GOLDMAN-CECIL MEDICINE GOLDMAN-CECIL MEDICINE 26TH EDITION Volume 1 EDITED BY LEE GOLDMAN, MD Harold and Margaret Hatch Professor Chief Executive, Columbia University Irving Medical Center Dean of the Faculties of Health Sciences and Medicine Columbia University New York, New York ANDREW I. SCHAFER, MD Professor of Medicine Director, Richard T. Silver Center for Myeloproliferative Neoplasms Weill Cornell Medical College New York, New York Elsevier 1600 John F. Kennedy Blvd. Ste 1600 Philadelphia, PA 19103-2899 GOLDMAN-CECIL MEDICINE, TWENTY-SIXTH EDITION ISBN: 978-0-323-53266-2 Volume 1 ISBN: 978-0-323-76018-8 Volume 2 ISBN: 978-0-323-76019-5 INTERNATIONAL EDITION ISBN: 978-0-323-64033-6 IE Volume 1 ISBN: 978-0-323-75998-4 IE Volume 2 ISBN: 978-0-323-75999-1 Copyright © 2020 by Elsevier, Inc. All rights reserved. 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The following contributors are US government employees and their contributions are in public domain: David Atkins – Chapter 12 John O’Shea – Chapter 33 Leslie Biesecker – Chapter 36 Amy Klion – Chapter 161 Donna Krasnewich & Ellen Sidransky – Chapter 197 Lynnette Nieman – Chapter 208, 214, 218 Richard Siegel & Daniel Kastner – Chapter 245 Roland Sutter – Chapter 276 Paul Mead – Chapter 296 Joseph Kovacs – Chapter 321 Louis Kirchhoff – Chapter 326 Theodore Nash – Chapter 330 Neal Young – Chapter 347 Jeffrey Cohen – Chapter 351 Notice Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2016, 2012, 2008, 2004, 2000, 1996, 1991, 1988, 1982, 1979, 1975, 1971, 1963, 1959, 1955, 1951, 1947, 1943, 1940, 1937, 1933, 1930, 1927 by Saunders, an imprint of Elsevier Inc. Copyright renewed 1991 by Paul Beeson. Copyright renewed 1979 by Russell L. Cecil and Robert F. Loeb. Copyright renewed 1987, 1975, 1971, 1965, 1961, 1958, 1955 by Elsevier Inc. Library of Congress Control Number: 2019909209 Publishing Director, Medical Reference: Dolores Meloni Content Development Manager: Laura Schmidt Publishing Services Manager: Catherine Jackson Senior Project Manager: Daniel Fitzgerald Designer: Maggie Reid Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2 1 ASSOCIATE EDITORS Mary K. Crow, MD Wendy Levinson, MD Joseph P. Routh Professor of Rheumatic Diseases in Medicine Professor of Medicine Weill Cornell Medical College Chair Emeritus Physician-in-Chief and Benjamin M. Rosen Chair in Immunology and Department of Medicine Inflammation Research University of Toronto Hospital for Special Surgery Toronto, Ontario, Canada New York, New York Anil K. Rustgi, MD Nancy E. Davidson, MD Irving Professor of Medicine Professor of Medicine and Raisbeck Endowed Chair Director President Herbert Irving Comprehensive Cancer Center Seattle Cancer Care Alliance Chief Senior Vice President and Director, Clinical Research Division NewYork-Presbyterian Hospital/Columbia University Irving Medical Fred Hutchinson Cancer Research Center Center Cancer Service Chief Columbia University Vagelos College of Physicians and Surgeons Division of Medical Oncology New York, New York University of Washington School of Medicine Seattle, Washington W. Michael Scheld, MD Bayer-Gerald L. Mandell Professor of Infectious Diseases Jeffrey M. Drazen, MD Professor of Medicine Distinguished Parker B. Francis Professor of Medicine Clinical Professor of Neurosurgery Harvard Medical School David A. Harrison Distinguished Educator Senior Physician University of Virginia Health System Department of Medicine Charlottesville, Virginia Brigham and Women’s Hospital Boston, Massachusetts Allen M. Spiegel, MD Dean Emeritus Robert C. Griggs, MD Professor of Medicine Professor of Neurology, Medicine, Pediatrics, Pathology & Laboratory Albert Einstein College of Medicine Medicine Bronx, New York University of Rochester School of Medicine & Dentistry Rochester, New York Donald W. Landry, MD, PhD Samuel Bard Professor and Chair Department of Medicine Columbia University Vagelos College of Physicians and Surgeons Physician-in-Chief