erlin Heidelberg Tokyo
`
`Ex. 1073 - Page 1
`
`Ex. 1073 - Page 1
`
`

`

`4 c
`
`e
`
`Tens',"
`
`(guanabenz acetate)
`Antihypertensive therapy
`that does not increase cholesterol
`
`Brief Summary
`Before prescribing, consult the complete package circular.
`Indication' and Usage: Treatment of hypertension, alone or in combination with
`a thiazide diuretic.
`Contraindication: Known sensitivity to the drug.
`Precautions, 1. Sedation: Causes sedation or drowsiness in a large fraction of pa.
`tients. When used with centrally active depressants, e.g.. phenothiazines, barbitu•
`rates and benzodiazepines. consider potential for additive sedative effects. 2.
`Patients with vascular insufficiency: Like other antihypertensives use with caution
`in severe coronary insufficiency, recent myocardial infarction, cerebrovascular dis.
`ease, or severe hepatic or renal failure. 3. Rebound, Sudden cessation of therapy
`with central alpha agonists like Wytensin may rarely result in 'overshoot" hyper.
`tension and more commonly produces increase in serum catecholamines and sub-
`jective symptomatology.
`INFORMATION FOR PATIENTS. Advise patients on Wytensin to exercise caution
`when operating dangerous machinery or motor vehicles until it is determined they
`do not become drowsy or dizzy Warn patients that tolerance for alcohol and other
`CNS depressants may be diminished. Advise patients not to discontinue therapy
`abruptly
`LAB TESTS In clinical trials. no clinically significant lab test abnormalities were
`identified during acute or chronic therapy. Tests included CBC, urinalysis, electro-
`lytes.SGOT, bilirubin, alkaline phosphatase, uric acid. BUN. creatininewlucose. cal.
`cium. phosphorus, total protein, and Coombs' test. During longterm use there was
`Man decrease in serum cholesterol and total triglycerides without change in high.
`density lipoprotein fraction. In rare instances occasional nonprogressive increase
`in liver enzymes was observed, but no clinical evidence of hepatic disease.
`DRUG INTERACTIONS Wytensin was not demonstrated to cause drug interactions
`when given with other drugs, e.g., digitalis, diuretics, analgesics. anxiolytics, and
`antiinflammatory or antiinfective agents, in clinical trials However. potential for in.
`creased sedation when given concomitantly with CNSdepressants should be noted.
`DRUG/LAB TEST INTERACTIONS: No lab test abnormalities were identified with
`Wylensia use.
`CARCINOGENESIS, MUTAGENESIS. IMPAIRMENT OF FERTILITY No evidence of
`carcinogenic potential emerged in rats during, two.year oral study with Wytensin
`at up to 9.5 mg/ kgday. i.e . about 10 times maximum recommended human dose. In
`the Salmonella microsomc mutagenicity (Ames) test system. Wytensin at 200.500
`mcg perplate or at 3050 mcwml in suspension gave dose.related increases in num.
`bet of mutants in one (TA 153') of five Salmonella typhimrium strains with or
`without inclusion of rat liver microsomes. No mutagenic activity was seen at doses
`up to those which inhibit growth in the eukaryotic microorganism, Scbizosaczbar•
`otnyas pontbe or in Chinese hamster ovary cells at doses up to those lethal to the
`cells in culture. In another eukaryotic system, Saccharottures cerevisiar,
`Wylensin produced no activity in an assay measuring induction of repairable DNA
`damage.Reproductive studies showed adecreased pregnancy rate in ratsgiven high
`oral doses (9 .6 mg/kg ). suggesting impairment of fertility. Fend ity of treated males
`( 9 6 mgig ) may also have been affected, as suggested by decreased pregnancy rate
`of mates, even though females received drug only during last third of pregnancy.
`PREGNANCY Pregnancy Category C. WYTENSINs MAY HAVE ADVERSE EFFECTS
`ON FETUS WHEN ADMINISTERED TO PREGNANT WOMEN. A teratology study in
`mice indicated possible increase in skeletal abnormalities when Wytensin is given
`orally at doses 3 to 6 times maximum recommended human dose of 1 0 rngtg.
