The incidence of rejection in this series was 100% and each patient had 2.5_+1 episodes of rejection. 88% of rejection episodes were mild or moderate which were treated with steroids and Olql3 and caused no graft loss. 12% of rejection episodes were severe and resulted in graft toss and death in 3 of 6 patients. One patient was retransplanted sucessfully and two patients were treated sucessfully with OKT3 following severe rejection. One patient had a single CMV infection postoperatively that was treated with Cytogsm and gsncyclovir. One patient had a posttransplant lymphoproliferative disorder which resulted in the death of this patient. Two patients died from infectious complications. Conclusions: Complications related to immunosuppression (CMV, posttransplant lymphoproliferative disorder, and sepsis) have been reduced. Graft and patient survival have improved since the addition of: daclizumab 1o the immunosuppressive regimen, rigorous CMV prophylaxis, and the use of zoom videoendos- copy for rejection surveillance.

259

The Protective Effect of Lactobacillu$ cr isl~tn on Dextron $ulfate-lndon~l Colitis Requires a Direct Interaction with Colonic Mucosa. Ignazio Castagliuolo, Dept Microbiology, Univ of Padua, Padua Italy; Francesca Galeazzi, Dept of Gastroenterology, Univ of Padua, Padua Italy; Chiara De Ros, Dept Microbiology, Univ of Padua, Padua Italy; Andrea Cavaggioni, Dept of Physiology, Univ of Padua, Padua Italy; Giacomo C. Sturniolo, Dept of Gastroenterology, Univ of Padua, Padua Italy; Debora Torroen, Natale Pennelli, Dept of Pathology, Univ of Padua, Padua Italy; Gianni Pozzi, Dept of Molecular Biology, LAMB, Siena Italy; Giorgio Palu', Dept of Microbiology, Univ of Padua, Padua Italy

Background and aims: The disruption of the homeostasis between endogenous intestinal flora and host immune system contributes to trigger inflammatory bowel disease. Furthermore, colonic microflora manipulation through antibiotic therapy or dietary supplementation with non-pathogenic intestinal microorganisms has been shown to influence the onset and the severity of colitis. Here we assessed the effect of dietary supplementation with Lactobacillus crispatus, a newly identified Lactobacillus from healthy human colon, on dextran sodium sulfate (DSS)-induced colitis and its effects on intestinal epithelial cells response to inflamma- tory stimuli. Methods and results: Colitis was induced in male Balb/c mice administering 5% DSS in drinking water for 5 consecutive days. Starting 24 hrs after the induction of coins mice were treated daily with L. crispatus (104 to 108 bacteria per dose). 0ral administration of L. crispatus (106 and 108 per dose), but not medium alone or spores of Bacteroides fraoilis (106 per dose), dose-dependently reduced the body weight loss associated with colitis (by 21% (p<O.05) and 78% (p<O,Ol), respectively]. Furthermore, 10 a L crispatus significantly (p<O.Ol) inhibited mucosal neutrophilic infiltration (assessed by myelopsroxidase activity) and colonic inflammatory damage (evaluated by a semiquantltative histological score, p<O.05), whereas lower doses of L crispatus (104bacteria) had no significant effects. We next evaluated whether a direct interaction between bacteria and intestinal mucona is required for L. crispatus to exert its protective effects. Administration of 108 heat killed bacteria or an adhesion deficient strain of L. crispatus were not protective during DSS-colltis. Furthermore,pre-iocubating monolayers of human colonic epithelial cells (HT-29) with L crispatos significantly reduced IL-1/~ induced IL-8 release in vitro. Summary and conclusion: Dietary supplementation with live/, crispatus reduces the severity of DSS-induced colitis in mice and IL-1/3 induced IL-8 release from intestinal epithelial cells. Furthermore, adhesion deficient bacteria were devoided of any protective effect on colitis indicating that the protective effects require a direct immuno- modulatory action on the intestinal mucosa.

