The British Society of Gastroenterology - Gut

Glut, 1984, 25, A541-A585

The British Society of Gastroenterology

The Spring Meeting of the British Society of Gastroenterology was held from 25-27 April 1984 at the University ofSalford under the presidency of Dr R B McConnell. The scientific programme included 116 spoken communications and46 poster communications selected by the programme committee. The abstracts are given below. Further details of themeeting appear on p. 540.

LIVER

T1-14

TIEstablishment of a cell-line (PLC/NUT/i)containing integrated hepatitis B virus(HBV) DNA from a hormone associatedhuman primary liver cell cancer

N J CURTIN. P G INCF, K L (GAUNT, M J F

FOWI ER, 0 F W JAMES, AND M F BASSENDINE

(Departments of Medicine and Pathology,University of Newcastle upon Tvne and CellBiology Laboratory, RoYal Free HospitalSchool of Medicine, Lonidoni) Acontinuous human cell line has beenestablished from the primary hepato-cellular carcinoma (PLC) of a Britishwoman. The patient had no serologicalmarkers of HBV infection (HBsAg.HBcAb, and HBsAb ELISA-Abott all-ve X2). She had received long term sexhormone treatment for endometriosis. Thetumour was alphafoetoprotein (AFP)secreting and arose in a non-cirrhotic liver.The cell line, designated PLC/NUT/ 1

grows as an adhering monolayer; the cellsare of epithelial type and secrete alpha-foetoprotein. Karyotyping has shown achromosome mode of 63; 71% fallingwithin the range 51-67. There are eightidentifiable chromosomal markersconfirming a clonal origin. Despitenegative serum markers, HBV DNA wasshown to be integrated into the cellularDNA of PLC/NUT/1 by nucleic acidhybridisation using a cloned HBV(32P)DNA probe. Digestion with a restrictionendonuclease enzyme. Hind III, whichdoes not cut HBV DNA. yielded only onemajor and two minor fragments (largerthan hepatitis B virion DNA) containingHBV DNA sequences. This suggests thatthere are at most only three integrationsites of HBV DNA in these cells unlike thePLC/PRF/5 (Alexander) cell line in whichthere are 8+. When PLC/NUT/1 is hetero-transplanted subcutaneously into male

athvmic mice. tumours develop at the siteof inoculation. These are primary livercancer similar in morphology to theoriginal tumour and immunoperoxidasestaining is positive for HBsAg and AFP.These results suggest involvement of HBVin this hormone associated PLC. Thepaucity of sites of integration of HBVDNA into the DNA of this human PLC cellline will facilitate study of the oncogenicityof HBV.

T2Antiviral therapy for chronic hepatitis Bvirus (HBV) infection: treatment outcomeand influence of pretreatment factors

D M NOVICK. A S F LOK. P KARAYIANNIS. M J F

FOWLER. J MONJARDINO. S SHERLOCK, AND iiC THOMAS (Academic Departmenit ofMedicinie, Royal Free Hospital, PonidStreet, Hampstead, Lonidoni) Arandomised trial of adenine arabinosidemonophosphate (ARA-AMP) versuslympho-blastoid interferon (IFN) in thetreatment of chronic HBV infection is inprogress. ARA-AMP was given at adosage of 1i) mg/kg/day for five days andthen 5 mg/kg/day im 12 hourly for a total ofeither four or eight weeks. Interferon wasgiven at 1() MU/m'/day intra-muscularlydaily for five days and then thrice weeklyfor a total of 12 weeks. All 45 patients wereHBV carriers with raised transaminaseconcentrations for more than six months.All were hepatitis B e antigen (HBeAg)and HBV-DNA positive, and all hadbiopsy-proven chronic liver disease.Fifteen. 14 and 16 patients received ARA-AMP (four or eight weeks) or IFN.respectively. To date, a persistent loss ofHBV-DNA has been observed in fivepatients treated with IFN and three withARA-AMP (four weeks). All fiveresponders to IFN lost HBeAg and two lostHBsAg; two responders to ARA-AMP lostHBeAg and one lost HBsAg. Interferonwas better tolerated than ARA-AMP.

A541

which caused neurotoxicity or mvalgia in11 of 29 patients. Because only a minorityof patients respond to antiviral therapy. wereviewed the clinical features of 38 maleHBeAg-positive HBV carriers in this andprevious antiviral trials who had beenfollowed for one year or longer. The aimwvas to identify pretreatment factorspredicting a favourable response. definedas loss of HBeAg and HBV-DNA. Onlvtwo of 19 (11 % ) homosexual menresponded. compared with 10 of 19 (53%I )heterosexual men (p<()0()2). Both homo-sexual responders had received IFN. Noneof 13 homosexual men, but eight of 16heterosexual men, responded to ARA-AMP or ARA-A (p<().()l). Respondershad higher transaminase concentrationsthan non-responders but were otherwisesimllar.

Interferon may be more effective andbetter tolerated than ARA-AMP. Homo-sexual men respond less frequently toantiviral therapy, especially ARA-AMP.than do heterosexual men.

T3Significance of the delta antigen in acutehepatitis B

D A KELLY, D CARROLL. A C. SHiATTOCK, B MMORGAN E O CONNOR, AND D G WEIR(Departmenit o:f Medicinie, TrinitY College,Dlublin anid Departmenit of Medical Micro-biology, Universit-y College, Duiblini)During a recent hepatitis B epidemic inparenteral drug abusers. 29%(- of patientswere found to have associated deltaantigenaemia. We have followed up 30delta positive drug abusers in order toascertain: (i) the clinical course of theirliver disease, (ii) the extent of transmissionof both hepatitis B surface antigen(HBsAg) and the delta antigen (bAg) toclose contacts.

All patients presented with acutehepatitis B. Using an ELISA assay toestimate the bAg and anti-delta2. 20(

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patients were positive for bAg and 10 hadanti-delta (anti-b) on initial testing. Theclinical course was uneventful in 25/30)patients. 5/3(0 patients had a prolongedillness with cholestasis, none of the patientsdeveloped fulminant hepatitis. All patientscleared both HBsAg and bAg, and therehas been no progression, as yet, to chronicliver disease.A total of 53 family contacts were traced.

50) contacts had no evidence of positivemarkers for either hepatitis B or deltainfection. Three famillv contacts hadantiHBs. one of these was positive foranti-delta. Many patients denied or refusedto name sexual contacts and oniv eightwere traced. Five out of eight of thesecontacts had positive hepatitis B markers(3-HBsAg; 2-anti-Hbs) and two of thesehad bAg; one had anti-delta. All three alsoadmitted to parenteral drug abuse whereasthe two patients with negative deltamarkers were not drug addicts.

It is concluded that in this group ofpatients the combination of acute hepatitisB and simultaneous delta infection has nothad an adverse effect on their liver disease,and while there was a low rate of trans-mission of HBsAg to family and sexualcontacts, transmission of b(Ag) wasconfined to parenteral drug abusers.

T4Genetic factors in the response to hepatitisB virus? A study in 34 sets of siblings

M CHIARAMONTE, A FLOREANI, C SCANDOLA, E

PORNARO, M G BERLANDA, AND R NACCARATO

(Departmenit of Internial Medicine (Divisiono)f Gastroenterology,) and Blood BankUniversitv of Padova, Italy) The aim ofthis study was to investigate the respectiveroles of the following factors in the familialclustering of HBsAg carriers:consanguinity. sex, age at the infection andvertical transmission. To that, we studied34 kindreds (total sibs n=98) and 52spouses of HBsAg carriers. We correlatedthe response to HBV infection with sex.age, infection in parents and sequence ofsibs in the family (assuming that thedifferent responses to HBV might be dueto the different ages of sibs at the entry ofthe infection into the family).The overall prevalence of HBV infection

was 79C( in spouses, 97%C in adult sibs and70%/c in child sibs, while HBsAg+ve/HBV+ve rate was 14',k in spouses. 76% inadult sibs and 81 c'S in child sibs. In 14kindreds, all the siblings were HBsAg+ve;in five, all the infected sibs were

HBsAg+ve; \vhile in 15. anti-HBs+vesubjects were present along with HBsAgcarriers. Parents (either the mother or thefather) were HBsAg+ve in 64'S, of the firstgroup, in 75%/c of the second group and in38%X. of the third group families. In threefamilies of the third group, both parentswere HBV-ve, while the parcnts from theother families had antiHBV antibodies. Norelationship was found between theresponse to HBV and age, sex, or sequenceof the sibs in the familv.The subjects negative for HBV \vere

then vaccinated (HEVAC-B. Pasteur).The antiHBs titres in both vaccinatedsubjects and in spontaneously antiHBsproducers were similar in spouses andsiblings.

In summary, being that the risk of HBVinfection is similar for spouses and siblings,the blood relatives have a high risk ofremaining HBsAg+ve. This trend is notstrictly correlated to the vertical trans-mission. We conclude that these results areconsistent with the existence of a 'genetic'predisposition to the failure of HBsAgclearance, which, however, seems not toinvolve the antiHBs production. Thisgenetic factor is independent from, andpossibly stronger than, age and sex.

T5Pancreatitis in fulminant hepatic failure

R J EDE, K MOORE, W' MARSHALL. AND R

WILLIAMS (Liver Unlit anid Departitnenit ofChemical Pathology, King's CollegeHospital, London) Acute pancreatitis is arecognised complication of acute viralhepatitis and has also been reported inassociation with fulminant hepatic failure(FHF). We now report a prospective studyof 36 patients admitted to this unit withfulminant hepatic failure, all of whom wereexamined for serum enzvme evidence ofpancreatic injury.Serum lipase and total serum amvlase

were measured (Boehringer and Phadebasrespectively) and pancreatic iso-amylaseactivity was determined by electrophoreticfractionation on cellulose acetate using amodification of the method of Legaz andKenny. Electrophoresis was performed at4cC for 90 minutes with a constant currentof 0(5 mA/cm and isoenzvmes. stained bvPhadebas reagent. were quantified as apercentage of total amaylase activitv.

Total amylase activitv was increased(>300 IU/1) in 24 of the 36 patients and in11 patients activity was greater than 10 10(1)0IU/1. Isoenzyme electrophoresis performed

in the 29 patients with total amylaseactivity >20)0 IU/I revealed a distinct P,band, indicative of acute pancreatitis. in 22cases. In four of the patients with totalamvlase >11)1)0 IU/I the PI isoenzyme wasabsent and the increased activity wasattributable mainly to an increase in thesalivary SI isoenzyme of uncertainaetiology. Serum lipase activity was raised(>40)0 IU/I) in 31 patients (86C/c) and wasincreased in all but one of the patients withdetectable PA isoenzxme. The highfrequency of pancreatic enzymeabnormalities found in this study suggeststhat acute pancreatitis may be morecommon than previously suspected infulminant hepatic failure.

T6Evaluation of terfenadine compared withother drugs in the treatment of biliarvpruritus

1i J KENNEDY, J S DUNCAN. AND D R TRIGER(Departmenit of Medicinie, RoyialHallamshire Hospital, She eldd) Pruritusis a troublesome symptom of chronicobstructive liver disease. Antihistaminesand cholestyramine are widelv used butboth cause adverse side effects. We havecompared terfenadine (a new HI specificantihistamine reported to be free ofsedative effect) with cholestvramine. chlor-pheniramine. and placebo in a single blindrandomised crossover trial in 11) patientswith long standing pruritus secondary tochronic liver disease.

Objective assessment was made bvpsychometric testing and electroencephalo-graphy. In addition. the patients kept adaily record of pruritus and of side effects.Each drug was taken for a two week periodin random order.

Cholestyramine (up to 12 g daily) andterfenadine (61) mg twice daily) both hadsignificant antipruritic activity whencompared with placebo (Wilcoxon's ranksum test p>0.05). Substantial benefit wasoften found with one or other of thesedrugs rather than both. Chlorpheniramine(up to 4 mg tds) was ineffective and causedside effects in three patients. Cholestyra-mine caused gastrointestinal svmptoms infive patients. Terfenadine was welltolerated and did not produce any clinicalor electroencephalographic deterioration.We conclude that terfenadine is of value inthe management of some patients withbiliarv pruritus. There may be a place forconcurrent use of terfenadine and chole-stvramine in some individuals.

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T7Primary biliary cirrhosis (PBC): a newprognostic index

J L SHAFFER, R BENNETT, W JONES J D KBROWN, AND M N MARSH (Departments ofMedicine, Radiology and Medical Physics,Hope Hospital and University ofManchester, School of Medicine, Salford)Primary biliary cirrhosis usually runs a

prolonged asymptomatic course. The onsetof liver failure and decompensation ispreceded by progressive rises in bilirubinconcentrations. Our aim in this study was

to predict impending hepatic dysfunctionby prospectively analysing E-HIDAkinetics in primary biliary cirrhosis. Thetest, which was repeated annually over

three years, was carried out on 11 patients(9F/2M: age range 47-75 years) who eachreceived IV 75 MBq 99T,n'-E-HIDA.Plasma decay curves, based on 16consecutive venous samples over 24 hours,were used to determine (i) the interval forplasma radioactivity to reach 5% of theinjected dose (ts,) and (ii) the total areaunder the concentration-time curve(AUC). Total urinary radioactivity was

measured over 24 hours. Hepatic uptake oftracer was monitored at minute intervalsafter intravenous injection for two hourswith a computerised y-camera. From theseobservations the rates of liver uptake andclearance of tracer were determined. Theabove data were then subjected to a

principal components analysis from whicha radioactive index (RAI) was derived.Values for RAI (range 13-277) showed a

highly significant correlation with plasmabilirubin (r=0'83; p>0'001). In three offour patients who died from liver failureduring the course of the study, the RAIexceeded 100 12-18 months before theaccelerated rise in plasma bilirubin was

noted. Serial measurements of RAI in theremaining seven patients have remainedunchanged, and treatment of five of theselatter subjects with D-penicillamine neitherappeared to alter plasma bilirubin con-

centrations, or RAI. Thus, the RAI is (i) a

reproducible index of liver function in

PBC, and (ii) appears to be much more

sensitive than plasma bilirubin concentra-tions in predicting the onset of terminalliver failure.

T8'Plugged' percutaneous liver biopsy. A safemethod for patients with impaired bloodcoagulation

S A RILEY, W R ELLIS, D J LINTOTT, H C IRV ING,A T R AXON, AND M S LOSOWSKY (St James'sUniversity Hospital, and The GeneralInfirmary, Leeds) Tissue diagnosis is

often desirable in patients with severe liverdisease, but percutaneous liver biopsy is

usually avoided in those patients whoseprothrombin time is prolonged by threeseconds or more or whose platelet count isless than 8(x 10"/l. Alternative methods,such as transvenous biopsy, are not alwayssatisfactory. We use a simple modificationof the percutaneous method, in which,under ultrasound or fluoroscopic control,the needle track is plugged with gel-foamon withdrawal. Either a modified 'Tru-cut'needle is used in which the outer sheathcan be left in the liver on removal ofobturator plus specimen, or a 'Medicut'(18G) sheath is placed over the biopsyneedle beforehand and passed into theliver before withdrawal of needle andsample. The procedure requires breathholding for about 15 seconds and has beenused in 18 patients with disturbedcoagulation. Biopsies were between 0(4and 2 2 cm in length, in 17 cases wereadequate for diagnosis, and contributedinformation with potential to influencemanagement. One patient, alreadymoribund with severe, rapidly progressiveliver disease, could not cooperate and bledsignificantly from the biopsy site, dyingsubsequently. No detectable bleedingoccurred in the other patients whosehaemoglobin levels did not fall after theprocedure.We conclude that plugged biopsy is

useful, safe, and easily performed, butpatient cooperation is essential.

T9Cirrhosis in young adults: might trans-plantation alter the outcome?

J J KEATING, R D JOHNSON, P J JOHNSON, ANDROGER WILLIAMS (Liver Unit, King'sCollege Hospital, London) Resultsrelating to survival after liver transplanta-tion vary between centres and are likely todepend both on the nature and stage of theliver disease. The decision as to when theoperation should be performed requires a

knowledge of the natural history of suchpatient groups. We have, therefore,performed a retrospective analysis of theclinical course and survival of 75 youngadults (aged 15-30) years) presenting forthe first time with cirrhosis between 1970and 1983 (median follow up period, 4'5

years). The aetiology of the cirrhosis was,autoimmune chronic active hepatitis (38),cryptogenic (16), Wilson's disease (9) andother varieties ( 11).

Only one death has occurred in the 37patients with well compensated liverdisease (33 Child's grade A and 4 Child'sgrade B) whereas of the 38 patients withdecompensated liver disease (Child's gradeC) 22 (88/c) of the 25 treated conserva-tivelv have died. In contrast seven (54%/s)of the 13 Child's grade C patients under-going liver transplantation are alive andwell. Comparison of survival in the twogroups by life table analysis (log-rank test)showed that the transplanted groupsurvived significantly longer (p<0'05).50%)c survival being 50 and 15 monthsrespectively.

T1OUnexpected effect of vitamin K on factorVIII in liver disease

D A KELLY, S MIKAMI, E G D TUDDENHAM,AND J A SUMMERFIELD (Department ofMedicinie and Haemophilia Centre, RovalFree Hospital School of Medicinie, London)Factors V and VIII are now thought to besynethesised in the liver and inactivated byprotein C, a recently discovered vitamin Kdependent protease, which is alsosynthesised in the liver. In order toascertain the effect of liver disease on theseglycoproteins we estimated factor V using abioassay; factor VIIIC using both bioassay(VIIIC) and immunoassay (VIII:CAg);and protein C antigen using radioimmuno-assay, in 35 patients before and afterparenteral vitamin K 10 mg. Using theprothrombin ratio and its response tovitamin K as an index, 22 patients wereconsidered to be vitamin K replete (13 hadparenchymal liver disease and nine hadprimary biliary cirrhosis on maintenancevitamin K). Thirteen patients with extra-hepatic cholestasis were vitamin Kdeficient. The plasma concentration ofVIII:CAg was raised in both groups(vitamin K replete - 2 7±0 4 units/ml;vitamin K deficient - 4.2±0.1 units/ml,mean ± SEM, normal range 0 5-2t0units/ml) while VIIIC was minimally raisedin the vitamin K deficient group only(2'5±t()2 units/ml). There was a significantfall in the plasma concentrations of bothVIIIC (38%) and VIII:CAg (36%) follow-ing vitamin K (p<0-001). Factor V levelswere low in the vitamin K replete group(0)54+0'1 units/ml, mean ± SEM, normal

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range 0-5-1-5 units/ml) and twice that levelin the vitamin K deficient group (1 2+0 1units/ml, p<0(001). Protein C levels were

low in both groups (0 70±0 1,mean + SEM, normal range 0-74-1 39units/ml). There was no significant changein either factor V or protein C antigenlevels following vitamin K. The datasuggest: (i) that the raised factor VIII: CAglevels and, (ii) the reduction in both VIIICand VIII:CAg following vitamin K in liverdisease were not mediated by protein C;(iii) that protein C has little effect on

circulating levels of Factors V and VIII invivo.

TllEffects of A [32-blocker (ICI 118, 551) on thehepatic haemodynamics

S A JENKINS, J JOHNSON, P DEVITT, J N

BAXTER, AND R SHIELDS (Department ofSurgery, Royal Liverpool Hospital,Liverpool) Although propranolol may beeffective in lowering portal pressure, [3-blockade sometimes makes resuscitationdifficult should the patient experience,;ecurrent variceal haemorrhage. This studywas therefore carried out to investigate theeffect of varying rates of an exclusive[32-blocker (ICI 118, 551) infusion onhepatic haemodynamics in the rat.Male Wistar rats received a 20 minute

infusion at either 0, 1 25, 2 5, 5-0, 100) or

20 00 ,ug/min/kg bw 32-blocker. Portalpressure, portal venous flow, arterial bloodpressure and pulse were recorded con-

tinuously throughout the experiment.Liver blood flow was measured by theclearance of xenon-133 before and after theinfusion of f12-blocker.

Infusions of 0, 1-25, 2-5 and 5o Ag/min/kg bw P12-blocker had no significant effecton hepatic haemodynamics. After an

infusion of 10 ,g/min/kg bw [3,-blocker,there were significant reductions in portalpressure (6.6±0.9 to 3 7±0 8 mm/Hg)portal venous flow (34 6+1 8 to 26±2 3ml/min) and liver blood flow (37-6+4 1 to25-8±2.6), without significant reduction inpulse or arterial blood pressure (Student's ttest). Greater reductions in portal pressureand liver blood flow were obtained after an

infusion of 20 /min/kg bw Pl2-blocker.The results suggest that an exclusive

f32-blocker (ICI 118, 551) can modifyhepatic haemodynamics without a cardiaceffect and may be of value in the treatmentof portal hypertension.

T12Role of free oxygen radicals in rat models ofhepatic injury

M J P ARTHUR, I BENTLEY, A R TANNER, AND

RALPH WRIGHT (Department of Medicine,Southampton General Hospital,Southampton). Free oxygen radicals pro-mote injury in a variety of tissues, but thereis limited evidence of their role in thepathogenesis of liver damage. We havestudied the role of free oxygen radicals in

rat models of mild and severe hepaticinjury produced by intravenous C Parvumadministration with or without thesubsequent administration of intravenousendotoxin. The effect of superoxidedismutase (SOD) and allopurinol (Allo) inpreventing such injury was studied. On day1, 100 male Wistar rats received C Parvum.On Day 6, 50 rats received endotoxin and50 received normal saline. They were thensubdivided into groups of 10 and treated as

follows: controls, normal saline intra-venous: experimental groups, superoxidedismutase 5000 u/kg intravenous:allopurinol 100 mg/kg po for three days+50 mg/kg intravenous; combined SODand Allo as above; heat inactivated SOD(HI-SOD). Assessment included mortality,serum alanine aminotransaminase (ALT)and isocitrate dehydrogenase (ICDH) con-

centrations at the time of death or whenkilled on day 7.

In the severe hepatic injury model,mortality was decreased in the SOD (0/10,p<r((0.005), Allo (2/10) and combined SOD/Allo groups (2/10) compared with control(6/10) and HI-SOD groups (7/10). Further-more, there was a significant reduction inserum ALT concentrations (Mean + SDIU/I) in the SOD (132±128, p<0O01) andcombined SOD/Allo groups (448+885, p0.05) compared with controls (778±783),whereas ALT concentrations in the HI-SOD group were not significantly different.Similar changes were found for serum

ICDH levels. In addition, the same trendsin ALT and ICDH concentrations were

observed in the mild hepatic injury model.These results indicate that free oxygenradicals may play an important role in thepathogenesis of hepatic injury.

T13Impaired platelet function and prolongedbleeding time in chronic alcholics

W J JENKINS, D P MIKHAILIDIS, M A

BARRADAS, J U JEREMY, AND P DANDONA

(Departments of Medicine and Chemical

Pathology, Royal Free Hospital, London)High concentrations of ethanol are knownto impair platelet aggregation and therelease of thromboxane A2 (TXA,) acutelyin volunteers. Impaired platelet functionand a prolonged bleeding time secondaryto alcohol abuse may contribute to theincreased incidence of upper GIhaemorrhage in chronic alcoholics.Seventeen consecutive patients with

alcoholic liver disease of varying severitywere studied after admission for alcoholwithdrawal. Bleeding times were measuredby the Simplate II modification of thetemplate method. Platelet aggregation wasinduced in platelet rich plasma by addingeither adrenaline 5 ,umol/l, ADP 10 ,umol/lor collagen 1 mg/l and TXA, generationwas measured by radioimmunoassay ofTXB,. Eight patients with the longestbleeding times were studied serially afterone and two weeks abstinence.The mean bleeding time in chronic

alcoholics on admission (10-5, range 4 5-26 5 minutes) was significantly prolonged(controls mean=5 6, range 2 5-9.5minutes) (p<0O05). Prolongation of thebleeding time correlated significantly withimpaired platelet aggregation induced invitro by ADP, adrenaline, or collagen(p<0(05) and reduced TXAM genera-tion/10 platelets (p<0.05). Serial studiesshowed that these abnormalities of plateletfunction persisted after alcohol withdrawalbut corrected together with the bleedingtime after two weeks abstinence.Chronic alcohol abuse is associated with

impaired platelet function and prolongedbleeding times, which persist for up to twoweeks after alcohol withdrawal. This maypredispose to upper GI haemorrhage.

T14Chronic liver disease in abusers of alcoholand parenteral drugs: a report of 204consecutive biopsy-proven cases

D M NOVICK, R J STENGER, A M GELB, J MOST, SR YANCOVITZ, AND M J KREEK (INTRODUCEDBY H C THOMAS) (Departments of Medicineand Pathology, Beth Israel Medical Center,and Mount Sinai School of Medicine, andThe Rockefeller Universitv, New York,New York, USA) Abusers of parenteralheroin or cocaine frequently developchronic active hepatitis (CAH), chronicpersistent hepatitis (CPH), or non-specificreactive hepatitis (NSRH) as a result ofpersistent virus infections or adulterants ofthe drugs. Alcohol abuse (AA) may occurbefore or after parenteral drug abuse

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(PDA), but little has been published onliver diseases in patients with both AA andPDA. In a hospital for addictive diseases,we evaluated 204 consecutive patients whounderwent liver biopsy because chronicliver disease was suspected. Patientsthought to have acute viral hepatitis werenot biopsied. The addictive diseasesconsisted of alcohol alone in 23, parenteraldrug abuse alone in 34, and both alcoholabuse and parenteral drug abuse in 147.Cirrhosis was found in seven patients(30%) with AA alone, three (9%) withparenteral drug abuse alone, and 76 (52%)with both (p<0.001). Chronic activehepatitis was found in one (4%) withalcohol abuse, 15 (44%) with parenteraldrug abuse, and 17 (12%) with both(p<0.001). For other diagnoses, nodifferences in addictive diseases werefound. Twenty six of the 204 patients hadalcoholic hepatitis, 23 had fatty infiltration,10 had chronic persistent hepatitis, ninehad non-specific reactive hepatitis, one hadhepatocellular carcinoma, and 16 had otherdiagnoses. Evidence of decompensatedliver disease was more common in patientswith both AA and PDA. The 147combined abusers included 39 with AAand PDA at the time of liver biopsy and 96with AA who had stopped PDA. Cirrhosiswas found in 10 (26%) of the former groupand 58 (60%) of the latter (p<0-005). Weconclude that abuse of both alcohol andparenteral drugs is associated with a moresevere chronic liver disease than that seenwith either AA or PDA alone.

SMALL BOWELT15-28

T15Characterisation of the stimulus initiatingthe ileal brake in man

R C SPILLER, I F TROTMAN, Y C LEE, M A

GHATEI, S R BLOOM, J J MISIEWICZ, AND D B A

SILK (Department of Gastroenterology andNutrition, Central Middlesex Hospital,London, and Department of Medicine,RPMS, Hammersmith Hospital, London)We have previously shown that ilealinfusion of partially hydrolysed triglycerideinhibits jejunal motility and delays jejunaltransit. The present study was designed toidentify the component of the triglyceridemolecule responsible for activating the ilealbrake in man. Oleic acid (9.6 g), triolein(10 g), medium chain triglycerides (MCT,10 g), and glycerol (3-1 g) were emulsified

with bile salts, rendered isotonic, andseparately infused at 5 ml for 30 minutesvia an ileal port situated 175 cm from themouth of 13 healthy volunteers. Through-out the study a fat free nutrient solutionwas infused at 3 ml/min just beyond theduodenojejunal flexure and jejunal intra-luminal pressures were recorded throughwater perfused ports opening 15, 25. and35 cm further distally. Jejunal motility wasstrikingly inhibited by ileal oleic acid(n=6), percentage duration of activitybeing only 6±2 (mean ± SEM) of the first30 minutes after oleic acid infusion com-pared with 41±2 during the control hour(n=13, p<O01). Pressure activity thenrecovered rapidly to 31±71%. one and ahalf hours after completing the oleic acidinfusion (NS vs control). After ileal trioleininfusion jejunal inhibition was slower inonset, percentage activity falling to 26±4and 20±6 (p<0-01, n= 13), 30 and 60minutes after completing the infusion.Recovery was more gradual, reachingcontrol values (38± 11) only after twohours. Ileal MCTs produced significantjejunal inhibition (n=6, p<0-01) inter-mediate in magnitude and time coursebetween oleic acid and triolein, while ilealglycerol had no significant effect (n=6,p>0 10). These findings indicate thatreceptors for the ileal brake reflex are moreresponsive to free fatty acids than to intacttriglyceride, suggesting that intraluminallypolysis is essential if the ileal brake is tobe activated by malabsorbed fat in man.

T16Functional significance of the ileal brake incoeliac disease

R C SPILLER, Y C LEE, C EDGE, D N L RALPHS,S R BLOOM, J S STEWART, AND D B A SILK(Central Middlesex Hospital, London,RPMS, Hammersmith Hospital, MiddlesexHospital, and West Middlesex Hospital,London) Mouth-caecum transit of a testmeal is delayed by ileal fat infusion innormal man suggesting that in patients withfat malabsorption excess ileal fat may exerta similar inhibitory effect. We have there-fore measured the mouth-caecum transittime of a mixed liquid test meal (400 Kcal,labelled with 16 g lactulose) in 12 controlsand 26 coeliac patients, using the breathhydrogen technique, assessing the ileal fatload by measuring the 24 hour faecal fatexcretion. Transit was significantly delayedin coeliacs with steatorrhoea, being189±17 minutes (n=15) compared with119±18 minutes (n= 11) for coeliacs

without steatorrhoea (p<001) and 91±9minutes for 12 healthy controls (p<O0l1).Slow transit was not associated withdelayed gastric emptying as assessed bygamma-camera in 10 of the coeliac patientsbut was associated with various indices ofjejunal injury including impaired release ofthe upper 'gut' hormones cholecystokinin,gastric inhibitory polypeptide, and insulin(r=0-38, 0 35, and 0 40, all p<005,n=31). Slow transit was also associatedwith the raised fasting levels, delayedpostprandial rise, and reduced integratedincremental postprandial response ofplasma cholylglycine (all p<005, n=14),results consistent with delayed gall bladderemptying as previously described incoeliacs. Of all the variables assessed,however, the best predictor of delayedtransit was the 24 hour faecal fat excretion(r=0 52, n=26. p<0.01). Our findingssupport the hypothesis that jejunal injuryand impaired pancreatico biliary secretionsare associated with delayed transitbecause, by impairing fat absorption andincreasing ileal fat load, they activate theileal brake, thereby slowing small boweltransit.

T17Ileocolonic junction - phasic and tonicspecialisation at a gastrointestinal sphincter

E M M QUIGLEY, S F PHILLIPS, B CRANLEY, B M

TAYLOR, AND J DENT (The Gastro-enterology Unit, Mayo Clinic and Founda-tion, Rochester, MN, USA) The ileo-colonic junctional region contains a zone ofsustained tone, the ileocolonic sphincter(ICS) and also shows unique patterns ofphasic motor activity. Our aim was todelineate the topographic distribution ofthese motor patterns. Studies of fastingileocolonic motor activity were performedfor a total of 90 hours in seven consciousdogs using multiple closely spaced perfusedcatheters (five dogs) and extraluminalstrain gauge transducers (two dogs). Pull-through pressure measurements at the ileo-colonic junction were then carried out atlaparotomy in each dog and areas ofsustained tone marked under direct visualand radiograph control. After removal ofthe bowel the anatomical features of thesehigh pressure zones were defined by lightmicroscopy.Unique phasic patterns were recorded

from a 35 cm segment incorporating theileocolonic sphincter, 30 cm distal ileum,and 5 cm proximal colon; discrete bursts ofrhythmic activity progressively replaced

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irregular phase II type activity as the ICSwas approached while at a mean interval of115 minutes distinctive, high amplitudepropulsive waves swept through thesegment. In contrast, sustained tonicpressures (10-70 cm H,O) were recordedonly from a 1-2 cm zone at the ileocolonicjunction. Rises of tonic pressure related tophasic bursts were greater here (55.5±5.1cm H,O) than in distal ileum (12-8±2) orproximal colon (19.5±6-7) (p<0.05) andepisodes of tonic relaxation were confinedto this zone. Pull-through studies similarlyidentified a narrow (mean length 2 cm)high pressure zone (mean amplitude 34 cmH,O) which corresponded to theanatomical ICS. Thus motor specialisationis evident at two levels in this region; tonicresponses being confined to the anatomicalsphincter while unique phasic patternsidentify a more extensive functionallydistinct segment.

T18Demonstration of receptors for prosta-glandin E2 on rat small intestinal epithelialcells

G SMITH, G WARHURST, AND L A TURNBERG(Department of Medicine, Hope Hospital(University of Manchester School ofMedicine), Salford) Prostaglandins, pro-duced in the small intestine by sub-epithelial tissues and degraded by theepithelium, may have a role in control ofintestinal secretion. We report here studiesperformed to examine the possibility thatprostaglandins act by a receptor mediatedmechanism. Plasma membrane fractionsfrom rat small intestine epithelial cellsshowed a small but significant specificbinding of 3H PGE, (total binding22-23±2 2, non-specific 19-85±1 77 andspecific binding 2 38±0+48 fm/mg protein,p<0 02, paired t test).

Biochemical studies support the con-clusion that a receptor mediatedmechanism activates epithelial adenylatecyclase. Solubilisation of plasma mem-brane adenylate cyclase with Lubrol PXmarkedly inhibited prostaglandin E2 stimu-latable activity of the cyclase. Thisprocedure separates the receptor moiety ofadenylate cyclase from the catalytic unit.Similar results were obtained with VIPstimulated activity. Non-receptor mediatedstimulation, with ysGTP, forskolin orfluoride which directly activate thenucleotide binding or catalytic units,however, was unaffected by solubilisation.