Columbia University Irving Medical Center New York, New York PREFACE In the more than 90 years since the first edition of the Cecil Textbook of Medicine others in our offices have shown extraordinary dedication and equanimity in was published, almost everything we know about internal medicine has changed. working with authors and editors to manage the unending flow of manuscripts, Progress in medical science is now occurring at an ever-accelerating pace, and figures, and permissions. it is doing so within the framework of transformational changes in clinical This edition of Goldman-Cecil Medicine includes many new authors. We practice and the delivery of health care at individual, social, and global levels. would also like to thank outgoing authors, who often provided figures that This textbook and its associated electronic products incorporate the latest are included in this edition as well as tables that have been included or modi- medical knowledge in multiple formats that should appeal to students and fied for this edition. Furthermore, because of the templated format and extensive seasoned practitioners regardless of how they prefer to access this rapidly editing that are characteristic of Goldman-Cecil Medicine, some new chapters changing information. incorporate principles, concepts, and organizational aspects from those prior Even as Cecil’s specific information has changed, however, we have remained chapters, often revised extensively prior to publication. Among prior authors true to the tradition of a comprehensive textbook of medicine that carefully who deserve our appreciation, in the numerical order of their chapters, are explains the why (the underlying genetics, genomics, and pathobiology of Victoria M. Taylor, Steven A. Schroeder, Thomas B. Newman, Charles E. disease) and the how (now expected to be evidence-based from randomized McCulloch, Thomas H. Lee, F. Daniel Duffy, Lawrence S. Neinstein, Steven controlled trials and meta-analyses). Descriptions of physiology and patho- E. Hyman, Grant W. Cannon, Cem Gabay, Carlo Patrono, Jack Hirsh, Adam physiology include the latest genetic advances in a practical format that strives Perlman, Sandesh C.S. Nagamani, Paweł Stankiewicz, James R. Lupski, Sekar to be useful to the nonexpert so that care can truly be as precise and personal- Kathiresan, David Altshuler, Göran K. Hansson, Anders Hamsten, L. David ized as possible. Hillis, Bruce W. Lytle, William C. Little, Donna Mancini, Yoshifumi Naka, Medicine has entered an era when the acuity of illness and the limited time Dennis E. Niewoehner, Frank J. Accurso, Emanuel P. Rivers, Marsha D. Ford, available to evaluate a patient have diminished the ability of physicians to Geoffrey K. Isbister, Itzchak Slotki, Mark L. Zeidel, David H. Kim, Perry J. satisfy their intellectual curiosity. As a result, the acquisition of information, Pickhardt, Martin J. Blaser, Stephen Crane Hauser, H. Franklin Bunn, Gordon quite easily achieved in this era, is often confused with knowledge. We have D. Ginder, Martin H. Steinberg, Aśok C. Antony, Ayalew Tefferi, Michael attempted to address this dilemma with a textbook that not only informs but Glogauer, Marc E. Rothenberg, William L. Nichols, Lawrence T. Goodnough, also stimulates new questions and gives a glimpse of the future path to new Adrian R. Black, Kenneth H. Cowan, Susan O’Brien, Elias Jabbour, Marshall knowledge. Grade A evidence is specifically highlighted in the text and refer- R. Posner, Charles D. Blanke, Douglas O. Faigel, David Spriggs, John D. Hain- enced at the end of each chapter. In addition to the information provided in sworth, F. Anthony Greco, Clay F. Semenkovich, Stephen G. Kaler, Bruce R. the textbook, the Cecil website supplies expanded content and functionality. Bacon, Bruce R. Bistrian, Stephen A. McClave, Mark E. Molitch, Matthew In many cases, the full articles referenced in each chapter can be accessed Kim, Paul W. Ladenson, Kenneth R. Hande, Robert