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SECTION Ⅰ Introduction to Molecular Medicine 1

1 THE MOLECULAR BASIS OF HUMAN DISEASE Joseph Loscalzo 3

Deoxyribonucleic Acid and the Genetic Code 3

Regulation of Gene Expression 5

Genetic Variation, Population Diversity, and Genetic Polymorphisms 7

Genes and Human Disease 8

Gene Mapping 9

Identifying Mutant Genes 10

Molecular Diagnostics 11

Genetic Therapies 12

Promising Advances 12

SECTION Ⅱ Decision-Making in Medical Practice 13

Searching for Relevant Information 15

2 EVIDENCE-BASED MEDICINE Awny S. Farajallah Susan S. Beland 15

Critical Appraisal of the Literature 16

Evaluating Evidence About Diagnostic Tests 16

Evaluating Evidence About Outcome 17

Evaluating Evidence About Treatment 17

Including the Patient in the Decision Process 18

SECTION Ⅲ Cardiovascular Disease 19

3 STRUCTURE AND FUNCTION OF THE NORMAL HEART AND BLOOD VESSELS Eric H. Awtry Joseph Loscalzo 21

Microscopic Anatomy 21

Gross Anatomy 21

The Circulatory Pathway 22

The Conduction System 23

Circulatory Physiology and the Cardiac Cycle 24

Physiology of Contraction 24

Neural Innervation 24

Cardiac Performance 25

Physiology of the Coronary Circulation 27

Physiology of the Systemic Circulation 28

Physiology of the Pulmonary Circulation 28

Cardiovascular Response to Exercise 29

4 EVALUATION OF THE PATIENT WITH CARDIOVASCULAR DISEASE Eric H. Awtry Joseph Loscalzo 30

History 30

Physical Examination 34

Auscultation 37

5 DIAGNOSTIC TESTS AND PROCEDURES IN THE PATIENT WITH CARDIOVASCULAR DISEASE Lisa A. Mendes Joseph Loscalzo 43

Chest Radiography 43

Electrocardiography 43

Abnormal ECG Patterns 45

Long-Term Ambulatory ECG Recording 47

Stress Testing 48

Echocardiography 50

Nuclear Cardiology 52

Cardiac Catheterization 52

Right-Sided Heart Catheterization 53

Other Procedures 53

Noninvasive Vascular Testing 55

6 HEART FAILURE AND CARDIOMYOPATHY Lisa A. Mendes Joseph Loscalzo 56

Forms of Heart Failure 56

Adaptive Mechanisms in Heart Failure 56

Evaluation and Treatment of Patients with Heart Failure 57

Treatment 59

Refractory Heart Failure 60

Acute Pulmonary Edema 61

Diastolic Dysfunction 61

Cardiovascular Assist Devices 61

7 CONGENITAL HEART DISEASE Lisa A. Mendes Joseph Loscalzo 63

General Considerations 63

Fetal and Transitional Circulations 63

Congenital Aortic Stenosis 63

Coarctation of the Aorta 64

Pulmonic Valve Stenosis 65

Tetralogy of Fallot 65

Atrial Septal Defect 66

Ventricular Septal Defect 67

Other Congenital Abnormalities 68

Patent Ductus Arteriosus 68

8 ACQUIRED VALVULAR HEART DISEASE Lisa A. Mendes Joseph Loscalzo 69

Aortic Stenosis 69

Aortic Regurgitation 70

Mitral Stenosis 72

Mitral Regurgitation 74

Mitral Valve Prolapse 74

Tricuspid Stenosis 75

Tricuspid Regurgitation 75

Pulmonic Stenosis and Regurgitation 76

Multivalvular Disease 76

Rheumatic Heart Disease 76

Endocarditis Prophylaxis 77

Prosthetic Heart Valves 77

9 CORONARY HEART DISEASE Eric H. Awtry Joseph Loscalzo 79

Epidemiology 79

Pathophysiology of Atherosclerosis 79

Risk Factors 80

Nonatherosclerotic Causes of Cardiac Ischemia 81

Pathophysiology and Consequences of Myocardial Ischemia 82

Angina Pectoris 82

Acute Myocardial Infarction 90

10 CARDIAC ARRHYTHMIAS Eric H. Awtry Joseph Loscalzo 100

Mechanisms of Arrhythmogenesis 100

Approach to the Patient with Suspected Arrhythmias 103

Management of Cardiac Arrhythmias 104

Specific Arrhythmias 111

Heart Block 120

Clinical Syndromes 122

Principles of Cardiopulmonary Resuscitation 125

11 MYOCARDIAL AND PERICARDIAL DISEASE Lisa A. Mendes Joseph Loscalzo 127

Myocarditis 127

Cardiomyopathy 128

Amyloidosis 131

Pericardial Disease 132

12 OTHER CARDIAC TOPICS Lisa A. Mendes Joseph Loscalzo 137

Cardiac Tumors 137

Traumatic Heart Disease 138

Cardiac Surgery 139

Noncardiac Surgery in the Cardiac Patient 140

Specific Cardiac Conditions 142

Cardiac Disease in Pregnancy 142