In addition VIP and PGE2 stimulation ofadenylate cyclase required GTP whichnon-receptor mediated stimulation byfluoride did not. These data support amodel in which subepithelially producedprostaglandins stimulate epithelialsecretion by a receptor mediated activationof adenylate cyclase. The studies haveimplications for secretory diarrhoealdiseases in which locally produced prosta-glandins may be an important mediator.

T19Intestinal permeability in patients withlongstanding psychiatric disease

N C WOOD, A M J SHAPIRO, S KHAN, P QUIRKE,K MCGUIGAN, I HAMILTON, R S H MINDHAM, J

ROTHWELL, AND A T R AXON The Gastro-enterology Unit, The Professorial Depart-ment of Psychiatry, and ProfessorialDepartment of Pathology, The GeneralInfirmary, Leeds) The cellobiose/mannitol test which is based on the differ-ential absorption of two different sizedmolecules is a reliable screening test forcoeliac disease and is also abnormal inother conditions characterised by abnorm-alities in intestinal permeability such asCrohn's disease and dermatitis herpeti-formis. Previous studies have suggested anincreased incidence of coeliac disease inschizophrenia and to investigate this thecellobiose/mannitol test was performed in32 longstay psychiatric patients. Abnormalresults were found in 11 (34%), and ofthese six were well into the range normallyfound in coeliac disease. Ten patients withabnormal and 10 with normal tests werestudied in greater depth. In order toexclude a metabolic as opposed to anabsorptive explanation for the findingseach group was given intravenous cello-biose and mannitol, but no difference inexcretion ratios was found. Duodenalbiopsies were taken from the 20 patientsand on light microscopy all but one werewithin normal limits, as were representa-tive samples taken for electronmicroscopy.All 32 patients were interviewed by apsychiatrist and classified as suffering from'definite' schizophrenia, 'probable' schizo-phrenia. or non-schizophrenic psychiatricillness according to Feighner's criteria. Norelationship was shown between intestinalpermeability, psychiatric diagnosis, or drugtherapy.There appears to be a large subgroup of

patients with chronic psychiatric diseasewho have abnormal intestinal perme-

ability; the significance of this is unclear,but it is not because of coeliac disease andfurther studies are required.

T20Screening for small intestinal mucosaldamage using the lactulose L-rhamnosesugar permeability test

I A SANTANA, M B TALBOT, B K SHARMA, AND

R E POUNDER (Academic Department ofMedicine, Royal Free Hospital School ofMedicine, London) It is often difficult toidentify the minority of patients withorganic disease from the majority withfunctional disorders. In a prospectivestudy, patients presenting with diarrhoeahave been screened for small intestinalmucosal damage using a sugar permeabilitytest.The test, using lactulose and L-rhamnose

as probe molecules, can detect untreatedvillous atrophy or Crohn's disease. It isnon-invasive and is performed at home: thefasting patient swallows 4.7 g lactulose, 1 gL-rhamnose, and 12 ml glycerol made up to100 ml with water. Urine is collected forthe next five hours, and the concentrationof the probe sugars in the urine measuredusing thin layer chromatography.Seventy seven consecutive new

outpatients with diarrhoea were fullyinvestigated: nine were found to haveulcerative colitis, 10 Crohn's disease, sixvillous atrophy, and 52 were thought tohave a functional disorder. All the patientswho presented with either Crohn's diseaseor villous atrophy had an abnormal sugartest; there were no false negative results.Forty nine of the 52 patients with afunctional disorder had a normal test. Twoof nine patients with ulcerative colitis hadan abnormal sugar test, but no otherevidence of small intestinal disease.The lactulose L-rhamnose sugar

permeability test is a simple, safe, and anon-invasive screening procedure for smallintestinal mucosal damage.

T21Non-invasive assessment of the superiormesenteric artery blood flow in man

M I QAMAR, A E READ, R SKIDMORE, J MEVANS, AND P N T WELLS (UniversityDepartment of Medicine, Bristol RoyalInfirmary Department of Medical Physics,Bristol General Hospital, Bristol) Methods

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available for the assessment of superiormesenteric artery blood flow (SMABF) areinvasive and difficult to perform. In thepresent study transcutaneous Dopplerultrasound was used to estimate SMABF.A duplex scanner, which consists of areal-time imaging system associated with aDoppler ultrasound flowmeter. was used tostudy the SMABF in 46 healthy subjects.By processing the Doppler shift signals ofthe superior mesenteric artery theinstantaneous average velocity of the bloodflow over the cardiac cycle was calculated.Both the diameter of the vessel and theangle between the vessel and Dopplerbeam were measured from the real timeimage. The mean (+SEM) resting SMABFwas 561±32 ml/min. There was nostatistical difference in flow between thesexes or in different age groups. In thesecond group of 15 healthy volunteers theSMABF was measured before and after amixed meal (683 kcal) for two hours. Theblood flow increased within five minutes ofthe end of the meal by 61% and more thandoubled within 15 minutes.The potential application of the method

in the diagnosis of chronic intestinalischaemia will be discussed.

T22Peptide chain length of protein hydrolysatesinfluences jejunal nitrogen absorption

R G REES, G K GRIMBLE. P P KEOHANE. B E

HIGGINS. M WEST. R C SPILLER, AND D B A

SILK (Departmzents of Gastroenterologvand Nltrition anid Chemical Pathology.Central Middlesex Hospital, Londoni) Thenature of the enzymic digestion and thestarter protein composition influence theabsorption characteristics of partialenzymic hydrolysates of protein in man.The present study was carried out toinvestigate the influence of peptide chainlength on absorption.Three highly purified, low MW,

ovalbumin hvdrolvsates of similar aminoacid composition were prepared and nonecontained significant amounts of peptidesof greater than five amino acid residues.The short chain preparations (OHI and0H2) contained only 16 and 291% oftheir amino acid content as peptides con-taining three to five residues, whereas amedium chain preparation (0H3) con-tained 68%r/ of amino acids in this chainlength range.An in vivo jejunal perfusion technique

was used in normal human subjects tocompare absorption of nitrogen from the

three hydrolysates. Isotonic test solutions,containing 3t) or 100 mmol/l aNH2 I wereinfused in random order in two sets ofexperiments.

Nitrogen absorption occurred signifi-cantly faster from both short chainpreparations (OHI and OH2) than fromthe medium chain preparation (OH3) at 30mmol/l (p<0(02) as well as at 100 mmol/l(p<0)(5).These data are the first demonstration,

in man, that subtle increases in peptidechain length slow the rate of absorptionfrom partial enzymic hydrolysates ofdietary protein. Furthermore, optimumabsorption occurs from preparationscontaining a predominance of di- andtripeptides.

T23Fasting and postprandial ileal function inadapted ileostomates and normal subjects

S D IlADAS, P F T ISAACS, G M MURPHY. Y

QUERESHI, AND G E SLADEN (Gastro-enterologv Unit, Guy 's Hospital, London)The reduction from the estimated dailyflow through the normal ileum of 1-5-2-5I/day to the 0 5-0(8 I/day output of a welladapted ileostomy could be because ofincreased electrolyte absorption inresponse to salt depletion or to a reductionof postprandial flow secondary to delayedtransit and increased mucosal contact time.We compared the output of 11 well

adapted ileostomies (after ulcerativecolitis) with the ileal flow measured byintestinal perfusion in five normal subjects.fasting and in response to a liquid meal.The oro-ileal transit of the meal marker(phenol red) was the same in the twogroups. but ileostomy output was less thannormal ileal flow, both fasting (16 3+10-9vs 62 4±11 5 ml/h, p<0-001) and post-prandially (35.4±27 vs 96 1±20 2 ml/h,p<0.00Ol). K concentration was higher inileostomy fluid (p<0.05) than in normalileal content but Na concentrations did notdiffer. In fresh samples, osmolality washigher in ileostomy fluid than in ileal fluidboth fasting (353±63 vs 287±5 mOsm/kg.p<0.05) and postprandially (347±47 vs283±7 mOsm/kg. p<002) but the meanpH was alkaline in both ileostomy fluid(7 2-7-5. fasting - postprandial) andnormal ileal content (7-4-7 8). Previouslyreported acid pH of ileostomy fluid wasprobably because of fermentation of thesamples.The reduction of both the fasting and

postprandial ileal flow and the increased

luminal potassium concentration in theabsence of changes in transit time suggestthat adaptation to ileostomy is primarily aresponse to chronic salt depletion ratherthan an altered response of the ileostomateintestine to meals.

T24HLA-DR typing in coeliac disease anddermatitis herpetiformis: evidence forfurther genetic heterogeneity

A ELLIS, C J TAYLOR, M DILLON-REMMY, SLEWIS-JONES, J C WOODROW, R B MCCONNEL,AND C F H VICKERS (Gastroenterology Unit,Broadgreen Hospital, Department of ChildHealth and Tropical Child Health, AlderHev Children's Hospital, Department ofMedicine and Department of Dermatology,Universitx' of Liverpool, Liverpool) Wehave previously shown that adult coeliacdisease (ACD) differs genetically fromjuvenile coeliac disease (JCD). Both formsof the disease have a significantly increasedfrequency of HLA-DR3 compared withcontrols but in addition juvenile coeliacshave an increased frequency of HLA-DR7and a decreased frequency of HLA-DR2compared with both controls and adultcoeliacs. Dermatitis herpetiformis (DH) isalso strongly associated with HLA-DR3. Alarge proportion of patients with thiscondition have a gluten sensitiveenteropathy which is frequently not dis-covered until after the skin diseasepresents. usually after the age of 20. Thuspatients with DH should have HLA-DRfrequencies similar to adult coeliacs. Thirtyseven patients with DH. 63 patients withJCD (less than 20 years). and 46 patientswith ACD (greater than 20 years) havebeen HLA-DR typed. All three conditionshave a significantly increased frequency ofHLA-DR3 (100. 89-1, and 88-9%respectively) compared with controls(26-2%). Whereas, however, HLA-DR2 isreduced in JCD (4-8%) it is normal inACD (26.1%) and DH (29.7%) (controls28.6%) and HLA-DR7 is increased in JCD(57 1%), normal in ACD (26.1%), andreduced in DH (10-8%) (controls 29.2%).Thus HLA-DR typing indicates furthergenetic heterogeneity among patients withgluten sensitive enteropathies.

T25Coeliac disease and dermatitis herpeti-formis: antibody classes to wheat gliadin

P J CICLITIRA, H J ELLIS, P D HOWDLE, R M

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MACDONALD, AND R H DOWLING (Gastro-enterologv, Units, Gus's atnd St ThlomasHospitals, London, Department ofMedicine, St James' Hospital, Leeds, andDepartmenit of Dermatology, Guy'sHospital, London) Coeliac disease (CD)and dermatitis herpetiformis (DH) arelinked. Dermatitis herpetiformis is thoughtto be caused by skin deposition of wheatgliadin IgA immune complexes. Weinvestigated circulating gliadin antibodytitres in patients with DH to assess theneed for jejunal biopsy.

IgG, IgA. and IgM gliadin antibodytitres were measured by ELISA in normalcontrols (10). patients with Crohn's disease(10), ulcerative colitis (10),CD on a normaldiet (ND, 10). CD on a gluten free diet(GFD, 10), DH patients without CD on aND (six). DH patients with CD on a GFD(13), and DH patients with CD on a ND(two).

Titres, median + range of: IgG normalcontrols 512 (32-4096), ulcerative colitis512 (64-16, 384). CD on ND 8192 (1024-65, 536), DH without CD on ND 512(512-4096), DH with CD on GFD 1024(128-4096), and DH with CD on ND16 384 (16 384); IgA - normals 128 (32-512), ulcerative colitis 128 (64-512),Crohn's disease 256 (64-256), CD on GFD256 (64-1024), CD on ND 2048 (256-270.344), DH without CD on ND 192 (64-512),DH with CD on GFD 256 (128-512), andDH with CD on ND 512 (128-512); IgM-normals 1024 (256-2048), ulcerative colitis1024 (256-4096), Crohn's disease 1536(1024-8192), CD on GFD 1024 (256-2048), CD on ND 1024 (64-32, 768). DHwithout CD on ND 1t)24 (256-8, 192), DHwith CD on GFD 512 (16-8, 192), and DHwith CD on ND 12 288 (8X192-16 384).

Raised IgG and IgA gliadin antibodytitres were only seen in patients with CD,and not in DH patients without CD. IgMgliadin antibody titres were similar in allthe groups. Dermatitis herpetiformispatients with high IgG or IgA gliadinantibody titres require a jejunal biopsy.

T26ay-Gliadin antibodies in childhood coeliacdisease - a screening test

JACINIA KEl.l.Y, C O FARREI LY, C O MAHONY,A THOMPSON, J P REES, C FEIGHERY, AND D GWEIR (Departments oJ Immunology, andClinlical Medicinie, Trinity College, StJames 's Hospital, and The NationalChildren's Hospital, Duiblin) The diag-nosis of coeliac disease is established by the

demonstration of a typical histologicallesion with reversal of this lesion aftergluten withdrawal. We have previouslyreported that the measurement of oc-gliadinantibodies (AGAs) is a useful screeningtest in adults. The purpose of this study wasto determine whether this screening testcould be applied to a paediatric popula-tion.AGA of IgG class was initially measured

in 54 control children, whose ages rangedfrom 15 months to 15 years. A gradualincrease in AGA levels was observed andparalleled the increase in the subject's age.AGA levels were then measured in 43children undergoing jejunal biopsy. Tenhad jejunal mucosal changes consistentwith coeliac disease and all except one hadraised AGA (IgG class) levels. Of 38patients with normal biopsies. 32 hadnormal antibody levels and this included allpreviously diagnosed coeliac patients(seven) who were observing a gluten freediet. Measurements of AGAs in thispopulation was therefore found to have aspecificity of 82%c and a sensitivity of 90%.These results show that measurement of

AGAs is of value in screening a paediatricpopulation for coeliac disease and may beused to measure dietary compliance.

T27Evidence that intestinal histiocyticlymphoma is immunologically distinct fromcoeliac disease

CLIONA 0 FARRELLY, C O MAHONY, SO BRIAIN, C FEIGIHERY, AND D G WEIR(Departments of Immunology and ClinicalMedicine, TrinitY College, Dublin, Ireland)The characteristic histological feature ofboth coeliac disease and intestinallymphoma is partial villous atrophy (PVA)of the small intestinal mucosa. In coeliacdisease the mucosal lesion usually respondsto dietary exclusion of gluten. A smallpercentage of adult coeliac patients,however, fail to improve.From a total of 200 patients with PVA

initially diagnosed as having coeliac diseaseand treated with a gluten free diet, eightfailed to respond either clinically or histo-logically. Four patients were subsequentlyshown to have intestinal histiocyticlymphoma and four, by definition, hadnon-responsive adult coeliac disease. Thelatter four patients had maintained a strictgluten free diet for nine to 12 months. Atthe commencement of dietary therapy, alltour patients showed raised o-gliadinantibody levels using an enzyme linked

immunosorbent assay. (Previous investi-gations showed that this test is 82%sensitive and 87% specific for coeliacdisease.) The cs-gliadin antibody levelsreturned to normal within six months ofgluten withdrawal (in a similar manner tothose coeliac patients who respond satis-factorily to dietary restriction).The four patients who were ultimately

diagnosed as having intestinal histiocyticlymphoma had normal (x-gliadin anti-body levels throughout the period ofobservation.These findings suggest that the ct-gliadin

antibody levels in patients with PVA maybe of prognostic significance and may helpin dissociating those patients with non-responsive coeliac disease from those withunderlying intestinal histiocytic lymphoma.

T28Mucosal lymphocyte response to glutenchallenge in coeliac disease (CD)

R J l EIGH AND M N MARSH (Department ofMedicine, Hope Hospital (University ofManchester School of Medicine), Salford)It has been held that the epithelium inuntreated CD is 'infiltrated' with lympho-cytes, a view that has not been substanti-ated by recent morphometric analyses. Asa peptic-tryptic digest of gluten (Frazer'sFraction 3 or FF3) is known to damagecoeliac mucosa we set out to determinewhether oral challenge with small gradeddoses of FF3 causes lymphocyte infiltrationand whether this effect is dose dependent.

Treated CD patients, and volunteers,were challenged orally with either FF3(100, 500, 1000, 1500 mg) or 500 mg ofcontrol protein B-lactoglobulin (LG). Onemicrometre toluidine blue stained eponsections of biopsies obtained before, and12, 36, 60, and 84 hours after eachchallenge, were analysed morphometric-ally: (1) the absolute number (N) of ELoverlying a constant test area of 104 ,um2 ofmuscularis mucosae was determined foreach biopsy; t2) the mean nuclear diameter(MND), per cent immunoblasts (MND >6,um) and per cent mitotic index (per centMI/3000 EL), as indicators of lymphocyte'activation' were determined; (3) the ratioof EL penetrating basement membrane toN - that is, flux ratio (FR) - gave someestimate of EL turnover across theepithelial basement membrane; (4)cryostat sections (5 ,um) were reacted withanti-T lymphocyte monoclonal antibodiesfor qualitative analysis of EL.A progressive dose related increase in N

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(per cent increment over control biopsy)occurred in CD mucosae at 12 hours withFF3 (500 mg. p<0'01- 1000 mg, p<0'05;1500 mg. p<0(005), waning by 36 hours.The 12 hour infiltrate comprisedsuppressor' phenotype (T8' ) smalllymphocytes. There was no evidence oflymphocyte 'activation', and FR did notchange. Crohn's disease mucosa did notrespond to LG, nor controls to eitherimmunogen.

Oral challenge with FF3 causes dosedependent. time related infiltration of CDepithelium by 'suppressor' lymphocytes.

EN D)OSCOPYT29-33

T29Prospective multicentre study of Britishsphincterotomy: initial results and com-plications

R A FROST (FOR THE BRI1ISH CO1 iABORATIVESTUDY OF ERCP) (The Middlesex Hospital,Londoni) Since 1981, endoscopists from13 British centres have collaborated in aprospective study of patients presenting forERCP. A computer sheet was designedwhich contained 430 numbered pieces ofinformation concerning presentingfeatures, investigations, procedures, andfinal conclusions.Two thousand two hundred and sixty

seven patients have now been entered onthe data base of a main frame computer.Seven hundred and twenty one have cometo sphincterotomyv with a total of 822procedures, including 91 precuts and 6(0extensions of sphincterotomy. There havebeen 20 sphincterotomies of tumour andfive pancreatic sphincterotomies.

Six hundred and four patients withcommon bile duct stones presented forsphincterotomy. Cannulation was achievedin 97% and sphincterotomy was successfulin 97% of those cannulated. Aftersphincterotomy the duct was shown to beclear of stones in 85%/c. The overall successrate for sphincterotomy and duct clearancewas therefore 8(1%.Of the 721 sphincterotomy patients, 11 C/

developed a complication, the overallmortality being 1 %. The three mostcommon complications were haemorrhage,cholangitis, and pancreatitis, all with anincidence of 3%. The incidence of retro-peritoneal perforation was 1 c/I, there beingno deaths in this group. Surgical treatmentwas required for 40% of bleeds, 14% of

cholangitis, 11 ' of perforation. and 5(1( ofpancreatitis.

T3()Successes, failures and complications ofendoscopic sphincterotomy

T LEESE, D 1. CARR-ILOCKE. AND JN EOPTOLEMOS (Gas troenterology Uniit,Leicester Royal Infirmnary, Leicester)During a six year period, 2(011 ERCPs and394 endoscopic sphincterotomies (ES)were performed in one centre by oneendoscopist. Indications for ES werecommon duct stones (319), papillarystenosis (37), ampullary tumours (24),endoprosthesis (eight), sump syndrome(four), and biliary dilatation (two).

Successful ES was accomplished in95 4%/r overall and successful clearance ofstones achieved in 93 4%,,, both figuresimproving with experience. A nasobiliarycatheter was used in 19 patients. eight withsuccessful mono-octanoin dissolutiontherapy.

Failure of ES and/or CBD. clearanceoccurred in 21 patients with common ductstones (6 6%), 18 later undergoing surgicalbile duct exploration, two of whom diedpostoperatively. Reasons for failure wereinaccessibility of the papilla- for example,duodenal diverticulum - inability toperform ES or achieve an adequateincision, large stones and a narrow bileduct below a stone.

Complications occurred in 40 patients(10%): haemorrhage (19), acutepancreatitis (eight), cholangitis (six).impacted basket (three). retroperitonealperforation (three), and gall stone ileus(one). Emergency surgery was required in15 patients: six for haemorrhage. one forpseudocyst, three for retained stones andcholangitis, two for impacted baskets, twofor retroperitoneal perforation, and onefor gall stone ileus. Overall mortalitywithin one month of ES was 12/394 (3%1c) ofwhich three were directly related to ES(0 8% of total, 7 5% of complications).The complication rate was higher after ESfor papillary stenosis.

Endoscopic sphincterotomy is a highlysuccessful technique for treating papillaryand biliary disease but awareness of thepossibility and frequency of complicationsis essential to instigate appropriate treat-ment when these occur.

T31Value of precut papillotomy at ERCP and

endoscopic sphincterotomy

I) F MARIIN AND D i. F TWEFIDFE (Depart-nenit.s of Radiology antd Surgery, UniversityHospital o Snouth Manchester, Manchester)In 196 patients undergoing retrogradeexamination of the bile ducts a cholangio-gram was obtained with ease in 166 (85%/ ).In 10 patients in whom biliary pathologytreatable endoscopically was suspected aprecut papillotomy allowed chol-angiography in nine (total success 89%/ ).Pancreatitis occurred in four patients, oneof whom had precut. Retroperitonealleakage of contrast was seen in one precutpatient. All patients with complicationsrecovered. Of 94 patients requiring endo-scopic sphincterotomy (ES), 90( with bileduct stones, this was easily achieved in 74(78%). In the other 2(1 patients precutpapillotomy allowed full sphincterotomy in17, giving an overall success rate for ES of97%. In the 90 patients with bile ductstones there were removed or passed spon-taneously in 82 (91%/'c). Complicationsoccurred in seven of the 94 ES patients,one of whom died. Of the 2(1 precutpatients, one developed cholangitis andone pancreatitis but both recovered. It isconcluded that precut papillotomy ishelpful in achieving a cholangiogram inselected patients and in performingsphincterotomy where deep cannulation ofthe bile ducts is not possible. There are noparticular complications of the procedure.

T32Management and outcome of endoscopicperforations of the pharynx and oesophagus

K R HINF AND M AI'KINSON (UniversityHospital, Queen's Medical Centre, Notting-ham) In recent years the increasing use oftherapeutic endoscopy has led to anincrease in instrumental perforations of theoesophagus and pharynx. The manage-ment of such perforations is still a matter ofdebate.We have treated 28 endoscopic

perforations of neoplasms of theoesophagus or gastric cardia and inaddition have dealt with eight pharyngealperforations sustained during endoscopy.The perforation was recognised endo-scopically in 18, by the immediate develop-ment of surgical emphysema of the neck inthree and by radiology (including contrastradiology) in the remaining 15. Ten ofthose detected only by radiology wereasymptomatic.

All patients were treated conservatively

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using hroad spectrum antibiotics, avoidingany oral intake of food or fluid and feeding T34-40)the patient cither parenterally or through afine bore feeding tube.

Seven of the 36 patients died as a result T34of the perforation (all oesophageal) and Non-invathis included four in whom the tear oesophagextended into the pleural cavity. drugs anInstrumental tears differ from

spontaneous and foreign body perforations J DAWS(of the oesophagus as, when recognised Queen Iearly. extravasation of food or barium into Propranthe mediastinum can be prevented. With becomeearly recognition, appropriate conservative managertreatment results in an 80% survival rate varices.from the tear often allowing several howevermonths of comfortable life before the f-blockepatient succumbs to the neoplasm itself. lated ac

therapyHithertothe invmeasureevaluate

T33 which cSelection of patients for upper gastro- endoscolintestinal endoscopy without sedation pressure

This '+S D lADAS AND S A RAPTIS (Gastro- showingenterology Unit, 2d Propaedeutic Medical pulp priUnit of the Athens National University, diseasesEvangelismos Hospital, Athens, Greece) pressureSedation for upper gastrointestinal more,endoscopy occasionally produces serious pressureside effects, adversely affects the ability of therapythe patient to work or drive a car, and The gacauses delays in a busy endoscopy unit. for efficAssessment of the patient's response to Intraducdigital examination of the pharynx (finger- causing;throat test) predicts which patients will produce(tolerate gastroscopy without sedation. eight ciriOf l()( consecutive patients (age 18-87 as a ther

years) 84 were tolerant to pharyngeal Studiesexamination (positive finger-throat test) therapy!and had gastroscopy without sedation. The patent i

toleration of gastroscopy was excellent in different56, satisfactory in 24, and poor in only similar ffour. There was no significant difference in progressthe ages of the patients with excellent definitivtoleration (n =56) 55 6±16-9 (mean ± SD) posed byears old, satisfactory toleration (n=24) pressure53-4±11-7 years. and endoscopy aftersedation (n=16) 55-9±16 0 years. p=0'9.Fourteen patients were offered a follow up T35examination, none refused, and their Origintoleration of endoscopy was the same as in painthe first examination.As the predictive value of a positive test J G C KIN

is 0.95, it is concluded that the finger-throat ment o)test can accurately predict which patient mew's ewill tolerate gastroscopy without sedation evidencewith a standard forward viewing chronicendoscope. with fat

asive endoscopic measurement ofgeal variceal pressure: effect ofid sclerotherapy

ON (Department of Medicine,Elizabeth Hospital, Birmingham)olol and sclerotherapy haveestablished therapies in the

ment of bleeding oesophagealA number of problems remain.r notably the potential toxicity ofrs in liver disease and the postu-dverse effects of partial sclero-on pressure within residual varices.

studies have been impeded by,asive techniques necessary toe portal pressure. We haved a pneumatic pressure gauge-an be attached to a standardpe and measure non-invasively thedirectly from a varix.variceal pressure' was validated bya close correlation with splenic

*essure (r=0-97) in diverse liverand with hepatic venous wedge(r=0(92) in cirrhotics. Further-

predicted changes in varicealwere observed after propranololand bolus somatostatin.auge can be applied to screen drugsacy in lowering portal pressure.Adenal isosorbide dinitrate in dosesa profound fall in arterial pressured no change in variceal pressure inrhotics. This drug is thus valuelessrapeutic alternative to propranolol.in patients after partial sclero-showed no pressure rise in residualvarices. The gauge also readilytiated patent varices from visuallyfibrous tags. Prospective studies in

will, from a single procedure, give,e information on the relative risks)y variceal size, appearance, andin predicting a future bleed.

of chronic right upper quadrant

qGHAM AND A M DAWSON (Depart-f Gastroenterology, St Bartholo-fospital, London ECJ) Despitee from several authorities thatright upper quadrant (RUQ) painintolerance rarely originates from

the biliary tract, the myth of chroniccholecystitis persists. The cause of suchpain is ill defined but our preliminaryobservations suggested that it could arisefrom the gut. We have studied 16consecutive patients referred for investi-gation of severe chronic RUQ pain. Themajority (12) were women. Symptoms hadbeen present for two to 23 years. All hadundergone repeated investigations of thepancreaticobiliary, gastrointestinal.urinary, and even gynaecological systemswithout a satisfactory diagnosis and 20abdominal operations had been performedon 10 patients in unsuccessful attempts tocure their pain. The aim of this study wasto reproduce the patient's customary painby balloon distension of the alimentarytract at various sites along its entire length.The oesophagus and small intestine wereapproached by mouth with a weightedlatex balloon (40 ml) on a fine tube. Thecolonic balloon (250 ml) was introducedtaped alongside a standard colonoscope. In15 of 16 patients their customary pain wascompletely and reproducibly mimicked bvinsufflation of the balloon in at least onesite. The pain always subsided withdeflation of the balloon and returned withreflation. The trigger sites were ileum (10).jejunum (10). right colon (seven), andduodenum (five). In nine more than onetrigger site was found. Close questioningrevealed features of the irritable bowelsyndrome in the majority (10) anddepression in many (eight) though thesymptoms were not spontaneouslvvolunteered. Reproduction of pain hasprovided a convincing demonstration tothis difficult group of patients that theyhave a sensitive gut.

T36Does bowel rest have any role in thetreatment of acute colitis?

P B MCINTYRE. J POWELL-TUCK. S R WOOD. J E

LENNARD-JONES. E LEREBOURS. P HECKETS-

WEILER, J-P GALMICHE. AND R COLIN (StMark's Hospital, London, and HospitalCharles Nicolle, Rouen Cedex, France) Totest the efficacy of 'bowel rest' a group ofpatients with severe acute non-infectivecolitis starting treatment with intravenousprednisolone were randomised to continueoral food or not. An adequate nutritionalstate was maintained in those who took nonourishment by mouth by the intravenousroute. The two groups were comparable interms of age. sex, disease extent, andweight loss during the present attack. Of

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the 27 patients who received no nutrientsby mouth, 11 required urgent surgicaltreatment during that admission (one post-operative death), and of the 20 patientswho continued to eat, five required urgentsurgical treatment (two postoperativedeaths). Daily stool weights(mean ± SEM) tended to be less withbowel rest' than oral food after sevendays, 253±45.6 g compared with 312±59-4g, and after 14 days, 229±64.3 g comparedwith 309±69.7 g. The final diagnoses basedupon pathological criteria were ulcerativecolitis (27), indeterminate colitis (four),and Crohn's colitis (16). Among thepatients with ulcerative colitis, five of 12who continued to eat needed urgentsurgery compared with nine of 15 who tookno food. Of the four patients with indeter-minate colitis, one continued to eat; of thethree who had 'bowel rest' two requiredurgent surgery. Among the 16 patients withCrohn's disease none required urgentsurgical treatment. Within the first 14 days,all nine treated with 'bowel rest' but onlyfive of seven who continued to eat,improved. During a follow up of five to 60months, three patients who responded tomedical treatment later required electivesurgery. There is no evidence that 'bowelrest' was effective in acute ulcerative orindeterminate colitis. In this trial Crohn'scolitis needed urgent surgical treatmentless often than acute ulcerative (p<0'01) orindeterminate colitis (p<0(05) but thereason for this is unclear.

T37Oesophagitis lowers the angina threshold

H ALBAN DAVIES, Z DANZIGER, AND E RUSH(Department of Medicine, IpswichHospital, Suffiolk) Heberden observedthat angina was often aggravated by eating.We have investigated whether experi-mental oesophagitis affected the exercisetolerance of five patients with ischaemicheart disease. They all had positiveexercise tests (ST segment depression > 1 .5mm) and four had significant coronaryartery stenosis shown angiographically.Subjects walked on a treadmill while theoesophagus was perfused with saline or O) IN HCI. Each subject performed four testsin sequence and two solutions of each typewere perfused in a 'blind' order. Thedistance to the angina point was 261 m(±294) with the saline and 134 m (±58)with the acid perfusion tests. At equivalentdistances during the acid and saline walksthe cardiac work, indicated by the rate-

pressure product, was similar(13 726±2116; 14 668±2658, respectively).ST segment depression was 0-8 mm(±0+27) during acid and 1 15 mm (±0+45)during the saline walks. No patient hadpain during a preliminary perfusion periodof 20 minutes before each walk.

Acid oesophageal perfusion lowered theangina threshold in four out of fivepatients, although the mechanism isunclear. This may have clinical relevanceas the treatment of myocardial ischaemiaincludes nifedipine and nitrites, drugswhich are known to decrease the loweroesophageal sphincter pressure and mayinduce oesophagitis. Mean values ± SD.

T38Is childhood coeliac disease declining?

R F A LOGAN, ANNE FERGUSON, S COLE, L J H

ARTHUR, G K T HOLMES, M J S LANGMAN, ANDR E MCCONNELL (University Hospital,Nottingham; Western General Hospital,Edinburgh; Common Services Agency,Edinburgh; Derbv Royal Infirmary, Broad-green Hospital, Liverpool) To investigatereports of a decline in the incidence ofchildhood coeliac disease we have useddata from (1) a hospital based register ofcoeliacs in Edinburgh, (2) records of 1 1million local authority school entry medicalexaminations in Scotland 1967-81, (3)hospital records in Derby, and (4) CoeliacSociety membership records 197t-81.

All four sources show a marked declinein numbers of childhood coeliacs bornsince 1976. In Edinburgh and Lothian theprevalence of coeliac disease at age <2years fell from 73 to 38/100 000 for births in1970-75 and 1976-198() respectively andfrom 101 to 45/100 000 for children of allages born in these periods. The prevalenceof coeliac disease reported at Scottish localauthority school entry medical examina-tions having averaged 69 and 62/100 000 inchildren born in the 1960s and 1970-75respectively, had fallen to 19/100 000 inchildren born in 1976 (peak of 84/100 000for 1972 births). Hospital records in Derbyshow a 50% decline in numbers diagnosedsince 1976 and Coeliac Society membershiprecords from eight regions of England andWales show a decline from 25 to 13 coeliacsaged <2 years at diagnosis for birth years1970-76 and 1977-80.These data show that in births since 1976

throughout Great Britain there has been anapproximate halving of the number ofchildren who have developed coeliacdisease. The geographic extent and the size

of the decline suggest that neither localfactors, such as epidemic infections, norsmall increases in frequency and durationof breast feeding are sufficient explana-tions. The decline does coincide with theremoval of gluten from some widely usedbaby foods. Whether this represents pre-vention, postponement, or only decline inseverity of coeliac disease in unknown.