`These abnormalities. principally costal and vertebral, were not noted in similar
`studies in rats and rabbits. However. increased fetal loss has been observed after
`oral Wysensin given to pregnant rats ( 14 mpikg ) and rabbits ( 20 mtzkg ). Repro-
`ductive studies in rats have shown slightly decreased livehirth indices. decreased
`fetal survival rate and decreased pup body weight at oral doses of 6.4 and 9.6 mw
`kg. There are no adequate. well.controlled studies in pregnant women. Wysensin
`should be used during pregnancy only if potential benefit justifies potential risk to
`fetus.
`
`NURSING MOTHERS: Because no information is available on Wysensin excretion
`in human milk, it should not be given to nursing mothers.
`PEDIATRIC USE. Safety and effectiveness in children less than 12 years of age have
`not been demonstrated. use in this age group cannot be recommended.
`Adverse Reactions: Incidence of adverse effects was ascertained from controlled
`clinical studies in U.S. and is based on data from 869 patients on Wytensin for up
`to 3 years. There is some evidence that side effects are dose-related. Following table
`shows incidence of adverse effects in at least 5% of patients in study comparing
`Wytensin to placebo. at starting dose of 8 mg b.i.d.
`
`Adverse Effect
`
`Dry mouth
`Drowsiness or
`sedation (cid:9)
`Dizziness
`Weakness (cid:9)
`Headache (cid:9)
`
`Placebo (%
`n= 102
`
`Wytensin (%
`n= 109
`
`28
`
`39
`
`10
`
`12
`
`6
`
`In other controlled clinical trials at starting dose of 16 mwday in 4'6 patients, in.
`cidence of dry mouth was slightly higher ( 38% I and dizziness was slightly lower
`(12% ), but incidence of most frequent adverse effects was similar to pluebo-con-
`trol led trial Although these side effects were not serious. they led to discontinua..
`bon of treatment about 15% of the time. In more recent studies using an initial dose
`of 8 mgiday in 2,4 patients, incidence of drowsiness or sedation was lower, about
`20% Other adverse effects reported during clinical trials but not clearly dist in-
`guishable from placebo effects and occurring with frequency of 3% or less: Car-
`diovascular—chest pain. edema, arrhythmias. palpitation, Gastrointestinal —
`nausea. epigastric pain. diarrhea. vomiting, constipation. abdominal discomfort.
`Central nervous system—anxiety, ataxia. depression, sleep disturbances. ENT dis-
`orders—nasal congestion. Eye disorders—blurring of vision. Musculoskeletal—
`aches in extremities, muscle ache, Respiratory—dyspnea. Dermatologic—rash,
`pruritus. Urogenital—urinary frequeuy,disturbances of sexual function. Other—
`gynecomastia. taste disorders.
`Drug Abuse and Dependence: No dependence or abuse has been reported.
`Cherdosage:Accidental ingestion caused hypotension,somnoleacciethargy,irrit.
`ability, nuosis, and bradycardia in two children aged one and three years. Gastric
`lavage and pressor substances, fluids, and oral activated charcoal resulted in corn
`pick and uneventful recovery within 12 hours in both. Since experience with ac-
`cidental overdosage isl imi led, suggested treatment is mainly supportive while drug
`is being eliminated and until patient is no longer symptomatic Vital signs and fluid
`balance should be carefully monitored. Adequate airway should be maintained and,
`if indicated. assisted respiration instituted. No data are available on Wytenakt
`dialytability
`Dosage and Administration: Individualize dosage. A starting dose of f mg hi.d.
`is recommended, whether used alone or with a thiazide diuretic. Dosage may be
`increased in increments of 4 to 8 nigiday every one to two weeks, depending on
`response. Maximum dose studied has been 32 mg hi.d., but doses this high are
`rarely needed.
`How Supplied: lguaivabena. acetate) Tablets, 4 mp, honks of 10(1 and SOD. 8 mg and
`16 nip, bottles of MO. (cid:9)
`Revised /Th/85
`Wyeth Laboratories
`Philadelphia. Pa 19101
`
`• 1984, Wyeth Laboratories.
