea.
There is no definitie treatment.   Patients  are instructed to avoid alcohol,
arising rapidly from a supine position, large meals and straining.  The usual
measures that are  employed  for  orthostatic  hypotension  may  be  helpful.
Fludrocortisone  .1-.5 mg/day, indomethacin 25-50 mg TID PO, propranolol, and
pindolol all may be useful.

                        -SICKLE CELL ANEMIA-
Sickle  cell  anemia  is  a  hemoglobinopathy  transmitted  as  an  autosomal
recessive  in  blacks  and  characterized  by  a  a chronic hemolytic anemia,
episodes of painful crises and  increased infections.  The homozygous form is
known as sickle cell disease and the heterozygous form  is  the  sickle  cell
trait.   In  sickle  cell  disease  there  a  functional asplenia and delayed
physical  and  sexual  maturation.    Hemoglobin   S  is  manufactured  by  a
substitution of valine for glutamic acid in the sixth amino acid position  of
the  beta  chains  of  the  hemoglobin  molecule.   If  Hemoglobin  S becomes
deoxygenated, the characteristic sickling begins.  The sickle cells are rigid
and fragile and cause stasis and blockage of small arterioles and capillaries
which causes ischemia and infarction.  As a result, sickle cell complications
can be  divided  into  several  types  as:  VASO-OCCLUSIVE: Vaso-occlusive or
painful crisis is the most  common.   One  type  of  painful  crisis  is  the
Hand-foot  syndrome  which  occurs only in infants and children.  In children
and adolescents,  pain  is  common  in  the  abdomen,  chest and extremities.
Adults will have pain in the low back and the extremities.  The  pain  crises
will  usually last 2-6 days.  HYPERHEMOLYTIC CRISIS: In Hyperhemolytic crisis
there  is  an  increase  in  the  intensity  of  hemolysis  and  this  can be
precipitated by bacterial infections.   SEQUESTRATION  CRISIS:  Sequestration
crisis causes the abnormal cells to be trapped in the spleen.  This condition
occurs  only  in  infants  and  young children.  The condition usually occurs
below the age  of  2  and  presents  as  a  life  threatening anemia which is
extremely rapid with engorgement of the spleen and depletion of the red  cell
pool.    Sequestration   is   frequently  triggered  by  a  viral  infection.
SUSCEPTIBILITY TO INFECTION: Susceptibility to infection is increased because
of a poorly functioning  spleen  and  a  defect  in  the alternate pathway of
complement activation.  Patients are particularly susceptible to  Haemophilus
influenzae  and  Streptococcus  pneumonia  because  of  autoinfarction of the
spleen.  Patients that are treated with  deferoxamine for iron binding can be
infected with  Yersinia  entercolitica  and  present  as  an  acute  abdomen.
Salmonella   typhimurium  osteomyelits  can  occur  also.   APLASTIC  CRISIS:
Aplastic crisis is frequently triggered by the parvovirus B19, the virus that
causes erythema infectiosum.  In this  condition,  there is a marked decrease
of red cell precursors in the bone marrow with a  severe  diminution  in  the
hemoglobin  and  reticulocyte  count.   This will last about 1-2 weeks.  Many
complications may results from Sickle cell  anemia such as the following: The
Acute chest syndrome which is caused by infarction and or infections and  may
be  difficult to differentiate.  The syndrome is characterized by chest pain,
dyspnea, cough, fever and lung infiltrates.  Patients may develop chronic leg
ulcers, priapism, bone infarcts, aseptic  necrosis of the femoral head, CVA's
manifested by strokes in children and  hemorrhage  in  adults,  gall  bladder
stones,  hematuria  and hyposthenuria resulting from microvascular infarction
of the renal  medulla  (can  occur  in  Sickle  cell  disease  or the trait),
osteomyelitis, meningitis, pyelonephritis, hemosiderosis from multiple  blood
transfusions  and  cardiac  enlargement and its sequelae.  Any condition that
leads to  dehydration,  acidosis,  hypoxia,  exposure  to  cold  or strenuous
physical exercise can induce sickling and subsequent crises.   Pregnancy  can
be difficult and dangerous, especially the 3rd trimester and during delivery.
There  may  be  toxemia,  phlebitis,  pulmonary  infarction  and  increase in
infections and severity of the crisis.  There is an increase of abortions and
stillbirths with  a  fetal  mortality  that  may  approach 35-40%.  Placental
infarction  can  occur  and  result  in  low  birthweight.   LABORATORY:  The
Sickledex  test  is  usually  performed  for  screening.   Following  this  a
hemoglobin electrophoresis can be done which  will  show  a  predominance  of
Hemoglobin S, no Hemoglobin A, and varying amount of hemoglobin F. There is a
reticulocytosis  usually  between  10-20%  and  leukocytosis.  Band forms are
normal in the absence of infection.  The bilirubin is usually mildly elevated
and the fecal and  urinary  urobilinogen  high.   There  is a chronic anemia.
TREATMENT: INFECTION:  In  a  patient  in  whom  you  suspect  infection  the
following  should  be  obtained if appropriate in the clinical setting: blood
cultures,  CBC,  reticulocyte  counts,  chest  x-ray,  lumbar  puncture,  and
arterial blood gases.  Antibiotics should be started such as cefuroxime which
will cover S. pneumoniae  and  ampicillin resistant H. influenzae.  Hydration
should be maintained at  1.5  times  daily  maintenance  fluid  requirements.
Penicillin  prophylaxis  (Penicillin  V  125  mg  bid  beginning at the age 3
months; the dose is increased to 250  mg bid at 3 years of age.  Erythromycin
can be used if the patient is allergic to penicillin), Pneumococcal  vaccine,
hepatitis  B  vaccine, haemophilus b and meningococcal vaccines should all be
given to children.  A booster dose  of  pneumococcal vaccine may be needed at
about 5 years of age.  The risk of meningitis and septicemia  is  highest  in
the  first  decade of life but declines after this.  LUNG DISEASE: Infectious
lung disease is often  caused  by  Mycoplasma  pneumoniae, S pneumoniae and H
influenzae.  Analgesics are needed  but  not  in  doses  that  will  suppress
breathing.   Nerve  blocks  may  be  needed.   Hydration  and  and oxygen are
important.  In 50% of the cases, an  infectious cause cannot be found and the
acute chest syndrome may be caused by pulmonary infarction or  fat  embolism.
Bone  marrow  necrosis occurs which causes the fat embolism.  Symptoms of fat
embolism include lipemia retinalis,  upper thorax and conjunctivae petechiae,
confusion, dyspnea, thrombocytopenia, hypocalcemia, hyperuricemia and  severe
bone  pain.  Obtain a urine, sputum and biopsy of petechiae.  These will show
the  lipid  droplets.   Treatment   for   fat   embolism  is  early  exchange
transfusion.  Ventilation/perfusion scan and pulmonary  arteriograms  may  be
necessary.   Blood  transfusion  should  be given to keep the hemoglobin S at
less than  50%.   SPLENIC  SEQUESTRATION:  Splenic  sequestration  is seen in
children mainly, but rarely can be seen in adults.  Blood transfusion therapy
to maintain the hemoglobin levels between 10 and 11 grams  should  be  given.
If   the   patient  has  repeated  or  life  threatening  sequestration  then
splenectomy may be needed.  APLASTIC  CRISIS: Parvovirus usually precedes the
aplastic crisis producing  a  severe  anemia  and  reticulocytopenia.   Blood
transfusions are needed to maintain the hemoglobin until there is spontaneous
resolution  of  the  bone  marrow  which may occur at about 10 days.  CENTRAL
NERVOUS SYSTEM: Cerebral infarction usually  occurs in children under the age
of 10.  MRI should be done and the patient treated immediately with  exchange
transfusions  followed  by  chronic  transfusion and chelation for at least 3
years, maintaining the hemoglobin levels between  10  and 11 grams per dl and
the hemoglobin S at less than 30%.  If, in spite of this, there is  continued
infarction, the transfusion should be increased to keep the Hemoglobin S less
than  15%  and  give ASA or dipyridamole.  Cerebral hemorrhage (intracerebral
and subarachnoid) occurs in older  patients and should prompt an arteriogram,
which should be preceded by an exchange  transfusion,  because  the  contrast
load   will   increase  the  sickling.   EYE  DISEASE:  Sickle  cell  retinal
proliferative disease can occur in sickle cell disease, but is more common in
Hb SC or Hb S Thalassemia.   Patients may develop hyphema after ocular trauma
with increased intraocular  pressure.   Laser  photocoagulation  can  prevent
bleeding  and  retinal detachment.  Vitrectomy or scleral buckling procedures
may be  needed.   If  these  are  done  patients  should  have prior exchange
transfusion, oxygenation, and hydration.  RENAL DISEASE: A painless  type  of
hematuria occurs with sickle cell disease and trait.  One must rule out other
causes  of  hematuria  such  as renal calculi, AV malformation and infection.
Papillary necrosis  is  common.   Treatment  includes  alkalinization  of the
urine, hydration, and bed rest.   If  the  bleeding  is  refractory,  epsilon
aminocaproic  acid can be used at a dose of 2-8 grams per day.  Be aware that
Amicar can cause clot formation  in  the ureter and renal pelvis.  Therefore,
hydration should be maintained to keep urinary output at  3  ml  per  kg  per
hour.    Erythropoietin   appears   to  decrease  the  need  for  transfusion
requirement in  those  with  chronic  renal  disease.   GALL BLADDER DISEASE:
Bilirubin  levels  may  reach  very  high  levels  such  as  40  mg/dl   with
cholestasis.   These  patients  may  be  asymptomatic.  The transaminases are
usually less than 300 IU per  liter.   Only supportive care is needed as this
benign form will resolve  in  about  one  month.   If  there  is  progressive
cholestasis  with  fever  and  hepatic  failure,  exchange transfusion may be
needed.  The  large  load  of  bilirubin  leads  to  gallstones.   Surgery is
recommended  if  there  are   common   duct   stones   causing   obstruction,
cholecystitis   associated  with  bacteremia  or  two  or  more  episodes  of
cholecystitis.  The cholecystectomy should  be  delayed  for about 6 weeks if
possible  to  decrease  the  risk  of  thrombosis.   Pre-  surgery   exchange
transfusions  should  be given to prevent thrombosis.  PRIAPISM: The priapism
may be sustained for many hours or  there may be minor episodes of stuttering
priapism.   The  pain  may  be  relieved  somewhat  with  warm   baths,   and
masturbation.   Nifedipine  10  mg bid or tid may be of some benefit in minor
episodes.  For  sustained  episodes,  hydration,  analgesics,  aspiration and
exchange transfusion should be done.  If there is  no  improvement  after  36
hours,  a  more definitive surgical approach should be considered such as the
Winter  procedure,  as  impotence  increases  after  36  hours.   ORTHOPEDIC:
Avascular necrosis of the femoral head can occur and should be suspected if a
patient has a limp, pain in  the  hip  and MRI is compatible.  Replacement of
the hip joint may be needed.  The hand- foot syndrome is common  in  children
and  should be treated with analgesics and hydration.  Any one with bone pain
and fever should  be  suspect  for  osteomyelitis.  Differentiation from bone
infarction may be difficult.  Aspiration for culture should be done.

                        -SICK SINUS SYNDROME-
In this syndrome  there  is  a  variety  of  abnormaliteis  of the sinus node
including persistent sinus bradycardia, sinoatrial exit block  presenting  as
S-A  Wenckeback,  and  sinus  arrest  where  an impulse fails to activate the
atria.  If there is failure  of  a subsidiary escape paemaker developing, the
patient  will  present  with  syncope.   Sinoatrial  exit  block  is  usually
asymptomatic unless  there  are  lengthy  pauses  similar  to  sinus  arrest.
Besides  sinus  node  dysfunction,  many  cases  are associated with AV nodal
abnormaliteis.  There also  is  a  variant called the bradycardia-tachycarida
syndrome  where  atrial  fibrillation  and  atrial  flutter  alternate   with
prolonged  asystolic  periods.   CLINICAL:  Many  patients  with  sick  sinus
syndrome  are asymptomatic, but others may have syncope, dizziness, fainting,
confusion, palpitations, angina and  heart  failure.   Many of these symptoms
are non-specific and the  symptoms  must  be  shown  to  correlate  with  the
arrhythmia.   This will require either prolonged ambulatory ECG monitoring or
the use of an event recorder.   If  the patient has the tachy-brady syndrome,
symptoms may be related to the long pauses that  follow  the  termination  of
atrial  fibrillation,  atrial  flutter  or  paroxysmal re-entry tachycardias.
ETIOLOGIES: Many  drugs  may  affect  the  sinus  node  that  will produce or
exacerbate the syndrome.  These  include  digitalis,  beta  blocker,  calcium
channel  blockers, sympatholytic agents.  In the elderly, there may be patchy
involvement of the sinus node  and  the conduction system by fibrosis.  Other
causes  include   Chagas'   disease,   cardiomyopathies,   amyloidosis,   and
sracoidosis.   TREATMENT: Most patients with sick sinus syndrome will require
pacemaker interventions.  Since there is  involvement  of the AV node as well
as the sinus node, dual chamber or ventricular pacers  are  required,  unless
electrophysiologic  studies  show normal AV conduction.  Dual chamber systems
as the  DDI,  DDDR,  DDIR  may  delay  or  prevent  the  occurrence of atrial
fibrillation.  If AF is already  established,  a  VVI  or  VVIR  pacer  would
suffice.  Once the pacemaker is in place, the associated tachyarrhythmias may
be  treated  with  digoxin  and  other  antiarrhythmic  agents, which if used
without a pacemaker would exacerbate the sinus node.

                       -SIDEROBLASTIC ANEMIA-
Sideroblastic  anemia  (SA)  is   due   to   defective  iron  utilization  in
erythropoietic cells.  The available iron is not used for  the  synthesis  of
hemoglobin.   In  the  normal  patient  30-50%  of developing red blood cells
contain cytoplasmic non-heme iron which  can be visualized with Prussian blue
staining.   These  cells  are  known  as  siderocytes,   or   if   nucleated,
sideroblasts.   When  iron  deficiency intervenes these cells are reduced and
when the iron supply  exceeds  utilization  as  in the arrested maturation of
megaloblastic  anemia  or  thalassemia,  the   sideroblasts   increase.    In
sideroblastic anemia, there is accumulation of iron in the mitochondria which
produces  a  perinuclear aggregate distribution.  With Prussian blue staining
such cells appear to have a ring of iron granules surrounding the nucleus and
therefore are called ringed sideroblasts.   For the ringed sideroblasts to be
significant 3 criteria must be met.  The perinuclear iron  granules  must  be
abnormally  large,  must be greater than six, and must form a ring around the
nucleus  of  one-third  or  more.   The  iron  granules  must  reside  in the
mitochondria  as  cytoplasmic  accumulation  is  normal.    The   causes   of
sideroblastic anemia are numerous, but can broadly be divided into congenital
or  hereditary, and acquired.  The acquired causes are the most common.  They
may be occasionaly associated  with  systemic lupus erythematosus, metastatic
carcinoma, uremia, and rheumatoid arthritis.  Hematologic  diseases  such  as
acute  and  chronic  leukemias, multiple myeloma, lymphomas, aplastic anemia,
hemolytic anemia and myeloproliferative disorders  all may be associated with
sideroblastic anemia.  Multiple drugs may also lead to a sideroblastic anemia
including   alcohol,   lead,   chloramphenicol,    isoniazid,    cycloserine,
pyrazinamide,  busulfan,  copper  deficiency, and penicillamine.  Some causes
are  unknown  and  are  termed  idiopathic  refractory  sideroblastic anemia.
LABORATORY: On examination of  the  blood  there  is  usually  two  different
populations  of  red  blood  cells,  microcytic  and  macrocytic.  There is a
variable population of each depending  on  the cause.  This difference in RBC
populations is known as  a  dimorphic  anemia.   Polychromatophilic  stippled
target RBCs may be seen and if present provide a clue that there is defective
heme  synthesis  that  may  be  due to sideroblastic anemia.  There is normal
radiolabeled iron  transfer  from  plasma  transferrin  to  the  bone marrow,
but	this iron does not appear in the peripheral RBC at a  normal  rate.   The
serum  iron  is elevated.  Transferrin saturation and serum ferritin are also
elevated.  There may be basophilic  stippling,  particularly if there is lead
poisoning.  The red cell distribution  (RDW)  is  elevated.   Leukocytes  and
platelets  are  usually  normal,  but  may  be depressed, normal or elevated.
Examination of the marrow  reveals  the  typical Prussian blue stained ringed
sideroblasts with as many as  90%  of  marrow  erythroid  precursors  ringed.
Marrow  macrophages  are  saturated  with hemosiderin iron.  SPECIFIC CAUSES:
HEREDITARY: This is usually  a  X-linked  recessive  disease with males being
clinically affected.  However, females may  have  significant  iron  overload
later in life due to the defective iron utililization.  The anemia is usually
mild and most patients have hypochromic and microcytic populations.  The iron
rings  occur  only  in  late  normoblasts.  About 50% of the patients develop
hepatosplenomegaly due to the tissue iron overload, and diabetes mellitus and
cardiomyopathy will develop in about 33%.  It has been observed that there is
a decrease of  delta  aminolevulinic  acid  synthetase  (ALA).   About 50% of
patients will respond to 200 mg of pyridoxine daily.  However,  response  may
be delayed for several months.  Although the hemoglobin may return to normal,
there  usually  remains  a  hypochromic,  microcytosis of the RBCs.  Patients
should be routinely monitored for iron  overload with serum iron and ferritin
levels.  Phlebotomies are needed to keep the serum ferritin levels below  200
ug/L.   IDIOPATHIC  ACQUIRED  SIDEROBLASTIC ANEMIA: The idiopathic variety of
sideroblastic anemia is a  disease  of  later  life  that affects females and
males with an average age of about 65.  About 50% of the patients  will  live
for  at  least  15  years  with  little supportive treatment.  However, about
10-15% will develop a myelodysplastic syndrome.  A clue to the transformation
into  the  myelodysplastic  is   the   development  of  thrombocytopenia  and
leukopenia.  As opposed to the hereditary causes, the idiopathic variety  has
a  preponderance  of  the  macrocytic  RBC  population,  but  there  also are
hypochromic  populations.   Early  in  the  disease,  the  platelets  may  be
increased in about a third of  the patients.  All stages of the erythroblasts
have ringed sideroblasts with up to 90% being affected.  The  ALA  synthetase
is  decreased  as  in  the congenital forms.  Megaloblasts may be seen in the
marrow and a decrease of folic  acid  is  common.  There is no good treatment
for the idiopathic sideroblastic variety as only about 5%  of  patients  will
respond  to  pyridoxine.   DRUG  INDUCED: Ethanol is a fairly common cause of
sideroblastic anemia.   Alcoholic  patients  may  be  a  diagnostic challenge
because they typically also have folic acid, B12 and  hypochromic  microcytic
anemias   due   to  iron  deficiency.   Alcohol  causes  a  decrease  of  the
delta-aminolevulinic acid synthetase, the initial  and rate limiting event of
heme synthesis.  If this enzyme is inhibited there is  production  of  ringed
sideroblast in the bone marrow.  These alcoholic patients have elevated serum
iron,  increased  saturation  of  total  iron  binding capacity and decreased
reticulocytes.   There   also   may   be   elevated   bilirubin  and  lactate
dehydrogenase.  The smear is dimorphic with microcytes and  macrocytes  seen.
The   macrocytosis   usually   predominates   and  hypersegmentation  of  the
neutrophils may be seen.   The  red  blood  cell  distribution width (RDW) is
increased, and there may be basophilic stippling.  Ringed sideroblastosis  is
not  a  prominent  feature  in alcoholic patients who are well nourished.  In
most cases less than 10%  of  early  and intermediate erythroblasts will show
the classic iron laden rings while most of the early  precursors  demonstrate
vacuolization.   Treatment  is abstinence from alcohol.  Sideroblastic anemia
secondary to isoniazid (INH)  can  be  prevented  by giving pyridoxine 200 mg
daily.  Use of the antituberculous drugs produces a sideroblastic  anemia  in
which  microcytosis  predominates the peripheral blood smear along with a low
MCV.  However, the RDW  is  typicallhy elevated.  DIFFERENTIAL DIAGNOSIS: The
most common anemia that sideroblastic anemia is  confused  with  is  an  iron
deficiency anemia that can present with a hypochromic, microcytic anemia, and
an  elevated  RDW.   However,  in  iron deficiency anemia, the serum iron and
ferritin levels are low, and the  bone marrow aspiration does not show marrow
sideroblasts.  If, by chance, sideroblastic anemia is mis-diagnosed  as  iron
deficiency  anemia,  iron  is usually given which will unfortunately increase
the iron stores in  the  tissues  leading to complications.  The thalassemias
may also be confused with sideroblastic anemia as they may have  a  low  MCV,
and  high  serum  iron.   However,  there  are  no ringed sideroblasts in the
marrow, even though there are increased marrow iron stores.  Also, hemoglobin
A2 and F levels are elevated.

                        -SIGNAL AVERAGED ECG-
Signal averaged ECG is a technique using high fidelity signal  amplification,
computer  averaging,  and  filtration  methods  to reduce noise which has the
capability of  displaying  post  QRS  complex  late  potentials.  Most deaths
following  MI  are  thought  to  be  caused  by  ventricular  tachycardia  or
fibrillation.  There has been a direct correlation between  the  presence  of
late  potentials  detected  on  the  signal-averaged  ECG  and spontaneous or
induced  ventricular  tachycardia  in   diseases  such  as  left  ventricular
aneurysm,  congestive  and  hypertrophic  cardiomyopathy,  right  ventricular
dysplasia and post MI.  Following  acute  myocardial  infarction  during  the
first  week  there  is fluctuation of the signals resulting in appearance and
disappearance.  Folowing this there is  stabilization of the late potentials.
During the first month post MI, there is a prevalence rate of 20-50%  of  the
late  potentials  with  progressive  declines  over the next 5 years.  If the
patient initially does not develop late  potentials early after MI, he or she
will rarely develop  them  later  unless  there  is  additional  ischemia  or
infarction.   Markers  for  developing  these  late  potentials include those
patients with decreased ejection fractions,  those that develop CHF and those
with large infarcts associated with high creatine kinas levels.   It  appears
that  the  best time to record these late potentials would be after the first
week post MI, since sudden death and  cardiac events are highest in the first
6 months.  Therapy is difficult.  Antiarrhythmic drugs  will  not  erase  the
late potentials.  Electrophysiologic testing should be done in those patients
with  late  potentials  and  decreased  ejection  fractions.   If ventricular
tachycardia  can  be  induced,  drug  suppressing  trials  are  carrried out.
Caution, however, is indicated as the CAST study showed  increased  mortality
with  encainide  and  flecainide  and  this may apply to other drugs as well.
When the signal average  ECG  is  used  alone,  the specificity for high risk
sudden death and ventricular tachycardia  is  low.   However,  combining  the
signal  averaged ECG with Holter monitoring and radionuclide ventriculography
has improved the specificity.  In one  study, it was found that positive late
potentials combined  with  complex  ventricular  ectopic  activity  found  on
ambulatory  ECG  monitoring or an ejection fraction < .4 would identify those
high risk post MI patients with a  sensitivity of 65-80% and a specificity of
89%.  Therefore, this may be another step toward risk stratification after an
acute myocardial infarction.

                         -SINUSITIS (Fungal)-
Most  invasive  fungal  sinusitis  in  immunocompromised  patients  is due to
Aspergillus, Rhizopus,  Rhizomucor,  and  Mucor.   ASPERGILLUS SINUSITIS: The
most commonly involved species is Aspergillus  fumigatus.   This  fungous  is
seen  in  patients that are receiving steroids, chemotherapy, antibiotics and
those with granulocytopenia.  It usually presents unilaterally, affecting the
maxillary or ethmoid sinuses.  It may  present as an acute invasive disorder,
chronic invasive, allergic or as a mycetomal disorder.  In the acute invasive
form, invasion of the frontal sinus is uncommon.  It usually  starts  in  the
maxillary  sinus and spreads to the ethmoid sinuses, orbit, and nasal cavity.
The spread can destroy the base  of the skull, with ultimate dissemination to
the lung, liver, and spleen.  This dissemination can occur within a few days.
Once it spreads to the sphenoid sinus, the prognosis is  grave.   Aspergillus
has  an  affinity  for invasion into the vascular and connective tissue which
causes thromboses of the  vessels  and coagulation necrosis.  Clinically, the
earliest symptoms and signs include crusting of the inferior turbinate,  with
thick  mucoid  secretions.   There  is  local  pain and swelling, followed by
chemosis, proptosis, and ophthalmoplegia.   The  maxillary sinus fills with a
greasy fluid, the antrum is lined with  thick  granulations,  with  green  to
black  cheesy  material.   Sinus  X-rays  usually  do not reveal fluid levels
because of  the  neutropenia.   CT  will  demonstrate  orbital invasion, bone
erosion, and the extent of the mucoperiosteal involvement.  MRI is  best  for
demonstration  of intracranial and cavernous sinus invasion.  Early treatment
includes biopsy of this  crusty  material, extensive debridment, and drainage
of the sinuses.  Amphotericin B is the  drug  of  choice.   Chronic  invasive
Aspergillus  sinusitis  is an indolent process.  This form is common in areas
that have a high spore density such as Sudan, Saudi Arabia.  The usual fungus
is Aspergillus flavus.   The  disease  may  exist  insidiously  for months or
years, but is progressive.  The  spread  may  be  painful  or  painless  with
extension  from  the  maxillary  sinus  to  the  ethmoid, orbit, sphenoid and
frontal lobes.   Biopsy  will  reveal  the  hyphae,  Langerhans  giant cells,
vasculitis, perivascular fibrosis, necrotizing and  noncaseating  granulomas,
and foreign body reaction.  Treatment again is with debridement, drainage and
amphotericin B. Allergic fungal sinusitis typically affects young adult males
with  a  male  preference  of  3:1.   It usually targets atopic patients with
chronic allergic rhinitis, and patients that have asthma and nasal polyposis.
There may be a history of several  sinus surgeries.  It may be caused by many
of the dematiaceous fungi.  The IgE is usually increased.  CT  usually  shows
multiple   sinus  involvement  with  various  areas  of  high  signal.   Bone
destruction may be seen in  30-50%  of  cases.  The sinuses show thick mucus,
hyperplastic   mucosa,   cellular   debris,   increased    eosinophils    and
Charcot-Leyden  crystals.   Fungal  hyphae  are  difficult  to  find, and are
usually distorted.  Culture  and  silver  staining  shuld be done.  Treatment
includes various drainage procedures.   Antifungal  agents  are  usually  not
given  unless  there  is evidence of tissue invasion, orbital or intracranial
spread.  Antibiotics  are  used  for  bacterial  infections.  Sometimes nasal
steroids are helpful.  Mycetoma is usually due to Aspergillus fumigatus.  The
mycetoma usually remains in the maxillary sinus for months to  years  without
invasion  or spread.  Patients complain of chronic nasal drainage that may be
black, yellow or green.  The  color  of  the rhinorrhea usually coresponds to
the condidial head of the fungus.  Aspergillus niger  has  a  black  fruiting
head,  Aspergillus  flavus has a yellow green head, and Aspergillus fumigatus
has a green head.  Treatment  is  a  Caldwell  Luc procedure, excision of the
mycetoma,  curettage,  and  treatment  of  secondary  bacterial   infections.
MUCORMYCOSIS:  Mucormycosis is caused by Rhizopus, Mucor and Absidia species.
These fungi are found everywhere.  They  occur  in air, soil and bread.  They
innoculate the sinus by inhalation.  Following this, they  invade  the  blood
vessels,  causing  thrombosis and necrosis.  The most common is cause is with
species of  Rhizopus.   It  occurs  in  patients  that are immunocompromised.
About 70% will have diabetes and ketoacidosis.  It also can occur in patients
with multiple myeloma, infant diarrhea, steroid therapy, burns, chemotherapy,
ionizing radiation, post transplantation patients,  leukemia,  renal  disease
and  septicemia.   Rhinocerebral  mucormycosis is a common presentation.  The
patient may present with facial  swelling, periorbital pain, proptosis, nasal
discharge blindness, ophthaloplegia, and ulcers of the palate  with  eventual
coma.   Examination of the nasal mucosa will reveal gangrene, and a black-red
discoloration  of  the  turbinates.   Treatment  is  aggressive  debridement,
curettage, correction of acidosis  and  hyperglycemia,  and correction of any
infection.  Amphotericin B, given IV, is the treatment  of  choice.   Orbital
and  paranasal  sinus  irrigation with amphortericin is also recommended on a
daily basis.  This is accomplished  by  using  10-20 ml of amphotericin given
through indwelling catheters.

                        -SJOGREN'S SYNDROME-
Sjogren's syndrome (SS) is usually  a  disease  of  women with a ratio of 9:1
which affects the exocrine glands producing decreased secretion of saliva and
tears.  The average age is around 40.  There may be a genetic  predisposition
as there is a common association with HLA antigens B8, and DR3.  In about 50%
of  the  cases there is another autoimmune disease found such as scleroderma,
Hashimoto's  thyroiditis,  polyarteritis,  interstitial  pulmonary  fibrosis,
polymyositis, rheumatoid arthritis (33%),  SLE  or primary biliary cirrhosis.
Raynaud's occurs in 20% of cases.  There also is an  increased  incidence  of
lymphoma  in  this  disease.   The  prognosis  in  general  is related to the
extraglandular autoimmune diseases  that  may  be  present,  and  if there is
transition  to  a  malignant  lymphoma  or  Waldenstrom's  macroglobulinemia.
CLINICAL: DRY EYES: There is lymphocyte and plasma cell infiltration  of  the
lacrimal  glands  that produce itching, burning, impaired tear production and
thick secretions.  There is  photosensitivity,  conjunctivitis, and a foreign
body sensation in the eyes.  Staphylococcal conjunctivitis is  not  uncommon.
There  is  ketatoconjunctivitis sicca which is characterized by erosive areas
of the bulbar conjunctiva and the  cornea.  These ulcerations are a result of
the dryness  of  the  bulb.   DRY  MOUTH:  There  is  dryness  of  the  mouth
(Xerostomia), with possible ulcerations of the tongue, lips and buccal mucosa
due  to decreased salivary gland secretion.  Also, there may be dysphagia due
to impaired secretion of the esophageal mucosal glands.  The patient may have
some difficulty in talking and  may  have  dental caries secondary to the dry
mouth.  Some of the  patients  will  also  have  dryness  of  the  nose  with
epistaxis,  throat, larynx causing hoarseness, vagina (dyspareunia) and skin.
There may be loss of smell and  taste.  ENLARGED PAROTID GLANDS: There may be
enlargement of the parotid glands in 80% of patients and they may  be  mildly
tender.   The  glands may fluctuate in size due to infiltration of the glands
with lymphocytes.  These glands are firm  to  touch as opposed to the parotid
enlargement secondary to diabetes mellitus,  cirrhosis,  hyperlipoproteinemia
and malnutrition, which are soft.  HEART: Fibrinous pericarditis may develop.
NERVOUS  SYSTEM:  A  peripheral  sensory  neuropathy  may  occur,  especially
involving  the  second and third division of the trigeminal nerve.  Blindness
and other multiple sclerosis  like  symptoms  may  develop in 20%.  RENAL: In
about 20% of cases there is a renal tubular acidosis which is typically  type
I.  There  may  be  interstitial  nephritis.   Occasionally  there  is a rare
glomerular lesion secondary to  cryoglobulinemia.   These  patients have a 44
times  increased  incidence  of   malignant   lymphomas   and   Waldenstrom's
macroglobulinemia.   Also,  a  pseudolymphoma  may develop.  GI: There may be
mucosal, and submucosal atrophy with plasma cell and lymphocyte infiltration.
There is decreased gastric  acid  secretion  and pancreatic insufficiency may
develop.  LABORATORY: Rheumatoid factor may be present in  70%  of  patients.
If  the  patient  only  has  Sjogren's  disease  without the other autoimmune
diseases mentioned  above,  then  there  are  antibodies  against cytoplasmic
antigens SSA-A or Ro and SS-B or La.  Antibodies to SS-B  are  more  specific
for Sjogren's syndrome since it is less positive in SLE.  SS-A antibodies are
more associated with extraglandular symptoms of Sjogren's syndrome.  There is
a  polyclonal  hypergammaglobulinemia  in 50%.  ANA antibodies are present in
50-80% of cases.  Many  patients  will  have  anemia, leukopenia and elevated
sedimentation rate.  Use the Schirmer test to measure the quantity  of  tears
secreted  in 5 minutes.  A piece of filter paper is placed on the conjunctiva
and a positive test is less than  5  mm of wetting.  Most normal young people
will wet the filter paper to 15 mm.  If the person  is  elderly  and  normal,
wetting  may  be only about 10 mm.  There may be 15% false positive and false
negative results in Sjogren's syndrome.   Rose  bengal staining of the cornea
may reveal the erosions of the cornea.  Slit lamp exam will show sloughing of
the corneal.  Biopsy of the the labial salivary glands will make a  diagnosis
if  lymphocytes  and plasma cells are seen with atrophy of the acinar tissue.
Lymphocytic infiltration of the labial glands is seen in 94%.  TREATMENT: The
dry eyes can be treated  with  .5%  methylcellulose eye drops.  The dry mouth
can be helped by sucking sour sugarless candy.  Vaginal dryness may be helped
with Gyne-Moistrin vaginal moisturizing gel.   The  patient  should  practice
good  dental  hygiene  with  flossing  and  plaque control.  Avoid diuretics,
decongestants and antihistamines because  of  their desiccating effects.  The
salivary gland pain is controlled with analgesics.  Staph  conjunctivitis  is
treated  with  erythromycin ophthalmic preparations.  Steroids should only be
used for severe renal or pulmonary  disease, severe parotid swelling and pain
or other life threatening complications.

                            -SLEEP APNEA-
Symptoms:  Excessive   daytime   somnolence   and   heavy  nocturnal  snoring
periodically interrupted by silences from 30-90 seconds terminated by a  loud
snort  and  then  hyperventilation  for  a  short  period is usually present.
Morning headaches, disorientation  and  non-refreshing sleep, depression, and
anxiety are common.  Some report nocturnal enuresis and  impotence.   May  be
daytime   hypertension,   pulmonary   hypertension,  polycythemia  and  right
ventricular  failure.   Nocturnal  arrhythmias   can   occur  such  as  sinus
arrhythmia,  sinus  arrest,  PVCs,  ventricular  tachycardia  and  AV  block.
Uusually seen in middle  aged  overweight  men.   DIAGNOSIS:  Polysomnography
includes  an EEG, electromyogram, electro-oculogram, airflow detection at the
nose and mouth,  pulse  oximetry  and  measurement  of respiratory effort and
breathing pattern.  Must differentiate between obstructive and central apnea.
Obstruction is diagnosed  if  airflow  ceases,  but  thoracic  and  abdominal
movements  continue in an uncoordinated, ineffective and possibly paradoxical
manner.  If both  airflow  and  chest  and  abdominal movement cease, central
apnea  is  present.   There  may  be  mixed  apnea.   Significant  apnea   is
characterized  by  at  least  a 4% decrease in the arterial oxygen saturation
with the oxygen saturation commonly  falling  to  below  80% and even to less
than 60% in severe  cases  of  obstructive  apnea.   DIFFERENTIAL  DIAGNOSIS:
Narcolepsy  causes  daytime  somnolence,  but  occurs  in young adults with a
family history of narcolepsy.   Also  may  be  cataplexy, sleep paralysis and
hypnogogic hallucination.  Short  daytime  naps  usually  refresh  narcolepsy
patients,  whereas  there  is no benefit with sleep apnea.  A human leukocyte
antigen marker is now available  to  help diagnose narcolepsy.  Also rule out
chronic sleep  deprivation,  psychophysiologic  hypersomnolencwe,  idiopathic
hypersomnolence,  nocturnal  myoclonus, drugs and alcohol.  TREATMENT: Weight
reduction,  avoiding  supine   position,   avoiding  alcohol  and  sedatives,
treatment of nasal congestion, elevation of the head  of  the  bed,  all  may
improve  the  disorder.  Medroxyprogesterone is usually only helpful if there
is daytime CO2  accumulation  secondary  to obestiy hypoventilation syndrome.
Vivactil helps, but causes dry mouth  and  urinary  retention.   It  acts  by
decreasing   REM  sleep.   The  best  treatment  is  with  nasal  CPAP,  with
improvement of daytime sleepiness  within  1-2  days.  However, patients have
difficulting in adjusting.  Tracheostomy can be used in  patients  unable  to
tolerate   nasal  CPAP  and  have  life  threatening  arrhythmias,  pulmonary
hypertension and heart failure.   Removal  of  tonsils and adenoids may help.
Uvulopalatopharyngoplasty (UPPP) will eliminate heavy snoring in  almost  all
cases,but  is  only  useful for sleep apnea in about 50-60%.  Extremely obese
patients and those with small or hypoplastic mandibles do not benefit.  Nasal
pharyngoscopy and cephalometric roentgenography  may be useful in identifying
patients with significant pharyngeal obstruction who are  likely  to  benefit
from  UPPP.   Craniofacial abnormalities as micrognathia and retrognathia may
benefit from mandibular advancement surgery.

                     -SNAKE BITES (Rattlesnake)-
Most snake  bites  are  due  to  North  American  pit  vipers  which includes
copperheads, rattlesnakes, and water moccasins, but also a  small  number  of
coral snakes.  The venom of the coral snake is predominantly neurotoxic while
pit viper's venom is predominantly cytolytic with the exception of the Mojave
rattlesnake  (Crotalus  scutulatus scutulatus) which produces predominantly a
neurotoxin.  Neurotoxins  will  cause  respiratory  paralysis while cytolytic
venoms will cause tissue destruction  by  digestion  and  hemorrhage  due  to
hemolysis.   The first treatment consists of placing a tournequet proximal to
the bite to slow  down  the  absorption.   This should obstruct lymphatic and
superficial venous return  but  not  arterial  and  deep  venous  flow.   The
tournequet  should  not  be removed until the patient is receiving antivenin.
The antivenin therapy for North  American pti vipers is Crotalidae polyvalent
antivenin.  The contents of 5 vials of this antivenin is reconstituted in  50
mL of lactated Ringer's solution and piggy backed to a peripheral IV infusion
of lactated Ringer's solution which is running at 2-3 mL/kg/hour or about 200
mL/hr  in  healthy  patients.   The  patient  is  then given 1 mL/min over 10
minutes.  Remove  the  tournequet  at  this  point,  and  if  the patient has
tolerated  the  first  10  minutes  without  side  effects,  give  additional
antivenin at 1 ml/min until the 5 vials have  been  given.   If  the  patient
develops  signs  of  anaphylaxis  or  allergy  after  the first 10 minutes of
antivenin  administration,  such  as   dyspnea,  itching,  urticaria,  cough,
hyperthermia, and tachycardia,  discontinue  the  antivenin  and  treat  with
epinephrine, diphenhydramine (Benadryl), or hydroxyzine and observe for 10-20
minutes.   If  the  patient  is  stable  after  this  interlude, continue the
antivenin at a  slower  rate.   Usually  about  15-20  vials of antivenin are
needed to treat a rattlesnake bite, but as many as 40 could be  needed.   The
bites of copperheads and water moccasins usually need less antivenin and some
do not require any at all.  If the patient is not stable and has had moderate
or  severe  envenomation,  the patient is given 1 gram of methylprednisolone,
hydrated, and after 45 minutes,  one  vial  of antivenin should be diluted in
100 mL of fluid and infused very slowly as tolerated.  If  the  patient  when
initially  seen  is  severely affected, (hypotension, respiratory difficulty,
facial swelling, tachycardia) 1  gram  of methylprednisolone sodium succinate
(Solu-Medrol) is given IV followed by antivenin.   The  antivenin  should  be
given  without  hypersensitivity  testing.   In  this  setting,  the  diluted
antivenin  is  given  at  a  rate  of  10  ml/min  (not to exceed 20 vials of
reconstituted antivenin) until the  acute  symptoms improve.  Blood should be
drawn from the opposite extremity for PT, PTT, fibrin  degradation  products,
fibrinogen  level,  BUN,  CBC,  platelets,  creatinine,  calcium, phosphorus,
aminotransferases, lactic dehydrogenase, electrolytes, bilirubin and ECG.  UA
should be checked for  hemoglobin,  protein  and  myoglobin.  Pit viper venom
characteristically lyses  fibrinogen,  consumes  platelets  and  can  produce
hemoglobinuria.   Developing  coagulopathy	will  demonstrate a decrease in
fibrinogen with an increase  in  split  products.  Serosanguineous fluid will
develop around the wound.  If  coagulapthy  continues,  full  blown  DIC  can
develop  with  bleeding  from  wounds, hematuria, hemoptysis and hematemesis,
which will require replacement of  specific blood factors and platelets.  The
patient should be treated  in  the  intensive  care  unit  and  observed  for
respiratory  symptoms  also.   Neurologic symptomatolgy usually improves with
antivenin, but intubation and ventilation  may  be needed along with frequent
suctioning for  copious  secretions.   Other  non-specific  measures  include
having  the  patient  rest  in  a recumbent postion with the bitten extremity
placed in a neutral position at  the  level  of  the heart.  The wound can be
gently cleansed  with  soap  and  water  and  dried.   Debridement,  surgical
excision   and   aggressive   cleaning  should  not  be  done.   Prophylactic
antibiotics at this point are not indicated and tetanus prophylaxis should be
given if indicated.  The patient should be kept stable at all times by giving
additional antivenin should  the  patient  deteriorate  at any time.  Fascial
compartment syndrome is rare and fasciotomy is rarely  indicated,  but  there
can  be considerable swelling and all bracelets, rings, and jewelry should be
removed.   Do  not  apply  ice  to   the  bite  site  or  incise  the  wound.
Transportation to a hosptial should be arranged immediately after the bite.

                     -SOLITARY PULMONARY NODULE-
Solitary pulmonary nodule  (SPN)  is  a  single  circumscribed  round or oval
density that is less than  5  cm  in  diameter  that  is  surrounded  by  air
containing  lung  without other pulmonary disease.  Nodules that are > 5-6 cm
are almost always malignant, where as  SPNs that are are densely calcified on
chest x-ray are usually always benign.  About 25% of  cases  of  bronchogenic
carcinoma  present as a solitary nodule.  If the cancerous nodule presents in
this way, the 5 year survival rate is about 50% which is much better than the
10-15% 5 year overall survival rate.  When bronchogenic carcinomas present as
asymptomatic SPNs, total surgical resection can  be accomplished in up to 90%
of cases.  Statistically, about 60% of all solitary lung nodules  are  benign
and  40%  malignant.   DIFFERENTIAL  DIAGNOSIS:  The  differential  diagnosis
includes  granulomas  (histoplasmosis,  blastomycosis, TB, aspergillosis, and
coccidioidomycosis),   Benign    tumors    (hamartomas),   Malignant   tumors
(bronchogenic  carcinoma,  carcinoids  and  single  metastatic   tumor)   and
Miscellaneous  (pseudotumor  from  locualted  fluid  in a fissure, rheumatoid
nodule,  arteriovenous  malformation,   rounded  atelectasis,  bronchial  and
hydatid  cysts).   Hamartomas  constitute  about  6%  of   SPNs,   metastatic
malignancies  3-5%, bronchial adenomas 2% and miscellaneous causes (pulmonary
infarction, arteriovenous malformations,  pulmonary  lymph  nodes), 5%.  SPNs
that occur in non-smoking  patients  less  than  35  years  of  age,  have  a
malignancy  in  less  than  2%.   However,  SPNs  are  malignant in 15-30% of
patients 35-45 years of age and in > 50% older than 50.  The predictive value
for cancer increases in heavy  smokers.   Factors  that favor a benign lesion
include young age, small size (< 2 cm), presence of satellite lesions, smooth
margins on tomography, and a volume doubling time < 30 days or more than  500
days  if  the  lesion  has  central, clustered or laminated calcium patterns.
Features that suggest lung  metastases  include  smooth or lobulated margins,
location in the lower lobes, absence of satellite lesions and  peripheral  in
location.   Calcification  in  the SPN (dense central calcification, multiple
punctate, or  a  laminated  pattern)  are  signs  of  benignancy.  Hamartomas
characteristically have large  clumps  of  calcification  within  the  lesion
(popcorn  pattern).   Eccentric  calcifications  can  occasionally be seen in
carcinomas.  Satellite lesions around a nodule usually indicate the lesion is
benign, but  is  not  100%  diagnostic.   Most  benign  lesions  have  smooth
margins, but 40% of cancers have smooth margins.  Patients  that  have  large
centrally located pulmonary nodules should have cytology.  Sputum cytology is
rarely  diagnostic in peripheral solitary nodules.  Comparison with old chest
x-rays is very important in determining  if  this  is  a new nodule or an old
nodule that has remained static or increased in size.  Thin section 1-5 mm CT
scanning is  helful  in  diagnosing  calcification  within  the  nodule.   In
asymptomatic  patients with a single pulmonary nodule, extensive testing such
as IVP, GI series, bone, brain,  and  liver scanning, bone marrow biopsy, etc
are not indicated, as the yield is less than  3%.   Bronchoscopic  brush  and
biopsy   has  a  60%  diagnostic  yield  for  cancer.   Transthoracic  needle
aspiration using CT  or  fluoroscopic  guided  methods  has an 85% diagnostic
yield for cancer, but  with  a  20%  risk  for  pneumothorax.   The  role  of
fiberoptic bronchoscopy and needle aspiration of SPN is controversial because
the  accuracy in confirming benign lesions is less impressive than diagnosing
cancer.  Therefore, some would go directly to thoracotomy.  A minithoracotomy
is accomplished  by  making  a  small  midaxillary  or anterolateral incision
extending 3-5 inches is usually sufficient to identify and resect most benign
SPNs.  This procedure differes from the standard posterolateral  thoracotomy.
If the  lesion  proves to be cancerous by frozen section, the minithoracotomy
incision can be extended in order to sample mediastinal and hilar lymph nodes
and carry  out  a  lobectomy  or  pneumonectomy.   Patients  that have benign
lesions based on the calcification pattern, its stability over >  2  or  more
years,  and  tissue biopsy confirming a granuloma, hamartoma or other, should
be followed clinically and by x-ray.  In summary, it may be said that lesions
> 2.5 cm in size with grossly irregular or spiculated margins are very likely
malignant, while lesions that have distinctive calcification patterns (dense,
diffuse, central, laminated or  popcorn  pattern)  and  x-ray stability for a
least  2  years  are  probably  benign.   If  the  lesions   have   eccentric
calcification,  cavitation,  smooth margins, are less than 2.5 cm in size and
have satellite lesions, the diagnosis  at  best is an indeterminate one.  The
course of treatment for a noncalcified SPN depends on the size of the  nodule
and  the age of the patient.  For patients that are less than 30 years of age
and have a nodule less than 2 cm, a chest x-ray should be done every 3 months
for 1 year.  If there  is  no  change  after  that time, no further workup is
required.  For patients who are > 30 year of age and have  a  nodule  of  any
size,   diagnosis  of  malignancy  can  be  ascertained  by  bronchoscopy  or
transthoracic needle aspiration  biopsy.   If  malignancy is found, immediate
surgery is performed.  If no malignancy is  found,  repeat  the  chest  x-ray
every 3 months.  If the doubling time points to malignancy, surgery should be
done immediately.