W. Rebar, Deborah Grady, from the Cecil website. The website is also continuously updated to incorporate Elizabeth Barrett-Connor, Samuel A. Wells, Jr., Stephen I. Wasserman, Larry subsequent Grade A information, other evidence, and new discoveries. Borish, Suneel S. Apte, Joel A. Block, Carla Scanzello, Robert M. Bennett, The sections for each organ system begin with a chapter that summarizes Ilseung Cho, S. Ragnar Norrby, Lionel A. Mandell, Donald E. Low, Kenneth an approach to patients with key symptoms, signs, or laboratory abnormalities L. Gage, Atis Muehlenbachs, Stuart Levin, Kamaljit Singh, Richard L. Guer- associated with dysfunction of that organ system. As summarized in E-Table rant, Dirk M. Elston, Larry J. Anderson, Martin Weisse, Mark Papania, Letha 1-1, the text specifically provides clear, concise information regarding how a M. Healey, Tamsin A. Knox, Christine Wanke, Kristina Crothers, Alison Morris, physician should approach more than 100 common symptoms, signs, and Toby A. Maurer, Thomas S. Uldrick, Robert Yarchoan, Robert Colebunders, laboratory abnormalities, usually with a flow diagram, a table, or both for easy Ralph F. Józefowicz, Michael Aminoff, Eelco F.M. Wijdicks, Myron Yanoff, reference. In this way, Cecil remains a comprehensive text to guide diagnosis Douglas Cameron, David H. Chu, James C. Shaw, Neil J. Korman, and Ronald and therapy, not only for patients with suspected or known diseases but also J. Elin. We also thank Michael G. House, who contributed to the chapter on for patients who may have undiagnosed symptoms or signs that require an “Diseases of the Gallbladder and Bile Ducts,” and Anna Louise Beavis, who initial evaluation. contributed to the chapter on “Gynecologic Cancers.” Chapters written by Just as each edition brings new authors, it also reminds us of our gratitude public employees reflect recommendations and conclusions of the authors to past editors and authors. Previous editors of Cecil include a short but remark- and do not necessarily reflect the official position of the entity for which they ably distinguished group of leaders of American medicine: Russell Cecil, Paul work. Beeson, Walsh McDermott, James Wyngaarden, Lloyd H. Smith, Jr., Fred At Elsevier, we are most indebted to Dolores Meloni and Laura Schmidt, Plum, J. Claude Bennett, and Dennis Ausiello. As we welcome a new associate and also thank Lucia Gunzel, Dan Fitzgerald, and Maggie Reid, who have editor—Nancy Davidson—we also express our appreciation to James Doro- been critical to the planning and production. show and other associate editors from the previous editions on whose founda- We have been exposed to remarkable physicians in our lifetimes and would tion we have built. Our returning associate editors—Mary K. Crow, Jeffrey like to acknowledge the mentorship and support of several of those who M. Drazen, Robert C. Griggs, Donald W. Landry, Wendy Levinson, Anil Rustgi, exemplify this paradigm—Eugene Braunwald, the late Lloyd H. Smith, Jr., W. Michael Scheld, and Allen M. Spiegel—continue to make critical contribu- Frank Gardner, and William Castle. Finally, we would like to thank the Goldman tions to the selection of authors and the review and approval of all manuscripts. family—Jill, Jeff, Abigail, Mira, Samuel, Daniel, Morgan, Robyn, Tobin, Dashel, The editors, however, are fully responsible for the book as well as the integra- and Alden—and the Schafer family—Pauline, Eric, Melissa, Nathaniel, tion among chapters. Caroline, Pam, John, Evan, Samantha, Kate, Sean, Patrick, and Meghan—for The tradition of Cecil is that all chapters are written by distinguished experts their understanding of the time and focus required to edit a book that attempts in each field. Two of those authors, Frank A. Lederle, author of the chapter to sustain the tradition of our predecessors and to meet the needs of today’s on “Diseases of the Aorta,” and Ronald Victor, author of the chapter on “Arte- physician. rial