T39Endoscopic retrograde cholangiopancreat-ography (ERCP) in pancreatitis with con-tinuing pain

P A WINSTANLEY, A P MANNING, D J LINTOTIl,AND A T R AXON (The General Infirmary,Leeds) The role of ERCP in the diagnosisof chronic pancreatitis is established but itsvalue in those already known to havepancreatitis and with continuing abdominalpain has not been evaluated. We thereforestudied the ERCPs of patients known byother criteria to have pancreatitis and withrecurring or persistent abdominal pain.Radiographs were examined by two experi-enced observers; terminology and gradingof chronic pancreatitis followed the Cam-bridge Classification 1983; clinical datawere obtained from Unit records and casenote review. One hundred and seventy onepatients fulfilled the entry criteria; 35ERCPs were unavailable and 20 designatedas technically inadequate. Of theremaining 116 (66 men, 50 women; meanage 46 years, range 9-80 years), 82 hadrecurrent and 34 persistent pain diagnosedas pancreatitis. Radiological changes ofchronic pancreatitis were graded mild in13, moderate in 24, and marked in 38; 69had diffuse and six had localised changes.Forty ERPs were normal or equivocal; onepatient who fulfilled the entry criteria hadpancreatic carcinoma. Twenty six ERPsshowed lesions which were potentiallysurgically remediable: three had changeslocalised to the tail, six had one or morelarge cavities and 17 had main pancreaticduct obstruction/stricture, in five cases witha large cavity. ERC, performed in 73patients, showed gall stones in 14, of whomseven had common bile duct (CBD)stones; in 12 the stones had not beendiagnosed before ERCP. In all, 38 patients(33%) were shown to have pancreatic orbiliary lesions theoretically amenable toconservative surgery. We conclude, there-fore, that all patients diagnosed by othercriteria as having pancreatitis and con-tinuing to have pain should undergoERCP.

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T40Long term mortality after vagotomy anddrainage

P C H WATT, C C PATTERSON, AND T 1

KENNEDY (Departments of Surgerv andMedical Statistics, The Queen's Universitvof Belfast) Long term survival aftergastrectomy is known to be reduced duemainly to smoking related disease. Thesignificance of postgastric surgery cancer iscontroversial. Little is known of the longterm survival after vagotomy and drainage(V+ D).We examined the mortality in 735

patients (576 men, 159 women) who hadvagotomy and drainage procedures forduodenal ulcer in one hospital between1957 and 1967 and compared it withexpected age and sex specific mortalityrates from the Registrar General's reportsfor Northern Ireland. On 1 September1982, 430 were still alive, 281 were dead,and 24 were lost to follow up. The expectednumber of deaths in the group was only 184(p<0.000 1).Cause specific death rates were also

examined using death certificateinformation. Lung cancer was the cause ofdeath in 46 patients but was expected inonly 13, giving an observed to expectedratio of 3-5 (p<0l0001). Deaths from allsmoking related diseases were 1 4 timesmore common in the V+D patients thanexpected (p<0(0001). Gastric cancer wasthe cause of death in 16 patients and wasexpected in only five, giving an observed toexpected ratio of 3 3 (p<0.000(1).

It was concluded that after V+D there ismarked increase in mortality due to bothsmoking related diseases and gastriccancer.

INFLAMMATORY BOWEL DISEASEFI-10

FlEvaluation of short term treatment ofCrohn's disease with slow release 5'aminosalicylic acid

S SAVERYMUJTU, A KESHAVARZIAN. S GUPTA,B DONOVAN, AND H J F HODGSON Depart-ment of Medicine, Royal PostgraduateMedical School, London, and FerringPharmaceuticals, Feltham, Middx) Theactive principle of salicylazosulpha-pyridine, 5'amino salicylic acid, is effectivein the treatment of ulcerative colitis ifadministered in a form which reaches the

colon. In an open trial, an oral preparationof 5ASA has been reported to be of valuein the treatment of Crohn's disease. Wehave now performed a short term doubleblind placebo controlled trial of thispreparation, Pentasa, in the outpatienttreatment of mildly active Crohn's disease.Disease activity was measured objectivelyby quantifying faecal excretion of "'In-labelled autologous granulocytes, whichdirectly reflects gastrointestinal inflam-mation.Twelve patients with active disease were

randomised, six to receive 1 5 g 5ASAdaily and six to receive placebo. At entry,the mean "'In excretion by the 5ASAtreated group was 20 1% of injected dose;the placebo treated group excreted 17 1%;normal individuals excrete <2%. After 10days therapy, mean faecal excretion in theSASA group was reduced by 24%'c fromentry (significance p<0.05). In the placebogroup there was also a fall in faecalexcretion, by 10%, but this was notsignificant. The results indicate that slowrelease 5ASA is a well tolerated prepara-tion which merits further longer term trialsin the management of Crohn's disease.

F2Crohn's disease in Blackpool 1968-80

F I LEE AND F T COSTEILLO (Department ofGastroenterology, Victoria Hospital, Black-pool) The occurrence of Crohn's diseasehas been studied in a population ofapproximately 300 000 in a seaside town innorthern England for the period 1968-8(0.Information has been obtained from colitisclinic records, department of histo-pathology records, information in the casenotes of physicians and surgeons, andhospital activity analysis data maintainedby the North West Regional HealthAuthority in relation to hospital admission.These sources were studied and thediagnosis of Crohn's disease reviewedaccording to the standard criteria involvingclinical features, macroscopic features atlaparotomy, microscopic features, andtypical radiological appearances. Between1968 and 1980, 156 patients resident in thearea were diagnosed as having Crohn'sdisease - an annual incidence of four per105. For the years 1971-75, the incidencewas 3 3 per 105 and for 19756-80 it was 6-1per 105. The trend is upwards but there wasan apparent fall in incidence in 1974-75.Over the period of study, there was anincrease in all three anatomical types, smallintestinal, large intestinal, and mixed

disease but this increase was most markedfor purely large intestinal disease. Of the156 cases, 35% had small intestinal diseaseat presentation. 35% had large intestinaldisease, and 30% had mixed disease. Theoverall sex ratio was F:M=1 89:1, buthighest for large bowel disease, 2 60:1.Analysis at age of presentation at differentsites shows a unimodal distribution forsmall intestinal and mixed disease with apeak in the third and fourth decades. Largebowel Crohn's disease shows a bimodaldistribution with peaks in the third andeighth decades. During the period of studywe identified 185 cases of Crohn's diseasein the study population. On 31 December1980, 141 patients with the condition wereliving, a prevalence of 47 per 1>.

F3Diarrhoea in acquired immune deficiencysyndrome (AIDS)

C BORIES, M SALMERON. Y l.E CHARPENTIER, B

MESSING, A GALIAN, J C RAMBAUD, AND R

MODIGLIANI (Gastroenterologv andPathology Department, H6pital Saint-Lazare, Saint-Denis, Paris Cedex 10,France) Chronic diarrhoea is frequent inAIDS but has been poorly investigated asyet. We report here four male AIDSpatients who underwent complete digestiveinvestigations. All patients had at leastthree opportunistic infections, a profoundcellular immune deficiency. and a lowOKT4/OKT8 lymphocyte ratio (<0.08;n=2-3). Diarrhoea was a presentingsymptom in all subjects; in three of them itwas watery (daily stool outputs exceedingfrequently 11 and not influenced byfasting). Xylose and vitamin B,2 werefrankly malabsorbed in all cases;steatorrhoea (17 and 24 g/24 h) was foundin the two patients who could ingest signifi-cant amounts of fat; faecal I-antitrypsinclearance was increased (45 to 112 ml/24 h;N<15) in three subjects. Search forpathogens in stools, jejunal fluid, and gutbiopsy specimens (optical and electronmicroscopy) showed Cryptosporidium (C)in two cases, Isospora belli (IB) in onecase, and in the last case Microsporidians(M) (genus still undescribed) and Giardia;Candida albicans was present in threepatients; otherwise there was partial villousatrophy and slight inflammatory infiltrateof the duodenojejunal mucosa. In one casewith C. the slow marker intestinal per-fusion technique showed a profuse fluidsecretion in the duodenum and proximaljejunum, with water and ion reabsorption

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in the more distal small intestine and thecolon. All patients needed prolonged totalparenteral nutrition. C and M could not beeradicated despite multiple drug trials.Isospora belli was transiently cured bysulphadiazine-pyrimethamine; CA and Gwere eradicated without change indiarrhoea. Only one patient is presently athome; two still need TPN and one diedafter six months of TPN.

F4Colonic crypt cell production rate is fasterin the relapse, compared with the remissionphase, of ulcerative colitis

A ALI-AN, T ROSSER, J B BRISTOL, AND R C N

WILLIAMSON (University Department ofSurgery, Bristol Royal Infirmari, Bristol)Existing studies of colonic epithelial cellkinetics in patients with ulcerative colitisrely on static methods and give discrepantresults. We report the measurement ofcrypt cell production rate (CCPR) usingstathmokinetic methods in rectal biopsyspecimens maintained in organ culture.Rectal biopsy specimens were obtainedfrom patients with ulcerative colitis andfrom patients with a normal rectum.Organ culture of biopsies was carried out

for 16 hours followed by a further threehours over vincristine containing medium.Electron microscopy revealed goodpreservation of histological architectureduring culture. Vincristine arresteddividing cells in metaphase and after cryptmicrodissection these metaphase figureswere counted to derive the CCPR.

Linear accumulation of metaphasefigures by cultured biopsies was observed,p<0 001. Optimal doses of vincristine toinduce metaphase arrest in normal andcolitic mucosa were established. Mucosafrom colitic patients in histologkcal relapseshowed a faster CCPR (14 2±SE, 0-78cells/h, n=8) than mucosa from coliticpatients in remission (CCPR 9 78±SE 0 48cells/h, n=14, p<001). The CCPR ofcolitic patients in remission was not signifi-cantly faster than the CCPR of patientswith histologically normal mucosa (CCPR8-58+SE, 0 36, n=14, p<0.1). Thesefindings are at variance with previousresults founded on static methods.

F5Audit of a stomatherapy service

R P PHILLIPS, W K PRINGLE, AND M R B

KEIGHLEY (Department of Surgery,

General Hospital, Birmingham) We haveanalysed the activities of a stomatherapyservice in one hospital over three years(1980 to 1982). The service is used by sixgeneral surgeons, but only two specialise ininflammatory bowel disease.Two hundred and seventy six

colostomies were constructed, 72% ofpatients had malignant disease, 17% wereperformed as emergency operations, and51% were temporary stomas. Only 45% ofthe colostomy patients were counselledbefore operation. In surviving patients(243, 88%), 11% received no regularfollow up. Complications were recorded in60 surviving patients (25%): skinexcoriation 8%, leakage 7%, sepsis 8%,hernia 5%, prolapse 2%, retraction 2%,stenosis 1%, infarction 1%, and bleeding1%. Only 25 of these patients (1U%),however, required surgical refashioning.One hundred and eighty four ileostomies

were constructed, 52% of the patients hadulcerative colitis and 41% had Crohn'sdisease, 13% were performed asemergency operations and only 11% weretemporary, 83% of ileostomy patientsreceived preoperative counselling. Therewere nine hospital deaths (5%) and 98% ofthe surviving patients (n= 175) haveattended for follow up. Complicationsoccurred in 99 surviving patients (51%):skin excoriation 27%, flux 17%, sepsis10%, leakage 9%, retraction 9%, hernia4%, bleeding 4%, prolapse 3%, andstenosis 10%. Only 32 of these patients(18%), however, required surgical'refashioning.

This audit indicate' that far too fewpatients having colostomy are properlycounselled before operation and thatcomplications occur in at least half of allpatients having ileostomy.

F6Is continuous sulphasalazine (SASP)necessary in patients with ulcerative colitis(UC)?

R J DICKINSON, A KING, D G D WIGHT, GNEALE, AND J 0 HUNTER (Departments ofMedical Gastroenterology and Pathology,Addenbrooke's Hospital, Cambridge)Sulphasalazine is probably effective inpatients with ulcerative colitis (UC)because it is anti-inflammatory. Sulpha-salazine taken continuously thereforewould maintain remission by lowering'background' inflammation or by inhibitingminor relapse. The latter might also beachieved by 'on demand' SASP taken at

the first symptoms of relapse. Thishypothesis has been tested in a prospectivetrial. Patients with UC in remission whohad been taking continuous SASP for atleast six months were followed closely in ahospital clinic. By random allocation group1 patients took SASP 2 g/day continuouslyand group 2 patients took SASP 3 g/day atthe first symptoms of relapse. No othertherapy was given. Rectal biopsies weretaken at 0, four, eight, and 12 months andif relapse occurred (symptoms persistingfor over one week). Rectal biopsies werescored 'blind' on a 0-9 point scale. The trialwas completed at relapse or after 12months. Twenty eight patients completedthe trial. Of the 10 patients in group 1,three relapsed. Of the 18 patients in group2, seven relapsed, five took SASP at sometime during the trial but did not relapse,and six remained well off therapy. Themean rectal biopsy inflammation score was1 3 (n=28) at the start of the trial. Themean score at four months, eight months,and 12 months in those maintaining remis-sion in groups 1 and 2 were 0-8 and 2-1(NS), 0-6 and 2-8 (NS), and 2() and 16(NS). The mean score in patients whorelapsed was 6-2 (p<0-01). Persistentinflammation was not significantly greaterin patients not on continuous SASP and 'ondemand' SASP may be as effective ascontinuous therapy in the maintenance ofremission in ulcerative colitis.

F7Postoperative bleeding and Latamoxefprophylaxis in surgery for colorectal andinflammatory bowel disease

P J FABRICIUS, D L MORRIS, G OZUNER, B

SCAMMEL, R N ALLAN, AND M R B KEIGHLEY

(Gastroenterology Unit, General Hospital,Birmingham) Latamoxef is a broadspectrum antibiotic particularly suitable forsurgical prophylaxis which we have nowused in 177 patients, though latterly wesuspected that it might be associated withan increased incidence of postoperativebleeding.Of 102 patients undergoing surgery for

colorectal disease there were 10 cases ofserious postoperative bleeding. Thesepatients received two doses of Latamoxef(2 g) with or without Metronidazole. Therewere only five episodes of bleeding after286 comparable operations performed inthe preceding three years when otherantibiotics were used (p<0-01). Serial pro-thrombin times were measured in 16 of the102 patients and of these seven had pro-

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longed prothrombin times in excess of fiveseconds compared with preoperativelevels.Of 52 patients undergoing surgery for

inflammatory bowel disease six cases ofserious postoperative bleeding were

observed. All patients received Latamoxeffor five days (6 g/day) with three doses ofMetronidazole (500 mg intravenously) over24 hours. We observed only one bleedingepisode in the preceding 25 consecutiveoperations when other antibiotics were

used. Eleven of the 52 patients had serialprothrombin times of whom eight hadprothrombin times at least five secondslonger than preoperative values.

Recently 23 surgical patients withcolorectal disease were given two doses ofLatamoxef (2 g) together with vitamin K 10

mg intravenously. Despite this seriousbleeding was observed in four patients andprolonged prothrombin times in two.We conclude that Latamoxef causes

serious postoperative bleeding in some

patients which cannot always be preventedby the addition of vitamin K.

F8Rectal function after pelvic irradiation

J S VARMA AND A N SMITH (UniversityDepartment of Surgery, Western GeneralHospital, Edinburgh) Radiotherapy isbeing increasingly applied to malignantdisease of the prostate, bladder, andcervix. Varying degrees of damage to therectum are accompanied by symptoms suchas frequency, urgency, and faecalincontinence.

Rectal function has been compared incontrols and in symptomatic men (n=10)who had received external beam radio-therapy for prostatic carcinoma two to fiveyears previously. A proctometrogram was

obtained by inflating a highly compliantrectal balloon at a constant rate (67 mlsH2,min) and monitoring pressure by a

microtransducer. Volumes (V mls) andpressures (Pcm H2() were recorded atthreshold and constant sensation andmaximal tolerance. Rectal compliance

AV ml/cm H2,AP

was calculated on the linear position of thecurve.

There is a significant reduction in rectalvolume in the irradiated group comparedwith controls (threshold sensation 96±23SEM vs 224±31, p<0*01; constant sensa-tion 122±27 vs 303±23, p<0001;

maximum tolerable volume 224±30 vs493±25, p<0001). Rectal compliance was

also significantly reduced (2-5±0+4 vs9+0-5, p<0.00(1). Comparabie pressuremeasurements showed no significant differ-ence.

These results explain many of thesymptoms of chronic radiation proctitis.Reduction in volume and compliance is notalways obvious radiologically but sigmoid-oscopy can give some indication of thedamage. The proctometrogram gives a

quantitative assessment and may be ofvalue as a prognostic indicator.

F9High frequency of adenomatous polyps inulcerative colitis

G C STURNIOLO, R D INCA, A MARTIN, G

GURRIERI, A CECCHETTO, AND R NACCARATO

(Cattedra di Malattie dell'ApparatoDigerente ed Istituto di Anatomia edIstologia Patologica, Policlinico Universitddi Padova, Padova, Italy) Polypsfrequently occur in ulcerative colitis (UC):they are generally considered inflammatorywithout premalignant significance, but an

unknown proportion of them can beadenomatous. We studied 157 patients (76women, 81 men, aged 8-70 years) with UCin order to assess the frequency of adeno-matous polyps (AP). Two hundred andtwenty four colonoscopies were performedshowing pancolitis in 72 patients and leftsided colitis in 85. The duration of thedisease was more than seven years in 37patients, more than one and less than seven

years in 64, and less than one year in 56.We found and removed 15 suspiciouspolyps - that is, those peduncolated or witha base larger than 0 5 cm or with anirregular surface or with a reddish colour.Eleven of these turned out to be adeno-matous (seven tubular, one villous, threemixed) while four were inflammatory.Eight polyps were localised in the left colonand three more proximally. Four patientswith AP were under 40 years old. Norelationship was found between theduration or the extension of the diseaseand the presence of AP. Out of a total ofcases of moderate or severe dysplasia, sixhad an AP. In conclusion: (1) we found a

high frequency (7%) of AP in UC; (2)dysplasia is frequently associated with AP;(3) AP are frequent also in relatively youngpatients but there is no correlation withduration and extension of the disease; (4)we suggest that colonoscopy should beused in the follow up of patients with UC

and every suspicious lesion should beremoved and examined histologically.

FIOEye lesions in inflammatory bowel disease

A A SANTOS, E AREIAS, F QUERIDO, L M SERRA,AND J P CORREIA (Department of Medicine2 and Department of Ophthalmology,University Hospital Santa Maria Center ofGastroenterology, Lisbon, Portugal) Aprospective study was designed to elucidatethe prevalence and evolution of eye lesionsin IBD. Sixty seven patients were seen (34with ulcerative colitis) and 33 with Crohn'sdisease, with a total of 100 examinations(47 in UC and 53 in CD). Patients ageranged between 14-74 years in UC and10-62 years in CD. Activity of IBD wasmeasured by a modification of Best et alactivity index. Eye complaints were regis-tered only in three patients. Correlationsbetween the activity of intestinal diseaseand the occular lesions were analysed.

In active UC (11 observations) one case

of uveitis, four keratoconjunctivitis sicca,two reduced Schirmer's test, three non-

specific lesions, and one normal werefound. In non-active UC (36 observations)there was also one uveitis, 11 kerato-conjunctivitis sicca, 12 reduced Schirmer'stest, three non-specific lesions, and ninenorml observations. In active CD (14examinations) four had uveitis, threekeratoconjunctivitis sicca. three reducedSchirmer's test, one non-specific lesions,and three no alternation. In non-active CD(39 examinations) three had uveitis, sixkeratoconjunctivitis sicca, eight reducedSchirmer's test, eight non-specific lesions,and 14 were normal.We conclude that eye lesions seem more

frequent in UC (65 8%) than in CD(47 1%) but no difference was foundbetween active (63-6%) and non-active(66-6%) UC. On the other hand in CD,eye lesions were more frequent in activedisease (71-4%) than in non-active(43 5%).

OESOPHAGO/GASTRICF 1-22

FllAngelchik antireflux prosthesis: post-operative clinical and objective asessment at12 months

R M WEAVER AND J G TEMPLE The Queen

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The British Societi' of GastroenterologyEliZabeth Hospital, Edtgbastoni, Birminig-hatn) The Angelchik prosthesis was

inserted into 23 patients with intractablegastro-oesophi1geal reflux.

Postoperative clinicall assessmentshowed that of 21 patients at three monthsand 17 patients at 12 months available forfollow up. 17. and 15 respectively were

asyrnptomatic or had verv mild symptoms.Two prostheses disrupted aind were

replaced. Two further prostheses migratedinto the chest aind angula ted causing

dysphagia. for which further surgers was

necessary.

Manometric aind overnight pH studieswere performed preoperatively in 19patients. These were repeated in 17patients after three months and 10 patientsafter 12 months. Results were analvsedusing the t test for paired comparisons.The mean percentage of time that intra-

oesophageal pH was <4 fell significantlvfrom 37 6%( (rainge 2 7-92%4 ) pre-operativelv. to 10(3%X (range 0-39-7%/c) atthree months. aind 8X34%( (range 0-64 5%)ait 12 months (p<00) I1). Mean loweroesophageail barrier pressure rose signifi-cantlv from 1-41 mm Hg (range 06-6( mm

Hg) to 6-48 mm Hg (range 1-15-3 mm Hg)at three months, and 9 06 mm Hg (range1.9-186 mm Hg) at 12 months (p<0)()l).Thesc results suggest that the Angelchik

prosthesis gives good and continuedsymptomatic relief with significantreduction in acid reflux and improvementin function ot the lower oesophagealsphincter.

F12Histological and histochemical changes inthe columnar lined (Barrett's) oesophagus

JANE E PATTERSON. D W I)AY. AND C J

STODDARD (Departmenits of Suirgers antidPathology. Universits of Liverpool, Liver-pool) A columnar lined oesophagus(CLO) is an acquired condition whichpredisposes to the development of an

oesophageal adenocarcinoma. Patientswith intestinal type columnar metaplasia(IM) may be at greatest risk. We havestudied the histological and histochemicalchanges in the oesophageal epithelium andtheir incidences in patients with a CLO.Over a 26 month period upper

alimentary endoscopies were performed in

24(19 patients. Oesophagitis was present in

438 patients (18-2%; ) of whom 39(0 (89-0%)had a squamous lined oesophagus and 48(11 (0%6/) a CLO. Five of the patientswith a CLO (10-4%/k ) had a coexistent

oesophageal adenocaircinoma. Multipleendoscopic oesophageal biopsies weretaken for histological and mucin histo-chemical evaluation. Intestinal typecolumnar metaplasia was observed in 41 ofthe 48 patients with CLO (X56,;%) beingpresent focally in 21. predominantlv in 18(375%/c). and extensively in two (422%).Of the patients with IM 61% had IM ofincomplete type with sulphomucin pro-duction. Seven patients (six with IM)showed dvsplasia of the columnarepithelium and three had anl associatedadenocarcinoma. Four of the five patientswith carcinoma had IM of the incompletetyvpc.These results show that IM is common in

patients with a CLO. Patients with anincomplete type of IM. especialiv in thepresence of dvsplasia. mav be particularlvat risk of developing an oesophagealadenocarcinoma.

F13Significance of oesophageal motilitvdisorders

J BANCEWICZ, H- OSUGI (INTRODUCEiD BY M H

IRVING) (Departmentt of Slurgery, HopeHospital (University of Manichester Schoolof Medicinie), Salford) Oesophagealmotility disorders have recently attractedattention, particularly as a cause of chestpain. The nature of these disorders andtheir treatment, however, is still uncertain.Between June 1979 and June 1982

oesophageal manometry was performed on202 patients with symptoms of chest pain.abdominal pain, or dysphagia. Most alsohad a Bernstein test and prolonged ( 12 or24 hours) recording of oesophageal pH. Allbut two had prior endoscopy or radiologyand 139 had both investigations withnegative results in 51. Most of theremainder had minor abnormalities ofuncertain significance.Oesophageal dysmotility was found in

142 patients (7()6/e of total) including 45(88%) of those with negative radiology andendoscopy. Ninety seven (68%) of thosewith dysmotility also had significant gastro-oesophageal reflux and 55 came to surgery(51 Nissen, four Roux-en-Y loop). Fivepatients without reflux had surgery: twoHeller's procedure: three extendedmyotomy for diffuse spasm.

After surgery for reflux 25 of 29 patients(86%) with symptoms clearly attributableto the motility disorder - for example.

dysphagia or anginal' pain - wereimproved. This suggests that these dis-orders were secondary to reflux.

Oesophageal manometry often revealsabnormalities not demonstrable by radi-ology or endoscopy. Prolonged recordingof oesophageal pH. however, is a morerelevant investigation for severe symptomsas reflux can be corrected by surgerv withgood results. Primarv motilitv disorders areless common and do not usuallv producesevere symptoms.

F14Gastro-oesophageal scintiscanning in theassessment of gastro-oesophageal reflux

M M MUGHAI, NI OGDEN. M MARPILES. J

BANCEWICZ (INTRODUCED BY M H IRVING)(Departmenit of SurgerY, Hope Hospital(UniversitY of Manchester School ofMedicinie), Salford) Upper gastro-intestinal endoscopy and barium studiesare often misleading in patients withsvmptoms of gastro-oesophageal reflux. Insuch cases. 24 hour pH monitoring may berequired to provide a definitive answer.Whereas pH studies are uncomfortable.gastro-oesophageal scintiscanning (GOS)is both rapid and non-invasive. It isreported to be more sensitive than bariumstudies and endoscopy. as well as beingsemi-quantitative.The use of GOS was studied in 17

asymptomatic volunteers and in 31 patientswith symptoms of gastro-oesophagealreflux. All patients also underwentendoscopy. barium meal. and 24 hour pHmonitoring. The results of GOS wereexpressed as a reflux index (RI).The upper limit of normal RI was deter-

mined to be 7-2 by adding two standarddeviations to the mean RI of 17 asympto-matic volunteers. The results of 24 hour pHmonitoring were expressed as DeMeesterscores and endoscopy was consideredpositive on detection of macroscopicoesophagitis or free reflux.The sensitivity and specificity of GOS

was 36%/e and 82%/r. of endoscopy 43c%c and71%. and of barium meal 29%/e and 65%respectively. The correlation between RIand DeMeester score was r=-055(p=(0()005).

Gastro-oesophageal scintiscanning is ahighly specific test for gastro-oesophagealreflux which mav be useful when thediagnosis is still in doubt after endoscopy.It is not sensitive enough to either replaceendoscopy or to be of use as a screeningtest.

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The Britishl Societv of Gastroenterology

F15Teeth and oesophageal stricture

D (G MAXiON. S 1. (RAINGER. C.C AINL iE. ANDR P HFI-iOMIPSON (GastrointestinalLaboratory, The Rav!ne Inistitutte, StThlomas' Hospital, London ) Theaetiology of benign oesophageal stricturesis unknown, although hiatus hernia andoesophageal reflux are important. Wenoted that patients wvith benignoesophageal strictures are often edentulousand examined the relationship betweendentition and oesophageal disease in ourendoscopv population. The age. finaldiagnosis. and dentition ot all patientsattending for endoscopx was recorded.Ages were divided into under 30). 30-44.45-59. over 60). and pathological groupscompared.Of patients over the age ot 60). 33 of 37

with benign oesophageal strictures wereedentulous compared with 116 of 169patients with a normal endoscopv (p<()0()2.72=6 4) There was no significant correla-tion with dental state in the few patientsaged under 60 with strictures. Fhe presenceof oesophagitis or hiatus hernia atendoscopy was not associated with eitherpartial or total lack of teeth in any agegroup.Absence of teeth is associated with

benign oesophageal strictures in the over60)s. but not with hiatus hernia oroesophagitis. The diet of the edentulous.however. will he towards more liquid foodsthat do not dilate the inflamed oesophagus.while a prolonged reduced volume ofsaliva, which is known to predispose toearly caries and tooth loss. mav notadequately neutralise refluxing acid. Bothmechanisms mav contribute to thedevelopment of oesophageal stricture.We conclude that patients with benign

oesophageal disease should be encouragedto use their dentures to eat solid food.

F16Effect of cimetidine and alginate treatmenton oesophageal pH and bile acid concen-trations in reflux oesophagitis

J R BENNE'LII'. M R SMITli, AND K BUCKTON(Department of' BiocheinistrY, UniiversitY ofHlull, atid Gastro-initestitial Unit, HullRosnal InfirmarY, Hlull) A double blindtrial was performed to evaluate the com-bination of cimetidine with alginate antacid(Gaviscon) in patients with acid gastro-oesophageal reflux (GOR). Forty patientswith symptomatic acid GOR shown bv

oesophageal pH measurement wererandomly allocated to receive alginate andplacebo or alginate and cimetidine I gdaily, for six weeks. Bile acid concen-trations were measured in fasting gastricjuice and in oesophageatl fluid aspirated atthe same time as 15 hour oesophageal pHmeasurements before and in the sixth weekof the trial.Intra-oesophageal bile acid con-

centrations in the post-evening mealsamples were significantly lower (p=0)06)in the alginate/placebo treated group(n=9) when compared with the alginate/cimetidine treated group (n=9). There wasa significant decrease after treatment withalginate/cimetidine in the number of refluxepisodes (p=()-()2() and percentage timepH<5 (p= (014). There was also asignificant decrease after both treatmentsin the percentage time pH<4 (p=()0()36 foralginate/placebo and p=() ()25 for alginate,'cimetidine). When changes were comparedbetween the two groups. however. nosignificant difterences were observed.These results confirm the eftectiveness of

both alginate antacid and cimetidine inreducing acid GOR. Alginate antacidalone also reduced postcibal oesophageallbile acid concentrations. The failure toreduce postcibal oesophageal bile acids bycombined alginate/cimetidine therapy mavbe explained by a reduction in the gastricjuice volume response to meals causing arelative rise in gastric bile acid concen-trations.

F17Bile acid levels in stomach and oesophagusof patients with acid gastro-oesophagealreflux

M R SMITH, G K BUCKTON, AND J R BENNE[r

(Department of Biochemistry, UniversitY ofHlull, and Gastro-intestinal Unit, HullRoval Infirmars. Hull) Bile acids havebeen implicated as one of the causativeagents of reflux oesophagitis. Previousstudies have utilised either bile acid per-fusion of the oesophagus in experimentalanimals or man. or surgery designed toincrease oesophageal bile reflux in animals.such as duodeno-oesophageal anastomosisor cholecystogastrostomy. There has beenno study of bile acid concentrations in theoesophageal fluid of humans with clinicallysignificant acid gastro-oesophageal reflux(AGOR). We measured total bile acidconcentration (TBC) by an enzyme-fluorometric method in the fasting gastricand oesophageal fluid of 40 patients

with acid gastro-oesophageal reflux. Oeso-phageal samples were aspirated in fourhour collections for 15 hours with simul-taneous intraluminal pH recording. Themean fasting gastric TBC was 55-6/iM± 1615 (n =37) with a median of 7(1/iM (range 0-94(0 uM). Oesophageal TBCsranged from 0-1()0)M with bile acids mostfrequently detected in the post-mealsamples (n=58. x=89 u+M± 10() median 8X0uiM. range (f-4(0 uM). The concentrationsof bile acids found in this study differconsiderably in magnitude from those usedin experimental studies. Perfusion experi-ments have used 2-5 to 10 mM (2500-(10 0)0 AM) bile acid concentrations andthe level of bile acids in gall bladder bile isalso of this magnitude. Thus. althoug[there is evidence that bile acids mav be ofsignificance in the development ofoesophagitis in man. the experimentalstudies have clearly used concentrations ofbile acids much higher than those in theoesophageal fluid of patients with acidgastro-oesophageal reflux.

F18Ambulatorv pH monitoring in the distaloesophagus using radiotelemetrv - threeyear results

D F EvANS. F J BRANICKIi. I JONFIS. ANt) .1 t)

HARDCASTI (DIepartnent o.f' SurgersYUnihersity Hospital, Nottingham) Twentyfour hour ambulatorv monitoring ofoesophageal pH has proved to be asensitive test in the evaluation of gastro-oesophageal reflux (GOR) in oesophagitiswhen compared with equivalent tests per-formed in hospital. A pH sensitive radio-telemetry capsule and portable receivingsystem have been used to investigatepatients with symptoms of GOR to assessthe presence and degree of reflux. In thelast three years we have performed 2(03tests on 9(0 patients with symptoms of GORand 30 normal subjects. Twenty nine(12% ) of the tests failed due to eithertechnical reasons or capsule intolerancebut after repeat studies left a total of 183(90%) for analysis. Abnormal reflux wasdefined as those episodes falling to belowpH5 that occurred more frequently than1 7 episodes/hour and of greatercumulative duration than 6-6 min/h thislimit being determined by the highest value(95% confidence limit) seen in our normalgroup. Using this criteria of a total of 90(patients. 36 (40(1%) fell within the normalrange, 16 (18%/c) showed moderate refluxand 37 (41%lc) were defined as having

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severe reflux. Twenty four of the patientsstudied were recommended for antirefluxsurgery and at 30 months after surgery only

two (8%S) had any further symptoms.Ambulatory monitoring of oesophageal pHis a useful test in the discrimination ofgastro-oesophageal reflux from pain due toother causes and has proved helpful in themanagement of patients with oesophagitisbv assessing the benefits of medication andidentifying those who may benefit mostfrom antireflux surgery.

F19Early detection of gastrointestinal cancer -

is computer aided analysis necessary?

F I t)i I)OMBAi. J S WENHAM. M R KOTWAt.

ANI) .I M BROWN (Clinical InformationScience Groulp, Univer.sit'v Department ofSurgerY, St James Hospital, Leeds) Atprevious BSG meetings. studies have sug-

gested that computer aided analvsis mav be

of value in early detection of GI cancer.