                              -SOTALOL-
Sotalol  is  a  very  effective  drug  that  has  potent  antiarrhythmic  and
antifibrillatory properties.  It is more effective as an antiarrhythmic agent
than  conventional  beta  blockers  for  supraventricular   and   ventricular
arrhythmias.    It   has  a  success  rate  of  20-30%  in  reverting  atrial
fibrillation, and a success rate of  about 60% in reverting atrial flutter to
sinus rhythm.  In this regard, it is more effective than propranolol, and has
about equal success as propranolol  in  reverting  and  preventing  AV  nodal
reentrant tachycardia.  It may reduce the frequency of paroxysmal ventricular
arrhythmias   post   surgery,   and   is   more   successful  in  suppressing
supraventricular  arrhythmias  post  CABG  in  a  dose  of  240  mg/day  than
metoprolol at 150  mg/day.   Sotalol  is  also  effective  in lengthening the
anterograde   effective   refractory   period    of    bypass    tracts    in
Wolff-Parkinson-White  syndrome,  and therefore preventing AV nodal reentrant
or interatrial reentrant  tachycardias.   Sotalol  is  also  effective in the
treatement  of  AV  reciprocating  tachyarrhytmias  that  are  refractory  to
digitalis, calcium channel blockers, beta blockers and class I drugs.  In the
Electrophysiologic  Study  Versus  Electrocardiographic  Monitoring   (ESVEM)
evaluation,   sotalol   was   evaluated   against  imipramine,  procainamide,
quinidine, mexiletine, propafenone, and  pirmenol, in patients with malignant
ventricular arrhythmia and > 10 VPDs  for  48  hours  of  Holter  monitoring.
Sotalol  was the only treatment that was found to be an independent predictor
of reduced risk of recurrence, and  to demonstrate a correlation with reduced
mortality on multivariate analysis.  It also was more effective  in  guarding
against   electrical   inducibility   than   the   other  agents.   It  is  a
noncardioselective beta  adrenergic  blocking  agent  that  has  no intrinsic
sympathomimetic or membrane stabilizing properties.   It  has  been  used  in
supraventricular   arrhythmias,   sustained   and   unsustained   ventricular
arrhythmias.   It  prolongs  the duration of the action potentials, lengthens
the  QT  interval  and  increases   the   refractory  period  in  the  atria,
ventricular, AV node, the His-Purkinje system and the atrioventricular bypass
tracts.   It  decreases  the  heart  rate,  and  slows  conduction   in   the
atrioventricular  node, as other beta adrenergic receptor blockers.  However,
sotalol  has  no  negative   inotropic   effects  as  other  beta  adrenergic
antagonists.  Sotalol is absorbed orally in greater than 90%  at  2-3  hours.
Peak  plasma  concentrations usually occur 2-4 hours following the oral dose.
It is secreted in the  urine  unchanged, and the pharmacokinetics in patients
with liver disease are essentially the same as normal patients.   It  is  not
bound  to  plasma proteins.  The mean elimination half-life is 8 +/- hours in
patients with normal renal function  as  compared  with 24 +/- hours in those
with moderate kidney failure.  In patients with moderate kidney failure  with
a creatinine clearance > 60 ml/min, the starting dose of sotalol should be 80
mg  BID,  with  careful  upward titration.  In patients with end-stage kidney
disease the elimination half life is  about  41 hours, and patients should be
given the drug at intervals of 24-48 hours.  Patients that have overdoses  of
sotalol  can  be treated effectively with hemodialysis.  Patients with normal
renal function are usually started on sotalol at 80-160 mg daily given in two
equal doses.  The dose may be increased if needed every 3-4 days to a maximum
of 640 mg/day.   Increasing  the  dose  of  sotalol  from 160-640 mg/day will
increase the QT interval by 40-100 msec.  The prolonged QT interval should be
monitored as excessive  prolongation  may  lead  to  polymorphic  ventricular
tachycardia.   It  is  recommended  that  the  QTc  should  not be allowed to
increase beyond 500 msec, because  of  its  proarrhythmic effects as the dose
and  QT  interval  are  increased.   USE  OF  SOTALOL   IN   SUPRAVENTRICULAR
ARRHYTHMIAS: Sotalol has been used to treat atrial fibrillation, using IV and
oral  doses, and also as a prophylaxis for recurrence of atrial fibrillation.
IV sotalol has terminated 33% of atrial flutter and 20% of episodes of atrial
fibrillation.  Sotalol has also been  used to treat acute atrial fibrilaltion
and flutter following open heart surgery using 1 mg/kg IV bolus, followed  by
.2  mg/kg  IV  over  12 hours.  Given in this setting, it was as effective as
digoxin plus disopyramide.   Sotalol  has  also  been  used to maintain sinus
rhythm  following  direct  current  cardioversion  of  atrial   fibrillation.
Patients  that  were  treated  with  160-320  mg  of sotalol/day showed a 52%
maintenance of sinus  rhythm  for  six  months.   Side  effects in this study
mandated discontinuation of the  sotalol  in  11%.   Sotalol  has  also  been
effective  in  preventing  reoccurence  of  atrioventricular  nodal reentrant
tachycardia  in   patients   with   Wolf-Parkinson-White  syndrome.   Sotalol
depresses all parts of the reentrant circuits, including the accessory bypass
tracts,  atria,  ventricles  and  AV  node.   USE  OF  SOTALOL  IN  SUSTAINED
VENTRICULAR ARRHYTHMIAS: Sotalol has been compared with procainamide, as  far
as   electrical   reinduction   of  ventricular  arrhythmias.   Induction  of
arrhythmias was  prevented  in  33%  of  patients  treated  with  sotalol, as
compared with 22% with  procainamide.   One  study  has  demonstrated  a  42%
efficacy   in   preventing  ventricuular  tachycardia  or  fibrillation  with
electrical stimulation when sotalol was  used  in doses of 240-640 mg orally.
USE OF SOTALOL IN UNSUSTAINED VENTRICULAR ARRHYTHMIAS: Sotalol used in  doses
of  160-320  mg given in divided doses BID has shown efficacy rates of 34-71%
in patients with unsustained ventricular  arrhythmias.  Sotalol has proved to
be superior when compared with procainamide and propranolol, and was  similar
to  quinidine.   Furthermore,  sotalol  will suppress unsustained ventricular
arrhythmias as effectively in patients with reduced left ventricular function
as it does in those with normal left ventricular function.  SIDE EFFECTS: The
side effects are either  secondary  to  its  beta  blocking properties or its
ability to prolong the QT interval.   Typical  side  effects  from  its  beta
blocking   properties   include,   fatigue,   headache,  dyspnea,  dizziness,
bronchospasm, sinus bradycardia and hypotension.   Its effect on CHF has been
somewhat controversial.  Several studies  have  demonstrated  no  significant
decrease in the ejection fraction prior to and during treatment with sotalol.
However,  rarely,  in  some  patients  sotalol may exacerbate LV dysfunction.
Prolongation of the QT interval  can  lead to torsade de pointes.  Therefore,
other predisposing factors, such as  hypokalemia,  hypomagnesemia,  Class  IA
antiarrhythmics,   tricyclic   antidepressant   drugs  (imipramine,  doxepin,
thioridazine,    amitriptyline),    and    other    QT    prolonging    drugs
(erythromycin),	should be addressed.

                      -SPINAL CORD COMPRESSION-
Common  neoplasms  that produce spinal cord compression include lung, breast,
prostate and lymphoma.  Also multiple myeloma and melanoma and GU tumors will
metastasize and cause  neurologic  impairment.   Usually  there is neoplastic
metastatic  involvement  of  the  pedicle  or  vertebral  body  erosion  with
subsequent  invasion  into  the  epidural  space  which   causes   neurologic
dysfunction.  However, with lymphoma or myeloma the tumor extends through the
intravertebral  foramen  from  the  paravertebral  space  to produce epidural
compression.  It is estimated  that  5%  of patients with systemic malignancy
will end up with epidural spinal cord compression.  CLINICAL: Most  of  these
patients  have  premonitory  signs  and symptoms before there is devastating,
irreversible paralysis.  The initial symptom in  95% of patients is pain that
is local or radicular.  The pain is usually gradual  in  onset,  but  becomes
progressively more severe.  The pain is usually worse at night, with sneezing
or  coughing  or  extreme  flexion,  extension or rotation of the spine.  The
radicular pain can be sharp and intermittent and can readily be confused with
cholecystitis, pleurisy  or  coronary  artery  disease.   As  the compression
progresses, the patient complains of weakness and heaviness in the legs.  The
gait may be clumsy and sensory changes involving the  legs  may  be  present.
Involvement of the corticospinal tract will cause hyperreflexia, and positive
Babinski.   Later,  there  may  be  loss of sphincter control, and ultimately
there  is  paraplegia   or   quadriplegia.    There   may  be  vibratory  and
proprioceptive changes in the feet.  The bladder may be  palpable  due  to  a
large  postvoiding  residual.   If there is involvement at T12 or L1 there is
sphincter impairment and loss of sensation  in the perineum, absent anal wink
and  bulbocavernosus  or  cremasteric  reflexes.   If   there   is   cervical
involvement  there  is  segmental  motor  and  sensory  changes  in the arms.
Percussion of the spinal cord should be  done to elicit the localized area of
tenderness which overlies the pathology.  The thoracic  spine  is  the  usual
site of epidural metastases in about 59%, followed by the lumbar spine (16%),
Cervical  spine  (15%)  and the sacral spine (10%).  LABORATORY: X-ray of the
spine should be the first test  done.   If  the X-ray is negative, then think
about other conditions  as  herniated  disc,  osteoarthritis,  osteomyelitis,
rheumatoid  arthritis, spondylosis, tuberculosis and aortic aneurysm.  Spinal
X-rays should be followed with  MRI  which  can  show the bony metastases and
cord compression as well as any paravertebral masses.  Bones scans can detect
the  vertebral  metastases  but  is  not  useful  for  detecting   the   cord
compression.   DIFFERENTIAL DIAGNOSIS: There are numerous causes of back pain
and all of  these  would  have  to  be  ruled  out  such  as herniated discs,
infections as osteomyelitis, discitis, bursitis,  herpes  zoster  and  spinal
tuberculosis.   Tumors  can  produce intramedullary, epidural, leptomeningeal
and vertebral involvement.  Paget's  disease  is another condition that would
be  in  the  differential.   TREATMENT:  Diagnosis  and  treatment  are  both
considered emergencies  in  order  to  avert  the  neurologic  deterioration.
Radiation of the involved spinal cord area along with high dose dexamethasone
usually  is the first line of treatment.  The patient typically receives 3000
cGy in 10 fractions over  2  weeks  with portals extending 1-2 segments above
and below the involved area.  Dexamethasone is usually given as a 100  mg  IV
bolus  followed  by  24 mg po every 6 hours which is then tapered.  Emergency
surgery is done if  there  is  spinal  cord  compression, but no diagnosis of
malignancy, and for those patients  who  have  received  maximal  amounts  of
radiation.   If  the  patient  has vertebral instability, particularly of the
cervical spine, then  surgery  may  be  indicated.   Any  patient that has an
epidural abscess should have a biopsy.  If there  is  neurologic  progression
despite   radiation   and   steroids   than  laminectomy  may  be  indicated.
Chemotherapy is used in  treating  lymphomas  and multiple myeloma along with
the radiation.  It has been shown that 60% of patients who were ambulatory at
diagnosis will remain so after  surgery,  but  only  7%  of  those  who  were
paraplegic at diagnosis are ambulatory after treatment.

                 -SPONTANEOUS BACTERIAL PERITONITIS-
Spontaneous bacterial peritonitis (SBP)  is  a  common complication of severe
chronic  liver  disease  with  significant  mortality.   There  is  a  10-27%
prevalence of SBP with routine paracentesis on hospital admission in patients
with cirrhosis and ascites.  There is an absence of a obvious cause.  In this
condition there is a spontaneous bacteremia  with  seeding  of  the  ascites.
Clinically,  the  patient presents with fever, abdominal pain and tenderness,
encephalopathy,  deteriorating  hepatic  and  renal  function,  and worsening
ascites, but none of these are pathognomonic .  The initial diagnosis of  SBP
rests  upon  the  combination  of  the clinical syndrome and an ascitic fluid
polymorphonuclear  leukocyte  count  of  >  250  /cu  mm.   The  diagnosis is
confirmed with the finding of positive ascitic fluid cultures, generally  for
enteric  organisms.  Although organisms are seen on Gram stain of the ascitic
fluid in about 60% of patients with SBP, the bacteria are not the same as the
culture in all cases.  Cultures  should  be  obtained by inoculating 10 ml of
ascitic fluid into each of two sets of aerobic and  anaerobic  blood  culture
bottles.   If this is done, the sensitivity is greater than 90%.  Cultures of
the blood are done, but positive  cultures  are obtained in only about 50% of
patients.  SBP usually is caused by only one type of bacteria.  About 1/3  of
patients do not respond to antibiotic therapy and will die.  A further 50% of
patients will die during the hospitalization from complications of the severe
chronic  liver  disease.   CLINICAL:  About  54%  will  present  with  fever,
abdominal  pain  (50%),  abdominal tenderness (53%), encephalopathy (42%), no
fever or abdominal pain (14%), and leukocytosis > 10,000 (54%).  The clinical
presentation is similar  in  patients  with  various  cirrhotic liver disease
which doesn't help with the diagnosis of SBP.   Alcoholic  cirrhosis  is  the
most  common  cause  of  liver  disease,  but  SBP  has  been  reported  as a
complication of cryptogenic cirrhosis,  hepatitis  B cirrhosis, autoimmune or
lupoid cirrhosis, alpha-1 antitrypsin deficiency,  hemochromatosis,  Wilson's
disease  and  in  ascites  complicating acute viral hepatitis.  PARACENTESIS:
There is no association between  a  previous  paracentesis and SBP.  With SBP
there is a single organism reported in 90%% of cases, whereas in  peritonitis
caused by perforation there are multiple organisms.  Paracentesis can be done
in   patients   with   severe   chronic  liver  disease  without  significant
complications.  The relatively  avascular  midline  should  be  used to avoid
hemorrhage, unless surgical scars  are  present.   The  lower  quadrants  are
preferable  to  the  upper  quadrants.   There  is  controversy regarding the
"normal" values for WBCs  and  PMN  leukocytes  in sterile ascites of chronic
liver disease.  The generally accepted values are a WBC > 300/cu mm and PMN <
25%.  However, higher values without evidence of infection are not  uncommon.
The glucose in SBP in peritoneal fluid is not lowered as in bacterial CSF and
pleural  fluid  infection.  Tuberculosis and bowel perforation, however, will
lower the peritoneal fluid glucose.   The  most common gram negative bacteria
in SBP is Escherichia coli which represents  about  55%  of  total  isolates,
followed  by Klebsiella pneumoniae.  Other isolates that can be found include
Salmonella  sp.,  Enterobacter   cloaci,   Pseudomonas  sp.,  Neisseria  sp.,
Aeromonas sobria, Proteus sp., Citrobacter, Acinetobacter, Campylobacter  sp.
and  Serratia.   The most common gram positive bacteria is Enterococcus which
represents only about 5%  of  total  isolates.   Other gram positive isolates
include  Streptococcus  pneumoniae,  and  Staphylococcus  aureus.   Anaerobic
bacteria include Bacteroides, which represents only  2%  of  total  isolates.
Other anaerobic isolates include Clostridium sp.  and Lactobacillus.  Candida
albicans  is  present  in less than 1 % of total isolates.  DIAGNOSIS OF SBP:
Diagnosis is made by finding a  positive ascitic fluid culture, ascitic fluid
PMN > 250/cu mm,  ascitic  fluid  pH  <7.40,  an  arterial-ascitic  fluid  pH
gradient, and an ascitic fluid lactate > 25 mg/dl.  DIFFERENTIAL DIAGNOSIS OF
SBP:   The  differential  would  include  pancreatitis  ascites,  Tuberculous
peritonitis, malignant ascites from a hepatoma, or other cancers, as ovarian.
In  particular, perforation should be ruled out.  In GI perforation the total
ascitic white cell count is usually >  10,000, whereas in SBP it is usually <
10,000.  In perforation the ascitic  fluid  glucose  is  generally  low,  the
protein  is  usually  high,  and  the  LDH  is  equal to the serum level.  In
contrast, in SBP the  glucose  of  ascitic  fluid  is  usually >50 mg/dl, the
protein content <2.5 g/dl, and the LDH less than that of serum.  The  finding
of   pneumoperitoneum  on  KUB  or  chest  x-ray  is  not  pathognomonic  for
perforation,  as  cases  of   spontaneous  bacterial  peritonitis  caused  by
Bacteroides fragiles and Clostridia species have been seen.   However,  these
latter organisms are not common.

                          -SPOROTRICHOSIS-
Sporotrichosis  is  caused  by  Sporothrix  schenckii, and causes 3 different
forms of disease and occurs world-wide.   The 3 forms are the lymphocutaneous
form, pulmonary, and disseminated  form.   The  disease  is  most  likely  in
horticulturists,  miners, nursery workers, landscapers, florists, carpenters,
farmers  and  gardeners.   CLINICAL:  The  lymphocutaneous  form  presents as
movable subcutaneous nodules, ulcers and abscesses usually affecting the skin
of the arms, hands and finger.  The lesions are painless and non-tender,  but
they  can  progress  to  larger discolored fistulas and ulcers.  There are no
associated  chills,  fatigue  or  fever.   Additional  lesions  appear  along
adjacent  lymph  node  chains.   Onset  occurs  from  20-90  days  after  the
inoculation of Sporothrix schenckii.  Sporothrix schenckii is found on thorny
rosebushes, mulches, sphagnum moss, barberry  bushes, hay and timber.  If the
fungus is inhaled it may cause pneumonia with infiltrates or cavities,  hilar
adenopathy,   pleural  effusion  and  pulmonary  fibrosis.   The  disease  is
sometimes associated with Tuberculosis  and  Sarcoidosis.  The pneumonic form
is chronic and usually mild.  The disseminated  form  occurs  most  often  in
people   over   the   age   of  60,  chronic  alcoholism,  and  drug  or  HIV
immunocompromise, and affects bone,  synovium  and  periosteum resulting in a
suppurative arthritis and osteomyelitis in about 80%.   Muscle  and  eye  can
also  be  involved..   Rarely,  the  CNS (chronic meningitis), spleen, liver,
kidney and genitalia are affected.   LABORATORY:  The fungous is diphasic but
the yeast form (cigar shaped),  arranged  in  asteroid  bodies  is  found  in
tissue.  Culture of sputum, pus or bone drainage, done at 22 degrees, results
in  a  leathery  distinctive  mycelian  growth.   Slide staining with PAS and
Gomori stains from fixed tissue of  skin  results in a poor yield.  There are
no serologic tests available at the current time.   TREATMENT:  Treatment  of
the  cutaneous  form  is with a saturated solution of potassium iodide (SSKI)
starting at 1 ml orally tid and  increased  by 1 ml/day to an optimal dose of
about 4 ml  tid.   This  should  be  added  to  a  beverage  because  of  the
distinctive  taste.   The  SSKI  should be continued for 1-2 months after the
lesions have healed.   Iodism  may  develop  with conjunctivitis, stomatitis,
rashes, laryngitis, and bronchitis.  If this does occur, discontinue the SSKI
for 1-2 weeks and then restart at a low dose.  Watch for hyperkalemia if SSKI
is taken with amiloride, spironolactone  or  triamterene.   Itraconazole  has
fewer  side effects and can be used for the lymphocutaneous form in a dose of
100-200  mg  daily  for  three  to  six  months.   For  osseous  or pulmonary
sporotrichosis therapy is with IV Amphotericin B, 1.5-2.5 Grams  being  given
for  a  total  dose.   Amphotericin  B  can  cause  chills, fever, nausea and
vomiting Amphotericin  B  has  been  only  modestly  effective.   SSKI is not
effective at all and ketoconazole generally is not  effective.   In  clinical
trials,  Itraconazole  appears to be as good as Amphotericin B and has only a
few side affects.  Itraconazole may cause  an increase in digoxin levels, and
cyclosporine levels.  Terfenadine and  astemizole  should  not  be  given  to
patients  taking  itraconazole  because of arrhythmias.  Antacids, sucralfate
and H2 receptor  antagonists  will  decrease  the absorption of itraconazole.
Phenytoin,  rifampin  and   carbamazepine   increases   the   metabolism   of
itraconazole   and   may  allow  progression  of  the  fungus.   DIFFERENTIAL
DIAGNOSIS:  Tularemia,  sarcoidosis,  Tuberculosis,  Bacterial osteomyelitis,
neoplasm, cat scratch disease and atypical mycobacterial infection should all
be ruled out.

                  -STAPHYLOCOCCUS AUREUS BACTEREMIA-
Staphylococcus aureus bacteremia (SAB) has  two  major  causes;  Endocarditis
secondary to illicit IV drugs, and catheter related bacteremia.  ENDOCARDITIS
DUE  TO  ILLICIT  IV  DRUG  USE:  IV drug abusers may have involvement of the
tricuspid, aortic and mitral valves.   These patients may present with fever,
chills, sweating  and  hypotension.   Tricuspid  involvement  may  result  in
embolization  of  the  vegetations  to the lung producing multifocal areas of
pneumonitis.  Murmurs are only present in  about 50% of those presenting with
acute bacterial endocarditis, and splenomegaly,  Janeway  spots  and  Osler's
nodes  are  rare.   Any IV drug addict with fever should have 3 sets of blood
cultures.  With this number of blood  cultures,  there is a 95% of recovering
Stap aureus.  The chances for a positive Staph aureus culture  are  increased
if one uses a resin containing media, but using this type of media can reduce
the  recovery  of  other  organisms.   It has been difficult to differentiate
staphylococcal endocarditis from bacteremia.   Tests  that  have been used in
the past included teichoic acid antibodies, immune complexes with  Raji  cell
assays,   and   measuring   rheumatoid   factor.   However,  sensitivity  and
specificity using these methods  are  less  than obtaining blood cultures and
echocardiography.  Transesophageal echocardiography is capable of recognizing
2-3  mm  sized  vegetations  and   myocardial   abscesses.    Treatment   for
endocarditis  is  with  nafcillin in those patients that have sensitive Staph
aureus.  The dose is 150-200 mg/kg/day, given  in equal doses q 4-6 hours for
4 weeks.  The cure rate for right sided endocarditis using  this  regimen  is
100%.   Another regimen that has a 94% cure rate for right sided endocarditis
is nafcillin +  tobramycin  for  2  weeks.   For  left sided endocarditis, in
patients with sensitive staph  aureus,  the  preferred  therapy	is  nafcillin
150-200  mg/kg/day,  given  in  equal  doses  q  4-6  hours  for  4-6 weeks +
gentamicin 5 mg/kg/day, given in equally divided doses every 8 hours IV for 1
week.  Vancomycin is reserved for  those  who  fail  beta lactam drugs or who
have allergy to beta lactam regimens.  It is  used  as  30  mg/kg/day,  given
every  12 hours in equally divided doses for 4-6 weeks + rifampin 600 mg/day.
This regimen is used in methicillin sensitive and methicillin resistant Staph
aureus.   All  cases  of  endocarditis  must  be  monitored  for  efficacy by
measuring the serum bactericidal activity.  Peak serum bactericidal titers of
1:64 or more, and trough serum bactericidal  titers  of  1:32  or  more,  are
associated  with  a 100% bacteriologic cure.  CATHETER RELATED STAPHYLOCOCCAL
BACTEREMIA: The incidence has increased because of increasing use of Hickman,
Broviac, Pic, and central catheters to treat illnesses that require long term
therapy, such  as  osteomyelitis,  cancer  and  fungal  infections.  In these
patients, it is difficult to make a diagnosis because clinically they present
with non specific findings, and it is difficult to differentiate between skin
contamination  and  those  due  to  catheter  related  bacteremia.   Clinical
findings  usually  consist of fever and leukocytosis.  There may be increased
heat and tenderness along the  venous  insertion  site or over the Hickman or
Broviac tunnel.   In  order  to  establish  a  catheter  related  bacteremia,
cultures  must  be obtained from the catheter (the intracutaneous segment and
the tip), and  from  two  peripheral  sites.   In  the  absence of underlying
cardiac valvular disease  and  echocardiographic  findings,  the  patient  is
usually  treated  for about 2 weeks with antistaphylococcal drugs.  Catheters
that are contaminated with Staph  aureus  should  be removed, and not changed
over  a  guidwire.   All  exit  wounds  for  the  catheters  should  be  kept
meticulously clean using daily saline  washes,  and  application  of  sterile
antibiotic ointments.

                        -STATUS EPILEPTICUS-
The most common cause is the failure of epileptics to take their anti-seizure
drugs.  Also, are structual brain lesions from infarct or tumor, anoxia, drug
intoxication, (especially from cocaine), drug withdrawal, metabolic disorders
as  hypoglycemia and fever.  Patients with status due to cocaine or tricyclic
overdose usually respond  to  benzodizepines,  except  isoniazid which can be
refractory (the antidote pyridoxine, 1mg for each mg  of  isoniazid  ingested
should   be   given).    Drugs   associated   with  status  include  alcohol,
amphetamines, antihistamies, theophylline,  isoniazid,  cocaine and tricyclic
antidepressants.  Treatment includes intubation and pulse oximetry to monitor
oxygenation.   Watch  for  hypotension,  ECG  monitoring,   foley   catheter,
nasogastric tube and check IV access to ensure it is patent.  Blood should be
obtained  for  Mg,  Ca,  P04, glucose, electrolytes, BUN, Liver function, PT,
PTT, toxicology screen, alcohol  level, CBC with differential, anticonvulsant
drug levels, UA, pregnancy testing in all women of childbearing age.  CT scan
and lumbar punctures are also useful.  Initial treatment consists of Thiamine
100 mg IV to all alcoholics or malnoursihed patients first before dextrose is
given in order to prevent Wernicke's encephalopathy.  Magnesium  1-2  gm  IV,
antibiotics  if  infection  is  supected,  and  Dextrose  may  be  indicated.
Lorazepam  2 mg/min IV up to 10 mg may be given using .1 mg/kg at 1-2 mg/min.
The anticonvulsant activity lasts for 2-3  hours as opposed to diazepam which
only lasts for 20-30 min following a dose of diazepam given at .2 mg/kg at  2
mg/min up to 20 mg.  Both are equally efficacious in seizure control.  At the
same  time  Phenytoin should be given, 18 mg/kg, at 25-50 mg/min.  If patient
is already on phenytoin give a total  of 9 mg/kg.  If seizures continue, give
a second phenytoin infusion of 9 mg/kg or phenobarbital, 10-20 mg/kg  at  100
mg/min.  If seizures still continue give pentobarbital anesthesia, 5 mg/kg at
25  mg/min  followed by 2.5 mg/kg/hr or give one of the following: Isoflurane
general anesthesia, Chloral hydrate, 30  mg/kg  per rectum, or lidocaine, 100
mg bolus IV.

                      -STEVENS JOHNSON SYNDROME-
Steven Johnson syndrome (SJS)  is  also  known  as erythema multiforme major.
The patient may develop a prodrome of malaise, fever, malaise and myalgia  in
1/3  of  cases  before developing the typical erosions of the skin and mucous
membranes.  The classic picture involves  the lips and peri-oral area.  There
may also be a sore throat, vomiting, diarrhea, and join pains.  The  patients
appear  extremely  ill and can have tachypena and tachycardia.  Stomatitis is
present with vesicles appearing on  the  tongue, lips and buccal mucosa.  The
vesicles then rapidly turn into erosions and ulcers, covered  by  hemorrhagic
crusts.    There  may  be  conjunctivitis,  corneal  ulcers,  balanitis,  and
vulvovaginitis.  The esophagus, trachea,  bronchi,  urethra and larynx can be
involved.  Typical target lesions of erythema multifore  minor  may  also  be
seen.   Complications  include  dehydration, blindness, nephritis, pneumonia,
hepatitis, pericarditis,  arthritis,  cardiac  arrhythmias,  and myocarditis.
The mortality can approach 10-15%.  SJS may  develop  secondary  to  allergic
reactions,  especially  sulfonamides and anticonvulsants, and from infections
such as mycoplasma  pneumonaie,  Yersinia, Streptococcus, histoplasmosis, TB,
and herpes simplex.   Treatment  is  usually  supportive.   Implicated  drugs
should  be  withdrawn,  and  the  patient monitored for secondary infections.
Cool compresses, followed by application of mupirocin ointment is helpful for
crusting and infection.   Hydration,  nutrition,  and  electrolytes should be
addressed.  Hydrogen peroxide mouth wash, viscous lidocaine or a  mixture  of
diphenhydramine  and  maalox  can help the pain.  Steroids are controversial.
Eye  involvement  should  be  attended  to  by  an  ophthalmologist.  Topical
sulfonamide-containing eye drops should not be used as  they  can  exacerbate
the condition.

                          -STROKE (Causes)-
HEMATOLOGIC CAUSES: Include white blood cell disorders (leukemias), Red blood
cell  disorders   (polycythemia,   sickle   cell   disease,   and   malaria),
thrombocytosis  and  thrombocytopenia,  Procoagulant factors (protein S and C
deficiency,   antithrombin   III   deficiency,   and   lupus  anticoagulant),
Hyperviscosity (myeloma, lymphoma,  polycythemia),  Anticoagulants  (heparin,
warfarin, aspirin), Procoagulants (estrogens and aminocaproic acid).  CARDIAC
CAUSES:  Valvular  disorders (infective endocarditis, nonbacterial thrombotic
endocarditis, rheumatic mitral stenosis  and insufficiency, aortic sclerosis,
mitral valve prolapse, and prosthetic heart valves), Cardiac muscle disorders
(cardiomyopathies,  ventricular  aneurysms  and  akinesis,  acute  myocardial
infarction, atrial  myxoma  and  septal  defects  with  paradoxical  emboli).
ARRHYTHMIAS: atrial fibrillation, sick sinus syndrome.  HEMORRHAGIC: Ruptured
aneurysms,  hypertensive  hemorrhage,  bleeding  arterio-venous malformations
(AVM).  OTHER: drug abuse  (cocaine,  amphetamine abuse), birth control pills
and smoking, complicated migraine (usually involves the occipital lobes), and
carotid dissection.

                        -STROKE IN THE YOUNG-
When a young person presents with symptoms of a  stroke,  two  key  questions
should  be asked:  "Are you taking any drugs, either legal or illegal, and do
you  have  any  neck  pain?".   DRUGS  CAUSING STROKES: Many young people are
taking cocaine  or  other  sympathomimetic  drugs  which  can  cause vascular
constriction and inflammatory infiltrates in the vascular wall.  Some illegal
drugs have impurities that  produce  embolization  or  inflammation  if  used
intravenously.   Over-the-counter  drugs  such  as  diet  pills  and  various
stimulants  have  the potential of causing strokes.  CAROTID DISSECTION: Neck
pain  is  important  information  to  elicit  because  carotid  and vertebral
dissection will cause this.  Carotid dissection causes about 20%  of  strokes
in  the young person under 50 years of age.  The average age is about 42, but
there is a range from children up  to the elderly.  Females are involved more
frequently than males.  Approximately 50% will have a history  of  trauma  to
the  neck.   Trauma can be major as accidents, swimming and diving accidents,
falls and gunshot wounds.  Others are minor, and consist of minor neck strain
as in lifting heavy objects, swimmers  who constantly turn their heads in and
out of water and wrestlers.  The dissection typically begins at the  base  of
the skull and dissects down the carotid artery.  This pathway of extension is
explained  by the fact that the artery is fixed at the base of the skull, and
the dissection takes  the  line  of  least  resistance,  dissecting the plane
between the intima and the media.  This will  narrow  the  lumen,  thrombosis
will   form,  and  then  embolize  to  the  brain.   Adequacy  of  collateral
circulation and other factors will dictate  the degree of symptoms.  This may
be associated with  Horner's  syndrome  (  miosis,  ptosis,  enopthalmos  and
decreased  sweating),  as the sympathetic fibers travel with the carotid from
the  superior  cervical  ganglion  to   the  dilator  muscle  of  the  pupil.
FIBROMUSCULAR DYSPLASIA: Fibromuscular dysplasia is another disorder that may
lead to stroke with or without dissection.  Arteriograms will demonstrate the
characteristic beading.  Fibromuscular dysplasia can also involve  the  renal
arteries.   OTHER  CAUSES  OF  STROKES:  If  occlusion or constriction of the
cerebral vessels is seen on  the  arteriogram  then  one would rule out heart
disease embolization, coagulation disorders and some systemic diseases.   The
angiogram  may  suggest  premature atherosclerosis resulting from a metabolic
abnormality of cholesterol  with  a  family  history  of  premature stroke or
death.  Hypercoagulable states would also  have  to  be  ruled  out.   It  is
important  to  obtain a CT to rule out hemorrhage, and possibly a MRI will be
needed to rule out  multiple  sclerosis  which  can  present as stroke at the
onset in 20-25% of patients.  If lesions are seen on the CT and MRI, then  an
arteriogram  should  be done within 5 days, as vascular events as embolus and
thrombosis can lyse within a week  and render the arteriogram normal.  If the
patient  has  a  heart  murmur  and  fever,  then  endocarditis  would  be  a
consideration.  A transesophageal echocardiogram should be done in this  case
as  chamber  clots  and  valve  vegetations  can  embolize.   Systemic  lupus
erythematosus  can  present as a stroke rarely.  Rash, pleuritis, arthralgia,
renal failure, alopecia,  etc  would  lead  one  to  this diagnosis.  ANA and
antiphospholipid antibodies should be  done  as  these  are  associated  with
venous   thrombosis,   abortion   and  strokes.   Prothrombin  time,  partial
thromboplastin time, sickle cell  test,  lumbar  puncture, and blood cultures
are other lab tests that might be done.  Meningitis can cause  thrombosis  of
the  meningeal  vessels,  commonly  in  meningitis due to fungi, spirochetes,
mycobacteria and neoplasm.  Oral  contraceptives  can cause stroke.  Migraine
can present as a stroke-like onset.  Most of these  do  not  cause  an  overt
stroke,  but  occasionally one does result from migraine.  Other causes would
include intracranial tumors, arteriovenous malformations and hypertension.

                         -STRONGYLOIDIASIS-
Strongyloidiasis  is  caused  by   the  nematode  Strongyloides  stercoralis,
commonly known as the threadworm.  The  infection  is  endemic  in  Kentucky,
Tennessee and Ohio.  It occurs in warm moist areas that have poor sanitation.
Risk   factors   include   male   sex,   white,  prior  gastric  surgery  and
immunocompromise.  If the patient  is  not immunocompromised the infection is
usually benign.  If the patient has been taking steroids, has  a  hematologic
malignancy,  AIDS,  etc., then the mortality can be as high as 70% because of
dissemination.  LIFE  CYCLE:  The  infective  filariform Strongyloides larvae
live in moist sandy soils.  They can penetrate the skin of the host and  then
migrate  to  the  lungs  via  the circulation.  From there they travel up the
trachea to the pharynx where  they  are  swallowed.   They then travel to the
duodenum where maturation occurs in the upper  duodenum.   The  adult  female
which  measures  about  2 mm then lay eggs in the duodenal crypts.  After the
eggs hatch the rhabditiform larvae are  passed  into the stool into the soil.
If the soil climatic conditions are  optimal  the  rhabditiform  larvae  will
metamorphose  into  infective  filariform  larvae  and  are  then  capable of
repeating the cycle.  If  the  patient is immunocompromised, the rhabditiform
larvae undergo metamorphosis in  the  gut  rather  than  in  the  soil.   The
infective  larvae  in  the  gut  are  then able to penetrate the gut wall and
disseminate throughout the entire body.  As they penetrate the gut they carry
enteric bacteria into the  blood  which  can  set  up a polymicrobial sepsis,
meningitis and adynamic  ileus.   The  disseminated  form  is  known  as  the
hyperinfection  syndrome.   CLINICAL:  There  may be itching where the larvae
penetrate the  skin.   With  migration  into  the  lung  there  may be cough,
wheezing, dyspnea and infiltrates seen on x-ray.  If the patient has a  minor
infection  with  Strongyloides there may not be any GI symptoms.  If there is
heavy infestation the patient  may  experience vomiting, diarrhea, epigastric
pain and  malabsorption  symptoms  such  as  greasy  foul  stools,  bloating,
peripheral  edema  with hypoalbuminemia, and weight loss.  LABORATORY: Stools
should be collected  looking  for  the  larvae.   However,  the stools may be
negative.  The encapsulated string test or endoscopic  duodenal  samples  may
reveal  the  larvae.   Eosinophilia is very common with Strongyloidiasis.  An
ELISA test can be obtained.   If  there  is  dissemination, the sputum may be
examined.  TREATMENT: Treatment consists of thiabendazole 25 mg/kg po bid for
2 days in the immunocompetent patient.  If the patient  is  immunocompromised
the same dosage should be given for 5 days with a repeat treatment in about 1
week.   Potential  patients should always wear shoes and sanitation should be
improved.

                         -SUBDURAL HEMATOMAS-
ACUTE SUBDURAL HEMATOMA (ASH): The two common causes of traumatic ASH are (1)
those   associated   with   severe   underlying  primary  brain  injury  with
accumulation around the parenchymal  laceration  which  is usually located in
the frontal or temporal lobe.  There often is no  lucid  interval  and  focal
signs occur later OR (2) there is tearing of surface or bridging vessels from
cerebral  acceleration  and  deceleration.   Primary brain damage is less and
there may  be  a  lucid  interval  with  a  later  rapid  deterioration.  The
mortality may range from 50-90% and is primarily from  the  underlying  brain
injury and not the hematoma.  If patients are on anticoagulants the mortality
may  be  90%.   In  the past it has been demonstrated that patients that were
operated on within 4 hours of injury  had  a 30% mortality compared to 90% if
the surgery was delayed to > 4 hours.  More recently is has been  shown  that
the  overall  mortality  is  66%  with  a  functional  recovery of 19%.  Post
operative seizures occur in about 19%.   The worst outcome is with motrocycle
accidents, with 100% mortality if patients were not wearing helmets  and  33%
if they were wearing helmets.  CT SCAN: CT will demonstrate a crescentic mass
of  increased  attenuation adjacent to the inner table with edema often being
present.  The mass is usually over the  convexity, but may also be seen along
the tentorium, posterior fossa or interhemispheric.  If the CT is done within
1-3 days the mass is hyperdense; if done 4 days to 2 or 3 weeks, the mass  is
isodense  with  the  only  clues  being obliteration of sulci and lateralized
shift (the latter may be absent  if  there are bilateral hematomata).  If the
CT is done greater than 3 wks and less than 3-4 months the mass may  approach
the  density  of  the  CSF  (hypodense).  After about 1-2 months the mass may
become lenticular  shaped  (as  in  an  epidural  hematoma)  with the density
greater than the CSF, but less than fresh blood.  TREATMENT:  Subdurals  that
are  greater  than  about  1 cm at the thickest point or greater than 5 mm in
pediatric patients, should rapidly be evacuated surgically.  CHRONIC SUBDURAL
HEMATOMAS:  These  lesions  usually   start   out  as  acute  hematomas,  but
fibroblasts develop within several days and form membranes  on  the  cortical
and  dural  surface.   These are usually described as characteristic of motor
oil.  The patient may  present  with  confusion, headache, TIA like symptoms,
coma, hemiplegia, language difficulties, seizures (usually  focal,  but  less
often  can be generalized).  These patients are usually elderly.  Head trauma
is identified in less than 50% and  this can be trivial head trauma.  Chronic
subdurals are bilateral in about 1/4 of cases.  Other  risk  factors  include
those  with seizures, alcohol abuse, those on anticoagulation, CSF shunts and
those  patients  that  have  hemiplegia  from  previous  strokes.  TREATMENT:
Surgical evacuation is indicated in those with focal deficit,  mental  status
changes,  and subdurals with a maximum thickness > 1 cm.  Complete resolution
of the  fluid  collection  on  CT  is  not  required,  with residual subdural
colections commonly occurring in 78% of cases on post op day 10 and 15% after
40 days.  It may take up to 6 months for complete  resolution.   Prophylactic
seizure  control  may  be started using phenytoin at 17 mg/kg.  If no seizure
has occurred after several weeks, the phenytoin may be discontinued

                  -SUPERIOR VENA CAVA OBSTRUCTION-
The superior vena cava (SVC)  is  a  thin-walled  vein that is located in the
right anterior mediastinum and is surrounded by lymph nodes.  The pressure in
the SVC is very low.  This makes it vulnerable to any adjacent mass that  may
encroach  upon  it.   Lung  cancer accounts for about 75% of the obstructions
with lymphoma and metastatic neoplasms  each accounting for about 10%.  About
2% of all primary lung cancers will develop the syndrome.  The  primary  lung
cancer  is  usually a small cell or squamous type.  Benign conditions are far
less  common  and  are   caused   by   inflammatory  masses,  or  thrombosis.
Histoplasmosis can cause a fibrosing mediastinitis with  dense  fibrosis  and
areas  of  calcification  and  fibrocaseous  material  that  infiltrates  the
mediastinum and extends into adjacent mediastinal structures.  Histoplasmosis
also  can  cause  a  granulomatous  enlargement of the lymph nodes which matt
together and cause obstruction of the SVC rarely.  Other causes would include
metastatic breast cancer,  thyroid  goiter,  syphilitic aneurysm, tuberculous
mediastinitis,   pericardial   constriction   and    idiopathic    sclerosing
mediastinitis.   CLINICAL:  Symptoms  tend to develop slowly over a period of
weeks.  There may be edema of  the  face, arms and neck, headache, dizziness,
facial plethora, distention of the neck veins and the superficial collaterals
over the chest.  The patients have orthopnea, cough and  chest  pain.   There
may  be  cyanosis,  conjunctival edema, proptosis, stridor, Horner's syndrome
and visual disturbances.  These  patients  tend  to remain sitting as bending
over or lying down will bring on the symptoms.  LABORATORY: Chest x-ray  will
show  a  superior  mediastinal  mass.   Some patients presenting with the SVC
syndrome will not have  a  previously  known diagnosis of malignancy.  Sputum
cytology, bronchoscopy with brushings, washings and biopsy of lymph nodes may
be  done.   Either  a  contrast  superior  venacavagram  can   be   done   or
alternatively  a Tc99m injection.  MRI scanning may demonstrate thrombosis of
the  SVC.   TREATMENT:  Treatment  is  usually  for  the  underlying disease.
Chemotherapy should be given  for  small  cell  lung  cancer  and  lymphomas.
Following  chemotherapy  about  95%  of  patients with lymphomas will achieve
relief of the  symptoms,  whereas  70%  of  lung  cancer  will obtain relief.
Antifungal or anti-tubercular medications should be used if  tuberculosis  or
fungal  disease  are  the  cause of SVC syndrome.  Steroids and diuretics may
help to relieve the edema.  Mediastinal  radiation may be needed depending on
the cause.

                         -SWEET'S SYNDROME-
Is  also  known  as  acute  febrile  neutrophilic  dermatosis.   Usually   is
idiopathic,  but is associated with malignancy in approximately 20% of cases.
It occurs most often in acute myelogenous leukemia, but also with hematologic
disorders and solid tumors.  The  most  common signs are fever, neutrophilia,
and  painful  cutaneous  plaques.   Systemic   manifestations   can   include
arthritis,   myalgias,  conjunctivitis,  proteinuria,  hematuria  and  rarely
pulmonary and  hepatic  infiltrates.   If  the  patient  has anemia, abnormal
platelet count  suspect  an  underlying  hematologic  disease.   Differential
diagnosis  include  leukemia  cutis,  drug eruption and systemic infection by
bacterial  or  fungal   organisms.    Corticosteroids  therapy  brings  rapid
improvement of skin and extracutaneous lesions in patients  with  or  without
malignancy.