13 VASCULAR DISEASES AND HYPERTENSION Eric H. Awtry Joseph Loscalzo 145

Systemic Vascular Disease 145

Venous Thromboembolic Disease 152

Pulmonary Vascular Disease 155

Hypertension 157

SECTION Ⅳ Pulmonary and Critical Care Medicine 165

14 APPROACH TO THE PATIENT WITH RESPIRATORY DISEASE Bonnie S. Slovis Kenneth L. Brigham 167

Common Presenting Complaints 167

Physical Examination 169

15 ANATOMIC AND PHYSIOLOGIC CONSIDERATIONS Bonnie S. Slovis Kenneth L. Brigham 172

Anatomy 172

Physiology 173

Abnormalities of Pulmonary Gas Exchange 177

16 DIAGNOSTIC TECHNIQUES AND THEIR INDICATIONS Bonnie S. Slovis Kenneth L. Brigham 181

Imaging Procedures 181

Evaluation of Lung Function 181

17 OBSTRUCTIVE LUNG DISEASE Bonnie S. Slovis Kenneth L. Brigham 185

Pathophysiology of Air Flow Obstruction 185

Asthma 186

Chronic Obstructive Pulmonary Disease 187

Bronchiectasis 189

Cystic Fibrosis 189

Treatment 190

18 INTERSTITIAL AND INFILTRATIVE LUNG DISEASE Bonnie S. Slovis Kenneth L. Brigham 194

Pathophysiology and Clinical Manifestations 194

Pleural Disease 201

19 DISORDERS OF THE PLEURAL SPACE, MEDIASTINUM, AND CHEST WALL Bonnie S. Slovis Kenneth L. Brigham 201

Mediastinal Disease 203

Chest Wall Disease 203

20 NEOPLASTIC DISEASES OF THE LUNG Bonnie S. Slovis Kenneth L. Brigham 206

Risk Factors 206

Pathology 206

Clinical Presentation 206

Diagnosis and Evaluation 207

Solitary Pulmonary Nodule 208

Treatment and Prognosis 209

21 DISORDERED BREATHING Bonnie S. Slovis Kenneth L. Brigham 210

Sleep Apnea Syndrome 210

Other Breathing Disorders 211

Air Pollution 213

22 ENVIRONMENTAL AND OCCUPATIONAL INJURY Bonnie S. Slovis Kenneth L. Brigham 213

Pneumoconioses 213

Noxious Gases and Fumes 214

Smoke Inhalation 214

High-Altitude Injury 215

Drowning and Near-Drowning 215

23 ESSENTIALS OF PULMONARY CRITICAL CARE MEDICINE Bonnie S. Slovis Kenneth L. Brigham 216

Shock 216

Acute Respiratory Failure 217

Oxygen Therapy 217

Mechanical Ventilation 218

Complications of Endotracheal Intubation and Mechanical Ventilation 219

Systemic Inflammatory Response Syndrome, Sepsis, Multiple Organ Dysfunction Syndrome, and Adult Respiratory Distress Syndrome 219

SECTION Ⅴ Renal Disease 221

24 ELEMENTS OF RENAL STRUCTURE AND FUNCTION Dinesh K. Chatoth 223

Elements of Renal Structure 223

Elements of Renal Physiology 226

25 APPROACH TO THE PATIENT WITH RENAL DISEASE Yousri M. H. Barri Sudhir V. Shah 232

Assessment of the Patient with Renal Disease 232

The Major Renal Syndromes 234

Radiologic Imaging of the Urinary Tract 236

Renal Biopsy 237

26 FLUID AND ELECTROLYTE DISORDERS Thomas E. Andreoli Sameh R. Abul-Ezz 238

Volume Disorders 238

Osmolality Disorders 241

Hyponatremia 242

Hypernatremia 244

Disturbances in Potassium Balance 245

Disturbances in Acid-Base Balance 248

27 GLOMERULAR DISEASES Sudhir V. Shah 253

The Glomerulus 253

Mechanisms of Glomerular Injury 253

Clinical Manifestations of Glomerular Disease 253

Approach to the Patient with Glomerular Disease 255

Acute Nephritic Syndrome 255

Rapidly Progressive Glomerulonephritis 257

Nephrotic Syndrome 258

Asymptomatic Urinary Abnormalities 263

28 MAJOR NONGLOMERULAR DISORDERS Dinesh K. Chatoth 266

Tubulointerstitial Nephropathy 266

Cystic Diseases of the Kidney 269

Urinary Tract Obstruction 271

Nephrolithiasis 272

Renal Neoplasia 275

29 VASCULAR DISORDERS OF THE KIDNEY Yousri M. H. Barri 278

Renal Arterial Occlusion 278

Ischemic Renal Disease 278

Arterioles and Microvasculature 279

Atheroembolic Diseases of the Kidney 279

Chronic Hypertensive Nephrosclerosis 280

Malignant Nephrosclerosis 280

Scleroderma 280

Hemolytic-Uremic Syndrome and Thrombotic Thrombocytopenic Purpura 281

Antiphospholipid Syndrome and the Kidney 281

Renal Vein Thrombosis 282

30 ACUTE RENAL FAILURE Sudhir V. Shah 283

Definition and Etiology 283

Differential Diagnosis and Diagnostic Evaluation of the Patient 283

Clinical Presentation, Complications, and Management of Acute Tubular Necrosis 287