However, others have suggested thatimproved detection rates are due toimproved clinical practice. not to computeranalysis; and that diagnostic difficult'increases with age.

In this study. 468 patients were studiedin five health centres. Mean age was 6(1years, and all presented with two weeks of.new' gastrointestinal symptoms to theirgeneral practitioner. A detailed interviewwas carried out by a nursing sister using a

structured questionnaire. Subsequently thefull patient case record was reviewed by a

clinician, and the nurse's interview dataanalysed by computer.Of the 468 patients, 27 eventually proved

to have cancer. The clinician's analysisdetected 17 of these (with 125 false posi-

tives). Computer aided analysis of thenurse's interview data detected 22 cancers(with 75 false positives). Replacement ofthe computer analysis by a scoring system(based on likelihood ratios) resulted in a

further marginal improvement. 23 out of 27cancer cases being detected at the expenseof only 61 false positives.

Attempts to use a recently published,simple' scoring system (Mann et al 1983).however, were unsuccessful. withunacceptable false positive and falsenegative rates (whatever cut off point was

adopted).These results strongly suggest that GI

cancer can be detected earlier than atpresent; and that this detection isdependent upon detailed careful interviewtogether with multivariate analysis of all

symptoms. The results also suggest,however, that such an analysis need notnecessarily be computer based.

F20)Recent changes in perforated peptic ulcer

R M WATKINS, A R DENNISON, AND J COLltIN

(INTRODUCE:D BY A R BERRY) (Nu (fieldDepartmenit of SurgerY. John RadcliffeHospital. Headington. O.ford) There hasbeen a marked fall in the number ofelective operations for peptic ulcerationsince 1976. Our aim was to assess recentchanges in the incidence and pattern ofperforated peptic ulcer.An 18 year review of perforated peptic

ulcers in Oxford is presented. Theincidence in 1965-76 wsas 8X4 per 100 000

population compared with 6'9 per 1()( 000

in 1977-82. There was a significant fall inthe male:female ratio from 1965-70 to1971-76 (4'9:1 to 2 1: -y2= 1.7. p<0(001)and a further fall 1977-82 (1-9: 1). Theratio of duodenal to gastric ulcers duringthe periods 1965-70. 1971--76. and 1977-82were respectively 6-0:1. 6-4: 1, and 8-2:1.One hundred and sixty six patients

(mean age 60-9 years) treated 1977-82were reviewed in detail. The overallmortality was I37,r (22%/c for gastric ulcersand 11I for duodenal perforations). Onehundred and eight patients had an acuteulcer and 52 a chronic ulcer of whom eightwere taking cimetidine. Twenty six per

cent of patients were taking non-steroidalanti-inflammatory drugs at the time ofperforation. Six patients had previouslyhad a perforation and 12 a haematemesis.Nine patients (5-4%/ ) were treated withoutoperation, of whom seven died. Ninetyfour patients (56'6%) had simple closure ofthe perforation and 38(0% definitive ulcersurgery (58 vagotomy and drainage, fivegastrectomy).We conclude that marked changes have

occurred in the sex incidence and type ofperforated peptic ulcers in the last twodecades. Two thirds of perforations are

now of acute ulcers and hence are unlikelyto be prevented by improved therapy forchronic peptic ulceration.

F21Inhibition of early and late postgastrectomydumping by somatostatin infusion

R G LONG. T E ADRIAN, AND S R BLOOM

(Gastrointestinal Laboratorv, St Thomas'sHospital. London, and Department of

Mledicine, Roval Postgraduate MedicalSchool, London) Somatostatin (SRIF)inhibits small intestinal secretion and therelease of many pancreatic and gastro-intestinal hormones. As such factors hiavebeen implicated in the pathogenesis ofdumping, we induced the symptoms ofearly dumping in six patients with either 5f)or 100 g oral glucose as a 25%-r solution.Intravenous SRIF (Serono UK Ltd. 70pmol/kg/min) was infused on a subsequentday. With SRIF infusion, the symptoms ofearly dumping were abolished or reducedin five of the six patients and there wa1s asignifcant reduction at 30 minutes in thepulse rate (87±4 vs 67±3 beats/min,p<0(005), the packed cell volume (PCV)(0-46±00-1 vs 0-43±00-1, p<0-005). andthe serum glucose (10(9+1 7 v's 7-8±1'2mmol/l. p<0.)-05). At 30 minutes. the meanplasma levels of vasoactivc intestinal poly-peptide, neurotensin, enteroglucagon.insulin, gastrin, pancreatic polypeptide,gastric inhibitory polypeptide, and motilinwere also reduced during SRIF. The serumglucose fell to a nadir of 3-2 mmol/l or lessin five of the six patients on the controlday, but during SRIF, later mean glucoscvalues were higher- for example. at 120min. 4 8+ 18 s.S 14-7± 1-0 mmol/l, p<0-005- and the mean insulin response wasreduced. Thus SRIF abolishes earlydumping symptoms. the tachvcardia, therise in PCV, and the early glucose peakprobably by reducing hormone and smallintestinal secretion, it also preventsreactive hypoglycaemia by blocking insulinrelease.

F22Does eating influence blood alcohol levelsafter partial gastrectomy?

F P MOORE, P G MURPHY. F V FLYNN, AND C G

Cl,ARK (Departments of Surgery andChemical Pathology, University CollegeHospital, and Facultv of Clinical Sciences,Universitv College Lonidon, London) It iswell recognised that patients who haveundergone partial gastrectomy absorbalcohol more rapidly than normal subjects.To test the hypothesis that food alters boththe timing and magnitude of peak bloodalcohol concentrations, we investigated sixnormal male subjects and nine patientswho had undergone a Billroth II partialgastrectomy. All subjects were investigatedon two occasions, at least one week apart,after an overnight fast. They were given 50ml gin in 115 ml tonic (standard double ginand tonic) either in the fasted state or 30

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minutes after eating a snack (toasted sand-wich and an apple). Blood for alcoholestimation was collected at 0, 5, 10, 15, 20,25. 30. 45. 60, 90, and 120 minutes.Alcohol estimation was by gas liquidchromatography. Results confirmed thatpartially gastrectomised patients achieve ahigher alcohol peak (mean level=8-8mmol/l at 25 min=41 mg/100 ml) thannormal subjects (7-7 mmol/l at 25 min=35mg/100 ml). After a snack, however,patients achieved a higher peak morerapidly (9-5 mmol/1=44 mg/100 ml at 15min) than normal subjects. in whom thepeak was lower and delayed (7-0 mmol/l at30 min=32 mg/100 ml). The results suggestthat gastrectomised patients may be evenmore vulnerable to intoxication after com-bining eating and drinking. While thedifferences found were not statisticallysignificant, the trend shown appears to beclinically important; one of the patientsachieved a peak blood alcohol level abovethe legal limit for driving (17 mmol/1=80mg/100 ml) only when the 50 ml gin wasingested after eating a snack.

HEPATO-PANCREATICF23-34

F23Endoscopic manometric evaluation ofexogenous cholecystokinin octapeptide onthe pancreatic and biliary sphincters in man

D L CARR-LOCKE AND S BENTLEY (Gastro-enterology Unit, Leicester Royal Infirmary,Leicester) Cholecystokinin is assumed tohave a physiological action on the sphincterof Oddi in man. An endoscopic mano-metric method, using a pneumohydrauliccapillary infusion system and a perfusedtriple lumen catheter with distal openingsspaced 10 mm apart. was u.5ed to study 18subjects during duodenoscopy undermidazolam sedation. Ten were asympto-matic subjects after previous cholecystec-tomy and in these common bile duct(CBD) and bile duct sphincter (BDS)-ecordings were obtained. Eight wereasymptomatic after previous endoscopicsphincterotomy and provided pancreaticduct (PD) and pancreatic duct sphincter(PDS) recordings. Ductal and sphinctericpressures were measured in the basal stateand during stepped increasing doses ofexogenous cholecystokinin octapeptide(CCK-OP, Kinevac, Squibb) infused at2-5, 5, 10, 20, 40 and 80 ng/kg/h. All basalrecordings were within previously

established normal ranges. Pancreatic ductpressure fell from 16-7+2 4 mmHg(mean ± SE) to 11 7±2 9 nmmHg andCBD pressure fell from 3 3±1 3 mmHg to0 at 10 ng/kg/h of CCK-OP. Phasic wavefrequency in both PDS and BDS zonesslowed significantly with infusions of 10ng/kg/h and greater and were completelyabolished at 80 ng/kg/h, as with anintravenous bolus of 20 ng/kg. Pancreaticduct sphincter and BDS phasic pressureswere significantly decreased with CCK-OPinfusions of 20 and 40 ng/kg/h and wereunrecordable at 80 ng/kg/h.We conclude that CCK-OP has a potent

relaxing effect on the PDS and BDS zonesat physiological and pharmacologicallevels.

F24C4 genotype in children with autoimmunechronic active hepatitis (CAH)

D VERGANI, L WELLS, E T DAVIS, G MIELI-VERGANI, AND A P MOWAT (Departmnenits ofImmunology and Child Health, Kintg'sCollege Hospital, London anid AlatiotnalBlood Transfusioni Service, Birmingham)We have shown that children with auto-immune CAH have genetically determinedlow levels of the complement componentC4 and we suggested that this is apredisposing factor as similar findings areassociated with autoimmune disorders inexperimental animals. C4 is coded for bytwo separate loci situated in the majorhistocompatibility region of chromosome6. Twelve or more allotypes including 'null'variants have been described at each ofthese loci. To investigate whether C4deficiency in CAH is associated withspecific alleles, we have studied 11 suchchildren and their parents. C4 phenotypewas determined by immunofixation ofelectrophoresed desialated samples. C4serum levels by nephelometry and C4function by haemolytic assay. At least onenull allotype was found in nine of 10 CAHpatients whose genotype was deduced,eight having low C4 concentration orfunction. The genotype was known in 15parents: 12 had null variants, six of whomhad low C4 levels. Null allotypes werepresent in 42 of 100 blood donorssignificantly less frequently than in thepatients (X2=8.4, p<0005) or theirparents (X2=7-5. p<001).

This study shows an association betweendeficient C4 and null variants of C4 inCAH but its pathogenic significanceremains to be established.

F25Value of serum liver specific protein anti-bodies as a predictor of relapse in auto-immune chronic active hepatitis

J E HEGARTY, C MCSORLEY, B MCFARI-ANE, I (iMCFARLANE, AND ROGER WILLIAMS Liver

Unit, King's College Hospital, London)As previous studies have shown that con-ventional biochemical, immunological andhistological indices are of no value inpredicting the outcome of corticosteroidwithdrawal in patients with autoimmunechronic active hepatitis (CAH), we haveprospectively evaluated the use of serumliver specific protein antibodies (anti-LSP).measured by radioimmunoassay, as apredictor of outcome in a group of patientswith CAH who were participating in a trialof treatment withdrawal.The 22 patients in whom corticosteroids

were withdrawn over a 12 week period hadbeen in clinical, biochemical (AST<4t)IU/I) and histological (chronic persistenthepatitis) remission for one to nine years.and of these 16 had a relapse of disease, asdefined by an increase in AST>120 IU/Iand piecemeal necrosis on liver biopsy. Ofthe 22 patients. eight were anti-LSPpositive (titre 1/470 to 1/93t)) ait entrv intothe trial, and all subsequently relapsed. Ofthe 14 patients who were initially anti-LSPnegative. six achieved sustained remissionand remained anti-LSP negative. In sevenof the eight remaining pattients. anti-LSPantibodies developed during the course oftreatment withdrawal. their appearanceantedating the rise in AST by three to 10weeks, while in one patient relapsecoincided with the appearance of anti-LSP.The results indicate that serum LSP

antibodies are a sensitive predictor ofoutcome in patients with aiutoimmuneCAH in whom treattment is beingwithdrawn.

F26Bone loss in corticosteroid treated patientswith HBsAg negative chronic activehepatitis (CAH)

A J STELLON, A DAVIES. ANI) R S WIItLIAMSLiver Unit, King's College Hospital.,London) Cortical bone loss has beendetected in 25,/c of corticosteroid treatedpatients. with parenchvmal liver disease,using metacarpal morphometrv. Thismethod may not reflect bone changes aitother sites, however, and correlates poorlywith trabecular bone loss. This presen tstudy evaluates the degree of cortical anld

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trabecular bone loss and its relationshipwith dose and duration of corticosteroidtherapy in asymptomatic patients withCAH.

Thirty four women (15 premenopausal)with inactive CAH, aged 20-65 years, onprednisolone 7-5-12 5 mg/day underwentiliac crest biopsy to determine totaltrabecular bone volume (TBV) and corticalplate thickness (CT). Photon absorptiondensitometry at 3 cm and 8 cm from theradial styloid process was performed toestimate the mean mineral content.Estimation of the cortical area: total arearatio (CA/TA) of the 2nd metacarpal andassessment of spinal score was performedusing conventional radiology.

Trabecular bone volume and CT weredecreased (>2SD mean of age matchedcontrols) in 21% and 33% patientsrespectively. Mean mineral content (BMC/W) at both radial sites and the CA/TAratio was decreased (>2SD in 15% and12% patients respectively), with only onepatient having developed wedged vertebra.No correlation was found between dose/duration of therapy (mg/years) and any ofthe indices, although a correlation existedwith TBV in the post-menopausal group(r=-0 59; p=0-.05). The results show thatmany patients with CAH on corticosteroidshave accelerated asymptomatic bone lossand suggest that treatment measuresshould be instituted early in the course ofthe disease.

F27Controlled trial of azathioprine withdrawalin HBsAg negative chronic active hepatitis

A J STELLON, J E HEGARTY, A L W F

EDDLESTON, B PORTMANN, AND R WILLIAMS(Liver Unit, King's College Hospital,London) Although randomised placebocontrolled clinical trials have establishedthat azathioprine alone is of no value in thetreatment of HBsAg negative chronicactive hepatitis (CAH), it is neverthelesswidely used in this disease in combinationwith corticosteroids on the basis that itexerts a steroid sparing effect. As such aneffect implies that azathioprine is con-tributing to control of disease, arandomised controlled trial of azathioprinewithdrawal was undertaken in 50 patientswith CAH who were maintained in clinical,biochemical, and histological remission forprolonged periods (one to five years) on acombination of azathioprine (50-100 mg/daily) and prednisolone (5-12.5 mg/daily).The group of 27 patients in whom azathio-

prine was discontinued was similar withrespect to age, sex, duration of disease,and remission, previous treatment.presence of cirrhosis, autoantibody statusand frequency of previous relapses to the23 patients who remained on combinationtherapy. Over a median follow up period of20 months, reactivation of disease, definedby a three fold increase in serum trans-aminase concentrations (> 120 IU/I) and/orliver biopsy showing the histologicalfeatures of CAH, occurred significantlymore often in the azathioprine withdrawalgroup (seven of 27 versus one of 23;p<0 02, X2 analysis). The results of thestudies showing a therapeutic effect ofazathioprine suggests that its use, in higherdoses, may allow withdrawal of corti-costeroid treatment or a reduction in thedose to levels which minimise their longterm complications.

F28Sclerosing-cholangitis-like changes inpatients with pancreatic disease

R J L ANDERSON. F WARWICK, AND J MBRAGANZA (The University Department ofGastroenterology and the RadiologyDepartment, Manchester Royal Infirmary,Manchester) While abnormal pancreato-grams have been noted as an incidentalfinding in up to 50% of patients withsclerosing cholangitis, the frequency ofabnormal intrahepatic bile ducts in patientswith pancreatic disease is unknown. Therecent finding of abnormal bile in patientswith pancreatic disease prompted thisretrospective analysis.

Retrograde cholangiograms of patientsreferred for pancreatic investigation werestudied. When the diagnosis was doubtfulor follow up inadequate patients wereexcluded, as were those known to havechronic liver disease, or previous sphinc-terotomy and bile duct exploration. Thestudy group finally consisted of 47 patientswith chronic pancreatitis, 12 with acutepancreatitis, seven with pancreatic cancerand eight with spastic colon syndrome.Cholangiograms were assessed forroughening, irregularity and strictures ofthe extra-hepatic duct, and alsoirregularity, roughening, strictures, prun-ing or nipping of the intrahepatic biliarytree. The frequencies of the variousabnormalities in the different groups werecompared using Fisher's exact test.Cholangiographic abnormalities werefound in 83% of patients with pancreaticdisease (p<0.00l compared with controls);

abnormalities were found in 83%, 75% and100% of patients with chronic pancreatitis,acute pancreatitis or pancreatic cancerrespectively. Excluding patients withconstricted distal common bile ducts, 70%with chronic pancreatitis, 55% with acutepancreatitis and 67% with pancreaticcancer displayed cholangiograhicabnormalities. Abnormalities of the intra-hepatic biliary tree accompany pancreaticdisease, and these are not solely due tocompression of the intrapancreatic bileduct. The link between sclerosingcholangitis and pancreatic disease might lieat the level of the hepatocyte.

F29Pulmonary amine metabolism in experi-mental obstructive jaundice

A BOMZON, 0 S BETTER, M B H YOUDIM, L MBLENDIS (Departments of Pharmacology,and Nephrology, Technion Medical Schooland Rambam Hospital, Haifa, Israel)Patients with obstructive jaundice have anincreased risk of postoperative shock. Ithas recently been shown that the lungshave the potential for regulating arterialblood concentrations of vasoactive amines.Studies in chronic bile duct ligated animals(CBDL), up to seven days, have shownchanges in systemic haemodynamics andaltered responsiveness to sympatheticstimulation. Therefore, pulmonarynoradrenaline (NA) metabolism wasstudied in three day postoperative CBDLrats using the isolated lung perfusion tech-nique and lung homogenates. Mean serumbilirubin concentrations in CBDL rats were197±27 ,umol/l vs 9-4±2+4 gmol/l(p<0-001) in sham-operated rats. Meantotal metabolites formed from a threeminute infusion of 15 uM'4C NE wassignificantly increased in the CBDL rats:22 8±2 9% vs 15 1±1 7% in sham rats(n=17, p<005). This increase wasassociated with an increase in meanpulmonary uptake of NA in CBDL rats:1910±322 vs 970±166 nM/g lung/min insham rats (n= 13, p<0 02). In contrast,there were no significant differences inpulmonary catabolic enzyme activitiesbetween the two groups - that is. catechol-0-methyl transferase 947±252 (CBDL) vs772±200 (sham) nM/g protein/h; mono-amine oxidase type A 2 7±0 7 vs 2 6±0 5and type B 1-7±0-4 vs 1-6±0 4 nM/mgprotein/min. In a separate experiment,mean pulmonary metabolism of 15 uM'4CNA of CBDL rats at five to six days44 8± 1 1% (n =6) was significantly greater

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than that at three days (p<0-001). Theseresults show that obstructive jaundicealters pulmonary metabolism of NA whichincrease with time. This abnormality maybe associated with the altered responsive-ness to sympathetic stimulation in theseanimal models. This study was supportedby a Ministry of Health Grant, and theMinistry of Absorption.

F30Role of cholecystokinin in the pancreaticexocrine response to intraluminal aminoacids and fat

R S STUBBS AND B E STABILE (INTRODUCED BYL H BLUMGART) (VA Medical Center, WestLos Angeles, California, USA) Contro-versy continues over the relative contribu-tion of hormonal and neural mechanisms inproducing the exocrine pancreatic responseto ingested food. Using Proglumide, a drugrecently shown to be a specific chole-cystokinin (CCK)/gastrin receptorantagonist we have revaluated the role ofCCK in this process. Duplicate experi-ments were performed in each of five adultmongrel dogs prepared with chronic gastricand pancreatic fistulae. Dose responsestudies to intravenous octapeptide of CCK(CCK-OP), intravenous bethanechol,intraduodenal amino acids (AminosynR)and intraduodenal fat emulsion (LiposynR)were conducted with and withoutsimultaneous intravenous infusion ofProglumide 300 mg/kg/h. Ten minutepancreatic juice samples were analysed forprotein, volume and bicarbonate outputs.Proglumide infusion competitivelyinhibited the pancreatic responses to intra-venous CCK-OP but produced only minorand not significant inhibition of theresponses to intravenous bethanochol.Almost total inhibition of all doses ofintraduodenal amino acids and intra-duodenal fat was observed from theinfusion of Proglumide.These results strongly suggest that chole-

cystokinin is indeed the major mediator ofthe intestinal phase of pancreatic enzymesecretion.

F31Oral dissolution therapy - a valid option inmanagement of biliary duct stones

W R ELLIS, K W SOMERVILLE, B H WHITrEN,T W BALFOUR, AND G D BELL (Departmentof Therapeutics, City Hospital,Nottingham) Reports of oral therapy forbile duct stones are few, but suggest less

than 30% efficacy for chenodeoxycholicacid (CDCA): 50% success was recordedin the only trial of ursodeoxycholic acid(UDCA), but many patients withdrewbecause of persistent symptoms orcomplications. Our experience exceeds anypreviously published, comprising 31patients (aged 31-83 years, mean 69 years,24 cases over 60 years) each with one tonine radiolucent duct stones (4-22 mm,mean 10, 23 over 7 mm). Nineteen patientstook Rowachol, a terpene preparation,eight (42%) achieving complete stonedisappearance (CSD) in three to 48months. Fifteen (including three of theabove) took Rowachol with bile acid (11CDCA, four UDCA) for three to 60months: 11 (73%) achieved CSD within 18months. Persistent symptoms or complica-tions necessitated withdrawal in only fourcases. Eight patients required hospitaladmission during treatment (two biliarycolic, one obstructive jaundice, fourcholangitis, one pancreatitis). All settledon conservative management, but the lastdied of intercurrent illness during recovery:the others continued treatment, twoachieving CSD.We conclude that Rowachol and bile

acid combination treatment for chole-docholithiasis is superior to bile acids usedalone both in efficacy and symptomcontrol. Oral dissolution therapy is areasonably safe and effective alternative tosurgery when endoscopic sphincterotomy isnot feasible, or unavailable.

F32Incidence and outcome of adenocarcinomaof the extrahepatic biliary tree

J B ANDERSON, M J COOPER, AND R C NWILLIAMSON (University Department ofSurgery, Royal Infirmary, Bristol) Fiveyear survival rates of 4-8% have beenreported for adenocarcinoma of the extra-hepatic biliary tree, with most studiesemanating from North America. To deter-mine the incidence and outcome of thesetumours in Great Britain, the records of243 consecutive patients with cancer of thebiliary tree presenting over a 15 yearperiod were reviewed. There were 87patients with carcinoma of the gall bladder,68 of whom were submitted to laparotomywith a 54% operative mortality; only fivesurvived longer than one year with onelong term (five year) survivor whosediagnosis was made incidentally on histo-logical examination of a cholecystectomyspecimen. Among 31 patients with

carcinoma of the ampulla of Vater therewas a 27% operative mortality, but 12 werealive at one year and three survived fiveyears. Of 125 bile duct cancers 63 aroseproximal to the cystic duct entry; seven ofthese patients obtained useful palliation byintubation and seven of eight survivedresection, but none lived two years. Distalcholangiocarcinomas carried a similardismal prognosis; resection was accom-panied by a 75% operative mortality, withonly three patients surviving for two years.For all carcinomas of the biliary tree therewas a two year survival rate of 5% and afive year survival rate of 2%.Modern imaging techniques should

facilitate early and accurate diagnosis ofthese neoplasms. Referral to specialistcentres might help to improve the survivaland prognosis of these lethal cancers.

F33Choledocholithiasis: discrepancies betweenultrasound and retrograde cholangiogramfindings

M V TOBIN, I T GILMORE, AND G H R LAMB

(Royal Liverpool Hospital, Prescot Street,Liverpool) While ultrasound is of provenvalue in distinguishing medical and surgicalcauses of jaundice, with accuracy rates ofup to 90%, it is important for clinicians torealise that it may be less successful inparticular subgroups such as those withcommon bile duct stones. We haveexamined the results in 101 consecutivepatients who later had a definitive retro-grade cholangiogram performed. Of 26with choledocholithiasis eight (31%) had anormal ultrasound, and in a further fiveultrasound was technically unsatisfactory;in only 2/26 (8%) were stones detected andin 10/18 biliary dilatation correctlydiagnosed. In eight patients with stones butno biliary dilatation, only two (25%) hadabnormal ultrasound examinations.Overall, ultrasound examination correctlyidentified a normal biliary tree in 54/64patients (84%) and distinguished dilatedfrom non-dilated ducts in 83%, confirmingprevious reports.Thus, while the overall results are

excellent, it should be appreciated thatultrasound examination of the biliary treemay be unreliable in choledocholithiasis,particularly when the biliary tree is notdilated as is the case in approximately 30%of patients. Retrograde cholangiographyremains an important investigation whencommon bile duct stones are clinicallysuspected.

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F34Comparison of cholecystography and ultra-sonography for detection of gall stones

R P JAZRAWI, A E A JOSEPH, A G WILSON, ANDT C NORTHFIELD (Departments ofRadiology, Ultrasound and Medicine, St.George's Hospital Medical School,London) Ultrasonography is a safe,simple, and sensitive method of diagnosinggall stones, but its accuracy relative to oralcholecystography is still a matter of con-troversy. We have therefore carried out adouble blind comparison of (a) 102 con-secutive patients whose symptomssuggested a diagnosis of gall stones. Wealso compared the two techniques for (b)diagnosis of complete gall stone dissolutionin 71 patients undergoing bile acid therapy;and for (c) diagnosis for gall stonerecurrence in 28 patients after a confirmeddiagnosis of complete dissolution. In (a)oral cholecystogram showed gall stones in22 patients, was judged normal in 76, andin four showed no opacification of the gallbladder. Ultrasonography showed gallstones in three of the 76 normal chole-cystograms and in three of the four patientswho failed to opacify, and in all six patientsgall stones were found at surgery. Itconfirmed the presence of gall stones in 21out of the 22 with a positive oral chole-cystogram, but not in one patient in whomthe true diagnosis was not clarified bysurgery. In (b) complete gall stonedissolution was diagnosed by oral chole-cystogram in 31 patients, whereas ultra-sound showed the persistence of gall stonesin five of these patients. In three of the five,the ultrasound became negative followingcontinued bile acid therapy. In (c)recurrence of gall stones was shown byultrasound in six patients, whereas chole-cystogram detected recurrence at the sametime in only three of these patients. Arepeat cholecystogram in the next threemonths confirmed recurrence of gall stonesin all six of these patients. We concludethat ultrasonography provides a moresensitive method of diagnosing gall stones,and of monitoring progress during andafter bile acid therapy.

COLORECTALF35-46

F35Haemoccult testing in general practice forearly diagnosis of colorectal cancer

R J LEICESTER, D G COLIN-JONES, R H HUNT,J MILLAR, AND A I LEICESTER (Royal NavalHospital Haslar and Queen Alexandra'sHospital Cosham, Hants) Many studieshave advocated haemoccult as a screeningtest for colorectal cancer, but compliancerates are often low. In a previouslyreported study of symptomatic outpatientswe found a high sensitivity for colorectalcancer and good compliance rates but aconsiderable delay from first reportingsymptoms to final diagnosis.

In a prospective study we have evaluatedhaemoccult testing in symptomatic patientspresenting in general practice. Patientsover 40 years, with any abdominal or bowelcomplaints were allocated randomly tohaemoccult testing or control groups.Control patients and those with a negativetest were managed conventionally by theirgeneral practitioners including specialistreferral if appropriate. Patients with apositive test underwent flexible sigmoido-scopy and double contrast barium enema atthe earliest opportunity, followed byurgent outpatient consultation and colono-scopy where indicated.Three hundred and fifteen patients (121

men, 194 women, mean age 58-2±13-9years) were entered into the study, 161(99-4%) in the haemoccult group compliedwith the test and 25 (15.5%) had a positiveresult; significant colorectal disease beingfound in 80% (four cancer, six polyps, fivediverticular disease, two Crohn's and threecolitis). False negativity was 44% forcancer (two advanced, obstructing lesions)and 44% for polyps. Eleven cancers andnine polyps were detected amongst 154controls. Delay to diagnosis wassignificantly less in patients with a positivetest (3-51±1.8 weeks) than controls(8-8±5.3 weeks, t=3-7, p<0-001).Haemoccult testing is easily carried out

in general practice and well accepted bysymptomatic patients. A positive test is auseful indicator of significant colorectaldisease, allowing earlier referral anddiagnosis.

F36Screening of first degree relatives ofpatients with bowel cancer

N C ARMITAGE AND J D HARDCASTLE(Department of Surgery, UniversityHospital, Nottingham) There is evidencethat first degree relatives of patients withbowel cancer have a three to four timesincreased risk of developing colorectaltumours. We have screened the families of

patients under follow up after operation forcolorectal cancer. A full family history wastaken, including the names and addressesof all first degree relatives. These werecontacted by letter and if agreeable weresent faecal occult blood tests. Thosepatients who returned tests that were foundto be positive were investigated by flexiblefibreoptic sigmoidoscopy and doublecontrast barium enema. A control group ofage/sex matched subjects was identifiedfrom asymptomatic subjects at the time ofentry into a population screening study.

Thirteen patients had no suitable livingrelatives, and the remaining 112 patientshad 436 potentially contactable relatives ofwhom 267 were able to be contacted bypost. Of those contacted, 155 (58%)replied to the first letter and were sent thetests. 120 (45%) completed the tests ofwhich 11 (9 1%) were found to be positive.To date three adenomatous polyps havebeen identified in these patients. In thecontrol group 104 (40%) individualscompleted the tests, of which six (6%)were positive; in these one adenoma hasbeen diagnosed.A detection rate of nearly 3% of

adenomas in first degree relatives ofpatients with colorectal cancer comparedwith 1% in a randomly selected asympto-matic population sample would appearconsistent with an increased risk ofneoplastic disease.

F37Colorectal carcinoma in the first fourdecades

H C UMPLEBY AND R C N WILLIAMSON(University Department of Surgery, BristolRoyal Infirmary, Bristol) Colorectalcarcinoma in young people is reported tobe associated with a poor prognosis. Wereviewed 85 patients aged 40 or less whopresented over a 32 year period withcolorectal carcinoma. The incidence was2-5% of all patients with large bowelcancer (n=3426). Predisposing causesincluded familial polyposis (eight),panproctocolitis (ulcerative one, Crohn'sone) and irradiation (one); four patientswere pregnant. Symptoms and signs werethe same as at all ages, yet seven patientshad an avoidable delay in diagnosis of fiveto eight months. Twenty eight patients(33%) presented as emergencies: 12 withintestinal obstruction. Fifty nine per cent oftumours were Dukes' C, 31% poorlydifferentiated and 18% of the mucinoustype. Overall five year survival rate was

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41% and after 'curative' resection in 61(73%) was 59%. Survival was equivalentfor elective and emergency cases and formucinous, and non-mucinous carcinomasof moderate histological differentiation.Five year survival rates were poorer whenthe history was <3 months than >3 months(20% vs 45%, p=0-02) and for rectal andrectosigmoid tumours than colonictumours (31% vs 50%: p=O-05). Four offive patients with involvement of adjacentviscera and four of six patients withresectable recurrence survived beyond 10years after radical surgery.

Colorectal carcinoma in the first fourdecades reflects the disease of the usualolder population. Any increase inunfavourable types or stages of the tumourseems to be balanced by greater toleranceto emergency operation. Radical resectionof advanced primary disease and of localrecurrence is well worthwhile and can beassociated with long term survival.

F38Diet preceding large bowel cancer:increased energy-to-fibre ratio

J B BRISTOL, P M EMMETT, K W HEATON, H CUMPLEBY, AND R C N WILLIAMSON(University Departments of Surgery andMedicine, Royal Infirmary, Bristol) Therole of diet in the aetiology of colorectalcancer remains unclear. Studies comparingthe diets of patients and healthy controlshave been inconclusive, and amongpossible reasons is the inclusion of patientswhose eating habits have changed as aresult of their symptoms. Further, mostprevious reports have not assessed dietary(as opposed to 'crude') fibre intake. In thepresent case control study, colorectalcancer patients were included only if theymet the following criteria: no knownpredisposing diseases, no previous majorgastrointestinal surgery, no appetite loss,no recent weight loss >6-3 kg, no nausea orvomiting. Fifty patients fulfilling thesecriteria (28 M, 22 F) were interviewedabout premorbid eating habits seven to 14weeks after operation, by the sameexperienced dietitian using a foodfrequency questionnaire. Fifty healthycontrols matched for age (± three years),sex, social class and marital status weresimilarly interviewed. Data were analysedby computer to obtain the mean dailyintake of energy. nutrients, and dietaryfibre. Colorectal cancer subjects hadhabitually consumed 14% more energy(2p<0 001), 37% more fibre depleted

('refined') sugar (2p<0.01), 14% morecarbohydrate from other sources(2p<0(002), 16% more fat (2p<0 01), and6% more total protein (2p<005) (t test).No difference was found in the dailyintakes of total dietary fibre (patients17 8±0 9 vs controls 19 4±0 7 g), cerealfibre, vegetable fibre, or natural sugar.Energy intake per gram of dietary fibre was23% higher in cancer subjects (0 58±0 02vs 0-47±0+02 MJ/g, 2p<0O001). Thus thisgroup of colorectal cancer patients havetended to eat a diet with a high energy-to-fibre ratio.

F39Flexible fibreoptic sigmoidoscopy in anoutpatient setting

N C ARMITAGE AND J D HARDCASTLE(Department of Surgery, UniversityHospital, Nottingham) Since 1979 flexiblefibreoptic sigmoidoscopy using a 60 cminstrument has been a regular outpatientprocedure in the diagnosis and follow up ofcolorectal conditions.A total of 1339 examinations have been

performed on 657 men and 682 women,mean age 59±13 years (range 15-91 years).

