`

`McGraw-Hill
`·\ /)11•1s,011 of 11,c McGm11••/Iill c ,,11,r,1111cs
`
`'tZ
`
`Note: Dr. Fauci and Dr. Longo 's works as editors and authors were
`performed outside the scope of their employment as U.S. government
`employees. These works represent their personal and professional
`views and not necessarily those of the U.S. govemmenl.
`
`Harrison's
`PRI'ICIPLES OF I'ITERNAL MEDICINE
`Fifteenth Edition
`
`Copyright © 2001. 1998, 1994. 1991, 1987, 1983, 1980, 1977, 1974, 1970, 1966,
`1962. 1958 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the
`United States of America. Except as penniued under the United States Copyright Act
`of 1976, no part of this publication may be reproduced or distributed in any fom1 or
`by any means, or stored in a data base or retrieval system. without the prior written
`pennission of the publisher.
`
`1234567890 DOWDOW 0987654321
`ISHN 0-07-007272-8 (Combo)
`0-07-007273-6 (Vol. I)
`0-07-007274-4 (Vol. 2)
`0-07-9 I 3686-9 (Set)
`
`FOREIGN LANGUAGE EDITIONS
`Arabic (Thirteenth Edition)- McGraw-Hill Libri Italia srl (est. 1996)
`Chinese (Twelfth Edition)-McGraw-Hill Book Company-Singapore© 1994
`C roatian (Thirteenth Edition)-Placebo, Split, Croatia
`French (Fourteenth Edition)-McGraw-Hill Publishing Co .. Maidenhead, UK© 1999
`German (Fourteenth Edition)-McGraw-llill Publishing Co., Maidenhead, UK © 1999
`Greek (Fourteenth Edition)- Parissianos, Athens, Greece © 2000
`Italian (Fourteenth Edition)- McGraw-llill Libri Italia srl, Milan © 1999
`Japanese (Eleventh Edition)- Hirokawa © 1991
`Polish (Fourteenth Edition)- Czclej Publishing Company, Lubin, Poland (est. 2000)
`Portuguese (Fourteenth Edition)-McGraw-llill lnteramericana do Brasil Ltda © 1998
`Romania (Fourteenth Edition)-Teora Publishers, Bucharest, Romania (est. 2000)
`Spanish (Fourteenth Edition)- McGraw-Hill lnteramericana de Espana, Madrid © 1998
`Turkish (Thirteenth Edition)- McGraw-1-lill Libri Italia srl (est. 1996)
`
`This book was set in Times Roman by Progressive lnfonnation Technologies. The
`editors were Martin Wonsiewicz and Mariapaz Ramos Engl is. The production director
`was Robert Lafller. The index was prepared by Irving C. Tullar. The text and cover
`designer was Marsha Cohen/Parallelogram Graphics.
`
`R. R. Donnelley and Sons, Inc. was the printer and binder.
`
`Library of Congress Cataloging-in-Publication Data
`
`Harrison's principles of internal medicine- I 5th ed./editors, Eugene Braunwald . . . [et al.].
`Includes bibliographical references and index.
`ISBN 0-07-913686-9 (set)- ISBN 0-07-007273-6 (v. 1)-
`I. Internal medicine. I. Braunwald, Eugene, date
`RC46.H333 2001
`616 dc21
`
`ISBN 0-07-0072744-4 (v. 2)
`
`p. cm.
`
`00-063809
`
`MPI EXHIBIT 1109 PAGE 2
`
`

`

`CONTENTS
`
`Contributors
`Preface
`
`xix
`xxxi
`
`SECTION 3
`NER\ OliS Svs·, E\I DYSFl.i~C"I 10"1
`
`Part One
`INTRODUCTION TO CLINICAL MEDICINE
`1 T he Practice of Medicine
`The Editors
`
`2 Ethical Issues in C linical Medicin e
`Bernard Lo
`
`3 Decision-Making in Clin ical Medicine
`Da11iel B. Mark
`
`4 Economic Issues in Clinical Medicine
`Daniel B. Mark
`
`5
`
`Influence of E nvironmental and Occupational
`Hazards on Disease
`Howard Hu I Frank E. Spei:er
`6 Women 's H ealth
`Anthony l. Komarojf I Celeste Robb-Nicholson I
`Andrea E. Dunaif
`
`7 Medical D isorders during Pregnancy
`Robert l. Barbieri I John T. Repke
`
`8 Adolescent H ealth Problems
`Me/1111 T. Da uani I C harles G .D. Brook
`9 Geriatric Medicine
`Neil M . Resnick
`10 Principles of Disease Prevention
`Maureen T.Connelly I Thomas S. l nui
`11 Alternative Medicin e
`Adria11e Fugh -Berman
`
`Part Two
`CARDINAL MANIFESTATIONS AND
`PRESENTATION OF DISEASES
`
`SECTION 1
`PAIN
`
`12 Pa in: Pathophysiology a nd Management
`Howard l . Fields I Joseph B. Martin
`13 Chest Discomfor t and Pa lpitations
`Thomas H. lee
`14 Abdominal Pa in
`William Si/en
`15 Headache, Includi ng M igraine
`and Cluster Headache
`Neil H. Raskin I Stephen J . Perowka
`16 Back a nd eek Pa in
`Joh11 W Engstrom
`
`5
`
`8
`
`14
`
`19
`
`21
`
`25
`
`31
`
`36
`
`46
`
`49
`
`55
`
`60
`
`67
`
`70
`
`79
`
`SECI ION 2
`Al, TERA1 IONS f"\/ BODY TEMPERATURE
`
`17 Fever and Hyperthermia
`Charles A. Di,wrello I Jeffrey A . Gelfand
`18 Fever and Ras h
`Elaine T. Kaye I Kenneth M . Kaye
`19 Approach to the Acutely Ill lnfecled Febrile Palicnt
`Tamar F. Bar/am I Dennis l. Kasper
`20 Hypothermia and Frostbite
`Dame/ F. Dan:/
`
`91
`
`95
`
`102
`
`107
`
`21 Faintness, Syncope, Dizziness, and Vertigo
`Robert B. Daroff I Mark D . Carlson
`22 Weakness, Mya lgias, Disorders of Movement,
`and Imbala nce
`Richard K. Olney I Michael J Aminoff
`23 Nu mbness, T ingling, and Sensor y Loss
`Arthur K. Asbury
`
`24 Acute Confusional Sta tes and Coma
`Allan H. Ropper
`
`25 Aphasias and Other Focal Cerebral Disorders
`M.-Marsel Mesulam
`26 Memory Loss and Dementia
`Thomas D. Bird
`27 Sleep Disorders
`Charles A. Czeisler I John W Winkelman I
`Gary S. Richardson
`
`SECTION 4
`D ISORDERS OF EYES, EARS, NOSE, A'.'ID THROAT
`
`28 Disorders of the Eye
`Jo11athan C. Horton
`29 Disorders of Smell, Taste, and Hearing
`Anil K. Lalwani I James 8. S11ow, Jr.
`Infections of the Upper Respiratory Tract
`Marlene Durand I Michael Joseph
`31 Oral Manifestations of Disease
`John S. Gree11spa11
`
`30
`
`SECTIO"\/ 5
`ALTERATIO"\/S IN CIRCULATORY A"\/0
`R ESPIRATORY FU1'CTIONS
`
`32 Dyspnea and Pulmonary Edema
`Rola11d fl. Ingram. Jr. I Eugene Braunwald
`33 Cough and Hemoptysis
`Ste1•e11 E. Weinberger I Eugene Bra umva/d
`34 Approach to the Patient with a Heart Murmur
`Patrick T. O"Gara I Eu.~ene Bra11111mld
`35 Approach to the Patient with Hypertension
`Gordon II. Williams
`36 Hypoxia and Cyanosis
`Eugene Braunwald
`37 Edema
`Eugene Braummld
`38 Shock
`Ronald V. Maier
`39 Cardiovascular Collapse, Cardiac Arrest,
`and Sudden Cardiac Death
`Ro/1ert J. Myerlmrg I Agustin Castellanos
`
`St<.,10, 6
`AL"llcRAl IO,s J', G.\SI ROI,._TEST1' \L Fl M .110,
`
`40 Dysphagia
`llaJ K. Goyal
`41 Nausea, Vomiting, and Indige~tion
`l\lillwm L. /las/er
`
`111
`
`119
`
`128
`
`132
`
`140
`
`148
`
`155
`
`164
`
`179
`
`187
`
`193
`
`199
`
`203
`
`207
`
`211
`
`214
`
`217
`
`222
`
`228
`
`233
`
`236
`
`MPI EXHIBIT 1109 PAGE 3
`
`