`
`iX
`
`~ tii j
`
`
`'171
`
`Specialty Review in Nephrology
`starts September 22, 1986
`
`ur practice
`is limited o
`CME
`N'19 Mall 1)011-Free 24 Hours
`o S00-621-4651
`
`By limiting your practice to Nephrology, you provide your
`patients with the expertise that comes with specialization.
`Likewise, our specialization has made us the experts in CME.
`Discover why your colleagues have placed their confidence in
`us. Discover The Graduate School — Your CME Specialist.
`
`THE ODUNTY
`GRADUATE
`SCHUDL MEDICINE
`Your CME Specialist
`
`Call toll-free
`in Illinois
`1-800-621-4649
`or write to us at
`707 South Wood
`Chicago, IL 60612
`
`KIDNEY FOUNDATION
`RESEARCH FELLOWSHIPS
`ALBERTA CANADA 1987-1988
`
`Applicants invited for Postdoctoral Medical Fellowships
`in Nephrology or Urology to run concurrently from July
`1, 1987 at the University of Alberta, Edmonton and the
`University of Calgary (Faculty of Medicine).
`
`Interdisciplinary training in basic research and/or clini-
`cal investigation available. Programs provide opportun-
`ity for full enrollment in School or Graduate Studies.
`
`Salary and benefits commensurate with qualifications
`and prior training (CMRC Canada guidelines) to maxi-
`mum $35,000.00 per annum.
`Fellowship is for one year but second year application
`anticipated. For application forms contact:
`
`Kidney Foundation of Canada
`Alberta Branch
`11636-149 Street
`Edmonton, Alberta
`T5M 3R3
`APPLICATIONS POSTMARKED AFTER JUNE 30, 1986
`WILL NOT BE ACCEPTED
`
`Ex. 107
`
`Ex. 1073 - Page 2
`
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`

`

`WyTensin
`
`(guanabenz acetate)
`Antihypertensive therapy
`that does not increase cholesterol
`
`Brief Summary
`Before prescribing, consult the complete package circular.
`Indications and Usage: Treatment of hypertension, alone or in combination with
`Ihlinde diuretic
`Contraindication: Known sensitivity to the drug.
`nteCaU9005: I Sedation, Causes sedation or drowsiness in a large fraction of pa.
`new When used with centrally active depressants, e.g., phenothiazines, barbitu.
`rates and benzodiszepines. consider potential for additive sedative effects 2
`patients with vascular insufficiency: Like other antihypertensives use with caution
`in severecoronary insufficiency, recent myocardial infarction. cerebrovascular dis.
`case, or severe hepatic or renal failure 3 Rebound. Sudden cessation of therapy
`with central alpha agonists like Wytensla may rarely result in 'overshoot- hyper,
`tension and more commonly produces increase in scrum catecholamines and sub-
`jective syniptomatology.
`INFORMATION FOR PATIENTS Advise patients on Wytensin to exercise caution
`when operating dangerous machinery or motor vehicles until it isdetermined they
`do not become drowsy or dizzy. Warn patients that tolerance for alcohol and other
`CNS depressants may be diminished. Advise patients not to discontinue therapy
`abruptly
`LAB TESTS: In clinical trials, no clinically significant lab test abnormalities were
`identified during acute or chronic therapy Tests included CBC. urinalysis, electro.
`htes.SGOT. bilirubin, alkaline phosphatase. uric acid, BUN. creatinine. glucose, cal.
`cium, phosphorus, total protein, and Coombs' test. During long-term use there was
`small decrease in serum cholesterol and total triglycerides without change in high.
`density lipoprotein fraction. In rare instances occasional rionprogressive increase
`in liver enzymes was observed, but no clinical evidence of hepatic disease.