Full examination, beyond 50 cm wasachieved in 1028 (76.8%), mean time 6.6minutes. Of those examinations terminat-ing before 50 cm, 84 (6.3%) were becauseof inadequate bowel preparation. 153(11.4%) because of patient discomfort orspasm, and 74 (5 5%) because ofinflammatory or neoplastic obstructions.Nine hundred and thirty one examina-

tions were performed for diagnosticreasons. Sixty patients were found to havecancer, 158 to have adenomas, 49 to haveinflammatory bowel disease and 129 tohave diverticular disease - a positivediagnosis in 396 patients (42-5%).The diagnostic yield of flexible sigmoio-

scopy for neoplastic disease and three tofour times that of rigid sigmoidoscopy.Two hundred and six colorectal cancer

f6tlow up examinations were performedwith four recurrent cancers and 46adenomas identified.One hundred and eighty eight adenoma

follow up examinations showed one patientwith a colorectal cancer and 60 with furtheradenomas.

Flexible fibreoptic sigmoidoscopy isquick, easily learned and safe. Theincreased diagnostic yield can play animportant role in the management ofcolorectal disease.

F40Place of colonoscopy in the diagnosis ofangiodysplasia

R SALEM, A HEMINGWAY, H REES, D ALLISONAND C B WOOD (Departments of Surgery,Radiology and Histopathology, RoyalPostgraduate Medical School, London)Angiodysplasia can be diagnosed byselective visceral angiography or bycolonoscopy. Colonoscopy can beperformed in most centres but detailedvisceral angiography is a more specialisedtechnique. The results of colonoscopy inpatients shown to have angiodysplasia byangiography were analysed.Forty five patients were diagnosed as

having angiodysplasia by angiography.Thirty one of these had colonoscopy, ofwhich 20 were positive, giving a diagnosticyield of 65%. Of the 11 negative colono-scopies, three had no evidence of angiodys-plasia and eight had incomplete examina-tions; one being due to the presence of acarcinoma at the hepatic flexure. Forcolonoscopies where adequate views of thecaecum were obtained, the diagnostic yieldwas 87%. Nine colonoscopies wererepeated at laparotomy and of these, eightwere positive. In patients who had surgery,the resected specimen was submitted forhistological and detailed microangio-graphic examination.We therefore conclude that colonoscopy

is a useful adjunct to angiography in theinvestigation of angiodysplasia, allowingvisualisation of the lesions with thetherapeutic possibility of fulguration.Visualisation at laparotomy is good andthus colonoscopy at operation is helpful inassessing the extent of angiodysplasiabefore resection.

F41Patients with constipation of different typeshave difficulty in expelling a balloon fromthe rectum

P R H BARNES AND J E LENNARD-JONES (StMark's Hospital, City Road, London)The defaecatory mechanism using aballoon model has been studied in 15control subjects with normal bowel habit(M8 F7) and 39 patients who complained ofconstipation, 31 with a normal bariumenema and eight with idiopathicmegarectum (M6 F2). Of the 31 patientswith a normal barium enema 14 femalepatients had prolonged whole gut transittimes as measured with radio-opaqueshapes and 17 (MI F16) had transit timeswithin normal limits. The ability of the

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subject to expel a rectal balloon containing50, 100, and 150 ml of water was tested inthe left lateral position (LLP) and ifunsuccessful, in the sitting position with theknees raised. The maximum intra-rectalpressure (IRP) outside the balloon wasmeasured with each straining effort andexpressed as a mean of the pressurerecorded with each balloon in eachposition. All but one of the patients withnormal bowel function could expel all ofthe balloons in LLP (mean IRP 107±43 SDcm H2O). Only five of 17 patientscomplaining of constipation with normaltransit rates could expel balloons in LLP(p<0.001 compared with controls) while afurther three were able to do so whensitting (mean IRP 103±33); nine of 17could not expel any balloon in eitherposition. None of the 14 patients withconstipation and slow transit could expelany balloon in the left lateral position(p<0-OOl) (mean IRP 90±37) althoughthree were able to do so when sitting (meanIRP 134±38). None of the megarectumpatients could expel any balloon in eitherposition (p<0.001) and the mean IRP was175±60 (p<0.01 compared to controls). Adisorder of the defaecatory mechanism ispresent in many patients with constipationbut is not apparently due to an inability toraise intra abdominal pressure.

F42Laser irradiation for symptomatic rectaltumours in patients unsuitable for surgery

A I MORRIS AND N KRASNER (Gastro-intestinal Unit, Walton Hospital, Liverpool)The treatment of patients with recurrentrectal tumours presents a difficult problemparticularly in the elderly as does themanagement of primary tumours in theunfit. We have treated a group of five suchpatients with either tumour recurrence inHartman's pouches, or with primaryanorectal tumour in those unfit for surgery.All patients were symptomatic withunpleasant smelling discharge and bleedingper rectum. One of the three patients witha Hartman's pouch recurrence had failed toimprove with deep x-ray therapy andchemotherapy. Treatment using aNeodynium Yag laser was chosen inpreference to further surgery or diathermyfulguration. Laser treatment with pulses ofup to 100 watts for 0-5-1-0 sec and with anaccumulated energy of up to 5000 Joulesper session was applied at weekly or.fortnightly intervals.

In all these patients there was a consider-

able reduction in discharge and bleeding,and in two complete relief of symptoms. Acirrhotic patient, unfit for surgery, hadcomplete ablation of all visible primaryrectal tumour and is alive and well at sixmonths, whereas one patient withinoperable primary anal canal carcinoma,which failed to respond to deep x-raytherapy or chemotherapy has had littlebenefit from laser therapy. The procedurerequires no preparation and can be under-taken with minimal or no sedation. Apartfrom transient rectal discomfort and aninitial transient increase in discharge due totumour sloughing no serious complicationshave occurred. The decrease in symptomshas been of major psychological help tothese patients. This preliminary seriessuggest a further use for laser irradiation inaddition to its use for oesophogealneoplasms, and in upper gastrointestinalhaemorrhage.

F43Influence of the method of internalsphincterotomy for chronic anal fissure andtime after sphincterotomy on the reductionin anal canal pressure

NAOMI CHOWCAT, J G C ARAUJO, AND P B

BOULOS (Department of Surgery, Facultyof Clinical Sciences, University CollegeLondon and The Rayne Institute, London)Internal sphincterotomy by relievingsphincter spasm and reducing anal canalpressure heals anal fissures. Incompletedivision results in recurrence. This studyexamines (1) whether division of thesphincter blindly by the subcutaneousmethod is as adequate in reducing the analcanal pressure as division under vision bythe open method and (2) the effect in thelong term of healing, where the sphincterhad been divided, on the reduction inpressure.Twenty eight patients with chronic anal

fissure were randomly allocated to eithermethod of sphincterotomy. In all patientsthe fissures were healed at one month andremained healed on completion of thestudy.The medians and ranges of the

preoperative resting anal canal pressurewere similar, 107 (51-138) cm H20 inpatients for subcutaneous and 97 (76-129)cm H20 in patients for opensphincterotomy. At one month aftersphincterotomy, the pressures decreasedsignificantly (p<0-01) to 52 (17-75) cmH20 and 47 (35-100) cm H20 respectivelywith 51 (22-77) and 50 (11-68) %

reduction of their respective preoperativemeasurements. There was no statisticaldifference in these results which justifiedpooling all the data for further analysis.

In 18 patients the measurements onemonth after sphincterotomy were 54 (17-100) cm H20 and at three months were 48(19-85) cm H20. In 10 patients themeasurements at one month, three, and sixmonths after sphincterotomy were 50 (17-68) cm H,O, 47 (19-68) cm H20 and 55(20-69) cm H20 respectively. Statisticalcomparisons showed no differences.These results show that both methods of

sphincterotomy are adequate in the extentof sphincter division, as measured byreduction in anal canal pressure which isnot transient and is maintained. Thisinformation adds to our knowledge on theeffectiveness of both methods ofsphincterotomy in the treatment of analfissures.

F44A randomised clinical trial to comparerubber band ligation with phenol injectionin the treatment of haemorrhoids

P C GARTELL, R J SHERIDAN, AND F P MCGINN(Department of General Surgery,Southampton General Hospital,Southampton, Hampshire) A prospectiverandomised clinical trial comparing rubberband ligation (RBL) with phenol injectionin 269 patients with symptomatichaemorrhoids presenting to one surgicalfirm over a period of six years has beencarried out. Questionnaires werecompleted by 215 patients (106 RBL and109 injection) with an average follow up of2-75 years. A successful outcome wasachieved in 89% of those receiving RBLcompared with 70% for injection(p<O-OOl). All symptoms and degrees ofprolapse responded more favourably toRBL but only in those patients with bleed-ing or 2nd degree haemorrhoids did theresults achieve statistical significance(p<O-Ol and p<0*001 respectively). Therewas no significant difference in the severityof pain experienced in the two groups, butthe duration of pain was significantlylonger in those receiving RBL (p<0-01). Itis concluded that RBL is a more effectivelong term therapy for first and seconddegree piles than phenol injection.

F45Prospective randomised trial of injectiontherapy against photocoagulation therapyin first and second degree haemorrhoids

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N S AMBROSE, J ALEXANDER-WILLIAMS, AND

M R B KEIGHLEY (Department of Surgery,General Hospital, Birmingham) Photo-coagulation has proved effective in thetreatment of haemorrhoids whencompared with rubber band ligation. Wehave now compared treatment with photo-coagulation (P) against injection sclero-therapy (IS) for first and second degreehaemorrhoids in outpatients.

Patients with haemorrhoids seen in our

rectal clinic were randomised to receivephotocoagulation (n=73) or injectionsclerotherapy using oily phenol (n=62).Patients were followed and assessed at one,four and 12 months as being excellent,better, the same, or worse. More patientsin the photocoagulation group underwentfurther similar therapy or other therapy(P= 15; IS=4) but similar number requiredoperation (P=4; IS=3). At one monththere was no significant difference betweenthe two groups. At four (P=88%;IS=72%) and 12 months (P=72%;IS=56%) a greater proportion of thoseundergoing photocoagulation were eitherexcellent or better.We conclude that photocoagulation may

require more treatment but is better in thelong term than injection sclerotherapy forthe outpatient treatment of first and seconddegree haemorrhoids.

F46Internal anal sphincter damage in radiationproctitis

J S VARMA AND A N SMITH (UniversitvDepartment of Surgery, Western GeneralHospital, Edinburgh) Urgency,frequency, and incontinence are common

symptoms after radiation injury to therectum. Many of these symptoms are

explainable by reduction in rectal volumeand compliance. In order to determinewhether there is associated sphincterdamage, 10 men with varying degrees ofchronic radiation proctitis after prostaticradiotherapy for carcinoma were assessed.Manometry was carried out to measure

maximum resting pressure (MRP cm

H,O), length of the high pressure zone

(HPZ cm), maximum voluntary contrac-tion (MVC cm H2O) and the presence,amplitude and recovery of the recto-sphincteric reflex (RSR cm H,O) inresponse to rectal balloon distension by 50ml of air. The results were compared with a

group of 10 normal men in the same agegroup.There is a significant reduction in MRP

(61-5±7 8 SEM vs 99±6 7, p<0.0)05), HPZ(2-65±0-2 vs 4 25±0-2, p<0.0l) and RSR(25±4 8 vs 46±2 7, p<();(05) in theproctitis group compared with controls. Inaddition one patient showed absence of theRSR and in four patients it was difficult toelicit and showed a very slow recovery.

Pelvic radiotherapy can result in internalsphincter damage and contributes to faecalincontinence in this group. There appears

to be no evidence of significant externalsphincter damage.

POSTERSF47-92

F47Oral carbenoxolone protects the gastricmucosa against indomethacin

A MARTIN, N ZARAMELLA, G C STURNIOLO,G GURRIERI, AND R NACCARATO Cattedradi Malattie dell'Apparato Digerente,Universita di Padova, Padova, Italy)Previous treatment with prostaglandins(PGs) protects the gastric mucosa againstthe damaging effects of non-steroidal anti-inflammatory drugs (NSAID). Theseexperiments have little clinical relevance,as it is impractical to pretreat patients withPGs before administration of NSAID. Ascarbenoxolone (CBNX) increasesendogenous PG levels through inhibitionof the PG metabolising enzymes, westudied whether simultaneous adminis-tration of CBNX could prevent the gastricmucosal damage produced by indo-methacin.Male Sprague-Dawley rats were used in

all experiments and drugs were given intra-gastrically through a plastic tube after a 24hour fast. All rats were given indomethacin20 mg/kg and while the 24 control ratssimultaneously received only saline, threegroups of 10 rats each received CBNX 1 5or 7-5 or 15 mg/kg.

Control rats had a lesion score (±SE) of42-41±3-87, while CBNX treated rats hada score of 19 70±3 42 (p<001, Wilcoxon'stest), 24 70±3-96 (p<0(05), and22 30±2 70 (p<0O01) for the three doses,respectively. In CBNX treated rats, gastricPGE, levels were significantly higher thancontrols.We conclude: (1) simultaneous adminis-

tration of even small quantities of CBNXgreatly reduces the gastric damage causedby high doses of indomethacin, (2) thiscytoprotection is likely to be mediated by

the increased mucosal levels of PGs, and(3) this effect could be exploited clinically.

F48Changing pattern of gastric ulcer: areanti-inflammatory drugs involved?

O M P JOLOBE AND R D MONTGOMERY (Depart-ment of Medicine, East BirminghamHospital, Birmingham) The changingclinical pattern of gastric ulcer (GU) hasbeen studied in a series of 528 patients seenin one hospital department during the past20 years. The male:female ratio in twogroups presenting before and after 1973has declined from 1 89 to 1 08, and ageadjusted figures show that this declineapplies equally to all age groups. There wasa significant decline in midgastric ulcers inmen (p<0.01). There was a significantfourfold increased incidence ofhaemorrhage in proximal as opposed toantral ulcers and a seven-fold excess ofhaemorrhage in older women as opposedto younger women. Gastric ulcer in womentaking non-aspirin non-steroidal anti-inflammatory drugs(NANSADs) showed an increasedtendency to bleeding (X2-=614, p<0-(25,corrected for age and ulcer site),accounting for 48% of all haemorrhages inwomen over 70 years. On statisticalanalysis, however, NANSAD associatedGU showed no other distinguishingfeatures, and NANSAD usage did notaccount for the changing sex ratio. There isstill no satisfactory evidence that thesedrugs cause chronic gastric ulcer.

F49Twenty four hour intragastric acidity andovernight acid output in duodenal ulcerpatients on a new once daily antisecretorydrug

P J MALE, M GRIESSEN, N GAROFLID, T

NICOLET, R DE PEYER, AND E LOIZEAU(Division de Gastroenterologie et Poli-clinique de Medecine, Departement deMedecine, H6pital Cantonal Universitaire,Geneve, Switzerland) Pyridil-2-tetra-hydrothiophene derivative (RP 40749) is anew potent and long acting inhibitor ofgastric secretion without anticholinergic orH,-receptor antagonist activity (Lancet1982; 1: 1179-80).Using a technique previously reported

(Gut 1976; 17: 133-8) we have measuredone hour of basal acid output, then 24 hourintragastric acidity and nocturnal acid

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secretion in five duodenal ulcer patients inremission. The patients were investigatedon three separate occasions: (1) during asingle day's treatment with cimetidine, (2)one week later during the first day, and (3)during the tenth day of RP 4t)749 treatment(cimetidine 200 mg tds, 400 mg nocte; RP40749 100 mg once daily).

Before treatment, mean basal acidoutput was 522±SEM 185 mmol/h; forthe corresponding hour after 10 days of RP40749 the mean acid output was 0(46±0+28mmol/h (p<0)(2). Overnight hourly acidoutput was t)82±0+26 mmol/h oncimetidine, 104+t)027 mmol/h on day 1 ofRP 4t)749, and was reduced to 0(37±0(06mmol/h on day 10 (NS).The mean intragastric H ' activity during

24 hours was 9 3±3 1 mmol/l/h oncimetidine, 5X8±13 mmol/l/h the first dayon RP 40749 (NS). and was reduced to0(31±0+13 mmol/l/h the tenth day(p<0O0l). On that occasion 90% of thesamples had pH>3-5.RP 40749 once daily is as effective as

cimetidine in the reduction of acidsecretion. In addition, in contrast withwhat has been shown previously for H,-receptor antagonists, its effect increasesmarkedly with duration of treatment, andthus RP 40749 deserves further considera-tion for duodenal ulcer treatment.

F5(Comparison of colloidal bismuth andcimetidine in the healing and early relapseof duodenal ulcer

I F TROTMAN, J MEYRICK-THOMAS, AND J J

MISIEWICZ (Department of Gastro-enterologv, Central Middlese.r Hospital,Londotn) Colloidal bismuth (bi-citro-peptide: BCP) 10 ml qds was comparedwith cimetidine 1 g daily in the treatment ofduodenal ulcer (DU) in a double blind,double dummy, endoscopically controlledtrial. The effect on timing of relapses wasalso studied. Sixty patients (37 men, 23women, mean age 43 years. range 21-69years) with DU were randomly allocated totreatment with either BCP (30 patients) orcimetidine (30 patients) for six weeks.Symptoms were recorded on diary cardsand at interview at 0, three, and six weeksand ulcer healing was determined byendoscopy at six weeks. In those who hadhealed, a further endoscopy was done atthree months, or earlier if symptomsrecurred. Three patients on BCP and oneon cimetidine were withdrawn for non-compliance. The groups were similar with

respect to age. sex, smoking. alcohol, andduration of ulcer symptoms. Twenty five of27 (92%/) healed on BCP, and 24 of 29(83C%c) on cimetidine (p=NS). Relief ofsymptoms was similar with both drugs andno adverse effects were reported. At threemonths, six patients of the 16 (37%7c) givenBCP, compared with 11 of 21 (52%,/c) givencimetidine. relapsed (p=NS). Only 43%Sc ofrelapses were symptomatic. This studyshows that healing of DU with BCP issimilar to that with cimetidine and thatcontrary to earlier reports the early relapserate is not different after healing witheither drug.

F51Comparison of tripotassium dicitratobismuthate (TDB) tablets and ranitidine inhealing and relapse of duodenal ulcers

G BIANCHI PORRO. L BARBARA, R CHEtIi, P RDAL MONTE, AND G MAZZACCA (Departmentof Gastroenterologx', L Sacco Hospital,Milano; 3rd Medical Clinic, University ofBologna; Department of Gastroenterologv,St Martino Hospital, Genova; Departmentof Gastroenterology, Bellaria Hospital,Bologna; Chair of Gastroenterologv,Universitv of Napoli, Italy) One hundredpatients with endoscopically diagnosedduodenal ulcer were allocated according toa double blind, double dummy protocol, toreceive for four weeks either ranitidine(150 mg bd) or TDB (four chewing tabletsdaily). If after one month ulcers, assessedendoscopically, were not found to behealed, treatment was continued andendoscopy performed again after a furtherfour week course of the same treatment.

In the TDB treated group one patientwithdrew due to constipation: of theremaining 49 patients, 40 (81.6%) and 47(95.9%) were found to have their ulcershealed after four and eight weeks' treat-ment respectively. In the ranitidine treatedgroup 34/50 (68%) of the patients werehealed after four weeks and 46/5() (92%)after eight weeks' treatment. No statisticalsignificance was found between the twotreatments regarding antacid consumptionand pain reduction, although both treat-ments were highly effective for theseparameters.

After active treatment, all patients weremaintained during the follow up phase oneither TDB or ranitidine placebo plus therespective placebo they had receivedduring the active phase according to thedouble dummy protocol. Proven relapse

was observed within six months in 14/44(32%) of patients whose ulcers had beenhealed during treatment with TDB incomparison with 30/46 (65%) who relapsedafter healing with ranitidine.Tripotassium dicitrato bismuthate

appears to be as effective as ranitidine inthe short term treatment of duodenal ulcer:moreover, the present findings reinforcethe suggestion that TDB may prevent earlyrelapse following treatment.

F52Twice daily cimetidine in the treatment ofgastric ulceration

P BROWN, G V H BRADBY, J M FINDLAY,C GILBERTSON. G D KERR. R MACHELL,J TEMPLE, A C B WICKS, AND J G WILLIIAMS

(Roi al Shrewsbury Hospital, SandwellDistrict General Hospital, Bradford RoyalInfirmary, Nevill Hall Hospital, Aber-gavenny, West Cornwall Hospital, QuieenElizabeth Hospital, Birmingham, LeicesterGeneral Hospital, Roval Naval Hospital,Plvmouth) Within the UK eight centrescontributed 137 patients with endoscopicevidence of gastric ulceration to a singleblind comparison of cimetidine 400 mg bid,and cimetidine 200 mg tid and 400 mgnocte. Six patients with malignant ulcerswere withdrawn, four identified at entry,and two at subsequent endoscopies.Twenty five other patients were excluded.mainly defaulters. Data from 106 patients(55 receiving cimetidine. qid and 51 bid)were statistically analysed for the effects oftreatment regimen, age, sex, smoking, andalcohol consumption on healing rates usingx2 tests and log linear analysis of con-tingency tables and the Mann-Whitney Utest.At endoscopy after six weeks' treatment,

73% of patients healed with the qid and76% with bid regimen (NS). This increasedto 94% with qid and 87% with bid after 10weeks' treatment. There was no effect ofsex, smoking, or alcohol consumption onhealing rate. There was a suggestion thatolder patients (an arbitrary age division of60 years was considered) who had nothealed at six weeks healed more frequentlyat 1t) weeks with the qid regimen. Therewas no difference between treatments inthe effect on symptoms or antacid con-sumption during the trial. Adverse eventswere mild and resolved in most cases by theend of the trial.

Cimetidine 40)t mg bid is as effective as1 g/day in producing healing and sympto-matic improvement of gastric ulceration.

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F53Comparison between ranitidine and con-ventional therapy in the management ofhaemorrhagic peptic lesions

A NOWAK, K GIBINSKI, E NOWAKOWSKA, C ZSADLINSKI, Z GORKA, J RUDZKI (INTRODUCEDBY J R WOOD) (Department of Gastro-enterology and Surgery, Silesian MedicalSchool, Katowice, Poland) Previousstudies have reported beneficial effects ofranitidine in the treatment of upper gastro-intestinal bleeding. Little is known,however, about the changes haemorrhagiclesions undergo during treatment.

In this study 150 patients with endo-scopically assessed upper gastrointestinalbleeding were randomly allocated toreceive either ranitidine or conventionaltreatment for 10 days. Both groups werecomparable for age, sex, and haemoglobinlevel.

Endoscopic findings and the need forsurgery were compared for the two groupsafter 10 days' treatment. In the ranitidinetreated group 7% of patients with gastriculcer (GU) required surgery comparedwith 39% on conventional treatment(p<0 01). Eight per cent of duodenal ulcer(DU) patients receiving ranitidine requiredsurgery compared with 14% of convention-ally treated DU patients (NS). In patientsdiagnosed as having gastritis, nonereceiving ranitidine and 8% receiving con-ventional treatment required surgery (NS).In total, 7% of ranitidine patients and 23%of conventionally treated patients requiredsurgical intervention (p<0-01).Endoscopic healing or improvement

after 10 days was seen in 87% of GUpatients receiving ranitidine and 43%receiving conventional treatment(p<0 05). Seventy three per cent of DUpatients on ranitidine showed healing orimprovement compared with 49% on con-ventional therapy (p<0.05). All patientssuffering from gastritis and receivingranitidine showed endoscopic improve-ment compared with 67% in the con-ventionally treated group (NS). Overall,endoscopic healing or improvement wasapparent in 81% of patients with ranitidineand 49% of patients by receiving con-ventional therapy (p<0.05).These results show a significant benefit

of ranitidine over conventional therapy inthe treatment of haemorrhagic pepticlesions. The superior efficacy of ranitidinemay be particularly beneficial to patientsbleeding from gastric ulcers.

F54Serum pepsinogen 1: a non-invasive markerof gastric dysplasia

C N HALL, J O'SULLIVAN, J S KIRKHAM, ANDT C NORTHFIELD (Departments of Gastro-enterology and Histopathology, St James'Hospital, and Department of Medicine,St George's Hospital Medical School,London) Detection rates for gastriccancer by endoscopy and multiple biopsiesare low even in the precancerous con-ditions of Polya gastrectomy (PG) andpernicious anaemia (PA). Epithelialdysplasia is a precancerous lesion whichmay delineate the highest risk individualsfor gastric cancer in whom endoscopicsurveillances may be more effective. Wehave previously shown that the incidenceand severity of epithelial dysplasia isincreased in stomachs of low acidity asdetermined by gastric aspiration studies.Measurement of serum pepsinogen 1 isreported to reflect gastric acid secretion.The aims of this study, therefore, were tovalidate serum pepsinogen 1 as an index ofgastric acidity and to investigate therelationship between pepsinogen 1 andgastric dysplasia. Accordingly 30 subjects(12 PG, nine PA, and nine healthyvolunteers) underwent endoscopy andmultiple biopsies (n= 12) and measurementof pepsinogen 1 in fasting serum by radio-immune assay. In 25 subjects 24 hourintragastric pH profiles were performed.Epithelial dysplasia was graded into mildand moderate forms (severe dysplasia wasnot seen) and scores were awarded forthese lesions. Serum pepsinogen 1 wasnegatively correlated with mean pH(r=-0-58; p<0005), and the incidenceand severity of epithelial dysplasia wasincreased in subjects (n= 15) with a serumpepsinogen 1 <20 ngm/ml (p=0-005).There were 5/15 cases of moderatedysplasia in the <20 ngm/ml group com-pared with 1/15 in the >20 ngm/ml group(p<0.025). These data show for the firsttime a close association between low serumpepsinogen 1 and epithelial dysplasia andsuggest that this non-invasive test may be auseful aid to the selection of high riskindividuals in whom endoscopicmonitoring for gastric cancer may prove ofvalue.

F55Gastroduodenal mucosal inflammation inpatients with non-ulcer dyspepsia - a con-trolled endoscopic and morphometric study

A U TOUKAN, M E KAMAL, S S AMR, M A

ARNAOUT, A S ABU-ROMIYEH (INTRODUCED BYT W WARNES) (Gastroenterology Unit,Jordan University Hospital, and Depart-ment of Pathology, Faculty of Medicine,Jordan University, Amman, Jordan)Proper control and quantification areimportant in the accurate evaluation ofgastroduodenal inflammation in dyspepticpatients without ulcers or erosions asproved by endoscopy. Thirty one patientspresenting to the GI clinic with non-ulcerdyspepsia (NUD) underwent endoscopy.An age matched group of 32 healthyvolunteers were also endoscoped. In bothgroups the body and antrum of the stomachand the duodenal cap were examined andbiopsied. The specimens were oriented ona cucumber slice and processed. Differ-ential cell counts of the mucosal inflam-matory cellular infiltrate were carried outwith a calibrated eyepiece micrometer.

Endoscopic erythematous changes andmucosal mamillations were noted in asimilar frequency and distribution in theNUD patients and the control group.Differential mucosal inflammatory cellcount showed a statistically significant(p=0-001) increase in the neutrophil countin the gastric body, antrum, and duodenalcap of the NUD patients as compared withthe control group, as well as a slight butsignificant (p= 005) increase in the roundcell and eosinophil counts of the duodenalmucosa alone. No correlation was foundbetween the endoscopic changes and anincrease in neutrophil count above anormal level determined by the mean ± 2SD of the controls. An endoscopicallynormal mucosa, however, was more likelyto be associated with a normal neutrophilcount.

In conclusion, dyspeptic patients withoutulcers or erosions have an increasedneutrophil infiltration in the gastro-duodenal mucosa, and this is not related toendoscopic changes, which are similar inoccurrence to healthy controls. Activeinflammation of the gastroduodenalmucosa likely accounts for the symptoms inpatients with NUD.

F56Histochemical demonstration of vagalinnervation of whole stomach

A P JAYARAJ, F I TOVEY, AND C G CLARK

(Department of Surgery, Faculty of ClinicalSciences, University College London, TheRayne Institute, University Street, London)Recurrent peptic ulceration has been

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claimed to be due to incomplete vagotomyor reinnervation of the stomach aftervagotomy. Although there are numerousinvestigations regarding the distribution ofvagus and its branches, there are no reportsto show the interlinking neuronal plexusesof the whole stomach.Ten Wistar rats (220 g) were killed and

stomach removed and washed well inTyrodes. The pylorus was ligated and thestomach inflated with 22 ml of air and theoesophagus ligated. The stomach wasfloated in the multiples of incubatingmedium containing 5 mg of nitro bluetetrazolium in 15 ml of 0 1 M sodiumsuccinate at 37°C for one hour and fixedovernight in 10% formalin. IThe stainingwas localised to the nerve fibres because oftheir succinic dehydrogenase activity.After cutting the stomach along the greatercurvature, the whole stomach was photo-graphed illuminating the surface with fibre-optic light. Microphotographs showedvagal nerve trunks with network ofnumerous plexuses. The area of the plexusin the lesser curvature was significantlyreduced at 0-87±0-75 mm2 compared witharea in greater curvature at 7-89±1 72 mm2(p<o.OO1).The new method visualises the inner-

vation of the whole stomach and is thussuitable for studying the effects ofvagotomy. It will be possible to follow theregenerative processes of nerves from thecut ends or collateral sproutings from thenerve trunks.

F57Acid and gastrin responses during intra-gastric titration in normal subjects andduodenal ulcer patients with G-cell hyper-function

R G COOPER, G J DOCKRAY, J CALAM, AND R JWALKER (MRC Secretory Control Group,Physiological Laboratory and Departmentof Medicine, University of Liverpool, andGastrointestinal Unit, Walton Hospital,Liverpool) The existence of a subpopula-tion of duodenal ulcer patients with raisedacid output and exaggerated plasma gastrinresponses to feeding has been previouslyrecognised. The term G-cell hyperfunctionoffers a convenient operational definitionfor this group. Acid normally inhibitsgastrin release and a failure of thismechanism would obviously account forthe hypergastrinaemia in G-cell hyper-function. This possibility was examined bycomparing amino acid induced acid andgastrin responses during intragastric

titration at pH 2 5 and 5 5 in normalsubjects and duodenal ulcer patients withG-cell hyperfunction. The latter wereidentified on the basis of raised basal andmaximal acid outputs and increased gastrinresponses to feeding. In normal subjectsthe mixed amino acid meal stimulated onlymodest increases in serum gastrin, and thehighest observed increase was about 30%that after a standard meal. In contrast, inthe G-cell hyperfunction group the highestgastrin concentrations were similar to thoseafter a standard meal. In the G-cell hyper-function group the increment in plasmagastrin at pH 2 5 expressed as a proportionof that at pH 5 5 was 0-29 indicating thatthe capacity of acid to inhibit gastrinrelease was well established in thesepatients. Acid secretory rates were close tomaximal at both pH 2 5 and 5 5 duringintragastric titration in the ulcer patients,but in normal subjects acid output wasabout 50% maximal at 2 5 and close tomaximal at 5 5. The results suggest that theenhanced gastrin response to feeding inG-cell hyperfunction patients is due toincreased sensitivity to amino acid stimula-tion rather than to diminished acidinhibitory mechanisms.

F58Dietary fibre intakes in health andfunctional bowel disease

M A IBBOTSON, J D O'BRIEN, W R BURNHAM,C A VALLANCE, J W DICKERSON, J E LENNARD-JONES, AND D G THOMPSON (Departments ofGastroenterology and Nutrition, OldchurchHospital, Romford; The London Hospital,London; The University of Surrey, Guild-ford, Surrey) The average British diet issaid to contain about 20 g of dietary fibre(DF) and a gradual increase has beenrecommended.

Patients with functional bowel disease(FBD) may eat less DF, but the evidencefor this is based upon retrospective assess-ment and may be inaccurate. We haveassessed prospectively (using a seven daydietary diary) the DF intakes of 40 con-secutive new patients with FBD diagnosedat a gastroenterology clinic and 40 age/sexmatched controls. Dietary fibre wascalculated using standard tables.

Dietary fibre intakes of controls (mean16.6+5.4 g/day) were lower than thosefound among the only other UK popula-tion previously reported. Dietary fibreintakes among the patients were signifi-cantly lower than the controls (12.4±4.2 g;p<0-01, Student's paired t test) and this

was mainly because of a lower intake of DFderived from fruit (0.8± 11 g/d vs 1 6±1 3g/d; p<0004) and vegetables (5 3+2.5 g/dvs 7(0±5+0 g/d; p<0)02).We conclude that the normal dietary

habits of populations must be establishedbefore appropriate changes are recom-mended. It remains to be seen whether thelow DF intake in FBD patients is a cause oreffect of the disease.

F59Motility of intestinal mononuclear cells ininflammatory bowel disease

P R GIBSON, A HERMANOWICZ, F PALLONE,AND D P JEWELL (Gastroenterology Unit,Radcliffe Infirmary, Oxford) The motilityof enzymatically isolated intestinal mono-nuclear cells (MNC) from patients withulcerative colitis and Crohn's disease wascompared with that of autologous andnormal peripheral blood MNC, andintestinal MNC from patients with miscel-laneous intestinal diseases. Chemotacticand random migration were assessed in amodified Boyden chamber by measuringthe distance of migration through Milliporefilters (8 ,u) of the leading front of cells.Zymosan activated plasma was used aschemoattractant. In both Crohn's diseaseand ulcerative colitis, the randommigration of peripheral blood MNC wasgreater than that from healthy controls.Intestinal MNC exhibited chemotactic andrandom migration similar to that ofautologous peripheral blood MNC exceptin Crohn's disease where the chemotaxis ofcolonic MNC was significantly reduced(111=15 ,u, n=13) compared withautologous (125±17, n=22) and normalperipheral blood MNC (127±9, n=35).Ileal MNC also tended to migrate moreslowly. Disease activity and drug therapydid not influence MNC motility. Patientswith Crohn's disease in whom granulomatawere not present, however, had signifi-cantly depressed chemotaxis (105+20 ,u,n=16) when compared with that of MNCfrom granulomatous mucosa (133±16 A,n=9) and from normal peripheral blood.