`

`X
`
`Content~
`
`Nohel l'riu i11 Physiology or Medicine , 1990
`I duard D{lllll(II/ 7 lwma•
`./o,Hph £dut11cl .\l1111tn
`
`Part Tltree
`GENETICS AND DISEASE
`65 Principles of Human Genetics
`J . Lari)' Jameson I Peter Kopp
`66 Ch romosome Disorders
`Terry llassold I Stuart Schwart:
`67 Diseases Caused by Genetic Defects
`of M itochond ria
`Donald R. Johns
`68 Screening, Counseling, a nd Pr evention of
`Genetic Disorders
`Susan Miesfeldt I J. Larry Jameson
`69 Gene T herapy
`Mark A . Kay I David W. Russell
`
`Nohel Prize i11 Physiology or Medicine, 1905
`Robe,t Ko,h
`
`Part Four
`CLINICAL PHARMACOLOGY
`70 Principles of Dr ug T hera py
`John A. Oa1es I Dan M. Roden I Gram R IV,Wnson
`71 Adverse Reactions to Drugs
`Alastair J J . Wood
`72 Physiology a nd Pha rmacology of the Autonomic
`Nervous System
`Lewis Landsberg I James B. Young
`
`374
`
`375
`
`396
`
`407
`
`412
`
`418
`
`419
`
`430
`
`438
`
`Part Five
`NUTRITION
`73 Nutritional Requirements a nd Dieta ry Assessment
`J ohanna Dwyer
`74 Malnutrition and Nutrit ional Assessment
`Charles fl. 1/alsted
`75 Vita min and T race M ineral Deficiency and Excess
`Robert M. R11Jsell
`76 E nteral a nd Parenteral utrition T her a py
`Lyn f/o,mrd
`77 Obesity
`Jeffrey S. Flier
`78 Eating Disorder s
`B. Timothy Walsh
`
`.isl
`
`.iss
`
`461
`
`470
`
`479
`
`"'86
`
`Part Six
`O~COLOGYANDHEMATOLOGY
`
`SEC 110'\ l
`1'EOPLASTIC DISORDERS
`
`43
`
`42 Diarrhea and Constipation
`Dm·id A Ahlqui.11 Mid1oel Cm111/len
`\\ eight Loss
`Carol M Reife
`44 Gastrointestinal Bleeding
`Loren Lmne
`45 Jaundice
`Daniel S Pro/I Marshall M. Kaplan
`46 Abdominal Swelling and Ascites
`Robert M. Glickman
`
`S1 .c110, 7
`ALTtRATlo,s" RE'\~I. \M) URJ'\AR\ TRAC T
`Ft '\CTIO'\'
`47 Azotemia and Urinary Abnormalities
`Bradley M. Denker I Bari) M. Brenner
`Incontinence and Louer Urinary Tract Symptoms
`Philippe E. Z1mmern I John D. McConnell
`49 F luid and Electrolyte Distur bances
`Gary G Singer Bari)· M. Brenner
`50 Acidosis and Alkalosis
`Thomas D. DuBose. Jr.
`
`48
`
`241
`
`250
`
`252
`
`255
`
`260
`
`262
`
`268
`
`271
`
`283
`
`SEC.TI0'\'8
`ALTERA I l0:--iS " SEXl AL FL1'C'I IO"i \!\D
`REPRODL CTION
`51 Erectile Dysfunction
`Kevm T. McVary
`52 Disturbances of Menstruation and Other Common
`Gynecologic Complaints in Women
`Bruce R. Carr I Koren D. Bradshaw
`53 Hirsut ism and Vir ilization
`Darid A. Ehrmann
`Infertilily a nd Fertility Control
`Janet E. Ila/I
`
`54
`
`Su f!O'\ 9
`Al.1 EIUTIO'\S 1, TIIE SKIN
`55 Approach to the Pa tient wilh a Skin Disorder
`Thomas J . Lawley I Kim B. Yancey
`56 Eczema, Psoriasis, C uta neous Infections, Acne,
`a nd Other Common Skin Disorder s
`Robert A . Swerlick I Thomas J . Lau1ey
`57 Skin M a nifesta tions of Internal Disease
`Jean L. Bolow1ia I /min M Brare,man
`Immu nologically Mediated S kin Diseases
`K1111 B. Yancey I Tlw11ws J um1,•y
`59 Cuta neous Drug Reactions
`Rober! S. Ste111 I 0/irier M Chosulow I Bruce U. \V11111011b
`60 Photoscnsiti, it} and Ot her Reactions to Light
`Dm id R Bider.,
`
`58
`
`s, ( " fl()'\ 10
`H I \I\ JOIOGI( Al I Fl<A f lO',S
`61 Anemia a nd Pol,l C) thcmia
`John IV Adamson I Dan L Ulll/iO
`62 Bleeding a nd T hrombosis
`Roh,•11 I Hant/111
`63 Enla rgement of the Lymph
`Patrick II 1/enry I Don L umgo
`6-J Di orders of G ran ulocytes a nd Monoc) le~
`Ste, en M /lo/land John I. Ga/1111
`
`'odes a nd Spleen
`
`291
`
`295
`
`297
`
`301
`
`305
`
`309
`
`315
`
`33 1
`
`336
`
`3-'2
`
`3-'8
`
`35-'
`
`360
`
`366
`
`80
`
`81
`
`82
`
`79
`
`Approach to the Patient with Cancer
`Dan L. umgo
`Prevention a nd Early Detection of Cancer
`Otis IV. Brawley I Barnell S Kramer
`Ca ncer Genetics
`Francis S. Collins I JefJrey M Tr,•111
`Cell Biolog) of Cancer
`Robert G Fe111011 I Dan L. Longo
`83 Angiogcn esis
`Judah Folkman
`
`-'91
`
`497
`
`503
`
`509
`
`517
`
`MPI EXHIBIT 1109 PAGE 4
`
`