`DRUG INTERACTIONS. Wytensin was not demonstrated to cause drug interactions
`when given with other drugs, e.g.. digitalis, diuretics, analgesics. ansiolytics, and
`antiintlammatory or antiinfective agents. in clinical trials. However. potential for in,
`creased sedation when given concomitantly with CNSdepressants should be noted
`DRUG LAB TEST INTERACTIONS, No lab test abnormalities were identified with
`Wytensin use
`CARCINOGENESIS. MUTAGENESIS. IMPAIRMENT OF FERTILITY. No evidence of
`carcinogenic potential emerged in rats during a two-year oral study with Wytensin
`at up to 9.5 mg/kgrday. Le. . about 10 times maximum recommended human dose. In
`the Salmonella microsome mutagenicity ( Ames) test system. Wytensin at 200500
`mem plate or at 30.30 mcgml in suspension gave dose.related increases in nun,
`her of mutants in one ( TA 153' 1 of five Salmonella typhimurium strains with or
`without inclusion drat liver microsomes. No mutagenic activity was seen at doses
`up to those which inhibit growth in the eukaryotic microorganism. Scbieosaccbar•
`ornyrespombe or in Chinese hamster ovary cells at doses up to those lethal to the
`cells in culture In another eukar yotic system. Sarcbaromyces cerevistae.
`Wytensin produced no activity in an assay measuring induction of repairable DNA
`damage Reproductive studies showed a decreased pregnancy rate in ratsgiven high
`oral doses(9.6
` mizikg ). suggesting impairment of fertility. Fertility of treated males
`19 6 mg,kg Imay also have been affected. as suggested by decreased pregnancy rate
`of mates, even though females received drug only during last third of pregnancy
`PREGNANCY. Pregnancy Category C. WYTENSINs MAY HAVE ADVERSE EFFECTS
`ON FETUS WHEN ADMINISTERED TO PREGNANT WOMEN. A teratology study in
`mice indicated possible increase in skeletal abnormalities when Wytensin is given
`orally at doses 3 to 6 times maximum recommended human dose of 1 0 mg/kg.
`These abnormalities. principally costal and vertebral, were not noted in similar
`studies in rats and rabbits. However, increased fetal loss has been observed after
`oral Wytensin given to pregnant rats ( 14 mg'kg ) and rabbits (20 ing,kg I Repro,
`ductive studies in rats have shown slightly decreased live.birth indices, decreased
`fetal survival rate. and decreased pup body weight at oral doses of 6 4 and 9.6 mg
`kg. There are no adequate, wencontrolled studies in pregnant women Wytensin
`should be used during pregnancy only if potential benefit justifies potential risk to
`fetus
`
`NURSING MOTHERS: Because no information is available on Wytensin excretion
`in human milk, it should not be given to nursing mothers.
`PEDIATRIC USE Safety and effectiveness in children less than 12 years of age have
`vol been demonstrated, use in this age group cannot be recommended.
`Adverse Reactions: Incidence of adverse effects was ascertained from controlled
`clinical studies in U S and is based on data from 859 patients on Wytensin for up
`o 3years There is some evidence that side effects are dose.related Following table
`shows incidence of adverse effects in at least 5% of patients in study comparing
`Wytensin to placebo, at starting dose of 8 mg b id
`
`Adverse Effect
`Dry mouth (cid:9)
`Drowsiness or
`sedation (cid:9)
`Dizziness
`Weakness (cid:9)
`Headache (cid:9)
`
`Placebo 1% 1 (cid:9)
`= 102 (cid:9)
`
`Wytensin ( %
`n= 109
`
`28
`
`39
`
`10
`
`12
`
`6
`
`In other controlled clinical trials at starting dose of 46 mg/day in 4'6 patients. in,
`cidence of dry mouth was slightly higher ( 38% I and dizziness was slightly lower
`(12% ). but incidence of most frequent adverse effects was similar to placcbo.con,
`trolled trial. Although these side effects were not serious, they led to discontinue'
`bon of treatment about IVA of the time. In more recent studies using an initial dose
`of 8 my/day in 2'4 patients, incidence of drowsiness or sedation was lower, about
`20% Other adverse effects reported during clinical trials but not clearly distin-
`guishable from placebo effects and occurring with frequency of 3% or less. Car.
`diovascular—chest pain, edema, arrhythmias. palpitations Gastrointestinal—
`nausea. epigastric pain, diarrhea. vomiting, constipation, abdominal discomfort.
