, (cid:9)
`•
`i 00 • "NUMBER
`
`•
`L DEVOOD.TO CLINICAL AND IASIC STUDIES OF THE DIGESTIVE TRACT AND -LIVER
`
`:STIVE DISEASE WEEK AND THE 92ND ANNUAL MEETING OF
`THE AMERICAN GASTROENTEROLOGICAL ASSOCIATION
`May 19-22, 1991, New Orleans, Louisiana
`
`DF THE ANNUAL MEETING OF THE AMERICAN
`TEROLOGICAL ASSOCIATION, THE AMERICAN ASSOCIATION FOR THE
`LIVER DISEASES, THE GASTROENTEROLOGY RESEARCH GROUP, THE
`XI SURGERY OF THE ALIMENTARY TRACT, AND THE AMERICAN
`)R GASTROINTESTINAL ENDOSCOPY
`
`3 OF PAPERS SUBMITTED TO THE AMERICAN GASTROENTEROLOGICAL (cid:9)
`DN
`
`3 OF PAPERS SUBMITTED TO THE AMERICAN ASSOCIATION FOR THE (cid:9)
`LIVER DISEASES
`
`tESEARCH ABSTRACTS (cid:9)
`
`IDEX (cid:9)
`
`IDEX (cid:9)
`
`P1
`
`Al
`
`A711
`
`A818
`
`A850
`
`A886
`
`SCIENITS 1. !PP
`
`F "
`
`AOR 1 7 1991
`
`l',/;acji:30,1, 1Nis. lis,106
`
`Sandoz v. AbbVie
`Sandoz Ex. 1077
`
`Ex. 1077 - Page1
`
`(cid:9)
`

`

`GASTROENTEROLOGY
`OFFICIAL PUBLICATION OF THE AMERICAN GASTROENTEROLOGICAL ASSOCIATION
`
`SCIENT'S
`
`APR 1 7 1991
`
`1305 Lindsn Or.
`Madison, Wis. 53706
`
`Editor
`Raj K. Goyal
`Beth Israel Hospital (LY 201)
`330 Brookline Avenue
`Boston, Massachusetts 02215
`FAX: (617) 731-5728
`
`Consulting Editor
`William Silen
`Beth Israel Hospital
`Boston, Massachusetts 02215
`
`Associate Editors
`Jose Behar
`Rhode Island. Hospital
`Providence, Rhode Island 02902
`
`Jules L. Dienstag
`Massachusetts General Hospital
`Boston, Massachusetts 02114
`
`John L. Gollan
`Brigham and Women's Hospital
`Boston, Massachusetts 02115
`
`James L. Madara
`Brigham and Women's Hospital
`Boston, Massachusetts 02115
`
`Allan Walker
`Massachusetts General Hospital
`Children's Hospital
`Boston, Massachusetts 02114
`
`Special Section Editors
`Selected Summaries Editor
`Mark Feldman
`Dallas, Texas
`
`Book Review Editor
`Helen M. Shields
`Boston, Massachusetts
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`This Month in Gastroenterology Editor
`Stuart Jon Spechler
`Boston, Massachusetts
`
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`Boston, Massachusetts
`
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`Boston, Massachusetts
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`Editorial Board
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`President
`David H. Alpers
`St, Louis, Missouri
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`Augusta, Georgia
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`Members of the Council
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`Tadataka Yamada, Ann Arbor, Michigan
`
`Ex. 1077 - Page2
`
`

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`GASTROENTEROLOGY: GASTAB 100(5) A1—A956 (1991)
`ISSN 0016-5085
`© 1991 by the American Gastroenterological Association
`
`Ex. 1077 - Page3
`
`

