Harrison’s Principles Of Internal Medicine, 21th Edition PDF by Joseph Loscalzo, Dennis L Kasper, Dan L Longo, Anthony S Fauci, Stephen L Hauser and J Larry Jameson

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Harrison’s Principles Of Internal Medicine, 21th Edition

By Joseph Loscalzo, Dennis L. Kasper, Dan L. Longo, Anthony S. Fauci, Stephen L. Hauser and J. Larry Jameson

Harrison’s Principles Of Internal Medicine, 21th Edition

Contents:

Contributors………………………………………………………………….. xviii

Preface …………………………………………………………………………. xxxix

Harrison’s Related Resources…………………………………………………xl

PART 1 The Profession of Medicine

1 The Practice of Medicine…………………………………………….1

The Editors

2 Promoting Good Health……………………………………………..8

Donald M. Lloyd-Jones, Kathleen M. McKibbin

3 Vaccine Opposition and Hesitancy………………………………13

Julie A. Bettinger, Hana Mitchell

4 Decision-Making in Clinical Medicine………………………..21

Daniel B. Mark, John B. Wong

5 Precision Medicine and Clinical Care…………………………..30

The Editors

6 Screening and Prevention of Disease……………………………37

Katrina A. Armstrong, Gary J. Martin

7 Global Diversity of Health System Financing

and Delivery……………………………………………………………42

Richard B. Saltman

8 The Safety and Quality of Health Care…………………………50

David W. Bates

9 Diagnosis: Reducing Errors and Improving Quality……….54

Gordon Schiff

10 Racial and Ethnic Disparities in Health Care…………………59

Lenny López, Joseph R. Betancourt

11 Ethical Issues in Clinical Medicine………………………………67

Christine Grady, Bernard Lo

12 Palliative and End-of-Life Care………………………………….72

Ezekiel J. Emanuel

PART 2 Cardinal Manifestations and Presentation of Diseases

SECTION 1 Pain

13 Pain: Pathophysiology and Management………………………91

James P. Rathmell, Howard L. Fields

14 Chest Discomfort…………………………………………………..100

David A. Morrow

15 Abdominal Pain……………………………………………………..108

Danny O. Jacobs

16 Headache………………………………………………………………112

Peter J. Goadsby

17 Back and Neck Pain………………………………………………..117

John W. Engstrom

SECTION 2 Alterations in Body Temperature

18 Fever……………………………………………………………………130

Neeraj K. Surana, Charles A. Dinarello, Reuven Porat

19 Fever and Rash………………………………………………………133

Elaine T. Kaye, Kenneth M. Kaye

20 Fever of Unknown Origin………………………………………..145

Chantal P. Bleeker-Rovers, Catharina M. Mulders-Manders,

Jos W. M. van der Meer

SECTION 3 Nervous System Dysfunction

21 Syncope………………………………………………………………..152

Roy Freeman

22 Dizziness and Vertigo……………………………………………..159

Mark F. Walker, Robert B. Daroff

23 Fatigue…………………………………………………………………162

Jeffrey M. Gelfand, Vanja C. Douglas

24 Neurologic Causes of Weakness and Paralysis………………165

Stephen L. Hauser

25 Numbness, Tingling, and Sensory Loss………………………168

Stephen L. Hauser

26 Gait Disorders, Imbalance, and Falls………………………….173

Jessica M. Baker

27 Confusion and Delirium………………………………………….178

Andrew Josephson, Bruce L. Miller

28 Coma…………………………………………………………………..183

Andrew Josephson, Allan H. Ropper, Stephen L. Hauser

29 Dementia………………………………………………………………189

William W. Seeley, Gil D. Rabinovici, Bruce L. Miller

30 Aphasia, Memory Loss, and Other Cognitive

Disorders………………………………………………………………195

M.-Marsel Mesulam

31 Sleep Disorders………………………………………………………204

Thomas E. Scammell, Clifford B. Saper, Charles A. Czeisler

SECTION 4 Disorders of Eyes, Ears, Nose, and Throat

32 Disorders of the Eye………………………………………………..215

Jonathan C. Horton

33 Disorders of Smell and Taste…………………………………….232

Richard L. Doty, Steven M. Bromley

34 Disorders of Hearing………………………………………………238

Anil K. Lalwani

35 Upper Respiratory Symptoms, Including Earache,

Sinus Symptoms, and Sore Throat……………………………..247

Rachel L. Amdur, Jeffrey A. Linder

36 Oral Manifestations of Disease…………………………………256

Samuel C. Durso

SECTION 5 Alterations in Circulatory and

Respiratory Functions

37 Dyspnea……………………………………………………………….263

Rebecca M. Baron

38 Cough………………………………………………………………….267

Christopher H. Fanta

39 Hemoptysis…………………………………………………………..270

Carolyn M. D’Ambrosio

40 Hypoxia and Cyanosis……………………………………………..272

Joseph Loscalzo

41 Edema………………………………………………………………….275

Joseph Loscalzo

42 Approach to the Patient with a Heart Murmur…………….278

Patrick T. O’Gara, Joseph Loscalzo

43 Palpitations……………………………………………………………286

SECTION 6 Alterations in Gastrointestinal Function

44 Dysphagia…………………………………………………………….287

Ikuo Hirano, Peter J. Kahrilas

45 Nausea, Vomiting, and Indigestion…………………………….291

William L. Hasler

46 Diarrhea and Constipation……………………………………….297

Michael Camilleri, Joseph A. Murray

47 Unintentional Weight Loss………………………………………309

  1. Larry Jameson

48 Gastrointestinal Bleeding…………………………………………311

Loren Laine

49 Jaundice………………………………………………………………..315

Savio John, Daniel S. Pratt

50 Abdominal Swelling and Ascites……………………………….321

Lawrence S. Friedman

SECTION 7 Alterations in Renal and Urinary Tract

Function

51 Interstitial Cystitis/Bladder Pain Syndrome…………………325

Christopher Doiron, J. Curtis Nickel

52 Azotemia and Urinary Abnormalities…………………………331

David B. Mount

53 Fluid and Electrolyte Disturbances……………………………338

David B. Mount

54 Hypercalcemia and Hypocalcemia……………………………..356

Sundeep Khosla

55 Acidosis and Alkalosis……………………………………………..359

Thomas D. DuBose, Jr.