`Central nervous system—anxiety. ataxia, depression. sleep disturbances. ENT die,
`orders—nasal congestion Eyc disorders—blurring of vision Musculoskeletal—
`aches in extremities. muscle aches. Respiratory—dyspnn Dermatologic—rash.
`pruritus Urogenital—urinary frequency. disturbances of sexual function. Other—
`gynecomasto. taste disorders
`Drug Abuse and Dependence: No dependence or abuse has been reported.
`Overdesagckcidental ingestion caused hypotension, somnolence, lethargy, irrit•
`ability. rniosis. and bradycardia in two children aged one and three years. Gastric
`lavage and pressor substances Rinds, and oral activated charcoal resulted in corn.
`plete and uneventful recovery within 12 hours in both. Since experience with ac-
`cidental overdmage is limited, suggested treatment is mainly supportivewhile drug
`mixing eliminated and until patient is no longer symptomatic Vital signs and Enid
`balance should be carefully monitored. Adequate airway should be maintained and,
`if indicated, assisted respiration instituted. No data are available on Wytensin
`dialyzability
`
`Dosage and Administration: Individualize dosage. A starting dose of 4 mg h i.d
`is recommended, whether used alone or with a thiazide diuretic Dosage may be
`increased in increments of 4 to 8 mgiday every one to two weeks, depending on
`response Maximum dose studied has been 32 mg (cid:9)
`but doses this high are
`rarely needed.
`
`Ho. Supplied: I guarrabem acetate) Tablets, 4 mp, bottles of 1101 and SOO: 8 mg and
`Hi ink, Mildly of 100. (cid:9)
`Revised 2/14/85
`Wyeth Laboratories
`PhdadelpNa Pa 19101
`
`019144. Wyeth laboratories.
`
`Specialty Review in Nephrology
`starts September 22, 1986
`
`Our practice
`is limited to
`CME
`11-Free 24 Hours
`GHT 0:1-800-621-4651
`
`Call (cid:9)
`
`By limiting your practice to Nephrology, you provide your
`patients with the expertise that comes with specialization.
`Likewise, our specialization has made us the experts in CME.
`Discover why your colleagues have placed their confidence in
`us. Discover The Graduate School — Your CME Specialist.
`
`THEE
`GRADUATE
`SCHCOL MEDICINE
`Your CME Specialist
`
`Call toll-free
`in Illinois
`1-800-621-4649
`or write to us at
`707 South Wood
`Chicago, IL 60612
`
`KIDNEY FOUNDATION
`RESEARCH FELLOWSHIPS
`ALBERTA CANADA 1987-1988
`
`Applicants invited for Postdoctoral Medical Fellowships
`in Nephrology or Urology to run concurrently from July
`1, 1987 at the University of Alberta, Edmonton and the
`University of Calgary (Faculty of Medicine).
`
`Interdisciplinary training in basic research and/or clini-
`cal investigation available. Programs provide opportun-
`ity for full enrollment in School or Graduate Studies.
`
`Salary and benefits commensurate with qualifications
`and prior training (CMRC Canada guidelines) to maxi-
`mum $35,000.00 per annum.
`Fellowship is for one year but second year application
`anticipated. For application forms contact:
`
`Kidney Foundation of Canada
`Alberta Branch
`11636-149 Street
`Edmonton, Alberta
`T5M 3R3
`APPLICATIONS POSTMARKED AFTER JUNE 30, 1986
`WILL NOT BE ACCEPTED
`
`Ex. 1073 - Page 3
`
`Ex. 1073 - Page 3
`
`(cid:9)
`

`

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`Published June 1986 (cid:9)
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`Printed in the United States. Second-class postage paid at New York, NY and additional mailing offices.
`
`ISSN 0085-2538
`
`1 (cid:9)
`
`1
`
`e (cid:9)
`
`•
`
`DESCI
`rnonob
`Eacn
`mg of a
`INDICT
`and ph'
`mende
`CONTI
`struvite
`oral), of
`PRECI
`Genes
`aUon c
`e eff
`degree
`of this r
`Duke
`diseasr
`acute r
`ease. a
`arrhos
`hypertt
`and ncl
`Inform
`therapy
`the use
`son of r
`Labore
`phorus
`Other
`phate
`
`lOWA—TF
`Division, [
`in nephrol
`transplant
`Eligibility
`tional trai
`plant imr
`abilities e
`cine.
