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SECTION Ⅰ Introduction to Molecular Medicine1

1 THE MOLECULAR BASIS OF HUMAN DISEASE Joseph Loscalzo3

Deoxyribonucleic Acid and the Genetic Code3

Regulation of Gene Expression5

Genetic Variation, Population Diversity, and Genetic Polymorphisms7

Genes and Human Disease8

Gene Mapping9

Identifying Mutant Genes10

Molecular Diagnostics11

Genetic Therapies12

Promising Advances12

SECTION Ⅱ Decision-Making in Medical Practice13

Searching for Relevant Information15

2 EVIDENCE-BASED MEDICINE Awny S. Farajallah Susan S. Beland15

Critical Appraisal of the Literature16

Evaluating Evidence About Diagnostic Tests16

Evaluating Evidence About Outcome17

Evaluating Evidence About Treatment17

Including the Patient in the Decision Process18

SECTION Ⅲ Cardiovascular Disease19

3 STRUCTURE AND FUNCTION OF THE NORMAL HEART AND BLOOD VESSELS Eric H. Awtry Joseph Loscalzo21

Microscopic Anatomy21

Gross Anatomy21

The Circulatory Pathway22

The Conduction System23

Circulatory Physiology and the Cardiac Cycle24

Physiology of Contraction24

Neural Innervation24

Cardiac Performance25

Physiology of the Coronary Circulation27

Physiology of the Systemic Circulation28

Physiology of the Pulmonary Circulation28

Cardiovascular Response to Exercise29

4 EVALUATION OF THE PATIENT WITH CARDIOVASCULAR DISEASE Eric H. Awtry Joseph Loscalzo30

History30

Physical Examination34

Auscultation37

5 DIAGNOSTIC TESTS AND PROCEDURES IN THE PATIENT WITH CARDIOVASCULAR DISEASE Lisa A. Mendes Joseph Loscalzo43

Chest Radiography43

Electrocardiography43

Abnormal ECG Patterns45

Long-Term Ambulatory ECG Recording47

Stress Testing48

Echocardiography50

Nuclear Cardiology52

Cardiac Catheterization52

Right-Sided Heart Catheterization53

Other Procedures53

Noninvasive Vascular Testing55

6 HEART FAILURE AND CARDIOMYOPATHY Lisa A. Mendes Joseph Loscalzo56

Forms of Heart Failure56

Adaptive Mechanisms in Heart Failure56

Evaluation and Treatment of Patients with Heart Failure57

Treatment59

Refractory Heart Failure60

Acute Pulmonary Edema61

Diastolic Dysfunction61

Cardiovascular Assist Devices61

7 CONGENITAL HEART DISEASE Lisa A. Mendes Joseph Loscalzo63

General Considerations63

Fetal and Transitional Circulations63

Congenital Aortic Stenosis63

Coarctation of the Aorta64

Pulmonic Valve Stenosis65

Tetralogy of Fallot65

Atrial Septal Defect66

Ventricular Septal Defect67

Other Congenital Abnormalities68

Patent Ductus Arteriosus68

8 ACQUIRED VALVULAR HEART DISEASE Lisa A. Mendes Joseph Loscalzo69

Aortic Stenosis69

Aortic Regurgitation70

Mitral Stenosis72

Mitral Regurgitation74

Mitral Valve Prolapse74

Tricuspid Stenosis75

Tricuspid Regurgitation75

Pulmonic Stenosis and Regurgitation76

Multivalvular Disease76

Rheumatic Heart Disease76

Endocarditis Prophylaxis77

Prosthetic Heart Valves77

9 CORONARY HEART DISEASE Eric H. Awtry Joseph Loscalzo79

Epidemiology79

Pathophysiology of Atherosclerosis79

Risk Factors80

Nonatherosclerotic Causes of Cardiac Ischemia81

Pathophysiology and Consequences of Myocardial Ischemia82

Angina Pectoris82

Acute Myocardial Infarction90

10 CARDIAC ARRHYTHMIAS Eric H. Awtry Joseph Loscalzo100

Mechanisms of Arrhythmogenesis100

Approach to the Patient with Suspected Arrhythmias103

Management of Cardiac Arrhythmias104

Specific Arrhythmias111

Heart Block120

Clinical Syndromes122

Principles of Cardiopulmonary Resuscitation125

11 MYOCARDIAL AND PERICARDIAL DISEASE Lisa A. Mendes Joseph Loscalzo127

Myocarditis127

Cardiomyopathy128

Amyloidosis131

Pericardial Disease132

12 OTHER CARDIAC TOPICS Lisa A. Mendes Joseph Loscalzo137

Cardiac Tumors137

Traumatic Heart Disease138

Cardiac Surgery139

Noncardiac Surgery in the Cardiac Patient140

Specific Cardiac Conditions142

Cardiac Disease in Pregnancy142

