April 2000

in the Chinese population based only on the results of the H2 breath test,lead to an underestimation . Based on the H2 breath test plus the 13C-lactosedigestion test prevalence is 99%. A significant difference in Ih 13C-glucosevalues was observed between Chinese medical students and Dutch students(1.2 :t 0.5 vs. 2.9 :t 1.3 mmoVl). The Chinese students were divided in agroup having complaints after consumption of 25 g lactose (lactose intol­erant) and a group without having complaints (non-symptomatic lactosemaldigesters). No significant difference was observed in the lh 13C_glucose concentration between both groups (I.l :t 0.5 vs. 1.3 :t 0.5mmol/l), indicating that lactose digestion was similar in both groups. Thesedata suggest that in lactose intolerance, besides low small intestinal lactaseactivity another factor is of importance. This resistance factor presumablyis associated with the colonic metabolism of lactose .

4987

EXPRESSION OF BUTYRATE AND GLUCOSE TRANSPORTERSIN HUMAN COLON; IN HEALTH AND DISEASE.Stuart Wood, Daniel W. Lambert , Soraya P. Shirazi-Beechey, The Univ ofLiverpool, Liverpool, United Kingdom.

Dietary polysaccharides such as resistant starch and dietary fibre, that arenot hydrolysed in the small intestine, are fermented in the colon by colonicmicroflora to short chain fatty acids (SCFA) acetate, propionate and bu­tyrate. Normal colonic epithelia derive 60-70% of their energy supply fromSCFA, particularly butyrate. Butyrate induces cell differentiation, andregulates the growth and proliferation of normal colonic mucosa. Treat­ment of colon carcinoma cell lines with butyrate leads to emergence ofpermanently differentiated cell lines. The treatment by rectal SCFA irri­gation results in an improvement in the condition of patients with ulcer­ative colitis, a pre-malignant condition in the colon. We have shown thatthe only glucose transporter expressed in human colon is the low affinityfacilitative glucose transporter, GLUTI; this protein is located on thebasolateral membrane of colonic absorptive cells . We have also identifiedthe membrane protein involved in the transport of butyrate across thecolonic lumenal membrane as a monocarboxylate transporter, isoform I(MCT I) . We have further shown by immunocytochemistry and westernblotting that the protein is confined to the lumenal domain of colonicabsorptive cells and that the abundance of butyrate transport proteindeclines in human colon during transition from normality to malignancy .We have assessed the expression of butyrate transporter protein and mRNAin healthy and cancerous colonic tissues. In addition we have also inves­tigated the expression of the facilitative glucose transporter isoformsGLUTl and GLUTI. Diseased, and paired histologically normal tissue,was removed in the course of surgery from patients suffering from bowelcancer. Western blotting of isolated membrane fractions indicated that thelevels of MCTI and GLUTI were significantly reduced in the diseasedstate. However, the levels of the high affinity transporter GLUT I were seento increase in the diseased state compared with the normal condition . Thechanges identified in protein expression were also demonstrated at themRNA level by northern blot analysis. The re-expression of GLUT I in thediseased colon could be in response to the lack of availabilty of butyrate asthe colonocyte s metabolic fuel, and the high energy requirement in thecancerous state.

4988PERIOPERATIVE ADMINISTRATION OF MYCOPHENOLATEMOFETIL INHIBITS EXTRACELLULAR MATRIX SYNTHESISDURING HEALING OF COLONIC ANASTOMOSES IN RATS.Jorg M. Zeeh, Bernhard Egger, Nora E. Riley, Roman Ingling, Olaf Dirsch,Guido Gerken, Univ of Essen, Essen, Germany; Univ of Bern, Bern,Switzerland .