SECTION 8 Alterations in the Skin

56 Approach to the Patient with a Skin Disorder………………369

Kim B. Yancey, Thomas J. Lawley

57 Eczema, Psoriasis, Cutaneous Infections, Acne,

and Other Common Skin Disorders…………………………..374

Leslie P. Lawley, Justin T. Cheeley, Robert A. Swerlick

58 Skin Manifestations of Internal Disease……………………..383

Jean L. Bolognia, Jonathan S. Leventhal, Irwin M. Braverman

59 Immunologically Mediated Skin Diseases…………………..400

Kim B. Yancey, Benjamin F. Chong, Thomas J. Lawley

60 Cutaneous Drug Reactions………………………………………407

Robert G. Micheletti, Misha Rosenbach,

Bruce U. Wintroub, Kanade Shinkai

61 Photosensitivity and Other Reactions to Sunlight…………417

Alexander G. Marneros, David R. Bickers

SECTION 9 Hematologic Alterations

62 Interpreting Peripheral Blood Smears…………………………424

Dan L. Longo

63 Anemia and Polycythemia………………………………………..431

John W. Adamson, Dan L. Longo

64 Disorders of Granulocytes and Monocytes………………….439

Steven M. Holland, John I. Gallin

65 Bleeding and Thrombosis…………………………………………450

Barbara A. Konkle

66 Enlargement of Lymph Nodes and Spleen…………………..457

Dan L. Longo

PART 3 Pharmacology

67 Principles of Clinical Pharmacology…………………………..465

Dan M. Roden

68 Pharmacogenomics…………………………………………………474

Dan M. Roden

PART 4 Oncology and Hematology

SECTION 1 Neoplastic Disorders

69 Approach to the Patient with Cancer………………………….481

Dan L. Longo

70 Prevention and Early Detection of Cancer…………………..490

Jennifer M. Croswell, Otis W. Brawley,

Barnett S. Kramer

71 Cancer Genetics…………………………………………………….498

Fred Bunz, Bert Vogelstein

72 Cancer Cell Biology………………………………………………..508

Jeffrey W. Clark, Dan L. Longo

73 Principles of Cancer Treatment…………………………………529

Edward A. Sausville, Dan L. Longo

74 Infections in Patients with Cancer……………………………..556

Robert W. Finberg

75 Oncologic Emergencies……………………………………………565

Rasim Gucalp, Janice P. Dutcher

76 Cancer of the Skin………………………………………………….578

Brendan D. Curti, John T. Vetto, Sancy A. Leachman

77 Head and Neck Cancer……………………………………………590

Everett E. Vokes

78 Neoplasms of the Lung……………………………………………594

Leora Horn, Wade T. Iams

79 Breast Cancer………………………………………………………..611

Daniel F. Hayes, Marc E. Lippman

80 Upper Gastrointestinal Tract Cancers…………………………626

David Kelsen

81 Lower Gastrointestinal Cancers………………………………..636

Robert J. Mayer

82 Tumors of the Liver and Biliary Tree………………………….643

Josep M. Llovet

83 Pancreatic Cancer…………………………………………………..657

Daniel D. Von Hoff

84 Gastrointestinal Neuroendocrine Tumors……………………663

Matthew H. Kulke

85 Renal Cell Carcinoma……………………………………………..673

Robert J. Motzer, Martin H. Voss

86 Cancer of the Bladder and Urinary Tract……………………..676

Noah M. Hahn

87 Benign and Malignant Diseases of the Prostate…………….681

Howard I. Scher, James A. Eastham

88 Testicular Cancer……………………………………………………689

David J. Vaughn

89 Gynecologic Malignancies……………………………………….695

David Spriggs

90 Primary and Metastatic Tumors of the

Nervous System……………………………………………………..701

Lisa M. DeAngelis, Patrick Y. Wen

91 Soft Tissue and Bone Sarcomas and Bone Metastases…………………………………………………….712

92 Carcinoma of Unknown Primary……………………………….716

Kanwal Raghav, James L. Abbruzzese, Gauri R. Varadhachary

93 Paraneoplastic Syndromes: Endocrinologic/

Hematologic………………………………………………………….721

Larry Jameson, Dan L. Longo

94 Paraneoplastic Neurologic Syndromes and

Autoimmune Encephalitis………………………………………..728

Josep Dalmau, Myrna R. Rosenfeld, Francesc Graus

95 Cancer Survivorship and the Long-Term Impact

of Cancer and Its Treatment……………………………………..736

Mark Roschewski, Dan L. Longo

SECTION 2 Hematopoietic Disorders

96 Hematopoietic Stem Cells………………………………………..743

David T. Scadden, Dan L. Longo

97 Iron Deficiency and Other Hypoproliferative

Anemias……………………………………………………………….747

John W. Adamson

98 Disorders of Hemoglobin…………………………………………754

Martin H. Steinberg

99 Megaloblastic Anemias……………………………………………766

  1. Victor Hoffbrand

100 Hemolytic Anemias………………………………………………..776

Lucio Luzzatto, Lucia De Franceschi

101 Anemia Due to Acute Blood Loss……………………………..791

Dan L. Longo

102 Bone Marrow Failure Syndromes Including

Aplastic Anemia and Myelodysplasia………………………….792

Neal S. Young

103 Polycythemia Vera and Other Myeloproliferative

Neoplasms…………………………………………………………….802

Jerry L. Spivak

104 Acute Myeloid Leukemia…………………………………………809

William Blum

105 Chronic Myeloid Leukemia………………………………………818

Hagop Kantarjian, Elias Jabbour, Jorge Cortes

106 Acute Lymphoid Leukemia………………………………………828

Dieter Hoelzer

107 Chronic Lymphocytic Leukemia……………………………….834

Jennifer A. Woyach, John C. Byrd

108 Non-Hodgkin’s Lymphoma……………………………………..841

Caron A. Jacobson, Dan L. Longo

109 Hodgkin’s Lymphoma……………………………………………..852

Caron A. Jacobson, Dan L. Longo

110 Less Common Lymphoid and Myeloid

Malignancies…………………………………………………………855

Ayalew Tefferi, Dan L. Longo

111 Plasma Cell Disorders……………………………………………..866

Nikhil C. Munshi, Dan L. Longo, Kenneth C. Anderson

112 Amyloidosis…………………………………………………………..878

John L. Berk, Vaishali Sanchorawala

113 Transfusion Therapy and Biology………………………………884

Pierre Tiberghien, Olivier Garraud, Jacques Chiaroni

114 Hematopoietic Cell Transplantation…………………………..897

Frederick R. Appelbaum

SECTION 3 Disorders of Hemostasis

115 Disorders of Platelets and Vessel Wall…………………………903

Barbara A. Konkle

116 Coagulation Disorders…………………………………………….910

Jean M. Connors

117 Arterial and Venous Thrombosis……………………………….919

Jane E. Freedman, Joseph Loscalzo

118 Antiplatelet, Anticoagulant, and Fibrinolytic

Drugs…………………………………………………………………..924

Jeffrey I. Weitz

PART 5 Infectious Diseases

SECTION 1 Basic Considerations in Infectious Diseases

119 Approach to the Patient with an Infectious Disease……….941

Neeraj K. Surana, Dennis L. Kasper

120 Molecular Mechanisms of Microbial Pathogenesis………..948

Thomas E. Wood, Marcia B. Goldberg

121 Microbial Genomics and Infectious Disease………………..960

Roby P. Bhattacharyya, Yonatan H. Grad, Deborah T. Hung

122 Approach to the Acutely Ill Infected Febrile Patient………973

Tamar F. Barlam

123 Immunization Principles and Vaccine Use…………………..981

Sarah Mbaeyi, Amanda Cohn, Nancy Messonnier

124 Health Recommendations for International Travel……….989

Jesse Waggoner, Henry M. Wu

125 Climate Change and Infectious Disease……………………. 1001

Aaron S. Bernstein

SECTION 2 Clinical Syndromes: Community-Acquired Infections

126 Pneumonia…………………………………………………………. 1009

Lionel A. Mandell, Michael S. Niederman

127 Lung Abscess………………………………………………………. 1020

Rebecca M. Baron, Beverly W. Baron, Miriam Baron Barshak

128 Infective Endocarditis…………………………………………… 1022

Sara E. Cosgrove, Adolf W. Karchmer

129 Infections of the Skin, Muscles, and Soft Tissues……….. 1034

Dennis L. Stevens, Amy E. Bryant

130 Infectious Arthritis………………………………………………. 1040

Lawrence C. Madoff, Nongnooch Poowanawittayakom

131 Osteomyelitis………………………………………………………. 1046

Werner Zimmerli

132 Intraabdominal Infections and Abscesses…………………. 1054

Miriam Baron Barshak, Dennis L. Kasper

133 Acute Infectious Diarrheal Diseases and Bacterial

Food Poisoning……………………………………………………. 1061

Richelle C. Charles, Regina C. LaRocque

134 Clostridioides difficile Infection, Including

Pseudomembranous Colitis……………………………………. 1066

Dale N. Gerding, Stuart Johnson

135 Urinary Tract Infections, Pyelonephritis, and Prostatitis……………………………………… 1070

Kalpana Gupta, Barbara W. Trautner

136 Sexually Transmitted Infections: Overview and Clinical Approach……………………………. 1078

Jeanne M. Marrazzo, King K. Holmes

137 Encephalitis………………………………………………………… 1094

Karen L. Roos, Michael R. Wilson, Kenneth L. Tyler

138 Acute Meningitis…………………………………………………. 1100

Karen L. Roos, Kenneth L. Tyler

139 Chronic and Recurrent Meningitis………………………….. 1110 ix

Avindra Nath, Walter J. Koroshetz, Michael R. Wilson

140 Brain Abscess and Empyema………………………………….. 1117

Karen L. Roos, Kenneth L. Tyler

141 Infectious Complications of Bites……………………………. 1124

Sandeep S. Jubbal, Florencia Pereyra Segal, Lawrence C. Madoff

SECTION 3 Clinical Syndromes: Health

Care–Associated Infections

142 Infections Acquired in Health Care Facilities…………….. 1128

Robert A. Weinstein

143 Infections in Transplant Recipients…………………………. 1136

Robert W. Finberg

SECTION 4 Therapy for Bacterial Diseases

144 Treatment and Prophylaxis of Bacterial Infections……… 1148

David C. Hooper, Erica S. Shenoy, Ramy H. Elshaboury

145 Bacterial Resistance to Antimicrobial Agents……………. 1163

David C. Hooper

SECTION 5 Diseases Caused by Gram-Positive Bacteria

146 Pneumococcal Infections……………………………………….. 1169

David Goldblatt, Katherine L. O’Brien

147 Staphylococcal Infections………………………………………. 1178

Franklin D. Lowy

148 Streptococcal Infections………………………………………… 1188

Michael R. Wessels

149 Enterococcal Infections…………………………………………. 1197

William R. Miller, Cesar A. Arias, Barbara E. Murray

150 Diphtheria and Other Corynebacterial Infections………. 1203

William R. Bishai, John R. Murphy

151 Listeria monocytogenes Infections……………………………… 1208

Jennifer P. Collins, Patricia M. Griffin

152 Tetanus………………………………………………………………. 1211

  1. Louise Thwaites, Lam Minh Yen

153 Botulism…………………………………………………………….. 1214

Carolina Lúquez, Jeremy Sobel

154 Gas Gangrene and Other Clostridial Infections…………. 1220

Amy E. Bryant, Dennis L. Stevens

SECTION 6 Diseases Caused by Gram-Negative Bacteria

155 Meningococcal Infections……………………………………… 1225

Manish Sadarangani, Andrew J. Pollard

156 Gonococcal Infections………………………………………….. 1234

Sanjay Ram, Peter A. Rice

157 Haemophilus and Moraxella Infections………………………. 1241