                             -SYNCOPE-
CARDIOVASCULAR    CAUSES    OF    SYNCOPE:   COMMON:   1....Aortic   stenosis
2....Arrhythmia - slow or fast 3....Carotid sinus hypersensitivity 4....Drugs
5....Low   cardiac   output   with   cardiomyopathy   6....Neurally  mediated
7....Orthostatic  hypotension  8....Vasovagal  UNCOMMON:  1....Atrial  myxoma
2....Cardiac  tamponade  3....Congenital  lesions  as  tetralogy  of  Fallot,
Eisenmengers   complex.    4....Obstructive    hypertrophic    cardiomyopathy
5....Primary   pulmonary   hypertension  6....Pulmonary  stenosis  CAUSES  OF
ORTHOSTATIC  HYPOTENSION:  COMMON:   1....Decreased   circulating  volume  as
bleeding,  dehydration,  fever,   widespread   burns,   pregnancy,   diabetes
insipidus,     hemodialysis    2....Deconditioning    3....Drugs    UNCOMMON:
1....Autonomic nervous system dysfunction as: 2....Bradbury Egglston syndrome
(sympathetic dysfunction in  older  men)  3....Shy-Drager syndrome 4....Riley
Day syndrome 5....Alcoholic or diabetic neuropathies  6....Subacute  combined
sclerosis 7....Tabes dorsalis 8....Spinal cord disease or trauma 9....Adrenal
insufficiency  10...Pheochromocytoma  11...Amyloidosis  DRUGS  THAT  COMMONLY
CAUSE SYNCOPE: 1....Antidepressants 2....Antihypertensives 3....Beta blockers
4....Calcium   channel   blockers   5....Cardiac   glycosides   6....Nitrates
7....Phenothiazine  derivatives  8....Diuretics 9....Antiarrhythmics - causes
proarrhythmias  10...Antidepressants   -   causes   arrhythmias  11...Cardiac
glycosides  -  causes  arrhythmias   12...Phenothiazine--causes   arrhythmias
TREATMENT   OF   REFRACTORY   ORTHOSTATIC   HYPOTENSION:  1....Atrial  pacing
2....Caffeine 3....Clonidine  4....Diet  high  in sodium 5....Fludrocortisone
acetate(Florinef)  6....Indomethacin  7....Elastic  stockings  8....Monoamine
oxidase inhibitors 9....Inderal  CARDIAC  WORKUP  FOR  SYNCOPE:  1....CAROTID
SINUS  MASSAGE - Put in an IV line in place and continuous EKG monitoring and
appropriate  medication  such  as   atropine  sulfate  should  be  available.
Response may be slowing  of  the  heart  (cardioinhibitory)  or  fall  in  BP
(vasodepressor  response)  or  a combination of the two.  One half seconds of
pressure per  side  should  be  done.   Only  unilateral  pressure  should be
applied.  An abnormal response is 5 seconds or more of  ventricular  asystole
or  a  fall  in  systolic  BP  of  more  than  30 mm Hg.  2....EKG - look for
arrhythmias,  left  ventricular  hypertrophy  as  in  hypertension  or aortic
stenosis, previous MI  that  may  predispose  to  arrhythmias,  prolonged  QT
interval  and  WPW.   3....HOLTER - The diagnostic yield is low.  4....ECHO -
Look  for  valvular  lesions,  poor  contraction,  and  pericardial effusion.
5....EXERCISE STRESS - Look for a positive test  for  ischemia.   6....SIGNAL
AVERAGED  EKG  -  This  test  is most useful for assessing the possibility of
ventricular tachycardia in a  patient  with  coronary artery disease.  A high
percentage of patients with sustained VT or subsequent sudden  cardiac  death
show  late  potentials on the surface EKG.  It has a high sensitivity but low
specificity.  It is most  useful  when  used  in  patients with known organic
heart disease in whom  the  absence  of  late  potentials  makes  significant
ventricular     arrhythmias    unlikely    as    a    cause    of    syncope.
7....ELECTROPHYSIOLOGIC  STUDY   -   is   expensive   and   is  invasive  and
uncomfortable and may result in complications.  It should be used only when a
complete noninvasive workup is unrevealing.  8....TILT TABLE TESTING  -  Beta
blocker,  Norpace,  Transderm  or  dual chamber cardiac pacing have been used
with varying degrees of success.  1....Head up tilt testing should be done in
young patients who have no  history  of  cardiac disease initially.  In older
patients LV function should be  assessed  by  echo  or  radionuclide  isotope
imaging.   Echo  can also identify LV outflow obstructive syndromes.  Head up
tilt testing will identify  patients  that have neurocardiogenic dysfunction.
2....Head up tilt test - Patients lie on a tilt table that  has  a  footboard
for  support.   The  head  of  the  table  is  elevated  to  70  degrees from
horizontal.  They  remain  in  this  position  for  15  minutes  during which
arterial pressure and EKG  leads  are  monitored  continuously.   If  syncope
occurs the test is discontinued.  If after 15 minutes there is no syncope the
table  is  placed in the horizontal position and infusion of Isoproterenol is
started to raise the heart rate by  20% over the baseline.  The table is then
placed in 70 degrees for another 15 minutes.  3....If the head up  tilt  test
is negative then an electrophysiologic study should be done to evaluate sinus
node  dysfunction,  AV conduction abnormalities, supraventricular tachycardia
and rarely ventricular tachycardia.   Supraventricular tachycardia remains an
important cause of syncope in young patients  with  or  without  evidence  of
overt  ventricular  preexcitation.   4....If  the  patient  has  had  an  old
myocardial  infarction,  or  has  Q  waves  on EKG from previous MI or has LV
ejection fraction less than 40  %  then ventricular tachycardia must be ruled
out if the patient has syncope.  A signal averaged electrocardiogram  may  be
useful.   If  this  reveals  abnormalities then electrophysiologic studies to
induce ventricular tachycardia is higher.  Twenty four hour ambulatory Holter
monitoring has a low  yield  for  detection  of arrhythmic syncope.  5....Get
potassium  and  magnesium  levels  as  these  can   precipitate   ventricular
tachycardia,  as  can transient myocardial ischemia, orthostatic hypotension,
LV outflow obstruction,  antihypertensives,  vasodilator therapy or autonomic
dysfunction.  TREATMENT OF CARDIAC SYNCOPE:  1....Patients  with  sinus  node
dysfunction  or  AV  block do well with permanent pacing.  In selected cases,
radiofrequency   modification   and   ablation   may   help  supraventricular
tachycardia arising in the AV junction.  Flecanide and Encainide are the most
effective drugs.  However, class I agents are useful.   2....For  ventricular
tachycardia,  class I and III, catheter or surgical ablation and implantation
of  an  automatic   cardioverter   defibrillator   may   be  used.   3....For
Neurocardiogenic dysfunction, drugs that decrease  the  force  of  myocardial
contraction  as  beta  blockers and disopyramide (Norpace) are helpful.  Beta
blockers are the best.  To predict  the efficacy of oral beta blocking agents
head up tilt testing sessions after treatment with IV Esmolol (Brevibloc) are
useful.  Oral theophylline and Transderm-Scop may also be helpful.

                          -SYNCOPE CAUSES-
Cardiovascular: carotid sinus syncope,  vasodepressor syncope, aortic, mitral
and  pulmonary  stenosis,  pulmonary   hypertension,   myxoma,   hypertrophic
cardiomyopathy, tetralogy of Fallot, neurocardiogenic, arrhythmic, structural
abnormalities,   cardiovascular   drugs,  postural  hypotension,  brain  stem
ischemia, cardiac tamponade, pulmonary embolism, aortic dissection, brady and
tachyarrhythmias,   pump   failure   due   to   myocardial   infarction   and
cardiomyopathy.   Neurologic  diseases:  cerebrovascular  disease,  seizures,
trigeminal   and   glossopharyngeal    neuralgia,   autonomic   neuropathies.
Psychiatric disorders: panic  disorder,  hysteria,  orthostatic  hypotension,
drug   induced  syncope,  metabolic  and  endocrine  disorders,  hypovolemia,
hypoglycemia, hyperventilation.

                              -SYNCOPE-
CARDIAC SYNCOPE: The  most  common  cause  of  obstructive stenosis is aortic
valvular  stenosis.   However,  other  causes  would   include   hypertrophic
cardiomyopathy which is typically exertional, but can be due to arrhythmia or
conduction   system  disease.   Primary  pulmonary  hypertension  and  severe
pulmonic stenosis are occasionally associated with effort syncope.  Tetralogy
of Fallot and other  cyanotic  congenital  heart  defects  with right to left
shunting  and  pulmonary  hypertension  and/or  right   ventricular   outflow
obstruction also can cause exertional syncope.  Left atrial myxomas may occur
with change of position secondary to obstruction of the mitral orifice by the
mass.   Thrombosis  of  a  prosthetic  valve may cause sudden obstruction and
syncope.  Arrhythmic syncope should be  a  concern if there are palpitations,
and underlying cardiac disease.  Advanced or high degree AV block is the most
common arrhythmia causing syncope as  the  Stokes-Adams  syndrome.   Most  of
these defects involve the His-Purkinje system post MI or in the elderly.  The
ECG  may  demonstrate  various combinations of fascicular block.  Heart block
may also be caused  by  drugs  such  as  digitalis, calcium blockers and beta
blockers.   Ventricular  tachycardia  and  fibrillation,  and  prolonged   QT
intervasl  may  degenerate  into  torsades  de  pointes causing syncope.  The
Roman-Ward syndrome is associated witha prolonged QT interval, as well as the
Jervell-Lange-Nielsen syndrome which also has associated congenital deafness.
Supraventricular arrhythmias may be  associated  with the sick sinus syndrome
that is  prevalent  postoperatively  in  congenital  heart  diseases  or  the
elderly.   Paroxysmal atrial tachyarrhythmias may cause syncope, particularly
in the elderly with  associated cerebrovascular disease.  Occasionally, young
patients  without  structural  heart  disase  will  develop  syncope  due  to
polymorphic  ventricular  tachycardia.   Patients   with   acute   myocardial
infarction  present  with  syncope in about 5-10% of patients, usually with Q
wave inferior infarctions.  EVALUATION: The  resting ECG may provide clues to
the cause of the syncope.  A prolonged QT interval  may  be  associated  with
polymorphic  ventricular  tachycardia.   Q waves may represent an old MI with
related ventricular arrhythmias or  hyerrtophic  cardiomyopathy that may also
cause ventricular arrhythmias.   A  bifascicular  block  might  indicate  the
patient    has    developed   bradycardic   syncope.    Other   findings   as
Wolff-Parkinson-White, atrial and ventricular ectopy  may be a clue.  Cardiac
monitoring will only reveal  the  cause  in  about  15%  of  cases.   Patient
activated  recorders  may  be  helpful.  Echocardiography can diagnose aortic
stenosis, hypertrophic cardiomyopthy and atrial myxoma.  Exercise testing for
exertional syncope  may  uncover  exercise  induced  ischemia or arrhythmias.
Invasive electrophysiologic studies are important for arrhythmic syncope  and
can  diagnose  the  mechanism  of  syncope  in about 66% of patients.  It can
elicit ventricular and suprventricular tachycardia and the response to pacing
and pharmacologic interventions.  Neurally  mediated syncope may be diagnosed
with a positive response  to  tilt  testing  with  or  without  isoproterenol
provocation.  The signal averaged ECG is important for defining post MI after
potentials   that   are   associated   with  sudden  death  and  arrhythmias.
Electrophysiologic testing is important  in  elucidating a bradyarrhythmia or
heart block as the cause of syncope.  For example  a  prolonged  HV  interval
longer  than  100  milliseconds,  a  prolonged sinus node recovery time, or a
pacing induced infranodal block would all  be  helpful.  If the patient has a
negative electrophysiologic study there is only a 20% liklihood of  recurrent
syncope and a low mortality risk.  Other tests that may be needed to rule out
non-cardiac  causes  would  include  serum glucose, electrolytes, hematocrit,
toxicology screen  for  alcohol  and  drugs,  head  CT, EEG, hyperventilation
testing, cough, micturition,  and  pain  syncope,  orthostatic  testing,  and
testing  for carotid sinus syncope.  This type of syncope usually occurs from
pressure  to  the  neck  as  tight  collars,  trauma  and  tumors.  Autonomic
dysfunction syncope can be caused by Parkinson's disease, Shy-Drager syndrome
or Wernicke's encephalopathy.   In  about  35%  of  patients  with  recurrent
syncope,  no  cause  can be found.  They have a 6% 1 year mortality.  Syncope
due to cardiac etiologies  have  a  20-30%  1  year mortality.  Patients with
bradyarrhythmias due to diffuse conduction system disease can be treated with
the appropriate type of pacemaker.  DDD or DVI pacemakers may be indicated in
these patients with sinus  rhythm  and  primary  conduction  system  disease.
Pacemaker  +  pharmacologic  therapy is needed in the tachycardia-bradycardia
syndrome.  Radiofrequency  ablation,  antitachycardia pacemakers, implantable
AICDs, and revascularization may be needed.

                     -SYNCOPE (Neurocardiogenic)-
Head  up  tilt testing includes continuous monitoring of arterial pressure by
an  intra-arterial  cannula  place   in   the  brachial  or  femoral  artery.
Initially, the test is carried out for 20 minutes at 70  degrees  in  a  drug
free  state.   If  the  test  does  not  show  hypotension  with  or  without
bradycardia, the patient is place in the supine position and IV isoproterenol
is started at 1 ug/min.  The infusion is increased gradually until there is a
20%  elevation  in  the heart rate.  At this point the test is repeated at 60
degrees for 20  min.   The  treatment  of  choice  is  a  beta blocker.  Some
patients do not respond to a beta blocker and in some the patient's  symptoms
are  aggravated.   Prediction of long term efficacy for a beta blocker can be
achieved by  a  negative  tilt  test  with  esmolol  infusion.  Disopyramide,
theophylline, ephedrine, fludrocortisone and  scopolamine  patches  have  all
been used with varying degrees of success.

       -SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE (SIADH)-
SIADH  is  an  inappropriate  excess  of  types  3-5  vasopression  producing
hyponatremia without  edema  in  the  face  of  plasma  hypo-osmolality.  The
syndrome includes hyponatremia associated with a  hypertonic  urine  (usually
greater  than  200  mOsm/kg,  but  even  100  may  be  inappropriately high),
decreased plasma osmolality, increased  urine  sodium (usually grater than 10
mEq/l), the absence of CHF, hypothyroidism, renal failure, porphyria, adrenal
or pituitary insufficiency, and the absence of drugs that can  stimualte  ADH
secretion.   Additional  clues  include  a  decrease  in  BUN  and  uric acid
concentrations  secondary  to  plasma  dilution  and  increased  excretion of
nitrogenous  compounds.   Despite  the  hypervolemia  there  is   no   edema.
Furthermore  there  is no orthostatic hypotension.  CAUSES: NEOPLASTIC: Small
cell  carcinoma  of  the   lung,   adenocarcinoma   of  the  lung,  olfactory
neuroblastoma, pancreatic carcinoma, prostatic carcinoma, thymoma,  carcinoma
of  the  duodenum,  Hodgkin's  disease,  lymphosarcoma,  and  reticulum  cell
sarcoma.   PULMONARY  CAUSES: Lung abscess, tuberculosis, status asthmaticus,
AV  malformation,  pneumonia,  empyema,  chronic  obstructive  lung  disease,
cavitary aspergillosis, recurrent pulmonary  emboli, and prolonged mechanical
ventilation.   CNS  CAUSES:  Subdural  hematoma,   aneurysm,   Guillain-Barre
syndrome,  subarachnoid  hemorrhage,  cerebral  vascular  thrombosis, trauma,
tumor,  herpes  encephalitis,  tuberculous  meningitis,  lupus erythematosus,
acute intermittent porphyria, cerebral abscess, cerebral atrophy,  and  skull
fracture.   DRUGS:  chlorpropamide, amitriptyline, fluphenazine, thiothixene,
thioridazine, acetaminophen,  morphine,  phenformin, vincristine, vinbastine,
general anesthesia, carbamazepine, cyclophosphamide, oxytocin,  barbiturates,
clofibrate,   thiazides,  and  isoproterenol.   MISCELLANEOUS  CAUSES:  acute
myocardial   infarction,   paroxysmal   cardiac   arrhythmia,   Ebstein-Barr,
mononucleosis, postoperative  and  post  traumatic stress, postcommissurotomy
dilutional  syndrome,  hypothyroidism,  positive  pressure  respiration,  and
occult malignancy.  CLINICAL: The rate of fall of the serum sodium is usually
more important that the absolute level.  Patients with serum levels of sodium
between 130-135 mmol/L may have nausea, vomiting and anorexia.  As the  serum
sodium  decreases  further, the patient becomes confused, irritable, restless
and  eventually  comatose,  if  no  intervention.   The  diagnosis  should be
entertained in any individual with hyponatremia, a urine  osmolality  greater
than  300  mmol/kg,  decreased BUN, uric acid, creatinine and albumin, absent
edema, and absent orthostatic  hypotension.   Secondary  causes must be ruled
out such as adrenal  insufficiency.   In  adrenalcortical  insufficiency  the
patient usually has an orthostatic hypotension with tachycardia and a high or
elevated BUN.  Primary polydipsia should be ruled out.  In this disease there
is  a  dilute  urine with an osmolality less than 150 mmol/kg, rather than an
elevated urine  osmolality  as  seen  in  SIADH.   Pseudohyponatremia  can be
produced by elevated glucose,  and  triglycerides.   TREATMENT:  The  primary
treatment  of  SIADH  is  fluid restriction.  This should be between 800-1000
mL/day.  This will result in  a  gradual,  but  progressive rise of the serum
sodium, reduction in weight and improvement of the symptoms.   Patients  that
are  severely  hyponatremic  with  confusion,  seizures  and  coma, should be
treated slowly with 5%  sodium  chloride,  giving  200-300  mL  over a 4 hour
period.  It is important to stress that the serum sodium should be  corrected
very  slowly  with  hypertonic  NaCL, as rapid correction can produce pontine
myelinosis, and CHF.  Demeclocycline  300-600  mg  PO  BID  may be tried when
fluid deprivation is ineffective.  Demeclocycline is a powerful inhibitor  of
vasopressin.   Patients  that  receive  demeclocycline shold be monitored for
renal  failure,   excessive   drug   induced   water   loss,   and  bacterial
superinfection.  Demeclyocycline should not be used in the presence of  liver
disease,  as  drug  accumulation  can lead to nephrotoxicity.  The underlying
disease causing the SIADH should be found and treated.

                   -SYSTEMIC LUPUS ERYTHEMATOSUS-
SLE is a protean autoimmune disease with exacerbations  and  remissions  that
has  a predilection for women aged 20-50.  The incidence is higher in blacks.
There are  several  interesting  subsets  of  Lupus  including Discoid lupus,
subacute cutaneous lupus, systemic lupus erythematosus, ANA  negative  lupus,
mixed  connective  tissue  disease (MCTD), drug induced lupus, and lupus with
antiphospholipid antibodies.  Also, there  are several associated serological
markers that will be discussed.  CCLINICAL: Many patients will  present  with
arthralgias,  arthritis,  Raynaud's  syndrome,  fever  and  skin  rash.   The
differential  for  this  array  of  symptomatology  is wide and would include
gonococcal sepsis, rheumatoid arthritis,  acute rheumatic fever, sarcoidosis,
infectious mononucleosis, rubella, serum sickness  and  hepatitis.   SLE  can
present  just as thrombotic thrombocytopenia purpura with a hemolytic anemia,
thrombocytopenia and CNS symptoms.   Chest  symptoms  are  common in SLE with
pleurisy and pericarditis causing chest pain.  Patients may complain about  a
receding  hair  line  and  alopecia, ulcers of the mouth and rashes about the
malar area that are  made  worse  by sunlight.  Seizures and neuropsychiatric
symptoms sometimes will occur.  Renal disease with hematuria and  proteinuria
can  be  present  and in some cases the renal disease is severe.  LABORATORY:
The patient may have a leukopenia  of  less than 4000 cells/mm3 in about 20%.
Thrombocytopenia will develop in about 25%.  The sedimentation rate  is  used
to  monitor  the  activity  of  the disease.  There may be a Coombs' positive
hemolytic anemia in 10%  which  is  more  common  if  the patient has a false
positive VDRL.  The anemia is usually a  normocytic  normochromic  anemia  of
chronic  disease.   Hyperglobulinemia, circulating anticoagulants, rheumatoid
factor,  hypocomplementinemia,  various  antinuclear  antibodies  can  all be
present.  The LE cell was discovered in 1948 and was  used  for  years  as  a
diagnostic  test.   This is no longer used.  The immunofluorescent ANA is now
used for screening diagnosis and  is  positive  in about 95% of patients with
active SLE.  Many diseases may have a positive ANA.  The double stranded  DNA
is  very specific but suffers from sensitivity.  If the patient has RBC casts
and proteinuria then active renal  disease  should be suspected and the dsDNA
may be positive.  If there is prominent photosensitivity  and  dermal  rashes
then  a  positive Ro/La (SS-A/SS-B) would indicate the patient might have the
subacute cutaneous lupus  subset.   Recurrent  abortions, arterial and venous
thrombosis, and migraines should trigger  testing  for  the  anti-cardiolipin
antibody  and  lupus  anticoagulant as found in the anti-cardiolipin antibody
syndrome.  If the patient  has  been  taking  drugs such as hydralazine, INH,
phenytoin, procainamide, PAS,  sulfonamides,  penicillin,  alpha  methyldopa,
tetracycline  or  propylthiouracil or the patient is elderly, and has cardiac
arrhythmias and pulmonary symptoms, the Antihistone antibody may be positive.
If the patient has  Raynaud's  syndrome,  telangiectasia, calcinosis and skin
involvement then you should get an anticentromere antibody as the patient has
the Crest syndrome.  If the patient is suspected of having  mixed  connective
tissue  disease  (MCTD), consisting of muscle weakness from polymyositis, and
scleroderma with tightening of  the  fingers  and  pleurisy, then a RNP (ENA)
should  be  ordered.   If  polymyositis  with  proximal  muscle  weakness  is
suspected, then a jo-1 antibody should be done.  If the patient complains  of
dry  eyes  and  mouth  the  diagnosis  may  be primary or secondary Sjogren's
syndrome.  This would prompt Ro/La (SS-A/SS-B) antibody testing.  SUSBSETS OF
LUPUS: ANA NEGATIVE LUPUS This occurs  in  less than 5%, but can present with
identical symptoms of Lupus erythematosus.  It is a rather benign form with a
low incidence of CNS and renal disease.  Anti-Ro antibodies  are  present  in
about  60-70%.  DISCOID LUPUS: In Discoid lupus systemic symptoms are minimal
or non existent in about 95%  of  patients.   The ANA is only present in 20%.
If the patient has extensive discoid disease, rather than local, there  is  a
tendency  for  progression  to  SLE.  The lesions usually affect the head and
consist   of   erythematous   plaques   with   scaling,   scarring,  atrophy,
telangiectasia  and  hyperpigmentation.   SUBACUTE  CUTANEOUS  LUPUS:   These
patients  have  widespread  papulosquamous  or annular cutaneous lesions that
tend to be symmetrical and  involve  exposed areas.  These lesions usually do
not scar or atrophy on healing as does discoid  lupus.   These  patients  may
complain  of  arthralgias,  malaise, fever and myalgias in about 50%.  Kidney
and CNS involvement is infrequent.   Sjogren's  syndrome may develop in about
10%.  Anti-Ro antibodies are found in 40-60% and anti-La antibodies sometimes
may be found.  CARDIOPULMONARY: Chest pain  may  be  caused  by  pericarditis
which  is  typically  made  worse  by  the  prone  position.   There may be a
pericardial rub or  paradoxical  pulse.   Echocardiography  should be done as
there may be pericardial effusion, tamponade  or  constrictive  pericarditis.
Patients  may  have  valvular  disease  which  is seen more frequently if the
patient has anti-cardiolipin antibodies.   Pleurisy  with or without effusion
may  be  present.   Examination  of  the  pleural  fluid  typically  shows  a
transudate, low WBC, normal glucose, decreased complement and  positive  ANA.
The  lung  also  may  show  infiltrates  and interstitial disease.  Pulmonary
hypertension doesn't develop in  SLE  commonly,  but does in mixed connective
tissue disease  and  scleroderma.   LUPUS  AND  ANTIPHOSPHOLIPID  ANTIBODIES:
Antiphospholipid  antibodies  consist of positive tests for anti- cardiolipin
antibody, lupus anticoagulant and false  positive VDRL.  These antibodies can
cause recurrent venous  and  arterial  thrombosis,  thrombocytopenia,  livedo
reticularis,  miscarriages,  usually  in  the  mid-trimester,  migraines  and
cardiac  valvular  lesions.   About 50% of the antiphospholipid syndrome will
have SLE.  The other 50%  that  is  not  associated  with SLE is known as the
primary antiphospholipid antibody syndrome which may or not  be  significant.
LUPUS  AND RENAL DISEASE: There are about 4 major histologic subsets of renal
disease that can be seen on biopsy.   CLinical renal disease occurs in 50% of
patients and can be the cause of death.  If nephrotic  syndrome  develops  in
SLE  suspect  MEMBRANOUS  NEPHRITIS.   It develops slowly and has an indolent
course.  Absence of  dsDNA  antibodies,  normal  complement and resistance to
high dose corticosteroids and immunosuppressive agents  is  typical  of  this
subset.   FOCAL  PROLIFERATIVE  NEPHRITIS has a good long term prognosis with
most having only mild hematuria and  proteinuria and failure to progress with
renal insufficiency.  A few in this subset will develop a more severe disease
and high dose corticosteroids,  or  immunosuppressing  agents,  may  suppress
progression of this disease.  DIFFUSE PROLIFERATIVE GLOMERULONEPHRITIS is the
most  severe  form of all.There is proteinuria and hematuria and many develop
renal  insufficiency  which  will   require   high  dose  corticosteroid  and
immunosuppressive agents.  There  is  usually  depressed  complement  levels,
positive  anti-dsDNA and an increase in the systemic manifestations of SLE as
well.  MESANGIAL NEPHRITIS is the  most  benign  form of renal involvement in
which there is segmental or focal hypercellularity isolated to the mesangium.
There may be immune complexes in these lesions.  There  is  mild  proteinuria
and hematuria.  There usually is no progression to renal insufficiency.  Even
though  mesangial  nephritis  is  mild  it  usually is associated with active
systemic disease and treatment of this is done rather than the renal lesions.
LUPUS AND THE CNS: Lupus involvement of the CNS occurs in 50% of patients and
is  characterized  by  psychosis,  depression,  seizure  disorders,  strokes,
movement  disorders,  peripheral  and  cranial  neuropathies,  and headaches.
Patients with CNS involvement often times have a poor prognosis and  must  be
treated  with  high  dose corticosteroid agents and immunosuppressive agents.
The difficulty is in associating the symptoms  of the CNS with SLE.  There is
no one positive test  that  definitely  confirms  the  diagnosis.   MRI,  and
cerebral  spinal fluid are both nonspecific.  Antilymphocyte and antineuronal
antibodies are present  in  some  and  there  is  an  association between the
presence of antiphospholipid antibodies and CNS lupus.  TREATMENT: SKIN:  Sun
screens  with  a  factor  of  at  least  15  should  be  given because of the
photosensitivity of patients  with  SLE.   For  facial cutaneous lesions, low
dose topical 1% hydrocortisone should be given.  Occasionally,  high  potency
creams  as  clobetasol  .05%  bid  may  be  needed  as  well as intralesional
Triamcinalone  injections.   If  all   this  fails,  then  hydroxychloroquine
(Plaquenil) 200 mg bid will usually help.  Patients should be seen by an  eye
specialist  every  6 months because of occasional retinal toxicity associated
with hydroxychloroquine.   If  the  patient  fails  to  respond adequately to
Plaquenil then try chloroquine or quinacrine (Atabrine).  As a  last  resort,
systemic  steroids  may be tried.  LUNG: Start with a NSAID and then progress
to prednisone if the NSAID fails.  If acute lupus pneumonitis occurs this can
be disastrous and should be treated  with  prednisone at 60 mg daily.  If the
patient has the antiphospholipid antibody, then there may be pulmonary emboli
and the patient should anticoagulated.  CENTRAL NERVOUS  SYSTEM:  If  patient
has  seizures  they  can  be  treated  the  same  as if they didn't have SLE,
utilizing the usual anticonvulsants.  High dose corticosteroids are indicated
for cerebritis and transverse  myelitis.   Cyclophosphamide may be used also.
HEMATOLOGIC SYSTEM: About 60% of SLE patients will  have  a  positive  direct
Coombs' but only a few will develop hemolysis.  If hemolysis does develop the
patient  may  be  treated with prednisone, 60 mg daily for 4-6 weeks and then
taper slowly.  If the  patient  doesn't respond then immunosuppressive agents
or splenectomy may be done.  If severe thrombocytopenia develops,  prednisone
can  also  be  given  at the same dosage given for hemolysis.  If the patient
doesn't  respond   to   the   prednisone,   then   IV   pulse   therapy  with
cyclophosphamide or azathioprine 2 mg/kg per day or danazol 200 mg qid or  IV
immunoglobulin   2   gram/kg   given   over  5  days.   If  the  patient  has
antiphospholipid antibodies and  associated  recurrent thrombosis, start long
term  warfarin.   RENAL  DISEASE:  The  worst  prognosis  is   with   diffuse
proliferative  or  membranoproliferative nephritis as seen with renal biopsy.
If the patient has mesangial nephritis  no  treatment is needed for the renal
disease.  Patients with focal and diffuse proliferative lupus  nephritis  may
be  treated  with  high  dose oral prednisone 80 mg per day and taper after 1
month.  When the tapering  begins,  give  cyclophosphamide  1- 3 mg/kg/day OR
azathioprine 1-3 mg/kg/day OR a combination of cyclophosphamide  1  mg/kg/day
and  azathioprine  1  mg/kg/day  OR  cyclophosphamide  500  mg per M2 of body
surface in 250 ml of normal saline IV.  (IV cyclophosphamide has been said to
be less toxic than the oral  form  and  more effective).  The patient is then
further hydrated with a liter or more or normal saline.  The next month,  the
patient  is  given  750  mg/M2  and  then  1000 mg/M2 the following month and
maintained at this level  for  about  6  months  of treatment.  CBC should be
followed with particular emphasis on the white  count  which  should  not  be
lower than 2000-3000 cells per mm3.  Many chemotherapy programs and schedules
have  been  devised  and  this  is  only one that may be tried.  Hypertension
should be treated to prevent progression and deterioration of renal function.
If the patient has membranous lupus  nephritis  then a trial of prednisone of
120 mg every other day may be given for 8 weeks and then  tapered  over  a  4
week  period.   ARTHRITIS: Arthritis can be be treated with NSAIDs, Disalcid,
low dose prednisone and Plaquenil.

             -SYSTEMIC LUPUS ERYTHEMATOSUS AND THE LUNG-
SLE affects the  respiratory  system  more  than  any other collagen vascular
disease.  About 50-70% of patients will have involvement of the lung sometime
during the course of  their  illness.   Most  causes  of  death  in  SLE  are
attributed to renal comlications and infections.  However, lung complications
as  acute alveolar hemorrhage can cause death.  The pleura is mostly involved
in  SLE  with  lymphocytic  and   plasma  cell  infiltration,  and  fibrosis.
Pleuritic pain, dyspnea, cough, tachycardia, pleural rub and fever are common
symptoms.  X-ray of the lungs in  patients  with  lupus  pleuritis  may  show
right,  left,  or  bilateral pleural effusions.  These may be associated with
either alveolar infiltrates  or  basilar  discoid atelectasis.  The effusions
typically  are  small  and  may  spontaneously  disappear.   The   fluid   on
thoracentesis  may  be  clear,  serosanguinous  or turbid.  The pH is usually
greater than 7.3 and the glucose is usually greater 60 mg/dl.  However, there
have been  reports  of  a  low  pH  and  glucose  in  drug  induced  and SLE.
Mononuclear cell predominance is usual in effusions that  have  been  present
for  >  2  weeks.  The WBCs have a range from 230-15,000 with a range of PMNs
from 21-100.  The  LDH  pleural  fluid:  LDH  serum  is  > 0.6, indicating an
exudate.  LE cells may be present in the effusions even in  patients  with  a
negative  ANAs.  Occasionally, there will be a low C3, C4 and total hemolytic
complement in the pleural effusion of SLE, but this finding is more typically
found in the pleural fluid of rheumatoid arthritis patients.  Double stranded
DNA may also be found in the  effusions  of  SLE, but is not diagnostic as it
also has been found in TB pleurisy and bronchogenic carcinoma.  The  activity
of  the  disease  is  closely  associated  with  the ANA titer of the pleural
effusions.  Titers  >  1:160  usually  occur  in  patients  with active lupus
pleuritis and may be considered diagnostic.  However, the isolated finding of
ANA positivity in pleural effusions is not diagnostic of SLE, as it also  may
be  found in lymphomas and malignancies.  Likewise, a pleural fluid:serum ANA
titer ratio  >  1  is  associated  with  active  disease.   Treatment  of SLE
pleuritis is with steroid therapy.  This usually results in a rapid relief of
the pain, fever and dyspnea.   LUPUS  PNEUMONITIS:  Acute  lupus  pneumonitis
(ALN) presents as a sudden onset of fever, dyspnea, diffuse infiltrates (more
prominent  in the lower lung fields), cough and hypoxemia.  There may also be
hemoptysis, pleuritis, chest pain  and  pleural  effusions.  ALP is rare, but
may present as the  first  manifestation  of  SLE.   There  is  an  increased
incidence  during  pregnancy  and  in  the  immediate postpartum period.  The
mortality rate in lupus pneumonitis  is  about  50%.  The pathogenesis may be
due to deposition of immune complexes in the tissues and vessels of the  lung
or  bacterial  infection.   Treatment  is  with  high dose steroids and broad
spectrum antibiotics with  the  possible  addition  of  cytotoxic drugs.  THE
SHRINKING LUNG SYNDROME: This syndrome presents as dyspnea on exertion or  in
the  recumbent position.  X-rays may show elevation of the diaphragms, linear
atelectasis and  small  clear  lungs.   Pulmonary  function  will show severe
restriction with decrease in the vital capacity and static lung volumes,  and
a  decrease  in lung compliance.  The diffusing capacity is usually normal or
slightly decreased.  This suggests that the restriction may involve the chest
wall or  neuromuscular  restriction,  such  as  diaphragmatic and intercostal
muscle weakness.  ALVEOLAR HEMORRHAGE:  The  clinical  presentation,  x-rays,
pathological appearance and natural history are very similar in patients with
alveolar  hemorrhage  and  lupus  pneumonitis.  Alveolar hemorrhage in SLE is
rare  occurring  in  about  .6-2%  of  patients.   They  present  with fever,
tachycardia, dyspnea and hypoxemia.  Hemoptysis may be  absent,  massive,  or
scant.  Chest x-rays will show patchy ill-defined acinar infiltrates that are
usually bilaterally and inferiorally located in the lung fields.  Usually the
hemoptysis  is  not  associated  with  coagulopathies,  but circulating lupus
anticoagulant may present  with  lung  hemorrhage, vasculitis and infarction.
The hematocrit tends to drop rapidly over the first 36  hours,  even  in  the
absence of overt hemoptysis.  There may be an increase in diffusing capacity.
Treatment  for alveolar hemorrhage in SLE is with prednisone 1-2 mg/kg/d or 1
gram/day.  Most patients are already  on  steroids for other symptoms of SLE.
If patients do not respond to prednisone  alone,  azathioprine  is  given  at
2-2.5  mg/kg/day  or  cyclophosphamide  at  1.5-2 mg/kg/day.  Broad sprectrum
antibiotics are also given.  Patients that do not respond to the above may be
given plasmapheresis.  INTERSTITIAL LUNG  DISEASE  AND  SLE: The incidence of
interstitial  lung  disease  is  only  about  3-5%.   These   patients   have
interstitial  infiltrates  on  chest x-ray and about 50% will have pleuritis.
There may also  be  elevation  of  the  diaphragms.   Fifty percent will have
restriction of the  lung  volumes  and  decrease  in  diffusion  capacity  by
pulmonary  function  testing.   Treatment  is with steroids for about 6 weeks
with a variable response.  PULMONARY HYPERTENSION: Pulmonary hypertension and
SLE is rare and may  be  secondary to pulmonary artery vasculitis, thrombosis
in situ, pulmonary thromboembolism  and  interstitial  pneumonitis.   Therapy
with  nifedipine,  captopril  and  hydralazine  are  ineffective.  Prednisone
response  is  variable.   A  combination  of  steroids,  cyclophosphamide  or
azathioprine, and anticoagulants may be of some benefit.

         -SYSTEMIC LUPUS ERYTHEMATOSUS LABORATORY DIAGNOSIS-
Since  systemic  lupus  erythematosus  (SLE)  can  mimic other diseases it is
imperative that there  be  laboratory  confirmation.   Most of the laboratory
tests are non specific, in that they may be positive with SLE, but  also  are
positive  in  other  diseases  as  well.  For example, most all patients with
mixed connective tissue disease will have a positive ANA test.  Approximately
33% of patients with rheumatoid arthitis  will  have a positive ANA test, but
usually in lower titers than SLE patients.  About 66% of diffuse  scleroderma
will be ANA positive.  Other rheumatic diseases that may be associated with a
positive   ANA   include  polymyositis,  Sjogren's  syndrome,  discoid  lupus
erythematosus and dermatomyositis.  Furthermore,  the  ANA may be positive in
non-rheumatologic disease such as chronic pulmonary, hepatic  and  infectious
disorders,  and malignancies as lymphoma.  In the past LE cells were used for
diagnosis, but  this  test  is  insensitive.   LE  cells  may  occur in other
collagen disease and chronic inflammatory conditions.  This test has now been
put to rest and the screening test of choice for SLE is now  the  antinuclear
antibody  test  (ANA).   If  the ANA test is negative it is highly improbable
that the patient has SLE.  However, if it is positive in high titers, further
testing must be done because  it  too  is non-specific in most instances.  As
one ages there is an increased chance of having a positive ANA in the absence
of any type of rheumatic disease.  Up to 50 years of age the incidence of ANA
positivity is about 5%.  After 50, about 5-10% will have a  "false  positive"
and by the age of 70 the incidence is up to 20%.  Medications can also induce
a  positive ANA test without actuually having SLE.  It is extremely common to
have a homogeneous ANA  pattern  in  patients  with drug induced SLE.  Common
drugs  that  may  induce   this   change   are   procainamide,   hydralazine,
anticonvulsants,  chlorpromazine,  captopril, quinidine, interferon-alpha and
penicillamine.  All of these drugs may  also  cause symptoms of SLE.  In drug
induced lupus, the extractable nuclear antibodies (ENA) are  negative  as  is
the  ssDNA  and complement.  The type of fluorescent pattern seen may be used
as a guide in  pointing  one  toward  the  correct  diagnosis.  If the ANA is
positive one should obtain double stranded antibodies for DNA, antibodies  to
extractable  nuclear  anitgens  (ENA), in particular, the anti-Sm antibodies,
and serum complement levels.  Other  tests  that may be complementary include
anticardiolipin antibody, partial thromboplastin  time,  platelets,  Coombs',
VDRL  and  cryoglobulins.   All  of these tests should be correlated with the
patients  clinical  findings.    Clinical   findings   in   SLE  include  the
characteristic malar rash  with  photosensitivity,  arthritis,  oral  ulcers,
pleuritis  and  pericarditis, renal disease, seizures, psychosis, leukopenia,
hemolytic anemia and thrombocytopenia.   ANTINUCLEAR ANTIBODIES: The ANA test
is positive in more than 98% of cases of  active  SLE.   The  titer  is  very
important in making a diagnosis of SLE.  The higher the titer the more likely
the patient may have a collagen disease.  If the titer is greater than 1:320,
further  testing should be done.  Fluorescent staining will yield 5 different
patterns;  homogeneous,   rimmed,   speckled,   nucleolar   and  centromeric.
HOMOGENOUS: This pattern if found in 65% of patients with  SLE,  but  is  not
specific  for  SLE.   It is produced by antinuclear antibodies against single
stranded  DNA  (ssDNA),  histones  and  other  nuclear  proteins.  Rheumatoid
arthritis patients usually have a homogeneous pattern.  RIMMED: The rimmed or
peripheral pattern is the most uncommon type of pattern and can be  secondary
to  antibodies against double stranded DNA.  However, if it is positive it is
the most specific  of  the  flurorescent  patterns  for  SLE.  SPECKLED: This
pattern is not specific for for SLE.  It is produced  by  antibodies  against
extractable  nuclear  antigens  (ENA)  and is present in 30% of patients with
SLE.  This pattern is also seen  in mixed connective tissue dissease in about
75% of patients.  NUCLEOLAR: The nucleolar test is rare in patients with  SLE
and  is  not specific for SLE.  It is produced by antiboides directed against
RNP.  If this test  is  positive  it  would  suggest scleroderma and not SLE.
CENTROMERIC: The centromeric pattern is produced by  antibodies  against  the
enzyme  topoisomerase  I,  which  is an enzyme used during DNA replication in
mitosis.  It is found in  the  CREST  syndrome,  a variant of scleroderma, in
about 66% of cases.  The CREST syndrome  consists  of  calcinosis,  raynaud's
phenomenon,   esophageal   dysfunction,  sclerodactyly  and  telangiectasias.
EXTRACTABLE NUCLEAR ANTIBODIES: The  extractible nuclear antibodies (ENA) are
divided into the  Anti-RNP,  Anti-SM,  Anti-Ro  (anti-SSA)  and  the  Anti-LA
(anti-SSB)  antibodies.   ANTI-RNP:  Anti-RNP antibodies are present in about
50% of SLE patients.  They are also  found in high titers in mixed connective
tissue disease.  ANTI-SM: Anti-Sm (Smith) antibodies are found in only 15-30%
of SLE patients, but when found they are extremely  specific  for  SLE.   You
cannot  follow  the disease activity of SLE with the titers of anti-SM as you
can with ds DNA.  It has been said that if SLE patients have positive anti-Sm
antibodies there is  greater  chance  of developing neuropsychiatric symptoms
such as seizures and psychosis.  ANTI-RO (SSA): Anti-Ro antibodies antibodies
are found in up to 40% of SLE patients.  About 70% of Sjogren's syndrome will
also have positive  anti-Ro  antibodies.   SLE  patients  that  express  this
antibody  have  a  tendency  for a more photosensitive dermatitis and usually
have, in general, a milder  disease.   Since the IgG anti-Ro antibodies cross
the placenta, neonates may develop congential heart block and  photosensitive
rashes.   ANTI-LA  (SSB):  Only  about  15%  of  SLE  patients will have this
antibody.  However, the antibody  is  present  in  about 50% of patients with
Sjogren's syndrome.  ANTI-DNA ANTIBODIES: If antibodies  to  double  stranded
DNA  (dsDNA)  are  positive  a  diagnosis  of SLE can be made with certainty.
However, only about 75%  of  the  time  will  these antibodies be positive in
patients with SLE.  If the patient has active lupus nephritis the  antibodies
may  have  an  incidence  of 75%.  These antibodies may be used to follow the
disease activity of SLE.  COMPLEMENT: All patients that are ANA positive with
a high index of suspicion  for  SLE  should  have C3, C4, and total hemolytic
complement (CH50).  Immune complexes in SLE  tend  to  activate  the  classic
pathway  which  will  lower  the C3, C4 and CH50 in about 70% of SLE patients
that have active disease.   ANTIPHOSPHOLIPID  ANTIBODIES: False positive VDRL
tests may be obtained in about 10% of SLE  patients,  but  is  also  seen  in
Sjogren's  syndrome,  rheumatoid  arthritis,  AIDS,  Hashimoto's thyroiditis,
idiopathic thrombocytopenic  purpura,  autoimmune  hemolytic  anemia  and the
antiphospholipid antibody syndrome.  If the patient has a  prolonged  partial
thromboplastin  time a lupus anticoagulant may be present.  This is tested by
mixing the patient serum with normal serum.  If the PTT doesn't correct there
is a lupus anticoagulant  present.   Anticardiolipin  antibodies may occur in
SLE patient in up to 50%.  Anticardiolipin  antibodies,  lupus  anticoagulant
and  false  positive  VDRL tests all make up the antiphospholipid antibodies.
Antiphospholipid antibodies may be found  in  SLE or diseases other than SLE.
If  they  occur  in  patient  that  do  not  have  SLE  they  occur  as   the
antiphospholipid  syndrome.   When  present they are associated with arterial
and venous thrombosis such  as  stroke, recurrent spontaneous abortions, deep
and superficial phlebitis, pulmonary emboli, etc.  In summary, when the above
tests are used in correlation with the clinical symptomatology  they  may  be
extremely  helpful  in  elucidating  the  various  rheumatic  diseases.   The
combination   of  a  positive  ANA  test,  plus  a  positive  anti-dsDNA  and
hypocomplementemia will make a  diagnosis  of systemic lupus erythematosus in
100% of the cases.

                       -TACHYCARDIA SCENARIOS-
The  first  step  in  managing  a  tachycardia is to classify it as a wide or
narrow complex tachycardia.   Following  this  decide  if  the wide or narrow
tachycardia is regular or irregular.  NARROW COMPLEX TACHYCARDIA:  IRREGULAR:
Atrial   fibrilation,   multifocal   atrial   tachycardia.   REGULAR:  Atrial
tachycardia, atrial flutter, AV reciprocating tachycardia associated with WPW
or concealed bypass tract,  and  non-paroxysmal junctional tachycardia.  WIDE
COMPLEX TACHYCARDIA: IRREGULAR: Torsades de pointes, atrial fibrillation with
aberrant conduction, atrial fibrillation associated  pre-excitation  of  WPW.
REGULAR:   Vetricular   tachycardia,   supraventricular   tachycardias   with
aberration,  pre-excitation  reciprocating  tachycardia  associated with WPW.
DECISIONS: If  it  is  determined  that  the  patient  has  a  narrow complex
irregular tachycardia, treatment can be  given  for  atrial  fibrillation  or
multifocal   atrial   tachycardia.   In  all  other  instances  IV  adenosine
(Adenocard) can be given ra;pidly using  6  mg, or if unsuccessful, repeat 12
mg as a rapid bolus.  Patients taking methylxanthine agents  as  theophylline
are  resistant  to  adenosine.   Adenosine  will  terminate  AV reciprocating
tachycardia, AV nodal areentrant  tachycardia and some intra-atrial reentrant
tachycardias.   Slowing  of  the  rhythm  with  adenosine   will   facilitate
identification  of  atrial fibrillation or flutter waves or an ectopic atrial
rhythm.  Adenosine will  only  convert  ventricular  tachycardia  in  < 2% of
cases.  Thus, conversion of the tachycardia essentially rules out ventricular
tachycardia.  Wide complex irregular tachycardia that doesn't change  at  all
with  IV  adenosine represents polymorphic VT (Torsades de pointes) or atrial
fibrillation with pre-excitation secondary to WPW.  If the rhythm slows after
IV adenosine, identification of the tell tale waves of atrial fibrillation or
multifocal atrial  tachycardia  with  aberration  can  be  seen.   It is also
possible to obtain other clues as to the origin of  the  tachycardia  on  the
surface  ECG.   Ventricular  origin  is suggested with QRS durations > 140 ms
with RBBB and >160 ms with  LBBB,  concordant QRS morphology in V1-V6 (+or-),
AV dissociation and fusion beats.

                 -TAMOXIFEN AND ENDOMETRIAL CANCER-
Tamoxifen is a safe and effective adjuvant tratment for women  with  estrogen
receptor  positive,  node  negative  breast  cancer,  but  is associated with
increased risk  for  endometrial  cancer.   Patients  with  abnormal bleeding
should  include  pelvic  exam,  endocervical  and  endometrial  curettage  or
aspiration.  Pap smears may show atypical  endometrial  cells,  but  are  not
reliable.