`

`ContenL,
`
`85
`
`84 Principles of Cancer Treatment
`Edll'ord A. So11s1·ille I Dan l . lcngo
`Infections in Patients ,1 ith Cancer
`Robert Finberg
`86 Melanoma and Other Skin Cancers
`Arthur J Sober I Holl'ord K. Koh I Gregory P, Wittenberg I
`Corl \f. \\'osh111gton, Jr.
`87 Head and Neck Cancer
`E,·erm £. Vokes
`88 Neoplasms of the Lung
`John D. Minna
`
`89 Breast Cancer
`More E. Uppmon
`
`530
`
`547
`
`554
`
`559
`
`562
`
`571
`
`110 Polycythemia Vera and Other MyeloproliferatiH
`Diseases
`Jerry l. Spimk
`111 Acute and C hronic Myeloid Leukemia
`Meir \Vet=ler I John C /Jy,d I Cierra D. Bloomfield
`
`112 Malignancies of Lymphoid Cells
`Jomes 0. Armitage I Dan l . lcngo
`
`113 Plasma Cell Disorders
`Dan l . lcngo
`114 Transfusion Biology and Therapy
`Jeffery S. D:iec:koll'sk, I Kenneth C. Anderson
`115 Hone Marrow and Stem Cell Transplantation
`Frederick R. Appelbaum
`
`xi
`
`701
`
`706
`
`715
`
`727
`
`733
`
`739
`
`745
`
`751
`
`758
`
`761
`
`762
`
`763
`
`767
`
`775
`
`780
`
`793
`
`799
`
`804
`
`809
`
`8 17
`
`SECTIO-.. 3
`DISORDERS OF H E\10S1 ASIS
`
`116 Disorders of the Platelet and Vessel Wall
`Robert/. 1/andin
`117 Disorders of Coagulation and Thrombosis
`Robert I. flandrn
`118 Anticoagulant, Fibrinolytic, and Antiplatelet
`Therapy
`Robert I. 1/andin
`
`Nobel Pri:e itt Physiology or M edicine, 1930
`Karl lanc/<1m1er
`
`Nobel Prize i11 Physiology or Medicitt r, 1962
`Franc,s Harn Complon Crill, Jmm.•.\ Dt'un n·arson
`Maurice liu11lr Freder1< i \\ ilk111 1
`
`Part Se,·e11
`FECTIOUS DISEASES
`
`SECTIO'I l
`B \SIC Co-..sJOER\TIO"S 1" hFECTIOL'S OISF \SES
`
`ll9
`
`Int roduction to Infectious Diseases: Host-Parasite
`Interactions
`lall'rence C. Modoff Demus l. Kasper
`120 Molecular Mechanisms of Microbial Pathogenesis
`Gerald B. Pier
`121 Laboratory Diagnosis of Infectious Diseases
`Andrew 8. Onderdonk
`Jmmuniwtion Principles and Vaccine Use
`Gerald T. Ke11.1t-/1 I Kmnet/r J Bart
`Ilea Ith Advice for International Travel
`J.S Keystone P.£. Kown()
`
`122
`
`123
`
`Si,;n 10-.. .2
`CU',((. \I s, ,nR0\11::s: C0\1\IL -..11,-.\ ( Ql IRl:.0
`1-..~ u 110-..-.
`
`124 Sepsis a nd Septic Shock
`Roherr S \/1111forcl
`125 Fc,cr of Unkno"n Origin
`JefJrey A Gelfand
`lnfecti1 c Endocardilis
`Adolf W Kan/1111er
`Infectious omplications of Bites and Burns
`l,mreme C Madoj)
`
`126
`
`127
`
`578
`
`588
`
`591
`
`90 Gastrointestinal Tract Cancer
`Robert J. Moyer
`91 Tumors of the Liver and Biliary Tract
`Jules l. Dienstog I Kurt J. lsselbocher
`92 Pancreatic Cancer
`Robert J. Moyer
`93 Endocrine Tumors of the Gastrointestinal Tract
`and Pancreas
`Robert T. Jensen
`94 Bladder and Renal Cell Carcinomas
`Holl'ard I . Seirer I Robert J. Motzer
`95 Hyperplastic and Malignant Diseases of the Prostate 608
`Howard I. Scher
`96 Testicular Cancer
`Robert J. Motzer I George J. Bos/
`
`593
`
`604
`
`616
`
`97 Gynecologic Malignancies
`Robert C. Young
`98 Soft Tissue and Bone Sarcomas and Bone
`Metastases
`Slrreyaskumor R. Pote/ I Robert S. Benjonun
`99 Metastatic Cancer of Unknown Primary Site
`Richard M. Stone
`100 Paraneoplastic Syndromes
`Bruce E. Johnson
`101 Paraneoplastic eurologic Syndromes
`Muhammad T. Al-lczi I Alan Pestronk
`102 Oncologic Emergencies
`Rosim Gucolp I Janice Dutcher
`103 Late Consequences of Cancer and Its Treatment
`Mic/roe/ C. Perry I Dan l. lcngo
`
`620
`
`625
`
`628
`
`632
`
`636
`
`642
`
`650
`
`Su,7·10-.. 2
`DISORD~.RS Of' HF"1ATOPOll 'SIS
`
`104 Hematopoicsis
`Peter J. Q11esenberry I Gerold A Colvin
`105 Iron Deficiency and Other llypop roliferative
`Anemias
`John \V. Adamson
`106 Hcmoglobinopathies
`Edward J. Bem, Jr.
`107 Mcgaloblastic Anemias
`Btrnard M. Babior / II Fronk/in 8111111
`108 Hemolytic Anemias a nd Acute Blood Loss
`fl Franklin 8111111 I \Yendell Rosse
`109 Aplas tic Anemia, Myelodysplas ia, and Related Bone
`Marro" Failure Syndromes
`Nt ol S Young
`
`653
`
`660
`
`666
`
`674
`
`681
`
`692
`
`MPI EXHIBIT 1109 PAGE 5
`
`