Timothy F. Murphy

158 Infections Due to the HACEK Group and

Miscellaneous Gram-Negative Bacteria……………………. 1246

Tamar F. Barlam

159 Legionella Infections……………………………………………… 1249

Steven A. Pergam, Thomas R. Hawn

160 Pertussis and Other Bordetella Infections………………….. 1257

Karina A. Top, Scott A. Halperin

161 Diseases Caused by Gram-Negative Enteric

Bacilli………………………………………………………………… 1261

Thomas A. Russo, James R. Johnson

162 Acinetobacter Infections…………………………………………. 1275

Rossana Rosa, L. Silvia Munoz-Price

163 Helicobacter pylori Infections…………………………………… 1279

John C. Atherton, Martin J. Blaser

164 Infections Due to Pseudomonas, Burkholderia, and

Stenotrophomonas Species………………………………………. 1284

Reuben Ramphal

165 Salmonellosis………………………………………………………. 1291

David A. Pegues, Samuel I. Miller

166 Shigellosis…………………………………………………………… 1298

Philippe J. Sansonetti, Jean Bergounioux

167 Infections Due to Campylobacter and Related

Organisms………………………………………………………….. 1302

Martin J. Blaser

168 Cholera and Other Vibrioses………………………………….. 1305

Matthew K. Waldor, Edward T. Ryan

169 Brucellosis………………………………………………………….. 1310

Nicholas J. Beeching

170 Tularemia…………………………………………………………… 1314

Max Maurin, Didier Raoult

171 Plague and Other Yersinia Infections……………………….. 1320

Michael B. Prentice

172 Bartonella Infections, Including Cat-Scratch

Disease………………………………………………………………. 1328

Michael Giladi, Moshe Ephros

173 Donovanosis……………………………………………………….. 1334

Nigel O’Farrell

SECTION 7 Miscellaneous Bacterial Infections

174 Nocardiosis…………………………………………………………. 1335

Gregory A. Filice

175 Actinomycosis……………………………………………………… 1340

Thomas A. Russo

176 Whipple’s Disease………………………………………………… 1344

Thomas A. Russo, Seth R. Glassman

177 Infections Due to Mixed Anaerobic Organisms…………. 1347

Neeraj K. Surana, Dennis L. Kasper

SECTION 8 Mycobacterial Diseases

178 Tuberculosis………………………………………………………… 1357

Mario C. Raviglione, Andrea Gori

179 Leprosy………………………………………………………………. 1382

Jan H. Richardus, Hemanta K. Kar,

Zoica Bakirtzief, Wim H. van Brakel

180 Nontuberculous Mycobacterial Infections………………… 1392

Steven M. Holland

181 Antimycobacterial Agents……………………………………… 1397

Divya Reddy, Sebastian G. Kurz, Max R. O’Donnell

SECTION 9 Spirochetal Diseases

182 Syphilis………………………………………………………………. 1406

Sheila A. Lukehart

183 Endemic Treponematoses……………………………………… 1413

Sheila A. Lukehart, Lorenzo Giacani

184 Leptospirosis………………………………………………………. 1417

Jiři F. P. Wagenaar, Marga G.A. Goris

185 Relapsing Fever and Borrelia miyamotoi Disease…………. 1421

Alan G. Barbour

186 Lyme Borreliosis………………………………………………….. 1425

Allen C. Steere

SECTION 10 Diseases Caused by Rickettsiae, Mycoplasmas, and Chlamydiae

187 Rickettsial Diseases………………………………………………. 1431

David H. Walker, J. Stephen Dumler, Lucas S. Blanton,

Chantal P. Bleeker-Rovers

188 Infections Due to Mycoplasmas……………………………… 1441

Doug Hardy

189 Chlamydial Infections…………………………………………… 1444

Charlotte A. Gaydos, Thomas C. Quinn

SECTION 11 Viral Diseases: General Considerations

190 Principles of Medical Virology……………………………….. 1453

David M. Knipe

191 Antiviral Chemotherapy, Excluding Antiretroviral

Drugs………………………………………………………………… 1460

Jeffrey I. Cohen, Eleanor Wilson

SECTION 12 Infections Due to DNA Viruses

192 Herpes Simplex Virus Infections…………………………….. 1470

Lawrence Corey

193 Varicella-Zoster Virus Infections…………………………….. 1479

Richard J. Whitley

194 Epstein-Barr Virus Infections, Including Infectious Mononucleosis…………………………………. 1483

Jeffrey I. Cohen

195 Cytomegalovirus and Human Herpesvirus

Types 6, 7, and 8…………………………………………………… 1487

Camille Nelson Kotton, Martin S. Hirsch

196 Molluscum Contagiosum, Monkeypox, and

Other Poxvirus Infections……………………………………… 1492

Inger K. Damon

197 Parvovirus Infections……………………………………………. 1495

Kevin E. Brown

198 Human Papillomavirus Infections…………………………… 1498

Darron R. Brown, Aaron C. Ermel

SECTION 13 Infections Due to DNA and RNA Respiratory Viruses

199 Common Viral Respiratory Infections, Including COVID-19…………………………………………………………. 1504

James E. Crowe, Jr.

200 Influenza……………………………………………………………. 1515

Kathleen M. Neuzil, Peter F. Wright

SECTION 14 Infections Due to Human Immunodeficiency Virus and Other Human Retroviruses

201 The Human Retroviruses………………………………………. 1521

Dan L. Longo, Anthony S. Fauci

202 Human Immunodeficiency Virus Disease: AIDS and Related Disorders………………………………….. 1527

Anthony S. Fauci, Gregory K. Folkers, H. Clifford Lane

SECTION 15 Infections Due to RNA Viruses

203 Viral Gastroenteritis…………………………………………….. 1597

Umesh D. Parashar, Roger I. Glass

204 Enterovirus, Parechovirus, and Reovirus Infections……. 1602

Jeffrey I. Cohen

205 Measles (Rubeola)………………………………………………… 1608

Kaitlin Rainwater-Lovett, William J. Moss

206 Rubella (German Measles)…………………………………….. 1612

Laura A. Zimmerman, Susan E. Reef

207 Mumps………………………………………………………………. 1615

Jessica Leung, Mariel Marlow

208 Rabies and Other Rhabdovirus Infections………………… 1618

Alan C. Jackson

209 Arthropod-Borne and Rodent-Borne Virus

Infections…………………………………………………………… 1624

Jens H. Kuhn, Ian Crozier

210 Ebolavirus and Marburgvirus Infections…………………… 1645

Jens H. Kuhn, Ian Crozier

SECTION 16 Fungal Infections

211 Pathogenesis, Diagnosis, and Treatment of

Fungal Infections…………………………………………………. 1652

Michail S. Lionakis, John E. Edwards Jr.

212 Histoplasmosis……………………………………………………. 1658

Chadi A. Hage, L. Joseph Wheat

213 Coccidioidomycosis……………………………………………… 1661

Neil M. Ampel

214 Blastomycosis……………………………………………………… 1664

Gregory M. Gauthier, Bruce S. Klein

215 Cryptococcosis…………………………………………………….. 1668

Arturo Casadevall

216 Candidiasis…………………………………………………………. 1671

Michail S. Lionakis, Shakti Singh, Ashraf S. Ibrahim,

John E. Edwards, Jr.

217 Aspergillosis……………………………………………………….. 1677

David W. Denning

218 Mucormycosis……………………………………………………… 1681

Brad Spellberg, Ashraf S. Ibrahim

219 Less Common Systemic Mycoses and Superficial

Mycoses……………………………………………………………… 1686

Carol A. Kauffman

220 Pneumocystis Infections…………………………………………. 1691

Alison Morris, Henry Masur

SECTION 17 Protozoal and Helminthic Infections:

General Considerations

221 Introduction to Parasitic Infections…………………………. 1696

Sharon L. Reed

222 Agents Used to Treat Parasitic Infections………………….. 1701

Thomas A. Moore

SECTION 18 Protozoal Infections

223 Amebiasis and Infection with Free-Living Amebae…….. 1714

Rosa M. Andrade, Sharon L. Reed

224 Malaria………………………………………………………………. 1720

Nicholas J. White, Elizabeth A. Ashley

225 Babesiosis…………………………………………………………… 1736

Edouard Vannier, Jeffrey A. Gelfand

226 Leishmaniasis……………………………………………………… 1741

Shyam Sundar

227 Chagas Disease and African Trypanosomiasis……………. 1748

François Chappuis, Yves Jackson

228 Toxoplasma Infections…………………………………………… 1757

Kami Kim

229 Protozoal Intestinal Infections and Trichomoniasis…….. 1764

Peter F. Weller

SECTION 19 Helminthic Infections

230 Introduction to Helminthic Infections……………………… 1768

Peter F. Weller

231 Trichinellosis and Other Tissue Nematode Infections…………………………………………………………… 1770

Peter F. Weller

232 Intestinal Nematode Infections………………………………. 1773

Thomas B. Nutman, Peter F. Weller

233 Filarial and Related Infections………………………………… 1778

Thomas B. Nutman, Peter F. Weller

234 Schistosomiasis and Other Trematode Infections……….. 1784

Birgitte Jyding Vennervald

235 Cestode Infections……………………………………………….. 1790

Clinton White, Jr., Peter F. Weller

PART 6 Disorders of the Cardiovascular System

SECTION 1 Introduction to Cardiovascular Disorders

236 Approach to the Patient with Possible Cardiovascular Disease…………………………………………. 1797

Joseph Loscalzo

237 Basic Biology of the Cardiovascular System………………. 1799

Joseph Loscalzo, John F. Keaney, Jr., Calum A. MacRae

238 Epidemiology of Cardiovascular Disease………………….. 1810

Thomas A. Gaziano, J. Michael Gaziano

SECTION 2 Diagnosis of Cardiovascular Disorders

239 Physical Examination of the Cardiovascular

System……………………………………………………………….. 1815

Patrick T. O’Gara, Joseph Loscalzo

240 Electrocardiography……………………………………………… 1824

Ary L. Goldberger

241 Noninvasive Cardiac Imaging: Echocardiography,

Nuclear Cardiology, and Magnetic Resonance/

Computed Tomography Imaging…………………………….. 1832

Marcelo F. Di Carli, Raymond Y. Kwong, Scott D. Solomon

242 Diagnostic Cardiac Catheterization and

Coronary Angiography…………………………………………. 1859

Jane A. Leopold, David P. Faxon

SECTION 3 Disorders of Rhythm

243 Principles of Clinical Cardiac Electrophysiology………… 1866

William H. Sauer, Bruce A. Koplan, Paul C. Zei

244 The Bradyarrhythmias: Disorders of the Sinoatrial Node……………………………………………………. 1873

William H. Sauer, Bruce A. Koplan

245 The Bradyarrhythmias: Disorders of the

Atrioventricular Node…………………………………………… 1880

William H. Sauer, Bruce A. Koplan

246 Approach to Supraventricular Tachyarrhythmias……….. 1888

William H. Sauer, Paul C. Zei

247 Physiologic and Nonphysiologic Sinus Tachycardia…….. 1891

William H. Sauer, Paul C. Zei

248 Focal Atrial Tachycardia………………………………………… 1893

William H. Sauer, Paul C. Zei

249 Paroxysmal Supraventricular Tachycardias………………… 1894

William H. Sauer, Paul C. Zei

250 Common Atrial Flutter and Macroreentrant and Multifocal Atrial Tachycardias……………………………….. 1899

William H. Sauer, Paul C. Zei

251 Atrial Fibrillation………………………………………………… 1903

William H. Sauer, Paul C. Zei

252 Approach to Ventricular Arrhythmias………………………. 1910

William H. Sauer, Usha B. Tedrow

253 Premature Ventricular Contractions, Nonsustained

Ventricular Tachycardia, and Accelerated Idioventricular Rhythm…………………………………………. 1915