                        -TEMPORAL ARTERITIS-
Temporal arteritis (TA) is a disease  of  the elderly.  Most of the cases are
over the age of 50 with a prevalence of 1 per 1000.  Women are affected  more
than  men.   It  may be associated with polymyalgia rheumatica.  The affected
arteries are in the head and  neck  and involve medium to large arteries.  It
is a segmental  disease  and  most  commonly  affects  the  temporal  artery,
internal  carotid or vertebral arteries, facial artery and ophthalmic artery.
CLINICAL: Patients may present with systemic symptoms of fatigue, malaise and
fever.  They also may have  temporal  or occipital headaches, visual loss and
aortic arch symptoms.  Visual loss can account for 15%  of  the  cases.   The
visual  aberrations  may  cause amaurosis fugax, scotomata, blurring, ptosis,
and diplopia.  There may  be  scalp  tenderness.  Physical examination of the
temporal artery may reveal tenderness,  prominence,  and  induration  of  the
artery.   Claudication  of  the masseters, and tongue may be present.  If the
patient also has  polymyalgia  rheumatica  there  will  be aching and morning
stiffness in the shoulder and  hip  girdles.   HISTOLOGY:  A  biopsy  of  the
temporal  artery  is  diagnostic  but  is often times negative because of the
segmental involvement.  Long segment  and  bilateral surgical sampling of the
artery may increase the diagnostic yield.  Typically there is a granulomatous
inflammatory infiltrate seen with lymphocytes, histiocytes and multinucleated
giant  cells.   There  is  degeneration  of  the  internal  elastic   lamina.
LABORATORY:  There is usually a normochromic normocytic anemia.  The alkaline
phosphatase may be increased  and  there  may be thrombocytosis, leukocytosis
and a polyclonal hyperglobulinemia.  The most characteristic finding,  albeit
non  specific  finding  is a marked elevation of the Westergren sedimentation
rate.  This elevation may be over 100  mm/hour.  In about 1 per cent of cases
the sed rate is normal.  Immunogenetic studies have shown that  there  is  an
association  of  temporal arteritis with the presence of HLA-DR4.  TREATMENT:
Because  of  the  potential  for  blindness,  prednisone  should  be  started
immediately.  The usual starting dose is 60 mg per day.  With this dose there
is usually rapid improvement.  The  prednisone  is maintained at his dose for
about 1 month and then slowly tapered at about 5 mg per week.  The ESR should
be used as a guide for adjusting the prednisone dose.  After one year some of
the patients can discontinue the prednisone, but in others  there  may  be  a
flare  and the prednisone may have to be restarted.  If prednisone is used in
high doses for prolonged  periods  then  azathioprine  or methotrexate may be
added.

                              -TETANUS-
Tetanus still mainly afflicts blacks  in  the  rural south, where exposure to
high  levels  of  Clostridial  spores  and  incomplete  immunity  are  strong
predisposing  factors.   Drug  abuse,  particularly  by  skin   popping   has
contributed  to  some  cases of tetanus.  The incubation period ranges from a
few days to a month  or  even  longer.   Short  incubation periods (a week or
less) are associated with severe and often fatal  disease.   CLINICAL:  LOCAL
TETANUS:  is  fairly  uncommon  and begins with stiffness and pain in muscles
near and proximal to  the  site  of  injury.  Gradually, the patient develops
continuous involuntary spasm  in  the  involved  area.   These  spasms  occur
spontaneously  or  in  response to a variety of stimuli such as noise, light,
and/or touch.  Without treatment, symptoms  may  persist for several weeks or
even months, finally disappearing entirely.  This is the  most  benign  form,
with an overall mortality of only about 1%.  GENERALIZED TETANUS: is the most
common  form.   The  characteristic initial sign is trismus.  The patient may
complain of  a  stiff  neck,  low  grade  fever,  dysphagia,  and rigidity in
abdominal, proximal limb, and or paraspinal muscles.  Persistent trismus  and
facial   spasm   may  produce  a  characteristic  facial  grimace,  or  risus
sardonicus.  A  vise-like  constriction  of  the  chest  muscles  and intense
persistent  spasm  of  the  back   musculature   results   in   opisthotonus.
Superimposed  paroxysms  of generalized, painful tonic contractions may occur
spontaneously or in  response  to  even  the  slightest external stimualtion.
Patients do not lose consciousness during  these  paroxysms.   There  may  be
convulsions.   Laryngospasms  or tonic contraction of the diaphragm and other
respiratory   muscles   can   prevent   adequate   ventilation  necessitating
endotracheal intubation and mechanical ventilation.  There may a mortality of
45-55%, even with treatment.  A minority of patients have no apparent site of
injury and no recollection of an injury, but this absence does not  rule  out
the  diagnosis  of  tetanus,  which  may also follow non-trauma surgery, burn
wounds, otitis  media,  dental  infection,  abortion,  and neonatal umbilical
stump  infection.   DIFFERENTIAL   DIAGNOSIS:   Hypocalcemic   tetany,   drug
withdrawal  (dilated  pupils,  pilorection, impaired consciousness), dystonic
drug reaction (rapid response to Benadryl), dental or retropharyngeal abscess
(lack of truncal and extremity findings), meningitis (abnormal spinal fluid),
retroperitoenal hematoma (lack  of  head  and  neck findings), and strychnine
poisoning (shorter duration and urine is positive for strychnine.  TREATMENT:
IMMUNOTHERAPY: Adults should receive receive 3000  units  of  tetanus  immune
globulin  IM,  with  a  range  of  1,500-10,000  units depending on the wound
severity.  Antitoxin of animal origin  is less desirable, since the patient's
serum antitoxin level is not as well maintained and there is a risk for serum
sickness.  However, if horse serum is used, the usual dose is 50,000 units IM
or IV.  Immune globulin or antitoxin can also be injected into the  wound  or
proximally.   Since  acute  infection  with  tetanus  does ot confer immunity
against subsequent infection,  0.5  ml  of  alum  precipitated tetanus toxoid
(vaccine) is given to adult patients IM during the first week, at 3 weeks and
at six weeks.  ANTIBIOTIC THERAPY AND WOUND THERAPY: Debridement of the wound
can safely be performed 1-2  hours  after  administration  of  antitoxin  and
institution  of antibiotic therapy.  Penicillin G 6-10 million units IV daily
remains the drug regimen of  choice  for eradication of Clostridium tetani in
adults.  Tetracycline 2 grams po/day may be used  in  those  with  penicillin
allergy.  Give for 10 days.  CONTROL OF MUSCLE SPASMS: Phenobarbigtal 100-200
mg  IV  or  IM every 3-4 hours + Thorazine 75-100 mg IM every 3-4 hours (with
methadone  10-15  mg  IM  every  4  hours  in  narcotic  addicts  to  prevent
withdrawal.  If muscle spasms persist, Valium  10  mg IV may be given instead
of phenobarbital and chlorpromazine, every 1-3 hours as  needed.   If  spasms
still  persist,  the patient requires mechanical ventilation and curare (9-15
mg IV over 10  minutes  every  hour,  tapered  gradually over days or weeks).
MANAGEMENT OF HYPERTHERMIA: Hyperthermia should respond to a  combination  of
Demerol  50  mg,  Thorazine 25 mg and Phenergan 25 mg IV.  MISCELLANEOUS: All
patients  with  tetanus  require  a   quiet  environment,  proper  fluid  and
electrolyte  replacement,  adequate  caloric  intake,   prophylaxis   against
pulmonary   embolization   and   gastointestinal   hemorrhage,  treatment  of
intercurrent infections and other  medical  problems, and physical therapy to
prevent contractures.

                        -TETRALOGY OF FALLOT-
Tetralogy  of  Fallot is composed of an overriding aorta, pulmonary stenosis,
ventricular septal defect and right  ventricular hypertrophy.  It is the most
common type of cyanotic heart lesion and accounts for  about  10-15%  of  all
cases  of  congenital  heart disease.  The ventricular septal defect (VSD) is
usually located in  the  membranous  portion  of  the septum.  Obstruction to
right ventricular outflow occurs at  the  infundibular  level  in  50-75%  of
cases,  at  the  valvular  level  rarely,  and  at both sites in 25% or more.
Severe obstruction to right ventricular outflow  and a large VSD results in a
right to left shunt, desaturation and cyanosis.  The magnitude of  the  shunt
dictates  the  degree  of  desaturation  and cyanosis.  The greater the right
ventricular outflow obstruction, the larger the ventricular septal defect and
the lower the systemic  vascular  resistance.   A  right sided aortic arch is
present in 25% of cases and an atrial septal defect in  15%.   CLINICAL:  The
clinical  findings  depend  upon  the  degree  of  right  ventricular outflow
obstruction.  Patients that have a  mild  amount of obstruction are minimally
cyanotic,  or  acyanotic  and  present  as  CHF.   Those  that  have   severe
obstruction  are  cyanotic from birth.  Most patients will have cyanosis by 4
months of age, which is  progressive.   Tetralogy  of Fallot can present in 2
ways.  Newborns often present with evidence of left  sided  failure  that  is
indistinguishable from that seen in large ventricular defects.  Children less
often  present  in  this  manner.  These patients usually have mild pulmonary
stenosis.  Older  children  and  adults  usually  present  with  cyanosis and
exercise intolerance of different degrees.  After walking  or  running,  they
tend  to  squat.   Cyanotic  spells  can also appear in uncontrollable crying
episodes.  The cyanotic spells are usually of sudden onset as is the dyspnea.
In severe episodes the patient  may  develop  syncope and the systolic murmur
can decrease in intensity or even  disappaear.   The  cyanotic  episodes  can
begin  in  the  neonatal period and continue until around the age of 5. It is
unusual for the initial episode to  occur  after the age of 2. These episodes
usually occur in the morning and can last from minutes to hours.   Growth  is
retarded,  and  there  is  easy  fatigabilty.  Physical exam in patients with
moderate to severe pulmonary  stenosis  will  reveal clubbing.  Patients with
mild tetraology of Fallot have  findings  on  physical  examination  that  is
indistinguishable  from  a  large  ventricular  septal defect.  A grade 1-3/6
rough systolic ejection murmur	is heard maximally at the left sternal border
in the third intercostal space.   It  is transmitted well to the suprasternal
notch.  No diastolic murmur is heard.  A systolic thrill may be felt  at  the
left  sternal  border  which transmits to the suprasternal notch, but usually
not to the carotids.  There is an apical ejection click due to a large aorta.
The second heart sound at the pulmonary  area  is soft, but there is a single
loud second sound (A2) which is heard best at the lower left  sternal  border
in  the  third  and fourth intercostal spaces.  LABORATORY: About 50-75% will
have increased hematocrits.   Severe  polycythemia  with a hematocrit greater
than 65% is unusual in infancy.  Chest x-ray in patients with a right to left
shunt shows a normal sized heart, with a right ventricular contour,  a  large
aorta  (right  aortic  arch  in  20%),  and  normal  or  decreased  pulmonary
vasculature.   The  right  ventricular  hypertrophy causes a boot shaped or a
Dutch wooden shoe configuration.  There is a decrease in the size of the main
pulmonary artery segment of the left  border  of the heart.  In some cases it
may appear concave.  The ECG will always show right  ventricular  hypertrophy
with  a  QRS  axis  between 90-150.  Peaked P waves may be present denoting P
pulmonale.  Echo/Doppler  examination  will  reveal  the subaortic malaligned
ventricular defect, and the infundibular stenosis.   Cardiac  catheterization
should  be  performed prior to surgery.  It is done to assess coronary artery
anatomy, pulmonary artery morphology and additional ventricular defects.  The
pressure tracings  show  essentially  identical  right  and  left ventricular
pressure pulses.  The pulmonary arterial pressure is  less  than  12  mm  Hg.
There may be a slight increase in the A wave in the right atrium.  There is a
small,  if  any,  left  to  right  shunt  at the ventricualr level.  There is
arterial blood desaturation  of  varying  degree.   The  right  to left shunt
exists at the ventricular level.  Systemic flow is normal while the pulmonary
flow is low at 1-3 L/m2 of body surface area.  An aortic  root  injection  or
selective  coronary  angiography  is necessary to reveal any anomalies of the
coronary artery.  Five percent of  patients will have the anterior descending
coronary artery originating from  the  right  coronary  artery.   Failure  to
recognize  this  anomaly can result in myocardial infarction.  COMPLICATIONS:
Cerebral vascular  accident  can  occur  after  a  hypoxic  spell,  during or
following  cardiac   catheterization   or   surgery,   and   brain   abscess.
Polycythemia,  although a common cause of CVA in adults, ir rarely associated
with CVA in infants and young  children.   Brain abscess may present with any
focal neurologic sign or headache in  a  cyanotic  patients.   Brain  abscess
secondary  to  infective  endocarditis  is  extremely  rare.   Patients  with
uncorrected   tetralogy  of  Fallot  are  prone  to  infective  endocarditis.
Involvement of the aortic  valve  is  a  common site.  TREATMENT: In general,
patients with tetralogy of Fallot should have elective surgery prior  to  the
age  of  1.  Earlier  surgery  can  be  done with essentially the same safety
profile.  Hospital mortality is  usually  less than 5%.  Palliative treatment
is usually recommmended for small infants with severe cyanosis  and  frequent
anoxic  episodes,  and  patients  with  an  anomalous  coronary artery (conus
coronary artery).  This is usually accomplished by the creation of a systemic
arterial to pulmonary arterial  anastomosis (Blalock-Taussig procedure).  The
Blalock-Taussig procedure anastomoses the subclavian artery to the  pulmonary
artery.   It  is  usually  done  on  the  side  opposite the aortic arch.  An
anastomosis between the ascending  aorta  and  the  main pulmonary artery may
also be performed.  The mortality for the Blalock-Taussig  surgery  is  about
1-3%,  depending on the age of the patient and the skill of the surgeon.  The
results are are very good with a decrease in the cyanosis and clubbing.  Most
surgeons consider this as a temporizing  measure and prefer to follow up with
a more definitive procedure after a year or two.  Total correction is carried
out using cardiopulmonary bypass and  consists  of  closing  the  ventricular
septal  defect  through  a  right  ventricular  approach, and alleviating the
obstruction to right ventricular outflow.   The  size of the pulmonary artery
and its branches can compromise  the  outcome.   The  mortality  rate  varies
between  2-15%.   The  post-operative  course may be complicated by pulmonary
regurgitation,  right   ventricular   dysfunction,  ventricular  arrhythmias,
residual pulmonary stenosis, residual VSD and sudden death.

                      -THEOPHYLLINE TOXICITY-
Theophylline toxicity is a very  common  problem because of the drug's narrow
therapeutic index.  Theophylline is almost entirely eliminated by  the  liver
using  the  cytochrome  oxidase  system.   About 90% is eliminated by hepatic
metabolism and about 10% by urinary excretion.   The half life of the drug is
contingent upon the age of the patient and co-administration of  other  drugs
and  illnesses.   Any  disease  that  causes  liver dysfunction can delay the
breakdown  of  theophylline   and   cause   toxicity.   Medications  such  as
cimetidine,   cephlalexin,   allopurinol,    caffeine,    nifedipine,    oral
contraceptives,   propranolol,  tetracycline,  ranitidine,  erythromycin  and
ciprofloxacin  can  increase  theophylline  levels.   Also  congestive  heart
failure, and  viral  diseases  such  as  influenza  can  lead to theophylline
intoxication.  The half life of the drug is about 20 hours in  newborns,  6-7
hours  in infants, 3-5 hours from ages 6 months to 18 years and 4-6 hours for
adults.   Theophylline  comes  as  intravenous  solutions  of  aminophylline,
capsules, tablets,  suspensions,  and  sustained  release formulations.  Peak
blood levels occur rapidly after  ingestion.   After  liquid  ingestion  peak
levels  are reached in about 1-1.5 hours.  After tablets, 1-3 hours and after
sustained  release  preparations  3-10  hours.   Protein  binding  is between
15-40%.  An acute single dose greater than 10 mg/kg will give  mild  toxicity
while if greater than 20 mg/kg will yield moderate toxicity.  Theophylline is
a  phosphodiesterase  inhibitor  which  produces an increase in intracellular
cAMP,  a  mediator  of  beta-adrenergic   effects.   Also,  at  toxic  levels
catecholamines are released.  The combination of  these  effects  produces  a
profound beta stimulation and is responsible for the clinical symptomatology.
CLINICAL:  There  are  two  types of theophylline toxicity-acute and chronic.
Acute toxicity is usually due  to  an intentional overdose.  Chronic toxicity
is usually seen in a person who has been on the medication, but due  to  age,
liver  disease,  erroneously  prescribed  doses,  concomitant illness or drug
administration,  congestive  heart  failure,  etc,  develops  toxicity.   The
patient with an acute overdose  will present with gastrointestinal complaints
while patients that develop toxicity on a  chronic  basis  usually  have  few
gastrointestinal  complaints.   Also,  in  chronic  overdose  there  is  poor
correlation  in  theophylline  serum levels and the severity of the overdose.
Patients that ingest massive doses  of theophylline can tolerate higher serum
levels than those with chronic intoxication.  Patients  with  acute  overdose
more  commonly  have  metabolic  alterations  such  as  hypokalemia  due to a
theophylline  induced  intracellualr   shift   of  potassium,  hyperglycemia,
metabolic  acidosis,  hypophosphatemia,  hypocalcemia   and   hypomagnesemia.
Theophylline  toxicity  can  cause  gastrointestinal, central nervous system,
gastrointestinal, and metabolic  changes.   Nausea  and vomiting are commonly
present, due to local gastric irritation and central nervous system  changes.
Diarrhea  and  gastrointestinal  bleeding  can develop.  The patient may also
manifest agitation, tinnitus,  tremors,  seizures,  coma, delirium, insomnia,
and tachyarrhythmias.  Ventricular and supraventricular tachyarrhythmias  are
common  and  are due to hypokalemia, high catecholamine levels and a decrease
of the ventricular  fibrillation  threshold.   These tachyarrythmias are much
more common in patients that  are  over  the  age  of  40  with  theophylline
concentrations higher than 50 ug/mL.  Younger patients with overdose, usually
require  a  higher  concentration  before tachyarrhythmias become bothersome.
Hypotension due  to  theophylline-induced  reduction  of  peripheral vascular
resistance is alos seen.  Seizures are particularly seen in infants less  tha
6  months  of  age  and  elderly  patients  greater  than 60.  Most often the
seizures  are  generalized,  but  can   be  focal.   Laboratory  findings  in
theophylline toxicity may  include  hypocalcemia,  hypomagnesemia,  increased
amylase,   uric  acid,  BUN,  and  creatinine,  leukocytosis,  hyperglycemia,
hypophosphatemia, hypokalemia, metabolic  acidosis, respiratory alkalosis and
ketosis.  Rhabdomyolysis may  produce  elevated  creatine  phosphokinase  and
myoglobinuria.   DIFFERENTIAL  DIAGNOSIS:  Any disease or medications that is
capable of  causing  beta  adrenergic  stimulation  can simulate theophylline
toxicity.   Such   diseases   and   medications   include   sympathomimetics,
anticholinergics,  hallucinogens,  epinephrine, MAO inhibitors, amphetamines,
drug  withdrawal,   psychiatric   diseases,   electrolyte   alterations,  CNS
infections, pheochromocytoma, hypoglycemia, hypocalcemia, and thryrotoxicosis
or thyroid storm.  THERAPY:  As  always,  in  any  emergency,  the  patient's
airway,  breathing, and circulation should be stabilized.  If the patient has
a  compromised  airway,   intubation   should   be   carried   out  prior  to
gastrointestinal decontamination.  If the patient has a gag reflex this would
be an indication that the patient may be able  to  protect  his  airway  from
aspiration.   Ipecac  may be given if the patient is responsive and has a gag
reflex.  However, in most  cases  gastric  lavage is probably better, because
the patient has already been vomiting due to the theophylline toxicity.  This
can be accomplished by passing a large bore tube such as a 36-40 French,  and
giving  200  cc  aliquots  of  water  or saline and then withdrawing.  If the
patient presents to the emergency  room  late, and has overdosed on sustained
releasing preparations, whole  bowel  irrigation  with  polyethytlene  glycol
solution may be indicated.  Following lavage, charcoal should be administered
at  a dose of 1 gram/kg and given every 2 hours.  Alternatively, a continuous
charcoal flurry drip can  be  given  at .25-0.5 grams/kg/hour via nasogastric
tube.  Charcoal has an avid affinity for binding theophylline in the lumen of
the gastrointestinal tract, and can also cause back diffusion from the  blood
stream  into  the  gut.   Sorbitol can be administered with the first dose of
charcoal to promote  excretion  of  stool  and  prevent constipation.  If the
patient vomits the charcoal, a nasogatric  tube  should  be  passed  and  the
charcoal given via the tube.  Metaclopramide, up to 1 mg/kg, ranitidine 50 mg
IV or droperidol 2.5 mg IV	 may be given to prevent the nausea and vomiting.
Seizures  are  treated  with  diazepam  initially.   If  diazepam fails, give
phenobarbital at 15 mg/kg at 100  mg/min  IV.   If the seizures are still not
controlled, thiopental may be given with a loading dose of 3-5 mg/kg followed
by a continuous infusion of 2-4 mg/kg/hour.  Phenytoin is not very  effective
in  theophylline  toxicity.   Treatment  of  supraventricular  and ventriular
arrhythmias is with propranolol at 1  mg  in adults or .02 mg/kg in children.
It is repeated every 5-10 minutes until the arrhythmia abates or a total dose
of .1 mg/kg has been given.   Remember,  however,  that  propranolol  may  be
contraindicated  in  asthma  or  COPD.   Propranolol,  however, has been used
successfully in theophylline toxicity.  Perhaps a shorter acting beta blocker
such as esmolol  would  be  safer.   If  there  is overt bronchoconstriction,
propranolol would  be  contraindicated.   Lidocaine  may  also  be  used  for
ventricular  arrhythmias.   Contributing  factors  for  arrhythmias,  such as
hypoxemia, hypokalemia, acidosis, hypomagnesemia, and hypocalcemia should all
be corrected.  Hypotension  is  treated  with fluid administration.  Charcoal
hemoperfusion should be started  if  the  patient  presents  with  refractory
status    epilepticus,   arrhythmias   and   is   hemodynamically   unstable.
Theophylline levels should  be  done  frequently  and  in  those with rapidly
rising levels in spite of conventional therapy, charcoal hemoperfusion may be
life saving.   Charcoal  hemoperfusion  is  4-6  times  more  effective  than
hemodialysis, and can lower theophylline levels to nontoxic levels in about 3
hours.   It  requires  that  the  patient  be anticoagulated and it may cause
thrombocytopenia and hypocalcemia.  Indications for charcoal hemoperfusion in
ACUTE ingestions is a theophylline level  greater than 100 ug/dL.  In CHRONIC
ingestions, hemoperfusion should be started if the level is 60-90  ug/dL,  or
the level is between 40-60 ug/dL and the age is less than 6 months or greater
than 60 years, or the patient has liver disease and congestive heart failure.
Any  patient that has refractory arrhythmias, seizures or hypotension is also
a candidate for charcoal hemoperfusion.

                   -THROMBOCYTOPENIA (Idiopathic)-
Is caused by an autoantibody which  is  usually  IgG that binds to a specific
platelet glycoprotein, usually IIb and  IIIa.   It  occurs  in  children  and
adults,  with  the  incidence  in  children  peaking  at 2-4 years of age and
frequently follows a viral  infection.   About 80% will spontaneously resolve
within 2-4 weeks and the mortality is < 1%.  The peak incidence in adults  is
20-40  years  of age and is more common in women.  CLINICAL: splenomegaly and
lymphadenopathy are almost never found, and  if these do occur, another cause
should  be  entertained.   Anemia  would  suggest  an  autoimmune   hemolytic
possiblity.   The  platelets  are reduced in number, but usually increased in
size.   Illnesses   that   are   associated   with   ITP  include  infectious
mononyucleosis, SLE, Hodgkin's disease,  and  chronic  lymphocytic  leukemia.
Obtain   antinuclear  antibodies,  rheumatoid  factor  and  thyroid  function
testing.  Bone marrow studies  may  show  normal or increased megakaryocytes.
Platelet associated IgG levels are usually  elevated  in  ITP.   ITP  usually
flares  after  a  viral  infection and may surface after ingesting aspirin or
alcohol.  TREATMENT: Platelet counts between 40,000-80,000, no bleeding and a
normal bleeding time probably do not  require treatment.  Severe acute ITP in
childhood should be treated with high dose intravenous immune globulin (IVIG)
1-2  g/kg  over  2  days.   IVIG  will  block  the  Fc   receptors   of   the
reticuloendothelial   system   and   also  can  neutralize  the  antiplatelet
autoantibodies.  Adults are treated with prednisone 1-2 mg/kg/day, which will
raise the platelets in 1-2 weeks.  Once platelets reach 100,000, tapering can
be begun.  Only about  10%  of  patients  trated  with prednisone have a long
lasting remission, and splenectomy will be needed in most adults.   Prior  to
surgery  the patient should receive pneumococcal vaccine, prednisone or IVIG.
Patients with low platelets  can  be  given  platelets transfusions after the
splenic pedicle has been clamped.  The surgeon should make sure all accessory
splenic  tissue  is  extirpated.   Patients  who  respond  temporarily  after
splenectomy and then relapse, should receive platelet scanning to find out if
splenic remnants are present.  Life threatening bleeding  should  be  treated
with  high  dose  IVIG  1  g/kg  over  6 hours for 2 days.  Refractory ITP is
treated with danazol, pulse dose steroids, azathioprine, cyclophosphamide and
Vinca alkaloids  vincristine).   ITP  in  pregnancy  is  common  and requires
treatment of the mother and fetus.  Steroids or high dose IVIG  is  given  to
pregnant  patients with severe ITP.  Incidental thrombocytopenia occurring in
pregnancy  with   counts   between   75,000-150,000   requires   no  therapy.
Approximately  50%  of  infants  born  to  mothers   with   ITP   will   have
thrombocytopenia.   Daily  platelet  counts are reqired in the infant because
the lowest paltelet count is not reached until several days after birth.

              -THROMBOEMBOLISM PROPHYLAXIS IN SURGERY-
Those  at  risk  include,  prolonged  anesthesia  or surgery, previous venous
thromboembolic  problems,  malignancy,   obesity,  immobilized  or  paralyzed
patients, estrogen use, varicosities and elderly  patients.   ORTHOPEDIC  HIP
FRACTURE  OR  ARTHROPLASTY:  the  risk  is  40-55%.   Should  be treated with
warfarin 10 mg the  night  before  surgery,  5  mg  the  night of surgery and
subsequent daily doses to produce a  PT  ratio  (Patient  PT/Control  PT)  of
1.2-1.3  until  the  patient  is ambulatory OR give similar therapy beginning
10-14 days prior to  surgery  and  continued until full ambulation.  Adjusted
low dose heparin may also be used by giving heparin 2 days prior  to  surgery
starting  at  3,500-5000 units subq q8h and increasing to achieve a PTT ratio
of 1.2-1.3 until  full  ambulation.   The  PTT  is  drawn  6 hours after subq
injection in order to adjust the dose.  Pneumatic compression and Dextran  70
may  also  be used.  GYNECOLOGIC BENIGN SURGERY: risk is 5-15%.  Give heparin
5000 units subq 2 hours prior  to surgery and q8-12h afterwards until patient
is ambulatory.  GYNECOLOGIC MALIGNANT SURGERY: Risk is 15-35%.  Use pneumatic
compression or Dextran 70.  GENERAL SURGERY: the risk is 15-35%.  Treat  with
Heparin  5000  U subq 2 hrs prior to surgery and every 8-12h until ambulatory
or pneumatic  compression.   UROLOGIC  OPEN  PROSTATECTOMY:  risk  is 20-50%.
Treat with heparin or pneumatic compression.

                        -THROMBOLYTIC THERAPY-
Thrombolytic therapy has now  become  the  main treatment in acute myocardial
infarction.  It is beneficial in those with ischemic  pain  of  less  than  6
hours, the earlier the better.  It is beneficial mainly in acute anterior MI,
but  also  of  some  benefit  in  inferior  acute  MI, especially if there is
extension laterally or posteriorly and if  there is a large transmural injury
current as indicated by ST elevation.  Thrombolytic therapy may be used up to
about 75 years of age in those that do not have any contraindications.  There
is proven benefit in left ventricular function  as  manifested  by  a  10-15%
increase in LV ejection fraction and a decrease in the size of the myocardial
infarction by 20-35%, if the therapy is given by 3-4 hours after the onset of
pain.   There is early coronary patency established in 70-80% of all patients
and mortality is  reduced  by  20-50%  for  patients  treated  under 6 hours.
CONTRAINDICATIONS: Active internal  bleeding,  history  of  hemorrhagic  CVA,
suspected  aortic  dissection,  recent  CNS  procedure of less than 2 months,
prolonged or traumatic CPR, history of stroke of any cause especially if less
than 6 months, BP greater  thean  200/120 mm Hg, known intracranial neoplasm,
pregnancy or early post  partum,  diabetic  hermorrhagic  retinopathy,  other
hemorrhagic  eye  conditions,  previous allergic reaction to the thrombolytic
agent,   and   recent   trauma,    organ   biopsy   or   surgery.    RELATIVE
CONTRAINDICATIONS: Recent trauma, surgery or organ biopsy  greater  than  two
weeks,  active  peptic  ulcer,  recent  GI or GU bleeding less than 6 months,
history of chronic severe hypertension  with or without drug therapy, current
use of full dose anticoagulants, known bleeding diathesis, significant  liver
dysfunction,  artificial  heart valves, known left ventricular mural thrombus
or aneurysm, prior use  of  streptokinase or APSAC (Anistreplase), especially
within 1 year.  STREPTOKINASE: Streptokinase  is  given  at  a  dose  of  1.5
million  units infused over 30-60 minutes.  ASA, 160-325 mg chewable is given
immediatley followed by enteric coated  ASA  325  mg daily.  Heparin is by IV
infusion at 1000 U/hr after 2-4 hours or when the PTT is less than 2-3  times
normal,  and  is continued for 2-5 days.  Alternatively, the heparin is given
SC at 12,500 Units  BID,  started  at  4-12  hrs  and continued for 3-7 days.
Streptokinase is not fibrin selective.  The cost is low compared to t-PA  and
APSAC.   However,  it  is  antigenic.  The reocclusion risk is low and stroke
risk is  reduced.   It  may  cause  hypotension  and  there  is lower, slower
reperfusion rates especially if given after 4 hours.  Diphenhydramine  50  mg
IV  push  and  methylprednisolone  250  mg  IV  push  may be given because of
streptokinases's  antigenicity.   PTT  and  fibrinogen  should  be  drawn  as
baseline prior to therapy and every 4  hours for 24 hours.  The PTT should be
maintained at 1.5-2 times control.  TPA: (Alteplase) (Activase) is given at a
dose of 100 mg that is infused over a 3 hour period  as  follows:  10  mg  is
given  over  a  10  minute  period  followed  by  50 mg over a 1 hour period,
followed by 20 mg given over a 1  hour period x 2. If the patient weighs less
than 60 kg, the total dose is adjusted to 1.5 mg/kg.  Chewable ASA  is  given
at  160-325 mg immediately followed by enteric coated ASA at a dose of 325 mg
daily.  A heparin loading dose of 5000 U  is given IV at the start of t-PA or
before the end of the t-PA infusion, followed by 1000 U/hr  and  titrated  to
keep  the  PTT  at  1.5-2.5  times  the  upper normal limits.  The heparin is
continued for 2-5 days.  The advantage  of  using  t-PA is that there is more
rapid early reperfusion rates, it is not allergenic  and  is  well  tolerated
hemodynamically.   The disadvantages are that it is the most expensive, has a
high reocclusion  risk,  has  a  long  complex  infusion,  requires immediate
heparin in order to maintain late patiency,  and  there  is  a  dose  related
increase  in risk for hemorrhage.  T-PA has a short half life of 5-10 minutes
and is fibrin selective,  but  is  not  antigenic as streptokinase and APSAC.
The GUSTO study demonstrated that by using a front loaded  regimen  a  higher
early patency rate could be achieved than by using the standard t-PA regimen.
For  the  front  loaded  regimen give a 15 mg IV bolus, then 50 mg IV over 30
minutes, followed by 35 mg over a  1  hour  period for a total of 100 mg.  In
the GUSTO trial, patients received 5000 units of heparin IV as a loading dose
followed by 1000 units per hour constant infusion and titrated every 6  hours
to  maintain an APTT of 60-85 seconds for at least 48 hours.  APSAC (Eminase,
Anistreplase) is adminstered as  a  30  unit  bolus  over  a 5 minute period.
Heparin is given as an IV infusion at  1000  units/hour  starting  4-6  hours
after  APSAC  is  given.   Chewable  ASA  is  given immediately as 160-325 mg
followed by enteric coated ASA at  325  mg  daily.  The half life of APSAC is
the longest of the three  thrombolytic  agents,  90  minutes.   The  cost  is
moderate  to high, and is antigenic just as streptokinase.  The advantages of
APSAC is easy administration,  high  early  patency and low reocclusion risk.
The disadvantages include slower reperfusion rates if given  after  4  hours,
moderately  expensive  and  it is antigenic.  Every subgroup of patients with
acute myocardial infarction will  benefit  from  thrombolytic therapy such as
those with prior bypass surgery, prior myocardial infarction,  inferior  wall
myocardial infarctions, LBBB and patients older than age 75.  It is true that
the  complication  rate is higher for patients older than 75, but the reduced
mortality rate is impressive.  Even  if  the patient presents to the hospital
between 6-12 hours after the onset of acute  myocardial  infarction,  benefit
has  been  shown  from thrombolytic therapy by the LATE study.  In this study
there was a 27% reduction in  mortality  using  t-PA between the 6th and 12th
hours.  SUMMARY: Even with all of the previous trials, there is still no real
solution as to which thrombolytic agent  should  be  given.   Several  points
however, can be made that might guide one in the right direction.  The agents
should  be  used  more often than they are presently being used and should be
administered  as  early  as   possible,   as  several  studies  have  clearly
demonstrated a thremendous survival advantage if any of the thrombolytics are
given within the first hour or two of  symptoms.   Alteplase,  given  by  the
front loading regimen will give high early patency rates, but is short acting
and  is  very  dependent on IV heparin to maintain patency.  Streptokinase is
inexpensive, but achieves a  lower  early  artery  patency  than t-PA and the
early artery patency in those  patients  that  present  late  may  be  lower.
However, because of its longer half life, the reocclusion rate may be lower.

           -THROMBOLYTIC THERAPY IN MYOCARDIAL INFARCTION-
In the Global Utilization  of  Streptokinase  and  t-PA for Occluded coronary
artery study (GUSTO), there were findings showing that accelerated  alteplase
and  heparin combination significantly reduced the mortality rate at 24 hours
and 30 days after a myocardial infarction.  This would mean 10 lives would be
saved per 1,000 patients that  were  treated.   In this study there were over
41,000 patients enrolled who had chest pain for up to 6 hours and EKG changes
compatible with MI.   They  received  aspirin  and  were  randomized  into  4
thrombolytic  groups:  There  was  a  front-loaded, weight adjusted alteplase
group where up to 100  mg  of  alteplase  over  90  minutes was given with IV
heparin.  The second group was front loaded, weight adjusted giving alteplase
up to 90 mg over 1 hour and streptokinase 1 million units over 1 hour with IV
heparin.  The third group included streptokinase 1.5  million  units  over  1
hour  with  IV heparin and the last group was streptokinase 1.5 million units
over 1  hour  with  subcutaneous  heparin.   ALTEPLASE:  Alteplase (Activase,
tissue plasminogen activator or t-PA) is a naturally  occurring  enzyme  that
has been cloned into a recombinant DNA drug.  Its half life is 5 minutes, and
the  usual  dose  is  100  mg  IV total for a patient weighing 65 kg or more.
Start by infusing 10 mg initially,  then  50 mg over the first hour, followed
by 20 mg per hour for 2 doses.  It is prepared by reconstituting 100  mg  tPA
(50 mg tPA per vial).  The dose for patients weighing less than 65 kg is 1.25
mg/kg total, and is given as 10% of the total dose IV bolus over 1-2 minutes,
then use an IV pump to infuse 50% during the first hour and 20% in the second
and  third  hours.   Using  the front loading method, the patient is given an
initial bolus of 15 mg, then 50  mg  over  the next 30 minutes and 35 mg over
the next 60 minutes for patients weighing greater  than  65  kg.   The  front
loading  dose  for  less than 65 kg is 15 mg IV bolus, then use an IV pump to
infuse 0.75 mg/kg over 30 minutes (up to 50 mg) and 0.5 mg/kg over 60 minutes
(up to 35 mg).  Because of the short  half life Heparin 5000 U by IV bolus is
given, followed by heparin 15 U/kg/h infusion after tPA and adjust to PTT  of
1.5-2  times  control.   Aspirin  325  mg  is  chewed  by patients also.  The
peripheral lytic  state  and  anticoagulant  effect  is  mild.   There  is no
hypotension or antigenicity.  If  administered  in  the  first  3  hours  the
reperfusion rates are about 70%.  There may be a higher incidence of cerebral
hemorrhage.   The reocclusion rate is 10-30%.  Alteplase binds to plasminogen
and catalyzes the conversion  of  plasminogen  to  plasmin in the presence of
fibrin.  Because of its attraction for fibrin, alteplase concentrates at  the
clot  site  which  results in only a minimal decrease in the fibrinogen.  The
cost of  alteplase  is  about  $2,200  per  dose.  ANISTREPLASE: Anistreplase
(APSAC, Eminase) is a complex of human plasminogen  bound  to  streptokinase.
This  complex  will bind to fibrin and convert plasminogen to plasmin.  There
is fibrinogen depletion because of the  peripheral clot lysis which can cause
bleeding complications.  Anistreplase has a half life of 90 minutes.   It  is
antigenic and may cause an allergic reaction.  The cost of an average dose is
about  $1,700.  Treatment consists of 30 units IV over 2-5 minutes along with
aspirin 325 mg chewed and Heparin 5000 U IV push and diphenhydramine 50 mg IV
and methylprednisolone 250 mg IV.  Heparin  is maintained at 10 U/kg per hour
IV to keep the PTT 1.5-2 times the control.  The coronary  recanalization  at
90  minutes  is  about  50-65%.  APSAC can cause hypotension.  Reocclusion is
between  5-20%.   There   is   a   moderate   amount   of  clot  selectivity.
STREPTOKINASE: Streptokinase (Kabikinase, Streptase) is a  bacterial  protein
that binds to plasminogen and catalyzes to plasmin formation.  There is a low
specificity  for clot selectivity with a peripheral lytic state induced.  The
Blood pressure can be reduced,  and  there is antigenicity.  The half-life is
20-25 minutes.  The reperfusion rate is 55-60% at 3 hours.  There is a  5-20%
reocclusion rate.  The cost per dose is about $400.00.  Treatment consists of
Streptokinase  1.5  million  IU  in  100 ml NS IV over 60 minutes, along with
Aspirin 325 mg chewed, and Heparin  5000  U IV push and Diphenhydramine 50 mg
IV and Methylprednisolone 250 mg IV.  Heparin maintenance is at 10  U/kg  per
hour   IV   to  maintain  the  PTT  1.5-2  times  control.   INDICATIONS  FOR
THROMBOLYTIC THERAPY: The patient  should  have  ST  segment elevation in two
contiguous EKG leads and a suspicion  of  Q  wave  infarction.   The  patient
should  be given the thrombolytic therapy under 6 hours for best results, but
if given later there may be  some  benefit.   Some  would give up to 12 hours
under certain circumstances, but this would be rare.  The patient should have
typical pain of myocardial infarction.  Chest pain secondary to peptic  ulcer
disease    and    aortic    dissection    would    be   a   contraindication.
CONTRAINDICATIONS: Contraindications would  include active internal bleeding.
Any history of intracranial neoplasm, arteriovenous malformation or aneurysm,
intracranial or intraspinal surgery, prolonged cardiopulmonary resuscitation,
pregnancy,  trauma  or  CVA  within  the   past   2   months   would   be   a
contraindication.  The systolic blood pressure should not be greater than 180
and  the  diastolic  should be less than 110.  PRECAUTIONS: Precautions would
include any  major  surgery,  obstetrical  delivery,  organ  biopsy, previous
puncture of a non-compressible vessel, GU or serious GI bleeding  and  trauma
within   the  past  10  days.   Acute  pericarditis  and  subacute  bacterial
endocarditis,    diabetic    retinopathy,     liver    dysfunction,    septic
thrombophlebitis or occluded AV cannula would all  deserve  attention  before
proceeding  with  thrombolytics.   Older  patients have a higher complication
rate, but do  benefit,  especially  if  the  infarct is large.  Intramuscular
injections should be avoided.  TREATMENT OF THROMBOLYTIC ASSOCIATED BLEEDING:
If  thrombolytic  associated  bleeding  occurs,  discontinue   thrombolytics,
aspirin  and  heparin.   Consider giving protamine sulfate, 1 mg IV for every
100 units of heparin infused in the  preceding 2 hours.  Dilute this in 50 ml
of fluid and give IV over 10-20 minutes.  (max of 50 mg in  10  min  period).
Watch for signs of anaphylaxis.  Give cryoprecipitate 10 units IV.  Repeat 10
units  if  still bleeding and the fibrinogen is < 1.0 g/L.  If still bleeding
give 2 units of fresh frozen plasma.  If still bleeding and the bleeding time
> 9 minutes  give  platelets,  8-16  units.   If  less  than  9 minutes, give
aminocaproic acid as a loading dose of 5 g (.1 g/kg)

                -THROMBOTIC THROMBOCYTOPENIC PURPURA-
Is characterized by  thromgbocytopenia,  anemia,  fever, neurologic signs and
renal abnormalities.  There is a microangiopathic hemolytic  anemia  that  is
normochromic-normocytic.     The    prothrombin   time,   activated   parital
thromboplastin  time,  fibrinogen  and  Coombs'  test  are  all  normal.  The
syndrome is related to pregnancy and oral contraceptives, but  the  cause  is
unknown  in most cases.  CLINICAL: Bleeding occurs in 96% of cases consisting
of hematuria, gingival bleeding,  melena, menorrhagia, petechiae and purpura,
retinal  bleeding,  hemoptysis  and  hematemesis.   Neurologic  signs  change
frequently and  are  remittant,  and  consist  of  mental  changes,  paresis,
seizures,  coma,  headache,  syncope,  aphasia,  dysarthria, visual symptoms,
vertigo,  agitation,  delirum  and   confusion.    Renal  changes  include  a
creatinine of > 1.5 in less than 20%, but  when  presnet  is  an  unfavorable
sign.   UA  will  show  hematuria, proteinuria, casts, and pyria.  Pathologic
changes include  widespread  intraluminal  hyaline  vascular  occlusions with
platelet  aggregates  and  fibrin  with  no  inflammatory  changes   in   the
capillaries or terminal arterioles.  The best biopsy site is the bone marrow,
but   gingiva,  skin,  muscle,  petechiae,  and  lymph  nodes  may  be  used.
TREATMENT: is with  plasmapheresis  with  replacement  of fresh frozen plasma
(plasma exchange).  Other treatments  include  dipyridamole  400-600  mg/day,
aspirin  300 twice a week to 600-1200 mg/day, and prednisone at 60 mg/kg/day.
The response rate to therapy is about 80-90%.

                     -THYROIDITIS (Hashimoto's)-
Hashimoto's  thyroiditis  is  also  known as chronic lymphocytic thyroiditis,
autoimmune  thyroiditis,   Hashimoto's   struma,   struma   lymphomatosa  and
lymphadenoid goiter.  It  is  probably  the  most  common  cause  of  primary
hypothyroidism.   It  is much more common in women with a ratio of 8:1 and is
seen most frequently between the ages of  30  and 50.  It is is thought to be
an autoimmune disease because of significant titers  of  anti-microsomal  and
antithyroglobulin  antibodies.  There commonly is a family history of thyroid
disorders.  There is  an  increased  incidence  in  patients with chromosomal
diseases such as Down's, Turner's and Klinefelter's syndrome.  It also has  a
higher   frequency   in  pernicious  anemia,  Addison's  disease,  rheumatoid
arthritis, Sjogren's syndrome,  idiopathic thrombocytopenic purpura, diabetes
mellitus, and myasthenia gravis.  There may  be  an  increased  incidence  of
papillary  carcinoma  and  thyroid  lymphoma in Hashimoto's thyroiditis.  Two
varieties of Hashimoto's thyroiditis may appear.  The most common form is the
goitrous type.  However, the  atrophic  and  fibrotic  variant may be seen in
elderly patients.  CLINICAL: The  onset  is  usually  insidious  and  may  be
variable.   Most  will  have  a  goiter  that  is diffusely enlarged, but the
enlargement may  be  asymmetrical,  and  there  may  be  some irregularity to
palpation.  Fine needle aspiration of these bosselations  may  be  needed  to
rule  out  malignancy.   Pain  and  tenderness, if present at all, usually is
mild.  About 25% of patients  will  present as hypothyroid and another 10-15%
will go on to hypothyroidism.  Lithium, iodide and amiodarone may convert  an
euthyroid state to the hypothyroid state.  Rarely, some patients will present
with  hyperthyroidism  that  is  associated with co-existing Graves' disease.
The radioactive iodine uptake is  increased  in these cases plus an elevation
of the antimicrosomal antibodies > 1:2000.  Most  patients  with  Hashimoto's
thyroiditis  will present with normal TSH, T3, T4 and elevated antimicrosomal
antibodies.   However,  with  time   there  is  autoimmune  thyroid  cellular
destruction that leads to an elevated TSH and normal thyroid hormone  levels.
With  further  progressive destruction of the gland there is a decrease of T4
levels leading to overt symptomatic hypothyroidism.  Biopsy usually shows the
characteristic lymphocytic infiltration, oxyphilic  changes in the follicular
cells, fibrosis and  atrophy.   The  differential  diagnosis  of  Hashimoto's
thyroiditis  includes  iodine deficient goiter, early Graves' disease, simple
goiter and lithium  induced  goiter.   TREATMENT:  The  goal  of treatment is
twofold.  The hypothyroidism must be corrected and an attempt to  reduce  the
size  of  the  gland.   Most  patients will respond to l-thyroxine 100-150 ug
daily.  In patients with heart disease start at 25 ug and cautiously increase
by 25 ug every 3-4 weeks.  The  size  of the gland will usually diminish with
l-thyroxine therapy which reduces TSH stimulation of the gland.  If the  size
of  the  gland continues to grow, suspect lymphoma or cancer.  The TSH should
be maintained in the normal range  to prevent increased risk of osteoporosis.
The dose of l-T4 may need to be  increased  in  pregnancy,  malabsorption  or
drugs such as Questran or phenytoin.

