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• RESULTS OF ENTEROSCOPY IN PATIENTS PRESENTING OCCULT DIGESTIVE BLEEDING WITH OR WITHOUT MELENA. A. Van Gossum, A. Schmit, F. Gay, M. Adler and M. Cremer. Dept of Gastroenterology, ULB, H6pital Erasme, B-I070 Brussels, Belgium.

Introduction : small bowel enteroscopy is a valuable method in the investigation of gastrointestinal bleeding of unknown origin. We compared the results in patients with or without melena. Material and Methods : from 1991 to 1994, 70 enteroscopies were performed in 66 patients with gastrointestinal bleeding of unknown origin. Our population consisted of 30 women with a mean age of 66 years (from 31 to 86) and 36 men with a mean age of 58 years (from 17 to 81). We used either the sonde-type enteroscope (n=14) (Olympus SIFSW) or the push-type enteroscope (n=56) (Olympus). Hemoccult was positive in every patient ; 30 patients experienced episodes of melena and 36 patients had no melena. Results : mean duration of sonde-enteroseopy was about 6 hours and push-enteroscopy lasted an average time of 35 minutes. Among 66 patients, a potential bleeding lesion was observed in 40 patients. The lesions were: oesophagitis (n=l), gastroduodenal ulcerations (n=6), small bowel tumor (n=2), Crohn's disease (n=2), gastroduodenal arteriovenous malformations (AVM) (n=3), small bowel AVM (n=20) and diffuse AVM (n=6). A small bowel lesion was observed in 47% of patients without melena and in 43% of patients with melena (NS)~ Detection of small bowel lesion was similar with the sonde or push enteroscope (50% and 43% respectively ; NS). Conclusions : there was no major difference in the efficiency of the two enteroscopy methods but the push-one is a much easier method than the sonde- one. Small bowel enteroscopy is an efficient method in patients with gastrointestinal bleeding of unknown origin, with or without melena.

BIOSYNTHESIS OF HUMAN SMALL INTESTINAL MUCINS. B.J.W. van Klinken, H.A. BOiler, J. Dekker, A.W.C. Einerhand. Pediatric Gastroente'ology & Nutrition, Acad Med Ctr, Amsterdam, The Netherlands

An important role of gastrointestinal mucins is to protect the epithelium trom luminal noxes. Inflammatory bowel disease may be associated with alterations in mucin composition or expression. Different human mucin genes (MUC1-7) have been described of which MUC2 and MUC3 were cloned from intestinal eDNA libraries. Muc2 is reported as the major secretory mucin in human colon (1). Aim: To study MUC2 and MUC3 mRNA expression and protein biosynthesis in human small intestine. Methods: Total RNA isolated from jejunum was Northern blotted and probed with MUC2 and MUC3 cDNAs. To analyse mucin biosynthesis, jejunum and duodenum were metabolically labeled with [35S]met/cys or [3H]galactose and immun0precipitated using specific cMuc2 and =Muc3 antisera and then analyzed by SOS-PAGE (1,2). To further identify mucin-precursors, digestion with Endo-H was performed. Results: Northern blotting showed that MUC2 and MUC3 probes strongly hybridized with small intestinal RNA. Immunoprecipitation of Muc2 from jejunal and duodenal homogenates after labeling with [35S]met/cys, showed a precursor of about 700 kD, which is comparable to the colonic Muc2-precursor (1). During chase- incubations the precursor-band was converted into a"higt~er molecular weight mature mucin, which was secreted. This mature mucin could also be labeled with [3H]galactose also being secreted. In contrast, human'colonic mature Muc2 has an apparent molecular mass of about 550 kD (1). Immunoprecipitation by anti-Muc3 antisera gave rise to a double band on SOS-PAGE of approximately 5501650 kD. Immunoprecipitation by ¢¢HCM, which was raised against Human Colonic Mucin and reacted with the 700 kD Muc2-precursor, recognized an extra band at about 500 kD, not precipitated by anti-Muc2 or anti-Muc3 antisera, suggesting the biosynthesis of an additional mucin, All putative mucin-precursor bands (i.e, 7 ~ 550/650, and 500 kD) were Endo-H sensitive. Conclusions: MUC2 and MUC3 mRNA are prominently expressed in human small intestine. Muc2 is biosynthesized in both duodenum and jejunum as a precursor of approximate(~} 700 kD, converted into mature mucin of higher molecular mass, and subsequently secreted. The mobility on SDS-PAGE of mature Muc2 from small and large intestine suggests that this mucin is differently glycosylated in these organs. Muc3-precursors were detected in small intestine as a double band of about 550/650 kD, suggesting allelic variation. The extra band immunoprecipitated at about 500 kD by cHCM suggests the biosynthesis of a third, yet not identified mucin. Refs: 1. Tytgat et al., Gastroenterology 1994;107:1352-1363; 2. Ho et aL, Cancer Res 1993;53;641-651. B,J.W. v a n K T i n k e n YS a n ASTRA r e s e a r c h {ellow