William H. Sauer, Usha B. Tedrow

254 Sustained Ventricular Tachycardia…………………………… 1919

William H. Sauer, Usha B. Tedrow

255 Polymorphic Ventricular Tachycardia and Ventricular Fibrillation…………………………………………. 1923

William H. Sauer, Usha B. Tedrow

256 Electrical Storm and Incessant Ventricular

Tachycardia…………………………………………………………. 1927

William H. Sauer, Usha B. Tedrow

SECTION 4 Disorders of the Heart, Muscles, Valves, and Pericardium

257 Heart Failure: Pathophysiology and Diagnosis…………… 1930

Michael M. Givertz, Mandeep R. Mehra

258 Heart Failure: Management…………………………………… 1940

Akshay S. Desai, Mandeep R. Mehra

259 Cardiomyopathy and Myocarditis……………………………. 1954

Neal K. Lakdawala, Lynne Warner Stevenson, Joseph Loscalzo

260 Cardiac Transplantation and Prolonged Assisted Circulation…………………………………………………………. 1973

Mandeep R. Mehra

261 Aortic Stenosis…………………………………………………….. 1978

Patrick T. O’Gara, Joseph Loscalzo

262 Aortic Regurgitation…………………………………………….. 1986

Patrick T. O’Gara, Joseph Loscalzo

263 Mitral Stenosis……………………………………………………. 1991

Patrick T. O’Gara, Joseph Loscalzo

264 Mitral Regurgitation…………………………………………….. 1995

Patrick T. O’Gara, Joseph Loscalzo

265 Mitral Valve Prolapse……………………………………………. 1999

Patrick T. O’Gara, Joseph Loscalzo

266 Tricuspid Valve Disease…………………………………………. 2001

Patrick T. O’Gara, Joseph Loscalzo

267 Pulmonic Valve Disease………………………………………… 2004

Patrick T. O’Gara, Joseph Loscalzo

268 Multiple and Mixed Valvular Heart Disease……………… 2005

Patrick T. O’Gara, Joseph Loscalzo

269 Congenital Heart Disease in the Adult…………………….. 2008

Anne Marie Valente, Michael J. Landzberg

270 Pericardial Disease……………………………………………….. 2019

Joseph Loscalzo

271 Atrial Myxoma and Other Cardiac Tumors……………….. 2025

Eric H. Awtry

272 Cardiac Trauma…………………………………………………… 2028

Eric H. Awtry

SECTION 5 Coronary and Peripheral Vascular Disease

273 Ischemic Heart Disease…………………………………………. 2030

Elliott M. Antman, Joseph Loscalzo

274 Non-ST-Segment Elevation Acute Coronary Syndrome

(Non-ST-Segment Elevation Myocardial Infarction

and Unstable Angina)…………………………………………… 2046

Robert P. Giugliano, Christopher P. Cannon, Eugene Braunwald

275 ST-Segment Elevation Myocardial Infarction…………… 2053

Elliott M. Antman, Joseph Loscalzo

276 Percutaneous Coronary Interventions and

Other Interventional Procedures…………………………….. 2066

David P. Faxon, Deepak L. Bhatt

277 Hypertension………………………………………………………. 2072

Theodore A. Kotchen

278 Renovascular Disease……………………………………………. 2088

Stephen C. Textor

279 Deep-Venous Thrombosis and Pulmonary Thromboembolism………………………………………………. 2091

Samuel Z. Goldhaber

280 Diseases of the Aorta……………………………………………. 2101

Mark A. Creager, Joseph Loscalzo

281 Arterial Diseases of the Extremities…………………………. 2107

Mark A. Creager, Joseph Loscalzo

282 Chronic Venous Disease and Lymphedema………………. 2115

Mark A. Creager, Joseph Loscalzo

283 Pulmonary Hypertension………………………………………. 2121

Bradley A. Maron, Joseph Loscalzo

PART 7 Disorders of the Respiratory System

SECTION 1 Diagnosis of Respiratory Disorders

284 Approach to the Patient with Disease of the Respiratory System………………………………………………. 2131

Bruce D. Levy

285 Disturbances of Respiratory Function……………………… 2133

Edward T. Naureckas, Julian Solway

286 Diagnostic Procedures in Respiratory Disease…………… 2140

George R. Washko, Hilary J. Goldberg, Majid Shafiq

SECTION 2 Diseases of the Respiratory System

287 Asthma………………………………………………………………. 2147

Elliot Israel

288 Hypersensitivity Pneumonitis and Pulmonary

Infiltrates with Eosinophilia…………………………………… 2160

Praveen Akuthota, Michael E. Wechsler

289 Occupational and Environmental Lung Disease………… 2166

John R. Balmes

290 Bronchiectasis……………………………………………………… 2173

Rebecca M. Baron, Beverly W. Baron,

Miriam Baron Barshak

291 Cystic Fibrosis…………………………………………………….. 2176

Eric J. Sorscher

292 Chronic Obstructive Pulmonary Disease………………….. 2180

Edwin K. Silverman, James D. Crapo, Barry J. Make

293 Interstitial Lung Disease……………………………………….. 2190

Gary M. Hunninghake, Ivan O. Rosas

294 Disorders of the Pleura………………………………………….. 2197

Richard W. Light

295 Disorders of the Mediastinum………………………………… 2200

Richard W. Light

296 Disorders of Ventilation………………………………………… 2201

John F. McConville, Julian Solway, Babak Mokhlesi

297 Sleep Apnea………………………………………………………… 2204

Andrew Wellman, Daniel J. Gottlieb, Susan Redline

298 Lung Transplantation…………………………………………… 2209

Hilary J. Goldberg, Hari R. Mallidi

299 Interventional Pulmonary Medicine…………………………. 2214

Lonny Yarmus, David Feller-Kopman

PART 8 Critical Care Medicine

SECTION 1 Respiratory Critical Care

300 Approach to the Patient with Critical Illness……………… 2217

Rebecca M. Baron, Anthony F. Massaro

301 Acute Respiratory Distress Syndrome……………………… 2225

Rebecca M. Baron, Bruce D. Levy

302 Mechanical Ventilatory Support……………………………… 2230

Scott Schissel

SECTION 2 Shock and Cardiac Arrest

303 Approach to the Patient with Shock………………………… 2235

Anthony F. Massaro

304 Sepsis and Septic Shock………………………………………… 2241

Emily B. Brant, Christopher W. Seymour, Derek C. Angus

305 Cardiogenic Shock and Pulmonary Edema……………….. 2250

David H. Ingbar, Holger Thiele

306 Cardiovascular Collapse, Cardiac Arrest, and

Sudden Cardiac Death………………………………………….. 2257

Christine Albert, William H. Sauer

SECTION 3 Neurologic Critical Care

307 Nervous System Disorders in Critical Care……………….. 2267

Claude Hemphill, III, Wade S. Smith, S. Andrew Josephson,

Daryl R. Gress

PART 9 Disorders of the Kidney and Urinary Tract

308 Approach to the Patient with Renal Disease or Urinary Tract Disease……………………………………………. 2279

Julian L. Seifter

309 Cell Biology and Physiology of the Kidney……………….. 2287

Alfred L. George, Jr., Eric G. Neilson

310 Acute Kidney Injury……………………………………………… 2296

Sushrut S. Waikar, Joseph V. Bonventre

311 Chronic Kidney Disease………………………………………… 2309

Joanne M. Bargman, Karl Skorecki

312 Dialysis in the Treatment of Kidney Failure………………. 2320

Kathleen D. Liu, Glenn M. Chertow

313 Transplantation in the Treatment of Renal Failure……… 2325

Jamil Azzi, Naoka Murakami, Anil Chandraker

314 Glomerular Diseases…………………………………………….. 2331

Julia B. Lewis, Eric G. Neilson

315 Polycystic Kidney Disease and Other Inherited

Disorders of Tubule Growth and Development………….. 2350

Jing Zhou, Martin R. Pollak

316 Tubulointerstitial Diseases of the Kidney………………….. 2357

Laurence H. Beck Jr., David J. Salant

317 Vascular Injury to the Kidney…………………………………. 2364

Ronald S. Go, Nelson Leung

318 Nephrolithiasis……………………………………………………. 2368 xiii

Gary C. Curhan

319 Urinary Tract Obstruction…………………………………….. 2373

Julian L. Seifter

320 Interventional Nephrology…………………………………….. 2377

Dirk M. Hentschel

PART 10 Disorders of the Gastrointestinal System

SECTION 1 Disorders of the Alimentary Tract

321 Approach to the Patient with Gastrointestinal Disease………………………………………………………………. 2381

William L. Hasler, Chung Owyang

322 Gastrointestinal Endoscopy…………………………………… 2387

Louis Michel Wong Kee Song, Mark Topazian

323 Diseases of the Esophagus……………………………………… 2423

Peter J. Kahrilas, Ikuo Hirano

324 Peptic Ulcer Disease and Related Disorders………………. 2434

John Del Valle

325 Disorders of Absorption………………………………………… 2458

Deborah C. Rubin

326 Inflammatory Bowel Disease………………………………….. 2469

Sonia Friedman, Richard S. Blumberg

327 Irritable Bowel Syndrome………………………………………. 2490

Chung Owyang

328 Diverticular Disease and Common Anorectal Disorders……………………………………………………………. 2497

Susan L. Gearhart

329 Mesenteric Vascular Insufficiency……………………………. 2506

Maryam Ali Khan, Jaideep Das Gupta, Mahmoud Malas

330 Acute Intestinal Obstruction………………………………….. 2508

Danny O. Jacobs

331 Acute Appendicitis and Peritonitis………………………….. 2513

Danny O. Jacobs

SECTION 2 Nutrition

332 Nutrient Requirements and Dietary Assessment………… 2517

Johanna T. Dwyer

333 Vitamin and Trace Mineral Deficiency and Excess………………………………………………………………… 2523

Paolo M. Suter

334 Malnutrition and Nutritional Assessment………………… 2534

Gordon L. Jensen

335 Enteral and Parenteral Nutrition…………………………….. 2539

John Hoffer, Bruce R. Bistrian, David F. Driscoll

SECTION 3 Liver and Biliary Tract Disease

336 Approach to the Patient with Liver Disease………………. 2546

Marc G. Ghany, Jay H. Hoofnagle

337 Evaluation of Liver Function………………………………….. 2553

Emily D. Bethea, Daniel S. Pratt

338 The Hyperbilirubinemias………………………………………. 2557

Allan W. Wolkoff

339 Acute Viral Hepatitis……………………………………………. 2562

Jules L. Dienstag

340 Toxic and Drug-Induced Hepatitis………………………….. 2584

William M. Lee, Jules L. Dienstag

341 Chronic Hepatitis………………………………………………… 2591

Jules L. Dienstag

342 Alcohol-Associated Liver Disease…………………………… 2617

Bernd Schnabl

343 Nonalcoholic Fatty Liver Diseases and Nonalcoholic Steatohepatitis…………………………………………………….. 2619

Manal F. Abdelmalek, Anna Mae Diehl

344 Cirrhosis and Its Complications……………………………… 2624

Alex S. Befeler, Bruce R. Bacon

345 Liver Transplantation……………………………………………. 2633

Raymond T. Chung, Jules L. Dienstag

346 Diseases of the Gallbladder and Bile Ducts………………….2641