13 VASCULAR DISEASES AND HYPERTENSION Eric H. Awtry Joseph Loscalzo145

Systemic Vascular Disease145

Venous Thromboembolic Disease152

Pulmonary Vascular Disease155

Hypertension157

SECTION Ⅳ Pulmonary and Critical Care Medicine165

14 APPROACH TO THE PATIENT WITH RESPIRATORY DISEASE Bonnie S. Slovis Kenneth L. Brigham167

Common Presenting Complaints167

Physical Examination169

15 ANATOMIC AND PHYSIOLOGIC CONSIDERATIONS Bonnie S. Slovis Kenneth L. Brigham172

Anatomy172

Physiology173

Abnormalities of Pulmonary Gas Exchange177

16 DIAGNOSTIC TECHNIQUES AND THEIR INDICATIONS Bonnie S. Slovis Kenneth L. Brigham181

Imaging Procedures181

Evaluation of Lung Function181

17 OBSTRUCTIVE LUNG DISEASE Bonnie S. Slovis Kenneth L. Brigham185

Pathophysiology of Air Flow Obstruction185

Asthma186

Chronic Obstructive Pulmonary Disease187

Bronchiectasis189

Cystic Fibrosis189

Treatment190

18 INTERSTITIAL AND INFILTRATIVE LUNG DISEASE Bonnie S. Slovis Kenneth L. Brigham194

Pathophysiology and Clinical Manifestations194

Pleural Disease201

19 DISORDERS OF THE PLEURAL SPACE, MEDIASTINUM, AND CHEST WALL Bonnie S. Slovis Kenneth L. Brigham201

Mediastinal Disease203

Chest Wall Disease203

20 NEOPLASTIC DISEASES OF THE LUNG Bonnie S. Slovis Kenneth L. Brigham206

Risk Factors206

Pathology206

Clinical Presentation206

Diagnosis and Evaluation207

Solitary Pulmonary Nodule208

Treatment and Prognosis209

21 DISORDERED BREATHING Bonnie S. Slovis Kenneth L. Brigham210

Sleep Apnea Syndrome210

Other Breathing Disorders211

Air Pollution213

22 ENVIRONMENTAL AND OCCUPATIONAL INJURY Bonnie S. Slovis Kenneth L. Brigham213

Pneumoconioses213

Noxious Gases and Fumes214

Smoke Inhalation214

High-Altitude Injury215

Drowning and Near-Drowning215

23 ESSENTIALS OF PULMONARY CRITICAL CARE MEDICINE Bonnie S. Slovis Kenneth L. Brigham216

Shock216

Acute Respiratory Failure217

Oxygen Therapy217

Mechanical Ventilation218

Complications of Endotracheal Intubation and Mechanical Ventilation219

Systemic Inflammatory Response Syndrome, Sepsis, Multiple Organ Dysfunction Syndrome, and Adult Respiratory Distress Syndrome219

SECTION Ⅴ Renal Disease221

24 ELEMENTS OF RENAL STRUCTURE AND FUNCTION Dinesh K. Chatoth223

Elements of Renal Structure223

Elements of Renal Physiology226

25 APPROACH TO THE PATIENT WITH RENAL DISEASE Yousri M. H. Barri Sudhir V. Shah232

Assessment of the Patient with Renal Disease232

The Major Renal Syndromes234

Radiologic Imaging of the Urinary Tract236

Renal Biopsy237

26 FLUID AND ELECTROLYTE DISORDERS Thomas E. Andreoli Sameh R. Abul-Ezz238

Volume Disorders238

Osmolality Disorders241

Hyponatremia242

Hypernatremia244

Disturbances in Potassium Balance245

Disturbances in Acid-Base Balance248

27 GLOMERULAR DISEASES Sudhir V. Shah253

The Glomerulus253

Mechanisms of Glomerular Injury253

Clinical Manifestations of Glomerular Disease253

Approach to the Patient with Glomerular Disease255

Acute Nephritic Syndrome255

Rapidly Progressive Glomerulonephritis257

Nephrotic Syndrome258

Asymptomatic Urinary Abnormalities263

28 MAJOR NONGLOMERULAR DISORDERS Dinesh K. Chatoth266

Tubulointerstitial Nephropathy266

Cystic Diseases of the Kidney269

Urinary Tract Obstruction271

Nephrolithiasis272

Renal Neoplasia275

29 VASCULAR DISORDERS OF THE KIDNEY Yousri M. H. Barri278

Renal Arterial Occlusion278

Ischemic Renal Disease278

Arterioles and Microvasculature279

Atheroembolic Diseases of the Kidney279

Chronic Hypertensive Nephrosclerosis280

Malignant Nephrosclerosis280

Scleroderma280

Hemolytic-Uremic Syndrome and Thrombotic Thrombocytopenic Purpura281

Antiphospholipid Syndrome and the Kidney281

Renal Vein Thrombosis282

30 ACUTE RENAL FAILURE Sudhir V. Shah283

Definition and Etiology283

Differential Diagnosis and Diagnostic Evaluation of the Patient283

Clinical Presentation, Complications, and Management of Acute Tubular Necrosis287

