GASTROENTEROLOGY Vol. 118, No.4 Al124 AGA ABSTRACTS 5182 5184 DUODENAL BIOPSY AND ENDOSCOPIC DIAGNOSIS OF COELIAC DISEASE IN A UK DISTRICT GENERAL HOSPITAL. Gabor Graehn, Gerard G. Robins, John O'Dowd, David G. Clements, Chris 1. Healey, Airedale Gen Hosp, Keighley, United Kingdom. Background: We serve a population of 195,000 (95,000 males) in Yorkshire, North England. Coeliac disease (CD) is readily treatable, yet often overlooked as a possible differential diagnosis. Aims: a) To study the indication for biopsy and frequency of histological diagnosis of CD in a typical UK district general hospital. b) To review the age and sex of first presentation of CD. A sub-analysis of Indian subcontinent patients was also performed. Methods: All duodenal biopsies from 1994-1998 inclusive were identified (with primary indication) from the pathology computer database, and notes if necessary. Indications were classified into 4 categories (A: Anaemia/Abnormal haernatinics; B: Abdominal symptoms; C: Weight loss/Failure to thrive; D: Other). First presentations of CD were analysed according to sex, age and ethnicity. Results: A total of 13452 OGDs was performed (6258 male) and 1209 (421 male) duodenal biopsies (age range I - 97) taken - a biopsy rate of 9%. There were a total of 86 biopsies showing villous atrophy; 61 (23 male) were first diagnoses. Positive biopsy rate was consistently around 5% until the age of 80 - older than this, there were no new cases. Positive biopsy rate for males was 5.5% and for females, 4.8%. Distribution curves were distinct for each sex - bell-shaped for males ; inverse sine for females. There were significant differences (p<O.OI) between the indications for each sex. In males the percentages for A,B,C and D were 33, 50, 5 and 12 respectively; in females it was 57,28, 4 and II. Ethnicity was not significant. Conclusions: Nearly twice as many females as males are undergoing duodenal biopsies, and we are seeing more CD diagnoses in females. We propose that women are more likely to get duodenal biopsy as they are more prone to anaemia, explaining some of the apparent observed sex ratio (often quoted at 1:2 male:female) in CD CYTOKINE EFFECTS ON COLONIC BARRIER AND TRANSPORT FUNCTION: A NEW IN VITRO MODEL FOR EPITHELIAL DYSFUNCTION IN IBD. Ingo Grotjohann, Heinz Schmitz, Michael Fromm, Jorg D. Schulzke, Ukbf, Berlin, Germany. Aims: In inflammatory bowel disease (mD) intestinal malabsorption and barrier dysfunction are prominent features which cause diarrhea and antigen penetration. Proinflammatory cytokines as TNFa and interferon-v have been shown to influence epithelial barrier function in cell line models as HT-291B6 and are elevated in lED. This study aimed to create an in vitro model for studying proinflammatory cytokine effects on colonic function and morphology. Methods: Rat distal colon was stripped off all muscular layers and incubated in specialized Ussing type chambers for 20 h at 37° C in oxygenated Ringer solution (pH 7.4) supplemented with 10% fetal calf serum. TNFa (100 nglm!) or IFN-y (1000 Ulml), either alone or together, were added to the basolateral side of the tissue. Morphological changes were determined from cross sections. Transepithelial resistance (R') and 3H-mannitol fluxes were measured for characterizing the paracellular pathway. In addition to conventional referencing of R' to the serosal area, it was also referenced to the mucosal surface area (R'?'), Thus e.g. area contribution of crypts is taken into account by R'?', Results: After 20 h incubation TNFa, mucosal thickness and crypt length were decreased resulting in reduction of the epithelial area due to apo~tic cell loss (see Table). IFN-y greatly enhanced the effect of TNFa. R was unchanged by TNFa and decreased by TNFa plus IFN-y. However, if referred to the mucosal surface, which is specific for the epithelial area, resistance (R'?') was decreased under both conditions. IFN-y alone had no effect (data not shown). This means that under TNFO' alone the reduction of R'?' is compensated by epithelial area reduction. In contrast, under TNFO' plus IFN-y the high rate of apoptosis does not allow for further compensation. Conclusion: A new lED in vitro model employing native colon is presented which allows for studying cytokine effects relevant in lED. An increase in apoptosis was accompanied by morphological changes with crypt rarefaction as observed in ulcerative colitis. A prominent feature is the impairment of epithelial barrier function. 