Specific Causes of Acute Renal Failure 288

31 CHRONIC RENAL FAILURE Mary Jo Shaver 291

Adaptation to Nephron Loss 291

Conservative Management 292

Clinical Manifestations 293

Treatment of End-Stage Renal Failure 296

SECTION Ⅵ Gastrointestinal Disease 301

Clinical Features 303

Causes of Abdominal Pain 303

A. Abdominal Pain Edgar Achkar 303

32 COMMON CLINICAL MANIFESTATIONS OF GASTROINTESTINAL DISEASE 303

Physiology 303

The Acute Abdomen 305

Chronic Abdominal Pain 305

B. Gastrointestinal Hemorrhage Gregory Zuccaro, Jr. 306

Acute Gastrointestinal Hemorrhage 306

Chronic Gastrointestinal Hemorrhage 309

C. Malabsorption Edy E. Soffer 310

Digestion and Absorption of Fat 310

Digestion and Absorption of Carbohydrates 310

Digestion and Absorption of Proteins 310

Mechanisms of Malabsorption 310

Clinical Manifestations of Malabsorption 311

Multiple Mechanisms 311

Tests for Malabsorption 312

Approach to the Patient with Suspected Malabsorption 314

Treatment 314

D. Diarrhea Edy E. Soffer 316

Definition 316

Normal Physiology 316

Pathophysiology 317

Evaluation of Diarrhea 318

33 ENDOSCOPIC AND RADIOGRAPHIC PROCEDURES IN GASTROENTEROLOGY John J. Vargo Ⅱ 321

Gastrointestinal Endoscopy 321

Esophagogastroduodenoscopy and Enteroscopy 321

Endoscopic Retrograde Cholangiopancreatography 322

Endoscopic Ultrasonography 323

Sigmoidoscopy and Colonoscopy 323

Radiographic Procedures 323

34 DISEASES OF THE ESOPHAGUS Joel E. Richter 326

Normal Esophageal Physiology 326

Clinical Symptoms of Esophageal Disease 326

Gastroesophageal Reflux Disease 327

Motility Disorders of the Oropharynx and Esophagus 329

Other Esophageal Disorders 330

35 DISEASES OF THE STOMACH AND DUODENUM Gary W. Falk 332

Gastroduodenal Anatomy 332

Gastroduodenal Mucosal Secretion and Protective Factors 332

Gastroduodenal Motor Physiology 333

Gastritis 334

Peptic Ulcer Disease 335

Zollinger-Ellison Syndrome 341

Delayed Gastric Emptying 342

Rapid Gastric Emptying 343

36 INFLAMMATORY BOWEL DISEASE Aaron Brzezinski 345

Etiology 345

Incidence and Epidemiology 345

Ulcerative Colitis: Clinical Features 346

Crohn s Disease: Clinical Features 346

Extraintestinal Manifestations 346

Other Complications 346

Treatment 347

Differential Diagnosis 347

Diagnosis 347

Colon Cancer 347

37 NEOPLASMS OF THE GASTROINTESTINAL TRACT Carol A. Burke 351

Esophageal Carcinoma 351

Gastric Carcinoma 352

Colorectal Polyps and Carcinoma 353

The Polyposis Syndromes 354

Carcinoid Tumors 355

38 DISEASES OF THE PANCREAS Darwin L. Conwell 356

Anatomy and Physiology 356

Acute Pancreatitis 358

Chronic Pancreatitis 361

Carcinoma of the Pancreas 362

SECTION Ⅶ Diseases of the Liver and Biliary System 365

39 LABORATORY TESTS IN LIVER DISEASE Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas 367

Clinical Approach to Liver Disease 367

Laboratory Tests of Liver Function and Disease 367

Liver Biopsy 370

40 JAUNDICE Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas 371

Bilirubin Metabolism 371

Laboratory Tests for Bilirubin 371

Clinical Classification 372

Approach to Diagnosis 374

41 ACUTE AND CHRONIC HEPATITIS Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas 376

Acute Hepatitis 376

Chronic Hepatitis 383

Treatment 385

Diagnosis 385

42 FULMINANT HEPATIC FAILURE Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas 385

Hepatic Transplantation 386

Prognosis 386

43 CIRRHOSIS OF THE LIVER AND ITS COMPLICATIONS Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas 387

Clinical and Laboratory Features 387

Specific Causes 387

Major Complications 388

Hepatic Transplantation 392

44 NEOPLASTIC, INFILTRATIVE, AND VASCULAR DISEASES OF THE LIVER Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas 394

Hepatic Neoplasms 394

Liver Abscess 395

Granulomatous Liver Disease 395

Vascular Disease of the Liver 396

Diagnostic Approach to Hepatic Lesions 396

45 DISORDERS OF THE GALLBLADDER AND BILIARY TRACT Michael B. Fallon Brendan M. McGuire Gary A. Abrams Miguel R. Arguedas 398