                       -THYROIDITIS (SILENT)-
Silent  thyroiditis  is  also  known  as  painless  thyroiditis  or  subacute
lymphocytic  thyroiditis,  and has some of the same features as granulomatous
thyroiditis except there is no  pain.   Both of these conditions have similar
evolutionary  features  as  early  transient  hyperthyroidism   followed   by
transient  hypothyroidism  during the recovery stage.  The clinical course is
essentially the same as  subacute  thyroiditis except that persistent goiter,
permanent hypothyroidism and recurrences of hyperthyroidism are more  likely.
Silent  thyroiditis  is mostly seen in post-partum thyroiditis.  This usually
occurs  2-4  months  following  childbirth  and  may  recur  after subsequent
pregnancies in about 25% of cases.  It is estimated that  up  to  7%  of  all
postpartum  women  will  develop  painless thyroiditis.  Differentiation from
post-partum depression should be  made.   The  disease  is  believed to be an
autoimmune  disorder  as  it  is   associated   with   elevated   titers   of
antimicrosomal  and  antithyroglobulin  antibodies  and  biopsy  demonstrates
lymphocytic   infiltration   that   is   indistinguishable  from  Hashimoto's
thyroiditis.  There may be mild  thyroid  enlargement, but tenderness or pain
is usually absent.  The radioactive thyroid iodine uptake is very low  as  in
subacute  thyroiditis,  factitious hyperthyroidism and iodine ingestion.  The
WBC is normal and the  ESR  is  either normal or mildly elevated.  TREATMENT:
Treatment  of  lymphocytic  painless  thyroiditis  is  similar  to   subacute
thyroiditis.   For symptoms of hyperthyroidism, propranolol may be used.  For
symptomatic hypothyroidism, L-thyroxine may be given.

                      -THYROIDITIS (Subacute)-
Subacute   thyroiditis   also   is   known   as  de  Quervain's  thyroiditis,
granulomatous or  giant  cell  thyroiditis.   It  is  caused  by  a  virus or
rickettsial infection.  Coxsackie and adenovirus are  mostly  involved.   The
disease  usually  occurs  in  females  in the second to fifth decade of life.
Histologic studies of the gland show  giant cell infiltration rather than the
characteristic lymphocytic  infiltration  seen  in  Hashimoto's  thyroiditis.
CLINICAL:  The  patient  usually  presents with a sore throat and pain in the
anterior neck which is associated with  a  low grade fever of 100-101 degrees
F. The patient may also complain of myalgias,  dysphagia  and  fatigue.   The
pain  may  be  aggravated by swallowing or turning the head.  The patient may
have an upper respiratory tract  infection  prior  to or during the course of
the disease.  Examination of the thyroid gland reveals it to  be  tender  and
enlarged,  and  the skin over the thyroid may be erythematous.  Only one lobe
of the thyroid may  be  involved  initially,  but  may spread to the opposite
lobe.  The anterior neck pain has a tendency to radiate to the ear, angle  of
the  jaw  or chest.  Subacute thyroiditis is self limited, but may take a few
months  to  do  so.   It  occasionally  recurs.   Because  there  is  ongoing
destruction of the follicular cells of  the thyroid, the patient will release
preformed hormone into the  circulation  which  will  cause  a  self  limited
hyperthyroid  state  that may last from 3-12 months.  While in this phase the
patient may  exhibit  tachycardia,  insomnia,  tremor,  weight  loss and heat
intolerance.  Following this about  25%  will  develop  hypothyroidism  which
usually  lasts  for  a few weeks to months.  The T4 early in the disease will
show an increase with a decrease  in  the radioactive iodine uptake, often to
less than 2%.  The radioactive  iodine  uptake  will  differentiate  subacute
thyroiditis as the cause of hyperthyroidism from Graves' disease in which the
uptake is elevated.  The TSH will be suppressed and the ESR will be elevated,
oftentimes  greater than 100 mm/hour.  The leukocyte count is usually normal.
Thyroid antibodies  may  be  transient  and  in  low  titer.   As the patient
recovers from the disease the T4 will be low and the TSH  will  be  elevated,
commensurate  with  the  onset  of  hypothyroidism.   This usually occurs 1-2
months after the hyperthyroid phase.   TREATMENT:  Treatment of the neck pain
is with ASA, acetaminophen or nonsteroidal agents.  If these fail to suppress
the inflammatory changes prednisone 10-15 qid will ease the pain in about  24
hours.   Decremental  doses  of  prednisone  should follow over the following
weeks in order to discontinue the  total  dose  in about one month.  The only
treatment recommended for the transient hyperthyroidism is propranolol  20-40
mg  qid which can be discontinued when the T4 returns to normal.  Antithyroid
drugs  and  radioactive  iodine  are   not  used.   If  the  patient  becomes
hypothyroid, as indicated by the elevated TSH, L-thyroxine can be given for a
few months, and then discontinued.  Usual doses are between  100-150  ug/day.
Persistent hypothyroidism is very unusual.

                     -THYROID NODULE (Solitary)-
Benign nodules consist of colloid (adenomatous) nodules that may present as a
dominant nodule but with scanning, ultrasound and surgery they are in reality
multinodular.   Most  of  these  are hypofunctioning by scan, but some may be
hyperfunctioning.  The cytology reveals  colloid and benign follicular cells,
but some are hemorrhagic nodules.  On the other  hand,  the  second  type  of
benign  tumor  (follicular  adenomas)  are usually single lesions with a well
defined capsule.  Malignant  nodules  consist  of  papillary tumors which are
very  cellular  with  large  nuclei  and  a  pale  ground  glass  appearance.
Medullary , anaplastic and lymphomas are the other types of malignant tumors.
The annual incidence of thyroid nodules in the USA is .1%.  The main  concern
is  that  the  nodule may be malignant but only a small number are malignant.
Even if you can only feel one  nodule,  there may be others, and this may not
represent a solitary nodule, but indeed a multinodular goiter which  is  only
rarely  malignant.   Seek  out key questions, as the younger the patient, the
more the probability that  the  nodule  will  be  malignant (The incidence of
cancer in surgically excised solitary nodules ranges from 14- 61%).  The risk
of malignancy is increased if the patient is male and  the  nodule  has  been
growing.  Check for the hardness of the nodule and if there is any associated
lymphadenopathy.   Prior  radiation,  particularly  a  high  dose  in a young
patient, increases the  chance  for  cancer.   Radiation  will also, however,
increase benign nodules.  Check thyroid function with TSH, T3, T4 to  see  if
there is a hyperfunctioning nodule which is uncommon.  These hyperfunctioning
nodules  are  hot  autonomous nodules that suppress TSH.  Hot nodules are not
malignant very often.  Other tests  that  can  be done include thyroid scans,
ultrasound exam and fine  needle  aspiration.   Radioiodine  131  or  123  is
preferable to the technetium scan, but in fact Technetium is used more often.
Radionuclide scans are useful mainly for identifying hyperfunctioning nodules
in   patients   with  indeterminate  or  suspicious  biopsy  who  don't  have
thyrotoxicosis.  About 85% of nodules are cold and 10% warm and 5% hot.  Most
malignant solitary nodules are cold (15%),  but in general, most cold nodules
will turn out to be benign.  Hot nodules are rarely malignant (1%).  About 9%
of warm nodules are cancerous.  Ultrasonography of the thyroid can detect 2-3
mm nodules, but can only determine whether they are solid or  cystic.   About
70%  of  thyroid nodules are solid and 30% cystic or mixed.  About 20% of the
solid tumors turn out to be malignant  and  10 % of the mixed.  Therefore, US
doesn't add that much at a cost of about $250.00 per exam.  US  is  sometimes
useful  for  following  proven  benign  nodules  for an increase in size.  In
recent years, it has been found that suppression of TSH with thyroid hormone,
and then observing the gland for  resolution  of  the nodule or growth is not
reliable.  In the past, it has been thought that if the  nodule  was  benign,
the  nodule  would shrink, and if there was no change in size or growth, then
the nodule  was  malignant.   Now  it  is  known  that  malignant nodules may
regress, and some benign tumors  may  not  decrease  in  size.   Fine  needle
aspiration  is  the  most  important procedure to be done.  The cost of about
$150.00-$200.00 is well worth the information that it provides.  The accuracy
of the biopsy (if an experienced  cytopathologist interprets the slide) is 95
%. About 80-90% of fine needle aspirations are diagnostic and about  20%  are
suspicious.   The procedure is very simple with low rates of complication and
can be done without anesthesia in the  office.  A 25 gauge needle is used and
the aspirated material is smeared on a glass slide and  fixed  in  95%  ethyl
alcohol  and  then  Pap  stained.   The  most important aspect of this is the
interpretation by  an  experienced  cytologist.   The  pathologist  will then
render the report in 3  categories:  benign,  malignant  or  suspicious.   If
malignant,  this  could  represent metastasis rather than primary (papillary,
medullary and  anaplastic).   Benign  tumors  include  cysts, thyroiditis and
colloid nodules.  Suspicious tumors that give the cytologist  difficulty  are
follicular  and  Hurthle  tumors.   If there is a paucity of cells recovered,
then another biopsy may be needed.   If the report returns as suspicious then
surgical excision may be indicated or an ultrasound may be done.  If  a  cold
nodule  is  identified  at  US,  then  surgery  is  indicated.   TREATMENT OF
MALIGNANT NODULES: Some surgeons will treat  small papillary cancers < 1.5 to
2.0 cm isolated to one thyroid lobe with lobectomy and  isthmectomy.   Others
would  do  a  near  total  thyroidectomy.   Large  tumors  or  those that are
multicentric, or metastatic to lymph  nodes,  should be treated with total or
near total thyroidectomy.  After the thyroidectomy  the  patient  returns  in
about  2  months  when  the  TSH should be above 35 mlU and the T4 around 1-2
ug/dl, and receives a radioiodine scan  to ascertain if there is any residual
thyroid tissue.  If some is found then radioiodine ablation is  carried  out.
If  none  is  found  then  the  patient has had a total thyroidectomy and the
patient is placed on suppressive levothyroxine  doses to suppress the TSH and
a T4 in the high normal range.  About 6 months following surgery the  thyroid
is discontinued, and when the patient is hypothyroid a whole body radioiodine
scan  is  performed.  If the scan is negative the levothyroxine is once again
started for life.  The TSH is  kept  at around 0.5 uU per milliliter (normal,
.5-5).  If the malignant  tumor  was  metastatic  or  locally  invasive,  not
completely  removed  or  ablated  by  postoperative radioiodine, then the TSH
should be kept in the  subnormal  range.  TRATMENT FOR INDETERMINATE NODULES:
Surgery is  probably  the  best  approach,  but  the  extent  of  removal  is
controversial.  Total thyroidectomy isn't usually done.  TREATMENT FOR CYSTIC
NODULES:  50%  of cystic nodules will disappear permanently after one or more
aspirations.  However, those that  recur  are  usually  > 4 cm, and moreover,
aspiration of these often yield blood and cannot be  examined  cytologically.
These should be surgically removed.  Thyroid therapy does nothing to suppress
a  cyst.   TREATMENT  FOR  BENIGN NODULES: Most of these are just followed by
observation.  Some  would  use  thyroid  suppressive  therapy.  In particular
children who have had radiation for benign conditions might benefit, as there
has been a 4.5 times higher incidence of recurrence when thyroid wasn't used.

                          -THYROID NODULE-
To evaluate a thyroid nodule,  obtain  a  TSH.   If  normal, do a fine needle
biopsy.  Malignant nodules should be removed  and  benign  nodules  followed.
Repeat   biopsy  if  insufficient  material  is  obtained.   If  results  are
indeterminate on biopsy do radionuclide  scan.   A cold or warm nodule should
be removed.  A hot nodule is followed.  Serum calcium and calcitonin are  not
indicated  routinely.   Antithyroid  antibodies  testing  does  not influence
management.  There is very  little  difference between benign nodules treated
with thyroxine and placebo.  If patient wants treatment for benign nodule can
treat with thyroxine for 6-12 months.

                        -THYROTOXIC CRISIS-
CLINICAL: Patients present with exaggerated symptoms of hyperthyroidism.  The
precipitating   factor   usually   is   a   pulmonary   infection,   diabetic
complications, pulmonary embolism, or  myocardial  infarction.   The  use  of
haloperidol,  recent  iodine  or  surgical  therapy, cessation of antithyroid
drugs may also be causative.  There may be diarrhea and altered mental state,
and young females are commonly  involved.   There may be atrial fibrillation,
elevated temperature, increased pulse pressure, goiter, exophthalmopathy, lid
lag,  arthritis,  pretibial  myxedema,  tender  hepatomegaly,   gynecomastia,
lymphadenopathy,  fine tremor, galactorrhea, and delirium.  LAB: There may be
increase glucose unless  there  is  adrenal  insufficiency, increased calcium
normocytic normochromic anemia, increased transaminases, BUN  and  bilirubin.
The ECG shows sinus tachycardia or supraventricular arrhythmias.  A T4 should
be  done (the T4 may be decreased to normal in the acutely ill).  Also obtain
a thyroid panel,  TSH,  cultures,  chemistries  and  CBC.  TREATMENT: Cooling
blankets and acetaminophen may be used for hyperthermia >104  F.  Salicylates
should not be given because they will displace thryroid hormones from binding
protein,  exacerbating  the  condition.  Cardiac monitoring should be carried
out.  Use B-complex and  IV  fluid  maintenance.   CHF  should be treated and
small doses of propranolol may be  beneficial  by  slowing  the  heart  rate.
Propranolol  is  given  at  2-5  mg  IV  at  1  mg/min  or  40-80  mg PO q6h.
Propranolol will block peripheral  conversion  of  T4  to T3 and decrease the
hyperadrenegrgic effects.  It should not be used in asthma or CHF that is not
due to tachyarrhythmia.  Sodium iodide 1 gm IV q8h or Lugol's solution 30  cc
po  daily  is  started  2 hours after Propylthiouracil is given.  Iodine will
block thyroid hormone release.  Propylthiouracil  is  given at 1 gm through a
nasogastric tube or by rectum as a loading dose, then 400 mg PO daily for 3-6
weeks.  Dexamethasone  is  given  at  2  mg  q6h  until  patient  is  stable.
Dexamethasone  will  block  the peripheral conversion of T4 to T3 and correct
any relative adrenal insufficiency.

                    -TICK BORNE RELAPSING FEVER-
Many patients with tick borne relapsing fever are not aware  that  they  have
been bitten by a tick, but there may be a tell-tale 2-3 mm pruritic exchar at
the site of the bite.  The incubation period is about 4-18 days with a median
of  7  days.   Death in this disease is rare, but occasionally is seen in the
elderly and infants.  If  the  patient  is  pregnant, spontaneous abortion or
transplacental infectivity may occur.  Many  different  strains  of  Borrelia
recurrentis  are responsible for this spirochetal disease.  It is transmitted
to humans by the bite of a  soft tick.  Chipmunks, tree squirrels and rodents
serve as a reservoir.  Tick borne relapsing fever (TBRF) occurs in the USA in
the western portion of the USA.  The vectors of tick  borne  relapsing  fever
are  various  species  of  ornithodoros ticks.  Ornithodoros hermsi transmits
Borrelia hermsii  in  forested  and  mountainous  areas  that  often  have an
elevation above 3000 feet.  Ornithodoros turicata transmits Borrelia turicata
and Ornithodoros parkeri transmits Borrelia parkeri.  TBRF  has  occurred  as
outbreaks  at  the northern rim of the Grand Canyon in Arizona and in western
Texas caves.  The incidence of TBRF  has  its  peak in the summer, but can be
found year-round.  Campers are especially at risk if they use log  cabins  or
mountain homes.  CLINICAL: The onset is sudden.  The patient will complain of
high  fever,  chills, headaches, myalgias and arthralgias, abdominal pain and
tiredness.  There  may  be  conjunctival  suffusion.   The  rash  is macular,
papular or petechial and develops in up to 50%  of  cases.   The  patient  is
markedly  febrile  for 3-6 days, and then has an afebrile period of 5-10 days
and then another febrile  period,  which  accounts  for its name of relapsing
fever.  Without treatment there may be up to 13 relapses, with a mean of 3-5.
Neurologic symptoms may  develop  in  5-10  percent  of  cases.   LABORATORY:
Leukocytosis,  thrombocytopenia and increased erythrocyte sedimentation rates
are common.  Diagnosis is made by demonstrating the spirochete in Giemsa's or
Wright's stained thick and thin  smears.   Dark  field microscopy may also be
used.  If the smears are made while the patient is febrile the sensitivity is
about 70%.  The sensitivity yield may be  increased  by  staining  the  fixed
smears  with  acridine  orange.   TRATMENT:  Various  antibiotics may used in
treatment of the  relapsing  fever.   Tetracyclines, erythromycin, penicillin
and chloramphenicol all may be used,  but  tetracyclines  are  the  drugs  of
choice.   Penicillin  G  has  been  associated  with relapse.  The patient is
usually treated for 5-10 days.   Ceftriaxone  has  also been effective IV.  A
Jarish-Herxheimer reaction may develop  in  patients  receiving  tetracycline
during  the  late  febrile period or between relapses.  It is caused by rapid
destruction of the spirochetes and  is characterized by sudden fever, chills,
hypotension  and  tachycardia.   This  will  usually  last  8-12  hours  with
recovery.  The hypotension is caused by a decrease in  the  total  peripheral
resistance and a compensatory increase in cardiac output.  The hypotension is
treated  with fluids.  Disseminated intravascular coagulation (DIC) is a rare
complication.  If this does develop  it  may  be treated with heparin 600-850
units/kg every 24 hours  via  IV  infusion.   Platelet  concentrates  may  be
needed.   Severe  abdominal  pain should prompt a search for possible splenic
rupture.  Prolonged prothrombin times if  severe and sustained may be treated
with vitamin K1 10 mg IM.

                         -TILT TABLE TESTING-
CLINICAL: Tilt table  testing  is  useful  in  diagnosing  neurally  mediated
syncope  (neurocardiogenic, vasovagal syncope).  Many patients with recurrent
unexplained  syncope  will  have   transient  periods  of  autonomic  nervous
instability which results in inappropriate  hypotension  and/or  bradycardia.
Tilt  table  testing  rarely  will  provoke syncope in normal persons.  Serum
catecholamine levels  rise  rapidly  before  syncope,  and  this  has  led to
low-dose isoproterenol infusions to increase the  sensitivity  of  the  test,
which  may  be  at the expense of specificity.  Normally, assuming an upright
position will provoke an increase in  venous pooling of the lower extremities
with a compensatory increase in  peripheral  vascular  resistance  and  heart
rate.   The  venous  pooling  causes a decrease in afferent impulses from the
cardiac  mechanoreceptors  located  in  the   base  of  the  right  and  left
ventricles, which leads to an increase  in  sympathetic  stimulation  by  the
medulla.   However,  there  may be paradoxical response of periperal vascular
dilatation and bradycardia that may be mediated by sudden fluctuations in the
levels of serotonin.  Therapies  now  evolving  are  base on these reflex and
chemical changes.  THERAPY: It has been known for some time that  lying  down
will  alleviate  the symptoms.  However, many patients do not have the luxury
of a warning prodrome.  Beta blockers have been used successfully by blocking
the ventricular mechanoreceptors,  via  their  negative inotropic properties.
Disopyramide functions  by  a  similar  mechanism  plus  its  anticholinergic
properties.    Transdermal  scopolamine  may  also  be  used  effectively  by
decreasing vagal tone.  Oral theophylline has  been used with success as well
as fluorohydrocotisone which is  a  volume  expander.   If  the  patient  has
warning  signs  sublingual  ergotamine  or hyoscyamine may abort or delay the
attack.  Patients that  are  refractory  to  oral  medications may be treated
witha  permanent  cardiac  pacing.   However,  about  35%  of  patients  with
ventricular pacemakers still have recurrent syncope.  This can be improved by
employing a dual chamber pacemaker which  has  a  tendency  to  decrease  the
magnitude  of hypotension, which lessens the number of drop attacks and leads
to a recognizable presyncopal  state.   New  sensor  technology is leading to
earlier detection of  hypotension,  which  is  usually  a  precursor  to  the
bradycardia.  Fluoxetine (Prozac) is one such useful drug.

                              -TINNITUS-
Tinnitus may either be subjective  or  objective.  In subjective tinnitus the
ringing, buzzing, roaring, hissing or whistling perception is  heard  by  the
patient.   In objective tinnitus, there is usually a vascular turbulence from
increased flow or partial obstruction, and  may be heard with the stethoscope
such  as  a  cranial  bruit.   Tinnitus  can  be  continuous,   intermittent,
pulsatile,  or  non-pulsatile,  and  there  may  associated  hearing deficit.
Causes of  pulsatile  tinnitus  occur  with  cerebral  AVMs (especially dural
AVMs),  carotid  cavernous  fistulas,   hypertension,   cerebral   aneurysms,
hyperthyroidism,  transmitted  bruits  from  aortic  stenosis and the carotid
artery, and glomus jugulare tumors.   Pulsatile tinnitus requires carotid and
vertebral  arteriograms  to  rule  out  aneurysms,  vascular  neoplasms,  and
vascular obstruction.  Causes of non pulsatile tinnitus include otosclerosis,
occlusion of the external ear (such as foreign bodies, cerumen),  middle  ear
infections,  arachnoiditis,  hypothyroidism,  anemia, hereditary sensoineural
hearing  loss,  noise  induced  hearing  loss,  head  trauma,  blast  injury,
petrositis,    syphilis,    meningitis,    eustachian    tube    obstruction,
cerebellopontine angle tumors, labyrinthitis,  carbon monoxide, heavy metals,
stapedial muscle spasms (as in  hemifacial  spasm),  otosclerosis,  Meniere's
disease, and drugs (salicylates, aminoglycoside toxicity, diuretics, alcohol,
and quinine).

                         -TORSADE DE POINTES-
CAUSES:  Torsades de pointes literally means a twisting of the points, and is
characterized as a polymorphic ventricular tachycardia that can be associated
with  QT  prolongation   from   such   drugs   as  Class  IA  antiarrhythmics
(procainamide, quinidine and disopyramide), Class IC  drugs  (flecainide  and
propafenone),  Class III drugs (bretylium, amiodarone and sotalol), potassium
or  magnesium  depletion,  ischemia,  bradycardia  (complete  heart  block or
congential long QT syndrome) and other drugs as phenothiazines, and tricyclic
antidepressants.  If astemizole (Hismanal) or ketoconazole (Nizoral) are used
concurrently with other QT prolonging drugs or in patients  with  electrolyte
abnormalities,  Torsades  de  pointes  may  occur.  THE LONG QT SYNDROME: The
idiopathic long QT syndrome  includes  a  long  QT  interval which is usually
0.5-0.7 seconds, recurrent syncope, ventricular arrhythmias and sudden death.
It is not common and was first described in deaf siblings.  The left stellate
ganglion may be instrumental in the etiology as  anesthetic  blocks  of  this
ganglion may be useful in refractory arrhythmias.  The best treatment for the
congenital  long  QT  syndrome  is  beta  blockers but phenytoin and class IB
agents as mexiletine and tocainide have been beneficial.  Agents that prolong
the QT interval from classes IA,  IC,  and III should be avoided.  TREATMENT:
The drug of choice in treating all acute cases of Torsades de pointes, except
those caused by bradycardia, is magnesium which is given  as  1-4  gm  in  IV
bolus  over  5-15  min  or  infuse  3-20  mg/min  for 7-48 hours until the QT
interval is < 0.5 seconds.  For  those that are caused by bradycardia, atrial
or ventricular pacing between 90-100 beats/min will shorten the QT  interval.
Isoproterenol  (Isuprel)  at  2-20  ug/min  (2  mg in 500 ml D5W) may also be
effective for conversion, or as a temporizing measure until a pacing catheter
can be placed.  Isoproterenol may  increase  ischemia and should be used with
caution.  Phenytoin (Dilantin), 100-300 mg IV given in 50 mg aliquots every 5
minutes may be used.  Propranolol 1-5 mg (0.15 mg/kg) IV  in  1  mg  aliquots
every 5 min has also been successful.

                        -TOURETTE'S SYNDROME-
Tourette's  syndrome  represents  one end of a spectrum of tic disorders, and
because of this may  not  be  diagnosed  for  years.  IMITATORS OF TOURETTE'S
SYNDROME: The mildest form of tic disorder is the transient tic  disorder  of
childhood,  which affects from 4-23% of all children.  Onset is common around
the age of 7 and rare before  age  4.  The  tic is gone after about 6 months.
The tics consist of single or multiple motor or vocal tics,  that  may  occur
many  times  a day, nearly every day, for at least 2 weeks.  Another disorder
known as the chronic tic disorder  is  common  in childhood and should not be
confused with Tourette's syndrome.  In this disorder there may be one or  two
motor  tics  that  affect  the  face or body.  There is not much variety, and
waxing and waning  is  unusual.   The  tics  may  occur  many  times a day or
intermittently for more than 1 year.  Vocal  tics  with  the  motor  tics  is
unusual.  This category of tics must be differentiated from Wilson's disease,
cerebral  palsy,  Sydenham's  chorea,  hyperthyroidism,  Tourette's syndrome,
carbon  monoxide  poisoning  and  neuroleptic  drugs.   CLINICAL:  Tourette's
syndrome is  the  worst  end  of  the  spectrum  of  a  disorder beginning in
childhood, consisting of both motor and vocal tics  which  wax  and  wane  in
severity,  and  last  more than 1 year.  The onset must be before 21 years of
age.  The tics tend to occur many  times a day in bouts.  Tourette's syndrome
occurs in about 2.6% of the general population.  It occurs more in males than
females by a ratio of 4.7:1, and the mean onset is around 6.5 years  of  age.
More than 90% will have symptoms before the tenth birthday.  The incidence of
behavioral   and   learning   problems  is  higher  in  males  than  females.
Neurological exam is essentially normal  in Tourette's syndrome.  The EEG may
show only minor non-specific findings that have  no  diagnostic  merit.   The
tics  are  involuntary sudden movements that can be suppressed for seconds to
minutes.  They tend to  be  more  pronounced  when  there is undue fatigue or
stress and tend to be less  frequent  if  the  patient  is  engaged  in  some
activity  or is sleeping.  There may be sudden head jerks, arm and leg jerks,
shoulder jerks, incessant eye  blinking  and  lip smacking or kicking.  There
also may be body gyrations, dystonic movements and self-destructive  behavior
as  hair  pulling, nail biting or biting of the tongue and lips.  Copropraxia
(lewd gestures with the hands or tongue) may be present along with Coprolalia
(involuntary  obscene   utterances).    Coprolalia   is   considered   to  be
pathognomonic of Tourette's syndrome, but doesn't occur with great  frequency
(60%),  and  may not develop until 6-35 years have passed since the diagnosis
of Tourette's syndrome.   There  may  also  be  echolalia  (repetition of the
speech of others), echopraxia (imitation of others' movements) and  palilalia
(repetition  of words or phrases).  Vocal tics are meaningless sounds such as
grunting, sniffing, throat clearing,  hissing, coughing and squeaking.  There
also may be words or phrases that change in  volume  and  rate.   Vocal  tics
begin  between  8-15  years of age, and almost always are in association with
motor tics.  Vocal  tics  by  themselves  account  for  less  than 5%.  Also,
included in Tourette's syndrome are behavioral problems,  such  as  attention
deficit/hyperactivity,  obsessive compulsive behavior, anxiety and depressive
syndromes, and increased emotional  lability.  TREATMENT OF TICS: Haloperidol
can be used at a starting dose of .5 mg/day at bedtime and  increased  by  .5
mg/wk  until  the  symptoms are controlled.  High doses of Haldol can produce
side effects as tremors,  akinesia,  rigidity,  drooling, masked facies, gait
disturbances,   dystonia,   lethargy,   depression   and   poor   educational
performance.   In  particular,  akathisia,  which  is  an  inner   sense   of
restlessness,  may  develop  as  a  side  effect  of  Haldol.   This  may  be
interpreted as a new tic, instead of Haldol induced.  The side effects can be
treated  with  trihexyphenidyl  (Artane) 1 mg bid, biperiden (Akineton) .5 mg
bid or benztropine  mesylate  (Cogentin)  .5  mg/day.   Pimozide  (Orap) is a
neuroleptic agent that can be used in Tourette's syndrome, that has the  same
efficacy as haloperidol, but has less sedation and may be better tolerated by
patients.   It  can  be  started  at 1 mg at bedtime or 1 mg bid.  It is then
titrated so that patients may eventually  receive  a  maximum of .2 mg per kg
per day divided into bid or tid doses.  The QT interval must be monitored  as
the  drug  can prolong the QT interval, and has been reported to cause sudden
death  at  high  daily  dosages  of   60-70  mg  per  day.   Other  drugs  as
trifluoperazine (Stelazine) and fluphenazine (Prolixin)  have  been  used  to
treat   Tourette's  syndrome.   These  drugs  have  the  same  capability  in
suppressing the tics as Haldol  and  Orap,  but are usually second line drugs
when failure has occurred with Haldol and Orap.   Clonidine,  also  has  been
used  to  suppress  the  tics.   This  drug,  however,  tends  to improve the
behavioral disturbances more than the  tics.   It  is less effective than the
other drugs, but doesn't cause akathisia and tardive dyskinesia as the  other
neuroleptics.   It  can  be  started  at  .05  mg per day and titrated to tid
dosing.  The total daily dose is  usually  not  more than .5 mg per day.  One
caveat is that the drug must be  continued  for  at  least  3  months  before
optimal  results  are  realized.   Clonidine  can  cause dizziness, headache,
insomnia, sedation and dry  mouth.   Clonazepam  (Klonopin)  has been used in
Tourette's syndrome with good results, but has not been studied  as  well  as
the  other  drugs.   Also,  calcium  channel blockers and reserpine are other
choices that can be tried.  TREATMENT OF BEHAVIOR DISORDERS: Treatment of the
obsessive compulsive  disorder  associated  with  Tourette's  syndrome may be
effected with fluoxetine (Prozac) starting at 20 mg each morning.   Some  may
require  up  to  60  mg  in  divided  doses.  Several weeks may be needed for
beneficial  results  to  occur.   Side  effects  include,  increased anxiety,
nervousness, insomnia and reduced appetite.   Clomipramine  (Anafranil)  also
can  be  used starting at a dose of 25 mg at bedtime and then titrating up to
around 150 mg per  day.   Side  effects  include  drowsiness and weight gain.
Treatment of the attention deficit/hyperactivity disorder is more  difficult.
About 60% these children, usually boys, will have the disorder in association
with  the  tics.  These children may be so disruptive the the schoolroom that
they must be assigned special  education classrooms.  Clonidine or imipramine
should be tried first, but these 2 drugs are often times ineffective, and the
child must be started on Ritalin 5-60 mg per day in divided doses or pemoline
(Cylert) 18.75 - 75  mg  each  AM.   Sometimes,  when  these  stimulants  are
started, the tics will become more frequent and the dose must be down graded.
Other tics actually improve with Ritalin.

                     -TOXIC EPIDERMAL NECROLYSIS-
Toxic epidermal necrolysis (TEN) is usually caused by a drug induced reaction
which causes  sloughing  of  the  skin  and  mucous  membranes.   There  is a
female:male ratio of 2:1 with all races and age groups affected.  Twenty-100%
of the skin surface can be involved.  The disease  starts  as  a  burning  or
painful  area  predominately  on the trunk and proximal extremities, but also
painful edematous erythema of the  palms  and  soles can be seen.  Nikolsky's
sign is present and the wet T shirt sign is also present.  Greater  than  90%
will  have ulcerations in the mouth.  The Tzanck test will reveal esoinophils
and basal cells with a  high  nuclear  to  cytoplasm ratio.  Skin biopsy will
show a subepidermal blister with necrotic  keratinocytes  in  the  epidermis.
Immunofluorescence   studies   are  not  positive.   It  may  be  seen  after
administration  of  allopurinol  (Zyloprim),  anticonvulsants,  barbiturates,
NSAIDs,  and   antibiotics.    Other   predisposing   factors  include  viral
infections, graft-versus-host disease, immunizations, SLE, seizure disorders,
brain tumors, and inflammatory bowel disease.  The average mortality for  TEN
is  about  30%,  with  sepsis  from Pseudomonas aeruginosa and Staphylococcus
aureus  predominating.   However,  the  patient  may  also  succumb  from  GI
bleeding,  pulmonary  embolism  and  pulmonary  edema.   In  particular,  the
prognosis is worse if there  is  extensive  involvement of the skin, advanced
age and an elevated BUN.  If the patient survives, re-epithelilzation usually
occurs in about 2-3 weeks without scarring.   The  patient  may  develop  eye
symptoms not unlike that of Sjogren's syndrome in 40-50% of cases.  There may
also  be  such  sequelae  as nail shedding, hyperhidrosis, vaginal synechiae,
phimosis  and  persistence  of  mucous  membrane  ulcerations.   Treatment is
supportive.  The patient should be placed in a burn  unit  and  treated  with
large  amounts  of  fluid,  local  care  and  adequate  nutrition.  Secondary
infections may be treated with silver nitrate solution 0.5% and chlorhexidine
gluconate (Hibiclens).   Prophylactic  antibiotics  are  not indicated.  Some
would advocate the use of porcine xenografts, allografts or skin  substitutes
following  debridement  of dead epidermis.  Steroid therapy, hypebaric oxygen
and plasmapheresis are not helpful.

                       -TOXIC SHOCK SYNDROME-
Toxic   shock   syndrome   is  a  multi-system  disease  that  presents  with
hypotension,  an  erythroderma  that  resembles  a  sunburn,  and  fever.  In
particular, emphasis in the differential diagnosis should be  placed  on  the
hypotension   as   there  are  several  diseases  that  can  mimic  TSS,  but
characteristically, don't  have  hypotension.   The  main  contender that may
present almost identically as TSS is the Toxic streptococcus syndrome.   This
syndrome is caused by an exotoxin producing species of group A beta hemolytic
streptococcus.   There  is hypotension, rash and multiple organ failure, just
as in TSS, but the source  of infection is usually obvious.  The differential
will be discussed more fully later.  TSS is caused by an  exotoxin  producing
species   of   Staphylococcus   aureus  that  produces  TSST-1  exotoxin  and
staphylococcal enterotoxins A, B  and  C.  However,  no antibodies to the TSS
toxin-1 (TSST-1) can be  found.   The  patient  can  have  nausea,  vomiting,
diarrhea,    mental   confusion,   renal   failure,   hepatic   failure   and
thrombocytopenia.  There can also  be  meningismus, vaginitis with discharge,
conjunctivitis,  periorbital  edema,  myalgias,  and  arthralgias.   TSS  was
initially reported  in  association  with  superabsorbent  tampons  in  young
menstruating females.  Since then, however, cases have arisen in surgical and
non-surgical  wounds, abscesses, osteomyelitis, pneumonia, sinusitis and post
partum infection.  Vaginal  diaphragms  and  contraceptive  sponges have also
been involved.  Many of the cases of TSS are occult for an obvious source  of
infection.   CRITERIA  FOR  DIAGNOSIS  OF  TSS:  The  CDC  has  proposed  the
following,  in  order  to  make  a  diagnosis  of  TSS:  MAJOR  criteria  are
Temperature  >  38.9  C,  Systolic  BP < 90 mm Hg, and a rash with subsequent
desquamation, especially on the palms and soles about 1 week after the onset.
MINOR criteria (must be 3 or  more  of the following): GI: (vomiting, profuse
diarrhea), Muscular: (severe myalgias or > fivefold  increase  in  creatinine
kinase),   Mucous  membranes:  (hyperemia  of  the  vagina,  conjunctivae  or
pharynx), Renal insufficiency: (BUN  or  creatinine  at least twice the upper
limit of normal, pyuria in the absence of urinary  tract  infection),  Liver:
(hepatitis  with  the bilirubin, SGOT, SGPT at least twice the upper limit of
normal),  Blood:   (thrombocytopenia   of   less   than   100,000/mm3),  CNS:
(disorientation without focal neurologic  signs).   There  must  be  negative
results  of  serologic  tests for Rocky Mountain spotted fever, leptospirosis
and measles.  DIFFERENTIAL DIAGNOSIS: MEASLES  can  occur  at any age, but is
more common in children  and  adolescents.   There  may  be  fever,  malaise,
conjunctivitis,  photophobia,  cough,  Koplik spots, nasal discharge and rash
that usually  follows  these  prodromal  signs  and  symptoms.   The  rash is
maculopapular  and  starts  on  the  face  progressing  to  the   trunk   and
extremities.   The  rash  may coalesce, which would then simulate the rash of
TSS.  There is no hypotension.  The  skin  rash usually fades in about 6 days
starting with the face.  ROCKY MOUNTAIN SPOTTED FEVER (RMSF) presents with an
abrupt temperature elevation, headache, chills and  a  macular  rash  on  the
extremities  that  progresses  to  the  trunk and extremities over 2-3 weeks.
Hypotension would again be  rare.   RMSF  is caused by Rickettsia rickettsiae
and is transmitted by a tick bite.  LEPTOSPIROSIS  occurs  in  patients  that
come  in  contact  with  infected animal tissue and urine.  Abattoir workers,
farmers and trappers are susceptible  to Leptospirosis.  Onset is with sudden
fever, headache, chills, myalgia, conjunctival and pharyngeal  injection  and
rash  on  the  trunk  which  can  be  macular,  maculopapular  or urticarial.
Leptospirosis is caused  by  the  spirochete  Leptospira.  Hypotension is not
present.  KAWASAKI'S DISEASE also needs  to  be  ruled  out.   However,  this
disease  typically  occurs  in children age 1-8.  It is a mucocutaneous lymph
node disease that presents with  fever, nonpitting edema, desquamation of the
skin and coronary artery aneurysms.  Other diseases to rule out would include
scarlet fever, drug  reactions,  staphylococcal  scalded  skin  syndrome  and
septic   syndromes.    LABORATORY:  There  may  be  a  positive  culture  for
Staphylococcus aureus from  the  vagina  or  surgical  wounds.   There may be
perineal or nasal carriage of Staphylococcus aureus.  There may be  increased
SGOT, SGPT, CPK, BUN, creatinine, bilirubin, decreased calcium, magnesium and
phosphate   and   pyuria.    Blood   cultures  are  almost  always  negative.
Leptospirosis and RMSF serology should be performed if doubt exists as to the
diagnosis.  PROGNOSIS: In 1980 TSS  had  a  mortality  of about 5%.  Now with
additional  acquaintance  of  the  disease,  the  prognosis  is  considerably
improved.  There is a recurrence rate, however, of  10-15%.   COMPLICATRIONS:
Adult respiratory distress syndrome, and acute renal failure are the two main
complications.   Rarely,  the patient may go on to disseminated intravascular
coagulation, cardiomyopathy,  sustained  fatigue,  memory  loss  and  a toxic
encephalopathy with ataxia.  TREATMENT: The main treatment is with IV  fluids
to  reverse  the hypotension, by giving normal saline .5 to 5 liters over 1-4
hours.  If this is ineffective  then  Dopamine 4-20 ug/kg/min should be given
IV.  Nafcillin or Oxacillin 2  grams  IV  q  4  hours  for  10  days  (reduce
Oxacillin  if  patient  has  renal insufficiency.  This is not necessary with
Nafcillin) OR Vancomycin (if allergic to penicillin)  500 mg IV q 6 hours, or
1 gram IV q 12 hours.  May also require Methylprednisolone 10 mg/kg q 8 hours
IV and Heparin 5000 U SQ q 12 hours.  Betadyne vaginal douche also may be  of
help.

                    -TOXOPLASMA GONDII AND AIDS-
Pyrimethamine, 50-100 mg PO qd, + sulfadiazine  1-2 gm PO q6h + folinic acid,
5-20 mg PO qd or Clindamycin,  450-600  mg  PO  q6h  or  600  mg  IV  q6h,  +
sulfadiazine, 1-2 gm PO q6h.  Maintenance therapy: Pyrimethamine, 25-50 mg qd
+  sulfadiazine 500-1000 mg PO q6h or Pyrimethamine 25-50 mg qd + clindamycin
300 mg PO q6h.

                 -TRANSESOPHAGEAL ECHOCARDIOGRAPHY-
Transesophageal echocardiography (TEE) is becoming an important  modality  in
examining   the   heart.   TEE  has  definite  advantages  over  conventional
transthoracic echocardiography (TTE).  The  earliest  probe that was attached
to the tip of a gastroscope was inadequate because it was limited to a single
transverse imaging plane.  Following the single plane, the biplane probe  was
introduced  which gave additional long axis views of the heart in which there
was better viewing of the interatrial septum, left ventricular outflow tract,
ascending aorta and  the  tricuspid  valve.   The  latest probe is multiplane
which allows better visualization of the  pulmonic  valve,  ascending  aorta,
aortic  valve  and  pulmonary  veins.  There are 3 primary imaging planes for
single plane  TEE.   Examination  of  the  basal  portion  of  the heart will
visualize the left atrium  and  left  atrial  appendage,  aortic  valve,  and
pulmonary veins.  The next view is obtained by moving the transducer distally
to  examine  the  4 chambers, interatrial septum, interventricular septum and
the atrioventricular valves.   With  the  probe  in  the stomach a transverse
short-axis view of the left ventricle may be  obtained.   DOPPLER:  TTE  will
allow  interrogation of the velocities from several areas including the apex,
subxyphoid, parasternal and suprasternal  portions  of  the chest making this
approach much better than TEE for calculation  of  aortic  and  mitral  valve
areas,  cardiac  outputs, and pressure gradients.  Doppler color flow mapping
is much better with TEE  in  assessing prosthetic valve regurgitation, patent
foramen ovale and atrial septal defects.  However, TTE is better for pulmonic
and  tricuspid  regurgitation.   Either  method  may  be  used  to   evaluate
ventricular  septal defects, mitral and aortic regurgitation.  MITRAL  VALVE:
TEE has its main utility  in  evaluating mitral valve regurgitation.  TEE can
give very good resolution of the papillary  muscles,  chordae,  leaflets  and
annulus  and  therefore  may be used to determine which patients are suitable
for mitral valve repair and  which  type  might be most appropriate.  TEE can
also  give  an  estimate  of  the  severity  of  the  mitral   regurgitation.
Furthermore,  TEE  is used during mitral valve reparative surgery in order to
determine the success of the surgery.  TEE doesn't add that much over TTE for
mitral stenosis because TTE can easily  identify and quantitate the degree of
mitral stenosis and also make the determination which patients  will  benefit
from  commissurotomy  versus  balloon  valvuloplasty.   TEE  is  superior  in
checking  for  left  atrial  thrombi  prior to balloon valvuloplasty.  AORTIC
VALVE: Single plane TEE is not  accurate  in assessing the severity of aortic
regurgitation or stenosis because the images are off axis.  Further work with
multiplane TEE should give excellent short and long axis views of the  aortic
valves which will be useful in aortic regurgitation.  TEE is not as effective
as  TTE  in  evaluating  for  aortic  stenosis.  TEE has great utility in the
diagnosis   of   aortic   vegetations,   abscess,   and   aortic  dissection.
ENDOCARDITIS: TEE is much better  than  TTE  for  detecting  vegetations  and
perivalvular  abscesses.   In  one  series  for detection of vegetations, the
sensitivity and specificity for TEE was  94% and 98% respectively as compared
to 69% and 92% for TTE.  In another  series  for  detection  of  perivalvular
abscesses the sensitivity and specificity for TEE was 87% and 95% as compared
with  28%  sensitivity for TTE.  Armed with this information one can make the
decision for early surgery  with  valve  replacement  or debridement of large
mobile vegetations versus a continued antibiotic conservative  approach.   At
any  time  during  the  course of endocarditis if CHF, AV block or persistent
fever develops TEE should be done.  Assessing vegetations in association with
prosthetic valves is difficult because  of acoustic shadowing.  Patients with
right sided endocarditis have a more benign course and TEE may not be  needed
as  TTE  may  be  just as effective.  PROSTHETIC VALVES: Patients that have a
mechanical prosthesis and endocarditis cannot  be assessed optimally with TTE
because the inability of the ultrasound beam to penetrate the prosthesis  and
evaluate  the opposite side of the prosthesis.  With TEE this can be overcome
somewhat by obtaining  acoustic  windows  behind  the  prosthesis in order to
evaluate abnormal perivalvular regurgitations and vegetations.  About 50%  of
these  abnormalities  will  be  missed with TTE as compared with TEE.  Mitral
valve  prosthetic  abnormalities  are  more  susceptible  to  detection  than
prosthetic  aortic  valve  abnormalities.   Therefore,  in  summary,  TEE  is
superior to TTE for detection  of prosthetic dysfunction.  AORTIC DISSECTION:
For the initial  evaluation  of  aortic  dissection  TEE  is  considered  the
modality  of  choice  because  of its portability and superior accuracy.  The
sensitivity and specificity for  detection  of aortic dissection is excellent
with TEE.  There is now  a  consensus  that  TEE  and  MRI  are  superior  to
angiography  and CT scanning in classifying the type of aortic dissection and
in the diagnosis  of  aortic  dissection.   A  negative  TEE examination will
effectively exclude an aortic dissection as the sensitivity  and  specificity
are  99%  and  98%,  respectively.   With  the  development of TEE multiplane
imaging  there  is  now  excellent  visualization  of  the  ascending  aorta.
Criteria for dissection should not  solely  rely  on detection of the intimal
flap, but should require detection of the entry site,  aortic  regurgitation,
pericardial  effusion  and thrombosis of the false lumen.  If a proximal flap
is visualized without the  other  ancillary  findings  of dissection, and the
patient is stable, an MRI should be obtained for confirmation.  If there is a
distal  dissection  an  MRI  also  will  give  assessment  of  branch  vessel
involvement.  Distal dissections are  treated  medically.   CONGENTIAL  HEART
DISEASE:  TEE is used in adults with congenital heart disease to evaluate for
corrected congenital heart disease, atrial septal defects, Ebstein's anomaly,
subaortic membrane disease  and  partial  anomalous  pulmonary venous return.
All three types of ASD may be classified as ostium secundum,  ostium  primum,
or  sinus  venosus.   CARDIOEMBOLIC  DISEASE:  TEE  is far superior to TTE in
visualizing the left atrial appendage, a sanctuary for thrombi.  However, all
masses seen in  the  left  atrial  appendage  are  not thrombi, but represent
prominent pectinate  muscles,  calcification  or  spontaneous  echo  contrast
swirling secondary to mitral stenosis and atrial fibrillation.  The yield for
thrombi  as  a  potential source for embolism is exceedingly low in a patient
without clinical heart disease.  Therefore,  the utilization of TEE even with
its capabilities is somewhat controversial  in  routine  examination  of  the
heart  in  stroke  patients.   Sources  for  embolization  in the heart would
include left atrial and left  ventricular thrombi, vegetations, atrial septal
aneurysm, patent foramen ovale,  mitral  valve  prolapse,  and  mitral  valve
annular  calcification.   Since  the  main  reason  for  performing TEE is to
ascertain whether the patient is  a candidate for anticoagulation, TEE should
only be performed if there is clinical  evidence  of  heart  disease  or  the
patient  is  less than 45 years of age and the 2D echocardiogram is negative.
In the face of a negative  2D  and a positive TEE then anticoagulation should
be given.  If the patient has no clinical evidence of heart  disease  and  is
over the age of 45, the carotids and cerebral circulation should be initially
evaluated.  If these are negative a 2D echocardiogram should be done.  If the
2D is negative a TEE should be done.  Anticoagulation should then be given if
the TEE is positive.  INTRAOPERATIVE MONITORING: TEE is useful for monitoring
valve  replacement  with  perivalvular  leaks, disk excursion limitation, and
mitral valve repair.  Left

             -TRANSIENT HYPOGAMMAGLOBULINEMIA OF INFANCY-
Transient hypogammaglobulinemia of infancy (THI) is a temporary deficiency of
immunoglobulin synthesis that usually starts around the age of 3-6 months and
usually persists for 6-18 months.  The normal full term infant  has  a  serum
IgG level that is essentially the same as that of the mother, which is due to
the active transportation of IgG transplacentally during the 3rd trimester of
the pregnancy.  The basic problem is a physiologic delay in the production of
immunoglobulin  by  the  infant.   The normal infant usually does not start a
significant production of IgG until  about  2-3  months of age.  The infant's
IgG that is derived from the mother is slowly catabolized and has a half life
of about 25-30 days.  The disorder affects both  females  and  males  and  is
usually  not  familial.  The B cells are present in normal numbers, but the T
helper cells may be reduced.   Mitogen  stimulation is normal.  Patients with
THI are capable of synthesizing specific antibodies to human  type  A  and  B
erythrocytes,  and  to  tetanus  toxoid  and diphtheria before immunoglobulin
concentrations become normal.  The  lymph  nodes  have decreased plasma cells
and the germinal centers are absent or very small.  Since the  circulating  B
cells  are  normal  in  number, it is thought that the basic defect is at the
terminal differentiation of  B  cells  into  antibody producing plasma cells.
Most of these infants will present after  6  months  of  age  with  recurrent
infections  of  the  upper  and  lower  respiratory  tract.   Bronchitis  and
recurrent  otitis  is  very  common.   However,  there is a rare incidence of
meningitis and cutaneous infections.  TREATMENT:  Most of these patients with
THI will do well without life threatening  infections,  and  do  not  require
gamma globulin replacement.  The IgG level is usually greater than 200 mg/dl.
If  the  patient  does have a severe infection, gamma globulin replacement is
usually given for  12-36  months.   Immunoglobulin  levels  should be checked
every 3 months.  Most of  these  patients  are  producing  immunoglobulin  at
normal rates by the age of 4 and have a good prognosis.

