Pantoprazole in patients with varying degree of liver impairment in comparison to heal thy controls

A6 AGAABSTRACTS

GASTROENTEROLOGY Vol. 114, No. 4

• G0019 PANTOPRAZOLE IN PATIENTS WITH VARYING DEGREE OF LIVER IMPAIRMENT IN COMPARISON TO HEAL THY CONTROLS. H.P. Breuel 1, J. Horak 2, M. Horejsova2, P.R. Heine 1, M. Hartmann 3, R. Huber3, R. Liihmann3, W. Wurst 3. lPhannacon Research, Berlin, Germany; 2Charles University Prague, Czech Republic; 3Byk Gulden, Konstanz, Germany

The aim of this open study with parallel group design was to investigate the pharmacokinetics of pantoprazole in patients with varying degree of liver impairment in comparison to a control group of healthy volunteers. Patients with liver cirrhosis Child A or B were divided by use of the I4C-aminopyrine breath test into two groups: moderate (N=8, 65-98 kg, 36-60 years) and severe (N=8, 64-89 kg, 31-57 years) liver impairment. A control group (N=8, 71-88 kg, 44-51 years) of healthy subjects was also included. Each subject was given a single oral dose of 20 mg pantoprazole. Serum concentrations were measured by HPLC. AUC, tvz and Cmax were calculated. Pantoprazole was well tolerated. No adverse events occurred. Median (N=8 each group) pharmacokinetic characteristics were: controls

moderate

severe

AUC (mgxh/I)

2.38

7.68

12.17

Cma~ (mg/l)

1.33

1.78

1.84

t w (h)

0.97

3.4

6.1

The pharmacokinetic characteristics of patients with moderate or severe liver impairment were increased by factors of 2.62 or 4.17 (AUC), 1.30 or 1.45 (Cmax) and 2.65 or 4.33 (tl/2) as compared to healthy controls. Therefore, patients with moderate liver impairment can be treated with the normal dose of 40 mg/day. Patients with severe liver impairment should be given 20 mg/day or 40 mg every other day. This research was funded by Byk Gulden, Konstanz, Germany. G0020 DIET AND THE RISK OF COLONIC ADENOMAS. B. BreucrKatschinski, K. Nemes, B. Rump, B. Leiendecker, A. Mart, N. Breuer, H. Goebell and the Colorectal Polyp Study Group. Dept. of Gastroenterology University Hospital Essen, FRG Background and aims: It has been postulated that high intakes of animal fat and protein and low intakes of fibre, calcium and antioxidants increase the risk of colorectal cancer. Adenomatous polyps are the precursors of colorectal cancer and studies of subjects with these lesions are less prone to bias because most c01orectal adenomas are asymptomatic. Methods: Dietary intake over the past year was studied according tO the diet history method by means of a case-control study. 182 patients with asymptomatic adenomas were interviewed and the habits of these patients compared with those of 178 hospital controls without colorectal adenomas and with those of 182 population controls. Conditional logistic regression analysis for matched sets was used to calculate relative risks (RR) and 95% confidence limits. Results: After adjustment for energy, relative weight and social class no associations were found for fat or protein in comparison with either control group. For fibre intake there was a significantly negative association in comparison with hospital controls, the RR being 0.47 (0.23-0.99), when the highest versus the lowest quintile was compared. Unexpectedly, carbohydrate intake was inversely related with adenoma risk in comparison with hospital controls, the RR being 0.29 (0.10 - 0.81) for quintile 5 versus 1. None of the antioxidants showed a significant protective effect except 13-carotene intake in comparison with hospital controls, the RR being 0.24 (0.11 - 0.50) for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile of intake being 3.6 (1.7-7.5) in comparison with hospital controls and 4.4 (1.6-12.1) in comparison with population controls. Conclusions: Our data support the protective role for carbohydrate intake and of [3-carotene intake in the etiology of colorectal adenomas and show a strong increased risk for developing adenomas in those with high meat intake. • G0021 SERUM ANTIOXIDANTS AND THE RISK OF COLORECTAL ADENOMAS. B. Breuer-Katschinski, K. Nemes, B. Rump, B. Leiendecker, A. Man', N. Breuer, H. Goebell and the Colorectal Polyp Study Group. Dept. of Gastroenterology, University Hospital Essen, FRG Background: It has been suggested that antioxidant vitamins protect against the development of colorectal cancer. Adenomatous polyps are the precursors of colorectal cancer and studies of subjects with these lesions are less prone to bias because most colorectal adenomas are asymptomatic. Methods: The relation between risk of colorectal adenoma and serum concentrations of vitamins A, C, and E and carotene was examined in a population-based case-control study of 105 cases of colorectal adenoma and a similar number of hospital controls showing no polyps at colonoscopy and a second control group of population controls. Relative risk estimates (RR) and 95% confidence limits (95% C1) were computed for quartiles of serum levels of vitamins on the basis of distributions among controls. In order to control