5183 CLINICAL EFFICACY OF ENTEROCLYSIS PERFORMED IN A TEACHING HOSPITAL. Priya Grewal, Bruce Javors, Olusola Olofinlade, James Robilotti, Nicholas Gualtieri, Matthew Karowe, St Vincent's Hosp, New York, NY. Background and Aim: Enteroclysis (EC) offers many advantages in the evaluation of small bowel disorders. EC bypasses the regulatory action of the stomach and pylorus, so larger amounts of barium and methylcellulose can be infused directly into the small bowel, allowing better distention and double contrast, with "see-through" ability to visualize the mucosa. EC accurately defines the presence, the grade and the cause of small bowel obstruction (SBO). EC is particularly useful when the obstruction is partial, intermittent or may have multiple causes. In Crohn' s disease, EC localizes the exact site of the fistula, as the small bowel is imaged in real time, as opposed to intermittent filming in a small bowel series. The aim of this study was to assess the clinical usefulness of EC as a non-invasive modality for the management of OJ disorders. Method: Medical chart review was done for 44 consecutive EC performed at our hospital. In 41 cases, a double contrast EC was performed. A 155 em long 13F tube was placed through the nose, with its tip in the proximal jejunum. Barium and methylcellulose were instilled using a dialysis pump (barium 200 ml to 600 ml; methylcellulose 800 ml to 2,000 ml). Infusion rates varied from 50-150 mil hour and the mean time to completion was 30 minutes. Findings: The indications for EC were occult bleeding (10 cases), iron-deficiency anemia (7), Crohn's disease (8), SBO (6), abdominal pain (6), diarrhea (4) and cancer (3). The study was positive in 17 of the 44 cases (38%). In patients with SBO (6), EC defined the grade of obstruction in 6 patients (and site and cause of obstruction in 4). In patients with Crohn's disease (8), EC made the initial diagnosis in 2, confirmed active disease (fistulas and sinus tracts) in 6, and led to a change in management in 3. In patients with a history of abdominal cancer (3), EC ruled out recurrent cancer (gastric and appendiceal carcinoid) in 2 patients, and confirmed small bowel metastasis in I patient with malignant melanoma. The diagnosis of cytomegalovirus enteritis was made in I patient with diarrhea. In patients with irondeficiency anemia (7), occult OJ bleeding (10) and non-specific abdominal pain (4), EC failed to reveal any pathology, which is consistent with the reports in the literature. Conclusion: The overall yield of 38% makes EC an excellent tool in diagnosing SBO, Crohn's disease and recurrent abdominal cancer. Thus, gastroenterologists should make EC a part of their arsenal. Control TNFa TNFa+IFNy Crypt length, flm Epithelial area, % Apoptotic index, % R',n'cm' Rtm,n'cm' 155±6 77± 3' 40± 7' 100 76± 5' 64+ 5' 67± 20 9.2± 29 29.4 + 5.2' 189±10 190 ± 10 101 + 10' 361 ± 19 276±15' 123+12' ·P<0.05 5185 RECOMBINANT BACTERICIDALIPERMEABILITY-INCREASING PROTEIN ATTENUATES REMOTE GUT MUCOSAL INJURY IN LOWER LIMB ISCHAEMIA-REPERFUSION INJURY. Denis W. Harkin, Aires Ab Barros D'Sa, George Parks, The Queen's Univ of Belfast, Belfast, United Kingdom; The Royal Victoria Hosp, Belfast, United Kingdom. Lower limb ischaemia-reperfusion injury (IRI) is associated with remote gut mucosal injury. Endotoxin not only directly damages enterocytes but stimulates a systemic inflammatory response syndrome (SIRS), compounding gut injury. Recombinant bactericidallpermeability-increasing protein (rBPI-21) is a novel antiendotoxin therapy with proven benefit in sepsis, we examined its potential role in modulating the remote gut injury in hind limb IRI. Male Wistar rats prospective randomised control trial (n=8 per group). Control group and two groups undergoing 3 hours bilateral hind limb ischaemia with 2 hours of reperfusion (IRI) were randomised to receive intravenous control protein Thaumatin or rBPI at 2 mg/kg at reperfusion, respectively. We used quantitative morphometric assessment of the small bowel as a measure of gut injury. Morphometric assessment of the small bowel showed a significant decrease in mean mucosal thickness in the IRI group, 0.47+/-0.01 mm, compared with control group, 0.58+/0.01 mm, and IRI rBPI treated group, 0.61 +/-0.Dl, (P<O.OOI). Villus height-to-crypt depth ratio was significantly decreased in th IRI group, 1.94+/-0.05, compared to control, 2.82+/-0.04, and IRI rBPI treated group, 3.39+/-0.1, (P<O.OOOl). Data represents mean +/- standard error mean. These results indicate hind limb ischaemia-reperfusion injury is associated with a remote gut mucosal injury. Modulation in part by rBPI-21 antiendotoxin therapy, suggests endotoxin is harmful to the gut directly or by indirectly stimulating systemic inflammation in this model.