`

`(cid:9) ECT OF HYDROXYCHLOROQUINE IN THE TREATMENT OF ACTIVE
`• EH-
`ULCERATIVE COLITIS: RESULTS OF THE OPEN LABEL PHASE OF THE
`CONTROLLED TRIAL.
`Lloyd Mayer, Penny Turtel, Daniel Present, Henry Janowitz,
`Richard Rosenberg, David Sachar, Mitchell Conn, Steve
`Itzkowitz, and Sarah Martin. Divisions of Clinical Immunology
`and Gastroenterology, Mount Sinai Medical Center, NY.
`Hydroxychloroquine has been used in the treatment of a
`number of autoimmune disorders. While its efficacy has been
`proven, its mechanism of action is unclear. We have described
`a 'defect in intestinal epithelial cells in IBD which appears to be
`corrected by HQ in vitro. We recently completed a double blind
`placebo Controlled trial testing the efficacy of HQ (400 mg/day)
`in 90 patients with steroid dependent (ST) and nonsteroid
`dependent (NS) active ulcerative colitis. Following the 6 week
`blinded portion of the trial, the patients had the option of
`being placed on open label drug for a period of 6 months. Of
`the 67 patients with at least 6 weeks of follow up on medication,
`42 demonstrated clinical and/or sigmoidoscopic improvement
`(62.6%) with 22 achieving clinical remission (32.8%),
`Including 3. In whom remission was induced during the trial.
`had moderate disease
`Of those patients who improved, most (cid:9)
`activity at initial assessment. 4 patients who achieved clinical
`remission flared after cessation of steroids, 3 requiring
`colectomy. Of the 25 patients who showed no improvement, 21
`wore stable while 4 worsened (3 during steroid taper). 26
`patients completed at least 6 months of HQ. 18 (69%) improved
`with 11 (42%) achieving remission. 52 patients had
`sigmoidoscopic follow up with 33 demonstrating improvement
`and 5 achieving normal appearance. Within the steroid treated
`(ST) group (n=36), 27 improved (75%) with 14 achieving
`remission (39%). 30 ST patients (83%) were able to taper their
`steroids (14 off and five <5mg), while 6 could not be tapered.
`Adverse reactions requiring cessation of the drug occurred
`In 3 patients [ocular toxicity (color blindness) in 2 patients
`after 12 and 16 months of therapy]. The ocular toxicity was
`minor in both cases. Thus HQ appears to be a safe, effective and
`steroid sparing agent in the treatment of mild to moderate
`ulcerative colitis.
`
`COMPUTED TOMOGRAPHY OF SACROILIAC JOINTS IN
`CROIINS DISEASE. C. McCarthy, N. McEniff, C.
`O'Morain, S. Hamilton. Depts. of
`Gastroenterology and Radiology, Meath /
`Adelaide Hospitals, Trinity College,
`Dublin, Ireland.
`The prevalence of asymptomatic sacroiliitis
`in patients with Crohns disease is not known.
`It has been reported between 1.8 % - 29 %.
`Unlilke peripheral arthropathy it is not
`related to the severity or extent of bowel
`disease. Plain radio-graphy, tomography
`and radio-nuclide scanning may not detect
`early sacroiliitis.
`We undertook this study to determine the
`prevalene of asymptomatic sacroiliitis in
`patients with Crohns disease ( no pain or
`tenderness over S.I joints, and no limitation
`of movement) using CT scanning.
`Twenty patients were studied (9 M:11 F)
`with Crohns disease of various activity with
`outany extraintestinal manifestations. A
`Toshiba 600 HQ :banner using 5mm * 5mm
`continuous slices through S.I joints with a
`Gantry angle parallel to the anterior surface
`of the S./ joint.The changes asgessed included
`joint irregularity / narrowing, sclerosis,
`erosions and intraaticular ankylosis.
`Four of the patients had CT changes - 2
`had erosion and 2 had joint space irregularity
`and this was not related to their Crohns
`disease activity.
`In conclusion, 20% of these patients with
`Crohns disease had significant asymptomatic
`sacroiliitis as assessed by CT. This has
`therapeutic implications to prevent the,
`progression of sacroiliitis.
`
`l'Anauplokly In A Large Cohort C4 Patients With
`Chronic Ulcerative Colitis In Ongoing Surveillance
`Programs.
`JBD McHugh, JD Bozdech, GH Warren, CRD Meyer, DJ Ahnen.
`Monroe Louisiana; Denver VAMC, Rose MC, Denver; Colorado; Cleveland
`Clinic, Cleveland, Ohio.
`
`Dysplasla (dyspl) Is a marker of cancer risk in chronic ulcerative colitis
`(CUC) , but it Is not an ideal marker, Aneuploldy, as detected by flow
`cytometric analysis (FCA) of mucosa! DNA content, appears promising as a
`marker of carcinogenesis.