`

`

`

`_ _ _ _ _ _ _ _ _ _ _ _ _.:C:::o:::";.:' •.:.:nl:2~ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ xiii
`
`173 Endemic Trcponemato~cs
`Sheila \ Lu~eharr
`174 Lcptospirosis
`Peter Speelman
`175 Relapsing Fever
`Da11d T Dennis Gram L. Camphell
`176 LJ me Borreliosis
`Allen C Steere
`
`S1Tno, 10
`RICJ.£1TSI I. M> COl'I 1S.111. \ ,o CIILA \tl'D/1
`
`177 Rickettsial Diseases
`Dand Walker I D,d,er Rao11l1 I J Srep/ren Dumler I
`Thomas Morrie
`178 Mycoplasma Infections
`William M McCormack
`179 Chlamydial Infections
`Walter£. Stamm
`
`SECTIO"\ 11
`VIRAL DISFASES
`
`180 Medical Virology
`Fred Wang I Ellio11 Kieff
`181 Antil'iral Chemotherapy, Excluding
`Antiretroviral Drugs
`Rap/roe/ Dolin
`
`SEC'! 10, 12
`D'\ \ VJRLSES
`
`182 Herpes Simplex Viruses
`Lawrence Corey
`183 Varicella-Zoster Virus Infections
`Richard J. Whitley
`184 Epstein-Barr Virus Infections, Including
`Infectious Mononucleosis
`Jeffrey I Cohen
`185 Cytomegalovirus and Human Herpesvirus
`Types 6, 7, and 8
`Marrin S. 1-/,rsc/r
`186 Smallpox, Vaccinia, and Other Poxviruses
`Fred Wang
`187 Parvovirus
`Ne,/ R Blacklo"
`188 Human Papilloma,iruscs
`Richard C. Re,c/rman
`
`SI-.( 1 JO'I 13
`DNA A'-D RNA RLSl'IIU10RY VmLSI-.S
`
`189 Common Viral Respiratory Infections
`Raphael Dolin
`Influenza
`Raphael Dol,n
`
`190
`
`SECTIO'I 14
`R"IA VrnLSFS
`
`191 The Human Retroviruses
`Am/rony S. Fauci I Dan L. Lbnga
`192 Viral Gastroenteritis
`I-Jarry B. Greenberg
`193 Entero, iruses and Reoviruses
`lrf/rt) I Cohen
`
`1053
`
`1055
`
`1058
`
`1061
`
`1065
`
`1073
`
`1075
`
`1084
`
`!092
`
`HOO
`
`JI06
`
`1109
`
`1115
`
`II 17
`
`1118
`
`11 20
`
`1125
`
`1131
`
`1138
`
`19-' Measles (Rubeola)
`\ 1111e Gershon
`195 Rubella (German Measles)
`Anne Gershon
`196 Mumps
`Anne Gershon
`197 Rabies Virus and Other Rhabdoviruses
`umrence Corey
`Infections Caused by Arthropod(cid:173)
`and Rodent-Borne Viruses
`CJ. Peters
`199 Filoviridae (Marburg and Ebola Viruses)
`CJ. Perers
`
`198
`
`Color Atlases/1168
`
`SFCIIO:-. 15
`FL"\G \I, \"\D ALGAL hFFLTIO'I/S
`
`200 Diagnosis and Treatment of Fungal Infections
`John £. Benne/I
`201 Histoplasmosis
`John £. Benne/I
`202 Coccidioidomycosis
`John £ . Benne/I
`203 Blastomycosis
`Jo/111 £ . Benne/I
`204 Cryptococcosis
`Jahn £ . Benne/I
`205 Candidiasis
`John £. Benne/I
`206 Aspergillosis
`John £ . Benne/I
`207 Mucormycosis
`John £. Benne/I
`208 Miscellaneous Mycoses and Algal Infections
`John £. Benne11
`209 P11e11111ocys1is cari11ii Infection
`Perer D IVal=er
`
`SECTIO'I/ 16
`l'IWTOZO \L "D HEL\11'\TIIIC 1'FFCTIO"\S:
`GF"\ER .\L co,slDt:R\TIO"\S
`
`210 Approach to the Patient uith Parasitic Infection
`l'eter f'. \Veller
`211 Laboratory Diagnosis of Parasitic Infections
`Charles £. Dm•is
`212 Therapy for Parasitic Infections
`Tho111111 A Moore
`
`S1cno, 17
`PROT0/0.\L 1'1 U 1 IO'<S
`
`213 Amebia~is and Infection,, ith Free-Li\ ing Amebas
`Sharan L. Reed
`214 Malaria and Babesiosb: Diseases Caused by
`Red Blood Cell Parasites
`Nidwlt1.1 J. \Vhue I Joel G Breman
`215 Leishmaniasis
`Bmbarn L 1/enmldt
`216 Tr) panosomiasis
`u1111.1 I K,rrMwh
`
`1143
`
`1145
`
`IJ47
`
`1149
`
`1152
`
`1166
`
`1168
`
`1171
`
`1172
`
`ll73
`
`117-'
`
`ll76
`
`1178
`
`1179
`
`1180
`
`1182
`
`1185
`
`1186
`
`LJ92
`
`1199
`
`1203
`
`1213
`
`121!1
`
`MPI EXHIBIT 1109 PAGE 7
`
`