Normal Biliary Physiology 398

Pathophysiology of Gallstone Formation(Cholelithiasis) 398

Clinical Manifestations of Gallstones 399

SECTION Ⅷ Hematologic Disease 403

46 HEMATOPOIESlS AND HEMATOPOIETIC FAILURE Eunice S. Wang Nancy Berliner 405

Hematopoietic Tissues 405

Stem Cell Theory of Hematopoiesis 405

Hematopoietic Differentiation Pathway 406

Disorders of Hematopoiesis 408

47 CLONAL DISORDERS OF THE HEMATOPOIETIC STEM CELL Eunice S. Wang Nancy Berliner 410

Myelodysplastic Disorders 410

Myeloproliferative Disorders 412

Chronic Myelogenous Leukemia 414

Acute Leukemias 415

48 DISORDERS OF RED BLOOD CELLS Nancy Berliner 419

Normal Red Blood Cell Structure and Function 419

Clinical Approach to Anemia 419

Evaluation of Hypoproliferative Anemia 420

49 CLINICAL DISORDERS OF NEUTROPHILS Nancy Berliner 431

Normal Granulocyte Development, Structure, and Function 431

Determinants of Peripheral Neutrophil Number 432

Evaluation of Leukocytosis (Neutrophilia) 433

Evaluation of Leukopenia (Neutropenia) 433

50 DISORDERS OF LYMPHOCYTES Jill Lacy 435

Cells of the Immune System: Lymphocyte Development, Function, and Localization 435