for confounding factors a multiple logistic regression analysis for matched sets was carried out Results:. There were no significant associations with serum concentrations of vitamins C and E and carotene. Serum concentrations of vitamin A were significantly inversely related to the risk of colorectal adenoma when cases were compared with both control groups. After adjustment for energy intake, smoking, alcohol, estrogen therapy, body-mass-index and social class the inverse association between vitamin A and colorectal adenoma was even more marked. For the highest versus the lowest quartile of serum levels the adjusted RR was 0.23 (0.07-0.73) in relation to hospital controls and 0.08 (0.02-0.25) in relation to population controls both RR estimates reaching statistical significance. Conclusions:. These findings suggest that the risk of developing colorectal adenomas is reduced in those with high vitamin A levels. G0022 UNEXPLAINED LEUKOCYTOSIS AS A HARBINGER AND SURROGATE MARKER OF CLOSTRIDIUM DIFFICILE INFECTION IN HOSPITALIZED PATIENTS WITH DIARRHEA, M. Bulusu and G. Triadafllopoulos. Gastroenterology Section, VA Palo Alto Health Care System and Stanford University, Stanford, CA.

Background: Clostridium di~cile is the etiological agent of antibioticassociated diarrhea and pseudomembranous colitis and a leading cause of nosocomial diarrhea. Although the manifestations of C.difficile infection are diverse, unexplained leukocytosis as a harbinger and a surrogate marker of C.difficile infection in hospitalized patients has not been evaluated. Aims: We aimed to examine if unexplained leukocytosis could be a harbinger and a surrogate marker of C. difficile infection in hospitalized patients. Methods: We retrospectively studied 70 hospitalized patients (35 C.d~cilepositive and 35 age- & sex-matched C.difficile-negative) who were treated over a 6 month period at a tertiary VA acute care facility. Clinical history, X-rays, and laboratory data were reviewed in all patients. In order to evaluate the relationship of increased WBC count and C.difficile infection, WBC counts were recorded for up to one month before and one month after C.diff~cile was tested. The diagnosis of C.difficile infection was based on detection of toxin A in stool samples using an enzyme-linked fluorescent immunoassay (ELFA, MiniVidas, BioMerieux Vitec Systems, St. Louis, MO). Leukocytosis was defined as the sudden elevation of WBC count greater than 2 standard deviations above the mean total leukocyte count of 7,500/mm 3 (range:4,500-11,000). Groups were compared using the Wilcoxon signed rank sum test. Results: C.difficile-positive patients (Group 1; 32M, 3F, mean age 62yrs) exhibited a significant leukocytosis (mean WBC count increased from baseline 8,900 to peak 15,800, range 6,000-33,000, p < 0.01). In contrast, C.difficile-negative patients (Group 2; 33M, 2 F, mean age 60yrs) maintained normal counts (mean WBC count at baseline 7,800 to peak 7,700). In Group 1, 3 pattems were recognized: (A) Prior antibiotic exposure; sudden rise in WBC count coinciding with symptoms of C.diJficile infection. Symptoms and WBC count respond to anti-C.d~ff[cile Rx. No delays in diagnosis. (B) No prior antibiotic exposure; sudden, unexplained rise in WBC count without symptoms of C.di)yici!e infection; empirical antibiotic Rx initiated; symptoms of C.diff~cile infection present days later. Significant delay in diagnosis/Rx with unnessecary diagnostic tests. Symptoms and WBC count respond to antiC.d~cile Rx. (C) Ongoing antibiotic therapy; sudden rise in WBC count coinciding with symptoms of C.difficile infection but symptoms are attributed to underlying disease. Significant delay in diagnosis/Rx with unnessecary diagnostic tests. Resolution of symptoms and leukocytosis after belated anti-C.dif]icile Rx. Conclusions: Sudden, severe leukocytosis may serve as a harbinger and a surrogate marker for C.difficile infection in hospitalized adults. Early testing and institution of effective antimicrobial therapy for C.d~ff~cile should be considered in hospitalized patients presenting with sudden leukocytosis to prevent costly, time-consuming tests and avoid diagnostic delay. This research was not funded. G0023 ARE CRITERIA TO EVALUATE THE APPROPRIATENESS OF PERFORMING COLONOSCOPY EVIDENCE BASED? B. Burnand, A. Fahmi, F. Froehlich, J.P. Vader, J.J. Gonvers, Institute of Social & Preventive Medicine and Division of Gastroenterology, University Hospital, Lausanne, Switzerland

OBJECTIVES: To assess the agreement between appropriateness criteria for the use of colonoscopy developed according to the RAND-UCLA method and evidence from published studies. DESIGN: In 1994, a national multidisciplinary panel of 9 experts used the RAND-UCLA method to develop criteria for the appropriateness of performing colonoscopy. Based on a comprehensive review of the literature, a list of 402 possible clinical indications for colonoscopy was developed. The panelists were provided with the literature review as a basis for evaluating the degree of appropriateness of each indication. These evaluations were consolidated into 3 categories: appropriate, uncertain, inappropriate. A similar categorization was made for indications retrieved from 16 studies (8 RCTs, 1 non-randomized trial, 7 observational studies) summarized in the literature review. Proportion of