Specific Causes of Acute Renal Failure288

31 CHRONIC RENAL FAILURE Mary Jo Shaver291

Adaptation to Nephron Loss291

Conservative Management292

Clinical Manifestations293

Treatment of End-Stage Renal Failure296

SECTION Ⅵ Gastrointestinal Disease301

Clinical Features303

Causes of Abdominal Pain303

A. Abdominal Pain Edgar Achkar303

32 COMMON CLINICAL MANIFESTATIONS OF GASTROINTESTINAL DISEASE303

Physiology303

The Acute Abdomen305

Chronic Abdominal Pain305

B. Gastrointestinal Hemorrhage Gregory Zuccaro, Jr.306

Acute Gastrointestinal Hemorrhage306

Chronic Gastrointestinal Hemorrhage309

C. Malabsorption Edy E. Soffer310

Digestion and Absorption of Fat310

Digestion and Absorption of Carbohydrates310

Digestion and Absorption of Proteins310

Mechanisms of Malabsorption310

Clinical Manifestations of Malabsorption311

Multiple Mechanisms311

Tests for Malabsorption312

Approach to the Patient with Suspected Malabsorption314

Treatment314

D. Diarrhea Edy E. Soffer316

Definition316

Normal Physiology316

Pathophysiology317

Evaluation of Diarrhea318

33 ENDOSCOPIC AND RADIOGRAPHIC PROCEDURES IN GASTROENTEROLOGY John J. Vargo Ⅱ321

Gastrointestinal Endoscopy321

Esophagogastroduodenoscopy and Enteroscopy321

Endoscopic Retrograde Cholangiopancreatography322

Endoscopic Ultrasonography323

Sigmoidoscopy and Colonoscopy323

Radiographic Procedures323

34 DISEASES OF THE ESOPHAGUS Joel E. Richter326

Normal Esophageal Physiology326

Clinical Symptoms of Esophageal Disease326

Gastroesophageal Reflux Disease327

Motility Disorders of the Oropharynx and Esophagus329

Other Esophageal Disorders330

35 DISEASES OF THE STOMACH AND DUODENUM Gary W. Falk332

Gastroduodenal Anatomy332

Gastroduodenal Mucosal Secretion and Protective Factors332

Gastroduodenal Motor Physiology333

Gastritis334

Peptic Ulcer Disease335

Zollinger-Ellison Syndrome341

Delayed Gastric Emptying342

Rapid Gastric Emptying343

36 INFLAMMATORY BOWEL DISEASE Aaron Brzezinski345

Etiology345

Incidence and Epidemiology345

Ulcerative Colitis: Clinical Features346

Crohn s Disease: Clinical Features346

Extraintestinal Manifestations346

Other Complications346

Treatment347

Differential Diagnosis347

Diagnosis347

Colon Cancer347

37 NEOPLASMS OF THE GASTROINTESTINAL TRACT Carol A. Burke351

Esophageal Carcinoma351

Gastric Carcinoma352

Colorectal Polyps and Carcinoma353

The Polyposis Syndromes354

Carcinoid Tumors355

38 DISEASES OF THE PANCREAS Darwin L. Conwell356

Anatomy and Physiology356

Acute Pancreatitis358

Chronic Pancreatitis361

Carcinoma of the Pancreas362

SECTION Ⅶ Diseases of the Liver and Biliary System365

39 LABORATORY TESTS IN LIVER DISEASE Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas367

Clinical Approach to Liver Disease367

Laboratory Tests of Liver Function and Disease367

Liver Biopsy370

40 JAUNDICE Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas371

Bilirubin Metabolism371

Laboratory Tests for Bilirubin371

Clinical Classification372

Approach to Diagnosis374

41 ACUTE AND CHRONIC HEPATITIS Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas376

Acute Hepatitis376

Chronic Hepatitis383

Treatment385

Diagnosis385

42 FULMINANT HEPATIC FAILURE Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas385

Hepatic Transplantation386

Prognosis386

43 CIRRHOSIS OF THE LIVER AND ITS COMPLICATIONS Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas387

Clinical and Laboratory Features387

Specific Causes387

Major Complications388

Hepatic Transplantation392

44 NEOPLASTIC, INFILTRATIVE, AND VASCULAR DISEASES OF THE LIVER Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas394