Norton J. Greenberger, Gustav Paumgartner, Daniel S. Pratt

SECTION 4 Disorders of the Pancreas

347 Approach to the Patient with Pancreatic Disease………… 2652

Somashekar G. Krishna, Darwin L. Conwell, Phil A. Hart

348 Acute and Chronic Pancreatitis………………………………. 2657

Phil A. Hart, Darwin L. Conwell, Somashekar G. Krishna

PART 11 Immune-Mediated, Inflammatory,

and Rheumatologic Disorders

SECTION 1 The Immune System in Health and Disease

349 Introduction to the Immune System………………………… 2671

Barton F. Haynes, Kelly A. Soderberg, Anthony S. Fauci

350 Mechanisms of Regulation and Dysregulation of the

Immune System…………………………………………………… 2701

Barton F. Haynes, Kelly A. Soderberg, Anthony S. Fauci

351 Primary Immune Deficiency Diseases……………………… 2709

Alain Fischer

SECTION 2 Disorders of Immune-Mediated Injury

352 Urticaria, Angioedema, and Allergic Rhinitis…………….. 2719

Katherine L. Tuttle, Joshua A. Boyce

353 Anaphylaxis………………………………………………………… 2727

David Hong, Joshua A. Boyce

354 Mastocytosis……………………………………………………….. 2729

Matthew P. Giannetti, Joshua A. Boyce

355 Autoimmunity and Autoimmune Diseases……………….. 2731

Betty Diamond, Peter E. Lipsky

356 Systemic Lupus Erythematosus………………………………. 2736

Bevra Hannahs Hahn, Maureen McMahon

357 Antiphospholipid Syndrome………………………………….. 2749

Haralampos M. Moutsopoulos, Clio P. Mavragani

358 Rheumatoid Arthritis……………………………………………. 2751

Ankoor Shah, E. William St. Clair

359 Acute Rheumatic Fever…………………………………………. 2766

Joseph Kado, Jonathan Carapetis

360 Systemic Sclerosis (Scleroderma) and

Related Disorders………………………………………………… 2771

John Varga

361 Sjögren’s Syndrome………………………………………………. 2787

Haralampos M. Moutsopoulos, Clio P. Mavragani

362 Spondyloarthritis…………………………………………………. 2790

Joel D. Taurog, Lianne S. Gensler, Nigil Haroon

363 The Vasculitis Syndromes……………………………………… 2802

Carol A. Langford, Anthony S. Fauci

364 Behçet Syndrome…………………………………………………. 2817

Yusuf Yazici

365 Inflammatory Myopathies……………………………………… 2819

Steven A. Greenberg, Anthony A. Amato

366 Relapsing Polychondritis……………………………………….. 2826

Carol A. Langford

367 Sarcoidosis………………………………………………………….. 2829

Robert P. Baughman, Elyse E. Lower

368 IgG4-Related Disease…………………………………………… 2837

John H. Stone

369 Familial Mediterranean Fever and Other

Hereditary Autoinflammatory Diseases……………………. 2840

Daniel L. Kastner

SECTION 3 Disorders of the Joints and Adjacent Tissues

370 Approach to Articular and Musculoskeletal Disorders……………………………………………………………. 2844

John J. Cush

371 Osteoarthritis……………………………………………………… 2854

David T. Felson, Tuhina Neogi

372 Gout and Other Crystal-Associated Arthropathies…….. 2862

Hyon K. Choi

373 Fibromyalgia……………………………………………………….. 2868

Leslie J. Crofford

374 Arthritis Associated with Systemic Disease,

and Other Arthritides…………………………………………… 2871

Carol A. Langford, Brian F. Mandell

375 Periarticular Disorders of the Extremities…………………. 2878

Carol A. Langford

PART 12 Endocrinology and Metabolism

SECTION 1 Endocrinology

376 Approach to the Patient with Endocrine Disorders…….. 2881

Larry Jameson

377 Mechanisms of Hormone Action……………………………. 2884

Larry Jameson

378 Physiology of Anterior Pituitary Hormones……………… 2891

Shlomo Melmed, J. Larry Jameson

379 Hypopituitarism………………………………………………….. 2896

Shlomo Melmed, J. Larry Jameson

380 Pituitary Tumor Syndromes…………………………………… 2902

Shlomo Melmed, J. Larry Jameson

381 Disorders of the Neurohypophysis…………………………… 2918

Gary L. Robertson, Daniel G. Bichet

382 Thyroid Gland Physiology and Testing…………………….. 2926

Larry Jameson, Susan J. Mandel, Anthony P. Weetman

383 Hypothyroidism…………………………………………………… 2933

Larry Jameson, Susan J. Mandel, Anthony P. Weetman

384 Hyperthyroidism and Other Causes of

Thyrotoxicosis…………………………………………………….. 2938

Larry Jameson, Susan J. Mandel, Anthony P. Weetman

385 Thyroid Nodular Disease and Thyroid Cancer…………… 2946

Larry Jameson, Susan J. Mandel, Anthony P. Weetman

386 Disorders of the Adrenal Cortex……………………………… 2955

Wiebke Arlt

387 Pheochromocytoma……………………………………………… 2976

Hartmut P. H. Neumann

388 Multiple Endocrine Neoplasia Syndromes………………… 2983

V. Thakker

389 Autoimmune Polyendocrine Syndromes…………………… 2992

Peter A. Gottlieb, Aaron W. Michels

SECTION 2 Sex- and Gender-Based Medicine

390 Sex Development…………………………………………………. 2997

Courtney Finlayson, J. Larry Jameson, John C. Achermann

391 Disorders of the Testes and Male Reproductive System……………………………………………………………….. 3006

Shalender Bhasin, J. Larry Jameson

392 Disorders of the Female Reproductive System…………… 3027

Janet E. Hall, Anuja Dokras

393 Menstrual Disorders and Pelvic Pain……………………….. 3033

Janet E. Hall, Anuja Dokras

394 Hirsutism…………………………………………………………… 3039

David A. Ehrmann

395 Menopause and Postmenopausal Hormone Therapy……………………………………………………………… 3043

JoAnn E. Manson, Shari S. Bassuk

396 Infertility and Contraception…………………………………. 3050

Anuja Dokras, Janet E. Hall

397 Sexual Dysfunction………………………………………………. 3055

Kevin T. McVary

398 Women’s Health…………………………………………………… 3063

Emily Nosova, Andrea Dunaif

399 Men’s Health………………………………………………………. 3069

Shalender Bhasin

400 Lesbian, Gay, Bisexual, and Transgender

(LGBT) Health…………………………………………………… 3078

Baligh R. Yehia, Zachary B. R. McClain

SECTION 3 Obesity, Diabetes Mellitus, and Metabolic Syndrome

401 Pathobiology of Obesity………………………………………… 3080

Stephen O’Rahilly, I. Sadaf Farooqi

402 Evaluation and Management of Obesity…………………… 3087

Robert F. Kushner

403 Diabetes Mellitus: Diagnosis, Classification, and Pathophysiology…………………………………………….. 3094

Alvin C. Powers, Kevin D. Niswender, Carmella Evans-Molina

404 Diabetes Mellitus: Management and Therapies……………3104

Alvin C. Powers, Michael J. Fowler, Michael R. Rickels

405 Diabetes Mellitus: Complications…………………………… 3120

Alvin C. Powers, John M. Stafford, Michael R. Rickels

406 Hypoglycemia……………………………………………………… 3129

Stephen N. Davis, Philip E. Cryer

407 Disorders of Lipoprotein Metabolism……………………… 3135

Daniel J. Rader

408 The Metabolic Syndrome………………………………………. 3150

Robert H. Eckel

SECTION 4 Disorders of Bone and Mineral Metabolism

409 Bone and Mineral Metabolism in Health and Disease…………………………………………………………. 3157

Richard Bringhurst, Henry M. Kronenberg, Eva S. Liu

410 Disorders of the Parathyroid Gland and Calcium

Homeostasis……………………………………………………….. 3169

John T. Potts, Jr., Harald Jüppner

411 Osteoporosis……………………………………………………….. 3191

Robert Lindsay, Blossom Samuels xv

412 Paget’s Disease and Other Dysplasias of Bone…………… 3209

Rajesh K. Jain, Tamara J. Vokes

SECTION 5 Disorders of Intermediary Metabolism

413 Heritable Disorders of Connective Tissue…………………. 3217

Joan C. Marini, Fransiska Malfait

414 Hemochromatosis………………………………………………… 3230

Lawrie W. Powell, David M. Frazer

415 Wilson’s Disease………………………………………………….. 3235

Stephen G. Kaler

416 The Porphyrias……………………………………………………. 3237

Robert J. Desnick, Manisha Balwani

417 Disorders of Purine and Pyrimidine Metabolism……….. 3248

John N. Mecchella, Christopher M. Burns

418 Lysosomal Storage Diseases…………………………………… 3254

Robert J. Hopkin, Gregory A. Grabowski

419 Glycogen Storage Diseases and Other Inherited

Disorders of Carbohydrate Metabolism……………………. 3261

Priya S. Kishnani

420 Inherited Disorders of Amino Acid Metabolism

in Adults…………………………………………………………….. 3268

Nicola Longo

421 Inherited Defects of Membrane Transport……………….. 3274

Nicola Longo

PART 13 Neurologic Disorders

SECTION 1 Diagnosis of Neurologic Disorders

422 Approach to the Patient with Neurologic Disease………. 3277

Daniel H. Lowenstein, S. Andrew Josephson, Stephen L. Hauser

423 Neuroimaging in Neurologic Disorders……………………. 3282

William P. Dillon

424 Pathobiology of Neurologic Diseases……………………….. 3293

Stephen L. Hauser, Arnold R. Kriegstein, Stanley B. Prusiner

SECTION 2 Diseases of the Central Nervous System

425 Seizures and Epilepsy……………………………………………. 3305

Vikram R. Rao, Daniel H. Lowenstein

426 Introduction to Cerebrovascular Diseases…………………. 3324

Wade S. Smith, S. Claiborne Johnston, J. Claude Hemphill, III

427 Ischemic Stroke…………………………………………………… 3335

Wade S. Smith, S. Claiborne Johnston, J. Claude Hemphill, III

428 Intracranial Hemorrhage……………………………………….. 3348

Wade S. Smith, J. Claude Hemphill, III, S. Claiborne Johnston

429 Subarachnoid Hemorrhage……………………………………. 3353

Claude Hemphill, III,Wade S. Smith, Daryl R. Gress

430 Migraine and Other Primary Headache Disorders……………………………………………………………. 3357

Peter J. Goadsby

431 Alzheimer’s Disease……………………………………………… 3370

Gil D. Rabinovici, William W. Seeley, Bruce L. Miller

432 Frontotemporal Dementia…………………………………….. 3378

William W. Seeley, Bruce L. Miller

433 Vascular Dementia……………………………………………….. 3381

Steven M. Greenberg, William W. Seeley

434 Dementia with Lewy Bodies…………………………………… 3385

Irene Litvan, William W. Seeley, Bruce L. Miller

435 Parkinson’s Disease………………………………………………. 3386

Warren Olanow, Anthony H.V. Schapira

436 Tremor, Chorea, and Other Movement Disorders……….. 3400

Warren Olanow, Christine Klein

437 Amyotrophic Lateral Sclerosis and Other Motor

Neuron Diseases………………………………………………….. 3410

Robert H. Brown, Jr.