Hypertension,” passed away after submitting their chapters, and we mourn their passing. LEE GOLDMAN, MD We are also most grateful for the editorial assistance in New York of Timothy ANDREW I. SCHAFER, MD Gahr, Maribel Lim, Eva Allen, and Magdalena Fuentes. These individuals and CONTRIBUTORS Charles S. Abrams, MD Deborah K. Armstrong, MD Francis C. Wood Professor of Medicine, University of Pennsylvania Professor of Gynecology and Obstetrics, Johns Hopkins University School Perelman School of Medicine, Philadelphia, Pennsylvania of Medicine, Baltimore, Maryland Thrombocytopenia Gynecologic Cancers Ronald S. Adler, MD, PhD M. Amin Arnaout, MD Professor of Radiology, New York University School of Medicine; NYU Professor of Medicine, Chief Emeritus, Division of Nephrology, Langone Health, New York, New York Department of Medicine, Massachusetts General Hospital and Harvard Imaging Studies in the Rheumatic Diseases Medical School, Boston, Massachusetts Cystic Kidney Diseases Cem Akin, MD, PhD Professor of Medicine, Internal Medicine, University of Michigan Medical Robert M. Arnold, MD School, Ann Arbor, Michigan Distinguished Service Professor, Chief, Section of Palliative Care and Mastocytosis Medical Ethics, University of Pittsburgh School of Medicine; Chief Medical Officer, UPMC Palliative and Supportive Institute, UPMC Allen J. Aksamit, Jr., MD Health Plan, Pittsburgh, Pennsylvania Professor of Neurology, Mayo Clinic College of Medicine and Science, Palliative Care Rochester, Minnesota Acute Viral Encephalitis David Atkins, MD, MPH Director, Health Services Research and Development, Office of Research Qais Al-Awqati, MB ChB and Development, Dept. of Veterans Affairs (10P9H), Washington, D.C. Robert F. Loeb Professor, Medicine, and Physiology & Cellular Biophysics, The Periodic Health Examination Columbia University Vagelos College of Physicians & Surgeons, New York, New York John P. Atkinson, MD Structure and Function of the Kidneys; Disorders of Sodium and Water Professor of Medicine, Division of Rheumatology, Washington University School of Medicine in St. Louis, St. Louis, Missouri Ban Mishu Allos, MD Complement System in Disease Associate Professor of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee John Z. Ayanian, MD, MPP Campylobacter Infections Alice Hamilton Professor of Medicine; Director, Institute for Healthcare Policy and Innovation, University of Michigan Medical School, Ann Jeffrey L. Anderson, MD Arbor, Michigan Professor of Medicine, Division of Cardiovascular Medicine, University of Disparities in Health and Health Care Utah School of Medicine; Distinguished Clinical and Research Physician, Intermountain Medical Center Heart Institute, Salt Lake City, Larry M. Baddour, MD Utah Professor of Medicine, Mayo Clinic College of Medicine and Science, ST Elevation Acute Myocardial Infarction and Complications of Myocardial Rochester, Minnesota Infarction Infective Endocarditis Derek C. Angus, MD, MPH Grover C. Bagby, MD Professor and Mitchell P. Fink Endowed Chair, Department of Critical Professor of Medicine, Molecular and Medical Genetics, Oregon Health & Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Science University, Portland, Oregon Pennsylvania Aplastic Anemia and Related Bone Marrow Failure States Approach to the Patient with Shock Barbara J. Bain, MBBS Gerald B. Appel, MD Professor in Diagnostic Haematology, Haematology, St Mary’s Hospital Professor of Medicine and Director, Glomerular Center, Columbia Campus of Imperial College London, London, United Kingdom University Irving Medical Center, New York, New York The Peripheral Blood Smear Glomerular Disorders and Nephrotic Syndromes Dean F. Bajorin, MD Frederick R. Appelbaum, MD Attending Physician and Member, Memorial Sloan Kettering Cancer Professor of Medicine, University of Washington School of Medicine; Center; Professor of Medicine, Weill Cornell Medical College, New Executive Senior VP and Deputy Director, Clinical Research Division, York, New