                     -TRANSIENT ISCHEMIC ATTACKS-
Transient ischemic attacks (TIA)  are  characterized  as  episodes  of  focal
neurologic loss secondary to vascular insufficiency.  The deficiency resolves
within 24 hour and usually lasts less than 1 hour.  There is a higher risk of
cerebral  infarction  in  the  first few months following a TIA.  Any patient
that has TIAs  should  also  be  checked  for  cardiac  disease as myocardial
infarction is  the  commonest  cause  of  death  in  these  patients.   Other
conditions  to  rule  out  include  focal  seizure, complicated migraines and
hypoglycemic hemiplegia.  If the focal  neurologic deficit has a sudden onset
but lasts longer than 24 hours, tumor, stroke and other mass  lesions  should
be  ruled out.  Patients that have more of a SUBACUTE onset should be checked
for subdural hematoma, demyelinating disease,  brain tumor and brain abscess.
If the diagnosis is TIA, then carotid artery ischemia should  be  ruled  out.
CLinical   symptoms  consist  of  weakness  or  sensory  loss  involving  the
contralateral face, arm and leg.  Aphasia may be present along with amaurosis
fugax.  Vertebralbasilar TIAs  present  with dysphagia, diplopia, dysarthria,
ataxia, blindness, and different types of limb weakness.  To evaluate  for  a
vertebral basilar TIA obtain an MRI which can assess the cerebellum and brain
stem.  Also obtain a CBC  with  differential,  PT, PTT, platelets, VDRL, ESR,
electrolytes, glucose, liver and kidney function, UA and lipid  profile.   An
ECG  and  chest  x-ray  should  also  be obtained and if there is evidence of
cardiac disease an echocardiogram and Holter  monitor may be done to rule out
thrombi or arrhythmias.  Transesophageal echocardiography may  be  needed  if
there  is  suspected embolic disease.  For carotid artery TIA, obtain a CT of
the head,  carotid  duplex  US  with  Doppler  which  can  detect  plaque and
stenosis.  TREATMENT: If carotid stenosis > 70%, carotid  endarterectomy  may
be  indicated.   Medical  treatment  is  with  aspirin 325-1300 mg/day.  If a
cardiac source  is  seen  anticoagulation  is  indicated.  Anticoagulation is
considered in patients with prosthetic valves, recent MI, chronic  arrhythmia
and  thrombi.   The  warfarin  is  continued  for  3-6  months.   Ticlopidine
hydrochloride  250  mg BID, is useful in patients that are allergic to ASA or
those TIAs that persist while on aspirin.   The CBC should be checked every 2
weeks  for  3  months  if  ticlopidine  is  used  because  of  the  risk  for
neutropenia.  Vertebrobasilar TIAs are treated with aspirin 325 mg daily.  If
symptoms persist while on ASA anticoagulation with heparin and then low  dose
warfarin for 3-6 months may be used.  Ticlopidine may also be used.

                        -TRAVELER'S DIARRHEA-
Traveler's  diarrhea  is  usually  caused  by bacteria in about 80% of cases.
Enterotoxigenic E. coli, Shigella  species  and  Campylobacter jejuni are the
most common pathogens. Other agents that  may  occasionally  be  instrumental
include Salmonella, Aeromonas, Giardia lamblia, Entamoeba histolytica and non
cholera  vibrios.  The risk for traveler's diarrhea is related to the country
that is visited.  The attack  rates  exceed  30% in those visiting Africa and
South America.  Mexico has an attack rate  of  38.8%,  Spain,  25.6%,  Israel
15.4%,  France  12.9%,  and the United Kingdom 2.5%.  Non cholera vibrios are
prevalent along the coastal areas  of  Asia, and Cryptosporidium is common in
Russia (especially St.  Petersburg).  Rotovirus and Norwalk virus are  common
in  Mexico, and Giardia may be seen in Russia and North America.  Salmonella,
Shigella and Aeromonas are common in Thailand.  CLINICAL: Most cases are self
limiting (2-4 days), and  mild.   Patients  may have abdominal cramps, fever,
nausea, vomiting, borborygmi, headache and myalgias.   The  diarrhea  usually
occurs  abruptly  producing  4-5  watery  bowel movement per day.  TREATMENT:
PROPHYLAXIS:  Prophylactic  Bismuth  subsalicylate  affords  some  protection
against traveler's diarrea.  It is cheap, has few side effects and is usually
adequate for most  high  risk  area.   It  is,  however,  less effective than
antibiotic therapy.  The dose is 2 tablets  (262  mg)  QID,  or  60  ml  QID.
Prophylactic   antibiotics   include  Trimethoprim-sulfamethoxazole  (160/800
mg)/day, ciprofloxacin 500 mg/day,  norfloxacin  400 mg/day and ofloxacin 300
mg/day.   The   fluoroquinolones   are   considered   the   most   effective.
Trimethoprim/sulfamethoxazole has a problem in  most underdeveloped areas due
to  resistance,  but  is  effective  in  inland  Mexico  during  the  summer.
Doxychycline  will  not  be effective due to the development of resistance in
most areas.  Traveler's should  be  warned  to  eat  only fruit that has been
peeled, vegetables that have been washed with bottled water or boiled  water,
and  drink  only  bottled  beverages such as alcohol or carbonated beverages.
Jellies, syrups, hot tea and coffee,  and  bread are usually safe.  Food that
is consumed should be fresh and steaming hot.  TREATMENT OF  ACUTE  DIARRHEA:
Dehydration  is usually not a problem in adults, but hydration is recommended
in children.  Small children will  need electrolyte containing solutions such
as Pedialyte, Lytren or similar solutions that may be found in pharmacies and
grocery stores abroad.  For  symptomatic  relief,  Bismuth  subsalicylate  is
given  as  30  ml every 30 minutes for a total of 8 oz/day.  If bloody stools
are not present loperamide is  given  as  4  mg,  followed by 2 mg after each
loose stool, not to exceed 16 mg/day.  For patients that have at least  three
stools/day  and  other  symptoms,  antibiotics  may  be  given.   Single dose
antibiotic therapy is given  as  follows:  Ciprofloxacin 1000 mg, norfloxacin
800 mg, ofloxacin 600 mg, and TMP/SMX 2 double  strength  tablets.   Patients
that have severe diarrhea manifested as greater than 3 loose stools/24 hours,
fever  and  bloody  diarrhea,  can be treated with the following antibiotics.
Ciprofloxacin 1000 mg, followed by 500 mg BID for 3 days, Norfloxacin 800 mg,
followed by 400 mg BID for 3  days,  Ofloxacin 600 mg, followed by 300 mg BID
for 3 days, and TMP/SMX 2 double  strength  tablets,  followed  by  1  double
strength tablets BID for 3 days.

                              -TREMORS-
POSTURAL (ACTION TREMORS): Are caused by cerebellar disease, benign essential
tremor,   hyperthyroidism,   fatigue,   anxiety,   drug  withdrawal,  mercury
poisoning, alcoholism,  pheochromocytoma,  uremia,  CO2  narcosis,  and liver
failure (asterixis).  The tremor occurs  during  an  attempt  to  maintain  a
posture.   Observe  the  patient  standing  with arms overhead with the hands
extended.  RESTING TREMOR: Occurs in  Parkison's disease and occurs while the
patient is at rest.  Observe the patient at rest.  INTENTION (ATAXIC) TREMOR:
Is caused by multiple sclerosis, phenytoin toxicity, and cerebellar  disease.
It  occurs only during a precise coordinated movement.  It is tested by using
the finger to nose and the  heel  to shin test.  Wilson's disease may present
as resting, postural or intention tremors.

                         -TREMOR (Essential)-
This disorder can start at any age, but the middle aged and older persons are
more commonly affected than others.  There  is a clear genetic component.  As
many as half are definitely hereditary, having an autosomal dominant mode  of
transmission.   The  hands  are  most  affected.   Tremor  is  present in the
postural (holding the hands  outstretched)  and  the kinetic position (during
movement), but not in the resting position.  In contrast, resting  tremor  is
characteristic  of  Parkinson's  disease,  which  is  usually associated with
bradykinesia and rigidity (factors that are not present in essential tremor).
The head and voice  can  also  be  affected  in  essential tremor (ET).  Head
tremor may be horizontal (no-no) or vertical (yes-yes).  Head tremors  almost
never  occur  in  Parkinson's  disease.   The voice in patients with ET has a
quivering intonation.  The legs and  trunk  are less frequently affected.  ET
is a slowly progressive condition.  Patients with a tremor  for  20-30  years
may   seek   medical   attention  for  the  first  time.   Difficulties  with
handwriting,  drinking  liquids  and  other  fine  manipulations  are  common
complaints.  TREATMENT: One alcohol drink  often reduces the tremor for 45-60
minutes.  Two drugs, Inderal (and other beta  blockers)  and  primidone  have
proved  to  be  effective  in  ET.  An estimated 50-70% of patients will have
symptomatic control with Inderal.   The  effective  dose range is from 80-320
mg/day.  Inderal LA may be used.  Primidone is effective in about  60-70%  of
patients,  and some will have almost total elimination of their tremors.  The
dose is less  than  that  used  in  epilepsy.   A  starting  dose of half the
pediatric formulation of 50 mg is recommended.  As  many  as  50%  will  have
adverse  reactions  as  dizziness,  malaise,  ataxia  for  several days after
administration of the initial  dose,  even  with  25  mg given at night time.
Patients should be told of the possibility of an ACUTE reaction and should be
encouraged to continue taking the drug.  Chronic side effects with  primidone
are  uncommon.   A  single  dose  of  250  mg at HS is often effective.  Many
patients benefit from a combination of primidone and Inderal.  One might want
to start with primidone  because  of  its  potential  for a greater degree of
suppression of tremors than with Inderal and because of its relative lack  of
side  effects  with long term usage.  Tolerance may develop in some patients,
but usually not.  Methazolamide  (Neptazane),  a carbonic anhydrase inhibitor
used in ophthalmology may work also.  Adverse reactions may be a  problem  if
the  dose is increased too rapidly.  It is effective in about 50% of patients
with ET.   Head  or  voice  tremor  is  remarkably  responsive.   Bone marrow
suppression is a rare, serious side effect.  It is started at 12.5-25 mg TID.
This dose is increased by 12.5-25 mg for each dose every 3-7 days  as  needed
and  tolerated.  CBCs are determined at 3-6 week intervals.  The average dose
that patients take without  side  effects  is  129 mg/day.  Phenobarbital and
alprazolam  are  sometimes  effective.   Diazepam,   clonazepam,   clonidine,
amantidine and alpha adrenergic blockers have limited efficacy.

                      -TRICUSPID REGURGITATION-
Seen more often in infants, and  toddlers.  There is a holosystolic murmur to
the immediate right or left of  sternum  which  is  a  grade  2-3  with  wide
splitting  of  S2  and  a  short  rumble  after  a loud S3.  Inspiration will
intensify the murmur.

                        -TRICYCLIC POISONING-
Gastric lavage with 10-20  liters, even  if  up  to  18 hours post ingestion.
Continuous nasogastric suction.  Activated charcoal slurry 75-100 grams  q4h.
Hypertension  is  usually mild and transient and need not be treated usually.
For seizures  use  valium  and  dilantin.   Tachycardia  usually doesn't need
treatment.  For hypotension refractory to alkalinization and fluids, levophed
4-8 mg in  500  ml  D5W  is  used.   For  conduction  defects  refractory  to
alkalinization  dilantin  5-7  mg/kg  IV  at  a  rate  of  50 mg/min is used.
Pacemaker  insertion  may   be   needed.   For  supraventricular  tachycardia
refractory to alkalinization use dilantin or cardioversion.  For  ventricular
tachycardia  refractory  to alkalinization use dilantin, lidocaine, bretylium
and overdrive pacing.  Avoid  quinidine, procainamide and dispyramide because
of AV block.  ALKALINIZATION: Add 50-100 meq Sodium bicarbonate to 1 liter of
normal saline and titrate IV to  maintain  a  pH  of  7.5  by  arterial  gas.
Monitor potassium levels.

                  -TRIGEMINAL NEURALGIA (Treatment)-
Tegretol (carbamazepine) produces significant pain relief in 60-70% and costs
twice as much as Dilantin.  Phenytoin is  effective  in  only  about  20%  of
patients,  but  produces  fewer complications.  Tegretol is started at 200 mg
daily or bid.  If 600  mg/day  brings  no  relief  after a week, increase the
daily dose by 200 mg once a week until the pain subsides or until therapeutic
blood levels are reached (8-12  ug/ml).   Common  side  effects  are  blurred
vision,  double  vision, drowsiness, dizziness, ataxia, headaches, nystagmus,
tinnitus, nausea and vomiting (all  of  these  are usually transient and dose
related).  Severe side effects include bone marrow depression associated with
leukopenia, thrombocytopenia, aplastic anemia, hepatoxicity,  aggravation  of
SLE,  CHF, hypertension, syncope, arrhythmia, hyponatremia, and inappropriate
antidiuretic hormone syndrome.  CBC, platelets,  SGOT,  and UA should be done
monthly for the first 3 months of therapy, every 3rd month for the  remainder
of  the  first  year  of  treatment  and  every  6  months thereafter.  Avoid
concomitant treatment with erythromycin.   Take Tegretol with food.  Patients
may develop an allergic measles type rash  all  over  the  body  that  occurs
within  the  first  week  of  therapy.   If  this  occurs discontinue without
tapering and switch to phenytoin.  Also, urticaria, photosensitivity, ataxia,
memory loss or tachycardia  may  occur.   If this happens discontinue without
tapering.  If the WBC declines to 4000, continue the  drug  without  changing
dosage,  but  get  weekly WBC counts.  In most patients suppression of WBC is
transient and  the  count  will  rebound  despite  continuation  of the drug.
Discontinue if the absolute polymorphonuclear cell count  falls  below  1,500
cells  per  uL.   Dilantin  (phenytoin) is started at 100 mg tid.  If after 3
weeks, and the drug concentration  has  reached  15-20 ug/mL, do not increase
the dosage.  Common side effects include dizziness, nystagmus, ataxia, double
vision, gingival hyperplasia,  hirsutism  and  upset  stomach.   Severe  side
effects  include  hypersensitivity  reaction,  exfoliative dermatitis, fever,
lymphadenopathy, folate deficiency  and  megaloblastic  anemia.  Obtain a CBC
annually.  Emphasize conscientious oral hygiene, by instructing  the  patient
to  brush  teeth  and  massage  gums  TID.  Surgery for trimgeminal neuralgia
includes gangliolysis with radio frequency heat, with a cryogenic probe or by
injection of glycerol into  Meckel's  cave,  or radio frequency neurolysis of
the peripheral nerve branches, or suboccipital craniectomy with decompression
of the trigeminal nerve root.

                          -TRIGGER FINGERS-
Trigger fingers develop from palmar trauma or irritation  causing  a  painful
catching  during  flexion.   Nodules  and thickened sheaths occur causing the
tendon fibers  to  bunch  at  the  annular  pulley.   35%  involve the flexor
pollicis and  50%  the  middle  or  ring  finger.   Treatment  is  perisheath
injection  with  Xylocaine  1%  1 ml + steroid.  More than 90% of the fingers
will remain free of triggering  after  one or two injections.  Alternatively,
the finger may be splinted in  extension  and  use  of  NSAIDs  for  1  week.
Surgical release is used only occasionally for refractory cases.

                   -TRIMETHAPHAN AND HYPERTENSION-
(Arfonad).    0.5-5   mg/min  as  IV  infusion.   Side  effects:  orthostatic
hypotension, blurred vision, bowel  and  bladder paresis, blurred vision, dry
mouth.

                   -TUBERCULOSIS (Drug resistant)-
Isoniazid 300 mg/day, rifampin 600 mg/day, pyrazinamide 20-30 mg/kg/day,  and
ethambutol  15-25  mg/kg/day + 2 additional second line TB drugs to which the
M. tuberculosis strain  is  susceptible,  depending  on local drug resistance
patterns.  Treatment is usually continued for 18-24  months,  but  length  of
therapy depends upon clinical, x-ray and bacteriologic response.

               -TUBERCULOSIS (Isoniazid intolerance)-
Rifampin  600  mg/day,  pyrazinamide  20-30  mg/kg/day,   ethambutol,   15-25
mg/kg/day.   Use  this  regimen  for 18 months or for 12 months after culture
converts to negative, whichever is longer.
 
         -TUBERCULOSIS (Possible drug resistant infection)-
Isoniazid 300 mg/day, rifampin 600 mg/day, pyrazinamide 20-30 mg/kg/day,  and
ethambutol  15-25  mg/kg/day.   Use this therapy for 2 months.  If sensitive,
continue isoniazid  and  rifampin  only.   If  resistant,  continue for 12-18
months.

                -TUBERCULOSIS (Rifampin intolerance)-
Isoniazid 300  mg/day,  pyrazinamide  20-30  mg/kg/day  and  ethambutol 15-25
mg/kg/day. Continue therapy for 18 months or for 12 months after the  culture
converts to negative, whichever is longer.

                 -TUBERCULOSIS (Second line drugs)-
Cycloserine  250-1000  mg/day  in  divided  doses, Ethionamide 250 mg bid-qid
daily, Amikacin 15  mg/kg/day,  5  days/week  IV  or IM, Para-aminosalicylate
12-16 gm/day in divided doses.   Kanamycin  15  mg/kg/day,  5  day/week,  IM,
Ciprofloxacin 500-750 mg bid, Ofloxacin 400 mg bid, Capreomycin 15 mg/kg/day,
5 days/week, IM, Clofazimine 200-300 mg/day and Rifabutin 150-300 mg./day.

                  -TUBERCULOSIS (Standard Therapy)-
Isoniazid  300  mg/day, rifampin 600 mg/day and pyrazinamide 20-30 mg/kg/day.
Use this regimen for 2 months, then  follow with isoniazid and rifampin for 4
months.

                        -TUBERCULOSIS DRUGS-
Isoniazid 5-10 mg/kg up to 300 mg PO  or  IM daily or 15 mg/kg PO or IM twice
weekly.  Side  effects:  hepatitis,  peripheral  neuritis,  hypersensitivity.
Monitor AST and ALT.  Rifampin 10-15 mg/kg up to 600 mg PO daily or 600 mg PO
twice  weekly.  Side effects: febrile reaction, hepatitis, drug interactions,
purpura.  Monitor AST and ALT.  Ethambutol  15-25  mg/kg PO daily or 50 mg/kg
PO twice a week.  Side effects: skin rash, optic neuritis which is reversible
with discontinuation of drug.  It is rare at 15 mg/kg.  Monitor visual acuity
and red-green color discrimination before therapy and  during.   Pyrazinamide
25  mg/kg  up  to 2 g PO daily.  Side effects: hepatotoxicity, hyperuricemia.
Monitor uric acid, AST-ALT.  Streptomycin  15  mg/kg  up  to  1 G IM daily or
15-25 mg/kg twice weekly IM.  Side effects: 8th  nerve  damage  (vestibular),
nephrotoxicity.   Monitor vestibular function, audiograms prior to and during
treatment, BUN and creatinine.  Capreomycin 12-15  mg/kg  up to 1 g IM daily.
Side  effects:  8th  nerve  damage  (auditory),  nephrotoxicity,   vestibular
toxicity  (rare).   Monitor vestibular function, audiograms, BUN, creatinine.
Kanamycin 12-15 mg/kg up to  1  g  IM  daily.  Side effects: 8th nerve damage
(auditory),  vestibular  toxicity  (rare),  nephrotoxicity.    Monitor   BUN,
creatinine,  vestibular  function,  audiograms.   Amikacin 15 mg/kg daily IM.
Side effects: auditory, vestibular,  renal.  Monitor BUN, creatinine, levels.
Ethionamide 15 mg/kg up to 1  g  PO  daily.   Side  effects:  hepatotoxicity,
hypersensitivity,  GI  disturbance.  Monitor AST, ALT.  P-Aminosalicylic acid
(aminosalicylic  acid)  150  mg/kg  up  to  12  g  PO  daily.   Side effects:
hepatotoxicity, hypersensitivity, sodium load, GI disturbance.  Monitor  AST,
ALT.   Cycloserine  15  mg/kg  up to 1 g PO daily.  Side effects: personality
changes,  rash,  convulsions,  psychosis.   Ofloxacin  600  mg  daily.   Side
effects: GI and rash.   Ciprofloxacin  500-750  mg daily.  Side effects: CNS,
GI.

                        -TUMOR LYSIS SYNDROME-
Tumor lysis syndrome results  from  an  extensive  release of potassium, uric
acid, and phosphate into the blood.  It is  usually  seen  in  patients  with
lymphoprofliferative  disorders,  hematologic  malignancies,  and bulky solid
tumors.  Tumor lysis syndrome is  particularly common after chemotherapy.  It
may be seen in acute leukemia and Burkitt's lymphoma.  Patients with  rapidly
growing  malignancies,  and patients that are being treated with chemotherapy
or radiation have large amounts of urinary uric acid excretion, which results
in  uric  acid  nephropathy,   uric  acid  nephrolithiasis  and  interstitial
nephritis.  Hyperphosphatemia can be very severe  with  levels  between  6-35
mg/dl  secondary to tumor cell lysis and renal failure.  Clinically, patients
present with azotemia,  renal  failure,  lethargy,  muscle cramps, tetany and
convulsions.   Hyperkalemia  and  hyperphosphatemia   are   usually  present.
TREATMENT:  Prophylaxis  is  very  important  in  those  patients  that   are
considered  at  risk.   This  is accomplished with hydration, allopurinol and
urine alkalinization.  Specific treatment for hyperkalemia includes emergency
treatment  with  50%  dextrose  and  insulin.   Sodium  polystyrene sulfonate
(Kayexalate) is also given as 20-30 grams every 6 hours.  If hyperkalemia  is
due  to  adrenal  insufficiency,  fludrocortisone  can be given at 0.05-.2 mg
daily.   For  patients  that  are   refractory  to  these  medical  measures,
hemodialysis may be needed.  Hyperuricemia and  hyperuricosuria  are  treated
with  hydration  and  alkalinization keeping the urine flow at > 100 ml/h and
the urine pH between 7-7.5.  Acetazolamide and sodium bicarbonate may also be
needed.  Patients with hematologic  and myeloproliferative diseases should be
given allopurinol at least 12 hours  prior  to  the  start  of  chemotherapy.
Hyperphosphatemia  is  treated  with  20%  glucose and insulin with a goal of
keeping the serum phosphate level  below  7  mg/dl.  Again hydration, is very
important.  Give oral fluids  at  a  rate  of  2-4  liters  every  24  hours.
Patients that have renal failure may need dialysis.

                             -URTICARIA-
Most cases  of  urticaria  are  idiopathic,  but  occasionally  uritcaria and
angioedema are due  to  infectious  diseases,  endocrine  diseases,  collagen
vascular  disorders, neoplasms, and allergies.  Urticaria can be divided into
acute and chronic.  Acute urticaria  and  angioedema usually regress within 6
weeks, whereas chronic urticaria can persists for months to years.  For acute
urticaria, a limited workup should be done and treat the uritcaria with an H1
antihistamine.  INFECTIOUS CAUSES: Occult bacterial infections of the  teeth,
gums,  sinuses, urinary tract and gall bladder may be present.  Urticaria may
be caused by hepatitis B,  Epstein-Barr,  and  Coxsackie A and B. Hepatitis B
and infectious mononucleosis can cause chronic urticaria.  Urticaria  can  be
caused  by  parasites.  When this is the case, the IgE and blood eosinophilia
are usually increased.  Fungal  infections  with  Candida and Tinea have also
caused urticaria.  ALLERGY CAUSES: Insect stings commonly cause urticaria  as
do  various  drugs.   Antibiotics and aspirin are common offending agents.  A
complete list of all  the  medicines  the  patient has been taking, including
over the counter medications, should be obtained.   Again,  eosinophilia  and
elevation of the IgE would suggest drugs as the cause.  However, aspirin does
not  cause  an elevation of the IgE.  PHYSICAL URTICARIA AND ANGIOEDEMA: Cold
urticaria can be caused  by  exposure  to  the  cold, holding cold objects or
swimming in cold water.  It  can  also  be  caused  by  essential  and  mixed
cryoglobulinemias,   cryofibrinogemia   and  cold  agglutinin  diseae.   Cold
urticaria may be seen in association with infectious mononucleosis, Raynaud's
diseases,  and  other  collagen  vascular  diseases.   Secondary  syphilis is
another  cause   which   is   mediated   by   an   IgG   hemolytic   antibody
(Donath-Landsteiner  antibody).   Patients  that  have  an elevated IgM and a
deficiency of the C4 component  of  complement  is  a rare cause.  To confirm
cold urticaria, hold an ice cube to the patients skin for 4 minutes, and if a
wheal develops at the site within 10 minutes the test is considered positive.
If positive, screening tests such as ANA,  RPR,  monospot  and  cryoglobulins
should  be  determined.   Treatment  of  cold  urticaria is treated with self
administration of  epinephrine,  and  cyproheptadine  4  mg QID.  Cholinergic
urticaria is caused by increased environmental temperature, emotional  stress
and  exercise.   It has an incidence of about 5% of chronic urticaria and can
be  associated  with  cold  urticaria  and  dermatographism.   Clinically  it
presents as 1-3 mm pruritic papules  on  the face and trunk after exposure to
the above incitants.  Treatment is with hydroxyzine.  Solar urticaria  occurs
within 3 minutes after exposure to light.  It is a rare disease.  There are 6
types  of  solar  urticaria, depending upon the particular wavelength that is
instrumental in causing  the  urticaria.   Type  VI occurs in protoporphyria.
The diagnosis can be made by an increase in protoporphyrins in  RBCs  and  in
protoporphyrins  and  coproporphyrins  in  the  feces.   Urine porphyrins are
normal.  Treatment is with beta-carotene 30-300 mg/day.  Sunscreens should be
used as well as avoiding  sunlight.   NEOPLASMS: Urticaria is associated with
malignancies of the rectum, colon, lungs, liver, and ovaries.   It  has  also
been  seen  in  Hodgkin's  disease.   Systemic  mastocytosis causes mast cell
infiltration of the lymph  nodes,  skin,  liver,  spleen,  bone marrow and GI
tract.  The release of mast cell mediators  can  cause  urticaria,  diarrhea,
bronchospasm  and shock.  There is elevation of plasma and urinary histamine,
and urinary prostaglandin D2 metabolites.   If  biopsy of the affected tissue
is done there will be high levels of histamine found.  Treatment is  with  H1
or  H2  antihistamines.   Cromolyn  100-200  mg qid can help the GI symptoms.
HEREDITARY  SYNDROMES:  Urticaria	can  be  caused  by  hereditary angioedema,
hereditary vibratory angioedema, familial  cold  urticaria,  C3b  inactivator
deficiency  and  a  hereditary syndrome of amyloidosis, urticaria, limb pains
and nerve deafness.  Hereditary  angioedema  can  be  life threatening and is
transmitted as an autosomal dominant trait.  Affected family members  do  not
have  urticaria,  but  have  recurrent  attacks  of  nonpruritic,  nonpitting
peripheral  edema.   There  may  be  painful  swelling  of the bowel wall and
laryngeal edema which can cause upper  airway obstruction.  It is caused by a
deficiency of  C1  esterase  inhibitor.   A  screening  test  for  hereditary
angioedema  is  done  by  measuring  the C4, which is always decreased during
attacks.  Danazol is used to  stimulate increased production of the deficient
C1 inhibitor.  Hereditary vibratory angioedema is initiated by  vibration  of
the  skin.   Treatment  is  with  diphenhydramine.   Caldwell's  syndrome (an
acquired   deficiency   of   C1    inhibitor   deficiency   associated   with
lymphoproliferative malignancies) is usually seen in  elderly  patients  that
have recureent episodes of angioedema that appear suddenly.  The CH50, C1, C4
and  C1 inhibitor levels are usually low.  ENDOCRINE CAUSES: Hyperthyroidism,
hypothyroidism,  diabetes   mellitus   and   hyperparathyroidism   have  been
associated with urticaria.  IMMUNE COMPLEX CAUSES: Urticaria can be caused by
serum sickness, secondary to the use of antimicrobial agents and immune serum
globulins,  such  as  antithymocyte  globulin  and  zoster  immune  globulin.
Hypocomplementemic urticarial vasculitis can  produce  typical  urticaria  or
appear   as   palpable  purpura  or  erythema  multiforme  (target  lesions).
Hypocomplementemic urticarial lesions usually last more than a day as opposed
to other urticarial lesions that usually  last 3-4 hours.  These patients may
also have myalgia, arthralgias, fever and leukocytosis.  Tests should include
a  sedimentation  rate,  skin  biopsy  for  histopathologic  exam   and   for
immunofluorescent  studies.   The biopsy usually shows necrotizing vasculitis
and  deposition  of  fibrin   and   nuclear   debris  in  the  vessel  walls.
Immunofluorescent  staining   will   show   staining   for   complement   and
immunoglobulins   deposited   at  the  dermal-epidermal  junction.   SLE  and
rheumatoid arthritis may be  associated  with a complement mediated urticaria
in 4-9% of cases.   HELPFUL  CLUES  FOR  A  DIAGNOSIS:  If  the  patient  has
constitution  symptoms (consider vasculitis, neoplasm and infection), Lesions
lasting  >  24  hours  (consider   vasculitis),  Presence  of  arthritis  and
arthralgias (consider vasculitis), Cold induced  urticaria  (consider  immune
complex  disease,  infection  and  physical urticaria), Recent foreign travel
(consider  parasites),  Presence  of   jaundice  and  hepatomegaly  (consider
infection, vasculitis, and neoplasm), Eosinophilia  (consider  parasites  and
drug  reactions), Leukocytosis (consider vasculitis, neoplasm and infection),
Sinusitis (consider  infection  and  allergy),  Elevated  sed  rate (consider
vasculitis, infection and neoplasm),  Dental  disease  (consider  infection),
Cyclical  urticaria (consider endocrine disorders), Unexplained rib fractures
(consider hyperparathyroidism), Abnormal  chest  x-ray (consider neoplasm and
infection), Weight loss (consider infection  and  neoplasm),  Lymphadenopathy
(consider  infection  and  neoplasm),  Angioedema  during childhood (consider
hereditary syndromes), Angioedema after the 4th decade (consider neoplasm and
Caldwell's syndrome), Anemia  (consider  parasites,  and neoplasm), Abdominal
complaints (consider parasites, neoplasm and  hereditary  syndromes),  Melena
(consider   neoplasm),  Photosensitivity  (consider  physical  urticaria  and
protoporphyria).  URTICARIAL INVESTIGATION: ALLERGY:  If allergy is suspected
obtain IgE, eosinophil count, RAST, skin tests and  do  drug  challenge,  and
diet  and  food  challenge.   PARASTITIC  INFECTION:  For suspected parasitic
infestation  obtain  IgE,  eosinophil  count,  and  stool  exam  for  ova and
parasites.   INFECTION:  For  suspected  infections  obtain,  strep   screen,
monospot  test,  sinus  x-rays,  fungal  cultures,  viral titers, gallbladder
ultrasound, hepatic enzymes  and  examination  of  teeth  and gums.  PHYSICAL
CAUSES: Obtain RBC protoporphyrins, perform exercise challenge, pressure  and
vibration  challenge,  methacholine  skin  test,  and  ice  cube  skin  test.
NEOPLASM:  For  suspected neoplasm obtain serum protein electrophoresis, bone
marrow biopsy, CEA,  imaging  studies,  CH50,  C3,  C4, C1Q.  VASCULITIS: For
suspected vasculitis obtain CH50, C3, C4, sedmimentation rate, cryoglobulins,
ANA, rheumatoid ractor, skin biopsy, HBsAg, C1q binding and Raji cell  assay.
ENDOCRINE:  For suspected endocrine causes obtain thyroid autoantibodies, T4,
glucose, ca, and phosphorus.

                              -UVEITIS-
Uveitis is an inflammation of  the  uveal  tract  which consists of the iris,
ciliary body, choroid and retina.  It may further be  divided  into  anterior
uveitis,  posterior uveitis, or panuveitis.  ANTERIOR UVEITIS (consitutes 80%
of all cases) is characterized  by  increased protein (flare) in the anterior
chamber, and corneal endothelium.  In nongranulomatous uveitis,  the  keratic
precipitates  are smaller than in granulomatous uveitis, and iris nodulations
are not seen.   Granulomatous  uveitis  will  characteristically reveal large
mutton, fat-like lesions with iris  nodules.   If  the  anterior  uveitis  is
severe,  there may also be a layered collection of white cells (hypopyon) and
fibrin in the anterior chamber.  The  major signs of anterior uveitis include
a perilimbal flush, miosis, and corneal endothelium  precipitates  visualized
by  the  slit  lamp.   There  is  decreased visual acuity, deep eye pain, and
photophobia.  Synechiae occur  in  many  areas,  such  as  the  pupil to lens
(posterior synechiae), iris to chamber angle (peripheral anterior synechiae),
and iris to cornea (anterior synechiae).  Cataract and glaucoma may  also  be
seen.   There  is  unilateral involvement in 95% of HLA-B27 associated cases.
Bilateral involvement  and  systemic  symptoms  such  as  fatigue, fever, and
abdominal  pain,  may  be  seen  in  patients  with  interstitial  nephritis.
POSTERIOR UVEITIS: In posterior uveitis, cells  are  seen  in  the  vitreous.
Retinitis  is frequently present.  Choroiditis is characterized by patches of
yellow, white and gray.  Later, as  these  areas scar, the areas become white
with a well defined dark area of pigment on the borders.  Macular  edema  can
cause  cysts  to  form  in  the macula.  The optic nerve may be involved as a
papillitis or retrobulbar neuritis.  Vasculitis is seen early with cuffing of
the vessels with gray-white cuffs.   Posterior uveitis usually has a gradual,
subacute visual loss, and  bilateral  involvement  is  common.   In  general,
posterior  uveitis  presents  as an eye with minimal redness and pain, unless
there is associated iritis.  CAUSES: The causes of uveitis are legion.  Acute
non-granulomatous anterior uveitis  may  be  commonly associated with HLA-B27
related   diseases   (ulcerative   colitis,   Crohn's   disease,   ankylosing
spondylitis, sacroilitis, psoriasis and Reiter's syndrome).   Herpes  simplex
and  zoster  can  also  cause  nongranulomatous  anterior  uveitis.  Behcet's
syndrome can cause an anterior uveitis associated with recurrent hypopyon, or
a posterior uveitis associated with  retinal vascular changes.  Diseases that
may  produce  granulomatous  anterior  or  posterior  uveitis   include   TB,
toxoplasmosis,  sarcoidosis,  syphilis,  and  Vogt-Koyanagi-Harada  syndrome.
Sarcoidosis  commonly presents as a bilateral uveitis.  SYSTEMIC DISEASES AND
UVEITIS: JUVENILE RHEUMATOID ARTHRITIS  is  usually associated with a chronic
bilateral iridocyclitis.  It occurs mainly  in  females  with  pauciarticular
joint  involvement,  and is associated with minimal symptoms, such as blurred
or decreased vision.  About  80%  will  have positive antinuclear antibodies.
Treatment is with topical corticosteroids and mydriatic therapy.   ANKYLOSING
SPONDYLITIS  is  more  common  in  males  and  is assoicated with HLA-B27 and
sacroilitis.  It is a  fairly  common  cause  of iridocyclitis.  Treatment is
with topical steroids and mydriatic drops.  REITER'S SYNDROME, also  is  seen
mainly in males and is assicated with HLA-B27.  It is a common cause of acute
iridocyclitis.   TOXOPLASMOSIS  is  a  common  cause  of  posterior  uveitis.
Toxoplasmosis  is  usually  transmitted  congenitally.  There is diminshed or
hazy vision due to recurrent  episodes  of acute focal necrotizing retinitis.
This may be associated with an iridocyclits that can present  as  a  painful,
red,  photophobic  eye.   Tests for toxoplasma antibodies is done by ordering
ELISA  or  indirect   fluorescent   antibody   testing.   Treatment  is  with
pyrimethamine, sulfonamides and systemic steroids.  TOXOCARIASIS is diagnosed
by ordering a serum, aqueous or vitreous ELISA for Toxocara.  Eosinophils may
be seen in the aqueous.  Toxocariasis is  common  in  children,  and  usually
causes   a  unilateral,  posterior  retinal  granuloma,  or  occcasionally  a
pan-inflammation of the  eye  (endophthalmitis).   Treatment is with systemic
steroids.  CYTOMEGALOVIRUS infection is  a  congenitally  acquired  infection
producing an acute necrotizing retinitis.  Viral inclusion bodies may be seen
in  the  urine and saliva.  Compliment fixation antibodies to CMV should also
be  ordered.   CMV  in  adults  is  usually  secondary  to  chemotherapy  for
malignancy and renal transplants.  Treatment  is  with ganciclovir given at 5
mg/kg IV bid for 2 weeks.  If patient has AIDS, CMV usually is recurrent, and
the patient will need long term prophylaxis.  HISTOPLASMOSIS  is  endemic  in
the  Ohio  and  Mississippi  valleys.   It  produces  multifocal choroiditis,
macular hemorrhagic lesions and  peripapillary  scarring.  The uveitis always
presents  months  to  years  after  acute  systemic  histoplasmosis.    Chest
radiographs  may  show typical calcification of histoplasmosis.  At this time
the complement fixation  is  usually  negative.   However,  the  skin test is
usually positive in about 80%, and most patients will have a positive  HLA-B7
if there is macular disease.  Treatment is with laser photocoagulation of the
macular  areas  and systemic and periocular steroid injections.  TUBERCULOSIS
uveitis is rare.  A PPD and  chest  x-ray  should be done.  Treatment is with
systemic corticosterids  and  antituberculosis  drugs.   HERPES  SIMPLEX  AND
ZOSTER  produces a severe acute peripheral retinitis.  Retinal detachment may
complicate the disease in 75% of cases,  but can be prevented by acyclovir IV
and laser treatment.  Most of the cases  start  as  unilateral  disease,  but
about  33%  may  develop  bilateral  disease  after  several  weeks to years.
Diagnosis may be made by  retinal  biopsy  which will show the viral capsids.
SYPHILITIC uveitis is rare and can occur in secondary,  tertiary,  or  latent
syphilis.     Laboratory    testing   includes   the   VDRL,   FTA-ABS,   and
hemagglutination  and  microhemagglutination  tests  for  Treponema  pallidum
antibodies.   Spinal  fluid  VDRL  may  also  be  done.   Treatment  is  with
penicillin and  steroids.   SARCOIDOSIS  produces  anterior  uveitis  in 35%,
posterior uveitis in 10% and panuveitis in 55% of cases.  Sarcoidosis  is  10
times  more  common in males than females.  Laboratory testing includes chest
x-ray that is positive in  80%,  serum calcium (elevated in 12%), angiotensin
converting enzyme, gallium scan of the head, neck and chest,  and  biopsy  of
conjunctival  or lacrimal granulomas, lymph nodes, skin and liver.  Treatment
is with steroids, either locally, periocular, or systemic.  BEHCET'S SYNDROME
is seen mostly in men aged 20-40,  most commonly in association with oral and
genital aphthae, thrombophlebitis, dermatitis  and  polyarthritis.   Behcet's
syndrome  is  rare  in the USA.  Laboratory findings should include biopsy of
any skin or mucous  membrane  lesions,  and HLA-B5, and HLA-DR5 autoantigens.
Patients   are   treated   with   local   and    systemic    corticosteroids,
immunosuppressive  drugs,  or  cyclosporine.   BIRDSHOT  CHOROIDOPATHY  is an
idiopathic  disease  characterized  by  chronic  bilateral  intermediate  and
posterior uveitis.  Multifocal areas of  choroidits, cystic macular edema and
diffuse vitritis are usually  seen.   About  95%  of  patients  will  have  a
positive   HLA-A29  antigen.   Treatment  is  with  periocular  and  systemic
steroids.  PARS PLANITIS  is  a  common  disorder  usually  occuring in young
adults or older children.  Symptoms consist of bilateral vitritis,  decreased
visual  acuity  and  blurring of vision.  There is cystoid macular edema, and
cells in the vitrious,  usually peripheral in position.  VOGT-KOYANAGI-HARADA
SYNDROME usually presents as bilateral episodes of acute  iridocyclitis  with
redness,  pain  and  photophobia.   Subsequently, there may be severe diffuse
choroiditis that causes  detachment  of  macular  areas,  resulting in visual
loss.  It is seen mostly in Orientals, aged 30-50.  It may be associated with
vertigo (30%), temporary deafness  (30%),  HLA-B22  (45%),  alopecia  areata,
poliosis,  vitiligo,  and  meningeal  headaches  which  can be fleeting.  The
headaches are associated with a CSF pleocytosis.  Treatment is with local and
systemic  corticosteroids  and   immunosuppressive  medication.   SYMPATHETIC
OPHTHALMIA presents as a sequelae following penetrating  injury  to  one  eye
which  produces a bilateral granulomatous uveitis.  It may occur in up to .5%
of nonsurgical, and less than .01%  of surgical penetrating eye wounds.  Most
cases (80%) will present 2-12 weeks post injury.  Rarely, it may  present  as
early  as  1  week,  or  as  late as 20-30 years following injury.  PSORIASIS
characteristically  involves  the  terminal   phalangeal  joints  and  ungual
alterations.  HLA-B17 and HLA-B27 are usually  present.   ULCERATIVE  COLITIS
may  also  be  associated  with  uveitis.   COMPLICATIONS OF UVEITIS: include
increased intraocular pressure with  acute angle closure glaucoma, synechiae,
cataract formation, keratic precipitate deposition on the  lens  and  cornea,
macular  edema,  vasculitis  with vascular occlusion, retinal infarction, and
optic nerve damage.  LABORATORY: There is  no specific test for the diagnosis
of uveitis.  However, tests for the associated diseases may be positive.  The
patient should have a CBC, BUN, and creatinine (interstitial nephritis), ANA,
and ESR (SLE, and Sjogren's syndrome),  PPD  (tuberculosis),  VDRL,  and  FTA
(syphilis),  HLA-B27  typing (ankylosing spondylitis, and Reiter's syndrome),
and Lyme  serology  (Lyme  disease)  Slit  lamp  examniantion  is  a must for
diagnosis.  Chest x-rays should be done  when  histoplasmosis,  tuberculosis,
sarcoidosis  and lymphoma are suspected.  Sacroiliac x-ray and CT imaging are
usful for  ankylosing  spondylitis.   TREATMENT:  In  general,  most cases of
anterior uveitis  are  treated  with  mydriatic/cycloplegic  drugs,  such  as
homatropine 2% ophthalmic solution (Isopto) 2 gtt to the affected eye twice a
day  to q 3 hours in severe cases, OR scopolamine .25% (Isopto-Hyoscine) TID,
OR cyclopentolate 1% (Cyclogyl), PLUS prednisolone 1% ophthalmic suspension 2
gtts every one hour initially followed by tapering.