438 Prion Diseases…………………………………………………….. 3416

Stanley B. Prusiner, Michael Geschwind

439 Ataxic Disorders………………………………………………….. 3422

Roger N. Rosenberg

440 Disorders of the Autonomic Nervous System……………….3427

Richard J. Barohn, John W. Engstrom

441 Trigeminal Neuralgia, Bell’s Palsy, and Other

Cranial Nerve Disorders……………………………………….. 3436

Vanja C. Douglas, Stephen L. Hauser

442 Diseases of the Spinal Cord……………………………………. 3445

Stephen L. Hauser

443 Concussion and Other Traumatic Brain Injuries………… 3456

Geoffrey T. Manley, Benjamin L. Brett, Michael McCrea

444 Multiple Sclerosis………………………………………………… 3462

Bruce A. C. Cree, Stephen L. Hauser

445 Neuromyelitis Optica……………………………………………. 3477

Bruce A. C. Cree, Stephen L. Hauser

SECTION 3 Nerve and Muscle Disorders

446 Peripheral Neuropathy………………………………………….. 3480

Anthony A. Amato, Richard J. Barohn

447 Guillain-Barré Syndrome and Other

Immune-Mediated Neuropathies…………………………….. 3501

Stephen L. Hauser, Anthony A. Amato

448 Myasthenia Gravis and Other Diseases of the

Neuromuscular Junction……………………………………….. 3509

Anthony A. Amato

449 Muscular Dystrophies and Other Muscle Diseases…….. 3516

Anthony A. Amato, Robert H. Brown, Jr.

SECTION 4 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

450 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome…………………………………………………………… 3532