York Fred Hutchinson Cancer Research Center, Seattle, Washington Tumors of the Kidney, Bladder, Ureters, and Renal Pelvis The Acute Leukemias Robert W. Baloh, MD James O. Armitage, MD Professor of Neurology, David Geffen School of Medicine at UCLA, Professor of Internal Medicine, University of Nebraska Medical Center Los Angeles, California College of Medicine, Omaha, Nebraska Neuro-Ophthalmology; Smell and Taste; Hearing and Equilibrium Non-Hodgkin Lymphomas viii Contributors Charles R.M. Bangham, BM BCh Hasan Bazari, MD Professor of Medicine, Faculty of Medicine, Imperial College London Associate Professor of Medicine, Massachusetts General Hospital and School of Medicine, London, United Kingdom Harvard Medical School, Boston, Massachusetts Retroviruses Other Than Human Immunodeficiency Virus Approach to the Patient with Renal Disease Jonathan Barasch, MD, PhD Jeffrey J. Bazarian, MD, MPH Samuel W Lambert Professor of Medicine, Professor of Pathology and Cell Professor of Emergency Medicine, University of Rochester School of Biology, Columbia University Vagelos College of Physicians & Surgeons, Medicine & Dentistry, Rochester, New York New York, New York Traumatic Brain Injury and Spinal Cord Injury Structure and Function of the Kidneys John H. Beigel, MD Richard L. Barbano, MD, PhD Associate Director for Clinical Research, Division of Microbiology and Professor of Neurology and Chief of the Movement Disorders Division, Infectious Diseases, National Institute of Allergy and Infectious Diseases, University of Rochester School of Medicine & Dentistry, Rochester, National Institutes of Health, Bethesda, Maryland New York Antiviral Therapy (Non-HIV) Mechanical and Other Lesions of the Spine, Nerve Roots, and Spinal Cord Elisabeth H. Bel, MD, PhD Bruce Barrett, MD, PhD Professor and Head of the Department of Respiratory Medicine, Professor, Department of Family Medicine and Community Health, Amsterdam University Medical Center, University of Amsterdam, The University of Wisconsin School of Medicine and Public Health, Netherlands Madison, Wisconsin Asthma The Common Cold George A. Beller, MD John R. Bartholomew, MD Emeritus Professor of Cardiology, Department of Medicine, University of Professor of Medicine and Section Head Vascular Medicine, Cleveland Virginia Health System, Charlottesville, Virginia Clinic Lerner College of Medicine, Cleveland, Ohio Noninvasive Cardiac Imaging Other Peripheral Arterial Diseases Joseph R. Berger, MD J.D. Bartleson, MD Professor of Neurology, University of Pennsylvania Perelman School of Professor of Neurology, Mayo Clinic College of Medicine and Science, Medicine, Philadelphia, Pennsylvania Rochester, Minnesota Cytomegalovirus, Epstein-Barr Virus, and Slow Virus Infections of the Central Mechanical and Other Lesions of the Spine, Nerve Roots, and Spinal Cord Nervous System; Brain Abscess and Parameningeal Infections Mary Barton, MD, MPP Paul D. Berk, MD Vice President, Performance Measurement, National Committee for Professor of Medicine, Columbia University Vagelos College of Physicians Quality Assurance, Washington, D.C. & Surgeons, New York, New York The Periodic Health Examination Approach to the Patient with Jaundice or Abnormal Liver Tests Robert C. Basner, MD Nancy Berliner, MD Professor of Medicine, Columbia University Vagelos College of Physicians H. Franklin Bunn Professor of Medicine; Chief, Division of Hematology, and Surgeons, New York, New York Brigham and Women’s Hospital and Harvard Medical School, Boston, Sleep Disorders Massachusetts Leukocytosis and Leukopenia; Histiocytoses Anne R. Bass, MD Professor of Clinical Medicine, Weill Cornell Medical College; Attending James L. Bernat, MD Physician, Hospital for Special Surgery, New York, New York Professor of Neurology and Medicine, Geisel School of Medicine at Immunomodulatory Drugs Dartmouth, Hanover, New Hampshire and Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire Stephen G. Baum, MD Coma, Vegetative