Hepatic Neoplasms394

Liver Abscess395

Granulomatous Liver Disease395

Vascular Disease of the Liver396

Diagnostic Approach to Hepatic Lesions396

45 DISORDERS OF THE GALLBLADDER AND BILIARY TRACT Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas398

Normal Biliary Physiology398

Pathophysiology of Gallstone Formation(Cholelithiasis)398

Clinical Manifestations of Gallstones399

SECTION Ⅷ Hematologic Disease403

46 HEMATOPOIESlS AND HEMATOPOIETIC FAILURE Eunice S. Wang Nancy Berliner405

Hematopoietic Tissues405

Stem Cell Theory of Hematopoiesis405

Hematopoietic Differentiation Pathway406

Disorders of Hematopoiesis408

47 CLONAL DISORDERS OF THE HEMATOPOIETIC STEM CELL Eunice S. Wang Nancy Berliner410

Myelodysplastic Disorders410

Myeloproliferative Disorders412

Chronic Myelogenous Leukemia414

Acute Leukemias415

48 DISORDERS OF RED BLOOD CELLS Nancy Berliner419

Normal Red Blood Cell Structure and Function419

Clinical Approach to Anemia419

Evaluation of Hypoproliferative Anemia420

49 CLINICAL DISORDERS OF NEUTROPHILS Nancy Berliner431

Normal Granulocyte Development, Structure, and Function431

Determinants of Peripheral Neutrophil Number432

Evaluation of Leukocytosis (Neutrophilia)433

Evaluation of Leukopenia (Neutropenia)433

50 DISORDERS OF LYMPHOCYTES Jill Lacy435

Cells of the Immune System: Lymphocyte Development, Function, and Localization435