Neoplasia of Lymphoid Origin 437

51 NORMAL HEMOSTASIS Henry M. Rinder 449

Vascular Wall Physiology 449

Platelet Physiology 450

Coagulation Cascade 453

Endothelial-Associated Fibrinolysis 456

52 DISORDERS OF HEMOSTASlS: BLEEDING Henry M. Rinder 457

Clinical Evaluation of Bleeding 457

Vascular Causes of Bleeding 457

Bleeding Caused by Platelet Disorders: Thrombocytopenia 459

Bleeding Caused by Platelet Disorders: Qualitative Platelet Defects 465

Fibrinogen Disorders 468

Bleeding Caused by Coagulation Factor Disorders 469

Bleeding in Patients with a Normal Laboratory Screen 471

53 DISORDERS OF HEMOSTASIS: THROMBOSIS Henry M. Rinder 473

Clinical Evaluation of Thrombosis 473

Vascular Causes of Thrombosis 473

Atherothrombosis 473

Inherited Risk Factors for Venous Thrombosis 475

Acquired Risk Factors for Venous Thrombosis 476

Hypercoagulability and Platelet Disorders 477

Laboratory Evaluation of Thrombosis 477

Therapy for Venous Thromboembolism 478

Venous Thromboembolism During Pregnancy 480

Perioperative Anticoagulation 480

Future Anticoagulant Strategies 481

SECTION Ⅸ Oncologic Disease 483

54 CANCER ETIOLOGY: ONCOGENES AND ENVIRONMENTAL/TOXIC FACTORS Christopher E. Desch 485

Cancer Phenotype 485

Cancer Genetics 485

Etiology 486

55 CANCER EPIDEMIOLOGY AND CANCER PREVENTION Jennifer J. Griggs 489

Cancer Epidemiology 489

Cancer Prevention 489

56 SOLID TUMORS Jennifer J. Griggs Christopher E. Desch 493

Lung Cancer 493

Gastrointestinal Cancers 495

Breast Cancer 498

Genitourinary Cancers 499

Melanoma 503

Spinal Cord Compression 505

57 COMPLICATIONS OF CANCER Jennifer J. Griggs 505

Superior Vena Cava Syndrome 506

Hypercalcemia 506

Paraneoplastic Syndromes 507

58 PRINCIPLES OF CANCER TREATMENT Christopher E. Desch 508

Radiology 508

Surgery 508

Radiation Therapy 508

Chemotherapy 509

Hormonal Therapy 510

Supportive Care 511

Biologic Therapy 511

Bone Marrow Transplantation 511

SECTION Ⅹ Metabolic Disease 513

59 EATING DISORDERS Peter N. Herbert 515

Obesity 515

Anorexia Nervosa and Bulimia Nervosa 519

60 PRINCIPLES OF NUTRITIONAL SUPPORT IN ADULT PATIENTS Peter N. Herbert 522

Nutritional Assessment 522

Route of Nutritional Support 522

Water 523

Calories and Protein 523

Vitamins and Minerals 524

Home Nutritional Support 524

61 DISORDERS OF LIPID METABOLISM Peter N. Herbert 526

Plasma Lipoprotein Physiology 526

Evaluation of Serum Lipoprotein Concentrations 527

Elevated Chylomicrons, VLDL, and IDL 528

Treatment of Hypertriglyceridemia 529

Elevated LDL 530

Treatment of Hypercholesterolemia 530

Lipids and Vascular Disease 531

62 DISORDERS OF METALS AND METALLOPROTEINS Peter N. Herbert 533

Wilson s Disease 533

Treatment 534

Hemochromatosis 534

Porphyrias 536

63 INHERITED DISORDERS OF CONNECTIVE TISSUE Peter N. Herbert 539

Collagen Disorders 539

Marfan s Syndrome 540

Pseudoxanthoma Elasticum 541

SECTION Ⅺ Endocrine Disease 543

64 HYPOTHALAMIC-PITUITARY AXIS Vivien Herman-Bonert 545

Anatomy 545

Anterior Pituitary Hormone Physiology and Testing 545

Neuroradiologic Evaluation of the Pituitary Gland 548

Pituitary and Hypothalamic Disorders 548

Pituitary Tumors 550

The Posterior Pituitary Gland 552

65 THE THYROID GLAND Vivien Herman-Bonert Theodore C. Friedman 555

Thyroid Hormone Physiology 555

Thyroid Evaluation 556

Hyperthyroidism 557

Graves Disease 557

Toxic Multinodular Goiter 559

Thyroiditis 559

Toxic Adenoma 559

Thyrotoxicosis Factitia 560

Rare Causes of Thyrotoxicosis 560

Hypothyroidism 560

Goiter 562

Solitary Thyroid Nodules 562

Thyroid Carcinoma 563

66 THE ADRENAL GLAND Theodore C. Friedman 564

Physiology 564

Adrenal Insufficiency 565

Hyporeninemic Hypoaldosteronism 568

Congenital Adrenal Hyperplasia 568

Syndromes of Adrenocorticoid Hyperfunction 569

Adrenal Medullary Hyperfunction 574

67 MALE REPRODUCTIVE ENDOCRINOLOGY Glenn D. Braunstein 575

Hypogonadism 575

Erectile Dysfunction 579

Gynecomastia 579

Testicular Tumors 580

Benign Prostatic Hyperplasia 581

Carcinoma of the Prostate 581

68 DIABETES MELLITUS Philip Barnett Glenn D. Braunstein 583

Definition 583

Diagnosis 583

Classification 585

Pathogenesis 586

Management 588

Complications 594

69 HYPOGLYCEMIA Philip Barnett 599

Definition 599

Physiology of Glucose Homeostasis 599

Clinical Classification of Hypoglycemia 600

Diagnostic Work-up of Hypoglycemia 603

Treatment 603

SECTION Ⅻ Women s Health 605

70 WOMEN S HEALTH: GENERAL CONCEPTS Sally L. Hodder Anne L. Taylor 607

Gender Differences in the Epidemiology of Disease by Age Group 607