State, and Brain Death Professor of Medicine and of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York Philip J. Bierman, MD Mycoplasma Infections Professor of Internal Medicine, University of Nebraska Medical Center College of Medicine, Omaha, Nebraska Julie E. Bauman, MD, MPH Non-Hodgkin Lymphomas Professor of Medicine, University of Arizona Cancer Center, Tucson, Arizona Leslie G. Biesecker, MD Head and Neck Cancer Chief, Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Daniel G. Bausch, MD, MPH&TM Bethesda, Maryland Director, United Kingdom Public Health Rapid Support Team, Public Clinical Genomics—Genome Structure and Variation Health England/London School of Hygiene and Tropical Medicine, London, United Kingdom Michael R. Bishop, MD Viral Hemorrhagic Fevers Professor of Medicine and Director of the Cellular Therapy Program, Section of Hematology and Oncology, University of Chicago Pritzker Arnold S. Bayer, MD School of Medicine, Chicago, Illinois Distinguished Professor of Medicine, David Geffen School of Medicine at Hematopoietic Stem Cell Transplantation UCLA; Senior Investigator-LA Biomedical Research Institute At Harbor-UCLA, Los Angeles, California Joseph J. Biundo, MD Infective Endocarditis Clinical Professor of Medicine, Tulane Medical Center, New Orleans, Louisiana Bursitis, Tendinitis, and Other Periarticular Disorders and Sports Medicine Contributors ix Joel N. Blankson, MD, PhD Lucy Breakwell, PhD, MSc Professor of Medicine, Johns Hopkins University School of Medicine, Epidemiologist, Global Immunization Division, Centers for Disease Baltimore, Maryland Control and Prevention, Atlanta, Georgia Immunopathogenesis of Human Immunodeficiency Virus Infection Diphtheria and Other Corynebacterium Infections William A. Blattner, MD David J. Brenner, PhD, DSc Chief Executive Officer, Salt Run Global Health and Research, Saint Higgins Professor of Radiation Biophysics, Center for Radiological Augustine, Florida Research, Columbia University Irving Medical Center, New York, New Retroviruses Other Than Human Immunodeficiency Virus York Radiation Injury Thomas P. Bleck, MD Professor of Neurology, Northwestern University Feinberg School of Laurent Brochard, MD Medicine; Professor Emeritus of Neurological Sciences, Neurosurgery, Keenan Chair in Critical Care and Respiratory Medicine and Professor of Medicine, and Anesthesiology, Rush Medical College, Chicago, Illinois Medicine and Interdepartmental Division Director for Critical Care, Arboviruses Affecting the Central Nervous System University of Toronto Faculty of Medicine; Division of Critical Care, Saint Michael’s Hospital, Toronto, Ontario, Canada Karen C. Bloch, MD, MPH Mechanical Ventilation Associate Professor of Medicine (Infectious Diseases) and Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee Itzhak Brook, MD Tularemia and Other Francisella Infections Professor of Pediatrics, Georgetown University School of Medicine, Washington, D.C. Henk J. Blom, PhD Diseases Caused by Non–Spore-Forming Anaerobic Bacteria; Actinomycosis Professor of Biochemistry of Inherited Metabolic Disease, Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Enrico Brunetti, MD Erasmus MC, Rotterdam, The Netherlands Associate Professor, Department of Clinical, Surgical, Diagnostic and Homocystinuria and Hyperhomocysteinemia Pediatric Sciences and Staff Physician, Department of Infectious and Tropical Diseases, San Matteo Hospital Foundation, University of Pavia, Olaf A. Bodamer, MD, PhD Pavia, Italy Park Gerald Chair of Genetics and Genomics, Department of Medicine, Cestodes Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts Amy E. Bryant, PhD Approach to Inborn Errors of Metabolism Associate Professor of Medicine, University of Washington School of Medicine, Seattle, Washington and Research Career Scientist, Infectious William E. Boden, MD Diseases Section, VA Medical Center, Boise, Idaho Professor of Medicine, Boston University School of Medicine; Lecturer in