Neoplasia of Lymphoid Origin437

51 NORMAL HEMOSTASIS Henry M. Rinder449

Vascular Wall Physiology449

Platelet Physiology450

Coagulation Cascade453

Endothelial-Associated Fibrinolysis456

52 DISORDERS OF HEMOSTASlS: BLEEDING Henry M. Rinder457

Clinical Evaluation of Bleeding457

Vascular Causes of Bleeding457

Bleeding Caused by Platelet Disorders: Thrombocytopenia459

Bleeding Caused by Platelet Disorders: Qualitative Platelet Defects465

Fibrinogen Disorders468

Bleeding Caused by Coagulation Factor Disorders469

Bleeding in Patients with a Normal Laboratory Screen471

53 DISORDERS OF HEMOSTASIS: THROMBOSIS Henry M. Rinder473

Clinical Evaluation of Thrombosis473

Vascular Causes of Thrombosis473

Atherothrombosis473

Inherited Risk Factors for Venous Thrombosis475

Acquired Risk Factors for Venous Thrombosis476

Hypercoagulability and Platelet Disorders477

Laboratory Evaluation of Thrombosis477

Therapy for Venous Thromboembolism478

Venous Thromboembolism During Pregnancy480

Perioperative Anticoagulation480

Future Anticoagulant Strategies481

SECTION Ⅸ Oncologic Disease483

54 CANCER ETIOLOGY: ONCOGENES AND ENVIRONMENTAL/TOXIC FACTORS Christopher E. Desch485

Cancer Phenotype485

Cancer Genetics485

Etiology486

55 CANCER EPIDEMIOLOGY AND CANCER PREVENTION Jennifer J. Griggs489

Cancer Epidemiology489

Cancer Prevention489

56 SOLID TUMORS Jennifer J. Griggs Christopher E. Desch493

Lung Cancer493

Gastrointestinal Cancers495

Breast Cancer498

Genitourinary Cancers499

Melanoma503

Spinal Cord Compression505

57 COMPLICATIONS OF CANCER Jennifer J. Griggs505

Superior Vena Cava Syndrome506

Hypercalcemia506

Paraneoplastic Syndromes507

58 PRINCIPLES OF CANCER TREATMENT Christopher E. Desch508

Radiology508

Surgery508

Radiation Therapy508

Chemotherapy509

Hormonal Therapy510

Supportive Care511

Biologic Therapy511

Bone Marrow Transplantation511

SECTION Ⅹ Metabolic Disease513

59 EATING DISORDERS Peter N. Herbert515

Obesity515

Anorexia Nervosa and Bulimia Nervosa519

60 PRINCIPLES OF NUTRITIONAL SUPPORT IN ADULT PATIENTS Peter N. Herbert522

Nutritional Assessment522

Route of Nutritional Support522

Water523

Calories and Protein523

Vitamins and Minerals524

Home Nutritional Support524

61 DISORDERS OF LIPID METABOLISM Peter N. Herbert526

Plasma Lipoprotein Physiology526

Evaluation of Serum Lipoprotein Concentrations527

Elevated Chylomicrons, VLDL, and IDL528

Treatment of Hypertriglyceridemia529

Elevated LDL530

Treatment of Hypercholesterolemia530

Lipids and Vascular Disease531

62 DISORDERS OF METALS AND METALLOPROTEINS Peter N. Herbert533

Wilson s Disease533

Treatment534

Hemochromatosis534

Porphyrias536

63 INHERITED DISORDERS OF CONNECTIVE TISSUE Peter N. Herbert539

Collagen Disorders539

Marfan s Syndrome540

Pseudoxanthoma Elasticum541

SECTION Ⅺ Endocrine Disease543

64 HYPOTHALAMIC-PITUITARY AXIS Vivien Herman-Bonert545

Anatomy545

Anterior Pituitary Hormone Physiology and Testing545

Neuroradiologic Evaluation of the Pituitary Gland548

Pituitary and Hypothalamic Disorders548

Pituitary Tumors550

The Posterior Pituitary Gland552

65 THE THYROID GLAND Vivien Herman-Bonert Theodore C. Friedman555

Thyroid Hormone Physiology555

Thyroid Evaluation556

Hyperthyroidism557

Graves Disease557

Toxic Multinodular Goiter559

Thyroiditis559

Toxic Adenoma559

Thyrotoxicosis Factitia560

Rare Causes of Thyrotoxicosis560

Hypothyroidism560

Goiter562

Solitary Thyroid Nodules562

Thyroid Carcinoma563

66 THE ADRENAL GLAND Theodore C. Friedman564

Physiology564

Adrenal Insufficiency565

Hyporeninemic Hypoaldosteronism568

Congenital Adrenal Hyperplasia568

Syndromes of Adrenocorticoid Hyperfunction569

Adrenal Medullary Hyperfunction574

67 MALE REPRODUCTIVE ENDOCRINOLOGY Glenn D. Braunstein575

Hypogonadism575

Erectile Dysfunction579

Gynecomastia579

Testicular Tumors580

Benign Prostatic Hyperplasia581

Carcinoma of the Prostate581

68 DIABETES MELLITUS Philip Barnett Glenn D. Braunstein583

Definition583

Diagnosis583

Classification585

Pathogenesis586

Management588

Complications594

69 HYPOGLYCEMIA Philip Barnett599

