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