• THE RECTAL GLUTEN CHALLENGE SHOWS EVIDENCE OF GLUTEN SENSITIVITY IN PATIENTS WITH PRIMARY BILIARY CIRRHOSIS. H. Vazquez, S. Pedreire, R. Dazi, G. Marraco, A. PodestA, E. SmecuoL, S. Niveloni, I. Doldan, R. Mazure, E. Maurido, V. Bernath, J. Valero, Z. Kogan, R. Terg, L. Boerr, J.C. eai. Hospital de Gastroenterologla. Buenos A~ms, Argentina. A non fortuitous association between primary biliary cirrhosis (PBC) and celiac disease

(CD) has been suggested but [s yet unproven. A defective T cell reactivity and disease- specific autoantibodies are, among others, common immunologic features to both disorders. However, a more direct evidence for gluten-sensitivity in PBC is lacking. The rectal gluten challenge, a novel, simple and reliable test for gluten sensitivity may be a useful tool to study this association. AIM: To determine features of gluten sensitivity in PBC patients. MATERIAL: Nine patients with PBC (stages: I n= 1; II n=!,; Ill n=4; IV n=3) were evaluated (9 female, mean age 47 yr, range 38-63 yr), Parameters of rectal gluten challenge were compared with those of 20 CD patients and 12 controls. METHOD~ Gluten sensitivity was evaluated by several tests: t) CD related serum antibodies: Antigliadin types IgA and IgG (AGA) and antiendomysium (EmA), 2) Small bowel histology: villous/crypt structure and intraepithelial lymphocytes (IEL) count. Rectal gluten challenge: where a 4 h local challenge with 6 g of crude gliadin was assessed. Intraepithelia[ lymphocyte count in surface and crypt epithelium of a test area (pan-T cell immunocytochemistry) was quantifie d by computerized image analyses. An IEL response after challenge of more than 15% above pre-challenge count was indicative of gluten sensitivity. The presence of the HLA DQA1 0501 and B1 0201 haplotype was also evaluated in PBC patients. RESULTS. At the rectal gluten challenge, 4 out of 9 PBC patients had IEL response consistent with gluten sensitivity.

Rectal Small bowel histology CD related HLA haplotype

Challenge atrophy IEL count >20% antibodies DQA 0501 - B 0201

Positive (n=4) 2/4 2/4 4/4 1/2

Negative (n=5) 015 0/5 0/5 2/4

In summary, the rectal gluten challenge showed evidence of gluten sensitivity in a high proportion of PBC patients. Furthermore, this gluten sensitivity was concordant with partial small bowel m ucosal atrophy in two patient, and C D related se rum antibodies were present in all of them. The HLA haplotype DQA 0501 and B 0201 was present 3 out of 6 PBC patients but does not seem to be related to gluten sensitivity. Further studies might address if this association is related to common etiopathogenic factors to both disorders.

LONG TERM EFFICACY OF OCTREOTIDE THERAPY IN SEVERE POSTGASTRECTOMY DUMPING. J. Vecht, F. van der Kleij, C.B.H.W. Lamers, A.A.M. Masclee.Dept Gastroenterology-Hepatology, University Hospital Leiden, The Netherlands.

The somatostatin analogue octreotide has been shown to suppress signs and symptoms of early and late dumping in short term intervention studies. Little is known however, on the long term clinical efficacy of octreotide therapy in these patients. We report on our experience with 20 patients (12 M, 8 F, mean age 54 yr, range 31-74 yr) treated with 0ctreotide s.c. between 1987 and 1994 because of severe and disabling dumping symptoms refractory to dietary measures or other medical therapy (13 patients with eady dumping, 1 with late and 6 with both early and late dumping), All patients previously underwent gastric surgery: partial gastrectomy n=l 1, total gastrectomy n=2, vagotomy n=7. Diagnosis of dumping syndrome was confirmed by positive provocation test with 50 g oral glucose, which became negative after pretreatment with octreotide. Mean treatment duration at follow up was 29 months, range 1 - 86 months. The dally dose of octreoUde varied from 50 to 200 mcg. Eleven patients currently use octreotide; 9 patients have discontinued octreotide therapy because of lack of improvement of symptoms on the long term in 3 patients, and because of side effects in 6 patients (diarrhoea n=3, alopecia n=l , painful injections n=l , weight loss n=l .) Of the 11 patients on octreotide therapy subjective improvement of symptoms varies from moderate (N=2) to excellent (N=9). Fecal weight was not influenced by octreotide (290-J:50 vs 315~50 g/24h) but fecal fat excretion increased significantly (p<0.01) during octreotide therapy from 17:L-6 g/24h tO 31+7 g/24h (normal value <7 g/24h), Despite an increase in steatorrhoea, a mean gain in body weight of 2.1:1:0.4 kg, was observed because of increased caloric intake. Conclusions: Octreotide is an effective symptomatic therapy in the long terrn management of patients with severe early and late postgastrectomy dumping. The occurrence of side effects often limits prolonged clinical use of octreotide. Steatorrhoea increases during octreotide therapy but does not result in further weight loss.