Definition599

Physiology of Glucose Homeostasis599

Clinical Classification of Hypoglycemia600

Diagnostic Work-up of Hypoglycemia603

Treatment603

SECTION Ⅻ Women s Health605

70 WOMEN S HEALTH: GENERAL CONCEPTS Sally L. Hodder Anne L. Taylor607

Gender Differences in the Epidemiology of Disease by Age Group607

Gender and the Patient-Physician Interaction608

Exercise Across the Feminine Life Cycle608

71 HORMONAL INFLUENCES ON WOMEN S HEALTH Sally L. Hodder Anne L. Taylor610

Normal Physiology610

Dysmenorrhea and Premenstrual Syndrome610

Amenorrhea612

Abnormal Uterine Bleeding613

Hirsutism616

Hormone Therapy616

72 DISEASES COMMON IN WOMEN Sally L. Hodder Anne L. Taylor620

Cardiovascular Diseases620

Osteoporosis621

Breast Cancer and Benign Breast Disease622

Cancer of the Cervix, Uterus, and Ovary623

Sexually Transmitted Diseases and Pelvic Inflammatory Disease623

Domestic Violence625

Urinary incontinence625

Disorders of Cognition and Affect626

SECTION ⅩⅢ Diseases of Bone and Bone Mineral Metabolism627

73 NORMAL PHYSIOLOGY OF BONE AND BONE MINERALS F. Richard Bringhurst629

Bone Structure and Metabolism629

Calcium Metabolism630

Phosphorus Metabolism632

Magnesium Metabolism634

Vitamin D636

Calcitonin637

74 THE PARATHYROID GLANDS, HYPERCALCEMIA, AND HYPOCALCEMIA Joel S. Finkelstein639

Normal Physiology639

Hypercalcemia640

Hypocalcemia645

75 OSTEOMALACIA AND RICKETS F. Richard Bringhurst649

Pathogenesis649

Specific Causes649

Clinical Manifestations652

Laboratory and Radiographic Features652

Diagnosis652

Treatment652

76 OSTEOPOROSIS Joel S. Finkelstein654

General Considerations654

Etiology and Pathogenesis654

Clinical Manifestations656

Radiographic Findings656

Diagnosis656

Treatment658

Glucocorticoid-Induced Bone Loss660

77 PAGET S DISEASE OF BONE Margaret P. Seton662

Incidence and Prevalence662

Etiology662

Pathology and Pathophysiology662

Clinical Picture662

Associated Conditions663

Laboratory Assessment663

Treatment663

SECTION ⅩⅣ Musculoskeletal and Connective Tissue Disease667

78 APPROACH TO THE PATIENT WITH RHEUMATIC DISEASE Joseph H. Korn669

Musculoskeletal History and Examination669

Laboratory Testing671

Radiographic Studies672

79 RHEUMATOID ARTHRITIS Joseph H. Korn673

Epidemiology and Genetics673

Pathology673

Pathophysiology673

Clinical Features674

Diagnosis675

Treatment675

Prognosis677

80 SPONDYLOARTHROPATHIES Peter A. Merkel678

Epidemiology678

Pathogenesis678

Clinical Features679

Radiographic Features680

Treatment681

81 SYSTEMIC LUPUS ERYTHEMATOSUS Peter A. Merkel682

Pathogenesis682

Clinical Manifestations682

Clinical Subsets683

Treatment684

82 ANTIPHOSPHOLIPID ANTIBODY SYNDROME Peter A. Merkel687

Etiology687

Clinical Features687

Diagnosis687

Treatment688

Clinical Features689

Pathology and Pathophysiology689

Epidemiology and Genetics689

83 SYSTEMIC SCLEROSIS (SCLERODERMA) Joseph H. Korn689

Diagnosis and Differential Diagnosis691

Treatment691

Prognosis693

84 IDIOPATHIC INFLAMMATORY MYOPATHIES Robert W. Simms694

Pathology and Pathophysiology694

Clinical Presentation694

Diagnosis696

Differential Diagnosis696

Treatment696

85 SJOGREN S SYNDROME Peter A. Merkel698

Clinical Features698

Diagnosis698

Treatment700

88 VASCULITIDES Peter A. Merkel701

Classification701

Pathogenesis701

Clinical Features702

Specific Types of Vasculitis702

Diagnosis704

Autoantibodies and Vasculitis705

Treatment705

87 CRYSTAL ARTHROPATHIES Joseph H. Korn707

Gout707

Calcium Pyrophosphate Deposition Disease711

Other Crystal Disorders711

Pathology712

88 OSTEOARTHRITIS Robert W. Simms712

Clinical Features and Diagnosis713

Treatment714

89 NONARTICULAR SOFT TISSUE DISORDERS Robert W. Simms715

Etiology and Pathogenesis715

Classification of Bursae715

Diagnosis of Nonarticular Soft Tissue Disorders716

Bursitis716

Tendinitis717

Fibromyalgia Syndrome717

90 RHEUMATIC MANIFESTATIONS OF SYSTEMIC DISORDERS Robert W. Simms720

Rheumatic Syndromes Associated with Malignancy720

Hematologic Disorders721

Gastrointestinal Diseases722

Endocrine Disorders723

Sarcoidosis724