It is concluded that, in inflammatorybowel disease, motility of intestinal MNCis generally similar to that of autologousperipheral blood MNC except in the sub-group of patients with Crohn's disease inwhom granulomata are not present. Thiscould suggest that the formation ofgranulomata in Crohn's disease may relateto the ability of macrophages toaccumulate at the site of inflammation.

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F60Histochemical studies of colonic mucus inulcerative colitis and Crohn's disease

J M RHODES, R R BLACK, R GALLIMORE, AND A

SAVAGE (Departments of Medicine, QueenElizabeth and Selly Oak Hospitals, andDepartment of Histopathology, Selly OakHospital, Birmingham) Human faecescontain sialidases and sulphatases capableof degrading colonic mucus (Rhodes et al,Gut 1983; 24: A1009). We have tested thehypothesis that ulcerative colitis and/orCrohn's disease may result from increasedsusceptibility of colonic mucus to desiala-tion or desulphation.

Rectal biopsies were taken from 21patients with inactive or mildly activeulcerative colitis (UC), 18 patients withileocolonic Crohn's disease (CD) and 17controls (patients with irritable bowelsyndrome; IBS). One section from eachbiopsy was incubated for 12 hours at 37°Cin a faecal filtrate prepared byhomogenising eight normal faecal samplesin 0-2M Tris-acetate buffer (pH 6.0) at a

concentration of 0-013 g/ml followed bycentrifugation and filtration of the super-natant through a 0 22 ,um filter. Anadjacent section from each biopsy was

incubated in Tris-acetate buffer (pH 6-0)for 12 hours at 37'C. Sections were thenstained with HID/Alcian blue (sialomucinsblue, sulphomucins black) and gradedblindly for staining intensity on a scale 0-5.

Crohn's disease rectal mucins provedconsiderably more resistant to desialationthan ulcerative colitis or controls: CD 11/18(61%) unchanged, mean change in grade-1 00±1 41 SD; UC 5/21 (24%)unchanged, mean change in grade-2 18±1 07 SD, p<0-02 by ANOVAR byranks. Similar resistance to desulphationwas shown by CD (94% unchanged), UC(75% unchanged), and IBS controlbiopsies (88% unchanged).

This increased resistance to desialationof mucus in Crohn's disease is unexpectedand deserves further study.

F61Persistence and location of adhesive andnon-adhesive E coli in ulcerative colitis

I F PINDER, E M COOKE, AND A T R AXON

(Gastroenterology Unit, The GeneralInfirmary, Leeds, and Department ofMicrobiology, The General Infirmary,Leeds) Patients with ulcerative colitishave a higher carriage rate of adhesive Ecoli than normal subjects, but the clinical

significance of these potential pathogens is

unknown. The possession of adhesiveproperties implies that these bacteria mightpersist in the host for longer periods thannon-adhesive strains and/or might be foundselectively in specific anatomical or patho-logical areas of the colon.

Thirty colitis patients were studied forpersistence of E coli in the stool. Thirteenof 15 patients carrying adhesive E coli intheir stool had the same serotype ninemonths to three years later compared withonly four of 15 with non-adhesive E colioriginally present (p<001).

Thirty colitis patients were studied forlocation of E coli in the colon. Pairedbiopsies taken with sterile biopsy forcepsthrough sealed channels of a twin channelcolonoscope were taken from inflamed andnon-inflamed colonic mucosae. Thebiopsies were thoroughly washed in sterilenormal saline, homogenised, and plated on

to culture medium. E coli isolated was

serotyped. In each case, and in 20 normalcontrols, the same E coli serotype found inthe stool was grown from the mucosa as

well.The serotype does not appear to deter-

mine the colonic location of E coli inulcerative colitis but the possession ofadhesive properties does seem to be a

major factor in the persistence of E coli inthis condition.

F62Regional differences in the electro-physiology of normal human colon

G I SANDLE, N K WILLS, W ALLES, J P

HAYSLETir, AND H J BINDER (Departments ofInternal Medicine and Physiology, YaleUniversity, New Haven, Connecticut, USA)Although proximal and distal portions ofmammalian colon have different ion trans-port characteristics which may beimportant for Na and K homeostasis, it isunclear whether regional differences incolonic ion transport exist in man. Thus,proximal and distal colon from patientsundergoing resection for diverticulardisease or cancer was studied in Ussingchambers which permitted cell impale-ments with conventional microelectrodes.

In distal colon (n=13), transepithelialvoltage (V-l-), total resistance (R1), baso-lateral membrane voltage (Vtl), apicalmembrane voltage (VA), and the resistanceratio (a=-ratio of apical and basolateralmembrane resistances) were -14±2 mV,138± 10 ohm/cm2, -39±3 mV, 24±3 mV,and 1-5±0 7 respectively under control

conditions, and changed to 1±2 mV(p<0.001), 164±14 ohm/cm2 (p<0.005),-33±2 mV (p<0 1). 34±3 mV (p<0.02),and 34±14 (p<O 1) respectively when theNa channel blocker amiloride (0-1 mM)was added to the mucosal solution. Inproximal colon (n=4), similar values wereobtained under control conditions, butamiloride only changed V-1- from -10±3 to-7±3 mV (p<0 02), and R1 from 124±5to 139±3 ohm/cm2 (p<0 1), while Vbl, VA,and ox were not affected. Junctional andbasolateral membrane conductances weresimilar in distal (n=8) and proximal (n=2)colon. Apical membrane conductance(GA) in distal colon (6.7± 1.1 mS/cm2) was

greater than in proximal colon (3-4 inS/cm2, mean of 2), and decreased to 30±07mS/cm2 (p<0 005) post-amiloride. Thus, incontrast with proximal colon, distal colonexhibits marked electrogenic Na transport(=Vl-1) which is inhibited completely byamiloride, and which may be influenced byendogenous aldosterone levels. GA issimilar in distal (post-amiloride) andproximal colon, and may represent anamiloride insensitive apical membrane Kconductance.

F63Controlled comparison of the faecal occultblood tests Haemoccult and Fecatwin FecaEIA in population screening for colorectalcancer

N C ARMITAGE, S S AMAR, T W BALFOUR, AND

J D HARDCASTLE (Departments of Surgeryand Radiology, University Hospital,Nottingham) An asymptomatic popula-tion may be screened effectively for colo-rectal cancer using chemical occult bloodtests. To improve the sensitivity and speci-ficity a recently introduced test, Feca EIA,has combined an immunological test forhuman haemoglobin with a simple guaiactest.Three thousand two hundred and twenty

five subjects aged over 45 years wereidentified from general practitioners' age/sex registers and sent by post anexplanatory letter, Haemoccult and FecaEIA tests sufficient for three days; 1,306(40-5%) returned the tests completed, ofwhich 21 were positive for both tests, 19were Haemoccult positive only, and 88were Feca EIA positive only.

All persons with a positive test resultwere investigated by physical exminationand flexible sigmoidoscopy; doublecontrast barium enemas are beingperformed on all. In the group positive for

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both tests, three cancers (all Dukes' StageA) have been identified and sevenadenomas greater than 1 cm.

In the Haemoccult positive group, 10adenomas greater than 1 cm have beenfound. In the Feca EIA positive group, onecancer (Stage C) and seven adenomasgreater than 1 cm were found. Sixty fivesubjects, however, were investigated andno neoplastic disease found.A total of four cancers, 3 1/1000 subjects

tested, and 24 adenomas greater than 1 cm,18-4/1000, were identified. Of these, FecaEIA increased the yield over Haemoccultby one cancer and seven adenomas.Because of the number of patients investi-gated in whom no neoplastic cause forbleeding was found, however, the test in itspresent form would seem unsuitable forpopulation screening.

F64Lactate dehydrogenase (LDH) isoenzymesand sialomucins in colorectal cancer

D S QUILL, R K S PHILLIPS, J E J BIGLIN, ANDH A F DUDLEY (Academic Surgical Unit, StMary's Hospital Medical School, London)Both the LDH isoenzyme muscle-/heart(M/H) subunit ratio and sialomucinsecretion are reported to undergo diffusechange in the cancer bearing colon. Thismay have diagnostic potential.We have quantitatively studied the LDH

M/H ratio and sialomucin concentrations inthe colon of 20 female Wag rats treatedwith dimethylhydrazine (DMH) (DMH 25mg/kg/week for 20 weeks). Twelve animalsdeveloped colon cancer. Ten untreatedanimals were used as controls. All animalswere killed at 25 weeks. The LDH M/Hratio was calculated following celluloseacetate electrophoresis. Sialomucins wereassayed colorometrically using theperiodate resorcinol technique.Our results (mean±SEM) show that

sialomucin concentrations (control:0-96±0 06 ,ug/mg) were only raised intumour tissue (1 46+0 23 atg/mg) (p<0.05,Mann-Whitney U). The LDH M/H ratio,however, was significantly raised (controls:2,02±0,04) in tumour (3 08±0-22), colonremote from tumour (2.40±0.05), as wellas in the colon of non-tumour bearinganimals (2 53±0 05) (p<0(05, Mann-Whitney U).

Similar studies in eight patients withcolorectal cancer showed a significant riseof the LDH M/H ratio in histologicallynormal mucosa between 20 cm proximaland 10 cm distal to tumour in comparison

with rectal biopsies from nine controlpatients with haemorrhoids or fissure(p<0.05, Mann-Whitney U).These results suggest diagnostic

potential for the LDH M/H ratio in coloncancer and document extensive fieldchange in the tumour bearing colon.

F65Cell proliferation in normal appearingmucosa as a marker for colon tumours

o r TERPSTRA, J DEES, AND M VAN BLANKEN-

STEIN (Departments of Surgery andGastroenterologv, University Hospital'Dijkzigt' and Erasmus University, Rotter-dam, The Netherlands) The developmentof colonic adenomas is associated with anincreased risk for colon cancer. Themajority of these adenomas and cancersarise in the distal large bowel. The aim ofthe present study was to investigate the cellproliferation in different parts of the colonin patients with neoplastic disease of thecolon.At colonoscopy biopsies were taken

from normal appearing mucosa in thecaecum, hepatic and splenic flexures,descending colon, midsigmoid, and recto-sigmoid. Autoradiography was performedafter in vitro labelling with 3H-thymidine asdescribed by Deschner (J Natl Cancer Inst1966: 36: 849). The labelling index (LI) anddistribution of labelled cells in the cryptswere determined in 21 patients with smalladenomas (diameter -1 cm) and in 13patients with large adenomas (diameter >1cm) or colon carcinoma. Individualswithout a history of colon neoplasm and anormal colon at colonoscopy served ascontrols (n= 16). At least 25 crypts perpatient were analysed.No differences in LI or labelling distribu-

tion between the proximal and distal coloncould be shown, neither in adenoma orcancer patients, nor in controls. The LI inpatients with large adenomas or cancer was8 4±1 9 (x±SD, p<0001 vs controls,p<0.02 vs small adenoma patients), whilethe LI in patients with small adenomas was6-1±1-5 (p<002 vs control patients inwhom LI was 4.9±0.8). In adenoma orcancer patients 23 3+6 2% of the labelledcells was found in the middle third of thecrypts, compared with 19-4+6 7% in thecontrol group (p<005). indicating anenlargement of the proliferative zone. Infive additional patients at risk for familialpolyposis coli an abnormal LI corres-ponded with the presence of polyps.These preliminary results suggest that

this method is a useful tool for thescreening and follow up of individuals atrisk for the development of colon cancer.

F66Effect of high and low dose warfarin onpreneoplastic changes and tumourincidence in induced colorectal cancer in therat

NICOLA GOETING, G A TROTUER, N KIRKHAM,T COOKE, AND I TAYLOR (University SurgicalUnit, Southampton General Hospital,Southampton) We have previously pre-sented to this society evidence to suggestthat preneoplastic changes occur in the ratcolon with induced carcinogenesis. Micro-adenomas were observed early duringinduction, and increased in size andnumber with time. In the present study, theeffect of low and high dose warfarin onmicro-adenoma formation, tumourincidence, and cell kinetics was assessed.One hundred and sixty eight male Wistar

rats receiving subcutaneous injections ofazoxymethane (12 mg/kg/week) wererandomly allocated to one of three groups:(1) azoxymethane alone, control (n=72);(2) azoxymethane + low dose warfarin,LDW (n=48); and (3) azoxy-methane + high dose ('therapeutic')warfarin, HDW (n=48). Warfarin wasgiven in drinking water for eight weeks andclotting times monitored using thethrombotest technique. Rats were killed atfive, 10, 15, 20, and 25 weeks after initialinjection. Scanning electron microscopyand crypt cell production rate calculationswere performed on segments of colon.The mean number of micro-adenomas

per low power field significantly reduced ateach time interval in both LDW and HDWgroups (at 20 weeks 9 5 in control, 0 76 inLDW, and 1 10 in HDW, p<005). Therewas no difference in size of micro-adenomas, number of crypts per micro-adenoma, or crypt cell kinetics. Thenumber of tumours at 25 weeks was signifi-cantly reduced in both LDW and HDWgroups (control 37, LDW 17, and HDW17, p<005).These results suggest that warfarin, even

at a low dose, reduces initiation of pre-malignant change at a cellular level, ratherthan preventing malignant transformationof adenomas.

F67Bile acid receptors and colorectal cancergrowth in the rat model

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J SUMMERTON, NICOLA GOETING, G TROlTER,AND I TAYLOR (University Surgical Unit,Southampton General Hospital, South-ampton) Previous studies have suggestedthat in human colorectal cancer specificreceptors to deoxycholic acid exist whichmay influence tumour growth. The role ofsuch a mechanism has been further investi-gated using the azoxymethane inducedcolorectal cancer model in the rat. Sixtymale Wistar rats were allocated to one offive groups: (1) azoxymethane alone, (2)azoxymethane and intrarectal saline threetimes weekly (A+IRS), (3) azoxymethaneand intrarectal deoxycholic acid threetimes weekly (A+DCA), (4) intrarectalsaline alone (IRS), and (5) intrarectaldeoxycholic acid alone (DOC).

After 26 weeks statistically significantlymore tumours (11.8±3.3) developed inA+DCA group than in the A+IRS group(5-8±2.4) p<005. More tumours werefound in the distal colon in A+DCA(8.3±3.0) than in A+IRS group (1.8±0.4)p<0*01. Deoxycholic acid receptors weremeasured using a dextran coated charcoaltechnique. More positive receptors wereobserved in tumours in A+DCA group(5/16) compared with A+IRS (1/12tumours).

Accordingly, local instillation of deoxy-cholic acid increases the incidence oftumours in the distal colon. The presenceof receptors to deoxycholic acid in thesetumours suggests that they may beimportant in enhancing tumour growthonce carcinogenesis has been initiated.

F68Failure of gamma glutamyl transpeptidaseand mean corpuscular volume to detectpotentially dangerous levels of alcoholconsumption in self referred 'drink-watchers'

I G BARRISON AND I M MURRAY-LYON (Gastro-enterology Departments, West MiddlesexHospital and Charing Cross Hospital,London) Gamma glutamyl transpeptidase(GGT) and mean corpuscular volume(MCV) are the most commonly used bloodmarkers of alcohol abuse. The value ofthese tests has been established mainly inmedical and psychiatric patients and inhealth screening programmes. The aim ofour study was to correlate levels of GGTand MCV with alcohol consumption andliver size and also to assess the sensitivity ofthese tests in detecting heavy drinking inself-referred individuals who wished tocontrol excessive drinking through our

'Drinkwatchers' project. Ninety subjects(37 men, 53 women, mean age 40 years),who had consumed more than 80 g alcohol/day for more than two years, were studied;37-8% had raised MCV, and 29 9% hadraised GGT. 28/90 (30-1%) had normalMCV and GGT. 13/26 patients withhepatomegaly had normal MCV and GGT.For the group as a whole, GGT correlatedsignificantly with current alcohol con-sumption (CALC) (r=0-27; p=0-005),liver size (r=0.42; p=0005), and MCV(r=0.22; p=0.018). MCV did not correlatewith CALC or liver size. The sensitivity ofMCV was 50% and GGT 28-8%; thesensitivity of MCV and GGT combinedwas 64*4%. Sixty per cent of women hadraised MCV, but only 18% had raisedGGT. Significantly more men than women(11/17 vs 2/9) with hepatomegaly hadnormal MCV and GGT (X2=6 1, p<0-01).We conclude that MCV and GGT will failto detect 30% of heavy drinkers overalland 50% of heavy drinkers with hepato-megaly. These blood tests are not adequatesubstitutes for detailed history taking andclinical examination.

F69Monocytosis: a feature of alcoholic liverdisease

U MCKEEVER, C O'MAHONEY, E LAWLOR,D G WEIR, AND C FEIGHERY (ImmunologyDepartment, St James' Hospital, Dublin)Altered cellular and humoral immuneresponses are present in patients withalcoholic liver disease (ALD). Thereported abnormalities in T cell suppressorfunction and number may explain thehypergammaglobulinaemia of ALD but donot explain the lymphocyte hypo-responsiveness. It has recently beensuggested that monocyte suppressor cellsplay a role in the peripheral lymphocytehyporesponsiveness of chronic liverdisease. With the exception of early reportson monocytosis, based on morphologicalcriteria, in cirrhosis, the literature con-cerning monocyte numbers in ALD isscarce.

Because of the reported defects in themonocyte function associated withcirrhosis the present study used the mono-clonal antibody MO-2 to precisely identifyand enumerate peripheral bloodmonocytes in 12 patients with acute-on-chronic ALD. These results werecompared with nine age and sex matchedhealthy laboratory volunteers. Peripheralblood T lymphocytes were also counted

using Leu 1, a monoclonal antibody whichis specific for these cells.Both proportions (mean=38±20%) and

absolute numbers (mean=0*87±0*69x 109/l) of MO-2 positive cells were signifi-cantly higher in the severe ALD groupwhen compared with healthy controls(661±1%; 1*5+0.5 x 109/l).

In this study, with the aid of a specificmonoclonal marker of monocytes, asignificant excess of these cells was dis-covered in the peripheral blood of severeactive ALD patients. In addition, asignificant T cell lymphopenia wasobserved. The combination of thesefindings may help explain the lymphocytehyporesponsiveness characteristic of severeALD.

F70Natural killer activity in hepatitis B positivechronic active hepatitis and the in vitroresponse to lymphoblastoid interferon

M G ANDERSON, M BAKHTIAR, A W L FEDDLESTON, I M MURRAY-LYON, AND RWILLIAMS (Liver Unit, King's CollegeHospital, and Gastroenterology Unit,Charing Cross Hospital, London) Theobservations that interferon (IFN) may beof value in the treatment of HBsAgpositive chronic active hepatitis (CAH),that natural killer (NK) activity may bereduced in this disease and that IFNincreases NK activity, had led us to investi-gate NK activity and its modulations byIFN in vitro in a group of patients withHBsAg positive CAH.

Natural killer activity of peripheralblood lymphocytes (PBL) was assessedusing a standard 91Cr release assay and thetumour cell line K562. Effector:target(E:T) ratios of 50:1, 25:1, and 12-5:1 wereused in four and 16 hour incubation. At anE:T ratio of 50: 1, NK activity in 15 healthycontrols after four hours was 55±15 (mean% cytotoxicity ± SD) and after 16 hours68±15. The values were not reduced in 21patients with HBsAg positive CAH (fourhours, 52±12; 16 hours, 68±14) or in fourHBsAg carriers with minimal liver disease(four hours, 65±8; 16 hours, 77±9). Asimilar pattern was seen at E:T ratios of 25and 12-5:1. NK activity was significantlyincreased after in vitro incubation of PBLfor one hour with a-IFN (1000 units/ml) inHBsAg CAH (four hours, 69±9), an effectcomparable to that in normal subjects (fourhours, 72± 11).The results indicate that NK activity in

HBsAg CAH is not impaired. The increase

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in activity after interferon treatment may inpart be responsible for the therapeuticeffect of this agent.

F71Do H2-receptor antagonists affect liverblood flow and why?

S L GRAINGER, C C AINLEY, AND R P HTHOMPSON (Gastrointestinal Laboratory,The Rayne Institute, St Thomas' Hospital,London) Ranitidine is a 'cleaner' H2-receptor antagonist than cimetidine, butstudies suggest both alter liver blood flow(LBF). H2-receptors, however, probablyhave no physiological role in the splanchniccirculation, and the methods of measuringLBF have not always been valid. We havemeasured LBF on these drugs from theplasma disappearance of IV indocyaninegreen (ICG) using an analysis that deter-mines hepatic extraction of ICG withouthepatic vein catheterisation.Twelve patients with normal liver

function and duodenal ulcer or duodenitiswere studied. Six received cimetidine 400mg bd and six ranitidine 150 mg bd. Liverblood flow measured was 0-25 mg/kg ICGafter an overnight fast, two hours afterdrug administration, three weeks afterstarting, and again at least three weeksafter stopping therapy.

Ranitidine had no effect on LBF butcimetidine reduced LBF by a mean 11%(mean change during and after cimetidine1-7 ml/kg/min, SE 0-6, p<0-025).Cimetidine but not ranitidine also reducedintrinsic hepatic clearance of ICG, ameasure of hepatocellular function (meanchange during and after cimetidine 11-7ml/kg/min, SE 5*3, p<005); this cannot bedue to the known inhibition of microsomalenzymes by cimetidine, because ICG is notmetabolised. We suggest: (1) cimetidine, incontrast with enzyme inducers, reducesliver mass by inhibiting liver enzymes; (2)this change is not mediated by H2-receptorblockade since ranitidine was withouteffect; and (3) the fall in blood flow simplyaccompanies reduced hepatic metabolicactivity.

F72Prednisolone pharmacokinetics and auto-immune chronic active hepatitis: effects ofcimetidine and spironolactone

B POWELL-JACKSON, J ENGLISH, AND R SWILLIAMS (Liver Unit, King's CollegeHospital, and Dental Schools, London, and

Department of Biochemistry, University ofSurrey, Guildford, Surrey) The widevariations in prednisolone dosage requiredto maintain sustained remission in patientswith autoimmune chronic active hepatitis(CAH) may be because of interindividualdifferences in prednisolone pharmaco-kinetics and to inhibition or induction ofdrug metabolism by concomitant adminis-tration of cimetidine and/or spironolactonerespectively.Four patients with 'unresolved' CAH

had lower prednisolone clearance(51-25±7-01 ml/min) and greater areaunder the concentration time curve(5526±813 ng/ml/h) than six patients withCAH in remission (96± 13-2 ml/min(p<0-05); and 3073±452 ng/ml/h (p<002)respectively) and six prednisolone treatedpatients without liver disease (76.8±5.2ml/min (p<0-02) and 3556±268 ng/ml/h(p<0-05)). In patients with inactivedisease, these parameters did not correlatewith prednisolone maintenance doses andwere not affected by cimetidine 400 mg bdand spironolactone 50 mg bd adminis-tration for 14 days in a randomised, doubleblind crossover trial. In one of the fourpatients with active disease, clearancedecreased by 23% with cimetidine and wasassociated with a decrease in serum ASTfrom 434 to 187 IU/I. With spironolactone,clearance increased by 41% and was asso-ciated with symptomatic relapse within oneweek and a rise in AST to 368 IU/l.These results indicate that prednisolone

pharmacokinetics are abnormal only inpatients with active disease and that clinic-ally significant interactions may occur withcimetidine and spironolactone. Variationsin the dose of prednisolone required tomaintain remission are not due to differ-ences in prednisolone metabolism.

F73Bile acid kinetics using a new labelled bileacid

R P JAZRAWI, R FERRARIS, AND T C NORTH-FIELD (Departments of Medicine andNuclear Medicine, St George's HospitalMedical School, London) 75Se tauro-chomocholic acid (SeHCAT) has beenadvocated as the ideal test substance formeasuring ileal function. The ileum is thesite of active absorption of taurine con-jugated bile acids, but other bile acids canbe absorbed elsewhere in the gastro-intestinal tract by passive non-ionicdiffusion. In vitro studies suggest thatSeHCAT, unlike conventional bile acids, is

not deconjugated by bacteria, but this hasnot been validly tested in vivo in man.SeHCAT might also provide a non-invasive method of measuring thefractional turnover rate of the bile acidpool. Thus, the aim of our study was tocompare 75SeHCAT with its more con-ventional , labelled analogue 14C-taurocholic acid with respect to fractionalturnover rate and fractional deconjugatedrate. In six healthy volunteers receiving25 ,uCi SeHCAT by mouth, fasting a-camera scans of the gall bladder werecarried out daily for five successive days. Alinear regression was obtained on semi-logpaper (r=0.99, p<0.05 in all cases), whoseslope gave a fractional turnover rate thatvaried from 0.23 to 0 37. In fourvolunteers, these values were comparedwith those for taurocholic acid usingclassical Lindstedt technique. The meanfractional turnover rate by the twotechniques was 0 33 and 0.32 respectively.Fractional deconjugation rates derivedfrom the bile samples for SeHCAT and fortaurocholic acid gave significantly differentslopes in all cases (mean values of 0 03 and0- 12 respectively). We conclude thatnegligible bacterial deconjugation ofSeHCAT occurs in vivo, so that its absorp-tion is specific for the ileum; and o-cameraimaging of the gall bladder provides anon-invasive method of assessing fractionalturnover rate of the bile acid pool in man.

F74Dietary protein supplementation fromvegetable sources in the management ofchronic hepatic encephalopathy

A KESHAVARZIAN, J H MEEK, C SUTTON, V MEMERY, E A HUGHES, AND H J F HODGSON(Royal Postgraduate Medical School,Hammersmith Hospital, London) Clinicaltrials suggest that patients with portalsystemic encephalopathy can toleratelarger intakes of vegetable than animalprotein. In a controlled crossover trial, wehave compared a conventional 40 g proteindiet (30 g animal and 10 g vegetable, dietA) with an 80 g vegetable protein supple-mented diet (30 g animal and 50 gvegetable, diet B) in the treatment of fivepatients with chronic stable portal-systemicencephalopathy, requiring dietary andlactulose therapy. Each diet was given, inrandom order, for five days in hospital.EEG, clinical indices of encephalopathy,and the plasma amino acid profile wasassessed at the end of each treatmentperiod.

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The incr.ase in vegetable protein intakewas associated with minor improvement inEEG and clinical performance in twopatients, and no change in the others.Fasting plasma phenylalanine and tyrosinewere higher on diet B (phenylalanine108-6±9-3 (SEM) umol/l vs 99-6±8-37,p<0 05 (paired t test); tyrosine 153±15-2gmol/l vs 140±14, p<0-05). Plasmabranched chain amino acid levels did notchange, and branched chain:aromaticamino acid ratio (BCCA/AAA) was loweron diet B (p<0.02). Faecal weights werenot significantly altered.These results indicate that patients with

chronic portal systemic encephalopathy aretolerant of protein supplementation fromvegetable sources. A minor improvementin parameters of encephalopathy was seenin some individuals, despite a lowering ofBCAA/AAA which some authors havethought important in the pathogenesis ofencephalopathy.

F75Hepatocyte and Kupffer cell function inliver disease assessed by single photonemission tomography (SPET)

E M ALSTEAD, A I MORRIS, I T GILMORE, J SGRIME, AND M CRITCHLEY (UniversityDepartment of Medicine and Department ofNuclear Medicine, Royal LiverpoolHospital, Liverpool) We have previouslydescribed and validated a technique forquantification of Kupffer cell uptake andliver volume measurement using 'Tcmsulphur colloid by SPET. In an attempt todifferentiate better between the type andseverity of various liver diseases we haveextended the above technique using '23Ibromosulphthalien (BSP) as a specifichepatocyte label. Seventeen patients withdiverse liver disease received 111 MBq (3mCi) 123I BSP intravenously. Tomographyusing an IGE 400T tomographic camerawas performed at 10 minutes after injectionbefore biliary concentration was apparent.Three dimensional reconstruction of theliver was obtained using SPET software,allowing absolute volume determinationand quantification of total BSP uptake. Allpatients also had tomography after 'Tcmsulphur colloid administration. The meanpercentage uptakes (±SD) of 1231 BSP andTcm sulphur colloid respectively were

40-4±8-1 and 19-4±5-2 in patients withdecompensated cirrhosis, 65-7±4-8 and39-3±5 in those with moderate liverdisease, and 75-3±11-6 and 56±7-1 inpatients with minimal hepatic dysfunction.

These results correlate well with clinical,biochemical, and histological findings.The technique offers the prospect of

both structural and functional hepatocyteassessment simultaneously and additionallywill permit the investigation of quantitativedifferences in Kupffer cell and hepatocytefunction in liver disease.

F76Alterations in hepatic adenine nucleotidemetabolism in patients with liverdysfunction

D LAMBERT AND P D WRIGHT (UniversityDepartment of Surgery and FreemanHospital, Newcastle upon Tyne) Thestructural and functional integrity of thecell requires the continual expenditure ofenergy in the form of adenosine tri-phosphate (ATP). Mechanisms controllingthe utilisation and resynthesis of ATP aretherefore of paramount importance.Animal studies have demonstrated thathepatic energy balance is disturbed invarious types of hepatic dysfunction. Thisstudy investigates these changes in patientswith normal and abnormal liver function.Three groups undergoing elective surgeryhave been studied: group 1, controls(n=20); group 2, obstructive jaundice(n=8); group 3, cirrhotics (n=7). A freezeclamp technique was used following liverbiopsy. Adenine nucleotides were deter-mined and hepatic energy chargecalculated from these values. Significantreductions in ATP levels were found inpatients with jaundice (2.9±0-11 mol/g)and cirrhosis (2-69±0.18) compared withcontrols (3-64±0-12). This reduction inATP was accompanied by a significantincrease in adenosine monophosphate anda reduction in the total adenine nucleotidepool. Energy charge was significantly lowerin group 2 and 3 patients and in group 2showed a negative correlation with theserum bilirubin (r=-0.75, p<0.05).These results indicate reduced avail-

ability of ATP to meet metabolic demandsin liver disease and also a relative lack ofthe precursors necessary for its resynthesis,as the total adenine pool is reduced. A shifttowards a less phosphorylated state isshown by the lowered energy chargevalues, indicating loss of normal metaboliccontrol. These findings have importanttherapeutic implications as clinicalmeasures specifically aimed at improvingthe hepatic energy economy should benefitoverall liver function.

F77Evaluation of the use of fluorescein duringinjection of oesophageal varices

K R HINE, D L MORRIS, P J TOGHILL, AND P WDYKES (University Hospital, Queen'sMedical Centre, Nottingham, and GeneralHospital, Birmingham) The managementof patients with oesophageal varices byinjection sclerotherapy is increasing inpopularity because of its simplicity andproven improvement in survival. Theoptimal site for injection is probably intothe varices themselves (intravariceal)rather than into the submucosa (para-variceal). Unless radio-opaque contrast ismixed with the sclerosant and radiographscreening is used, however, it is difficult tobe certain whether a particular injection isintravariceal or submucosal.

Fluorescein fluoresces bright yellowunder ultraviolet light and a standardendoscopic light source was shown toproduce sufficient ultraviolet light to givethis fluorescence. In initial animal studiesusing canine stomach submucosal injectionof fluorescein was visible as brightfluorescence whereas injection into agastric vein produced a different effect withfluorescence following a linear path andpartly flowing away. The samephenomenon was shown in humannecropsy material.

In four patients with oesophageal varicesundergoing a total of 10 courses ofsclerosant injections, the sites of injectionwere positively identified by the use offluorescein (0.5 ml of 10% solution mixedwith 5 ml of sclerosant). Submucosalinjection retained the fluorescence for along period whereas with an intravaricealinjection there was a very rapid loss offluorescence. Free sclerosant in theoesophageal lumen could very easily beidentified.The use of fluorescein mixed with

sclerosant may be of value in identifyingthe site of endoscopic injection ofoesophageal varices.

F78Small bowel: a source of gastrointestinalbleeding

A P HEMINGWAY AND D J ALLISON (RoyalPostgraduate Medical School, Hammer-smith Hospital, London) The purpose ofthis study is to determine the incidence ofsmall bowel lesions causing gastrointestinalbleeding detected at angiography.

Patients with acute and chronic gastro-

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intestinal bleeding in whom the cause hasnot been determined by endoscopy,barium studies, or isotope scans werereferred for selective visceral angiography.Over a six year period 246 angiograms

were performed in 222 patients with gastro-intestinal bleeding. Lesions in the smallbowel were shown on 30 occasions (12%).Active bleeding was shown in 10 cases; theremainder gave histories of chronicanaemia or intermittent blood loss. A widevariety of lesions was shown ranging fromminute vascular malformations to largetumours.We conclude that the small bowel repre-

sents an important although underrecognised source of significant gastro-intestinal haemorrhage. To the best of ourknowledge this is the largest series of suchpatients that has been analysed from asingle referral centre. Our presentation atthis meeting will give some typical casehistories, illustrated by superselectivesubtraction angiograms and histology.