`interest a
`applicant
`ical activi
`on the ac
`cations
`curricula
`Director,
`cine, E-3
`The Uni•
`
`IOWA_
`Sion, De
`of Dialy;
`bility in
`adminis
`includin
`The ap,
`indeper
`in teach
`will be I
`curricul
`Direct()
`nine, E.
`The Ur
`
`Ex. 1073 - Page 4
`
`Ex. 1073 - Page 4
`
`

`

`KIDNEY INTERNATIONAL
`
`Volume 29, Number 6, June 1986
`
`Official Journal of the International Society of Nephrology
`
`Le Journal de la Societe Internationale de Nephrologie
`
`Table of contents
`
`EDITORIAL REVIEW
`The regulation of renal acid secretion: New observations from studies of distal nephron segments.
`David Z. Levine and Harry R. Jacobson
`LABORATORY INVESTIGATION
`Increased urinary excretion of PGE2 during inappropriate antidiuresis induced by DDAVP.
`Patricia A. Craven, Joseph G. Verbalis, and Frederick R. DeRubertis (cid:9)
` 1110
`Accelerated renal cyst development in deconditioned germ-free rats. Kenneth D. Gardner, Jr (cid:9) ,
` 1116
`Andrew P. Evan, and William P. Reed (cid:9)
`Compensatory renal growth: Modulation by calcium PTH and 1,25-(OH)2D3. Jacques R. Jobin
` 1124
`and J. P. Bonjour (cid:9)
`Phosphate binding gels: Balancing phosphate adsorption and aluminum toxicity. Elizabeth A.
` 1131
`Larson, Stephen R. Ash, Joe L. White, and Stanley L. Hem (cid:9)
`Protein synthesis and degradation in skeletal muscle of chronically uremic rats. Jeanne B. Li and
` 1136
`Steven J. Wassner (cid:9)
`Canine chronic renal disease: Prevalence and types of glomerulonephritis in the dog. Dugald F.
` 1144
`Macdougal, Terence Cook, Adrian P. Steward, and Victoria Cattell (cid:9)
`Humoral control of water and electrolyte excretion during water restriction. David C. Merrill,
` 1152
`Meredith M. Skelton, and Allen W. Cowley Jr. (cid:9)
`Hypothyroidism protects against free radical damage in ischemic acute renal failure. Mark S.
` 1162
`Paller with the technical assistance of Joseph J. Sikora (cid:9)
`Acidification in the medullary collecting duct following ureteral obstruction. Carla Ribeiro and
` 1167
`Wadi N. Suki (cid:9)
`Nephron segment and calcium as determinants of anoxic cell death in renal cultures. Patricia D.
` 1172
`Wilson and Robert W. Schrier (cid:9)
`CLINICAL INVESTIGATION
`Side effects of cyclosporin A treatment in patients with rheumatoid arthritis. Knut Joachim Berg,
`OYstein Fore, Frithjof Bjerkhoel, Egil Amundsen, Ole DjOseland, Hans Erik Rugstad, and BjOrn
`131a
`
`Modulation of
` ... and platelet .. asopre . ... by cardiac function in patients with heart failure.
`Daniel G. Bichet, Claude Kortas, Bertrand Mettauer, Christiane Manzini, Julien Marc-Aurele,
`
`Jean-Lucien Rouleau, and Robert W. Schrier (cid:9)
`Sodium transport in red blood cells from dialyzed uremic patients. Dalila B. Corry, Michael L.
`Tuck, Arnold S. Brickman, Norimoto Yanagawa, and David B. N. Lee (cid:9)
`
`Guanabenz: A centrally acting, natriuretic antihypertensive drug. Marc Gehr, E. Paul MacCarthy,
`
`1099
`
`1180
`
`1188
`
`1197
`
`1203
`
`and Martin Goldberg ******************************************************************
`Impaired cellular immune responses in chronic renal failure: Evidence for a T cell defect. Peter
`Kurz, Hans Kohler, Stephan Meuer,Thomas Hi,itteroth, and Karl-Hermann Meyer zum
`BAtidsucith_oennfeseldt em ******* * ** ****** n.