Gender and the Patient-Physician Interaction 608

Exercise Across the Feminine Life Cycle 608

71 HORMONAL INFLUENCES ON WOMEN S HEALTH Sally L. Hodder Anne L. Taylor 610

Normal Physiology 610

Dysmenorrhea and Premenstrual Syndrome 610

Amenorrhea 612

Abnormal Uterine Bleeding 613

Hirsutism 616

Hormone Therapy 616

72 DISEASES COMMON IN WOMEN Sally L. Hodder Anne L. Taylor 620

Cardiovascular Diseases 620

Osteoporosis 621

Breast Cancer and Benign Breast Disease 622

Cancer of the Cervix, Uterus, and Ovary 623

Sexually Transmitted Diseases and Pelvic Inflammatory Disease 623

Domestic Violence 625

Urinary incontinence 625

Disorders of Cognition and Affect 626

SECTION ⅩⅢ Diseases of Bone and Bone Mineral Metabolism 627

73 NORMAL PHYSIOLOGY OF BONE AND BONE MINERALS F. Richard Bringhurst 629

Bone Structure and Metabolism 629

Calcium Metabolism 630

Phosphorus Metabolism 632

Magnesium Metabolism 634

Vitamin D 636

Calcitonin 637

74 THE PARATHYROID GLANDS, HYPERCALCEMIA, AND HYPOCALCEMIA Joel S. Finkelstein 639

Normal Physiology 639

Hypercalcemia 640

Hypocalcemia 645

75 OSTEOMALACIA AND RICKETS F. Richard Bringhurst 649

Pathogenesis 649

Specific Causes 649

Clinical Manifestations 652

Laboratory and Radiographic Features 652

Diagnosis 652

Treatment 652

76 OSTEOPOROSIS Joel S. Finkelstein 654

General Considerations 654

Etiology and Pathogenesis 654

Clinical Manifestations 656

Radiographic Findings 656

Diagnosis 656

Treatment 658

Glucocorticoid-Induced Bone Loss 660

77 PAGET S DISEASE OF BONE Margaret P. Seton 662

Incidence and Prevalence 662

Etiology 662

Pathology and Pathophysiology 662

Clinical Picture 662

Associated Conditions 663

Laboratory Assessment 663

Treatment 663

SECTION ⅩⅣ Musculoskeletal and Connective Tissue Disease 667

78 APPROACH TO THE PATIENT WITH RHEUMATIC DISEASE Joseph H. Korn 669

Musculoskeletal History and Examination 669

Laboratory Testing 671

Radiographic Studies 672

79 RHEUMATOID ARTHRITIS Joseph H. Korn 673

Epidemiology and Genetics 673

Pathology 673

Pathophysiology 673

Clinical Features 674

Diagnosis 675

Treatment 675

Prognosis 677

80 SPONDYLOARTHROPATHIES Peter A. Merkel 678

Epidemiology 678

Pathogenesis 678

Clinical Features 679

Radiographic Features 680

Treatment 681

81 SYSTEMIC LUPUS ERYTHEMATOSUS Peter A. Merkel 682

Pathogenesis 682

Clinical Manifestations 682

Clinical Subsets 683

Treatment 684

82 ANTIPHOSPHOLIPID ANTIBODY SYNDROME Peter A. Merkel 687

Etiology 687

Clinical Features 687

Diagnosis 687

Treatment 688

Clinical Features 689

Pathology and Pathophysiology 689

Epidemiology and Genetics 689

83 SYSTEMIC SCLEROSIS (SCLERODERMA) Joseph H. Korn 689

Diagnosis and Differential Diagnosis 691

Treatment 691

Prognosis 693

84 IDIOPATHIC INFLAMMATORY MYOPATHIES Robert W. Simms 694

Pathology and Pathophysiology 694

Clinical Presentation 694

Diagnosis 696

Differential Diagnosis 696

Treatment 696

85 SJOGREN S SYNDROME Peter A. Merkel 698

Clinical Features 698

Diagnosis 698

Treatment 700

88 VASCULITIDES Peter A. Merkel 701

Classification 701

Pathogenesis 701

Clinical Features 702

Specific Types of Vasculitis 702

Diagnosis 704

Autoantibodies and Vasculitis 705

Treatment 705

87 CRYSTAL ARTHROPATHIES Joseph H. Korn 707

Gout 707

Calcium Pyrophosphate Deposition Disease 711

Other Crystal Disorders 711

Pathology 712

88 OSTEOARTHRITIS Robert W. Simms 712

Clinical Features and Diagnosis 713

Treatment 714

89 NONARTICULAR SOFT TISSUE DISORDERS Robert W. Simms 715

Etiology and Pathogenesis 715

Classification of Bursae 715

Diagnosis of Nonarticular Soft Tissue Disorders 716

Bursitis 716

Tendinitis 717

Fibromyalgia Syndrome 717

90 RHEUMATIC MANIFESTATIONS OF SYSTEMIC DISORDERS Robert W. Simms 720

Rheumatic Syndromes Associated with Malignancy 720

Hematologic Disorders 721

Gastrointestinal Diseases 722

Endocrine Disorders 723

Sarcoidosis 724

SECTION ⅩⅤ Infectious Disease 725

91 ORGANISMS THAT INFECT HUMANS Michael M. Lederman 727

Viruses 727

Chlamydiae 727

Rickettsiae 728

Mycoplasma 728

Bacteria 728

Fungi 730

Protozoans 731

Helminths 732

Local Barriers to Infection 733

92 HOST DEFENSES AGAINST INFECTION Robert A. Salata 733

Components of the Immune System 734

Nonspecific Effector Mechanisms 737

Resistance to Extracellular Bacteria: Encapsulated Organisms 738

Resistance to Obligate Intracellular Parasites: Viruses 739

Resistance to Facultative Intracellular Parasites: Mycobacterium tuberculosis 740