Background & Aims: Immunosuppressive treatment in patients who haveundergone surgical procedures may cause severe wound healing deficits.Inadequate healing and subsequent leakage from bowel anastomoses are amajor cause of postoperative morbidity and mortality . The influence ofimmunosuppressants on intestinal anastomoses is not yet described . My-

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cophenolate mofetil (MMF), a compound that selectively inhibits lympho­cyte proliferation, is used as an immunosuppressant after organ transplan­tation and is being considered as a treatment for Crohn's disease . We havepreviously shown that mycophenolate inhibits extracellular matrix synthe­sis in rat colonic smooth muscle cells in culture. Therefore , we investigatedthe effect of MMF on the synthesis of extracellular matrix during healingof colonic anastomoses in rats. Methods: Rats underwent laparotomy,division of the left colon, and sigmoido-sigmoidostomy. There were fourgroups of rats (each group, n=6): two groups were treated i.p. with MMF(25mglkg) from three days previous to surgery until sacrifice at day 4 orday 6 and the other two groups were treated with vehicle in the samemanner. At sacrifice, the anastomoses were excised and a 3mm piece fromboth sides of the anastomotic line were frozen in liquid nitrogen. Proteinswere extracted from the frozen tissue and protein amounts in each extractwere measured using a Biorad protein assay kit. Equal ug amounts ofprotein from each sample were electrophoresed on 6%Tris-glycine gels andthen blotted onto nitrocellulose membranes . Westerns using antibodies torat fibronectin and collagen I were performed . Bound antibody was de­tected using HRP-labeled second antibodies and enhanced chemilumines­ence. Results: Analysis of the Western blots showed that fibronectin andcollagen I levels in the tissue from the MMF treated rats were not signif­icantly different from vehicle treated rats at day 4 (p=0.68, fibronectin,p=0.62, collagen I). However, at day 6 the MMF treated tissue containedsignificantly less collagen I protein (p<0.05) than the vehicle treated.There was still no difference in fibronectin content (p=0.24). Conclusion:Mycophenolate mofetil decreases collagen I synthesis in colonic anasto­motic tissue from rats. This decrease may affect healing time and anasto­motic stability after intestinal and colonic surgical procedures if patientsare treated concurrently with this immunosuppressant.

4989

HEPATITIS A PRESENTING WITH MENINGOENCEPHALITIS,N. Zeng, M. J. Zuckerman, Texas Tech Univ Health Sci Ctr, El Paso, TX.

Background: Meningoencephalitis may rarely herald the onset of infectioushepatitis . Case report: A 20 year old Hispanic male without previousmedical problems presented to the ER after having a seizure followed bydecreased mental acuity for 2 days. The seizure was initially tonic clonicand became partial jerking in nature, focused only on the face and left arm.Associated symptoms included fever, nausea, vomiting, drowsiness, andgeneralized muscle weakness. There was no rash, jaundice or history ofhead trauma, drug abuse, alcoholism, animal or insect bites, or bloodtransfusion . He recently traveled to Juarez, Mexico and ate seafood. Onexamination, he was afbrile, anicteric, slightly obtunded and disoriented .Physical exam was otherwise unremarkable . Initial laboratory investiga­tions showed normal CBC, electrolytes, liver function tests and chest x-ray.Blood and urine cultures were negative; Serology was negative for EBV,mv and VORL. Head CT scan, MRI and EEG were normal. Cerebrospinalfluid was normal. While in the hospital, his neurological condition im­proved. However, his SGOT and SGPT became elevated at day five (364and 412) peaking at day six (1768 and 888), with bilirubin elevated at daysix (1.8), peaking at day ten (3.7). The serum hepatitis A IgM antibody waspositive and HBsAg and anti-HCV were negative. The patient was dis­charged in stable condition and had no recurrent seizure. Hepatic enzymesgradually returned to normal. Review of literature: A total of 31 cases ofmeningoencephalitis preceding, coincident with or after the onset of theicteric phase of infectious hepatitis have been documented in the literature(17 cases were reported before current viral hepatitis serologies wereavailable, 12 cases were hepatitis A and I hepatitis B, one both A and C).Neurological manifestations in the 12 hepatitis A patients included mentalstatus changes (7) or generalized tonic-clonic seizures (5). All patientsrecovered without neurological sequelae. Conclusion: Meningoencephali­tis is a rare extrahepatic manifestation of HAV infection. The identificationof HAVasa cause of acute viral encephalitis by readily available serologicmethods reduces the need for extensive costly diagnostic evaluations andfor potentially toxic empiric treatment.