SECTION ⅩⅤ Infectious Disease725

91 ORGANISMS THAT INFECT HUMANS Michael M. Lederman727

Viruses727

Chlamydiae727

Rickettsiae728

Mycoplasma728

Bacteria728

Fungi730

Protozoans731

Helminths732

Local Barriers to Infection733

92 HOST DEFENSES AGAINST INFECTION Robert A. Salata733

Components of the Immune System734

Nonspecific Effector Mechanisms737

Resistance to Extracellular Bacteria: Encapsulated Organisms738

Resistance to Obligate Intracellular Parasites: Viruses739

Resistance to Facultative Intracellular Parasites: Mycobacterium tuberculosis740

93 LABORATORY DIAGNOSIS OF INFECTIOUS DISEASES Michael M. Lederman741

Diagnosis by Direct Visualization of the Organism741

Diagnosis by Detection of Microbial Antigens742

Diagnosis by Examination of Host Immune or Inflammatory Responses742

Assays that Detect Microbial Nucleoside Sequences743

Diagnosis by Isolation of the Organism in Culture743

Isolation of Fungi and Mycobacteria744

Bacterial Isolation744

Viral Isolation744

Isolation of Rickettsia, Chlamydia, and Mycoplasma744

94 ANTIMICROBIAL THERAPY Michael M. Lederman745

The Pathogen745

Site of Infection745

Characteristics of the Antimicrobial746

Route of Administration746

Duration of Therapy746

Combinations749

Monitoring of Antimicrobial Therapy749

Antiviral Agents749

Antifungal Agents749

Antimicrobial Resistance Testing749

Fever and Hyperthermia750

95 FEVER AND FEBRILE SYNDROMES Robert A. Salata750

Regulation of Body Temperature750

Acute Febrile Syndromes752

Fever of Unknown Origin760

Factitious or Self-Induced Fever763

96 BACTEREMIA Robert A. Salata765

Epidemiology765

Pathogenesis766

Clinical Manifestations767

Diagnosis769

Therapy769

97 INFECTIONS OF THE NERVOUS SYSTEM Robert A. Salata771

Meningitis772

Encephalitis778

Spectrum of Tuberculous, Fungal, and Parasitic Infections779

Rabies779

98 INFECTIONS OF THE HEAD AND NECK Michael M. Lederrnan782

Infections of the Ear782

Infections of the Nose and Sinuses782

Infections of the Mouth and Pharynx783

99 INFECTIONS OF THE LOWER RESPIRATORY TRACT Michael M. Lederman788

Pathogenesis788

Epidemiology789

Differential Diagnosis789

Diagnosis790

Specific Pathogenic Organisms791

Treatment and Outcome795

Prevention796

Infective Endocarditis798

100 INFECTIONS OF THE HEART AND VESSELS Michael M. Lederrnan798

Prosthetic Valve Endocarditis802

Prophylaxis of Infective Endocarditis803

Bacterial Endarteritis and Suppurative Phlebitis804

101 SKIN AND SOFT TISSUE INFECTIONS Michael M. Lederrnan805

Superficial Infections of the Skin805

Deeper Infections of the Skin and Soft Tissue809

102 INTRA-ABDOMINAL ABSCESS AND PERITONITIS Michael M. Lederrnan811

Intra-Abdominal Abscess811

Abscesses of Solid Organs811

Extravisceral Abscesses813

Peritonitis813

Types of Microbial Diarrheal Diseases815

103 INFECTIOUS DIARRHEA Michael M. Lederrnan815

Pathogenesis and Pathophysiology: General Concepts815

General Epidemiologic Considerations818

Diagnosis818

Management: General Principles of Electrolyte Repletion Therapy818

104 INFECTIONS INVOLVING BONES AND JOINTS Michael M. Lederrnan821

Arthritis821

Septic Bursitis823

Osteomyelitis823

105 INFECTIONS OF THE URINARY TRACT Michael M. Lederrnan825

Urethritis825

Cystitis and Pyelonephritis825

Prostatitis827

Approach to the Hospitalized Patient with Possible Nosocomial infection828

106 NOSOCOMIAL INFECTIONS Michael M. Lederrnan828

Infection Control828

Nosocomial Pneumonia829

Intravascular Catheter-Related Infections830

Pressure Sores831

Nosocomial Urinary Tract infection831

107 SEXUALLY TRANSMITTED DISEASES Robert A. Salata832

Genital Sores832

Urethritis, Cervicitis, and Pelvic Inflammatory Disease836

Proctocolitis in Homosexual Men840

108 HIV INFECTION AND THE ACQUIRED IMMUNODEFICIENCY SYNDROME Charles C. J. Carpenter Michael M. Lederman841

Epidemiology841

Pathophysiology843

Diagnosis and Testing for HIV Infection846

Sequential Clinical Manifestations of HIV-1 Infection847

Management of HIV Infection849

Management of Specific Clinical Manifestations of Immunodeficiency: A Problem-Oriented Approach852