93 LABORATORY DIAGNOSIS OF INFECTIOUS DISEASES Michael M. Lederman 741

Diagnosis by Direct Visualization of the Organism 741

Diagnosis by Detection of Microbial Antigens 742

Diagnosis by Examination of Host Immune or Inflammatory Responses 742

Assays that Detect Microbial Nucleoside Sequences 743

Diagnosis by Isolation of the Organism in Culture 743

Isolation of Fungi and Mycobacteria 744

Bacterial Isolation 744

Viral Isolation 744

Isolation of Rickettsia, Chlamydia, and Mycoplasma 744

94 ANTIMICROBIAL THERAPY Michael M. Lederman 745

The Pathogen 745

Site of Infection 745

Characteristics of the Antimicrobial 746

Route of Administration 746

Duration of Therapy 746

Combinations 749

Monitoring of Antimicrobial Therapy 749

Antiviral Agents 749

Antifungal Agents 749

Antimicrobial Resistance Testing 749

Fever and Hyperthermia 750

95 FEVER AND FEBRILE SYNDROMES Robert A. Salata 750

Regulation of Body Temperature 750

Acute Febrile Syndromes 752

Fever of Unknown Origin 760

Factitious or Self-Induced Fever 763

96 BACTEREMIA Robert A. Salata 765

Epidemiology 765

Pathogenesis 766

Clinical Manifestations 767

Diagnosis 769

Therapy 769

97 INFECTIONS OF THE NERVOUS SYSTEM Robert A. Salata 771

Meningitis 772

Encephalitis 778

Spectrum of Tuberculous, Fungal, and Parasitic Infections 779

Rabies 779

98 INFECTIONS OF THE HEAD AND NECK Michael M. Lederrnan 782

Infections of the Ear 782

Infections of the Nose and Sinuses 782

Infections of the Mouth and Pharynx 783

99 INFECTIONS OF THE LOWER RESPIRATORY TRACT Michael M. Lederman 788

Pathogenesis 788

Epidemiology 789

Differential Diagnosis 789

Diagnosis 790

Specific Pathogenic Organisms 791

Treatment and Outcome 795

Prevention 796

Infective Endocarditis 798

100 INFECTIONS OF THE HEART AND VESSELS Michael M. Lederrnan 798

Prosthetic Valve Endocarditis 802

Prophylaxis of Infective Endocarditis 803

Bacterial Endarteritis and Suppurative Phlebitis 804

101 SKIN AND SOFT TISSUE INFECTIONS Michael M. Lederrnan 805

Superficial Infections of the Skin 805

Deeper Infections of the Skin and Soft Tissue 809

102 INTRA-ABDOMINAL ABSCESS AND PERITONITIS Michael M. Lederrnan 811

Intra-Abdominal Abscess 811

Abscesses of Solid Organs 811

Extravisceral Abscesses 813

Peritonitis 813

Types of Microbial Diarrheal Diseases 815

103 INFECTIOUS DIARRHEA Michael M. Lederrnan 815

Pathogenesis and Pathophysiology: General Concepts 815

General Epidemiologic Considerations 818

Diagnosis 818

Management: General Principles of Electrolyte Repletion Therapy 818

104 INFECTIONS INVOLVING BONES AND JOINTS Michael M. Lederrnan 821

Arthritis 821

Septic Bursitis 823

Osteomyelitis 823

105 INFECTIONS OF THE URINARY TRACT Michael M. Lederrnan 825

Urethritis 825

Cystitis and Pyelonephritis 825

Prostatitis 827

Approach to the Hospitalized Patient with Possible Nosocomial infection 828

106 NOSOCOMIAL INFECTIONS Michael M. Lederrnan 828

Infection Control 828

Nosocomial Pneumonia 829

Intravascular Catheter-Related Infections 830

Pressure Sores 831

Nosocomial Urinary Tract infection 831

107 SEXUALLY TRANSMITTED DISEASES Robert A. Salata 832

Genital Sores 832

Urethritis, Cervicitis, and Pelvic Inflammatory Disease 836

Proctocolitis in Homosexual Men 840

108 HIV INFECTION AND THE ACQUIRED IMMUNODEFICIENCY SYNDROME Charles C. J. Carpenter Michael M. Lederman 841

Epidemiology 841

Pathophysiology 843

Diagnosis and Testing for HIV Infection 846

Sequential Clinical Manifestations of HIV-1 Infection 847

Management of HIV Infection 849

Management of Specific Clinical Manifestations of Immunodeficiency: A Problem-Oriented Approach 852