Nonpneumococcal Streptococcal Infections and Rheumatic Fever Medicine, Harvard Medical School; Scientific Director, Clinical Trials Network, Department of Medicine, VA Boston Healthcare System, David M. Buchner, MD, MPH Boston, Massachusetts Professor Emeritus, Department of Kinesiology & Community Health, Angina Pectoris and Stable Ischemic Heart Disease University of Illinois Urbana Champaign, Champaign, Illinois Physical Activity Guy Boivin, MD Professor of Microbiology, Immunology and Infectiology, CHU de Pierre A. Buffet, MD, PhD Québec-Laval University, Quebec City, Quebec, Canada Professor of Cell Biology, Faculty of Medicine, Paris University and Cytomegalovirus Consultant Physician, Institut Pasteur Medical Center, Paris, France Leishmaniasis Jean Bolognia, MD Professor of Dermatology, Yale University School of Medicine, New Haven, David A. Bushinsky, MD Connecticut John J. Kuiper Distinguished Professor of Medicine and of Pharmacology Infections, Hyperpigmentation and Hypopigmentation, Regional Dermatology, and Physiology, University of Rochester School of Medicine & Dentistry, and Distinctive Lesions in Black Skin Rochester, New York Nephrolithiasis William Bonnez, MD Professor Emeritus of Medicine, University of Rochester School of Vivian P. Bykerk, MD Medicine & Dentistry, Rochester, New York Associate Professor of Medicine, Weill Cornell Medical College; Associate Papillomavirus Attending Physician, Hospital for Special Surgery, New York, New York Approach to the Patient with Rheumatic Disease Robert A. Bonomo, MD Professor of Medicine, Case Western Reserve University School of John C. Byrd, MD Medicine; Chief of Medicine, Cleveland VA Hospital, Cleveland, Ohio Distinguished University Professor, Ohio State University, Columbus, Ohio Diseases Caused by Acinetobacter and Stenotrophomonas Species Chronic Lymphocytic Leukemia Sarah L. Booth, PhD Peter A. Calabresi, MD Professor of Nutrition, Tufts University; Director, USDA Human Nutrition Professor of Neurology and Neuroscience, Director of the Richard T Research Center on Aging; Director, Vitamin K Laboratory, USDA Johnson Division of Neuroimmunology and Neuroinfectious Diseases; Human Nutrition Research Center on Aging, Boston, Massachusetts Director of the Multiple Sclerosis Center, Johns Hopkins University Vitamins, Trace Minerals, and Other Micronutrients School of Medicine, Baltimore, Maryland Multiple Sclerosis and Demyelinating Conditions of the Central Nervous System Patrick J. Bosque, MD Associate Professor of Neurology, University of Colorado School of Medicine; Chief, Neurology Division, Department of Medicine, Denver Health Medical Center, Denver, Colorado Prion Diseases x Contributors David P. Calfee, MD, MS Lin H. Chen, MD Professor of Medicine and of Health Policy & Research, Weill Cornell Associate Professor of Medicine, Harvard Medical School, Boston, Medical College; Chief Hospital Epidemiologist, NewYork-Presbyterian Massachusetts and Director of the Travel Medicine Center, Division of Hospital/Weill Cornell, New York, New York Infectious Diseases and Travel Medicine, Mount Auburn Hospital, Prevention and Control of Health Care–Associated Infections Cambridge, Massachusetts Approach to the Patient before and after Travel Clara Camaschella, MD Professor of Medicine, Division of Genetics and Cell Biology, San Raffaele Sharon C-A Chen, MB, PhD Scientific Institute, Milano, Italy Professor of Medicine, University of Sydney and Centre for Infectious Microcytic and Hypochromic Anemias Diseases and Microbiology, ICPMR and Westmead Hospital, New South Wales, Australia Michael Camilleri, MD Cryptococcosis Atherton and Winifred W. Bean Professor of Medicine, Pharmacology, and Physiology, Mayo Clinic College of Medicine and Science; Consultant, William P. Cheshire, Jr., MD Division of Gastroenterology and Hepatology, Department of Medicine, Professor of Neurology, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, Minnesota Jacksonville, Florida