F79Jejunal secretory effect of intraduodenalperfusion of nutrients in man

R PALMA, B MIAZZA, J R LACHANCE, J ACHAYVIALLE, P JONARD, AND R MODIGLIANI(INSERM U54 - Hopital Saint-Lazare,Paris, and INSERM U45 - H6pitalEdouard Herriot, Lyon, France) Theeffect of the presence of food in theintestinal lumen on fluid transport by anintestinal loop isolated from nutrients isdebated and seems species dependent. Theaim of the present work was to investigatethis problem in man. Fluid and ion trans-port by a 30 cm jejunal loop was measuredby the perfusion of a plasma like solutionbelow an occlusive balloon inflated at theangle of Treitz. Meanwhile the duodenumwas infused at the papilla by saline (controlperiod, CP) or one of the following solu-tions (test period, TP): protein hydrolysate(P; 135 g/l), starch hydrolysate (S; 135 g/l),lipids (L; 20% Intralipid: 270 ml/1), mixednutrients (MN; P=25-4 g/l, S=53-6 g/l,20% Intralipid: 112 ml/l). The foursolutions (pH=7, 300 mOsm/l) wereinfused intraduodenally in six normlsubjects (order randomised). Each TP waspreceded and followed by a CP. Bloodsamples were taken for radioimmunoassaysof gastrin, secretin, CCK-PZ, motilin,VIP, GIP, PP, and somatostatin.

Intraduodenal MN reduced jejunal H2Oabsorption (ml/min/30 cm; mean + SEM;-=absorption, +=secretion) from

-1-06±0 27 to -0 42±0 23 (p<005), andstimulated plasma CCK and PP (p<0.02);Intraduodenal L and P reversed H,Ojejunal absorption to a secretion(respectively from -1 02±0 3 to+0 25+0 37, p<0.01, and from-0-64±0+52 to +0 21±0 49, p<0.01) andincreased plasma CCK, PP, and GIP(p<002). Intraduodenal G did not changejejunal H,0 transport and increasedplasma GIP (p<002). Moreover, L and Pstimulated and G decreased motilinaemia(p<0-10). Ion transport variationsfollowed those of H,O.We conclude that (1) an intraduodenal

mixed meal inhibits H,O and ionabsorption by a jejunal loop isolated fromthe nutrients; (2) this is due to the L and Pcontent of the meal; and (3) this effectmight be mediated by CCK and/or motilin.

F80Mucosal recovery and permeability ingluten sensitive enteropathy

I BJARNASON, M N MARSH, A J LEVI, A PRICE,AND T J PETERS (MRC Clinical ResearchCentre, Harrow, Middlesex, and UniversitvDepartment of Medicine, Hope Hospital,Salford, Manchester) The aim of thisstudy was to assess the 5 'Cr-EDTAabsorption test in the detection of alteredintestinal permeability (IP) in patients withcoeliac disease (CD) and dermatitis hepati-formis (DH), correlating such changes withmucosal structure and the effects of glutenwithdrawal.

Thirty four healthy Caucasians served ascontrols: 61 adults with CD (42 treated foran average of five years) and 16 with DH(11 treated by gluten withdrawal for anaverage of three years) were studied. A 100ACi dose of SICr-EDTA was taken orallyand results are expressed as the per cent 24hour urine excretion (mean + SD).Jejunal biopsies were obtained within aweek of study in CD patients and analysedmorphometrically and intraepitheliallymphocytes/100 enterocyte nuclei werecounted.

While controls excreted 1.9±0.5% of thetracer, increased excretion was found inCD, untreated (5.3±2.6%) or treated(4-2+2-4%) and DH, untreated(4-6±4-2%) or treated (3.0±0.6%). Alluntreated CD and DH had increased IP;83% of treated CD and 73% of treated DHpatients had increased IP. No significantdifference was found between the patientgroups. Intestinal permeability correlatedsignificantly with intraepithelial lympho-

cytes (r=0-33, p<0)l) and inversely withmucosal height/crypt depth ratio(r=-0 35, p<0-01) in CD patients.Although 21 treated CD patients hadnormal intraepithelial lymphocytes and 19normal morphometry, only 14 (33%) hadan entirely normal mucosa, 11 of whomhad abnormal IP.We conclude that (1) the 5 lCr-EDTA

absorption test is a sensitive reliablemeasure of IP, (2) intestinal permeability isincreased in all untreated CD/DH patientsand despite gluten withdrawal persists inapproximately 75% of patients, and (3) noCD patient treated for less than four yearshad a normal intestinal mucosa.

F81In vitro determination of ileal Na+dependent taurocholate uptake, valuesfrom colonoscopic ileal biopsies in relationto in vivo bile acid loss

F W M DE ROOIJ, J W 0 VAN DEN BERG, M VANBLANKENSTEIN, F P BOSMAN-JACOBS, AND A CTOUW-BLOMMESTEIJN (Department ofInternal Medicine 11, Erasmus UniversityRotterdam, POB 1738, 3000 DR Rotter-dam, The Netherlands) Increased faecalbile acid loss (FBAL) is found in a varietyof gastrointestinal diseases and may resultfrom ileal dysfunction or motor disturb-ances. We have been able to characteriseileal Na+ dependent taurocholate transport(INBAT) at the brush border membranelevel by preparing brush border membranevesicles (BBMV) from microquantities(15-200 mg) of ileum allowing the use ofendoscopic biopsy specimen, according toan adaptation of the Ca"+ precipitationmethod (Kessler et al). Uptake of 3H-taurocholate (4 ,gM) into the BBMV in thepresence of a 100 mM NaCI gradient isfollowed during one minute by sampling at20, 40, and 60 seconds. Taurocholateuptake was quantified in pmol/20 sec/mgmembrane protein. The assay wasvalidated on rabbit and human jejunumand ileum. Normal values were based ondata from ileal biopsies in 59 patients withendoscopic normal mucosa and no clinicalsigns of ileal disease. In 27 patients faecalbile acid loss (FBAL) was also measured.In seven patients with normal FBAL, anormal INBAT was found. In 20 patientswith increased FBAL, INBAT was normalin 12 patients and decreased in eightpatients.We conclude that this technique can be

applied in analysing the pathophysiology ofincreased FBAL.

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F82Complications of jejunoileal bypass - still atrisk after 12 years

R J MCFARLAND, J-C GAZET, AND T R E

PILKINGTON (St George's Hospital MedicalSchool, London) Effective andpermanent weight loss has been achievedin 175 morbidly obese patients by per-forming a 35 cm jejunoileal bypass duringthe years 1971-1982 with considerablepsychological and social benefit. Sixty percent of patients developed a complication,two thirds of these within two years.Fifteen per cent had simple electrolytedisturbance and a further 5% electrolytedisturbance and liver dysfunction asso-ciated with excessive weight loss. Sevenpatients died, one operative death and fivewithin the first two years. No patient hasdied in hospital since 1976, which weattribute to experience and a policy of earlyreversal for patients with serious metabolicdisturbance.Even up to 10 years after weight has

stabilised, however, patients are at risk ofserious complication which may be new,recurrent or precipitated by intercurrentillness. Twenty eight patients (15.5%) haverequired reversal; half of these more thanfive years after bypass. The commonindications for reversal after this intervalwere metabolic problems (five), urinarycalculi (four), and arthritis (three). Failureto associate the new problem with thebypass may lead to a delay in diagnosis-particularly of late metabolic failure whichbegins with insidious weight loss. Indefiniteoutpatient follow up is mandatory and thissets the limit on the number of patients thatcan be admitted to the programme.

F83Alpha gliadin binds specifically to coeliaclymphocytes

CLIONA O'FARRELLY, C A WHELAN, CO MAHONY, C FEIGHERY, AND D G WEIR

(Departments of Immunology and ClinicalMedicine, Trinity College, and St James'sHospital, Dublin, Ireland) The in vitroreactivity of cells from normal and coeliacsubjects with two wheat protein fractions,alpha gliadin, and crude gliadin wasinvestigated.

Using the leucocyte migration inhibitionfactor assay, crude gliadin was found tohave a non-specific effect on cells fromnormal individuals (12) and from untreated(11) and treated (10) coeliac patients inthat a variety of responses was elicited.

There was, however, no significant differ-ence between the groups tested. Inprevious experiments, alpha gliadin wasshown to significantly inhibit leucocytemigration in cells from coeliac patientswhile having no effect on control cells(p<O.001).To assess the specificity of binding of

crude gliadin to peripheral blood mono-nuclear cells (PBMCs), rosetting experi-ments were carried out using gliadinlabelled ox red blood cells (ORBCs).Gliadin coated ORBCs bound to similarpercentages of PBMCs from normalindividuals (10), untreated (six) andtreated (eight) coeliac patients. Respectivepercentages rosettes were 40± 1.5,4 5±1+0, and 3 5±1 6.

In further experiments, alpha gliadin wasshown to bind specifically to PBMCs ofcoeliac patients but not to control cells.Using a monoclonal antibody to alphagliadin and an indirect immuno-fluorescence technique, there was a five-fold increase in the percentage of PBMCsfrom treated (six) and untreated (five)coeliac patients which bound the purifiedwheat protein when compared with cellsfrom control subjects (eight), p<0001.These findings indicate that there is an

intrinsic difference between the cells ofcoeliac patients and those of normal indi-viduals in that the former bind alphagliadin. The lectin like properties of crudegliadin probably cause it to bind non-specifically to normal and coeliac cells. Thespecific binding of alpha gliadin to cellularplasma membranes in coeliac patients mayrepresent a central event in the patho-genesis of coeliac disease.

F84Immunoglobulin GM allotypes and HLAhaplotypes in coeliac disease

P J CICLITIRA, A DEMAINE, K WALSH, AND R HDOWIING (Gastroenterology Units, Guy'sand St Thomas' Hospitals, and TissueTyping Laboratory, Guy's Hospital,London) Coeliac disease is a hereditarydisease with 10% incidence in first degreerelatives. There are known associationsbetween the condition and the surface cellhistocompatibility antigens HLA-B8, DR3. and DR 7. Non-HLA-B8 patients havebeen reported to have a specific immuno-globulin allotype marker which is locatedon chromosome 14.We have investigated profiles of surface

cell histocompatibility markers andimmunoglobulin allotype markers to look

for possible associations which wouldconfirm evidence for a specific chromo-somal locus for this condition.

Forty two patients with coeliac diseasewere investigated for (1) HLA surface cellmarkers including DR typing, (2) immuno-globulin allotypes. HLA and DR loci weredetermined by standardised antisera in alymphocytotoxicity assay. Immunoglobulinallotyping was undertaken by a haem-agglutination inhibition assay. Immuno-globulin allotype markers included Glm(1, 2, 3), G3m (5, 11, 12).High incidences of the HLA types

included Al (80%), B8 (76%), DR 3(96%), and DR 7 (54%). Only one patienthad neither DR 3 nor DR 7. In contrastwith previous reports, no disturbance ofGm allotype frequencies was found for thelimited number of allotypes investigated.The association of coeliac disease with

HLA DR 3 and 7 is higher than thepreviously reported value. These resultssuggest a specific abnormal chromosomallocus in patients with coeliac disease.

F85Are routine duodenal biopsies useful duringendoscopy of patients with dyspepsia?

H W JONES, C J DURKIN, W GREY, AND A MHOARE (Wycombe General Hospital, HighWycombe, Bucks) No abnormality isfound at endoscopy in a large proportion ofpatients with dyspepsia. Biopsies of thesecond and third part of the duodenumhave been shown to be reliable in diag-nosing coeliec disease. Therefore biopsiesat initial endoscopy could pick up any ofthese patients who had coeliac disease.

This study of duodenal biopsies wastaken over two years from all patientspresenting with dyspepsia in whom nocause for the dyspepsia was found. Inaddition their symptoms were analysed tosee if a subgroup of patients requiringbiopsy could be selected.Over two years there were 2938 endo-

scopies of which 520 were negative endo-scopies in patients with dyspepsia. Four ofthese had villous atrophy and three giardiaon their biopsies. Their symptomsresponded to the appropriate treatment.Six of the seven patients had the followingfactors to suggest small bowel disease.Therefore duodenal biopsies need only beperformed if endoscopy is negative ifpatients have anaemia. weight loss,diarrhoea (however mild), or a familyhistory of coeliac disease in addition todyspepsia.

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F86Secretory dose-response studies in thepancreas made hyperplastic by pancreatico-biliary diversion (PBD) or 90% small bowelresection (SBR) in the rat

N H STACE, S VAJA, A BUTr, G M MURPHY, AND

R H DOWLING (Gastroenterology Unit,Department of Medicine, Guy's HospitalMedical School, London Bridge, London)Although pancreatic hyperplasia can beinduced by several methods, little is knownabout the secretory potential of these largeglands. Therefore, eight weeks aftersurgery, we measured exocrine secretion intwo models of pancreatic adaptation asso-ciated with hypercholecystokininaemia -PBD, achieved by interposing 50 cm ofjejunum between pylorus and ampulla, andSBR - and compared results with tran-sected controls (TC). The volume, protein,and trypsin outputs in pancreatic juicewere measured during a basal hour andover 6x30 minute infusion periods withcontinuous secretin (20 CU/kg/h)+ doubling doses of CCK-OP (0-25-8-0mg/kg/h) in fasting (24 hour), anaes-thetised, bile duct ligated rats (n=8).Both models induced pancreatic growth,

the pancreatic weight (mg/100 g bw)increasing from 351±22 in TC to 441±25(p<002) after SBR and to 587±43(p<0001) after PBD. In keeping with thishyperplasia, mean maximum volume (,ul 30min/kg) increased from 620±61 in TC to1002±77 (p<001) after SBR and to1567± 127 (p<0-001) after PBD. Meanmaximum protein and trypsin outputs (mgand U 30 min/kg) showed a similar patternwith 15 and 1U% increases after SBR (NS)and 41 and 66% increases after PBD(p<005 and 0.01). When expressed per gpancreatic weight, however, protein andtrypsin secretion were comparable in allthree groups although maximum trypsinwas still significantly higher in PBD.We conclude that (1) PBD induces

greater pancreatic growth than 90% SBR;(2) when stimulated maximally, thesehyperplastic glands secrete more pan-creatic juice than TC; (3) after PBD,maximum outputs of protein and trypsinwere markedly increased; after SBR, theincreases were modest and NS; (4) thisfunctional adaptation is due mainly tomore cells, with little or no change insecretion/unit weight pancreas.

F87A new approach to gall stone dissolution

R 0 KING, C J HAWKEY, A H SHORT, AND G D

BELL (Departments of Therapeutics andPhysiologylPharmacology, UniiversityHospital, Nottingham) A possibleexplanation for the lengthy dissolutiontimes observed with bile acid therapy forcholesterol gall stones is an interfacialbarrier between crystalline cholesterol andbile micelles. Benzalkonium chloride, a

cationic amphiphile, has been shown toincrease cholesterol dissolution rates byreducing interfacial resistance. In thepresent study, a rotating disc apparatus was

used to study the effects of drugs on thedissolution rates of compressed cholesterol('artificial gall stones') into sodium cholatesolutions and ox bile.

In 2% sodium cholate-phosphate buffer(pH 7-4) the following results were

obtained (activities given are drug rate/control rate ± SEM, ratios greater than I

indicate enhanced dissolution): 3 mMamitryptyline 6-74±0-70 (n=7), 3 mMdiphenhydramine 6 40±0+43 (n=8), 3 mMdicyclomine 5-91±0-44 (n=7), 3 mMpropantheline 5.01±0 38 (n=7), and 0 3mM loperamide 6 49±0+14 (n=3). Theseactivities were similar to 3 mM benzal-konium chloride (6 33±0 35, n=4).

In ox bile the following results were

obtained: 3 mM amitryptyline 192±0 14(p<0001, n=4), 3 mM propantheline1 67±0 12 (p<0 05, n=4), 3 mM dicyclo-mine 1 45±0 09 (p<001, n=4), and 3 mMdiphenhydramine 1 2±0 01 (p<001,n=4).

Structural features common to thesedrugs are (a) quaternary or tertiarynitrogen group and (b) a lipophilic ringsystem. If these drugs or their structuralanalogues are excreted in bile in sufficientquantities and in an active form, they mayrepresent a new approach to medical gallstone dissolution.

F88Reconstruction of the upper gastrointestinaltract after duodenopancreatectomy

N J LYGIDAKIS AND W H BRUMMELKAMP

(Department of Surgery, Academic MedicalCentre, Amsterdam, The Netherlands)Although a variety of reconstructive tech-niques have been reported after duodeno-pancreatectomy (DP), it seems likely thatnone had affected significantly the shortand long term results of the procedure. Thepresent study reports a new approach ofreconstruction. The proximal end of thedistal jejunum after removal of thespecimen of DP is closed and the jejunum

is again transected 30 cm distal to it. The socreated segment is transferred to the supra-mesocolic space and anastomosed end-to-side with the pancreatic remnant and thecommon bile duct. The distal jejunalsegment is anastomosed end-to-end withthe gastric remnant after hemigastrectomy.Bilateral truncal vagotomy is added and anend-to-side jejunostomy is carried out 60cm distal to the gastrojejunostomybetween the distal end of the proximaljejunal segment and the distal jejunalsegment. Fourteen patients underwent thistype of reconstruction. Two patients died,one because of haemorrhage and thesecond because of myocardial infarction.Two patients developed pancreatic anasto-motic leakage, but none required furthersurgery. Twelve patients were followed upthrough clinical history, weight measure-ments, physical examination, endoscopy,radio-isotope gastric emptying studies,Hida-scan, and gastric secretory studies.We conclude that after DP fashioning of

pancreaticojejunostomy and of hepato-jejunostomy in a separate intestinal seg-ment from the gastrojejunostomy afterhemigastrectomy and bilateral truncalvagotomy (1) makes early oral feedingfeasible, (2) because there is no foodpassage along dangerous anastomotic lines,healing along these lines is less interferedwith and any possible leakage is lessdangerous, (3) the construction reducesdumping, and (4) eliminates reflux gastritisand offers satisfactory quality of life.

F89Serum lipase, a better screening test foracute pancreatitis?

P G MCCULLOCH, S OATES, ROSALIND

CAMPBELL, AND C W IMRIE (Departments ofSurgery and Biochemistry, RoyalInfirmary, Glasgow) Serum lipaseconcentrations rise during acute pancreat-itis (AP). Complicated assay methods withpoor reproducibility have hithertominimised its value as an early diagnostictest, but more modern methods allowreassessment of this.

In a prospective trial involving 20patients with AP and 20 age and sexmatched controls admitted with severeacute abdominal pain of other origins,admission serum lipase was morefrequently diagnostic than admission serumamylase (100% sensitivity vs 40%).Specificity was 100% for both amylase andlipase estimations. There was a trend forhigher lipase values to occur in patients

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with pancreatitis associated with biliarytract disease compared with AP due toalcohol abuse, but this did not achievesignificance (0 l>p>0(05, unpaired t test).The assay used requires similar time and

technical ability to that needed forPhadebas amylase assay. Using modernmethods with improved speed and reli-ability, initial serum lipase appears to bemore sensitive than initial serum amylasein the early diagnosis of acute pancreatitis.

F90Connective matrix changes after acutepancreatitis (AP) in the rat

L USCANGA, R H KENNEDY, R CHOUX, J A

GRIMAUD, AND H SARLES (INSERM U 31,Marseille, and Institut Pasteur, Lyon,France) The changes following intra-pancreatic ductal injection in rats of 0-2 mgof trypsin solution (n= 12) or normal saline(n= 12), were compared with a controlgroup (n= 12). Three animals from eachgroup were killed at one, two, four, andeight days after operation and the tissueexamined by light microscopy. Indirectimmunofluorescence (IF) was used to labelspecific antihuman antibodies to collagentypes I, III, pro-III, and IV, fibronectinand laminin.

Light microscopy in the control groupwas normal apart from slight oedema intwo cases. After injection, acuteoedematous pancreatitis occurred in 12rats, all within four days. Perilobular andintralobular fibrosis was present at fourdays in four animals, but was minimal ateight days.Immunofluorescence in the control

group was normal. Fibronectin IF showeda strong amorphous reaction one day afterinjection in rats with AP. At four days itwas colocated with areas of fibrosis and ateight days the changes had disappeared.Collagen type III and pro-III reactionswere markedly increased at four days,being colocated with fibrosis and the fibro-nectin deposition. At eight days thereaction was again normal. In contrast,alterations in collagen types I, IV, andlaminin IF were minimal.Thus in the rat, AP produces an initial

fibronectin deposition, followed by revers-

ible type III/pro-Ill fibrosis. This may beanalogous to man and would explain thelack of progression to chronic pancreatitis.

F91Bile duct calibre - the value of ultrasonic

and cholangiographic measurement in thepostcholecystectomy patient

H J O'CONNOR, R J BARTLETT7, I HAMILTON, W R

ELLIS, J K WATrERS, D J LINTOlT, AND A T R

AXON (Gastroenterology Unit and Depart-ment of Radiology, General Infirmary,Leeds) The differential diagnosis ofjaundice by ultrasound is based on

measurement of bile duct diameter. In thepostcholecystectomy patient, however,where ductal changes may result fromprevious disease or surgery, it is not knownif assessment of bile duct calibre can beused to diagnose or exclude biliary tractobstruction. We have prospectivelyevaluated the role of ultrasound and therelation between ultrasound and radio-graphic bile duct measurements by per-forming dynamic biliary tract sonographyon 50 symptomatic postcholecystectomypatients two to three hours before endo-scopic retrograde cholangiography (ERC).At both examinations the maximumdiameter of the extrahepatic bile duct andits site were recorded; the diagnosis ofbiliary tract obstruction was based on thecholangiographic findings. The meanmaximum sonographic diameter was 7 9mm (SD =3.3 mm) compared with 13.1 mm(SD=4-5 mm) at cholangiography (t test,p<0-001). The sonographic diameter was

plotted against the corresponding ERCmeasurement and the correlationcoefficient was 0 730. Twenty three of 37patients shown to have duct dilatation atERC (>10 mm) had biliary tractobstruction (predictive value, 62%) com-

pared with 21 of 29 with sonographic (>6mm) dilatation (predictive value, 72%).Eight of 13 patients shown not to havedilated ducts at ERC were not obstructed(predictive value, 62%) compared with 14of 21 with non-dilatation at ultrasound(predictive value, 66%). We conclude thatin the symptomatic postcholecystectomypatient, bile duct calibre assessed by ultra-sound or ERC cannot be used to predictthe presence of biliary tract obstructionand significant discrepancy exists betweencholangiographic and sonographic bile ductmeasurements.

F92Remission of symptoms and shrinkage ofmetastasis with long term treatment withsomatostatin analogue

M E KRAENZLIN, J L C CH'NG, S M WOOD, ANDS R BLOOM (Department of Medicine,Royal Postgraduate Medical School,

London) Somatostatin is a potentinhibitor of peptide release and is potenti-ally useful in the treatment of patients withpeptide secreting tumours. The use ofsomatostatin has been limited, however, byits short half life. A long acting somato-statin analogue, SMS 201 995, has recentlybeen developed for subcutaneous use.

Short term administration of this analoguehas shown an effective suppression ofpeptide secretion from pancreatic endo-crine tumours. We have treated for eightmonths a patient with metastatic VIP-omain whom the conventional measures ofsurgery, chemotherapy, and hepatic arteryembolisation failed to control his severelife threatening diarrhoea. SMS 201 995reduced the VIP secretion from the tumourconsiderably (mean before treatment withSMS, 361±91 pmol/l; mean on SMS,161±68 pmol/l) and has prevented thetorrential diarrhoea ever since. Serial com-

puterised tomographic scanning has alsonow shown a marked reduction in the sizeof hepatic metastasis. Except for milddiscomfort at the time of injection, no

untoward effects of the SMS 201 995 havebeen observed.The long acting somatostatin analogue

SMS 201 995 provides a valuable newalternative treatment for the diarrhoea ofVIP-omas. The absence of growthinhibitors may be as important as the roleof growth factors in cancer formation andthis agent may therefore offer moregeneral tumour therapeutic possibilities.

LIVERF93-98

F93Congestive gastritis - a clinical andpathological entity

T T MCCORMACK, J GOEPEL, J M SIMMS, H

KENNEDY, D R TRIGER, AND A G JOHNSON

(University Departments of Surgery,Medicine and Pathology, RoyalHallamshire Hospital, Sheffield)Although oesophageal varices are the mostcommon cause of haemorrhage in portalhypertension, gastritis is an important,though often unrecognised cause of bloodloss. Over a four year period gastritisoccurred in 61 of 123 patients with portalhypertension. Thirty one patients had mildtransient gastritis and 30 patients hadsevere or persistent gastritis which causedclinically significant bleeding in 26 patients

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and accounted for 24-4% of the bleedsfrom all sources. Gastritis was independentof the type or severity of liver disease orthe rise of wedged hepatic venous pressure.There was no difference in the age, sex, orthe drugs prescribed in patients with orwithout gastritis but the mean follow upperiod and the number of sclerotherapytreatments was significantly greater(p<00005) in those with gastritis. Fullthickness gastric biopsies in 18 patients ( 11necropsy, seven surgical specimens)showed dilated and tortuous submucosalveins. Endoscopic biopsies in 13 of 23patients showed some degree of mucosalvascular ectasia. The clinical andpathological evidence suggests that gastritisis caused by a congested mucosa. Asinjection sclerotherapy improves survivalfrom variceal bleeding, congestive gastritismay become more common. The responseto conventional ('anti-erosive') therapy ispoor and the logical approach to treatmentis a reduction of the gastric portal pressureby medical or surgical means.

F94Portal hypertension in precirrhotic liverdisease

D J VAN LEEUWEN, P J SCHEUER, SHEILA

SHERLOCK, AND R DICK (Departments ofMedicine, Surgerv, Histopathology andRadiology, Royal Free Hospital and Schoolof Medicine, London) This study assessedportal hypertension, as measured by thewedged hepatic venous pressure gradient,in patients with chronic hepatitis before thedevelopment of cirrhosis. Thirty sevenpatients were investigated. Liver biopsieswere diagnosed by light microscopy aschronic active hepatitis (n= 12), chronicactive hepatitis in transition to cirrhosis(n=9), and cirrhosis (n=8). A controlgroup showed minor changes includingmild chronic persistent hepatitis (n=8).Hepatic venous pressure gradients weremeasured with a balloon catheter using thefemoral approach. The mean wedgedhepatic venous pressure gradients and theirstandard deviations were 6+2.6 mm Hg inchronic active hepatitis, 10-3±4 8 mm Hgin chronic hepatitis in transition to cirrhosisand 15 4±7 1 mm Hg in cirrhosis, but only3-4±+14 mm Hg when minor changes werefound, a figure in keeping with theaccepted normal values for the pressuregradient. The differences between thegroups were highly significant (p<0'005).We conclude that (1) relatively minor

alterations of hepatic architecture as seen

in chronic active hepatitis without cirrhosismay be accompanied by a significantdegree of portal hypertension. (2) Thepressure pattern reflects the progression ofdisease. (3) Pressure gradients might be auseful method of monitoring the efficacy ofdrugs intended to prevent the developmentof portal hypertension in chronic hepatitis.

F95Observer variation in the endoscopicassessment of oesophageal and gastricvarices

A THEODOSSI, D WESTABY, D J

SPIEGALHALTER, B R D MACDOUGALL, AND R

WILLIAMS (Liver Unit, King's CollegeHospital, London and MRC BiostaticsUnit, Cambridge) The presence of largeas compared with small varices has beensuggested as a risk factor to predict bleed-ing, and has been used to select patients forprophylactic therapy. To validate thegrading of varices it is important to show aclose agreement between differentobservers with respect to such assessment.To investigate the extent of this agreement,three experienced observers independentlyassessed, at endoscopy, the varices of 28patients with portal hypertension. Afterpassing the endoscope the patients wereexamined by each observer who noted thepresence or absence of oesophageal andgastric varices; the number of cords ofoesophageal varices and the size of thelargest varix (graded small or large) usingthe gastro-oesophageal junction as thereference point. In only one instance werevarices stated to be absent by one observerand present by the other two observers.Exact agreement on the number of varicealcords present occurred in 33 (40%) of the84 comparisons with a difference of two ormore cords between any two observers in12 instances (14%). Using Kappa statisticsthe agreement on the presence or absenceof gastric varices was no better thanexpected by chance alone. With respect tovariceal size, agreement occurred in 74%of comparisons, with a Kappa value of0-37; significantly better than expected bychance. In practical terms, however, theuse of variceal size to select patients fortreatment would lead to disagreementbetween two observers on management inone in four cases.

F96Factors affecting variceal recurrence afterendoscopic sclerotherapy

J D R ROSE AND P M SMITH (Department ofGastroenterology, Llandough Hospital,Penarth, S Glam) Fifty patients, (meanage 54-6 years, range 17-77 years) havebeen followed for 1184 patient months(mean 23-7 months) after endoscopicsclerosis of oesophageal varices; 64% morethan one year, 40% more than two yearsand 12%c more than three years. All eightnon-cirrhotics were Child's grade A and ofthe cirrhotics 21 were grade A, 14 B and 7C at the time of initial treatment. Thirteencirrhotics died, seven of hepatic failure,three of infection, two of gastric bleedingand one of hepatoma. The probability ofsurvival was 0-84 at one year, 0 75 at twoand 0 63 at three years and was worse forprimary biliary cirrhosis (PBC) comparedwith the eight non-cirrhotics (Gehanstatistic=3 94, p<005). The three yearsurvival for' 10 cryptogenic, 19 alcoholicand the 10 patients with PBC was 0 88,0 75 and 0 17 respectively. The survival ofcirrhotics with different Child's grades was,however, similar.Of 11 episodes of haemorrhage in 10

patients, only three were from recurrentvarices, all in grade A patients - a risk of0(0025 variceal bleeds/patient month. In 20patients varices recurred, 85% within thefirst year, unaffected by Child's grade butrecurring more in patients with PBC thanin non-cirrhotics (Gehan statistic=4 11,p<0(05).

Mortality and variceal recurrence aftersclerotherapy are determined by thepatient's diagnosis rather than the initialChild's grade. Bleeding is three times ascommon from sources other than varicesafter successful sclerotherapy, and varicealrecurrence after the first year is rare.

F97Results of oesophageal staple transectionfor acute variceal haemorrhage in a seriesof 53 patients

G HAMILTON AND K E F HOBBS (AcademicDepartment of Surgery, Royal FreeHospital School of Medicine, Pond Street,London) The results of treatment byoesophageal staple transection (OST) ofacute variceal haemorrhage uncontrolledby conservative means were analysed. Ofthe 53 patients treated there were 18postoperative deaths (34%: Child's B -two; Child's C - 16); two patients were lostto follow up. Sixteen patients have notrebled with a mean survival of 21 months(48X5%). Using Life Table Analysis,survival without rebleeding was 75% at six

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months, 52% at one year, 33% at 18months and 27% at two years. In the 17patients who rebled the mean time beforerebleeding was 8-4 months. Of the patientswho rebled there were none in Child's Cgroup (Child's A - five; Child's B - 12), butof those who did not rebled, seven were inChild's C group (Child's A - six; Child's B- three).

Oesophageal staple transection is aprocedure which will stop acute varicealhaemorrhage irrespective of the severity ofliver disease, with a reduction in therebleeding rate at one year. Injectionsclerotherapy (IS) for acute bleeding istechnically difficult, requiring multipleprocedures in the majority of patients, hasa similar mortality and carries acomplication rate of up to 55%. Theseresults suggest that OST comparesfavourably with IS in management ofvariceal haemorrhage and requires furtherevaluation by prospective randomised trial.

F98Effect of sclerosants used in oesophagealsclerotherapy on vein and muscle

J D R ROSE (Department of Gastro-enterology, Llandough Hospital, SouthGlamorgan) It is inevitable that duringvariceal injection sclerosants will extrava-sate. Their effect on vein and muscle hasbeen examined in 46 rats by perivenousinjections of physiological saline, 3%sodium tetradecyl sulphate (STD), 5%ethanolamine oleate and 5% hydroxypolyethoxy dodecanoic acid made next tothe femoral vein and compared with intra-venous injections of saline and STD. Theneurovascular bundle and adjacent musclewere removed at 30 minutes, two, six, 12and 24 hours, three and seven days, fourand eight weeks and examinedhistologically.

Intravenous saline produced no changebut after perivenous injection there wastransient inflammation from six and 12hours. Intravenous STD producedthrombosis from 30 minutes onwards withan increase in perivascular connectivetissue and conversion of the veins to fibrouscords with haemosiderin-containingmacrophages. There was no musclenecrosis. The changes after extravasationof all three sclerosants were indistinguish-able: immediate oedema of muscle andperivenous tissue with infiltration of poly-morphs at two hours and necrosis of musclemaximal at seven days. Thrombosisoccurred initially but after three days had

disappeared. Overlying connective tissuewas considerably thickened. Fibroblastconversion of necrotic muscle was begunby seven days and complete by four weeks.

Extravasated sclerosants increase con-nective tissue around veins, which they donot thrombose and are extremelydamaging to muscle.

CLINICAL PANCREASF99-106

F99Peptide YY, a new gut hormone, distribu-tion in the human intestine

T E ADRIAN, A J BACARESE-HAMILTON, G-LFERRI, J K POLAK, AND S R BLOOM (Depart-ment of Medicine and Histochemistry,Royal Postgraduate Medical School,London) Peptide YY (PYY) is a newlydiscovered 36 amino acid peptide localisedto endocrine cells of the intestinal tract;low dose infusion of PYY in man causes asubstantial reduction of pentagastrinstimulated, gastric acid and pepsinsecretion.The distribution of PYY in the human

gastrointestinal tract was measured insurgical tissues using a specific radio-immunoassay. PYY was found throughoutthe lower intestine with concentrationsincreasing distally (ileum 68±6 pmol/g,n=4; ascending colon 51±6, n=5; sigmoidcolon 176±34, n=6; rectum 528±69, n=8)PYY was undetectable (<3 pmol/g) in thefundus, antrum, duodenum and jejunum.