`

`xiv
`
`Contents
`
`217 Toxoplasma Infection
`l/oyd H. Kmper
`218 Protozoa! Intestinal Infections and Trichomoniasis
`Peter F Weller
`
`1222
`
`1227
`
`SECTIO'- 18
`H El.\11', I lllC I:\FECTIO,s
`
`220
`
`219 Tricllinella and Other Tissue Nematodes
`Leo X. U11 I Peter F. Weller
`Intestinal Nematodes
`Peter F. Weller I Thomas B. Nmman
`221 Filariasis and Related Infections (Loiasis,
`Onchocerciasis, and Dracunculiasis)
`Thomas B. N11tman I Peter F. Weller
`222 Schistosomiasis and Other Trematode Infections
`Adel A.F. Moh111011d
`223 Cestodes
`A. Clinton W/nte. Jr. I Peter F. Weller
`
`Nobel Prize in Physiology or Medicine, 1945
`Alexander Fle111111g Holl'ard Florey £11111 Chain
`
`Part Eight
`DISORDERS OF T HE
`CARDIOVASCULAR SYSTEM
`
`SECTION J
`D IAG NOSIS
`
`1231
`
`1233
`
`1237
`
`1242
`
`1248
`
`1252
`
`1253
`
`224 Approach to the Patient with Heart Disease
`Eugene Braumvald
`225 Physica l Examination of the Cardiovascular System 1255
`Robert A. O'Rourke I Eugene Braunwald
`226 Electrocardiography
`Ary L. Goldberger
`227 Noninvasive Ca rdiac Imaging: Echocard iography
`and Nuclear Cardiology
`Rick A. Nishim11ra I Raymond J. Gibbons I A. Jamil Tajik
`228 Diagnostic Cardiac Catheterization
`and Angiography
`Donald S. Baim I William Grossman
`
`1262
`
`1271
`
`1277
`
`SF.CJ ION 2
`DISORDEUS OF RII YTII M
`
`229 T he Bradyarrhythmias: Disorders of Sinus Node
`Function and AV Condition Disturbances
`Mark E. Josephson I Peter Zimetba11m
`230 The Tachyarrhythmias
`Mark E. Josephson I Peter Z1metba11111
`
`SECTIOI\ 3
`DISORDERS OF 1 J IE IIEA RT
`
`231 Norma l a nd Abnormal Myocardial Function
`E11ge11e Braunll'ald
`232 Heart Failure
`E11gene Braw1ll'ald
`233 Cardiac Transplantation
`John S. Schroeder
`234 Congenital Heart Disease in the Ad ult
`William F Friedman I John S. Child
`235 Rheumatic Fever
`Ed><·ard L. Kaplan
`
`1283
`
`1292
`
`1309
`
`1318
`
`1329
`
`1331
`
`236 Valvu lar Heart Disease
`Eugene Braummld
`237 Cor Pulmona le
`Eugene Bra1111wald
`238 The Cardiomyopathies and Myocarditides
`Joshua Wynne I Eugene Braumvald
`239 Pericardia! Disease
`Eugene Braummld
`240 Cardiac Tumors, Cardiac Manifestations
`of Systemic Diseases, a nd T r a umatic
`Cardiac Injury
`Wilson S. Colucci I Daniel T. Price
`
`SECTION 4
`VASCULAR DISEASE
`
`241 The Pathogenesis of Atherosclerosis
`Peter Libby
`242 Prevention and Treatment of Atherosclerosis
`Peter Libby
`243 Acute Myocardial Infarction
`Elliott M. Antman I Eugene Braunwald
`
`244
`
`lschemic Heart Disease
`Andrew P. Selwyn I Eugene Braunwald
`245 Percutaneous Coronary Revascularization
`Donald S. Baim
`246 Hypertensive Vascular Disease
`Gordo11 H. Williams
`247 Diseases of the Aorta
`Victor J. Dzau I Mark A. Creager
`248 Vascular Diseases of the Extre mities
`Mark A. Creager I Victor J. Dzau
`
`Part Nine
`DISORDERS OF THE
`RESPIRATORY SYSTEM
`
`SECTION 1
`D IAGNOSIS
`
`249 Approach to the Patient with Disease
`of the Respira tory System
`Jeffrey M. Draze11 I Steven E. Wei11berger
`
`250 Disturbances of Respiratory Function
`Ste ven E. Wei11berger I Jeffrey M. Draze11
`251 Di agnostic Procedures in Respiratory Disease
`Steve11 £. Wei11berger I Jeffrey M. Drazen
`
`SECTION 2
`DISEASES OF T H E R ESPIR <\T O RY S YST EI\I
`
`252 Asthma
`E.R. McFadden, Jr.
`253 Hypersensitivity Pneumonilis a nd Pulmonary
`In-filtrates with Eosinophilia
`Joel N. Kline I Gary W. Hw111inglwke
`254 E nvironmental Lung Diseases
`Fra11k E. Speizer
`255 Pneumonia, Including ecrotiz ing Pulmonary
`Infections (Lung Abscess)
`Matthew E. Le1•ison
`
`256 Uronchiectasis
`Stel'en E. Weinberger
`
`1343
`
`1355
`
`1359
`
`1365
`
`1372
`
`1377
`
`1382
`
`1386
`
`1399
`
`1410
`
`1414
`
`1430
`
`1434
`
`1443
`
`1446
`
`1453
`
`1456
`
`1463
`
`1467
`
`l -'75
`
`1485
`
`MPI EXHIBIT 1109 PAGE 8
`
`

