A266 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, No. 4

• EFFICACY OF TRIPLE THERAPY TO ERADICATE H. PYLORI AF- TER FAILURE OF OMEPRAZOLE/AMOXICILLIN. G. Zala, *R. Fhiry, ~:J. Wrist, Ch. Meyenberger, M. Fried, H.P. Wirth. Depts. of Medicine, Division of Gastroenterology, *Pathology and SMicrobiology, University Hospital, CH-8091 Zurich, Switzerland.

Helieobacter pylori (Hp) eradication rates with omeprazole/amoxicillin (OME/AMOX) range from 0 - 90%. The best regimen for retreatment after failure of OMEIAMOX has not been established so far. The aim of this prospective study was to evaluate the efficacy of a triple therapy with bismuth, tetracycline and omidazole in eradicating Hp after failure of OME/AMOX. Patients and methods: 79 duodenal ulcer patients with Hp infection were treated with peroral OME 40 mg bid and AMOX solute 750 mg tid. Eradi- cation rate was 28/79 (35%) and was distinctly lower in smokers (>10 cigarettes/day) vs. nonsmokers (10149 [20%] vs. 18/30 [60%], p <0.001). 37 patients with persistent Hp infection in whom OME/AMOX failed, agreed to retreatment with triple therapy. Persistence of Hp was conCh'reed by histology (3 antral and 2 gastric body biopsies; H&E, Criemsa), urease test ~CLO®) and/or Hp culture. Resistance testing for metronidazole (MTZ) was performed using a disk diffusion test (E-test, AB Biodisk, Sweden), MTZ resistance was defined as minimal inhibitory concentration for MTZ >8 pg/ml. Eradication retreatment consisted of bismuth-subei- trate 4x120 mg/d for 28 days (d 1-28), tetracycline 4x500 mg/d and omi- dazole 3X500 mg/d for 10 days (d 1-10): Control endoscopy was done 30 days after the end of treatment. Criteria for Hp eradication were negative urease test, culture and histology. Results: 34•37 patients (6 f, 28 m; 39 [23-64] years) completed the study, 24/34 smokers, 10/34 nonsmokers. 3•37 patients dropped out because of side effects (n=l) or insufficient compliance (n=2). Hp subcultures for resistance testing were possible in 32/34 patients: Hp was MTZ-sensitive in 11132 (1 f, 10 m; 38 [24-55] years; 9 smokers, 2 nonsmokers) and MTZ-resistant in 21/32 (5 f, 16 m; 40 [23-64] years; 13 smokers, 8 nonsmokers). The overall Hp eradication rate of the triple therapy was 27134 (79%). Hp was eradicated in 19124 (79%) smokers and in 8/10 (80%) nonsmokers. Eradication rate for MTZ-sensitive Hp was 11/11 (100%) vs. 14121 (67%) for MTZ-resistant Hp (p = 0.012). Conclusions: 1. Triple therapy is successful and safe in eradicating Hp in patients after failure of OME/AMOX. 2. Smoking has no negative effect on the eradication rate of the triple therapy after failure of OMF_/AMOX. Eradication failures were due to MTZ-resistance.

THE NEGATIVE INFLUENCE OF SMOKING ON H. PYLORI ERADI- CATION DEPENDS ON THE THERAPY REGIMEN. G. Zala, St. Schwery, *R. Flury, Ch. Meyenberger, M. Fried, H.P. Wirth. Depts. of Medicine, Division of Gastroenterology, and *Pathology, University Ho- spital, CH-8091 Zurich, Switzerland.

We have recently shown that H. pylofi (Hp) eradication with omeprazo- le/amoxicillin (OME/AMOX) is impaired in smokers. Little is known ab- out a compromising effect of smoking on other therapy regimens. The gtm Of this study was therefore to compare Hp eradication rates in smokers vs. nonsmokers of four different therapy regimens. Patients and methods: 113 Hp positive duodenal ulcer patients were treated and 34 of these retre- ated in an open prospective study with four different regimens. Patients smoking >10 cigarettes/day were classified as sm0kersl ~p infection was confirmed by histology (3 antral and 2 gastric body biopsies; H&E, Giemsa), CLO®-test and/or culture. Patients characteristics (sex, age) in the four groups were similar. In groups A, B and C eradication therapy consisted of peroral OME 40 mg bid and AMOX solute 750 mg tid for 10 days (OME/AMOX) preceded or followed by OME 20 mg daily for 20 days. A: 36 patients took OME/AMOX before OME. B: 43 patients took OME/AMOX after OME~ C: 34 patients were treated as in group B, but N-acetylcysteine (NAC) solute 600 mg bid was added during eradication therapy (d 21-30). In group D 34 patients of groups A and B with persi- stent Hp infection after OME/AMOX were retreated with a triple therapy consisting of bismuth-subcitrate 120 mg qid for 28 days (d 1-28), tetracy- cline 500 mg qid and ornidazole 500 mg tid for 10 days (d 1-10). Control endoscopy was done 30 days after the end of treatment. Criteria for Hp er- adication were negative histology, CLO and culture. Results: Tl~erapy regimen H. pylori eradication rates

Smokers Nonsmokers p A: OME/AMOX before OME 5/26 (19%) 6/10 (60%) <0.02 B: OME/AMOX after OME 5/23 (22%) 12/20 (60%) <0.02 C: OME/AMOX+NAC after OME 11/17 (65%) 10/17 (59%) n.s.

ID: Triple therapy 19/24 (79%) 8/10 (80%) n.s.