`
`-term follow-up. Fernando o (cid:9)
`****** ***** i;g
`Cameron, E.F. Heywood, Jackie Hicks, Chisholm Ogg, and D. Gwyn Williams
`Contents continued on next page
`
`* J.
`
`
`Stewart
`
`1209
`
`1215
`
`•
`
`• •
`
`0
`
`•
`
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`4 0
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`• • •
`
`0 1,
`
`'13 '74
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`
`of
`
`C).'t‘
`
`•
`
`Ex. 1073 - Page 5
`
`Ex. 1073 - Page 5
`
`(cid:9)
`

`

`continued
`Contents continued
`Serum and urinary high density lipoproteins in glomerular disease with proteinuria. Colin D.
`Short, Paul N. Durrington, Netar P. Mallick, Linda P. Hunt, Lesley Tetlow, and Monica Ishola . .
`IgA synthesis by lymphocytes from patients with IgA nephropathy and their relatives. F. Bryson
`Waldo, Linda Beischel, and Clark D. West (cid:9)
`
`TECHNICAL NOTE
`Renin—containing cells in kidney transplants into the anterior eye chamber. Marco R. Celio (cid:9)
`NEPHROLOGY FORUM
`Hospital—associated hyponatremia. Robert J. Anderson (cid:9)
`ABSTRACT
`17. Kongress der Gesellschaft fiir Nephrologie (cid:9)
`INTERNATIONAL SOCIETY OF NEPHROLOGY
`Announcements (cid:9)
`Awards and Grants (cid:9)
`REFEREES (cid:9)
`INDEXES TO VOLUME 29
`
`
`
`
`
`
`
`
`
`
`
`•
`
`1224
`
`1229
`
`1234
`
`1237
`
`1248
`
`1265
`1268
`1270
`
`For a B1
`
`Ex. 1073 - Page 6
`
`

`

`•
`
`•
`
`A
`
`o
`
`1,9 7
`
`S • •
`
`rte.
`
`0
`°
`
`•
`
`A
`
`Kidney International, Vol. 29 (1986), pp. 1180-1187
`
`Renal side effects of CyA in arthritis (cid:9)
`
`1181
`
`CLINICAL INVESTIGATION
`
`Table 1. Individual renal function tests for the cyclosporine treated patients before (C-0), after 26 weeks of treatment (N = 11), and nine
`months after treatment (C-II) (N = 7)
`
`Side effects of cyclosporin A treatment in patients with
`rheumatoid arthritis
`
`KNUT JOACHIM BERG, OYSTEIN FORRE, FRITHJOF BJERKHOEL, EGIL AMUNDSEN,
`OLE DJOSELAND, HANS ERIK RUGSTAD, and BJORN WESTRE
`
`Medical Department B, Institute for Surgical Research, Department for Clinical Pharmacology, Department of Pathology, University Clinic,
`Rikshospitalet, and Oslo Sanitetsforenings Rheumatism Hospital, Oslo, Norway
`
`S-creatinine
`amolesIliter
`
`S-beta2-microglobulin (cid:9)
`',Lerner (cid:9)
`
`C-creatinine
`mliter/min
`
`U-beta2-microglobulin (cid:9)
`gg124 hr (cid:9)
`
`U-kallikrein
`units/24 hr
`
`U-albumin
`µg/min
`
`Pat C-0 26 C-II C-O (cid:9)
`
`26 (cid:9)
`
`C-II C-O 26 C-lI C-O (cid:9)
`
`26 (cid:9)
`
`C-II C-O 26 C-II C-O 26 C-II
`
`71
`53
`380
`71
`88
`71
`71
`
`AB
`AS
`OT
`RH
`AP
`MAJ
`ES
`TL
`BH
`IS
`TH
`
`58
`53
`1 1 I
`58
`80
`53
`62
`80
`84
`97
`58
`
`133
`88
`292
`71
`133
`80
`53
`80
`203
`124
`80
`
`2625
`2625
`4725
`1575
`2365
`2260
`2195
`1575
`2835
`4935
`3150
`
`7140
`3780
`13200
`1470
`2730
`1260
`905
`1900
`3780
`3360
`1680
`
`2625
`2205
`21000
`1575
`2295
`1890
`1385
`
`101
`107
`10
`156
`47
`96
`122
`
`128
`116
`49
`96
`50
`89
`106
`174
`79
`50
`84
`
`60
`61
`22
`115
`39