`

`Contents
`
`281 Urinary Tract Obstruction
`Julia11 L. Seifter I Barry M. Brenner
`
`Nobel Prize in Physiology or M edicine, 1956
`\Verna Tht1odor 0110 Fm.ummm
`-1,u/r,.. F1t•dcri< Cow11a11d
`/J1d 1mon Woudt 1,j) RIC /1em ls, J,
`
`Part Eleven
`DISORDERS OF THE
`GASTROINTESTINAL SYSTEM
`
`SECTION l
`DISOR0ERS OF THE ALIME:\TARY TRACT
`
`282 Approach to the Patient with
`Gastrointestinal Disease
`Daniel K. Podolsky I Kurt J. lsselbacher
`283 Gastrointestinal Endoscopy
`Mark Topa:ian
`284 Diseases of the Esophagus
`Raj K. Goyal
`285 Peptic Ulcer Disease and Related Disorders
`John Del Valle
`286 Disorders of Absorption
`Henry J. Binder
`Inflammatory Bowel Disease
`Sonia Fried111an I Richard S. Blumberg
`Irritable Bowel Syndrome
`Chung Owyang
`289 Diverticular, Vascular, and Other Disorders
`of the Intestine and Peritoneum
`Kurt J . lsselbacher I Alan Epstein
`
`287
`
`288
`
`290 Acute Intestinal Obstruction
`William Si/en
`291 Acute Appendicitis
`William Si/en
`
`SECTIO, 2
`LIVER \:,..1) BILIARY TRACT DISEASE
`
`xv
`
`1627
`
`1630
`
`1631
`
`1635
`
`1642
`
`1649
`
`1665
`
`1679
`
`1692
`
`1695
`
`1703
`
`1705
`
`257 C) stic Fibrosis
`Ricl,ard C Boucl,er
`
`258 C hronic Bronchitis, Emphysema, and Airways
`Obstruction
`Enc G. Honig Rolo11d H Ingram, Jr.
`Interstitial Lung Diseases
`Talmadge E. King. Jr.
`
`259
`
`260 Primary Pulmonary Hypertension
`Stuart Rich
`261 Pulmonary Thromboembolism
`Samuel z. Goldl,aber
`262 Disorders of the Pleura, Mediastinum,
`and Diaphragm
`Ricl,ard W. L1gi,1
`
`263 Disorders of Ventilation
`Eliot A. Phillipson
`264 Sleep Apnea
`Eliot A. Pl,illipson
`
`265 Acute Respiratory Distress Syndrome
`Marc Moss I Roland 1-1. lngra111. Jr.
`266 Mechanical Ventilatory Support
`Edward P. Ingenito I Jeffrey M. Drazen
`267 Lung Transplantation
`Janet R . Maurer
`
`Nobel Prize i11 Physiology or Medicine, 1985
`Midwel Stuart Bro".,,
`Iosep/, Leonard Golt/stem
`
`Part Te11
`DISORDERS OF THE KID EY
`AND URINARY TRACT
`268 Disturbances of Renal Function
`Robert M. Brenner I Barry M . Brenner
`269 Acute Renal Failure
`l-lugh R. Brady I Barry M . Brenner
`270 Chronic Renal Fail ure
`Karl Skorecki I Jacob Green I Barry M . Brenner
`271 Dialysis in the Treatment of Renal Failure
`Ajay K. Singh I Ban }' M . Brenner
`272 Transplantation in the Treatment of Renal Failure
`Cl,arles 8 . Carpenter I Edgar L. Milford I
`Mohamed II. Sayegh
`273 Pathogenesis of G lomerular Injury
`Hugh R. Brady I Barry M . Brenner
`274 The Major Glomerulopathies
`Hugh R Brady I Y,·onne M . o· Meara I Barry M. Brenner
`275 Glomerulopathics Associated with
`Multisystem Diseases
`Y\'On11e M O ' Meara / I fugl, R. Brady I /Jarry M . Brenner
`276 Hereditary Tubular Disorders
`John R. Asplin I Fredric L. Coe
`277 Tubulointersl itial Diseases of the Kidney
`Alan S L Yu I Barry M . Brenner
`278 Vascular Injury to the Kidney
`Ka111al F. Badr I Barry M Brenner
`279 Nephrolithiasis
`Jol,n R. Asplm I Fredric L. Coe I M urray J. Fa vus
`rinary Tract Infections and Pyelonephritis
`Walter E. Stamm
`
`280
`
`1487
`
`1491
`
`1499
`
`1506
`
`1508
`
`1513
`
`1517
`
`1520
`
`1523
`
`1526
`
`1531
`
`1534
`
`1535
`
`1541
`
`1551
`
`1562
`
`1567
`
`1572
`
`1580
`
`1590
`
`1598
`
`1606
`
`1610
`
`16 15
`
`1620
`
`292 Approach to the Patient with Liver Disease
`Marc Glu111y I Jay II. lloofnaglt'
`293 Eval uation of Liver Function
`Daniel S. Prau I Marshall M. Kaplan
`294 Bilirubin Metabolism and the Hyperbilirubinemias 1715
`Paul D. Berk I Allan \V. Wolkoff
`295 Acute Viral Hepatitis
`Jules l . Diemtag I Kull J. /s,e/bacher
`296 Toxic and Drug-Induced Hepatitis
`Jules L. Dienstag I Kurt J. lsse/bacher
`297 Chronic Hepatitis
`Jules L. Die11swg I Kurt J. l ssellJllcher
`298 Alcoholic Li,·er Disease
`Mad E. Mailliard I M1dwel F Sorrell
`299 C irrhosis and Its Complications
`Raymond T. Clu111g I Daniel K Podolsk-.,
`Infiltrative, Genetic, and Metabol ic Diseases
`Affecting the Liver
`Daniel K Podolsky
`30 1 Lh·er Transplantation
`J ulel L. Dien.HOK
`
`1707
`
`1711
`
`1721
`
`1737
`
`1742
`
`1752
`
`1754
`
`1767
`
`1770
`
`300
`
`MPI EXHIBIT 1109 PAGE 9
`
`