                             -VAGINITIS-
Vaginitis  may be due to trichomoniasis, candidiasis, bacterial vaginosis, or
atrophic vaginitis.  CANDIDIASIS: The  patient  usually complains of burning,
itching and irritation of the vulvovaginal area.  There may also be a vaginal
discharge and pain with intercourse.  The discharge is classically  a  sticky
cottage  cheese  like  discharge.   However,  the  discharge can be normal or
anywhere in between  this  spectrum.   The  vaginal  pH is normal.  BACTERIAL
VAGINOSIS: Bacterial vaginosis is the most common  cause  of  vaginitis.   It
occurs  when  Gardnerella  vaginalis, Mycoplasma hominis, Mobiluncus species,
and nonfragilis Bacteroides  species  (normal  vaginal  flora) overwhelms the
Lactobacillus species.  Bacterial vaginosis  can  cause  pelvic  inflammatory
disease,   cervicitis,   intraamniotic  infection,  recurrent  urinary  tract
infections,  preterm  labor,  postpartum  endometritis,  and posthysterectomy
vagninal cuff cellulitis.  These patients typically have an increased vaginal
discharge that has a foul fishy odor, and  is  worse  with  menses  or  after
unprotected  intercourse.   The discharge is a white to grayish color.  These
patients have a vaginal pH of 5 or more.  TRICHOMONIASIS: The patients have a
foul smelling, profuse yellow discharge that may be frothy.  There is genital
itching and irritation.  There may be  redness of the introitus, vagina and a
strawberry appearing cervix.  The vaginal pH is 5  or  more.   LABORATORY:  A
swab  sample  should  be  obtained from the posterior fornix and smeared on a
slide.  After applying one  drop  of  saline  to  the  sample a cover slip is
applied.  This is then inspected with microscopy.  Trichomonas may be seen as
motile oval flagellates.  Clue cells (bacteria coated epithelial  cells)  are
indicative  of  bacterial vaginosis.  A second swab sample should be obtained
from the wall of the vagina and applied  to another slide.  To this 1 drop of
10% potassium hydroxide (KOH) is applied and covered with a coverslip.  After
applying the KOH, a  pungent  fishy  odor  will  be  generated  if  there  is
bacgterial  vaginosis.   If  yeast  are  present  on the KOH slide, they will
appear as thread like hyphae and  budding yeast.  Heating the slide may yield
a better field for viewing the yeast, by lysing the cells  that  can  obscure
the field.  Patients may have mixed infections so don't expect to always find
just  one  type  of infection.  The third step in establishing a diagnosis is
the vaginal pH.  This is done by  applying a sample obtained from the vaginal
wall or posterior fornix to pH paper.  Typically candidiasis has a normal  pH
of  between 4-4.5.  A pH of 5 or more is seen in trichomoniasis and bacterial
vaginosis.    THERAPY:   CANDIDIASIS:    Clotrimazole    vaginal   cream   1%
(Gyne-Lotrimin, Mycelex-7, Fem Care) is a pregnancy category B drug,  and  is
used  as  one  applicator  at  bedtime  for  7-14 days.  Clotrimazole vaginal
tablets 500 mg (Mycelex-G) is used as one 500 mg tablet at bedtime for 1 day.
Clotrimazole vaginal tablets 100  mg  (Gyne-Lotrimin, Mycelex-7, Fem Care) is
used as one 100 mg tablet at bedtime for 7 days or  two  100  mg  tablets  at
bedtime  for 3 days.  Butoconazole nitrate vaginal cream 2% (Femstat) is used
as one applicatorful at bedtime for 3 days.  It may be extended for 6 days if
needed.  It is a pregnancy category  C  drug,  and  should not be used in the
first trimester of pregnancy.  Ticonazole vaginal ointment 6.5%  (Vagistat-1)
is  used  as  one  applicatorful  at  bedtime  for  1 day.  It is a pregnancy
category C and should  only  be  used  in the first trimester	if absolutely
indicated.  Terconazole vaginal cream  0.4%  (Terazol  7)  is  given  as  one
applicagtorful at bedtime for 7 days.  Terconazole vaginal cream 0.8% is used
as  1 applicatorful at bedtime for 3 days.  Terconazole vaginal suppositories
80 mg (Terazol  3)  is  given  as  one  suppository  at  bedtime  for 3 days.
Terconazole is a pregnancy category C drug and can cross aminiotic membranes.
Miconazole  nitrate  vaginal  cream  2%  (Monistat  7)  is   given   as   one
applicatorful   at   bedtime   for   7   days.   Miconazole  nitrate  vaginal
suppositories 100 mg (Monistat  7)  are  given  as  one 100 mg suppository at
bedtime  for  7  days.   Miconazole  nitrate  vaginal  suppositories  200  mg
(Monistat 3) are used as one 200  mg  suppositroy  at  bedtime  for  3  days.
Miconazole  is a pregnancy category B drug.  Nystatin vaginal tablets 100,000
units  (Mycostatin)  are  given  as  one  tablet  at  bedtime  for  14  days.
Occasionally, oral  medications  may  be  indicated  for vaginal candidiasis.
Indications for their use would include those patients who are  reluctant  to
use the creams or suppositories, those that are allergic to the preservatives
(methylparaben  and propylparaben), those that have AIDS, and those that have
refractory candidiasis.  However, the oral  drugs should be used with caution
as they are associated with more serious side effects.  They  should  not  be
used  in  patients  with  liver disease, pregnant patients, or those patients
that are also taking terfenadine  (Seldane)  or astemizole (Hismanal) as they
can cause ventricular arrhythmias.  Fluconazole  (Diflucan)  is  given  as  a
single  150  mg dose.  Itraconazole (Sporanox) may be given as 200 mg/day for
three days or 400 mg x 1 dose.  Ketoconazole (Nizoral) is given as 200 mg bid
for 5-7 days.  For those  patients  that  have recurrent vaginitis (3 or more
episodes in 6 months), prophylactic treatment with fluconazole at 100-200  mg
orally once a week may be tried.  Alternatively, clotrimazole (Mycelex-G) 500
mg  vaginal  tablet  may  be given weekly for six months, or ketoconazole has
also been used at 100  mg/day  for  6  months.   At  the  end of 6 months the
prophylaxis is discontinued and the patient is observed.   If  the  vaginitis
recurs,   treat   the   acute   infection,   and  continue  the  prophylaxis.
TRICHOMONIASIS TREATMENT:  The  treatment  of  choice  for  trichomoniasis is
metronidazole (Flagyl, Protostat) that can be given as a single 2 gram  dose,
or  given  as  250  mg  TID  for  seven days.  Sexual partners should also be
treated as this is  a  sexually  transmitted  disease.   A  side effect is GI
distress, and for this reason it should be taken  with  food.   It  also  may
cause  a  metallic  taste.   Patients  should  be  advised that alcohol taken
during, or within 24 hours of the  last dose may experience a disulfiram like
reaction.   Metronidazole  is  contraindicated  in  the  first  trimester  of
pregnancy.  It may be used in the second and third trimesters, and should  be
given  as  the 7 day regime.  During the first trimester, clotrimazole 100 mg
tablets,  or  vinegar   douches   may   be   helpful.   BACTERIAL  VAGINOSIS:
Metronidazole (Flagyl, Protostat) is given as 500 mg BID for seven  days,  or
as  a single 2 gram dose.  The single 2 gram dose is less effective and there
is a higher recurrence  rate.   Clindamycin  (Cleocin  HCL) may also be given
orally  as  300  mg  bid  for  7  days.   Intravaginal  therapy  consists  of
clindamycin  phosphate  vaginal  cream  2%   (Cleocin),   and   metronidazole
(MetroGel-Vaginal).    Clindamycin   (Cleocin)   vaginal   is  given  as  one
applicatorful at bedtime for  seven  nights.  Metronidazole MetroGel) vaginal
is given as one  applicatorful  bid  for  5  days.   For  patients  that  are
pregnant,  the  patient  may  be  given  clindamycin vaginal cream during the
second and third trimesters.   Some  authorities  would consider treating the
sexual parrtner with oral metronidazole.   DIFFERENTIAL  DIAGNOSIS:  Patients
may  complain  of  itching  and vaginal discharge due to other causes.  These
include enterobiasis, Giardiasis, Herpes  simplex  virus,  types 1 & 2, human
papillomavirus, vaginal irritants  such  as  deodorants,  douches,  perfumes,
soaps,  sanitray  napkins,  tampons, toilet tissue, spermacides, condoms, hot
tubs or various  topical  medications.   Gonorrhea,  syphilis, and chlamydial
infections should always be ruled out.

                         -VANCOMYCIN DOSING-
Vancomycin is given based on  the creatinine clearance (mL/min).  The initial
dose is 15 mg/kg.  If the CrCl is >94 give q12h.  If  75-94  give  q18h.   If
55-74  give  q24h.   If  35-54  give  q36h.  If 25-34 give q48h.  If <25 then
adjustment  based  on   serum   concentrations.    An  alternate  method  for
calculating the dose in patients with renal disease uses the  formula:  Total
daily  dose=150 + 15 (CrCl).  This formula is used for daily dosing after the
patient has been given a initial loading dose of 15 mg/kg.

                     -VASCULITIS - AN OVERVIEW-
Vasculitis  tends to be a difficult diagnosis to make, mainly because some of
the symptoms  are  so  mundane  and  of  the  garden  variety  type, that the
diagnosis is never even entertained.  There is usually a long time gap before
someone eventually makes the diagnosis.  There have  been  many  attempts  to
classify  the  vasculitides,  but  none  is  perfect because there is so much
overlap between some of the  diseases.   Perhaps,  one of the most simple and
most helpful plans is dividing the syndromes into primary, in which the serum
tests will show little evidence of an immune  mechanism,  and  the  secondary
syndromes.   The  PRIMARY  VASCULITIS  SYNDROMES consist of the Churg-Strauss
syndrome (allergic granulomatosis),  Classic  polyarteritis nodosa, Wegener's
granulomatosis, Schonlein-Henoch purpura, giant cell  or  temporal  arteritis
and  Takayasu's  arteritis (aortic arch arteritis).  The SECONDARY VASCULITIC
SYNDROMES consist  of  RHEUMATIC  diseases  (rheumatoid  arthritis, rheumatic
fever,  mixed   connective   tissue   disease,   dermatomyositis,   SLE   and
dermatomyositis),  INFECTIOUS  diseases (bacterial endocarditis and hepatitis
B),  HYPERSENSITIVITY  diseases   (serum   sickness,  drug  hypersensitivity,
allopurinol vasculitis and amphetamine  abuse),  secondary  CRYOGLOBULINEMIAS
(essential mixed cryoglobulinemia, multiple myeloma and lymphoma).  CLINICAL:
CONSTITUTIONAL  SYMPTOMS  consist of fever, weight loss, and night sweats and
these occur in over  90%.   ABDOMINAL  PAIN  is usually nonspecific, but some
patients may have the typical postprandial pain of mesenteric  insufficiency.
ARTHRALGIA  AND  MYALGIA-  Many will have severe pain in the extremities, but
usually without synovitis.  There  may  be  some tenderness around the joints
and a constant ache in the joints and extremities.  SKIN LESIONS may  present
as   petechiae,   livedo   reticularis  with  ulceration,  palpable  purpura,
petechiae, splinter hemorrhages and  gangrene  of  the digits.  RENAL DISEASE
occurs in about 50% of the patients  with  systemic  necrotizing  vasculitis.
Urinalysis  may  show  proteinuria, and hematuria.  If a biopsy is done there
usually is  focal  segmental  necrotizing  glomerulonephritis  sometimes with
crescents.  Hypertension and uremia may develop.   NEUROLOGIC  LESIONS-  This
occurs   in  about  50%  also.   A  specific  form  of  neuropathy  known  as
mononeuritis multiplex is sometimes present  that involves both the motor and
sensory  nerves.   These  neuropathies  develop  either   simultaneously   in
different  nerves  or  within  a  few days of each other and involve the long
nerves as the median, ulnar, and peroneal.  The most common, but non-specific
neurologic finding is a  peripheral sensory neuropathy.  Cranial neuropathies
can occur  also  as  well  as  strokes  and  transverse  myelitis.   The  CNS
vasculitis  is  a  small vessel occlusion with perivascular inflammation, and
not  the  necrotizing  arteritis  that   is  seen  elsewhere.   EYE  DISEASE-
Episcleritis is fairly common, and even though the lesions look terrible, the
symptoms are usually minor.  There may be some mild  tenderness  of  the  eye
ball  unless  an  iritis develops, which then will lead to pain, photophobia,
decreased vision and a small pupil.  Diplopia may develop with involvement of
cranial nerves 3, 4 and 6. The  optic  nerve may be damaged by vasculitis and
cause blindness that is sudden.  Funduscopy will show a pale optic  disc  and
some  hemorrhages.   If there is retinal vasculitis the vision is blurred and
there are scattered  hemorrhages.   Temporal  arteritis  usually involves the
optic nerve.  DIAGNOSIS is made  by  laboratory  testing,  arteriography  and
biopsy.  LABORATORY: Laboratory findings show an increased sedimentation rate
in  almost  100%  of cases and in many there will be anemia and leukocytosis.
Again, these are all non-specific findings,  but when put together with other
lab findings, will point toward the diagnosis.  In  the  appropriate  setting
the  following should be ordered: antinuclear antibodies, hepatitis B surface
antigen,   cryoglobulins,   serum   complement,   antineutrophil  cytoplasmic
antibodies,  eosinophil  count  and  serum  protein   electrophoresis.    The
antineutrophil  cytoplasmic  antibody (ANCA) directed against proteinase 3 is
very  specific  for  Wegener's   granulomatosis.   ANCA  perinuclear  pattern
directed against  myeloperoxidase  is  also  seen  in  Wegener's,  idiopathic
cresenteric  glomerulonephritis and microscopic polyarteritis nodosa.  Biopsy
- Excisional biopsy is better than  punch biopsy.  Biopsy of palpable purpura
may be very helpful, as is sural nerve and gastrocnemius  muscle  biopsy,  if
there  is  symptomatic neuropathy and nerve conduction studies show a delayed
sural  nerve  conduction.   Blind  biopsies  will  yield  varying  degrees of
diagnosis.  Hepatitis B vasculitis is widespread and biopsy of the quadriceps
or deltoid may be  helpful.   Arteriography  may  be  useful  in  Takayasu's,
arteritis  involving  the  aortic  arch,  periarteritis  involving  the renal
arteries with aneurysms and  mesenteric aneurysms and occlusions.  TREATMENT:
Steroids  are  used   in   temporal   arteritis,   aortic   arch   arteritis,
leukocytoclastic  cutaneous  vasculitis, Churg-Strauss syndrome and hepatitis
B. Corticosteroids are usually given in  a starting dosage of prednisone of 1
mg/kg  in  divided  doses.   Steroids   plus   cytotoxic   drugs:   Wegener's
granulomatosis  responds  extremely  well to cyclophosphamide and prednisone.
Steroids and  cytotoxic  drugs  may  also  be  used  in Polyarteritis nodosa,
fulminant cases of allergic granulomatosis and hepatitis B, and some cases of
rheumatoid vasculitis.  Plasmapheresis may be used in  cryoglobulinemia.   No
therapy  is given with Schonlein-Henoch purpura and serum sickness vasculitis
from drugs.

                   -VENOUS HUM (Innocent murmur)-
Is detected during early school years.  The murmur disappears on  supination,
compression  of  the  jugular  vein  or  turning  the  head.  The murmur is a
continuous murmur at the clavicles.

                         -VENOUS THROMBOSIS-
The differential diagnosis of unexplained venous thrombosis in a young person
is   as   follows:    Antiphospholipid   syndrome   (anticardiolipin,   lupus
anticoagulant), Nephrotic syndrome (UA, serum albumin, 24 hr urine  protein),
Protein   C  deficiency  (Protein  C),  Protein  S  deficiency  (protein  S),
Antithrombin III deficiency (antithrombin III), Malignancy (history, physical
and lab and radiology tests).

                        -VENTILATOR WEANING-
MAJOR CRITERIA FOR WEANING: Vital capacity (VC) >10-15 ml/kg  of  ideal  body
weight,  Tidal  volume/vital  capacity  ratio  (VT/VC  <  0.5,  Peak negative
pressure (PNP) or inspiratory  force  at  least  30 cmH2O, Minute ventilation
(VE) < 10 liter/min, Maximum voluntary ventilation (MVV) >  2  x  VE.   MINOR
CRITERIA:  Dead  space/tidal  volume ratio (VD/VT) < 0.6, Qshunt/Qtotal ratio
<25-30% which corresponds  approximately  to  pO2  >300-350 on FiO2=1.00.  In
addition the patient should not have any anemia or severe  systemic  disease,
excessive  thick  secretions,  and  swallowing  and  gag  response  should be
adequate to prevent aspiration.  If  all  of  the major criteria are met, the
patient should be p;alce on a T-piece for 1 hour.  At the end of this time if
ABG is unchanged, then extubate, otherwise weaning can  be  accomplished  by:
1-T-piece  weaning  by  gradually  increasing  the  duration  of  spontaneous
breathing, 2- IMV weaning by gradually decreasing mandatory respiratory rate,
or	3-pressure   supported   ventilation  (PSV)  using  positive  inspiratory
pressure to augment spongtaneous tidal volume.  The goal is to obtain a pO2 >
60 mmHG on FiO2 < 0.5 without dyspnea.

                     VENTRICULAR SEPTAL DEFECT
Ventricular  septal defect (VSD) is the most common congenital heart disease.
It is  usually  detected  in  childhood  and  repaired.   With  small defects
symptoms are less and the magnitude of left to right shunt  is  reduced  with
less  adverse  influence  on  the  pulmonary vasculature.  Most of these will
survive to  adulthood.   However,  large  defects,  can produce biventricular
overlaod and a marked increase  of  flow  to  the  pulmonary  system.   These
defects  must be closed or adulthood survival is not expected.  DIAGNOSIS: If
the shunt is large there  will  be  a  harsh  holosystolic murmur in the left
third and fourth interspaces in the left parasternal area.  There may also be
middiastolic flow murmurs and an S3  at  the  apex.   A  systolic  thrill  is
frequently  present.   There may be aortic regurgitation if the defect in the
VSD is high, caused by prolapse of  a  valve leaflet.  If the shunt is small,
the murmur may be heard only in early systole or a diamond shaped murmur.  If
the  murmur  decreases  over  time,  this  usually   means   that   pulmonary
hypertension  is  developing.   Ultimately,  if  not corrected, Eisenmenger's
complex develops with  equalization  of  right  and left ventricular systolic
pressures.  Depending on the size of the shunt, the ECG may show right,  left
or  biventricular  hypertrophy.   Chest  x-ray  will  show enlarged pulmonary
arteries and increased  vascularity  plus  enlargement  of  the right or left
ventricle or biventricular enlargement.  Doppler ultrasound  can  assess  the
size of the VSD shunt and the pulmonary artery pressure.  Echo may detect the
defect  as  well  as  the chamber enlargement.  Radionuclide flow studies are
able to quantify pulmonary to systemic  flow  ratios.  MRI may detect the VSD
defect.  Cardiac catheterization can quantify pulmonary  vascular  resistance
as  well as render a definitive diagnosis.  PERIMEMBRANOUS VSD: Small defects
in this area can close spontaneously.   Most  of these close in the first few
months of life, but rarely later in adolescence.  If they do not close  there
is  a  potential  for  endocarditis as well as LV volume overload.  LV volume
overload development mandates repair.   Also,  if  the  patient has an aortic
regurgitation murmur, surgery is usually indicated in small VSDs.  Most large
perimembranous VSDs are associated with symptomatic heart failure by 4 months
of age.  These infants may be treated temporarily for CHF with furosemide  in
a total daily dose of 1-4 mg/kg/day given in divided doses.  Digoxin is given
at  6-10 ug/kg/day given as a BID dose.  Surgery should not be delayed beyond
1-2  years  of  age  in  large  defects,  since  pulmonary  hypertension  and
irreversible  pulmonary  vascular   obstruction  will  produce  Eisenmenger's
syndrome.  If surgical repair is done  prior  to  the  development  of  these
events  in  the  first  1-2  years of life, mortality approaches those of the
normal population.  About 2% will develop  complete AV block as a consequence
of the VSD surgery and require a permanent  pacemaker.   TRABECULAR  MUSCULAR
VSD:  These  defects  are  just  about  as  common as perimembranous VSDs and
represent the second most common type  of VSD.  As the septal muscle thickens
and grows in the  first  few  months  of  life,  many  of  these  will  close
spontaneously.   Rarely,  a  few of these are large and will require surgical
closure which can be  technically  difficult  because  of the location of the
defect.  EISENMENGER'S SYNDROME: Patients that have a large VSD will  have  a
gradual  increase  in  the  pulmonary vascular resistance and eventually will
become excessive over a time  period  of  3-20 years.  The pulmonary vascular
resistance is usually > 600 dynes/sec/cm-5 at this point and the  murmur  and
the  left-to-right shunt will decrease or even disappear.  Once the pulmonary
vascular  resistance  reaches  about   800  dynes/sec/cm-5,  surgery  is  not
indicated.  Clincially, patients at this point will have hemoptysis, dyspnea,
syncope and chest pain.  Physical exam will disclose clubbing,  polycythemia,
right  ventricular parasternal lift, and cyanosis.  These patients should not
receive oral contraceptives or become  pregnant.   The only treatment at this
point is combined  heart/lung  transplant.   SUMMARY:  Small  shunts  with  a
pulmonary  to  systemic  flow ratio less than 1.5 in asymptomatic patients do
not need surgery.  Patients with  large  shunts should be repaired to prevent
heart failure and irreversible pulmonary vascular obstruction and resistance.
Patients who have systolic pulmonary arterial pressures > 85 mm Hg with small
left to right shunts and pulmonary hypertension have a surgical mortality  of
50%.  In reversed shunts surgery is contraindicated.

                     -VENTRICULAR SEPTAL DEFECT-
Congenital  lesion,  common  in   fetal   alcohol  syndrome,  Down  syndrome,
precordial hyperactivity mayb be present.  Well localized holosystolic murmur
usually at LLSB, thrill may be present, soft.  In newborns a very  small  VSD
can  produce  a  vibratory  high  ptiched  blowing murmur over the sternum or
slightly to the left or right.   This  murmur  can be loud and disappear in a
few days due to a drop in pulmonary artery pressure.

                      -VENTRICULAR TACHYCARDIA-
NONSUSTAINED: Nonsustained ventricular tachycardia  (NVT)  is defined as runs
of 3 or more  beats  lasting  less  than  30  seconds.   If  the  patient  is
asymptomatic  and  has  no  associated  organic  heart  disease, treatment is
probably not necessary as the prognosis is good.  Patients who have had an MI
and develop NVT, the risk is  high  for  sudden death.  If no late potentials
are recorded on signal averaged ECG and the LV ejection fraction  is  normal,
the  prognosis  is good.  However, in many patients that do have registration
of late potentials and LV dysfunction, do not become symptomatic, which again
sets  them  up  for  sudden  death.   This  subset  of  patients  should have
ventricular stimulation, and those that have inducible sustained VT should be
treated with class III agents, sotalol or amiodarone,  because  proarrhythmia
is  less  prevalent,  and  some  studies  have shown an improved outcome.  To
assess the  efficacy  of  this  treatment,  ambulatory  ECG monitoring and/or
repeat stimulation studies should be carried out.  Signal averaged ECG is not
useful  in  following  these  patients.   Beta  blockers  such  as  atenolol,
metroprolol, naldolol and propranolol are occasionally effective and  may  be
tried  initially prior to using sotalol or amiodarone.  SUSTAINED VENTRICULAR
TACHYCARDIA: Sustained VT,  whether  symptomatic  or  asymptomatic, should be
treated with suppressive therapy.  Studies  should  be  carried  out  in  the
electrophysiology  laboratory.   Most laboratories start with Class IA agents
such as procainamide, quinidine, disopyramide,  but the success rate of these
drugs only approaches about 20-25% in suppressing the induced VT.   Adding  a
Class  IB  agents  such as mexiletine to the Class IA drugs will increase the
efficacy to 30-35%.  Currently, the best  drugs  to suppress VT are Class III
drugs such as amiodarone and sotolol.  These are effective in  about  40-55%.
Even  if  VT  can  be  induced,  amiodarone and sotolol have been shown to be
effective in the real life situation.   Patients with sustained VT who do not
respond  to  the  above  medications  may  be  candidates  for  an  automatic
implantable cardiac defibrillator (AICD).  The cost of an AICD is  >  $20,000
and is associated with a morbidity and mortality of about 5%.  AICD has a 95%
5  year  efficacy  rate  in  preventing  recurrent sudden death in those with
sustained VT.  About 40-55%  of  patients will require antiarrhythmic therapy
in conjunction with AICD to reduce the rate of the VT.

                -VENTRICULAR TACHYCARDIA (Treatment)-
STABLE  VENTRICULAR  TACHYCARDIA:   LIDOCAINE:   To  convert  polymorphic  or
monomorphic VT start  with  either  lidocaine  or  procainamide  (Pronestyl).
Lidocaine  HCL  (Xylocaine  HCL) is given by an IV bolus of .7-1.4 mg/kg.  If
the patient doesn't convert, repeat the dose  in 5 minutes giving the drug up
to a total of 200-300 mg in one hour.  If the patient converts,  but  the  VT
resumes,  the  patient  may  be  given  100  mg  of lidocaine and placed on a
continuous drip of lidocaine at 2  mg/min.   A  second bolus of 100 mg may be
given in about 20 minutes to keep the blood level up.  The benefits of  using
lidocaine  is  that  lidocaine  has  no effect on myocardial contractility or
blood pressure and will  not alter autonomic tone.  PROCAINAMIDE:Procainamide
is given at a dose of 2 mg/min IV until 1.0 gram  has  been  given,  the  QRS
widens  beyond  50%  of  baseline  or  hypotension  supervenes.  Procainamide
maintenance doses are safer  than  quinidine  because  of  the risk of sudden
death with quinidine.  Procainamide may be given orally at 500 mg to  1  gram
every  6  hours.   It  may  be  given  with a beta blocker such as metoprolol
tartrate (Lopressor) at a dose of 50  mg bid.  Procainamide may be given as a
first line drug against VT or may  be  considered  as  a  secondary  drug  if
Lidocaine  is  ineffective.   Prolonged use of procainamide may be associated
with a lupus erythematosus-like syndrome  and the patient should be monitored
with antinuclear antibody titers.   BRETYLIUM  TOSYLATE:  Bretylium  tosylate
(Bretylol),  a  type  III  drug, will convert VT and can be used at a dose of
5-10 mg/kg given  IV  slowly  over  a  10  minute  period.   The  drug may be
maintained at a dose of 5-10 mg/kg given every 6 hours.  Postural hypotension
is common.  MEXILETINE HCL:Mexiletine HCL (Mexitil), a type IB drug, given at
200 mg tid with a beta blocker such as metoprolol may  effectively  terminate
VT.   This  drug  has a tendency to produce severe GI distress, dizziness and
tremors which may be limiting  factors in its administration.  Mexiletine may
worsen congestive heart  failure  and  may  cause  hypotension.   PROPAFENONE
HCL:Propafenone  HCL  (Rythmol), a type IC agent given at 150 mg tid also may
be effective in converting VT  to  a  normal  rhythm.  If the initial dose is
ineffective increase to 250-300 mg tid  after  3-4  days.   This  drug,  like
flecanide, may increase mortality in patients who have had a prior myocardial
infarction  or  have  coronary artery disease.  Do not use propafenone if the
patient  has   severe   congestive   heart   failure.   FLECAINIDE:Flecainide
(Tambocor), a type IC agent, should only  be  used  if  there  is  good  left
ventricular function.  There is increased mortality if this drug is used with
patients  that  have  had  a a prior myocardial infarction or coronary artery
disease.  The drug may precipitate heart  block in about a third of patients.
Flecanide also is very proarrhythmic.  The appropriate setting may  be  in  a
young patient who is otherwise healthy.  Start at 50 mg bid and then increase
by 50 mg increments up to 200 mg bid.  SOTALOL:Sotalol (Betapace), a type III
agent  has mild beta blocking action and is safer than other drugs because it
has less of a tendency for proarrhythmic effects.  It has been more effective
in conversion of VT than type  IA  drugs.   Because of its mild beta blocking
properties there may be a slight diminution  of  left  ventricular  function.
Start  the  drug at 80 mg bid and increase every 2-3 days up to a total daily
dose of 480 mg.  AMIODARONE HCL:Amiodarone HCL (Cordarone), a type III agent,
is only used if other agents  fail  to  convert  the VT.  The drug has a high
side  effect  profile  including  a  proclivity  to  produce  proarrhythmias.
Amiodarone blood levels must be done frequently to avert toxicity.  It should
only be started while in the hospital at a loading  dose  of  1.2  grams  for
approximately  5 days, then 800 mg for 5 days and then maintenance of 200-400
mg/day.  The IV dose is 5 mg/kg IV  over 5 minutes followed by 1.8 grams over
24 hours.  Liver and  thyroid  function  testing  must  be  done.   Pulmonary
fibrosis  is another side effect and must be monitored.  QUINIDINE:Quinidine,
a type IA drug is given in a  dose  of 400-600 mg every 2-3 hours and is only
used if other drug regimes have been unsuccessful, as quinidine  has  a  high
side  effect  profile.   Gastrointestinal  side  effects  occur in about 30%.
DISOPYRAMIDE PHOSPHATE:Disopyramide phosphate (Norpace)  is another drug that
is only used  if  the  VT  proves  to  be  refractory  to  other  methods  of
conversion.   Norpace  can  produce  congestive  heart  failure  if  the left
ventricle has  compromised  function.   Disopyramide  also  may cause urinary
retention and hypotension.  TORSADES  DE  POINTES:  Torsades  de  pointes  is
frequently produced by certain drugs that can lengthen the QT interval.  Type
IA  drugs  such  as  quinidine,  disopyramide  and  procainamide are commonly
involved  in  producing   this   potentially   life  threatening  arrhythmia.
Tricyclic antidepressants and probucol (Lorelco) may also induce Torsades  de
pointes.   If astemizole (hismanal) is taken in higher than recommended doses
torsades  may  ensue.    Any   patient   taking   terfenadine  (Seldane)  and
erythromycin or ketoconazole (Nizoral) are also at risk  for  development  of
torsades.   Diuretics  may  produce hypokalemia and low magnesium levels that
set the scene for  torsades  de  pointes.   Torsades  de pointes usually will
respond to any method that has  a  tendency  to  speed  up  the  heart  rate.
MAGNESIUM:Magnesium  given  IV at a dose of 1-2 grams pushed slowly, followed
by  a  2-20   mg/minute   maintenance   drip   is  effective.   ISOPROTERENOL
HCL:Isoproterenol HCL (Isuprel) may be used to accelerate the heart rate  but
must be used with caution.  Start at 1-3 ug/min.  Isoproterenol should not be
used  in  patients  with coronary artery disease or in patients with allergic
asthma as it  contains  sulfites  which  may initiate bronchospasm.  ATROPINE
SULFATE: Atropine is started at .5 mg IV and may be increased  up  to  2  mg.
Again,  the  increase  in  cardiac  rate will sometimes terminate torsades de
pointes.   UNSTABLE   VENTRICULAR   TACHYCARDIA:   For  unstable  ventricular
tachycardia, cardioversion is given starting at 50-100 J, if the  ventricular
tachycardia is monomorphic.  If there is polymorphic ventricular tachycardia,
larger  amounts  of  energy  may be needed for the conversion.  Sedation with
midazolam HCL (Versed) may be given prior to the DC shock if time allows.  Be
cautious about DC cardioversion if  the patient has been receiving digitalis,
and	is hypokalemic.

                 -VERTIGO (Differential Diagnosis)-
CENTRAL CAUSES: Acoustic neuromas and  tumors of the cerebello-pontine angle,
vertebrobasilar insufficiency, multiple sclerosis, epilepsy,  cerebrovascular
accident,  subclavian  steal  syndrome,  metabolic  disease, post-concussion.
VESTIBULAR CAUSES: Meniere's  disease,  benign positional vertigo, vestibular
neuronitis, middle ear infections, ototoxic  drugs  as  aminoglycosides,  and
allergic    labyrinthitis.    OTHER   CAUSES:   volume   depletion,   anemia,
hypothyroidism,   syncope,   psychiatric,    as   anxiety,   hypervetilation.
PERIPHERAL OR VESTIBULAR LESIONS: There is  a  less  than  1  minute  latency
before  the  onset  of  nystagmus.  Calorics are decreased on the side of the
lesion (normal in benign  positional  nystagmus).   The vertigo is severe and
often rotational, vomiting is present  and  hearing  loss  and  tinnitus  are
frequently  present.   CENTRAL  LESIONS:  There  is  no  latency.  A verticle
nystagmus means there is a brainstem  lesion.  The vertigo is mild and nausea
is usually absent.  Hearing loss and tinnitus are absent (loss of high  tones
in acoustic neuroma).

                    -VIBRATORY MURMUR (Innocent)-
This  murmur  is  detected  during  early  school years and is intensified on
supination.  It is  a  systolic  murmur  between  the  LLSB  and  apex and is
musical.  Also known as Still's murmur.

                       -VINCRISTINE  TOXICITY- 
Vincristine  can  cause  headaches,  foot drop, loss of deep tendon reflexes,
diplopia,  ptosis,   photophobia,   cortical   blindness,  ataxia,  seizures,
paralysis, and optic atrophy.  The  neuropathy  can  be  sensory,  motor,  or
autonomic.   Autonomic  neuropathy may manifest as an acute intestinal ileus,
constipation, or  a  bladder  neuropathy.   Bowel  softners  are  helpful for
constipation along with mild laxatives.  In mild cases, the patient may  only
complain  of  pins  and  needles  in the fingers and toes.  As the neuropathy
advances, the sensory component  develops  into  pain  and finally into motor
paresis with weakness in the quadriceps muscle groups.   If  the  patient  is
unable  to perform deep knee bends or arise out of a chair without the aid of
the  arms,  the  vincristine  should  be  discontinued.   Some  patients will
complain of pain in the throat and jaw which may be a form of  trigeminal  or
glossopharyngeal   neuralgia.   Myelosuppresion,  alopeica,  rash,  and  skin
ulcerations may also occur.   Renal  complications include polyuria, dysuria,
bladder atony and urinary retention and SIADH.  Cardiopulmonary complications
include bronchospasm,  dyspnea,  hypertension  and  hypotension.   Phlebitis,
cellulitis, pain and necrosis can develop at the venous access site.

                          -VIOLENT PATIENTS-
The  violent  patient  is  usually calmed by using either a benzodiazepine or
haloperidol.  If the patient  is  not  psychotic,  lorazepam is usually used.
Patients that have  psychotic  episodes  such  as  schizophrenia  or  bipolar
affective  disorders,  haloperidol or droperidol are the best drugs.  In some
patients, both of  these  drugs  may  be  used.   This combination is usually
composed of 5 mg of haloperidol and 2 mg of  lorazepam  given  IM  every  2-3
hours until sedation.  This combination should not be given IV.  Lorazepam is
preferred  over  diazepam because it has a faster onset of action and shorter
duration of action.  Do not use  oral lorazepam.  IV lorazepam should be used
judiciously because of vein irritation.   Lorazepam  given  sublingually  has
been effective and works just as fast as IM injection.  If both lorazepam and
halperidol  are  being  given,  the  two can be mixed in the same syringe and
given IM.  Lorazepam is given at  1-2 mg every 1-2 hours, either sublingually
or IM until the patient is sedated or up to a maximum of 4 mg.  For  patients
with  renal,  or  COPD  or  the elderly, downward adjustments will have to be
made.  In these patients you should  start  with .5 mg.  Haloperidol is given
in small intramuscular boluses to treat schizophrenia  and  other  psychoses.
Extrapyramidal complications are side effects.  IV haloperidol is not routine
even though the literataure supports its safety and efficacy.  It can be used
if  a  violent  patient needs alleviation of agitation immediately.  Sedation
usually reaches its peak  at  about  20  minutes  after  an  IM dose and 5-10
minutes after IV.  Start with 5-10 mg of Halperidol as a slow IV push,  which
may be repeated every 10 minutes until calm is established.  Elderly patients
are  only given 1-2 mg IV every 10 minutes for 3 doses, and then the dose may
be escalated to 5 mg every 10  minutes if it is tolerated.  Patients that are
severely agitated may need up to  50-75  mg  IV  every  30-60  minutes.   Use
caution in patients that are ethanol intoxicated or other drug intoxications.
Haloperidol may also lower the seizure threshold.  Halperidol usually doesn't
impact  on  the  patient's vital signs or respiratory function when given IV.
Extrapyramidal reactions are rare and  tend  to be milder with IV Haloperidol
use, and usually do not occur during the first 24 hours.  Diphenhydramine  is
used  to  reverse  the  symptoms.   A  very  rare  side effect is neuroleptic
malignant  syndrome.   Droperidol,   may   have   fewer   side  effects  than
haloperidol.  The dosage is 2.5 to 5.0 mg via IV push.

                       -VITAMIN B12 DEFICIENCY-
The  intestinal  absorption  of  vitamin B12 is dependent upon a glycoprotein
known as the intrinsic factor which  is produced in the stomach.  The absence
of intrinsic factor causes pernicious  anemia.   In  pernicious  anemia,  the
atrophic  gastric mucosa does not secret adquate amounts of intrinsic factor.
Gastrectomy and myxedema can  also  cause  a deficient secretion of intrinsic
factor.  Over 96% of cases of B12 deficiency is due to  impaired  absorption,
due  to a deficiency of the intrinsic factor, or intestinal or liver disease.
Other causes of vitamin B12  deficiency include an inadequate diet (veganism,
alcoholism,  breast  feeding  of  infants  by  vegan   mothers),   indadquate
utilization   (liver  disease,  malignancy,  kidney  disease,  malnutrition),
inadequate  absorption  (small  intestine  disorders  such  as  sprue, celiac
disease, malignancy, drugs, fish tapeworm, blind loop  syundrome),  increased
excretion   (poor   binding  in  liver  and  renal  disease),  and  increased
requirements   (parasitic   infestation,   infancy,   hyperthyroidism,  alpha
thalassemia).  Vitamin B12 deficiency usually takes several months  to  years
to  develop  because  of  the  slow  rate of utilization, and large stores of
vitamin B12.  For  this  reason,  vitamin  B12  deficiency  is  rare in young
infants, except for breast fed infants  of  strict  vegetarian  mothers.   In
children, the development of B12 deficiency is contingent upon the intake and
the hygiene habits of the children.  B12 is produced by colonic bacteria, and
there  may  be  enough  self  contamination  with  B12 feces to slow down the
development of vitamin B12 deficiency.  CLINICAL:  As the large stores of B12
become depleted, the patient may develop glossitis,  weight  loss,  anorexia,
diarrhea, constipation and abdominal pain.  Neurologic signs and symptoms may
develop  even  if  the  patient  is  not  yet anemic.  Peripheral neuropathy,
characterized by numbness and  tingling  of  the  extremites, is the earliest
signs of neurologic damage.  If the spinal cord  becomes  involved,  combined
system  disease  can  develop with involvement of the dorsal column producing
loss of vibratory sensation  in  the  lower  extremities,  ataxia and loss of
position.  As the disease  progresses,  lateral  column  involvement  becomes
manifest   with   spasticity,  hyperactive  reflexes  and  a  Babinski  sign.
LABORATORY: A peripheral smear  will  reveal  macrocytosis with a MCV greater
than 100.  The differential of macrocytosis  should  include  liver  disease,
reticulocytosis,  folic  acid  deficiency,  multiple myeloma, hypothyroidism,
alcohol, myeloproliferative  diseases  such  as  myelofibrosis  and leukemia,
metastatic disease of the bone  marrow,  and  spurious  causes  due  to  cold
agglutination  disease  and  autoagglutination.   The  smear  will  also show
ovalocytosis, anisocytosis, poikilocytosis  and  basophilic  stippling of the
RBCs.  The RDW is high, and Howell Jolly bodies may be present.  One  of  the
earliest  findings  is  hypersementation  of  the  granulocytes  followed  by
neutropenia  at  a  later date.  Platelets are reduced in about 50% of cases,
and occasionally are bizarre in shape and  size.  LDH may be elevated (due to
ineffective erythropoiesis) along with  serum  bilirubin  elevation  (due  to
ineffective  hematopoiesis).   Examinatin  of  the  bone  marrow will show an
erythroid hyperplasia with megaloblastic maturation  in all three cell lines.
Vitamin B12 assay should be done.  Values below 150 pg/mL are compatible with
B12 deficiency.  Borderline cases include levels  that  are  between  150-250
pg/mL.   If  the patients B12 level falls in the borderline zone, measurement
of the serum methylmalonic acid  and  homocysteine should be done.  These are
usually elevated due to a block in the B12 dependent steps of their metabolic
pathway.  Methylmalonic aciduria may also occur, but  is  a  less  consistent
finding.   Most  patients  with  pernicious  anemia  will  have achlorhydria.
Achlorhydria can be confirmed if the pH elevates to between 6.8 and 7.2 after
receiving  histamine.   Autoantibodies  to  gastric  parietal  cells  can  be
established in 80-90% of patients with pernicious anemia.  Most patients will
also have autoantibodies to intrinsic factor.  The assay for intrinsic factor
antibodies must be done when the patient  has not received B12 for at least 2
hours.  Patients with pernicious anemia have  a  high  incidence  of  gastric
carcinoma,   and  should  receive  endoscopy/GI  x-rays  for  any  suspicious
symptoms.  The GI x-rays may  reveal  other causes for vitamin B12 deficiency
such as blind loops, intestinal diverticuli and abnormal small bowel patterns
consistent with malabsorption such as sprue.  The Schilling test measures the
absorption of radioactive B12 before (Schilling I test) and  after  intrinsic
factor  (Schilling  II  test).   The  Schilling I test is performed by giving
radiolabeled B12 by mouth followed in 1-6  hours with an injection of 1000 ug
of  B12.   Following  this  a  24  hour  urine  measures  the  percentage  of
radiolabeled B12 in the urine.  If  this  is  abnormally  low,  the  test  is
repeated (Schilling II test) by giving radiolabeled B12 with intrinsic factor
and  a subsequent determination of the percentage of radioactive B12 found in
the urine.  The patient must have normal  kidney function for the tests to be
valid.  Normally, the excretion of labeled B12 should be greater than  9%  of
the  total  dose  given.   If  the labeled B12 is less than 5% on the initial
Schilling I test, but the  labeled  B12  is  normal on the Schilling II test,
this would indicate pernicious anemia.   Should  both  the  Schilling  I  and
Schilling  II test yield low absorption, a Schilling III test should be done.
This is done by giving oral  tetracycline  for  2 weeks, and repeating the 24
hour determination of labeled B12 in the urine.  TREATMENT:	Treatment must be
directed at repleting the hepatic reserves.  For  this  reason,  vitamin  B12
should  be  given by administering 1000 ug of vitamin B12 every other day for
about 2 weeks.  Following this,  1000  ug  is  given as weekly injections for
about 4 weeks, and then monthly for life.  The clinical response  to  vitamin
B12  can  be  determined  by  a  hematologic  response  after  about 3-7 days
following as little as 1  ug  of  vitamin B12.  The pancytopenia is reversed,
and there is improvement in the hemoglobin and hematocrit.  It takes  several
weeks  for  the  macrocytic RBCs and the MCV to improve.  The serum potassium
should be monitored during this  time, as hypokalemia frequently develops due
to movement of potassium into the rapidly proliferating hematopoietic  cells.
This  is  especially  important in those patients that are receiving diuretic
therapy, and those that  are  receiving  digoxin.  Pernicious anemia patients
should have occasional guaiac determinations because about 2-3%  of  patients
will  develop gastric carcinoma.  Thyroid studies should also be monitored as
there is an increased incidence of autoimmune thyroid disorders.

               -VISUAL LOSS (Transient and Monocular)-
Any patient that presents with transient  monocular  visual  loss  should  be
checked   for   amaurosis  fugax.   Amaurosis  fugax  begins  usually  as  an
abnormality of vision  beginning  in  the  upper  field  of vision which then
progresses to involve the entire visual field.  Ocular disease such as  optic
neuritis,  glaucoma, anterior ischemic optic neuropathy, central retinal vein
occlusion,  hemorrhage,  and  papilledema  should  be  ruled  out.   Temporal
arteritis is  usually  associated  with  headaches  and  an  elevation of the
Westergren ESR.  If the patient has headache, visual loss and a  normal  ESR,
migraine  and  occipital  seizures should be ruled out.  These patients often
have a homonymous hemianopsia.   Ask  about scintillating scotomata which may
be seen in migraine  and  seizure  patients.   Temporal  arteritis  may  also
present  with  fever,  anorexia,  and  weight  loss  along  with  anemia, and
leukocytosis.  LABORATORY:  The  following  lab  tests  should  be performed:
Westergren sedimentation rate to rule out giant cell or Takayasu's arteritis,
fasting blood sugar to rule out diabetes, PTT to  rule  out  antiphospholipid
antibodies,  CBC,  differential  and  platelet  count  to  rule out leukemia,
thrombocytosis,  and  polycythemia,  and   a   lipid   profile  to  rule  out
hyperlipidemia.  A duplex B mode and Doppler ultrasound should be done of the
carotids.  Patients that have >  70%  stenosis  may  be  candidates  for  and
ipsilateral  carotid  endarterectomy.   Currently,  patients  between  30-69%
stenosis  are not treated surgically, but medically with ASA 325 mg daily and
modification of their risk factors.   Patients  that show no flow, indicating
total occlusion, on doppler ultrasound should have arteriography	to see if
this represents a tight stenosis rather than  total  occlusion,  which  would
then  warrant  surgery  rather  than  medical  treatment.   CT and MRI may be
warranted to rule out  silent  cerebral  infarctions and nonvascular lesions.
If the carotid artery study is normal or does not seem to  be  implicated  in
the visual loss, echocardiography is indicated to rule out embolic disease.