260

Benefit Of Helicobacter Pylorl Eradication In The Treatment Of Ul~r-Uke Dyspepsia In Primary Care Richard Stevens, East Oxford Health Ctr, Oxford United Kingdom; Garth Baxter, Wyeth Lab, Taplow United Kingdom

Background: The role of Helicobacter pylori (Hp) eradication in patients without confirmed ulcer is unclear. The majority of studies have been conducted in secondary care on patients with functional ulcer-like dyspepsia (i.e. confirmed absence of ulcer) with equivocal results. This study, conducted in primary care, examines the role of Hp eradication in a broader group of patients presenting with ulcer-like symptoms (epigsstric pain), merely excluding those with confirmed ulcer. Methods: 543 patients from 64 primary care centres in UK and Norway were enrolled into the study. 364 patients were assessed as Hp +ve (by near patient antibody blood test). 181 patients were randomised to receive eradication therapy (iansoprazole 30 mg, clarithromycin 250 mg and amoxycillin 10 all bd) for 1 week followed by lansoprazole 30 mg od for 3 or 7 weeks according to syroptorns. 183 patients received placebo antibiotics and lansoprazole 30 mg od for 4 or 8 weeks. Treatment was double blind. 179 Hp -va patients received open treatment with lansoprazole 30 mg od for 4 or 8 weeks. Epigsstric pain and other Gastro-lntestinal (GI) symptoms, GI consultations, GI prescriptions and Gi investigations were recorded during the treatment period and over a 12-month follow-up phase. Primary efficacy variable was the proporti!)n of patients with relapse during the 12 month follow-up period. Results: 394 patients, with Hp status correctly assigned at baseline (by ~3C-Urea Breath Test), completed the study. The average number of GI consultations and prescriptions was lower in the eradication group compared with the Hp +ve non-eradicated group (p<0.02 and p=O.05 respectively). Conclusion: Hp eradication resulted in a significant reduction in symptomatic relapse in patients presenting with ulcer-like dyspepsia in primary care. This was associated with a reduction in the number of GI consultations and prescriptions over the subsequent 12 months.

Treatment Group Relapse Rate % p-values Eradication 37.0 (47/127) ) 0.02 Lansoprazole (+re) 51.4 (73/142) ) ) Lansoprazole (-ve) 59.2 (74/125) ) 0.22

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Dyspepsia Management in Primary Care: A Reappraisal of Competing Strategies Brennan Mr Spiegel, Cedars-Sinai Medical Ctr, Los Angeles, CA; Nimish B. Vakil, Univ of Wisconsin Medical Sch, Milwaukee, Wi; Joshua J. ofman, Zynx Health Inc, Los Angeles, CA Background: Dyspepsia is a common disorder in the primary care setting. Current guidelines for the management of uncomplicated dyspepsia suggest initial H. pylori "teat-and-treat" iT&T), followed by upper endoscopy (EGD) for patients with persistent symptoms. Recent data, however, indicate that H. py/ofi eradication provides symptomatic relief for only a minority of patients, and that empiric proton pump inhibltors (PPIs) may be more effective for uninvestigated dyspepsia. Our objective was to reappraise the cost-effectiveness (C/E) of alternative empiric management strategies for dyspepsia. Methods: Decision analysis was used to calculate the C/E of four sequential strategies for simple uninvestigated dyspepsia. In each case, EGO is performed for non-responders: 1) Initial T&T (T&T • EGD); 2)Initial T&T, followed by a 6-week PPI trial for non-responders (T&T • PPI • EGD); 3) Initial PPI trial (PPI • EGD); and 4) Initial PPI trial, followed by T&T for non-responders (PPI • T&T • EGD). Cost estimates were based on Medicare reimbursement and average wholesale drug prices. Probability estimates were derived from a systematic review of the MEDLINE and HEALTHSTAR bibliographic databases. The time horizon for this analysis was 1 year and the outcome was cost per symptom-free patient. Assumptions were tested over a wide range in sensitivity analysis. Results: Of the four competing stategies, T&T • PPI • EGD was the most effective and iea~ expensive, yielding an average cost per symptom-free patient at 1 year of $2,670. The T&T • EGD strategy was the least effective and most expensive, yielding an average C/E ratio of $3,033. The average C/E ratios for PPI • EGD and PPI • T&T • EGD were $2,871 and $2,810, respectively. Compared to T&T • EGD, T&T • PPI • EGD resulted in a 20% reduction in the use of EGD while committing only 2% more patients to tong-term anti-secretory therapy. It would require 29 years of continuous PPI therapy before the T&T • EGD strategy realized a C/E advantage. The T&T • PPI • EGD strategy remained the most C/E approach under a wide range of clinical and cost assumptions. Conclusions: This analysis reveals that compared to current guidelines, interposing a 6-week PPI trial between T&T and EGO may achieve improved symptom relief at a lower overall cost by substantially reducing the eodoscopi¢ burden. Strategies that rely on initial PPIs, by contrast, appear slightly more expensive than T&T • PPI • EGD but may be more C/E than current guidelines. These findings suggest that prospective trials comparing these strategies are war- ranted.