Elizabeth R. Unger, Jin-Mann S. Lin, Jeanne Bertolli

SECTION 5 Psychiatric and Addiction Disorders

451 Biology of Psychiatric Disorders……………………………… 3534

Robert O. Messing, Eric J. Nestler, Matthew W. State

452 Psychiatric Disorders……………………………………………. 3540

Victor I. Reus

453 Alcohol and Alcohol Use Disorders…………………………. 3556

Marc A. Schuckit

454 Nicotine Addiction………………………………………………. 3563

David M. Burns

455 Marijuana and Marijuana Use Disorders………………….. 3567

Nora D. Volkow, Aidan Hampson, Ruben Baler

456 Opioid-Related Disorders……………………………………… 3569

Thomas R. Kosten, Colin N. Haile

457 Cocaine, Other Psychostimulants, and

Hallucinogens……………………………………………………… 3573

Karran A. Phillips, Wilson M. Compton

PART 14 Poisoning, Drug Overdose, and Envenomation

458 Heavy Metal Poisoning…………………………………………. 3579

Howard Hu

459 Poisoning and Drug Overdose……………………………….. 3582

Mark B. Mycyk

460 Disorders Caused by Venomous Snakebites and

Marine Animal Exposures……………………………………… 3596

Erik Fisher, Alex Chen, Charles Lei

461 Ectoparasite Infestations and Arthropod Injuries………. 3608

Richard J. Pollack, Scott A. Norton

PART 15 Disorders Associated with

Environmental Exposures

462 Altitude Illness……………………………………………………. 3617

Buddha Basnyat, Geoffrey Tabin

463 Hyperbaric and Diving Medicine……………………………. 3623

Michael H. Bennett, Simon J. Mitchell

464 Hypothermia and Peripheral Cold Injuries……………….. 3630

Daniel F. Danzl

465 Heat-Related Illnesses………………………………………….. 3635

Daniel F. Danzl

PART 16 Genes, the Environment, and Disease

466 Principles of Human Genetics………………………………… 3639

Larry Jameson, Peter Kopp

467 The Practice of Genetics in Clinical Medicine…………… 3662

Susan M. Domchek, J. Larry Jameson, Susan Miesfeldt

468 Mitochondrial DNA and Heritable Traits and

Diseases……………………………………………………………… 3668

Karl L. Skorecki, Bruce H. Cohen

469 Telomere Disease…………………………………………………. 3680

Rodrigo T. Calado, Neal S. Young

470 Gene- and Cell-Based Therapy in Clinical

Medicine……………………………………………………………. 3685

Katherine A. High, Marcela V. Maus

471 The Human Microbiome………………………………………. 3690

Neeraj K. Surana, Dennis L. Kasper

PART 17 Global Medicine

472 Global Issues in Medicine……………………………………… 3703

Joseph J. Rhatigan, Paul Farmer

473 Emerging and Reemerging Infectious Diseases………….. 3713

George W. Rutherford, Jaime Sepúlveda

474 Primary Care and Global Health…………………………….. 3718

Tim Evans, Kumanan Rasanathan

475 Health Effects of Climate Change…………………………… 3726

Eugene T. Richardson, Maxine A. Burkett, Paul E. Farmer

PART 18 Aging

476 Biology of Aging………………………………………………….. 3733

Rafael de Cabo, David Le Couteur

477 Caring for the Geriatric Patient………………………………. 3739

Joseph G. Ouslander, Bernardo Reyes

PART 19 Consultative Medicine

478 Approach to Medical Consultation………………………….. 3761

Jeffrey Berns, Jack Ende

479 Medical Disorders During Pregnancy………………………. 3762

Sarah Rae Easter, Robert L. Barbieri

480 Medical Evaluation of the Surgical Patient……………….. 3769

Prashant Vaishnava, Kim A. Eagle

PART 20 Frontiers

481 Behavioral Economics and Health…………………………… 3775

Kevin G. Volpp, George Loewenstein, David A. Asch

482 Complementary and Integrative Therapies

and Practices……………………………………………………….. 3784

Helene M. Langevin

483 The Role of Epigenetics in Disease and Treatment…….. 3790

Brian C. Capell, Shelley L. Berger

484 Applications of Stem Cell Biology in

Clinical Medicine………………………………………………… 3796

John A. Kessler

485 The Role of Circadian Biology in Health

and Disease…………………………………………………………. 3800

Jonathan Cedernaes, Kathryn Moynihan Ramsey, Joseph Bass

486 Network Medicine: Systems Biology in

Health and Disease………………………………………………. 3812

Joseph Loscalzo

487 Emerging Neurotherapeutic Technologies…………………. 3819

Jyoti Mishra, Karunesh Ganguly

488 Machine Learning and Augmented Intelligence

in Clinical Medicine……………………………………………… 3826

Arjun K. Manrai, Isaac S. Kohane

489 Metabolomics……………………………………………………… 3831

Jared R. Mayers, Mathew G. Vander Heiden

490 Circulating Nucleic Acids as Liquid Biopsies and

Noninvasive Disease Biomarkers…………………………….. 3836

Ash A. Alizadeh, Kiran K. Khush, Yair J. Blumenfeld

491 Protein Folding Disorders……………………………………… 3846

Richard I. Morimoto, G. Scott Budinger

492 Novel Approaches to Diseases of

Unknown Etiology…………………………………………………..3851

David Adams, Camilo Toro, Joseph Loscalzo

Index …………………………………………………………………………….I-1

Tract

308 Approach to the Patient with Renal Disease or

Urinary Tract Disease……………………………………………. 2279

Julian L. Seifter

309 Cell Biology and Physiology of the Kidney……………….. 2287

Alfred L. George, Jr., Eric G. Neilson

310 Acute Kidney Injury……………………………………………… 2296

Sushrut S. Waikar, Joseph V. Bonventre

311 Chronic Kidney Disease………………………………………… 2309

Joanne M. Bargman, Karl Skorecki

312 Dialysis in the Treatment of Kidney Failure………………. 2320

Kathleen D. Liu, Glenn M. Chertow

313 Transplantation in the Treatment of Renal Failure……… 2325

Jamil Azzi, Naoka Murakami, Anil Chandraker

314 Glomerular Diseases…………………………………………….. 2331

Julia B. Lewis, Eric G. Neilson

315 Polycystic Kidney Disease and Other Inherited

Disorders of Tubule Growth and Development………….. 2350

Jing Zhou, Martin R. Pollak

316 Tubulointerstitial Diseases of the Kidney………………….. 2357

Laurence H. Beck Jr., David J. Salant

317 Vascular Injury to the Kidney…………………………………. 2364

Ronald S. Go, Nelson Leung

318 Nephrolithiasis……………………………………………………. 2368 xiii

Gary C. Curhan

319 Urinary Tract Obstruction…………………………………….. 2373

Julian L. Seifter

320 Interventional Nephrology…………………………………….. 2377

Dirk M. Hentschel

PART 10 Disorders of the Gastrointestinal System

SECTION 1 Disorders of the Alimentary Tract

321 Approach to the Patient with Gastrointestinal

Disease………………………………………………………………. 2381

William L. Hasler, Chung Owyang

322 Gastrointestinal Endoscopy…………………………………… 2387

Louis Michel Wong Kee Song, Mark Topazian

323 Diseases of the Esophagus……………………………………… 2423

Peter J. Kahrilas, Ikuo Hirano

324 Peptic Ulcer Disease and Related Disorders………………. 2434

John Del Valle

325 Disorders of Absorption………………………………………… 2458

Deborah C. Rubin

326 Inflammatory Bowel Disease………………………………….. 2469

Sonia Friedman, Richard S. Blumberg

327 Irritable Bowel Syndrome………………………………………. 2490

Chung Owyang

328 Diverticular Disease and Common Anorectal

Disorders……………………………………………………………. 2497

Susan L. Gearhart

329 Mesenteric Vascular Insufficiency……………………………. 2506

Maryam Ali Khan, Jaideep Das Gupta, Mahmoud Malas

330 Acute Intestinal Obstruction………………………………….. 2508

Danny O. Jacobs

331 Acute Appendicitis and Peritonitis………………………….. 2513

Danny O. Jacobs

SECTION 2 Nutrition

332 Nutrient Requirements and Dietary Assessment………… 2517

Johanna T. Dwyer

333 Vitamin and Trace Mineral Deficiency and Excess………………………………………………………………… 2523

Paolo M. Suter

334 Malnutrition and Nutritional Assessment………………… 2534

Gordon L. Jensen

335 Enteral and Parenteral Nutrition…………………………….. 2539

John Hoffer, Bruce R. Bistrian, David F. Driscoll

SECTION 3 Liver and Biliary Tract Disease

336 Approach to the Patient with Liver Disease………………. 2546

Marc G. Ghany, Jay H. Hoofnagle

337 Evaluation of Liver Function………………………………….. 2553

Emily D. Bethea, Daniel S. Pratt

338 The Hyperbilirubinemias………………………………………. 2557

Allan W. Wolkoff

339 Acute Viral Hepatitis……………………………………………. 2562

Jules L. Dienstag

340 Toxic and Drug-Induced Hepatitis………………………….. 2584

William M. Lee, Jules L. Dienstag

341 Chronic Hepatitis………………………………………………… 2591

Jules L. Dienstag

342 Alcohol-Associated Liver Disease…………………………… 2617

Bernd Schnabl

343 Nonalcoholic Fatty Liver Diseases and Nonalcoholic

Steatohepatitis…………………………………………………….. 2619

Manal F. Abdelmalek, Anna Mae Diehl

344 Cirrhosis and Its Complications……………………………… 2624

Alex S. Befeler, Bruce R. Bacon

345 Liver Transplantation……………………………………………. 2633

Raymond T. Chung, Jules L. Dienstag

346 Diseases of the Gallbladder and Bile Ducts………………….2641

Norton J. Greenberger, Gustav Paumgartner, Daniel S. Pratt

SECTION 4 Disorders of the Pancreas

347 Approach to the Patient with Pancreatic Disease………… 2652

Somashekar G. Krishna, Darwin L. Conwell, Phil A. Hart

348 Acute and Chronic Pancreatitis………………………………. 2657

Phil A. Hart, Darwin L. Conwell, Somashekar G. Krishna

PART 11 Immune-Mediated, Inflammatory,

and Rheumatologic Disorders

SECTION 1 The Immune System in Health and Disease

349 Introduction to the Immune System………………………… 2671

Barton F. Haynes, Kelly A. Soderberg, Anthony S. Fauci

350 Mechanisms of Regulation and Dysregulation of the

Immune System…………………………………………………… 2701

Barton F. Haynes, Kelly A. Soderberg, Anthony S. Fauci

351 Primary Immune Deficiency Diseases……………………… 2709

Alain Fischer

SECTION 2 Disorders of Immune-Mediated Injury

352 Urticaria, Angioedema, and Allergic Rhinitis…………….. 2719

Katherine L. Tuttle, Joshua A. Boyce

353 Anaphylaxis………………………………………………………… 2727

David Hong, Joshua A. Boyce

354 Mastocytosis……………………………………………………….. 2729

Matthew P. Giannetti, Joshua A. Boyce

355 Autoimmunity and Autoimmune Diseases……………….. 2731

Betty Diamond, Peter E. Lipsky

356 Systemic Lupus Erythematosus………………………………. 2736

Bevra Hannahs Hahn, Maureen McMahon

357 Antiphospholipid Syndrome………………………………….. 2749

Haralampos M. Moutsopoulos, Clio P. Mavragani

358 Rheumatoid Arthritis……………………………………………. 2751

Ankoor Shah, E. William St. Clair

359 Acute Rheumatic Fever…………………………………………. 2766

Joseph Kado, Jonathan Carapetis

360 Systemic Sclerosis (Scleroderma) and

Related Disorders………………………………………………… 2771

John Varga

361 Sjögren’s Syndrome………………………………………………. 2787

Haralampos M. Moutsopoulos, Clio P. Mavragani

362 Spondyloarthritis…………………………………………………. 2790

Joel D. Taurog, Lianne S. Gensler, Nigil Haroon

363 The Vasculitis Syndromes……………………………………… 2802

Carol A. Langford, Anthony S. Fauci

364 Behçet Syndrome…………………………………………………. 2817

Yusuf Yazici

365 Inflammatory Myopathies……………………………………… 2819

Steven A. Greenberg, Anthony A. Amato

366 Relapsing Polychondritis……………………………………….. 2826

Carol A. Langford

367 Sarcoidosis………………………………………………………….. 2829

Robert P. Baughman, Elyse E. Lower

368 IgG4-Related Disease…………………………………………… 2837

John H. Stone

369 Familial Mediterranean Fever and Other

Hereditary Autoinflammatory Diseases……………………. 2840

Daniel L. Kastner

SECTION 3 Disorders of the Joints and Adjacent Tissues

370 Approach to Articular and Musculoskeletal

Disorders……………………………………………………………. 2844

John J. Cush

371 Osteoarthritis……………………………………………………… 2854

David T. Felson, Tuhina Neogi

372 Gout and Other Crystal-Associated Arthropathies…….. 2862

Hyon K. Choi

373 Fibromyalgia……………………………………………………….. 2868

Leslie J. Crofford

374 Arthritis Associated with Systemic Disease,

and Other Arthritides…………………………………………… 2871

Carol A. Langford, Brian F. Mandell

375 Periarticular Disorders of the Extremities…………………. 2878

Carol A. Langford

PART 12 Endocrinology and Metabolism

SECTION 1 Endocrinology

376 Approach to the Patient with Endocrine Disorders…….. 2881

Larry Jameson

377 Mechanisms of Hormone Action……………………………. 2884

Larry Jameson

378 Physiology of Anterior Pituitary Hormones……………… 2891

Shlomo Melmed, J. Larry Jameson

379 Hypopituitarism………………………………………………….. 2896

Shlomo Melmed, J. Larry Jameson

380 Pituitary Tumor Syndromes…………………………………… 2902

Shlomo Melmed, J. Larry Jameson

381 Disorders of the Neurohypophysis…………………………… 2918