`86
`100
`163
`42
`51
`71
`
`138
`56
`464
`67
`200
`45
`98
`62
`70
`46
`86
`
`3900
`1125
`16525
`172
`6800
`308
`179
`41
`97
`464
`185
`
`234
`181
`1200
`80
`676
`100
`147
`
`0.84
`1.06
`0.09
`0.16
`0.64
`1.56
`1.04
`
`1.18
`1.03
`0
`0.04
`0.50
`2.14
`0.67
`0.96
`0.03
`0.36
`0.44
`
`0.65
`0.23
`0.05
`0
`0.15
`0.85
`0.33
`0.30
`0.21
`0.28
`0.21
`
`3.7
`3.4
`16.0
`2.2
`5.2
`5.1
`2.9
`5.4
`3.7
`2.6
`19.4
`
`12.0
`5.1
`44.4
`3.1
`11.8
`86.1
`4.7
`4.9
`11.7
`4.6
`7.9
`
`2.0
`3.9
`7.4
`3.1
`11.9
`3.3
`5.0
`
`(range 1 to 17) in the CyA group and 8.8 ± 6.0 years (range 1 to
`18) in the azathioprine group.
`
`Study design
`
`Patients in the CyA group started with 10 mg/kg/day and the
`mean dose was gradually reduced to 6.4 ± 1.7 mg/kg/day at the
`end of the study according to blood levels. Dosage reduction
`was made according to the study protocol when serum creati-
`nine increased above 130 µmoles/liter or when whole blood
`CyA levels exceeded 1000 µg/liter during the first month and
`800 peg/liter later. Mean dose for the whole treatment period was
`7.8 ± 1.2 mg/kg/day. The other group of patients received Aza
`2.5 to 3.0 mg/kg/day throughout the study. All patients received
`prednisolone 5 mg/day at the onset of the study, and the mean
`prednisolone dose was gradually reduced to 2.9 ± 1.1 mg/day in
`the CyA group and to 4.7 ± 1.7 mg/day in the azathioprine
`group according to clinical effect.
`All patients in both treatment groups were kept on a stable
`dose of NSAIDs for at least one month before the trial. In the
`CyA group the dose of NSAIDs was unchanged in six, with-
`drawn in two (OT, AP, Table 1), reduced in two (MAJ, TH) and
`increased in one patient (TL) during the study. There were only
`minor adjustments of the NSAIDs dosage in the Aza group.
`Blood pressure, blood samples, morning urine and pooled 24
`hr urine were obtained twice during the control week and the
`means of the two results were used as the control value (C-0).
`During the 26 week treatment period, blood pressure, plasma
`remn activity (PRA), and plasma aldosterone were controlled at
`weeks ten and 26. The blood pressure was expressed as mean
`arterial blood pressure (MAP = Diastolic blood pressure + 1/3
`pulse pressure). Creatinine, beta2-microglobulin, sodium and
`potassium in serum and CyA in whole blood were determined
`weekly during the first ten weeks and then every second week
`during the last 16 weeks of study. Pooled 24 hr urine and
`morning urine were sampled during weeks 2, 6, 10, 18, and 26.
`beta2-microglob-
`Pooled 24 hr urine samples were assayed for
`ulin,
`w
`a s
`albumin,
`stodkaaltlik_rein, sodium, potassium and creatinine.
`N -acetyl-beta-glucosaminidase (NAG) was determined in morn-
`mg urine.
`All urine samples were stored without delay at + 4°C without
`preservatives.
`(cid:9) When 24 hr urine collection was completed, the
`urine
` 20°C for six months. This storage did not
`
`affect the parameters investigated. Urine aliquots were ana-
`lyzed im