`GOAL: To ascertain the frequency of aneuploidy In CUC patients
`enrolled In ongoing surveillance programs and to determine if aneuploidy
`Identifies dysplastic mucosa and/or correlates with the presence of
`dysplasla elsewhere In the colon.
`METHODS: 122 patients enrolled In ongoing surveillance programs
`were prospectively evaluated. Histology and FCA were performed on
`adjacent fresh tissue samples obtained at colonoscopy. Colonic biopsies
`were taken every 10 cm and of any suspicious lesion . Twelve normal
`controls were also analyzed. FCA of colonic mucosal DNA content and
`histology were performed Independently In a blinded fashion.
`RESULTS: (cid:9)
`Patients(%) (cid:9)
`Biopsies(%)
`Groups No. No. Aneu No. Dyspl (cid:9)
`No. No. Aneu No. Dyspl
`Control (cid:9)
`12 (cid:9)
`0 (0%) (cid:9)
`0 (0%) (cid:9)
`48 (cid:9)
`0 (0%) (cid:9)
`0(0%)
`Staved 119 52(44%1 3(2%1 13()9 231(17%) 811%1
`The mean coefficient of variation was 5,02 ± 1.50.
`Aneuploldy was significantly more common In dysplastic (100% of 8) than
`non dyspiastic (17% of 1309) biopsies; p<.001. Aneuploldy was also
`significantly more common In patients with one or more dysplastic biopsies
`(100% of 3) than In patients with no evidence of dysplasla In any biopsy
`(42% of 116); p<.05. In one patient aneuploidy without dysplasla was
`found at surveillance coionoscopy In 1988 and 1989 In 1990 a
`carcinoma developed In the region of previous aneuploidy.
`CONCLUSIONS; Aneuploldy occurs frequenty In patients with chronic
`ulcerative colitis. Aneuploldy can occur in histologically non-dysplastic
`mucosa but it occurs more commonly In dysplastic biopsies and in patients
`with established dysplasla. We believe that long term studies are warranted
`to determine if aneuploidy identifies patients that are at risk for colonic
`carcinoma In chronic ulcerative colitis.
`
`Supported by the Crohn's and Colitis Foundation of America.
`
`• HISTOLOGIC AND MICROBIOLOGIC FEATURES WITH NORMAL AND IN-
`FLAMED POUCHES. R.S. McLeod, D. Antonioli, J. Cullen, A.M.
`Dvorak, A.B. Onderdonk, W. Silen, J.E. Blair, R.A. Monahan-
`Earley, R.L.-Cisneros, 2. Cohen..University of Toronto,
`Toronto, Beth Israel Hospital and Brigham and Women's
`Hospital, Boston.
`A prospective study was undertaken to assess the elect-
`ron microscopic (EM) and microbiological findings in
`tissue biopsy samples from patients with pouchitis and to
`compare them to findings in patients with normal pouches,
`conventional ileostomies (CI) and normal ileum (NI).
`Tissue samples were obtained from 78 patients: 23 patients
`with normal pouches endoscopically and histologically
`(Group 1); 12 patients with endoscopic 'and histologic evi-
`dence of inflammation (pouchitis)(Group 2); 14 patients
`who had either endoscopic or histologic evidence of in-
`flammation but not both (Group 3); 20 patients with CI
`(Group 4); and 9 patients with NI (Group 5). Anaerobic
`and/or aerobic bacteria were cultured in 82% of specimens.
`The mean total aerobic counts (6.3 Logic) CFU/gm tissue)in
`the samples from the pouchitis patients were significantly
`higher when compared with biopsy samples from Groups 4 and
`5 (2.9 and 1.4 Log10 CFU/gm tissue:respectively) (p<0.03).
`Aerobes were detected in all pouchitis patients but only
`74% of normal pouch patients (p<0.06). There were no sig-
`nificant differences in the mean anaerobic counts amongst
`the 5 groups, but only 50% of samples from pouchitis
`patients yielded anerobes compared with 838' in normal
`pouches (p<0.043). Positive cultures were obtained in 90%
`of patients with pouches compared with 69% of patients
`with CI or NI (p<0.05). Intramural bacteria were observed
`on EM in specimens of 47% patients with pouches compared
`with 14% of patients with CI.or NI (p<0.05).,However, the
`proportion of patients with positive cultures or intra-
`mural bacteria was not increased in the pouchitis group
`compared with the normal pouch group. There was agreement
`between EM and microbiological findings in 79% of patients.
`In conclusion, intramural bacteria are seen with in-
`. (cid:9)
`creased frequency in biopsies of pouches. Anaerobic bact-
`eria are found with decreased frequency in pouchitis
`patients whereas aerobic bacterial counts are elevated and
`may play a role in its pathogenesis.
`
`IaPa]'S'f1 a mps) (cid:9)
`
`100.3
`
`Ex. 1077 - Page4
`
`