Gary L. Robertson, Daniel G. Bichet

382 Thyroid Gland Physiology and Testing…………………….. 2926

Larry Jameson, Susan J. Mandel, Anthony P. Weetman

383 Hypothyroidism…………………………………………………… 2933

Larry Jameson, Susan J. Mandel, Anthony P. Weetman

384 Hyperthyroidism and Other Causes of

Thyrotoxicosis…………………………………………………….. 2938

Larry Jameson, Susan J. Mandel, Anthony P. Weetman

385 Thyroid Nodular Disease and Thyroid Cancer…………… 2946

Larry Jameson, Susan J. Mandel, Anthony P. Weetman

386 Disorders of the Adrenal Cortex……………………………… 2955

Wiebke Arlt

387 Pheochromocytoma……………………………………………… 2976

Hartmut P. H. Neumann

388 Multiple Endocrine Neoplasia Syndromes………………… 2983

V. Thakker

389 Autoimmune Polyendocrine Syndromes…………………… 2992

Peter A. Gottlieb, Aaron W. Michels

SECTION 2 Sex- and Gender-Based Medicine

390 Sex Development…………………………………………………. 2997

Courtney Finlayson, J. Larry Jameson, John C. Achermann

391 Disorders of the Testes and Male Reproductive System………………………………………………………… 3006

Shalender Bhasin, J. Larry Jameson

392 Disorders of the Female Reproductive System…………… 3027

Janet E. Hall, Anuja Dokras

393 Menstrual Disorders and Pelvic Pain……………………….. 3033

Janet E. Hall, Anuja Dokras

394 Hirsutism…………………………………………………………… 3039

David A. Ehrmann

395 Menopause and Postmenopausal Hormone Therapy…………………………………………………. 3043

JoAnn E. Manson, Shari S. Bassuk

396 Infertility and Contraception…………………………………. 3050

Anuja Dokras, Janet E. Hall

397 Sexual Dysfunction………………………………………………. 3055

Kevin T. McVary

398 Women’s Health…………………………………………………… 3063

Emily Nosova, Andrea Dunaif

399 Men’s Health………………………………………………………. 3069

Shalender Bhasin

400 Lesbian, Gay, Bisexual, and Transgender (LGBT) Health……………………………………….. 3078

Baligh R. Yehia, Zachary B. R. McClain

SECTION 3 Obesity, Diabetes Mellitus, and Metabolic Syndrome

401 Pathobiology of Obesity………………………………………… 3080

Stephen O’Rahilly, I. Sadaf Farooqi

402 Evaluation and Management of Obesity…………………… 3087

Robert F. Kushner

403 Diabetes Mellitus: Diagnosis, Classification, and Pathophysiology…………………………………………….. 3094

Alvin C. Powers, Kevin D. Niswender, Carmella Evans-Molina

404 Diabetes Mellitus: Management and Therapies……………3104

Alvin C. Powers, Michael J. Fowler, Michael R. Rickels

405 Diabetes Mellitus: Complications…………………………… 3120

Alvin C. Powers, John M. Stafford, Michael R. Rickels

406 Hypoglycemia……………………………………………………… 3129

Stephen N. Davis, Philip E. Cryer

407 Disorders of Lipoprotein Metabolism……………………… 3135

Daniel J. Rader

408 The Metabolic Syndrome………………………………………. 3150

Robert H. Eckel

SECTION 4 Disorders of Bone and Mineral Metabolism

409 Bone and Mineral Metabolism in Health and Disease…………………………………………………………. 3157

Richard Bringhurst, Henry M. Kronenberg, Eva S. Liu

410 Disorders of the Parathyroid Gland and Calcium

Homeostasis……………………………………………………….. 3169

John T. Potts, Jr., Harald Jüppner

411 Osteoporosis……………………………………………………….. 3191

Robert Lindsay, Blossom Samuels xv

412 Paget’s Disease and Other Dysplasias of Bone…………… 3209

Rajesh K. Jain, Tamara J. Vokes

SECTION 5 Disorders of Intermediary Metabolism

413 Heritable Disorders of Connective Tissue…………………. 3217

Joan C. Marini, Fransiska Malfait

414 Hemochromatosis………………………………………………… 3230

Lawrie W. Powell, David M. Frazer

415 Wilson’s Disease………………………………………………….. 3235

Stephen G. Kaler

416 The Porphyrias……………………………………………………. 3237

Robert J. Desnick, Manisha Balwani

417 Disorders of Purine and Pyrimidine Metabolism……….. 3248

John N. Mecchella, Christopher M. Burns

418 Lysosomal Storage Diseases…………………………………… 3254

Robert J. Hopkin, Gregory A. Grabowski

419 Glycogen Storage Diseases and Other Inherited

Disorders of Carbohydrate Metabolism……………………. 3261

Priya S. Kishnani

420 Inherited Disorders of Amino Acid Metabolism in Adults…………………………………………………………….. 3268

Nicola Longo

421 Inherited Defects of Membrane Transport……………….. 3274

Nicola Longo

PART 13 Neurologic Disorders

SECTION 1 Diagnosis of Neurologic Disorders

422 Approach to the Patient with Neurologic Disease………. 3277

Daniel H. Lowenstein, S. Andrew Josephson, Stephen L. Hauser

423 Neuroimaging in Neurologic Disorders……………………. 3282

William P. Dillon

424 Pathobiology of Neurologic Diseases……………………….. 3293

Stephen L. Hauser, Arnold R. Kriegstein, Stanley B. Prusiner

SECTION 2 Diseases of the Central Nervous System

425 Seizures and Epilepsy……………………………………………. 3305

Vikram R. Rao, Daniel H. Lowenstein

426 Introduction to Cerebrovascular Diseases…………………. 3324

Wade S. Smith, S. Claiborne Johnston, J. Claude Hemphill, III

427 Ischemic Stroke…………………………………………………… 3335

Wade S. Smith, S. Claiborne Johnston, J. Claude Hemphill, III

428 Intracranial Hemorrhage……………………………………….. 3348

Wade S. Smith, J. Claude Hemphill, III, S. Claiborne Johnston

429 Subarachnoid Hemorrhage……………………………………. 3353

Claude Hemphill, III,Wade S. Smith, Daryl R. Gress

430 Migraine and Other Primary Headache

Disorders……………………………………………………………. 3357

Peter J. Goadsby

431 Alzheimer’s Disease……………………………………………… 3370

Gil D. Rabinovici, William W. Seeley, Bruce L. Miller

432 Frontotemporal Dementia…………………………………….. 3378

William W. Seeley, Bruce L. Miller

433 Vascular Dementia……………………………………………….. 3381

Steven M. Greenberg, William W. Seeley

434 Dementia with Lewy Bodies…………………………………… 3385

Irene Litvan, William W. Seeley, Bruce L. Miller

435 Parkinson’s Disease………………………………………………. 3386

Warren Olanow, Anthony H.V. Schapira

436 Tremor, Chorea, and Other Movement Disorders……….. 3400

Warren Olanow, Christine Klein

437 Amyotrophic Lateral Sclerosis and Other Motor

Neuron Diseases………………………………………………….. 3410

Robert H. Brown, Jr.

438 Prion Diseases…………………………………………………….. 3416

Stanley B. Prusiner, Michael Geschwind

439 Ataxic Disorders………………………………………………….. 3422

Roger N. Rosenberg

440 Disorders of the Autonomic Nervous System……………….3427

Richard J. Barohn, John W. Engstrom

441 Trigeminal Neuralgia, Bell’s Palsy, and Other

Cranial Nerve Disorders……………………………………….. 3436

Vanja C. Douglas, Stephen L. Hauser

442 Diseases of the Spinal Cord……………………………………. 3445

Stephen L. Hauser

443 Concussion and Other Traumatic Brain Injuries………… 3456

Geoffrey T. Manley, Benjamin L. Brett, Michael McCrea

444 Multiple Sclerosis………………………………………………… 3462

Bruce A. C. Cree, Stephen L. Hauser

445 Neuromyelitis Optica……………………………………………. 3477

Bruce A. C. Cree, Stephen L. Hauser

SECTION 3 Nerve and Muscle Disorders

446 Peripheral Neuropathy………………………………………….. 3480

Anthony A. Amato, Richard J. Barohn

447 Guillain-Barré Syndrome and Other

Immune-Mediated Neuropathies…………………………….. 3501

Stephen L. Hauser, Anthony A. Amato

448 Myasthenia Gravis and Other Diseases of the Neuromuscular Junction…………………….. 3509

Anthony A. Amato

449 Muscular Dystrophies and Other Muscle Diseases…….. 3516

Anthony A. Amato, Robert H. Brown, Jr.

SECTION 4 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

450 Myalgic Encephalomyelitis/Chronic Fatigue

Syndrome…………………………………………………………… 3532

Elizabeth R. Unger, Jin-Mann S. Lin, Jeanne Bertolli

SECTION 5 Psychiatric and Addiction Disorders

451 Biology of Psychiatric Disorders……………………………… 3534

Robert O. Messing, Eric J. Nestler, Matthew W. State

452 Psychiatric Disorders……………………………………………. 3540

Victor I. Reus

453 Alcohol and Alcohol Use Disorders…………………………. 3556

Marc A. Schuckit

454 Nicotine Addiction………………………………………………. 3563

David M. Burns

455 Marijuana and Marijuana Use Disorders………………….. 3567

Nora D. Volkow, Aidan Hampson, Ruben Baler

456 Opioid-Related Disorders……………………………………… 3569

Thomas R. Kosten, Colin N. Haile

457 Cocaine, Other Psychostimulants, and

Hallucinogens……………………………………………………… 3573

Karran A. Phillips, Wilson M. Compton

PART 14 Poisoning, Drug Overdose, and Envenomation

458 Heavy Metal Poisoning…………………………………………. 3579

Howard Hu

459 Poisoning and Drug Overdose……………………………….. 3582

Mark B. Mycyk

460 Disorders Caused by Venomous Snakebites and

Marine Animal Exposures……………………………………… 3596

Erik Fisher, Alex Chen, Charles Lei

461 Ectoparasite Infestations and Arthropod Injuries………. 3608

Richard J. Pollack, Scott A. Norton

PART 15 Disorders Associated with Environmental Exposures

462 Altitude Illness……………………………………………………. 3617

Buddha Basnyat, Geoffrey Tabin

463 Hyperbaric and Diving Medicine……………………………. 3623

Michael H. Bennett, Simon J. Mitchell

464 Hypothermia and Peripheral Cold Injuries……………….. 3630

Daniel F. Danzl

465 Heat-Related Illnesses………………………………………….. 3635

Daniel F. Danzl

PART 16 Genes, the Environment, and Disease

466 Principles of Human Genetics………………………………… 3639

Larry Jameson, Peter Kopp

467 The Practice of Genetics in Clinical Medicine…………… 3662

Susan M. Domchek, J. Larry Jameson, Susan Miesfeldt

468 Mitochondrial DNA and Heritable Traits and

Diseases……………………………………………………………… 3668

Karl L. Skorecki, Bruce H. Cohen

469 Telomere Disease…………………………………………………. 3680

Rodrigo T. Calado, Neal S. Young

470 Gene- and Cell-Based Therapy in Clinical

Medicine……………………………………………………………. 3685

Katherine A. High, Marcela V. Maus

471 The Human Microbiome………………………………………. 3690

Neeraj K. Surana, Dennis L. Kasper

PART 17 Global Medicine

472 Global Issues in Medicine……………………………………… 3703

Joseph J. Rhatigan, Paul Farmer

473 Emerging and Reemerging Infectious Diseases………….. 3713

George W. Rutherford, Jaime Sepúlveda

474 Primary Care and Global Health…………………………….. 3718

Tim Evans, Kumanan Rasanathan

475 Health Effects of Climate Change…………………………… 3726

Eugene T. Richardson, Maxine A. Burkett, Paul E. Farmer

PART 18 Aging

476 Biology of Aging………………………………………………….. 3733

Rafael de Cabo, David Le Couteur

477 Caring for the Geriatric Patient………………………………. 3739

Joseph G. Ouslander, Bernardo Reyes

PART 19 Consultative Medicine

478 Approach to Medical Consultation………………………….. 3761

Jeffrey Berns, Jack Ende

479 Medical Disorders During Pregnancy………………………. 3762

Sarah Rae Easter, Robert L. Barbieri

480 Medical Evaluation of the Surgical Patient……………….. 3769

Prashant Vaishnava, Kim A. Eagle

PART 20 Frontiers

481 Behavioral Economics and Health…………………………… 3775

Kevin G. Volpp, George Loewenstein, David A. Asch

482 Complementary and Integrative Therapies and Practices………………………………….. 3784

Helene M. Langevin

483 The Role of Epigenetics in Disease and Treatment…….. 3790

Brian C. Capell, Shelley L. Berger

484 Applications of Stem Cell Biology in Clinical Medicine………………………………. 3796

John A. Kessler

485 The Role of Circadian Biology in Health and Disease…………………………………………………………. 3800

Jonathan Cedernaes, Kathryn Moynihan Ramsey, Joseph Bass

486 Network Medicine: Systems Biology in

Health and Disease………………………………………………. 3812

Joseph Loscalzo

487 Emerging Neurotherapeutic Technologies…………………. 3819

Jyoti Mishra, Karunesh Ganguly

488 Machine Learning and Augmented Intelligence in Clinical Medicine……………………………………………… 3826

Arjun K. Manrai, Isaac S. Kohane

489 Metabolomics……………………………………………………… 3831

Jared R. Mayers, Mathew G. Vander Heiden

490 Circulating Nucleic Acids as Liquid Biopsies and

Noninvasive Disease Biomarkers…………………………….. 3836

Ash A. Alizadeh, Kiran K. Khush, Yair J. Blumenfeld

491 Protein Folding Disorders……………………………………… 3846

Richard I. Morimoto, G. Scott Budinger

492 Novel Approaches to Diseases of Unknown Etiology…………………………………………………..3851

David Adams, Camilo Toro, Joseph Loscalzo

Index …………………………………………………………………………….I-1

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