Mucocutaneous Diseases 853

Nervous System Diseases 855

Pulmonary Diseases 858

Gastrointestinal Diseases 860

Unexplained Fever 860

Weight Loss and Anorexia 861

AIDS-Associated Malignancies 861

Other Complications of HIV Infection 861

Prevention of HIV Infection 862

Disorders of Cell-Mediated Immunity 863

109 INFECTIONS IN THE IMMUNOCOMPROMISED HOST Robert A. Salata 863

Disorders of Humoral Immunity 864

Impaired Neutrophil Function 864

Neutropenia 865

Diagnostic Problems in the Compromised Host 865

Prevention and Treatment of Infections in the Patient with Neutropenia 866

110 INFECTIOUS DISEASES OF TRAVELERS: PROTOZOAL AND HELMINTHIC INFECTIONS Robert A. Salata 868

Preparation of Travelers 868

The Returning Traveler 870

Protozoal and Helminthic Infections 871

SECTION ⅩⅥ Neurologic Disease 875

111 NEUROLOGIC EVALUATION OF THE PATIENT Frederick J. Marshall 877

Taking a Neurologic History 877

The Neurologic Examination 878

Technologic Assessment 879

112 DISORDERS OF CONSCIOUSNESS Roger P. Simon 883

Pathophysiology 883

Diagnostic Approach 884

Prognosis in Coma 887

Coma-like States 887

113 DISORDERS OF SLEEP Roger P. Simon 890

Neurobiology of Sleep 890

Insomnia 890

Abnormal Arousal 890

Sleep Apnea 891

Parasomnias 891

Narcolepsy 892

Regional Syndromes 893

Anatomy 893

114 FOCAL BRAIN DISEASE Timothy J. Counihan 893

115 DEMENTIA AND MEMORY DISTURBANCES Frederick J. Marshall 896

Major Dementia Syndromes 896

Other Memory Disturbances 899

116 DISORDERS OF MOOD AND BEHAVIOR Frederick J. Marshall 901

Psychotic Disorders 901

Depression and Bipolar Disorders 902

Anxiety Disorders 904

Somatoform Disorders 904

Factitious Disorder 905

Dissociative Disorders 905

Personality Disorders and Substance Abuse 905

Hyperthermia 906

117 DISORDERS OF THERMAL REGULATION Roger P. Simon 906

Hypothermia 906

118 HEADACHE, NECK PAIN, AND OTHER PAINFUL DISORDERS Timothy J. Counihan 909

Headache 909

Neck and Back Pain 915

119 DISORDERS OF VISION AND HEARING Timothy J. Counihan 918

Disorders of Vision and Eye Movements 918

Hearing and Its Impairments 922

120 DIZZINESS Roger P. Simon 925

Approach to the Diagnosis 925

Treatment 928

121 DISORDERS OF THE MOTOR SYSTEM Frederick J. Marshall 929

Symptoms and Signs of Motor System Disease 929

Movement Disorders and Ataxia 930

Hypokinetic Movement Disorders 933

Hyperkinetic Movement Disorders 935

Cerebellar Ataxias 937

122 DEVELOPMENTAL AND NEUROCUTANEOUS DISORDERS Robert C. Griggs 939

Spinal Malformations 939

Chiari Malformations 939

Tethered Spinal Cord 939

Syringohydromyelia 939

Malformations of Cortical Development 940

Developmental and Neurocutaneous Disorders 940

123 CEREBROVASCULAR DISEASE Timothy J. Counihan 942

Epidemiology 942

Anatomy 942

Ischemic Stroke 943

Physiology 943

Major Stroke Syndromes 945

Diagnosis 947

Differential Diagnosis 947

Primary Stroke Prevention 947

Management of Acute Stroke 948

Intracerebral Hemorrhage 949

Intracranial Aneurysms 951

Vascular Malformations 952

124 TRAUMA TO HEAD AND SPINE Roger P. Simon 953

Head Injury 953

Spinal Cord Injury 955

Whiplash 955

Incidence and Etiology 956

Classification and Clinical Manifestations 956

125 EPILEPSY Robert C. Griggs 956

Definition 956

Diagnosis 960

Differential Diagnosis 961

Treatment 962

Prognosis 964

Discontinuing Antiepileptic Drugs 964

126 CENTRAL NERVOUS SYSTEM TUMORS Jennifer J. Griggs 965

Classification 965

Clinical Manifestations 965

Evaluation of the Patient 966

Treatment 966

Specific Tumors 967

Brain Abscess 969

127 INFECTIOUS DISEASES OF THE NERVOUS SYSTEM Robert C Griggs Roger P Simon 969

Subdural Empyema 970

Malignant External Otitis 970

Spinal Epidural Abscess 970

Septic Cavernous Sinus Thrombosis 971

Lateral Sinus Thrombosis 971

Septic Sagittal Thrombosis 971

Neurologic Complications of Infectious Endocarditis 971

Prion Diseases 972

128 DEMYELINATING AND INFLAMMATORY DISORDERS Robert C. Griggs 973

Multiple Sclerosis 973

Optic Neuritis 975

Neuromyelitis Optica 975

Acute Transverse Myelitis 977

Acute Disseminated Encephalomyelitis 977

129 NEUROMUSCULAR DISEASES: DISORDERS OF THE MOTOR NEURON AND PLEXUS AND PERIPHERAL NERVE DISEASE Robert C. Griggs 979

Diagnostic Tests 980

Diseases of the Motor Neuron (Anterior Horn Cell) 981

Plexopathy 982

Peripheral Nerve Disease 982

Common Mononeuropathies 983

Polyneuropathies 984

130 MUSCLE DISEASES Robert C. Griggs 988

Organization and Structure of Muscle 988

Assessment 988

Muscular Dystrophies 990

Congenital Myopathies 991

Metabolic Myopathies 991

Specific Mitochondrial Disorders Affecting Muscle 992

Channelopathies (Nondystrophic Myotonias and Periodic Paralyses) 993

Inflammatory Myopathies 994

Myopathies Caused by Endocrine and Systemic Disorders 996

Toxic Myopathies 996

Myoglobinuria 997

131 NEUROMUSCULAR JUNCTION DISEASE Robert C. Griggs 998

Myasthenia Gravis 998

Lambert-Eaton Myasthenic Syndrome 999

Drug-Induced Myesthenic Syndromes 1000

Organophosphate Intoxication 1000

SECTION ⅩⅦ The Aging Patient 1001

132 THE BIOLOGY OF AGING David A Lipschitz Robert J. Reis Dennis H. Sullivan 1003

Theories of Aging 1003

Demographics of Aging and Implications for Health Care 1005

Assessment of the Older Patient 1006

Common and Often Inadequately Assessed Medical Problems of the Elderly 1006

SECTION ⅩⅧ Substance Abuse 1011

133 ALCOHOL AND SUBSTANCE ABUSE Timothy E. Holcomb Jeffrey L. Clothier 1013

Screening 1014

Tobacco and Alcohol Abuse 1014

Prescription Drug Abuse 1018

?icit Drug Abuse 1020

APPENDIX Commonly Measured Laboratory Values 1023

INDEX 1029