Disorders of Gastrointestinal Motility Autonomic Disorders and Their Management Maria Domenica Cappellini, MD Arun Chockalingam, PhD Professor of Internal Medicine, Department of Clinical Sciences and Professor of Epidemiology, Medicine and Global Health, Dalla Lana School Community Health, University of Milan; and Ca’ Granda of Public Health, University of Toronto, Toronto, Ontario, Canada Foundation-Policlinico Hospital, Milan, Italy Global Health The Thalassemias David C. Christiani, MD Blase A. Carabello, MD Professor of Medicine, Harvard Medical School; Physician, Pulmonary and Professor of Cardiovascular Sciences and Chief, Division of Cardiology, Critical Care, Massachusetts General Hospital; Elkan Blout Professor of East Carolina University Brody School of Medicine, Greenville, North Environmental Genetics, Environmental Health, Harvard School of Carolina Public Health, Boston, Massachusetts Valvular Heart Disease Physical and Chemical Injuries of the Lung Edgar M. Carvalho, MD, PhD Edward Chu, MD, MMS Professor of Medicine, Federal University of Bahia, Oswaldo Cruz Professor and Chief, Division of Hematology-Oncology, Deputy Director, Foundation (Fiocruz), Instituto de Pesquisa Gonçalo Moniz (IGM), UPMC Hillman Cancer Center, University of Pittsburgh School of Salvador-Bahia, Brazil Medicine, Pittsburgh, Pennsylvania Trematode Infections Neoplasms of the Small and Large Intestine William H. Catherino, MD, PhD Theodore J. Cieslak, MD, MPH Professor and Chair-Research Division, Department of Obstetrics and Associate Professor of Epidemiology, Co-Medical Director, Nebraska Gynecology, Uniformed Services University of the Health Sciences, Biocontainment Unit, College of Public Health, University of Nebraska, Bethesda, Maryland Omaha, Nebraska Ovaries and Pubertal Development; Reproductive Endocrinology and Infertility Bioterrorism Jane A. Cauley, DrPH George A. Cioffi, MD Distinguished Professor of Epidemiology, Graduate School of Public Edward S. Harkness Professor and Chair, Jean and Richard Deems Health, University of Pittsburgh, Pittsburgh, Pennsylvania Professor of Ophthalmology, Columbia University Vagelos College of Epidemiology of Aging: Implications of an Aging Society Physicians and Surgeons, New York, New York Diseases of the Visual System Naga P. Chalasani, MD David W. Crabb Professor and Director, Division of Gastroenterology and Carolyn M. Clancy, MD Hepatology, Indiana University School of Medicine, Indianapolis, Clinical Associate Professor of Internal Medicine, George Washington Indiana University School of Medicine; Assistant Deputy Undersecretary for Alcoholic and Nonalcoholic Steatohepatitis Health, Quality, Safety and Value, Veterans Administration, Washington, D.C. Henry F. Chambers, MD Measuring Health and Health Care Professor of Medicine and Director, Clinical Research Services, Clinical Translational Science Institute, University of California, San Francisco, Heather E. Clauss, MD School of Medicine, San Francisco, California Associate Professor of Medicine, Section of Infectious Diseases, Lewis Katz Staphylococcal Infections School of Medicine at Temple University, Philadelphia, Pennsylvania Listeriosis Larry W. Chang, MD, MPH Associate Professor of Medicine, Epidemiology, and International Health, Daniel J. Clauw, MD Johns Hopkins University School of Medicine and Bloomberg School of Professor of Anesthesiology, Medicine (Rheumatology) and Psychiatry, Public Health, Baltimore, Maryland Director, Chronic Pain and Fatigue Research Center, University of Epidemiology and Diagnosis of Human Immunodeficiency Virus Infection and Michigan Medical School, Ann Arbor, Michigan Acquired Immunodeficiency Syndrome Fibromyalgia, Chronic Fatigue Syndrome, and Myofascial Pain David R. Clemmons, MD Kenan Professor of Medicine, University of North Carolina School of Medicine; Attending Physician, Medicine, UNC Hospitals, Chapel Hill, North Carolina Approach to the Patient with Endocrine Disease