282

Low Yield of EGD for D ~ I a on Proton Pump Inhibifors Edwardo Vefzoia, Festis, MO

Background: Evaluation of dyspepsia is controversial. The AGA in 1997 recommended empiric eradication of H. pyiofi and if Hp negative, empiric acid suppression or prokinetics in younger patients without alarm aymptoms. Endoscopy (EGD) is reserved for failure of empiric Rx. Others have recommended early EGD without empiric Rx. We believe EGD for persistent dyspepsia on therapy is low yield, particularly if Rx is proton pump inhibitors (PPI) Aims: determine the diagnostic yield of EGD in dyspeptic patients on: 1) no Rx; 2) H2 receptor antagonists (H2RA); 3) PPI. Methods: Dyspeptic patients referred for EGD at an open access endoscopy onif were interviewed, Heartburn was an exclusion. Patients currently Rx'd with H2RA or PPI -> 4 weeks were included as well as those on no prior Rx. Response to Rx was indicated by the patients on a O-lgg% visual analog scale. Results: 93 patients were included. Patients on PPI had significantly fewer endoscopic findings that might explain symptoms than patients on H2RA or no Rx (p<O.01 for each, see Table). Specifically, there were fewer patients with erosions and esophagltis compared to the other 2 groups. Despite fewer findings, symptom relief was similar for PPI and H2RA (46% and 43%). Symptom relief predicted EGD findings for H2RA but not PPI. Conversely, subjects on either Rx with less than 20% improvement in symptoms had no endoscopic abnormalities (0/17 vs 24/52 with improvement, p < 0.01). Conclusions: Dyspeptic patients with persistent symptoms on PPi have fewer endoscopic abnormalities that could explain symptoms than patients on H2RA or no Rx. For subjects with partial symptom relief PPI's may mask endoscopic findings. Interruption of PPI prior to EGD may increase diagnostic yield, particularly for reflux disease which may cause symptoms in the absence of erosive changes. Subjects with no symptom relief on Rx are unlikely to have endoscopic findings regardless of Rx.

FINDING~ No Rx (n=23) I-i2RA (n=38) PPI (n=32)

ESOPHAGITIS 9 6 2* ULCER 4 3 1 BARRETTS 1 I 2 GASTRODUODENITIS 1 9 0* TOTAL (%) 15 (65%) 19 (50%) 6* (19%)

IS Prompt EndOsCOpy Necessary in Uninvestigated Dyspeptics? Prevalence Of Upper GaslTotufoBttual Abnorma)illes - The CADET-PE Study. Alan B. R. Thomson, Univ of Alberta, Edmonton Canada; David Armstrong, McMaster Univ, Hamilton Canada; Alan N. G. Barkun, McGill Univ, Montreal Canada; Nanki Chiba, McMaster Univ, Guelph Canada; Sander J. O, Veldhuyzen van Zanten, Dalhousie Univ, Halifax Canada; Sandra Daniels, Bijan Chakraborty, Paul Sinclair, AstraZeneca Canada Inc, Mississauga Canada; The Cedet-Pe Study Group

AIM: To determine the prevalence of upper gsstrointestinal (GI)abnormallties as determined by prompt endoscopy (EGD)in young and older primary care patients with uninvestigated dyspepsia. METHODS: Dyspeptics (-> 18 yr) were recruited from 49 family physician (FP) centres across Canada. Dyspepsia was defined as -> 3-month history of any of the following

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