                     -VON WILLEBRAND'S DISEASE-
Von Willebrand's  disease  is  predominantly  a  familial  autosomal dominant
disorder of hemostasis with several subtypes.  It  is  due  to  deficient  or
defective  von  Willebrand  factor  (vWF)  which is a multimeric protein that
circulates  in  the  plasma  with  factor  VIII.   Von  Willebrand  factor is
manufactured  in  the  megakaryocytes  and  endothelial  cells.   There   are
different  sizes  of  the multimers.  Only the large multimers are capable of
bringing about platelet adhesion.  Any sized multimer may bind to factor VIII
coagulant (factor VIII:C).   Factor  VIII  coagulant  is  the protein that is
deficient in Classic Hemophilia.  CLINICAL: Von Willebrand's disease commonly
affects women and men, producing mucosal bleeding such as gingival  bleeding,
menorrhagia,  epistaxis  and  gastrointestinal  bleeding.   The  bleeding  is
variable  at  different times of the disease.  Dental extractions and surgery
usually will cause bleeding, but  the  bleeding  is  usually not as severe as
Hemophiliac bleeding.  Epistaxis may occur up to 63%, bruising and  hematomas
(42%)  and  menorrhagia  (37%).   Bleeding  after dental extraction occurs in
about 52%,  postpartum  bleeding  (23%),  postoperative  bleeding  (21%), and
gastrointestinal bleeding  (9%).   In  some  GI  bleeding  angiodysplasia  or
hereditary hemorrhagic telangiectasia may be present.  In other GI bleeds, no
mucosal  etiology can be found.  The above bleeding rates are only estimates,
as bleeding tends to be extremely  variable  in the same patient at different
times, and in patients within the same family.  Some  pregnant  patients  may
bleed  during  one  pregnancy  and not in another.  If the patient has a mild
form of the disease, bleeding may  only  occur after major surgery or trauma.
The bleeding tendency is made worse by aspirin, but  estrogen  and  pregnancy
usually  have  a beneficial effect with reduction in bleeding.  Bleeding into
joints is rare  in  conrast  to  Hemophilia  A.  SUBTYPES OF VON WILLEBRAND'S
DISEASE: TYPE I: Type I is the most common type of von Willebrand's  disease.
In  this  type,  which represents about 70-80% of the cases, all sizes of the
multimers of vWF  are  quantitatively  decreased  in  the  same amount as the
factor VIII:C is decreased.  In homozygotes there may be undetectable  levels
of  plasma  and  platelet von Willebrand antigen, and extremely low levels of
Factor VIII.  In heterozygotes the levels are not reduced to that extent, and
the bleeding is  much  milder.   In  type  I  there  is reduction of platelet
aggregation with Ristocetin.  TYPE IIA: In this type there is  a  qualitative
abnormality  in  protein  that prevents multimer formation.  Only the smaller
multimers are present, while the intermediate and large multimers are absent.
Since only the larger multimers  can  mediate platelet adhesion, the bleeding
is a result of the absence of these large multimers.  TYPE IIB: Type IIb is a
qualitative defect in the protein which leads to a  rapid  clearance  of  the
large  multimeric  forms.   This  lack of large multimeric forms again is the
cause of the bleeding by preventing  platelet adhesion.  In type IIb there is
increased platelet aggregation with low  levels  of  ristocetin.   TYPE  III:
Whereas  Types  I  and II are inherited as autosomal dominanance, type III is
autosomal recessive.  Factor VIII  procoagulant  activity is markedly reduced
and von Willebrand factor is either absent or present in only trace amount in
the cellular compartment and the plasma.  These patients have severe bleeding
and some may develop antibodies against  von  Willebrand  factor  after  many
infusions  of concentrates that contain the protein.  PSEUDO-VON WILLEBRAND'S
DISEASE: This is a very rare subset  of patients which is similar to type IIb
von Willebrand's disease, but the defect is in the platelet receptor for  von
Willebrand factor, which has has an attraction for the large multimeric forms
of  vWF  causing  a  clearance  of  the  large  multimers  from  the  plasma.
LABORATORY:  The  bleeding  time  is  usually prolonged, but may be normal at
different times.   The  bleeding  time,  if  prolonged,  correlates well with
clinical bleeding.  If aspirin is given and the bleeding time repeated, there
usually is prolongation of the bleeding time.  Von Willebrand  factor  levels
are  usually  reduced  in type I, but can be normal to reduced in Type I, and
II.  In Type III the level approaches zero.  Von Willebrand factor levels may
be checked by ordering factor  VIII antigen and ristocetin cofactor activity.
Factor VIII antigen may be normal or reduced in types I and II, but  is  near
zero  in  type  III.   Ristocetin cofactor activity is normal or decreased in
type I and IIb, but  is  near  zero  in  type  IIa and Type III.  Factor VIII
coagulant (factor VIII:C) may also  be  reduced  if  factor  VII  antigen  is
reduced.   If  the  level  of  factor  VIII:C  is  below  25% the PTT will be
prolonged.  Platelet aggregation  is  usually  normal  with ADP, thrombin and
collagen, but platelet aggregation is usually subnormal  with  ristocetin  in
about   70%  of  cases  except  type  IIb  which  causes  increased  platelet
aggregation with low concentrations  of  ristocetin.  Multimeric analysis for
composition of von Willebrand factor may be necessary is some cases in  order
to  diagnosis  von  Willerands's  disease  and  its  subsets.  Type I usually
responds to DDAVP  (desmopressin)  whereas  type  IIb  may be aggravated with
reduction of platelets and no response in type IIa.  DIFFERENTIAL  DIAGNOSIS:
If   the  patient  has  only  a  prolonged  PTT,  the  differential  includes
deficienciy  of  Factors  VIII,  IX,   XI,   XII,  and  lupus  and  anti-VIII
anticoagulants.   Measurement  of  factor  VIII:C  will   narrow   down   the
differential to Hemophilia and Von Willebrand's disease.  If all measurements
of  vWF  by ordering factor VIII antigen and ristocetin cofactor activity are
reduced, the diagnosis is  von  Willebrand's  disease.   If the patient has a
prolonged bleeding time, acquired and congenital platelet disorders  must  be
ruled  out.   If  the  patient  has decreased vWF testing and normal platelet
aggregation, the diagnosis is von Willebrand's disease.  If the patient has a
normal bleeding time and PTT,  the  diagnosis of von Willebrand's disease may
be made by giving aspirin and repeating the bleeding  time,  or  by  ordering
factor  VIII  antigen and ristocetin cofactor activity.  The diagnosis may be
particularly difficult in  pregnant  patients  or  in  those  that are taking
estrogen which tends to raise vWF levels.  TREATMENT: The  bleeding  time  is
the  best  test  for prediction of which patients will have bleeding.  If the
bleeding time is  prolonged,  the  patient  may  need  to be prophylactically
treated for minor or more major procedures.  In the past cryoprecipitate  has
been  the  treatment of choice.  Each unit will raise the vWF level about 3%.
Therefore, in  order  to  raise  the  vWF  to  about  30-50%,  10-15 units of
cryoprecipitate will be needed.  This is usually given at 12 hour  intervals,
but  depends  on  the  degree  of bleeding.  This will keep the factor VIII:C
levels elevated for about 24-48 hours, but only keeps the factor VIII antigen
level elevated for  about  12-18  hours.   Factor  VIII  concentrates are now
replacing plasma cryoprecipitate infusions which can transmit  hepatitis  and
and HIV.  Some of these preparations contain functional vWF such as Humate-P.
Humate-P  is  given  at  a dose of 20-50 units/kg.  If the patient has a mild
type I von Willebrand's disease, Desmopressin acetate (DDAVP) may be given at
a dose of .3 ug/kg in 30 ml  of  normal saline over a 30 minute period.  This
amount will raise the vWF levels two to threefold in about 30-90 minutes.  It
should only be given every 24 hours as the stores may  become  depleted  from
the  endothelial  cells.  Desmopressin should not be used in type IIb because
it may cause thrombocytopenia with  increased  bleeding.  It is not useful in
type IIa because there are no stores  in  the  endothelial  cells.   In  oral
surgery  aminocaproic  acid  given  at a dose of 4 grams po every 4 hours for
several days may be given after the patient is prepared with cryoprecipitate,
concentrate, or desmopressin.

                 -WALDENSTROMS'S MACROGLOBULINEMIA-
Waldenstroms's macroglobulinemia (WM) is a disease of the old with the median
age  being  65  years,  and  men are affected more than females.  Most of the
symptoms are  due  to  the  hyperviscosity  of  the  blood  due the malignant
proliferation of plasmacytoid lymphocytes that secrete a monoclonal IgM.  The
symptoms that are produced are rather non-specific and therefore do  not  aid
much  in  arriving at a diagnosis.  CLINICAL: The typical profile of a person
with WM would be an elderly  man that presents with fatigue, purpura, mucosal
bleeding and is complaining of a headache and visual disturbance.   He  might
report  a cold sensitivity of Raynaud's phenomenon due to cold agglutinins or
cryoglobulins.  He might report to  you  that he has had recurrent infections
recently.  Following  this  disclosure  you  would  check  for  splenomegaly,
lymphadenopathy and engorgement of the retinal veins that give the appearance
of  sausage.   There may be retinal hemorrhages and exudates.  Other symptoms
would include peripheral neuropathy, paresis  and paresthesias.  There may be
dizziness, and congestive heart failure  may  develop  as  a  result  of  the
hyperviscosity.   In  contrast  to multiple myeloma there is no bone pain and
renal failure would be unusual.   LABORATORY:  Examination of the bone marrow
will reveal increased numbers of plasma cells and  plasmacytoid  lymphocytes.
The  Coombs'  direct  antiglobulin  may  be  positive  due to malignant clone
production of an IgM  that  behaves  as  a  cold  agglutinin.  There may be a
hemolytic anemia from  the  positive  Coomb's.   Cryoglobulins  may  also  be
present  as  well  as  a positive rheumatoid factor.  X-rays of the spine and
bones are usually normal  as  there  are  no  lytic lesions in Waldenstroms's
macroglobulinemia.  A serum protein electrophoresis will  show  a  monoclonal
immunoglobulin   M   spike  in  the  beta  or  gamma  globulin  region.   The
immunoelectrophoresis shows that  this  immunoglobulin  is  IgM.   There is a
normocytic normochromic anemia and the peripheral smear  will  show  rouleaux
formation  of  the  RBCs  and  plasmacytic  lymphocytes.   There  also may be
thrombocytopenia,  and  leukopenia   with   a  relative  lymphocytosis.   The
sedimentation rate is usually very high.  Bence Jones protein in the urine is
found in about 10% of cases.  The normal serum viscosity is  between  1.4-1.8
times that of water.  Symptoms of hyperviscosity will usually be present when
there  is  a  serum viscosity of 4 or more.  DIFFERENTIAL DIAGNOSIS: A benign
monoclonal gammopathy may be  differentiated  from  WG  by examining the bone
marrow for the typical infiltration.  Multiple myeloma differentiation should
not be a problem.  In WM there are usually no osseous lytic changes and there
is no renal failure.  Serum protein  electrophoresis  monoclonal  spikes  are
usually  IgG  and  IgA in multiple myeloma.  About 5% of patients with B cell
non- Hodgkins's lymphoma may show a monoclonal IgM component.  PROGNOSIS: The
median period of survival in WM is  3-5 years, but some patients will survive
for 10 years or longer.  TREATMENT: Plasmapheresis is effective  in  reducing
the  serum  viscosity  which in turn will rapidly improve the hematologic and
neurologic symptoms.  Chlorambucil at  .03  to  .09  mg/kg/day is usually the
treatment of choice.  Alternatively, melphalan and  cyclophosphamide  may  be
given along with prednisone.
                              -WARFARIN-
Warfarin functions as an oral  anticoagulant  by inhibiting vitamin K epoxide
reductase.  This limits the carboxylation and function of vitamin K dependent
factors (prothromvbin, factors VII, IX, and X) and protein C and  protein  S.
Some  anticoagulation  is  present after 12-24 hours of warfarin therapy, but
the peak activity is not present for  about  3 days.  This is due to the fact
that the half life of factor VII is about 6.5 hours , while that of  II,  IX,
and  X is several days.  Heparin is usally given IV prior to warfarin because
of this delay in anticoagulation  with  oral warfarin.  Because the half life
of protein C is about the same as factor VII, its depletion  could  cause  an
increased  risk  of thrombosis during the first 12 hours of therapy.  Heparin
protects against this possibility.   SIDE  EFFECTS:  The  main side effect is
bleeding which is more common in those patients greater than  65  years,  and
those  with  renal failure, occult GI lesions, NSAIDs, ASA, cerebral vascular
disease, and anemia.  If the PT ratio (patient PT/control PT) is greater than
2, or the INR is  greater  than  3.5  there  is an increaed risk for bleeding
also.  Warfarin is contraindicated in patients that are pregnant, severe  and
uncontrolled  hypertension, bacterial endocarditis, peptic ulcer disease, and
recent GI bleeding.  Another side effect  of warfarin is skin necrosis, which
presumbably occurs due to the decreased	biologic activity of protein C, which
causes capillary and venule thrombosis.  The skin  necrosis  usually  appears
between  the  3rd  and 7th day of therapy.  MONITORING: Many physicians still
use a PT ratio of 1.4-1.7  as  a  therapeutic  end point.  However, it is now
recommended that the INR be used for monitoring patients  on  warfarin.   The
INR  (International  Normalized  Ratio)=(patient  PT/control PT)ISA.  The ISI
(International  Sensitivity   Index)   measures   the   responsiveness  of  a
thromboplastin to a decrease in the vitamin K dependent coagulation  factors.
In  most  cases,  (deep  venous  thrombosis,  atrial fibrillation) the INR is
maintained at 2-3.  Patients  with  mechanical  valves and recurrent systemic
embolization are kept between 3-4.5.  WARFARIN DRUG  INTERACTIONS:  INCREASED
ANTICOAGULANT   EFFECT:   Alcohol,   aminoglycosides,   ampicillin,  anabolic
steroids,  Amiodarone,  allopurinol,  ASA,  cephalosporins,  chloral hydrate,
chloramphenicol,    chlorpromazine,    chlortetracycline,     chlorpropamide,
clofibrate,  cimetidine,  ciprofloxacin, clofibrate, Co-trimoxazole, danazol,
dextrothyroxine,   diazoxide,    dipyridamole,   disulfiram,   nortriptyline,
dextrothyroxine,	erythromycin, ethacrynic acid,  fenclofenac,  fenoprofen,
flufenamic  acid,  fluvoxamine,  mefenamic acid, methotrexate, metronidazole,
monoamine oxidase inhibitors, nalidixic  acid, naproxen, enomycin, penicillin
in large doses IV, phenformin, phenylbutazone,  phenytoin,  propylthiouracil,
propafenone,    quinidine,   sulfinpyrazone,   sulfonamides,   tetracyclines,
tolbutamied,     tricyclic     antidepressants,     verapamil.     quinidine,
phenylbutazone,   vitamin   E,   Trimethaprim-sulfamethoxazole.     DECREASED
ANTICOAGULANT     EFFECT:     Antacids,     antihistamines,    carbamazepine,
cholestyramine,      colestipol,      corticosteroids,      cyclophosphamide,
dichloralphenazone, diopyramide,  glutethimide, griseofulvin, mercaptopurine,
oral  contraceptives,  pheneturide,  phenobarbitone,  primidone,  rifampicin,
vitamin K1 and K2, steroids, barbiturates,  diuretics,  estrogens,  rifampin,
phenytoin, and griseofulvin.

                              -WEAKNESS-
Patients with weakness may present as acute, subacute, or  chronic  weakness.
If  the  onset  is  acute,  botulism would have to be ruled out.  In subacute
presentations over a period of days  to  weeks, Guillain Barre and polio must
be  considered.   Chronic  conditions  include  myasthenia  gravis  and   the
myasthenic  syndrome.  BOTULISM: Botulism is caused by Clostridium botulinum.
The onset is acute, and there may  be a history of contaminated food, such as
home canned food.  Early on there  is  blurred  vison  due  to  paralysis  of
accomodation  followed  by  double  vision  later.   If  the  patient has had
extensive exposure  to  the  toxin  there  can  be  dysarthria, dysphagia and
generalized paralysis.  There may be  autonomic  disturbances,  such  as  dry
mouth  and  tachycardia,  and  facial  myopathies.  Physical exam will reveal
ptosis  and  respiratory  failure.   The   symptoms  of  botulism  can  mimic
myasthenia gravis.  There may be ptosis, involvement of  the  third,  fourth,
sixth,  and seventh cranial nerves.  Sensation is normal, as well as the deep
tendon reflexes.   EMG  findings  include  an  incremental  response  to fast
stimulation, decremental response to slow stimulations.  Stool  cultures  may
be  positive  and  clostridial  antibodies may be present.  Treatment is with
polyvalent antitoxins A, B, and E which will cover the more common subsets of
the disease.  MYASTHENIA GRAVIS: Myasthenia  gravis  is usually seen in young
women during adolescence or  early  adulthood.   The  patients  present  with
fatigue  that  is  related  to  physical  activity which increases as the day
preogresses.  Early in the morning  when  the  patient  gets up she will feel
fine, but as the day progresses,  weakness  becomes  more  pronounced.   Rest
periods  usually  refreshe  the  patient,  and  she  temporarily regains some
strength.  Ask the patient about  eating habits.  Often, patients will change
to soft foods as steak and such, as she tires after chewing solid foods.  Ask
about the daily routines such as brushing the  hair  which  causes  weakness.
The patient also complains of double vision which can fluctuate in time.  Not
all  patients  will  complain  of  diplopia,  and weakness of the extremities
predominate.  A few will  complain  of  slurring  of the speech with fatigue.
Advanced cases may include bulbar paralysis with trouble  on  swallowing  and
breathing.   Physical  exam  reveals  early drooping of the eyelids which may
only affect one eye.  To test for  drooping of the eyelids ask the patient to
elevate the eyelids, look  up,  and  hold  this  position.   The  eyelids  of
myasthenia  gravis  will  droop  after  a short time.  Examination of the eye
muscles may reveal abnormalities of  the  3,  4,  or  6th nerves.  If the 7th
nerve (facial nerve) is  involved,  the  patient  may  may  have  a  sneering
appearance  when she is asked to smile, as the upper lip retracts, baring the
teeth.  Also, test weakness of  the  extremities  by having the patient grasp
your hand and repetitively contract and relax their hand.  After a short time
the grip will collapse due to weakness, until the patient  has  had  time  to
rest.   Deep tendon reflexes and sensation will all be normal.  EMG will show
decremental  response   to   repetitive   stimulation.    Treatment  is  with
anticholinesterases  such  as  mestinon,  and   neostigmine,   steroids   and
thymectomy.   GUILLAIN-BARRE  SYNDROME:  Guillain-Barre  or Landry's syndrome
usually presents with a previous  upper respiratory infection, paresthesia or
dysesthesias, and weakness.  There may be a history of a recent  inoculation.
Patients  may  present  with tingling and numbness in the hands and feet with
progressive weakness.  Patients  may  have  a  bilateral  facial weakness and
ultimate respiratory failure.  These patients can be missed early on  as  the
muscle  strength  early  may be essentially normal and the only complaint are
dyesthesias and weakness.   These  patients  should  be  rechecked at a later
date.  Guillain-Barre syndrome doesn't affect cranial nerves 3, 4, or 6 as in
myasthenia gravis.  However, the 7th  cranial  nerve  can  be  affected  with
bilateral  facial weakness.  It's important to check the deep tendon reflexes
in Guillain-Barre as there is progressive  loss of the DTRs, as compared with
myasthenia  gravis  patients.   There  is   also   loss   of   sensation   in
Guillain-Barre,  which does not occur in any of the other diseases discussed.
Therefore, anyone complaining of  dysesthesias  and  weakness, check the DTRs
and sensation.  Guillain-Barre is a weakness that progresses from the  distal
to the proximal muscles, and is accompanied by several autonomic disturbances
such  as  sweating,  wide  fluctuations  in  the  blood  pressure  and pulse,
diarrhea, and urinary retention.   Patients  with Landry's syndrome will have
slow nerve conduction and the CSF will show high protein over 100,  but  with
few  cells.  Both of these lab tests may take time to develop, so they may be
initially absent.  MYASTHENIC  SYNDROME:  This  typically  occurs in a middle
aged male with the Eaton-Lambert syndrome secondary to an oat cell  carcinoma
of the lung.  This syndrome produces proximal muscle weakness as that seen in
polymyositis.  There may be weight loss seondary to an underlying cancer, and
there  may  be  muscle  atrophy  early in the proximal muscles as compared to
myasthenia gravis, in which the  atrophy  occurs later in the disease.  There
is no weakness of the eye muscles or face, no autonomic disturbances, and the
DTRs, and sensation are normal.  EMG will show incremental response  to  fast
stimulation,  decremental  response  to  slow  stimulation.   Chest x-ray and
bronchoscopy will reveal a  tumor.   Treatment  is  removal of the lung tumor
which will lead to an improvement  in  about  20-30%  of  the  patients  with
myasthenic  syndrome.   If the patient fails to improve, the removal may have
been incomplete.  PERIODIC PARALYSIS: is  a rare disease associated with low,
high or normal potasssium levels.  The respiratory muscles are not  affected.
These  patients  may have episodes of acute, severe paralysis that lasts from
an hour to several days that is relieved with potassium.  The hypokalemia may
be associated with hyperthyroidism.   The  ECG  may show hypokalemic features
such as diffuse low T waves and QT prolongation.  In the  hyperkalemic  form,
the  bouts  of  paralysis are usually shorter and milder.  The T waves may be
tall and peaked in  hyperkalemic  periodic paralysis.  Periodic paralysis may
be precipitated by a  period  of  rest  after  physical  exertion,  and  high
carbohydrates, which causes a shift of extracellular potassium into the cells
by the glucose.

                     -WEGENER'S GRANULOMATOSIS-
WG is a fairly rare disease (large centers may see about 5 cases  per  year),
predominantly  affecting  men  (3:2)  at  a  mean  age onset in the 40's, and
characteristically affects the upper airway, lung and kidney.  However, it is
a treatable disease with survivals of 75-90% at 5 years.  Prior to prednisone
and cyclophosphamide treatment, the disease  was invariably fatal with a mean
survival of about 5 months.  There is no known cause, but  it  is  an  immune
mediated  hypersensitivity  disorder  that  was  first  classified in 1936 by
Wegener as a variant of polyarteritis.  The diagnostic histologic lesion is a
necrotizing granulomatous inflammation of small arteries and veins.  There is
a limited form of  Wegener's  disease  that  affects  only the upper or lower
respiratory  tract.   CLINICAL:  About  70%  will  present   with   pulmonary
infiltrates  that  have  a  predilection for the upper lobes, and usually are
multiple and bilateral  nodules  and  cavities.   The  cavities  may be fluid
filled and there may be lobar  atelectasis,  and  pleural  effusion.   (20%).
Unusual findings would include paratracheal mass, mediastinal mass, calcified
nodules,  miliary  pattern  and  a  lower lobe interstitial disease.  If high
resolution, thin section CT  is  done  feeding  vessels into the cavities and
nodules can be  seen  along  with  peripheral  wedge  shaped  densities  that
probably represent ares of infarction.  These changes cause a cough with some
sputum  production  and  occasionally  minor  hemoptysis.   Sinusitis also is
common (67%) with  concomitant  rhinorrhea,  ulcers  and erosions, epistaxis,
pseudotumors, and saddle nose deformities.   The  kidney  is  also  involved,
usually  later  in  the  course  of  the  illness.  In most cases there is no
associated hypertension.  About 50%  of  patients  with WG who are clinically
asymptomatic will have evidence of disease activity on renal biopsy.   Immune
complex deposition is not common.  Histology reveals basically 2 types; focal
glomerulitis  and  crescentic  glomerulonephritis  (which is less common).  A
renal biopsy that  is  characteristic  plus  evidence  of chronic destructive
sinusitis and pulmonary nodules is presumtive evidence for WG.  However, open
lung biopsy is the best procedure for  a  definitive  diagnosis.   Diagnostic
renal  biopsies  can  be  seen  in  SLE  and  Goodpasture's  syndrome.  Other
symptoms, but less common,  would  include  the following: arthralgias.  (The
arthralgias are polyarticular, symmetric and involve large and small  joints.
Arthritis  is  less common than arthralgia).  Palpable purpura and ulcerative
infarcts, granulomatous uveitis,  (16%),  orbital  pseudotumor, otitis (25%),
fever (34%), hemoptysis (18%), weight loss (16%),  and  epistaxis  (11%)  may
also   be  present.   Rare  presentations  would  be  pericarditis,  coronary
vasculitis, cranial neuritis (particularly involving the 1, 7 and 8th cranial
nerves and mononeuritis multiplex.  LABORATORY: Rheumatoid factor is found in
60% of patients.  Circulating immune  complexes  are found in about 50%.  The
sedimentation rate  is  almost  always  elevated  with  mean  values  in  the
nineties.   There  is  usually  a leukocytosis and anemia of chronic disease.
Thrombocytosis can be seen  in  33%  and Cryoglobulins are occasionally seen.
The UA may reveal hematuria, with  or  without  RBC  casts  and  proteinuria.
Often  times the proteinuria is in the nephrotic range.  Of importance is the
fact that  hepatitis  B  surface  antigen,  ANA  and  anti-DNA antibodies are
usually negative.  The antineutrophil cytoplasmic antibody test  is  positive
in  about 90%.  There are two forms of this test.  The cytoplasmic pattern of
staining  (c-ANCA)  has  a  specificity  of  about  90%  for  Wegener's.  The
perinuclear staining (p-ANCA) is more non specific, but is seen in  Wegener's
and polyarteritis.  DIFFERENTIAL DIAGNOSIS: Differential diagnosis depends on
the presentation but would include SLE, Churg-Strauss syndrome, Goodpasture's
syndrome,  bacterial  endocarditis, uremic pneumonitis, sarcoidosis, systemic
sclerosis,  lymphomatoid  granulomatosis   and   pneumonia  complicated  with
glomerulonephritis.  To diagnose Wegener's requires a biopsy  revealing  both
necrotizing  vasculitis  and  granulomatous  inflammation.   Biopsy  of  skin
usually  only  shows  a leukocytoclastic vasculitis.  Ocular and upper airway
biopsy may show inflammatory changes  with or without granuloma or vasculitis
but rarely both.  Transbronchial biopsy is less effective than an  open  lung
biopsy  and  shows  inflammation  with  or  without  giant cells.  TREATMENT:
Prednisone, 1 mg/kg/day is given with oral cyclophosphamide 2 mg/kg/day.  The
prednisone may be given for about  1  month and then tapered to alternate day
treatment.  This may be gradually be discontinued over 2-6  months  depending
on  clinical  response.   The  cyclophosphamide  is usually continued for 1-2
years after the  patient  is  in  remission  and  tapered  slowly.  With this
combination there has been a 70-93% complete remission rate.  However, in 50%
of these remissions there may be relapses even as  long  as  10  years  after
remission.   About  13% will die from the disease or as complication from the
treatment.  Trimethoprim/sulfamethoxazole has been used alone with success in
some patients  with  the  limited  form,  and  in  those  who cannot tolerate
immunosuppressive drugs.

                            -WEIGHT LOSS-
Infections: bacterial endocarditis, parasitic  diseases,  AIDS,  TB,  chronic
bacterial  infections.   Neoplasms: gastric and esophageal cancer, pancreatic
cancer, lymphoma,  leukemia,  lung  cancer.   Catabolism:  diabetes mellitus,
hyperthyroidism.  Psychogenic: anxiety  and  depression,  dementia,  anorexia
nervosa   and   bulima.    Organic   causes:   alcoholism   and  drug  abuse,
malabsorption, neurologic disease,  poor  dentures  and painful oral lesions,
medications.  Endocrine: blood diseases such as pernicious anemia,  Addison's
disease,  panhypopituitarism.   Rheumatologic  diseases as temporal arteritis
and polymyalgia rheumatica can cause weight loss.  Initial tests consist of a
chest x-ray, CBC, sed rate and  chemistry panel.  If these are negative along
with an H&P, the chance for organic disease is < 5%.  Other  selective  tests
such  as  a  PPD  skin  test, PSA, ANA, HIV, and ACTH stimulating test may be
needed.

                          -WILSON'S DISEASE-
Wilson's disease (WD) is  an  autosomal  recessive disease first described in
1912 which results in copper  accumulation  in  the  liver,  brain,  kidneys,
skeleton  and  cornea.  The gene is located on chromosome 13.  The prevalence
is 1:20,000 with a carrier  frequency  of  1:90.  WD should be entertained in
anyone with prominent hepatic, neurological  or  psychiatric  manifestations.
The  average  age at onset is 16, and 80% of cases occur in person 6-20 years
of age.  Abdominal pain, lethargy  and  anorexia are often the first symptoms
followed by ascites and jaundice.  The hepatic onset  usually  appears  at  a
younger  age than the neurological component.  Primarily neurological disease
has a longer survival than primarily hepatic patients.  Neurological symptoms
include deterioration in  schoolwork,  drooling,  fixed  grin, masklike face,
tremor, dykinesia and akinesias as well as behavioral or personality changes.
LABORATORY: Low ceruloplasmin levels (less than 20 mg/dL) and  high  24  hour
urinary  copper  (more  than  100  ug) are the most reliable lab data.  Serum
copper is usually low  because  of  the  deficiency in ceruloplasmin to which
copper normallhy  binds.   In  hepatic  failure,  the  copper  rises.   Liver
function  tests  are  only slightly disturbed, although bilirubin may be high
with  fulminant  hepatic  failure  and/or  hemolysis.   In  fulminant  Wilson
hepatitis, transaminases levels are  not  markedly  elevated and the alkaline
phosphatase values are usually normal or low.  In fact  alkaline  phosphatase
may  not  be measurable.  Kaiser Fleisher rings are pathognomonic of Wilsons.
They can sometimes be  seen  with  the  naked  eye  but  usually slit lamp is
required.  The rings are brown or greenish brown.   CT  shows  mild  cerebral
atrophy and diffuse, symmetrical low density areas in the basal ganglia.  The
sensitivity  of  MRI  exceeds  that  of  CT.   Liver  biopsy  demonstrates  a
quantitatively high copper level.  Macroscopic and histologic features of the
liver often resemble either cirrhosis or chronic active hepatitis.  There may
be  frequent  hemolytic  anemia,  Fanconi's  syndrome,  bone  lesions, growth
retardation,  pancreatitis,  glucose  intolerance  and  gallstones.   Without
treatment amenorrhea and spontaneous  abortions are common.  Cardiac findings
include arrhythmias, cardiomyopathy, autonomic dysfunction and cardiac death.
Once diagnosis is made,  penicillamine  must  be  initiated  immediately  and
continued  for  the rest of the patient's life.  The usual dose is 500 mg tid
daily before meals.  Pyridoxine should be given as well because penicillamine
has weak  antipyridoxine  activity.   Sensitivity  reactions to penicillamine
include  thrombocytopenia,  leukopenia,  fever,  rash,  and  lymphadenopathy.
Platelets and WBC shuld be checked  before  treatment  because  hypersplenism
could  be  the  cause.   Pencillamine may also cause late reactions including
nephropathy, thrombocytopenia, LE,  myasthenia  gravis, and pemphigus.  Fatal
toxicity of the drug can occur after years of uneventful therapy, so patients
require lifelong monitoring at regular  intervals.   If  the  patient  cannot
tolerate pencillamine Trientine may be used at an initial dose 800 mg tid and
gradually  decreased.   At  least  8  healthy infants have been born to women
treated with Trientine given  throughout pregnancy.  Penicillamine also poses
little risk to a fetus and usage should  continue  through  pregnancy.   Zinc
alone  has  been  used  as  an alternative treatment, but works slower.  With
treatment patients can be asymptomatic and enjoy a normal life span.  Failure
to comply results in hepatic failure and death usually within 3 days.

                      -WISKOTT-ALDRICH SYNDROME-
Wiskott-Aldrich  Syndrome  (WAS) is an X linked recessive disorder, affecting
males  in   infancy,   and   characterized   by  thrombocytopenia,  recurrent
infections, and eczema.  There is a deficiency of B and T cell function which
results in pyogenic bacterial,  fungal,  viral  and  P.  carinii  infections.
Patients that live longer than 10 years are at increased risk for malignancy,
especially  acute  lymphoblastic  leukemia and lymphoma.  These patients have
poor antibody responses to  polysaccharide,  partial T cell immunodeficiency,
low levels of IgM, hypercatabolism of IgG, but normal IgG  levels,  cutaneous
anergy  and  elevated  levels of IgE and IgA.  The platelets in WAS are small
and decreased in number.  The platelets demonstrate impaired aggregation with
splenic sequestration and destruction.  The  WAS  gene has been mapped to the
proximal short arm of the X chromosome.  CLINICAL: Many of these  males  will
present  in  infancy  due  to  excessive  bleeding  at  circumcision, or with
gastrointestinal  bleeding.   They   may   have   bloody  diarrhea,  cerebral
hemorrhage and septicemia.  The main cause of death in  infancy  is  bleeding
and  infection,  but  later  in life, lymphomas become prevalent.  Infections
include sinopulmonary bacterial  infections,  otitis,  meningitis, and sepsis
from B cell dysfunction.  As T  cell  function  decreases  the  patient  will
develop  infections  from  Pneumocystis carnii, fungi, and viruses.  Patients
are diagnosed by finding very small platelets and thrombocytopenia.  There is
decreased thrombopoiesis.  The IgM is usually  low, while the IgA and IgE are
usually high.  The IgG  level  is  usually  normal  or  slightly  diminished.
Isohemagglutinins  are low or absent, and there is reduced cell surface CD45.
Isohemagglutinin responses to polysaccharide antigens are markedly decreased.
TREATMENT: Bone marrow transplantation  with  matched sibling marrow has been
very successful in reversing all of the defects in Wiskott-Aldrich  syndrome,
but  only  a minority of patients have suitable donors.  Splenectomy has been
helpful in increasing the platelets.   Immune  globulin given IV is useful in
preventing pyogenic infections, but will not  improve  the  thrombocytopenia.
Continuous antibiotics also have been used.

                  -WOLFF-PARKINSON-WHITE SYNDROME-
In 1930, Dr Paul Dudley White, together with John Parkinson reported  several
similar  cases  of healthy young people prone to paroxysmal tachycardia.  The
resting EKG  features  include  a  short  PR  interval,  delta  wave (slurred
upstroke at the beginning of the QRS) and a prolonged QRS interval (caused by
the delta wave).  WPW is the most common form of  ventricular  pre-excitation
and  is  due  to  an accessory pathway of Kent.  Sometimes, WPW is associated
with hypertrophic cardiomyopathy  and  Ebsteins's anomaly.  Approximately 50%
of WPW patients will experience tachycardias that are associated with 3  main
types  of  tachycardia  as follows.  Orthodromic AV re-entrant tachycardia is
the most common (about 95%).  In this tachycardia the wave front travels down
the AV node into the ventricles and  retrogradely to the atrium by way of the
Bundle of Kent.  This results in a narrow QRS  with  rates  between  160  and
220/minute.   There  is  no pre-excitation or delta wave.  The P waves follow
the QRS very closely with the RP interval shorter than the PR interval.  This
type of tachycardia  may  be  confused  with  the  classic  form  of AV nodal
re-entrant tachycardia, a circus movement within the AV  node.   This  latter
type  of  tachycardia  will  partially  or  completely  hide the P wave.  The
treatment of  orthodromic  tachycardia  consists  of  the  Valsalva maneuver,
facial immersion in ice cold water or sinus massage.   These  maneuvers  will
block   the   antegrade  propagation.   If  these  fail,  then  IV  adenosine
(Adenocard) 6 mg IV over  1-2  seconds  followed  by a saline flush is given.
This may be repeated using 12 mg IV after 2-3 minutes up to a maximum  of  30
mg.   Also,  Verapamil  may also be used by giving 10 mg IV slowly which will
block the AV node.   Alternatively,  Procainamide  may  be  used by giving 15
mg/kg IV as a total loading dose.  This is  achieved  by  giving  20  mg/min.
After  the  loading  dose,  an  infusion  may  be  given  at  2-6  mg/min  IV
maintenance.   The  procainamide  usually takes longer to work.  Procainamide
blocks the retrograde path.  If verapamil or procainamide are used, watch for
hypotension.  Antidromic tachycardia occurs  in  less  than  5% of cases.  In
this type, the wave front travels down the accessory pathway to the ventricle
and then back up the AV node.  This leads to a wide QRS.  There is a  P  wave
preceding  each  QRS if not obscured by the wide QRS.  If you have a previous
EKG to compare with, you will find that the orientation and morphology of the
WPW  complexes  resemble  those  during  sinus  rhythm.   This  will  help to
distinguish  it  from  Ventricular  tachycardia.   Treatment  of   antidromic
tachycardia  in  the  hemodynamically  stable patient is done by trying vagal
maneuvers or IV adenosine as  they  may terminate the antidromic tachycardia,
but have no effect on Ventricular tachycardia.  If this fails, then  give  IV
procainamide  as  for Orthodromic tachycardia.  Also, you may use 2-3 boluses
of 50 mg  of  LIdocaine  over  15  minute  periods  followed  by a 2-4 mg/min
infusion.  Both these drugs work by blocking the accessory pathway.   If  the
patient  is  hemodynamically  unstable, then DC cardioversion should be used.
DO NOT  USE  IV  VERAPAMIL  OR  DIGOXIN  IN  WIDE  QRS  TACHYCARDIAS.  ATRIAL
FIBRILLATION AND A WIDE QRS INTERVAL:   In this type of wide QRS tachycardia,
multiple wavepoints of depolarization in the atria bombard the  AV  node  and
the  accessory  pathway  at  rates  up to 600/min.  Because the AV node has a
relatively long refractory period,  it  can  only  conduct a portion of these
impulses and therefore can activate the ventricles at a slower rate  of  100-
150,  as  opposed  to  the  accessory  pathway which can conduct beats to the
ventricles between 200-400/min.  The QRS  is  wide and must be differentiated
from ventricular tachycardia.  In atrial fibrillation the rhythm is regularly
irregular as opposed to ventricular tachycardia.  The  Delta  waves  vary  in
size and there may be an occasional narrow QRS conducted through the AV node.
Again,  if  a  previous EKG is available, the complexes will resemble the WPW
ekg that was in sinus rhythm,  in orientation and morphologically.  This type
of  tachycardia  can  lead  to  ventricular   tachycardia   and   ventricular
fibrillation  and  sudden  death.   Also, in the differential would be atrial
fibrillation with ventricular  aberration,  but  this  usually  presents as a
classic  right  bundle  branch  block  pattern   and   Ashman's   phenomenon.
TREATMENT:  Treatment of atrial fibrillation with WPW is with IV procainamide
or Lidocaine which may  slow  accessory  pathways,  but in general, accessory
pathways conducting at a high rate are not very susceptible when procainamide
or lidocaine are used.  Procainamide may also convert the atrial fibrillation
to sinus rhythm.  If the patient is hemodynamically unstable  as  hypotensive
or  dyspneic,  then  DC conversion is needed.  Again, DO NOT USE VERAPAMIL OR
DIGOXIN because these may accelerate  the accessory pathways.  In summary, if
presented with a wide QRS tachycardia,  first  try  the  vagal  maneuvers  of
carotid  stimulation,  Valsalva  or  facial  immersion  in  ice  water  or IV
Adenocard, keeping the  thought  in  mind,  that  this  may  be an antidromic
presentation of WPW.  If it is, then  you  may  get  a  conversion  to  sinus
rhythm.  However, if the rhythm is ventricular tachycardia then there will be
no  effect  with  Adenocard.  If that is the case, proceed to Procainamide or
Lidocaine.  If these are ineffective,  then  proceed to DC cardioversion.  Do
not use verapamil or digoxin in wide QRS tachycardia.  CHRONIC  DRUG  THERAPY
FOR  WPW: If  the  patient  has  atrial fibrillation and WPW, the accessory
pathway should be blocked with Class IA agents as quinidine, procainamide and
disopyamide.  Class 1C agents  as  flecainide,  encainide and propafenone are
all highly efficacious in blocking the  accessory  pathway.   Flecainide  can
probably  be  used  safely  for  WPW  in patients with no other organic heart
disease.  Propafenone has a mild beta  blocking effect that may be helpful in
cases of catecholamine sensitive arrhythmias.  Amiodarone, a Class III  agent
can  suppress arrhythmias even in patients who have failed therapy with Class
I agents.  However,  side  effect  of  pulmonary  fibrosis, hepatic toxicity,
neurologic toxicity, photosensitivity and thyroid dysfunction  are  always  a
reason  for  consideration  to have electrical physiologic studies performed,
and then proceed to radiofrequency  current ablation.  Patients that have WPW
and are in sinus rhythm, may be treated if they have symptomatic tachycardia,
with digoxin and verapamil.  Common errors occur in diagnosing WPW.   Because
the delta wave distorts the QRS pattern, the resting EKG of a patient who has
WPW  can  be  misread  as  simulating  an old myocardial infarction or bundle
branch block.  Also, patients that have WPW have a high rate, of greater than
50%, false positive treadmill tests.  If you miss the typical findings of WPW
on an EKG  and  that  patient  has  atrial  fibrillation  and is treated with
digoxin or verapamil, there is increased risk  of  ventricular  fibrillation.
The  risk  for  ventricular  fibrillation  is  increased  if the accessory AV
pathway is <  270  milliseconds.   One  can  clinically assess this accessory
pathway by performing serial EKGs.  If the WPW pattern is  intermittent,  the
refractory  period  is  likely  to be long.  An exercise test that causes the
delta wave and short  PR  interval  to  disappear  is  associated with a long
refractory period.  If infusion of IV procainamide at 10 mg/kg over 5 minutes
abolishes the pre-excitation pattern the refractory period is probably  long.
If any of these tests indicate a short refractory period, then the

                   -WOLFF-PARKINSON-WHITE SYNDROME-
Wolff-Parkinson-White is  a  preexcitation  syndrome,  characterized by early
depolarization of  the  ventricular  myocardium  by  an  abnormal  electrical
connection  between the atria and the ventricles known as the bundle of Kent.
This results in a slurred  upstroke  of  the  QRS, a shortened PR interval of
less than 120 milliseconds,  a  widened  QRS  complex  of  greater  than  120
milliseconds and secondary ST-T wave changes.  The slurred portion of the QRS
complex  is  referred to as the delta wave.  Preexcitation tends to widen the
QRS  making   differentiation   between   ventricular   and  supraventricular
arrhythmias difficult.  CLINICAL: Many patients with WPW are asymptomatic and
most adults will have a  structurally  fit  heart  with  the  syndrome  found
unexpectedly when an ECG is done.  WPW sometimes is associated with Ebstein's
anomaly  (apical  displacement  of  the  tricuspid  leaflets  into  the right
ventricular  cavity).   Preexcitation  is  intermittent  and  varies  in each
patient over time.  The significance of the  syndrome  relates  to  the  high
frequency of associated paroxysmal tachycardia.  Reciprocating tachycardia is
common  because  the  electrical  impulse  is  capable  of traveling down one
component of the loop and up the other setting the potential for a variety of
different arrhythmias.   Although  reciprocating  tachycardias  are  the most
common, atrial fibrillation and flutter as well  as  ventricular  tachycardia
may  occur.  Atrial fibrillation can be extremely dangerous as it selectively
travels down the  accessory  pathway  producing  a rapid ventricular response
which can deteriorate into  ventricular  fibrillation.   TREATMENT:  Patients
with atrial fibrillation should not receive digitalis, verapamil or diltiazem
as  they  will  preferentially  slow  conduction  through  the AV node, while
facilitating conduction through  the  accessory  pathway.   If the patient is
stable  they  should  be  treated  with  IV  procainamide  or  if   unstable,
cardioversion.   Procainamide slows conduction through the accessory pathway.
For long term suppression  of  AF,  class IA agents (quinidine, procainamide,
disopyramide) and class IC agents  (flecainide  and  propafenone)  should  be
used.   These drugs will maintain sinus rhythm as well as block the accessory
pathway.  For maximum protection digoxin  or  a  beta blocker combined with a
class IA or IC may be effective.  As an alternate to drug  therapy,  surgical
or radiofrequency is highly effective.

                    -X-LINKED AGAMMAGLOBULINEMIA-
X-Linked   agammaglobulinemia    (Bruton's   aggamaglobulinemia,   congenital
agammaglobulinemia) is an X-linked male disorder characterized by IgG  levels
less than 100 mg/dL with low concentrations of the other immunoglobulins, low
or absent B cells, and absence of plasma cells in the lymphoid tissue.  The B
cell  defect is most probably the result of a maturation block in pre-B cells
to B cells.  The T  cells  are  normal  in number and function.  The disorder
affects male infants usually beginning at about 6 months  when  the  maternal
antibodies  start  to  disappear.   Since  the disorder is X-linked, a family
history may be a clue to the  disorder.   However, in about 33% of cases, the
presentation is due to new mutations.  Commonly  involved  bacteria	include
encapsulated   pyogenic  pathogens  such  as  streptococci,  hemophilus,  and
pneumococcus.   These  patients   are   also   prone   to  chronic  echovirus
encephalitis, hepatitis virus, enteric  cytopathogenic  human  orphan  (ECHO)
virus, enteroviruses, and vaccine induced poliovirus infections.  The patient
usually  presents  with  recurrent  chronic  respiratory  infections  such aa
sinusitis, bronchitis, bronchiectasis,  meningitis,  pyoderma, influenza, and
osteomyelitis.  The infections are treatable, but usually  recur  unless  the
patient  is given gamma globulin.  Patients may also have a form of arthritis
that affects the large joints, not unlike that of rheumatoid arthritis, which
affects about  33-50%  of  patients.   The  knee  and  ankle  are  most often
involved.  This arthritis resolves with Ig therapy.  Unfortunately,  some  of
these  patients  can  develop a fatal syndrome that resembles dermatomyositis
with  disseminated   ECHO   virus   infection.    LABORATORY:   There   is  a
panhypogammaglobulinemia characterized by IgG levels less than 100 mg/100 ml.
The IGA and IgM are severely depressed to  less  than  1%  of  adult  levels.
There  is  normal  cellular  immunity with normal T cells, normal response to
mitogens, allogeneic cells and antigens, and normal delayed hypersensitivity.
Most of  these  patients  do  not  have  circulating  lymphocytes coated with
surface immunoglobulin.   The  lymph  nodes  have  absent  plasma  cells  and
germinal   centers.    Carriers   of   this   disorder  can  be  detected  by
X-inactivation analysis.  The differential should include secondary causes of
hypogammaglobulinemia such as HIV  infection,  nephrotic syndrome and protein
losing enteropathy.  TREATMENT: Treatment	is  with  immune  serum  globulin
using 400 mg/kg/month to 600 mg/kg every 2-3 weeks.