`

`xvi
`
`Conlents
`
`302 Diseases of the Gallbladder and Bile Ducts
`N orton J. Greenberger I Gustm• Pau11111artner
`
`SECTIO'\ 3
`DISORUFRS OF 'J Ill•, P \ ,cRK\S
`
`303 Approach to the Patient with Pancreatic Disease
`P/111/ip P. Toskes I Norro11 J. Greenberger
`304 Acute and Chronic Pancreatitis
`Norro11 J. Gree11ber11er I PJ,i//1p P . Toskes
`
`Part Twelve
`DISORDERS OF THE IMMUNE SYSTEM,
`CONNECTIVE TISSUE, AND JOINTS
`
`SECTION l
`DISORDERS OF THE }M\1UNE SYSTEM
`
`305
`
`Introduction to the Immune System
`Barton F. Haynes I A11tl,011y S. Fauci
`306 The Major Histocompatibility Gene Complex
`Gerald T. Nepom I J oel D . Taurog
`307 Autoimmunity and Autoimmune Diseases
`Peter E. Lipsky I Betty Diamond
`308 Primary Immune Deficiency Diseases
`Max D. Cooper I Harry W. Scl,roeder, Jr.
`309 Human Immunodeficiency Virus (HIV) Disease:
`AIDS and Related Disorders
`A nrl,011y S. Fauci I H. Clifford la11e
`
`SECTION 2
`DISORDERS OF l:\I\tlJNE- MEDIATED INJURY
`
`310 Allergies, Anaphylaxis, and Systemic Mastocytosis
`K . Frank Austen
`311 Systemic Lupus Erythematosus
`Bevra Hannal,s Ha/111
`312 Rheumatoid Arthritis
`Peter E. Lipsky
`313 Systemic Sclerosis (Scleroderma)
`Bruce C. Gilliland
`314 Sjogren's Syndrome
`Haralampos M. Mow sopoulos
`315 Ankylosing Spondylitis, Reactive Arthritis,
`and Undifferentiated Spondyloarthropathy
`Joel D. Taurog I Peter E. Lipsky
`
`316 Beh~et's Syndrome
`1/aralompos M. M outsopoulos
`317 The Vascu litis Syndromes
`A111/,011y S. Fauci
`318 Sarcoidosis
`R o11ald G . Crystal
`319 Amyloidosis
`Jean D. Sipe, Alan S. Cohen
`
`SECTIO'I 3
`DISORDERS OF THE JOINTS
`
`320 Approach to Articular and Musculoskclctal
`Disorders
`Jol,11 J . Cusl, I Peter£. Li1,sky
`321 Osteoart hritis
`Ke1111etl, D . Brandt
`322 Gout and Ot her Crystal Arthropathies
`A ntonio J . Re1!,i11ato
`
`1776
`
`1788
`
`1792
`
`1805
`
`1830
`
`1839
`
`1843
`
`1852
`
`1913
`
`1922
`
`1928
`
`1937
`
`1947
`
`1949
`
`1956
`
`1956
`
`1969
`
`1974
`
`1979
`
`1987
`
`1994
`
`323
`
`Infectious Arthritis
`Scarr J . Thaler I James Ii. Maguire
`324 Psoriatic Arthritis and Arthritis Associated
`with Gastrointestina l Disease
`Peter II. Schur
`325 Relapsing Polychondritis and Other Arthritides
`Bruce C. Gilliland
`326 Periarticular Disorders of the Extremities
`Bruce C. Gilliland
`
`1998
`
`2003
`
`2005
`
`2016
`
`Part Thirteen
`ENDOCRINOLOGY AND METABOLISM
`
`SECTION l
`ENDOCRl1'0LOGY
`
`327 Principles of Endocrinology
`J. Larry Jameson
`328 Disorders of the Anterior Pituitary
`and Hypothalamus
`S!,lomo Me/med
`329 Disorders of the Neurohypophysis
`Ga,y L. Robertso11
`330 Disorders of the Thyroid Gland
`J . Larry Jameson I A11thony P. Weetman
`331 Disorders of the Adrenal Cortex
`Gordon H. Williams I Robert G. Dluhy
`332 Pheochromocytoma
`Lewis Landsberg I James 8 . Young
`
`333 Diabetes Mellitus
`Alvin C. Powers
`334 Hypoglycemia
`Philip E. C,yer
`335 Disorders of the Testes
`James E. Griffin I Jean D. Wilson
`336 Disorders of the Ovary and Female
`Reproductive Tract
`Bruce R. Carr I Karen D. Bradshaw
`337 Endocrine Disorders of the Breast
`Jean D. Wilson
`338 Disorders of Sexual Differentiation
`Jean D. Wilson I James E . Griffin
`339 Disorders Affecting Multiple Endocrine System
`Steven I. S!,er111a11 I Robert F . Gagel
`
`SECTI ON 2
`0 1S01Wtms OF UO"IE AND M l"IERAL METABOLIS:\1
`
`340
`
`Introd uction to Bone and Mineral Metabolism
`Michael F. /-lolick I Stephen M . Krane
`341 Diseases of the Parathyroid Gland and Other
`Hyper- and 1-Iypocalcemic Disorders
`J o/111 T . Potrs , Jr.
`342 Os teoporosis
`Robert Lindsay I F elicia Cosman
`343 Paget's Disease and Other Dysplasias of Bone
`Stephen M . Krane I A lan L . Schiller
`
`SECTI0'-13
`DISORDERS OF l"ITERI\IEDli\RY MET \BOLIS\I
`
`3-t4 Disorders of Lipoprotein Metabolism
`/-le111y N . Ginsberg I Ira J Goldberg
`
`2019
`
`2029
`
`2052
`
`2060
`
`2084
`
`2105
`
`2109
`
`2138
`
`2143
`
`2154
`
`2168
`
`2172
`
`2184
`
`2192
`
`2205
`
`2226
`
`2237
`
`224S
`
`MPI EXHIBIT 1109 PAGE 10
`
`