Conclusions: 1. The negative influence of smoking on Hp eradication de- pends on the therapy regimen used and seems to be a particular problem of OME/AMOX. 2. Addition of N-acetylcysteine to OME/AMOX eliminates this negative effect in smokers. 3. Smoking does not influence the efficacy of triple therapy with bismuth-subcitrate, tetracycline and ornidazole.

• DENSITY OF FUNDIC ECL CELLS DURING LONG TERM TREATMENT OF REFLUX ESOPHAGITIS BY OMEPRAZOLE OR HISTAMINE H2-RECEPTOR ANTAGONISTS. Zeito~n P*, Diebold MD*, Richardson S**, Duchateau A*, Bigard MA, Colin R, Cortot A and colleagues in 52 centers. *Reims, CHU, **INSERM,Unit#170. FRANCE

The main goal of this study was to evaluate the density of ECL cells in a control group and in patients treated with antisecretory drugs. Age, gender, duration of treatment (ttmt) and basal serum gastrin concentration (BSGC) were also taken into account. Patients and methods. Subjects in the omeprazole (OME) and H2-receptor antagonist (H2RA) groups were treated for at least 5 of the previous 6 months. The results from upper GI tract endoscopy were normal in controls (C). Antral ~ and fundic biopsies were made to search for gastritis and Helicobacter pylori and to count the ECL cells (Grimelius method). The BSGC was determine d . Results. The 3 groups were comparable in terms of age distribution. The duration of ttmt was lower in the OME group (n=201) than in the H2RA group (n=l18) (means = 27.0 and 36.5 months). The sex ratio in the C group (n=215) differed from that in the 2 other groups. Ten subjects in group C with fundic atrophic gastritis were excluded. The mean BSGC in the OME group (106.7 IU/I) was significantly higher than in the H2RA and C groups (61.6 IU/I and 58.7 IU/1) (p=0.0001); there was no difference between the H2RA and C groups in terms of BSGC. The ECL cell density was similar in the OME and H2RA groups and significantly higher than in the C group (p=0.0009 and p=0.035, respectively). There was a significant but weak link between the BSGC and ECL cell density. There was no significant difference in ECL cell density between the 3 groups after adjustment on BSGC. The results were unaffected by adjustment on gender, age or duration of ttmt. Conclusion. In this broad series of patients there was no difference in the ECL cell density between the OME and H2RA groups in spite of a higher BSGC in the OME group.

MUCOSAL PROTEIN TURNOVER, GROWTH FACTOR AND EGF RECEPTOR EXPRESSION IN DUODENAL ULCER PATIENTS FOLLOWING SUCCESSFUL TREATMENT WITH SUCRALFATE OR LANSOPRAZOLE. T. Zhan~, SJD O'Keefe, TA Winter, JM Ogden, GO Young, IN Marks~ GI Clinic, Grooto Sehuur Hospital and Dept of Medicine, University of Cape Town, Cape Town, South Africa. INTRODUCTION Experimental studies have shown that growth factors TGF- j c~, EGF and bFGF are important endocrine/parecrine regulators of gastric acid secretion and mucosal regeneration including epithelial proliferation and angiogenesis, which are essential for ulcer healing. AIM To determine the possible associations between gastro-dnodenal mucosal protein turnover (MPTO), growth factors TGF-~, bFGF and EGF receptor expression and duodenal ulcer (DU) healing following successful treatment with either sacralfate (Sc) or lansoprazole (Lz). METHODS 15 patients with an active DU were randomized to treatment with Sc lg qid (n=7) or Lz 20rag bid (n=8) for 4 weeks. Before and during treatment (day 10) and 2 weeks after healing, levels of mucosal bFGF (pg/mg protein), TGF-a (pg/mg protein) and EGF-R (Creel/rag protein) and the MPTO (%/day) were measured using endoscopic biopsies (fundns, antrum and ulcer edge) taken after a 4hr primed/continuous IV infusion of 1-14C-leacine tracer (20/~Ci/hr). Data were analysed and compared to values in 6 matched healthy volunteers (control) using Student's t-test. RESULTS Fundal MPTO was elevated in both groups prior to treatment (So 90.2:t:12.3, Lz 79.05:8.6 vs control 48.75:3.5, p<0.05) and fell to within the normal range during Lz treatment and after ulcer healing in both groups. Duodenal MPTO in the Sc group increased significantly during treatment and remained high following healing (76.45:20.0 and 57.55:10.7 vs control 31.3+2.5 p<0.05). Corresponding changes in growth factors were found in the duodenum but not the stomach in the Sc group. In the duodenum, TGF-~ increased at day 10 (22.65:6.8 vs control 12.8+ 1.3); EGF-R increased during and after ulcer healing (135.95:21.5, 125.4+12.9 vs control 70.9+11.1). Duodenal bFGF was lower than controls in both groups before treatment and increased to the normal range after ulcer healing with So. No changes in duodenal growth factors and EGF-R were found in the Lz group. CONCLUSION We have observed that patients with active duodenal ulcer have elevations i n gastric mucosal turnover and that successful medical treatment results in an acceleration of duodenal mu,~osal turnover. Our results suggest that the mechanism for healing induced by mucosal protective agents such as sueralfate is mediated by inci-eased growth factor expression Whilst that resulting from proton pump inhibitors such as lanzoprazole primarily acts through potent acid inhibition. This research was funded in part by Chugai Pharmaceuticals, Tokyo, Japan.