Mucocutaneous Diseases853

Nervous System Diseases855

Pulmonary Diseases858

Gastrointestinal Diseases860

Unexplained Fever860

Weight Loss and Anorexia861

AIDS-Associated Malignancies861

Other Complications of HIV Infection861

Prevention of HIV Infection862

Disorders of Cell-Mediated Immunity863

109 INFECTIONS IN THE IMMUNOCOMPROMISED HOST Robert A. Salata863

Disorders of Humoral Immunity864

Impaired Neutrophil Function864

Neutropenia865

Diagnostic Problems in the Compromised Host865

Prevention and Treatment of Infections in the Patient with Neutropenia866

110 INFECTIOUS DISEASES OF TRAVELERS: PROTOZOAL AND HELMINTHIC INFECTIONS Robert A. Salata868

Preparation of Travelers868

The Returning Traveler870

Protozoal and Helminthic Infections871

SECTION ⅩⅥ Neurologic Disease875

111 NEUROLOGIC EVALUATION OF THE PATIENT Frederick J. Marshall877

Taking a Neurologic History877

The Neurologic Examination878

Technologic Assessment879

112 DISORDERS OF CONSCIOUSNESS Roger P. Simon883

Pathophysiology883

Diagnostic Approach884

Prognosis in Coma887

Coma-like States887

113 DISORDERS OF SLEEP Roger P. Simon890

Neurobiology of Sleep890

Insomnia890

Abnormal Arousal890

Sleep Apnea891

Parasomnias891

Narcolepsy892

Regional Syndromes893

Anatomy893

114 FOCAL BRAIN DISEASE Timothy J. Counihan893

115 DEMENTIA AND MEMORY DISTURBANCES Frederick J. Marshall896

Major Dementia Syndromes896

Other Memory Disturbances899

116 DISORDERS OF MOOD AND BEHAVIOR Frederick J. Marshall901

Psychotic Disorders901

Depression and Bipolar Disorders902

Anxiety Disorders904

Somatoform Disorders904

Factitious Disorder905

Dissociative Disorders905

Personality Disorders and Substance Abuse905

Hyperthermia906

117 DISORDERS OF THERMAL REGULATION Roger P. Simon906

Hypothermia906

118 HEADACHE, NECK PAIN, AND OTHER PAINFUL DISORDERS Timothy J. Counihan909

Headache909

Neck and Back Pain915

119 DISORDERS OF VISION AND HEARING Timothy J. Counihan918

Disorders of Vision and Eye Movements918

Hearing and Its Impairments922

120 DIZZINESS Roger P. Simon925

Approach to the Diagnosis925

Treatment928

121 DISORDERS OF THE MOTOR SYSTEM Frederick J. Marshall929

Symptoms and Signs of Motor System Disease929

Movement Disorders and Ataxia930

Hypokinetic Movement Disorders933

Hyperkinetic Movement Disorders935

Cerebellar Ataxias937

122 DEVELOPMENTAL AND NEUROCUTANEOUS DISORDERS Robert C. Griggs939

Spinal Malformations939

Chiari Malformations939

Tethered Spinal Cord939

Syringohydromyelia939

Malformations of Cortical Development940

Developmental and Neurocutaneous Disorders940

123 CEREBROVASCULAR DISEASE Timothy J. Counihan942

Epidemiology942

Anatomy942

Ischemic Stroke943

Physiology943

Major Stroke Syndromes945

Diagnosis947

Differential Diagnosis947

Primary Stroke Prevention947

Management of Acute Stroke948

Intracerebral Hemorrhage949

Intracranial Aneurysms951

Vascular Malformations952

124 TRAUMA TO HEAD AND SPINE Roger P. Simon953

Head Injury953

Spinal Cord Injury955

Whiplash955

Incidence and Etiology956

Classification and Clinical Manifestations956

125 EPILEPSY Robert C. Griggs956

Definition956

Diagnosis960

Differential Diagnosis961

Treatment962

Prognosis964

Discontinuing Antiepileptic Drugs964

126 CENTRAL NERVOUS SYSTEM TUMORS Jennifer J. Griggs965

Classification965

Clinical Manifestations965

Evaluation of the Patient966

Treatment966

Specific Tumors967

Brain Abscess969

127 INFECTIOUS DISEASES OF THE NERVOUS SYSTEM Robert C Griggs Roger P Simon969

Subdural Empyema970

Malignant External Otitis970

Spinal Epidural Abscess970

Septic Cavernous Sinus Thrombosis971

Lateral Sinus Thrombosis971

Septic Sagittal Thrombosis971

Neurologic Complications of Infectious Endocarditis971

Prion Diseases972

128 DEMYELINATING AND INFLAMMATORY DISORDERS Robert C. Griggs973

Multiple Sclerosis973

Optic Neuritis975

Neuromyelitis Optica975

Acute Transverse Myelitis977

Acute Disseminated Encephalomyelitis977

129 NEUROMUSCULAR DISEASES: DISORDERS OF THE MOTOR NEURON AND PLEXUS AND PERIPHERAL NERVE DISEASE Robert C. Griggs979

Diagnostic Tests980

Diseases of the Motor Neuron (Anterior Horn Cell)981

Plexopathy982

Peripheral Nerve Disease982

Common Mononeuropathies983

Polyneuropathies984

130 MUSCLE DISEASES Robert C. Griggs988

Organization and Structure of Muscle988

Assessment988

Muscular Dystrophies990

Congenital Myopathies991

Metabolic Myopathies991

Specific Mitochondrial Disorders Affecting Muscle992

Channelopathies (Nondystrophic Myotonias and Periodic Paralyses)993

Inflammatory Myopathies994

Myopathies Caused by Endocrine and Systemic Disorders996

Toxic Myopathies996

Myoglobinuria997

131 NEUROMUSCULAR JUNCTION DISEASE Robert C. Griggs998

Myasthenia Gravis998

Lambert-Eaton Myasthenic Syndrome999

Drug-Induced Myesthenic Syndromes1000

Organophosphate Intoxication1000

SECTION ⅩⅦ The Aging Patient1001

132 THE BIOLOGY OF AGING David A Lipschitz Robert J. Reis Dennis H. Sullivan1003

Theories of Aging1003

Demographics of Aging and Implications for Health Care1005

Assessment of the Older Patient1006

Common and Often Inadequately Assessed Medical Problems of the Elderly1006

SECTION ⅩⅧ Substance Abuse1011

133 ALCOHOL AND SUBSTANCE ABUSE Timothy E. Holcomb Jeffrey L. Clothier1013

Screening1014

Tobacco and Alcohol Abuse1014

Prescription Drug Abuse1018

?icit Drug Abuse1020

APPENDIX Commonly Measured Laboratory Values1023

INDEX1029