`

`ContenL,
`
`345 Hemochromatosis
`Lo"rir \\ Po" ell Kurt J. ls.1elhac her
`346 The Porph) rias
`Rol,ert J Desm,·~
`347 Disorders of Purine and Pyrimidine Metabolism
`Rol>ert L. \\'ortma1111
`348 Wilson's Disease
`I lferbert Scl,emberfl
`349 Lysosomal Storage Diseases
`Gregon· A . GrahowsU
`350 GI) cogen Storage Diseases and Other Inherited
`Disorders of Carbohydrate Metabolism
`Y11a11-Tso11g Chen
`Inherited Disorders of Connective Tissue
`Darnm J. Prockop lfele11a K111m111emi I Gerard Tromp I
`Leena Ala-Kokko
`Inherited Disorders of Amino Acid Metabolism
`and Storage
`Nicolo Longo
`Inherited Defects of Membrane Transport
`Nicolo Longo
`354 The Lipodystrophies and Other Primary Disorders
`of Adipose Tissue
`Abl11mony11 Garg
`
`351
`
`352
`
`353
`
`Nobel Pri:e in Physiology or Medicine, 1923
`f , ,.J,.,.;d G 8 0111mg Jol,11 JR .\fuc/eod
`
`Part Fo11rtee11
`NEUROLOGIC DISORDERS
`
`SECTIO'- I
`DI \G'-OSIS OI '\FLROl,OGIC DtSORl>I RS
`
`355
`
`eurobiology of Disease
`Stephen L. lfouser I M . Flint Beal
`356 Approach to the Patient with Neurologic Disease
`Joseph B. Martin I Stephen L 1/ouur
`357 Electrophysiologic Studies of the Central a nd
`Peripheral Nervous Systems
`Michael J. Amino//
`358 Neuroimaging in eurologic Disorders
`Wi/1,am P. Dillon
`359 Molecular Diagnosis of Neurologic Disorders
`Joseph 8. Martin I Fran~ M. Lo11110
`
`St< I IO'- 2
`01\1 \SESOI 1111 CL:"I.IR\I '\LR\Ol',S,s11 :,1
`
`2257
`
`2261
`
`2268
`
`2274
`
`2276
`
`2281
`
`2290
`
`2301
`
`2309
`
`2316
`
`2320
`
`2321
`
`2326
`
`2331
`
`2337
`
`2342
`
`2354
`
`2369
`
`360 Seizu res and Epilepsy
`Domd II. Lo"·e1utei11
`361 Cerebrovascular Diseases
`Wade S. Smith / Stephen L. l/c111ur I J . Donald £mto11
`362 Alt heimer's Disease and Other Primary Dementias 2391
`Thomas D Bird
`363 Parkinson's Disease and Other Ext rapyramidal
`Disorders
`Micl,oel J. Aminofj
`364 Ata,ic Disorders
`Roger fl Rosenberg
`365 Amyotrophic Lateral Sclerosis a nd Other Motor
`Neuron Diseases
`Robert II. Bro11J1 , Jr
`
`2399
`
`2-106
`
`2-1 12
`
`366 Disorders of the Autonomic Nervous System
`Jol,11 IV Engstrom I Josr11h 8 Martin
`367 Common Disorders of the Cranial Nerves
`M. F/1111 Beal I Stephen L. /lamer
`368 Diseases of the Spinal Cord
`Stephen L. 1/auser
`369 Traumatic Injuries of the Head and Spine
`Allan fl. Ro11per
`370 Primary and Metastatic Tumors of the Nervous
`System
`Stephen M Sagar I Mark A. l.rrael
`371 Multiple Sclerosis and Other
`Demyelinating Diseases
`Stephen L. 1/auser I Donald£. Goodkin
`372 Bacterial Meningitis and Other Suppurative
`Infections
`Karen L. Roos I Kenneth L. Tyler
`373 Viral Meningitis and Encephalitis
`Kenneth L . Tyler
`374 Chronic and Recurrent Meningitis
`Walter J . Koroshetz I Morton N. Swart:
`375 Prion Diseases
`Stanley B. Prusiner I Patrtck Bosque
`376 Critical Care Neurology
`J. Claude Hempl,i/1 / M. Flim Beal I Daryl R. Gress
`
`SI·.CTIO'- 3
`DISOROL-RS OF '\~.RYE \'-I> \1l'SCLFS
`
`377 Approach to the Patient with Peripheral
`Neuropathy
`Arthur K. Asbury
`378 Guillain-Barre Syndrome and Other
`Immune-Mediated Neuropathies
`Arthur K. Asbury I Stephen L. Hauser
`379 Charcot-Marie-Tooth Disease and Other Inherited
`Neuropathies
`Phillip F. Chance I Thomas D. Bird
`380 Myasthenia Gravis and Other Diseases
`of the Neuromuscular Junction
`Daniel 8 . Dracl,man
`381 Approach to the Patient with Muscle Disease
`Jerry• R. Mendell
`382 Polymyositis, Dermatomyositis, and Inclusion
`Body Myositis
`Marinos C. Da/akl,s, Jr
`383 Muscular Dyslrophies and Other Muscle Diseases
`Robert II 8 ro1111, Jr. I Jerry R. Mendell
`
`SHII0'-4
`CIIRO'-H F \ I Ha ES\ '-ORO\IE
`
`384 Chron ic Fatigue Syndrome
`Stephen £ . Straus
`
`Sn 110'\' 5
`PS\ ( 111 \ I IHC DISORlll.RS
`
`385 Mental Di~orders
`\'/,tor I R,•111
`
`SI Cl 10'- (1
`\I ( OIIOI l'-\1 \ '\II l>Rl c; DI Pl. '-lll '\(,
`
`386
`
`lliolog) of Addiction
`Roh,·11 0
`\ /ewng
`
`xvii
`
`2416
`
`2421
`
`2425
`
`243-1
`
`2442
`
`2452
`
`2462
`
`2471
`
`2481
`
`2486
`
`2491
`
`2498
`
`2507
`
`2512
`
`2515
`
`2520
`
`252-1
`
`2529
`
`25-11
`
`2542
`
`2557
`
`MPI EXHIBIT 1109 PAGE 11
`
`

`

`X\ iii
`
`Conlcnl.S
`
`2561
`
`2567
`
`2570
`
`2574
`
`2577
`
`2578
`
`387 Alcohol and Alcoholism
`Marc A Schuc!..1t
`388 Opioid Drug Abuse and Dependence
`\fare A Schudit Darid S. Segal
`389 Cocaine and Orhcr Commonly