Layer separation of bowel showed thatthe PYY immunoreactivity was localised tothe mucosal epithelium. High resolution,isocratic, reverse phase HPLC of humangut, revealed a single, major peak ofPYY-like immunoreactivity which elutedin an identical position to the porcinestandard, suggesting that the humanpeptide may be identical to that alreadyisolated from the pig.Thus the new hormone PYY is present in

very high concentrations in the largebowel. The further investigation of the roleof this peptide may help explain colonicinfluence on digestive function.

F100Effect of truncal vagotomy and pyloroplastyand of highly selective vagotomy alone, ongall bladder emptying dynamics: a prospec-tive study

J N BAXTER, J S GRIME, M CRITCHLEY, AND R

SHIELDS (Departments of Surgery andNuclear Medicine, University of Liverpooland Royal Liverpool Hospital, Liverpool)In a previous report to this society it wasshown that truncal vagotomy and pyloro-plasty (TVP) often results in abnormal gallbladder emptying (GBE) patterns, to mealstimulation. The present study was under-taken to determine if highly selectivevagotomy (HSV) would protect against thedevelopment of these abnormal GBEpatterns.

Using a non-invasive dual-isotope tech-nique to measure simultaneously gastricemptying and GBE, 27 duodenal ulcerpatients were studied prospectively.Subsequently 15 patients underwent a TVPand 12 patients underwent a HSV.

Gall bladder emptying patterns wereevaluated in 13 TVP patients and 10 HSVpatients. Whereas GBE patterns wereconsiderably altered by TVP in 9/13patients, the GBE pattern was not alteredby HSV (p=0002). Onset of GBE was alsosignificantly delayed after TVP (p<0.001),but not after HSV. There was no significantalteration in onset of gastric emptying timeafter either operation. The effect of thesechanges was that the GBE wich occurredbefore the onset of gastric emptying,always seen preoperatively, wasmaintained after HSV but not after TVP.We conclude from this study that (a)

TVP, but not HSV, may result in consider-able disorganisation of preoperative GBEpatterns and (b) TVP, but not HSV, delaysthe onset of GBE.

F101Role of the pylorus and gall bladder inreflux associated gastritis

W A BROUGH, T V TAYLOR, AND H B TORRANCE(Department of Surgical Gastroenterology,Manchester Royal Infirmary, Oxford Road,Manchester) Duodenogastric reflux isincreased after vagotomy with pyloro-plasty, cholecystectomy, and gastricsurgery. Eighty four patients have beenstudied using r'Tc-EHIDA, measuring thebilirubin output of resting gastric juice,frequency and amount of duodenogastricreflux. The patients were divided into sixgroups: Asymptomatic controls (n= 10);vagotomy with pyloroplasty (VP, n=15);vagotomy with pyloroplasty and chole-cystectomy (VPC, n=15); modified highlyselective vagotomy (HSV, n= 15); modifiedHSV and cholecystectomy (HSVC, n=9)and cholecystectomy alone (n=20).

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Symptomatic patients after VP showed asignificant increase in amount of duodeno-gastric reflux (control p<0 002, HSVp<0002). VPC showed a significantincrease in the refluxate in the symptomaticpatients when compared with VP(p<0.002) but not when compared withpatients after cholecystectomy. The HSVgroup, with pyloric preservation showed nosignificant difference in frequency oramount of reflux, but the addition ofcholecystectomy resulted in a highlysignificant increase in both amount(p<O-OOl) and frequency (p<(-001) ofreflux. This study shows that chole-cystectomy alone, and when in combina-tion with either pylorus preserving ordeforming procedures can lead toincreased duodenogastric reflux. Wesuggest that such increased reflux may be acritical factor in the pathogenesis of bilegastritis after surgery.

F102Epigastric impedence: a non-invasivemethod of monitoring gastric volume?

J A SUTTON, SYLVIA THOMPSON, D LEVINE,AND R SOBNACK (Human PharmacologyUnit, Beecham Pharmaceuticals, Harlow,Essex, and The Medical Unit and Radio-isotope Department, The London Hospital,London) Impedance is an established,non-invasive and sensitive method ofmonitoring rates of change in cardiac orlung volumes which logically is applicableequally to the stomach. We measuredimpedance changes in a 100 KHz, 4 mAcurrent passing between two pairs of Ag/AgCl skin electrodes positioned so that thestomach lay between them. Whenvolunteers drank water or orange squash(conductivity 0 2-1-1 inS) large impedanceincreases 1-4 Q occurred during gastricfilling. Then followed a gradual decline,the rates and monoexponential patterns ofwhich suggested that it reflected thedispersal of the meal from the stomach.This decline was compared simul-

taneously with a dye-dilution method infive fasting volunteers in a 40-45° semi-recumbent position. Impedance groupmean half-emptying (xt2) of water of 6.7,SD 2 8 min was statistically comparablewith dye-dilution (4-2, SD 3 2 min). For5% glucose solutions both methodsrecorded an equally statistically significantslowing (Rt2 was 12-1, SD 7.7 min and 12 0,SD 10.9 min respectively). In a radio-isotope imaging comparison 150 ,uCi 99mTcDTPA was mixed in 600 ml dilute orange

cordial. The six male volunteers lay flat,drinking the meal through a wide-boretube. xt2 ws 30 4, SD 14 3 min and 35 2,SD 17 7 min for impedance and 99mTcrespectively (uncorrected for tissueattenuation). Within-subject correlationswere good. In eight normal volunteersmetoclopramide 10 mg iv produced xt2 of7 5, SD 6 9 min in a within-subject cross-over comparison with placebo (13 5, SD12 8 min: p<004 Student's t test).The non-invasiveness of epigastric

impedance permits serial assessments ofdrug effects or surgery. Equipment isrelatively inexpensive and produces a fullemptying pattern in real-time, idealattributes for a practical outpatientscreening method.

F103Prospective testing of a scoring system topredict the individual risk of seriouspathology in patients undergoing GIendoscopy

G HOLDSTOCK, C PATEL, AND M HARMAN

(Southampton General Hospital,Southampton) A recently describedscoring system to assess the individual riskof finding serious pathology in patientsundergoing endoscopy has beenprospectively tested in two hospitals withdiffering endoscopic practice. A total of749 patients were studied. The six featureswhich are involved are age, sex, smokinghabits, and a history of vomiting, priorpeptic ulcer or hiatus hernia. Patientsreferred to an open access system werefound to have significantly lower scoresthan those referred to a hospital-based one(p<0.006), mirroring the incidence ofserious pathology in the two units (24% vs34% p<0007). The incidence of seriouspathology varied from 1.5% in thosepatients scoring less than 350 points to 70%in those scoring more than 650 points. Byutilising the system and limiting examina-tion to those patients with a score of morethan 400, 23% fewer endoscopies would beperformed and only 2.5% with majorpathology missed. Restriction to a score ofmore than 450 would result in a 43%reduction examination and 15.6% of majorpathology being missed, but would stillresult in all malignant disease beingdetected. To date, 70 patients with GImalignancy have been studied and allscored more than 464 (mean 584±76),compared with a mean score of 444+99 forpatients in whom no abnormality wasdetected. A simple table is described which

allows for easy calculation of individualscore without the use of a computer. It issuggested that the scoring system can beused as a guide to the value of endoscopy inindividual patients and that it allows forrational development of open accessendoscopy service.

F104Therapeutic peritoneal lavage in patientswith severe acute pancreatitis

A D MAYER, M J MCMAHON, A P CORFIELD, M J

COOPER, R C N WILLIAMSON, A P DIXON, M G

SHEARER, AND C W IMRIE (The GeneralInfirmary, Leeds, The Royal Infirmary,Bristol and The Royal Infirmary, Glasgow)Peritoneal lavage therapy for severe acutepancreatitis was evaluated in a multicentre,prospective, controlled clinical trial.Patients referred to the study from 24hospitals were assessed by an investigatorfrom one of three participating centres andwere entered into the study if they fulfilledlaboratory criteria of severe pancreatitis orif more than 20 ml of ascitic fluid or darkcoloured ascitic or lavage fluid was foundon diagnostic peritoneal lavage. Patientsrandomised to the control group receivedintensive conservative treatment includingmonitoring of arterial oxygen and centralvenous pressure. Patients randomised tothe treatment group received, in addition,continuous peritoneal lavage (2 litres ofdialysis solution hourly) for three days.Seventy nine patients were included in thestudy. There were 12 deaths (29%) and 14major complications (34%) in the 41patients in the control group and 11 deaths(29%) and 11 major complications (29%)in the 38 patients in the treatment group.Eight of the deaths in the control group(67%) occurred within 10 days ofadmission compared with five (46%) in thetreatment group (NS). The probability thata 50% reduction in mortality had beenachieved in the treatment group was 2%.The results indicate that the regime oftherapeutic peritoneal lavage used in thisstudy may delay death from severe acutepancreatitis but does not reduce overallmortality.

F105Symptomatic gall stone disease: before andafter cholecystectomy

T BATES, J C MERCER, AND M HARRISON (TheWilliam Harvey Hospital, Ashford, Kent)In a prospective study of gall stone disease

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115 consecutive patients who were con-sidered to have gall stone relatedsymptoms completed a questionnairebefore cholecystectomy was carried out.One year later they were sent a follow upquestionnaire which was completed by allbut three patients who had died ofunrelated causes.

Previous hospital admission for gallstone disease had occurred in 39 patients(34%) and the majority had had periods oftime off work or being unable to cope athome. All patients had more or less typicalbiliary pain preoperatively althoughjaundice was the presenting symptom in 15patients (13%). Postoperative recoverywas slow in that 62% of patients did notreturn to work or resume normal house-hold activities within six weeks of theiroperation.Twelve months after cholecystectomy 49

patients (43%) still rated their operationless than completely successful. Thecommonest persisting symptoms wereexcessive flatulence (47%), indigestion(46%), abdominal distention (33%), andnausea (23%), although when these hadbeen mentioned specifically before theoperation it had been explained to thepatient that they would probably not berelieved by cholecystectomy. Abdominalpain, however, most often in or deep to thescar, persisted in 27% of patients. Twentytwo (19%) had consulted their generalpractitioner for persisting symptoms andnine had been referred back to hospital.

It is concluded that even when chole-cystectomy is limited to patients withtypical biliary pain or jaundice, nearly halfof them still have some symptoms a yearlater.

F106Operative cholangiography on selectedpatients - a safe alternative to routine use?

I P LINEHAN, A J SPRIGGINS, P B BOULOS, ANDC G CLARK (Department of Surgery,Faculty of Clinical Sciences, UniversityCollege London, The Rayne Institute,University Street, London) Operativecholangiography (OPC) is intended todefine stones in the biliary tree and also toavoid unnecessary common bile ductexploration (CBD) which is known toincrease mortality threefold. Its costeffectiveness, however, is disputed as 85%of routine OPC shows no abnormality. Theformer method of applying clinical criteriain selecting cases for OPC has beendisregarded and had not been carefully

evaluated. We have therefore examinedretrospectively the feasibility of adoptingsuch an approach by correlating definedclinical indications with the findings onOPC to determine whether a more selec-tive OPC can be used.

Preoperative criteria (history of jaundiceor pancreatitis, abnormal liver functiontests, ultrasound or radiological evidenceof CBD stones) and operative criteria(small stones, wide cystic or CBD,palpable stones in CBD) were used todivide patients into those in whom OPCwas mandatory and those in whom it wasnot. Of 129 patients studied, 45 (35%)would not have required OPC, all hadnormal cholangiograms. In 84 (65%) OPCwas indicated because of eitherpreoperative (70%) or operative (30%)criteria but only 22 (26%) proved to haveCBD stones on cholangiography. Therewere no demonstrable differences inclinical criteria in the remaining 62 patientsin this group to explain the discrepancy onthe cholangiographic findings.These results show that by adopting such

a policy, unnecessary OPC can safely beavoided in a third of routine chole-cystectomies. This made the detection rateof CBD stones higher, 26% compared with17% on routine OPC in this series, andavoided unnecessary exploration in themajority to justify its use in these selectedcases.

GAST/DUODENALF107-1 14

F107Trimoprostil vs cimetidine in duodenalulcer

K D BARDHAN, LESLEY WHITTAKER, R F C

HINCHLIFFE, KEVIN CLEUR, AND KALYAN BOSE

(District General Hospital, Rotheram andRoche Products Limited, Welwyn GardenCity, Herts) We have investigated a newantisecretory cytoprotective syntheticprostaglandin E, derivative Ro2l-6937,trimoprostil in duodenal ulcer patients. Ina double blind, double dummy study, 60patients with symptomatic duodenal ulcerproven by endoscopy were randomlyallocated to receive either trimoprostil 750,ug four times daily or cimetidine 200 mgthree times daily and 400 mg at bedtime,the drugs being taken half an hour beforemeals and at bedtime. The patients wereinterviewed again at two and four weeksand re-endoscoped at four weeks.

Thirty patients received trimoprostil and30 patients cimetidine. Patients in bothgroups were well matched for age, sex,duration and severity of symptoms, pastcomplications and smoking habits. At fourweeks, 62% of patients on trimoprostil hadhealed compared with 90% on cimetidine(p=002). At four weeks, daytime andnight time pain was less in patients oncimetidine (p=0-005 and p=0-06respectively). Nineteen patients on trimo-prostil and 12 on cimetidine had untowardevents; five patients on trimoprostil had tobe withdrawn from the study because ofcontinuing ulcer pain, nausea and vomit-ing, and another patient defaulted. Therewere no clinically significant laboratoryabnormalities.

Thirty three patients were followed upwith endoscopy after healing for periods upto one year, 11 after trimoprostil and 22after cimetidine. Seven and 14 patients ineach group respectively had an ulcerrecurrence with symptoms but nonesilently. At this dose trimoprostil was notas effective as cimetidine in healingduodenal ulcer.

F108Gastric antisecretory and cytoprotectiveactivity of MDL 646, a new PGE, analog, inman

G BIANCHI PORRO, M PETRILLO, M LAZZARONI,L M FUCCELI A, AND D SASSELILA (Gastro-intestinal Unit, L Sacco Hospital, LepetitResearch Labs, Milan, Italy) MDL 646 isa 16-methyl-16 methoxy PGE, analogwhich has been shown to inhibit gastricacid secretion and to protect the gastricmucosa against the damaging effects ofindomethacin, alcohol and stress in variousexperimental animals.No change in blood pressure or heart

rate nor any important side effects wereobserved in a preliminary single oral risingdose tolerability study carried out in 18healthy subjects given 1-400 mcg of thecompound.The efficacy of MDL 646 in reducing

pentagastrin stimulated acid secretion wasinvestigated in a randomised single blindplacebo controlled crossover study carriedout in 10 healthy male subjects given singleoral rising doses (32-56 years) in the range500-1000 mcg. The minimal antisecretorydose was found to be 800 mcg, whichcaused a 25% decrease of acid outputwithin 22 h after administration, withmaximal inhibition during the first hour.The results obtained with 1000 mcg suggest

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a dose-dependence of both the entity ofinhibition and the duration of action (about36% and 22 h respectively after 1000 mcg).

In another randomised single blind,placebo controlled crossover study, carriedout in eight male healthy subjects (30-72years), we tested the effect of single oraldoses of 500 mcg of MDL 646 in preventingthe fall in gastric potential difference (PD)induced by intragastric instillation of 60t)mg of aspirin. After pretreatment withplacebo, within 10 min after aspirinadministration, PD decreased by about26% and started recovering only one hourlater. MDL 646 completely prevented thisaspirin induced drop in potentialdifference, which on the contrary wasmaintained above baseline values for thewhole duration of the test (one hour afteraspirin challenge). No side effects norchanges in bowel habits were reported ineither study.We conclude that MDL 646. because of

its antisecretory and cytoprotectiveactivity, is a potential antiulcer agent and iswarrant of further investigation.

F109Is continuous or intermittent cimetidinetherapy better DU longterm?

D FINE, K BALASUBRAMANIAM, AND T CNORTHFIELD (Norman Tanner Gastro-enterology Unit, St James' Hospital,Balham, London) Cimetidinemaintenance treatment reduces duodenalulcer (DU) relapse rate, but is expensiveand entails indefinite continuous drugexposure. Intermittent therapy has beensuggested as an alternative, but nocontrolled comparison has been carriedout. We have randomly allocated 63patients with endoscopically healed DU tocontinuous bedtime treatment withcimetidine or placebo, and followed themfor periods of up to three years (mean 13months). Whenever symptomatic relapseoccurred, defined as a recurrence of thepatient's original DU pain on three succes-sive days, all patients were given a six weekcourse of full dose (1 g daily) cimetidinetreatment. Relapse rate was calculated byan actuarial method that allows fordifferences between subjects in the lengthof follow up. Symptomatic relapse rate(confirmed by endoscopy) was 11% forcontinuous but 45% for intermittenttherapy (p<0.01); it occurred once every180 and 27 patient months respectively.Monthly values for mean number of daysof pain were 0 9 for continuous but 1 6 for

intermittent therapy (p<0.01); for nightsof pain 0 06 and 0 42 respectively(p<0.01); for days of work lost nil and 0-05(NS); and for antacid tablets 1 3 and 5.1(p<0.05). Continuous therapy requiredseven times as many cimetidine tablets asintermittent therapy. We conclude thatcontinuous maintenance therapy withcimetidine causes a reduction in sympto-matic relapse rate by comparison withintermittent therapy that is statisticallysignificant, but clinically unimportantbecause intermittent therapy causes rapidrelief of these symptoms. Symptomaticrelapse is infrequent even on intermittenttherapy, which is therefore considerablycheaper.

FlIt)Comparison of ranitidine 150 mg twicedaily with ranitidine 300 mg as a singleevening dose in the treatment of duodenalulcer

A IRELAND, D G COLIN-JONES, P GEAR, P L

GOt.DING, J K RAMAGE, J G WILLIAMS, R J

LEICESTER, C SMITH, G ROSS, C DEGARA, T

GLEDHILL, AND R HUNT (Queen AlexandraHospital, Portsmouth, Haslar Hospital,Gosport, Southampton General Hospital,Hampshire, and McMaster University,Ontario, Canada) Recent studies haveshown that ranitidine 300 mg given as asingle night time dose inhibited nocturnalgastric acid secretion by 85% comparedwith a 54% reduction with 150 mg twicedaily (Gut 1983, 24; 904). We thereforeundertook a trial to assess the clinicalimportance of this acid secretion data. Onehundred and nine patients (69 men, 40women) aged 18-76 years (mean 45.6years) with endoscopically proven DUwere entered into a prospectiverandomised double blind trial in fourcentres. Fifty nine patients receivedranitidine 150 mg bid. (Two dropped out)and 50 received 300 mg before bedtime(five dropped out). There was aninsignificant preponderance of women inthe single dose group (M:F ratio 27:23compared with 42:17) and there was nosignificant difference in mean age or lengthof previous history between the twogroups. Of the 102 patients who completedthe study, 48 out of 57 (84%) had healedendoscopically after four weeks onranitidine 150 mg bid and 43 out of 45(95%) healed on 300 mg before sleep(O- 1>p<0-05 X2=3-364 with 1 DF). Nountoward effects were recorded in eithergroup.

We conclude that ranitidine 300 mg as asingle night time dose for the healing ofDU is at least as good - and probablybetter- than the conventional 150 mg bid.The trial also highlights the importance ofovernight gastric acidity in DU.

FIllIntragastric bacteria, nitrate, nitrite, andn-nitroso compounds before and aftertreatment with omeprazole

B K SHARMA, I A SANTANA, R P WALT, R E

POUNDER, M PEREIRA, P NOONE, P L R SMITH,AND C L WALTERS (Academic Departmentof Medicine and Department of Micro-biology, Royal Free Hospital, London, andLeatherhead Food Research Association,Surrey) Omeprazole is a potent inhibitorof gastric acid secretion. Omeprazole 30mg/day raises median 24 hour intragastricpH from 1 4 to 5 3 in duodenal ulcerpatients. The object of this study was tomeasure the bacterial flora, and the nitrate,nitrite, and N-nitroso compound con-centrations, of gastric contents before andafter omeprazole treatment.Ten healthy male volunteers were

studied before treatment, and one, four,seven, 10, and 16 days after 14 daily dosesof omeprazole 30 mg taken at 0900 h. Thesubjects ate a standard meal at 1730 h andwere intubated at 2030 h. The pH ofaliquots of gastric juice was measuredhourly from 2100 to 0700 h. The samples ofgastric juice aspirated at 0700 h werecultured for bacterial growth and alsoanalysed for nitrate, nitrite and N-nitrosocompound concentration.After 14 days of treatment with

omeprazole 30 mg/day, mean nocturnalintragastric acidity in these healthyvolunteers was decreased by 76%. Thenumber of bacteria in the gastric juice wasonly raised for 24 hours after the last doseof omeprazole. Similarly, mean intragastricnitrite and N-nitroso compound concentra-tions were raised one day after cessation oftreatment with omeprazole (14-fold andfour-fold, respectively), but three dayslater they were not significantly differentfrom the before treatment values. Intra-gastric nitrate concentration was notaffected by treatment with omeprazole.The results of this study show that during

treatment with omeprazole there is anincrease in the number of bacteria in thestomach, with increases of nitrite andN-nitroso compound concentration. Thechanges, however, disappear within threedays of stopping treatment.

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F1 12Evaluation of the nitrosamine hypothesis ofgastric carcinogenesis in man

C N HALL, A COOK, D DARKIN, N VINEY, JBARNARD, M J HILL, J S KIRKHAM, AND T C

NORTHFIELD (Norman Tanner Gastro-enterology Unit, St James' Hospital,Balham, London, Bacterial MetabolismResearch Laboratory, Porton Down, andSmith Kline Research Limited)Hypochlorhydric conditions such as Polyagastrectomy (PG) and pernicious anaemia(PA) predispose to gastric cancer. Accord-ing to the nitrosamine hypothesis, highintragastric pH leads to overgrowth ofbacteria, which convert nitrate into nitrite,and then nitrite plus dietary amines intocarcinogenic N-nitroso compounds. Wehave studied nine PG eight PA and ninematched control subjects by hourlymeasurement of intragastric pH, bacteria(total and nitrate-reducing), nitrite andN-nitroso compounds (total and stable)over a 24 hour period. Clear differenceswere not apparent between controls andPG or PA, because the control and PGgroups were heterogenous for gastricacidity. Although 8/8 PA subjects werehypoacidic (intragastric pH >4 for >50%of the time), only 5/9 PG subjects and 2/9control subjects were hypoacidic. Whensubjects were rearranged into hypoacidic(n= 15) and acidic (n= 11) groups, bacterialcounts (p<001) and nitrite concentrations(p<0.01) were higher, whereas total andstable N-nitroso compounds tended to belower in the hypoacidic group (NS). Inindividual subjects we found a positiveassociation between pH and both total andnitrate-reducing bacterial counts (r=82,p=OOOl) and between pH and nitriteconcentrations (r=0-61, p<0-001). Bycontrast, a negative association was foundbetween pH and both total (r=0.52,p<O.Ol) and stable (r-0.74, p<0001)N-nitroso compound concentrations. Weconclude that, although hypoaciditypredisposes to bacterial proliferation andnitrite generation, it does not enhancenitrosation. Thus, the nitrosaminehypothesis that bacteria mediatenitrosation at high intragastric pH is notsupported.

F1139Tcm red cell scintigraphy and rebleedingfrom peptic ulcers

W J KINNEAR, M BUXTON-THOMAS, E P

WRAIGHT, AND R J DICKINSON (INTRODUCED

BY G NEALE) (Departments of MedicalGastroenterology and Nuclear Medicine,Addenbrooke's Hospital, Cambridge)Patients who rebleed from peptic ulcersconstitute a 'high risk' group and theirearly identification would be desirable. Wehave evaluated the technique of 'Tcm redcell scintigraphy as a means of identifyingpatients at risk of significant rebleeding.Any patient admitted to hospital with

haematemesis or melaena in whom endo-scopy within 24 hours of admission showeda peptic ulcer was eligible for the study.Following endoscopy the patient's redblood cells were labelled in vivo with 750MBq. 99Tcm and scintigrams were obtainedat least once in the succeeding 24 hours.Twenty seven patients have been studied

to date. Eighteen (67%) had scintigraphicevidence of rebleeding. The rebleeding wasclinically significant in seven patients (infour of whom the scintigraphic evidence ofrebleeding antedated the clinical evidence)and four of them required emergencysurgery. Nine (33%) patients had negativescintigrams and none of these rebledclinically during hospital admission.Of the patients with positive. scans 14

(77%) had either active oozing or clot inthe base of their ulcers at endoscopyincluding five of the seven who rebledclinically. Two of the patients with negativescans (22%) had clot in their ulcers atendoscopy.These results show that rebleeding is

common, occurring in as many as 67% ofpatients admitted with bleeding pepticulcers, although this is often not clinicallymanifest. 'Tcm red cell scintigraphy maybe more reliable than endoscopic stigmataas a means of predicting which patients are

liable to significant rebleeding.

F1 14Somatostatin or surgery for massive uppergastrointestinal haemorrhage?

I MAGNUSSON, T IHRE, C JOHANSSON, USELIGSON, S TORNGREN, AND K UVNAS-MOBERG I (Department of Surgery,Sodersjukhuset, Stockholm and Depart-ment of Pharmacology', KarolinskaInstitutet, Stockholm, Sweden) Arandomised double-blind trial of somato-statin (SST) in the treatment of massiveupper gastrointestinal bleeding from pepticdisorders has been performed in 95consecutive patients during a 28 monthsperiod. All patients were endoscopedwithin eight hours of admission to thehospital, whereupon the source of bleeding

and types of stigmata were assessed. Fortysix patients were given a 72 hour infusionof SST, 250 Ag/h, and 49 received infusionQf placebo. No additional treatment exceptblood was given. The two groups were wellmatched regarding sex, age, and source ofbleeding. On the day after admission, acontrol endoscopy was done.A total of five patients in the SST-group

and 14 in the placebo group were operatedon (X2 p<0.O5). Rebleeding occurred in sixpatients in the SST-group, of which fiveexperienced rebleeding after completion ofthe SST treatment. In the placebo grouprebleeding occurred in five patients, ofwhich four rebled on the day afteradmission. The need of blood transfusionsand the mortality rate did not differbetween the two groups. No toxic sideeffects were found as a result of theinfusion of SST.

In conclusion, SST significantly reducedthe number of emergency operations incases of massive upper gastrointestinalbleeding. The protective effect of SSTagainst bleeding was also indicated by thefinding that rebleeding in the SST-groupoccurred when the infusion of SST was

completed.

BOWEL PROBLEMSF1 15-122

Fl 15Psychiatric assessment of patients withsevere constipation

D M PRESTON, J M PFEFFER, AND J E LENNARD-JONES (St Mark's Hospital, London andThe London Hospital, Whitechapel,London) Women with severe constipa-tion often appear to have a personalitydisorder. We therefore studied a series of20 consecutive patients (Mean age 24-5years) who complained of severeconstipation and who had a normal bariumenemas but slow whole gut transit time. Asa disease control group 20 patients withCrohn's disease matched for age, sex,length of hitory and number of hospitaladmissions were also studied. These groupswere compared with a normal populationof young women using the Crown CrispExperiential Index (CCEI) and theHostility and Direction of HostilityQuestionnaire (HDHQ). They alsocompleted the General Health Question-naire (GHQ) and a Quality of LifeQuestionnaire (QLQ). On the CCEIpatients with constipation showed less

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phobic anxiety (p<0-01) than normals andpatients with Crohn's disease. In contrastthe Crohn's disease patients showed morefree floating anxiety (p<005) and phobicanxiety (p<0-01) than normal subjects andsignificantly more obsessionality than theconstipated patients (p<002). Bothdisease groups had more somatic anxietythan normal subjects. On the HDHQ theCrohn's disease group showed an abnormaldegree of inwardly directed hostilitywhereas the constipated group werenormal (p<0005). There were nosignificant differences between the twogroups on the GHQ or the QLQ.The constipated patients were inter-

viewed by a consultant psychiatrist whofound a very high incidence of a disturbedchildhood, psychosexual problems, andpersonality difficulties. These findingswhich correspond with the impression ofmost clinicians are, however, at variancewith the assessment by questionnaire whichshowed a minimal deviation from normal,in contrast with another group of patientswith a similar degree of disability from agut disorder.

Fl 16

Is bran efficacioussyndrome?

in irritable bowel

M R LUCEY, M L CLARK, J LOWNDES, AND A M

DAWSON (Departments of Gastro-enterology and Medical Electronics, StBartholomew's Hospital, London) Despitewidespread use, it is uncertain whetheraddition of dietary fibre is efficacious inirritable bowel syndrome (IBS). We there-fore conducted a double blind placebocontrolled crossover trial of fibre supple-ments in patients with classical IBS.Patients were asked to add to their normaldiet a daily supplement of either 12 branbiscuits (1=0-87 g fibre) or 12 placebobiscuits (1=0-29 g fibre) each for threemonths. Biscuits were given in randomorder with crossover to the second biscuitsat three months. Assessment of dietaryfibre intake and symptoms were mademonthly and a score for single and totalsymptoms reckoned. Three day stoolcollection were made at three and sixmonths. Twenty eight patients completedthe study. Their age (median 32 years,range 22-78; 19 women, nine men)duration of symptoms (median 60 months,range 2-360) initial total symptom scoreand random allocation of treatment did notdiffer from the 16 patients who withdrew.

Daily stool weight which rose during brantreatment (bran, mean= 148 g; placebo,mean=125 g) was significantly correlatedwith dietary fibre intake (p<0-05). Afterthe initial three months therapy, there wasno significant differences in total symptomscores between the bran and placebotreated groups, but there were significantimprovements in symptom scorescompared with pretreatment in both thebran treated (p<0.01, n=14) and placebotreated (p<005, n= 14) groups. Whencrossover data were combined - that is,n=28 - separate and total symptom scoresafter three months treatment with bran didnot differ from those after treatment withplacebo.We conclude that these data suggest that

there are similar symptomatic improve-ments with both treatments and do notsupport the contention that bran isspecificially efficacious in IBS.

Fl 17Fimbriae of colonisation factor antigen IIpositive enterotoxigenic Escherichia coli:morphology and role in mucosal adherence

S KNUTTON, D R LLOYD, P RISTAINO, AND M MLEVINE (INTRODUCED BY A S MCNEISH)(Institute of Child Health, University ofBirmingham, Edgbaston, Birmingham andCentre for Vaccine Development,University of Maryland, Baltimore, USA)Three different surface antigens designatedcoli surface-associated antigens CS1, CS2and CS3 have been identified in enterotoxi-genic Escherichia coli (ETEC) bearingcolonisation factor antigen II (CFA/II).CS1 and CS2 have been shown to befimbrial in nature but the morphology ofCS3 has not been described. ETEC ofserotype 06:H16, biotype A possessing CS1and CS3 and ETEC of serotype 08:H9possessing only CS3 have been examinedby electron microscopy and for their abilityto adhere to human intestinal mucosa andto isolated human enterocytes. Both onbacteria (06:H16, biotype A and 08:H9strains) and in the pure state CS3 has beenfound to consist of thin (2 nm) flexiblefibrillar fimbriae. In contrast, CS1 exist aswider (6 nm) rigid fimbriae on the surfaceof 06:H16 biotype A strains. Using mono-specific antisera to CS1 and CS3 andimmuno gold labelling CS1 and CS3 werefound to be immunologically as well asmorphologically distinct.

In an enterocyte adhesion assay, 06:H16,biotype A and 08:H9 ETEC strains

possessing CS1 and CS3 were found toadhere to the brush border of isolatedhuman duodenal enterocytes to a muchgreater extent (2-2 and 1-7 bacteria/brushborder respectively) than the same strainsgrown at 18°C which lack CS1 and CS3 (0bacteria/brush border). In the same assayadhesion of a CFA/I producing 078:H11ETEC strain was 2-1 bacteria/brushborder. Immunoelectron microscopy ofhuman enterocytes with adherent bacteriashow that CS1 and CS3 fimbrial antigensboth function to promote brush borderattachment of bacteria and are thus bothprobably important in pathogenesis.

Fl 18Sigmoid hypermotility is not a feature of theirritable bowel syndrome (IBS)

I F TROTMAN AND J J MISIEWICZ (Depart-ment of Gastroenterology, CentralMiddlesex Hospital, London) Colonichypermotility is believed to be the basis ofIBS. In contrast with previous work mano-metric studies in the true sigmoid colonwere done in 20 subjects with IBS ( 11women: nine men; median age 43 years,range 22-73 years) and compared with 13controls (six women: seven men; medianage 49 years, range 25-80). Basal andstandard meal stimulated intraluminalpressures were recorded with four perfusedtubes positioned at colonoscopy 25-55 cmfrom the anus. Records were analysed forper cent activity and median maximalamplitude and a motility index (MI)derived as their product. All the IBSpatients had abdominal pain, 17 bloating,and 10 alternating constipation/diarrhoea.All were symptomatic at the time of studyand medication was stopped 48 hpreviously. Controls underwent colono-scopy for polyp check (five), rectal bleed-ing (five) and inconclusive barium enemas(three). All were asymptomatic. Colono-scopy was normal in both patients andcontrols. The meal equally and effectivelystimulated MI in both groups (p<0-01).Mean log MI was significantly lower in IBSbefore (IBS=3.102±0-46: control=3-46±0-22: p<0.02) and after the meal(IBS=3-38±0-49: control=3-69±0-156:p<0-01). Taking control mean log MI±2SD as the normal range, sigmoid hyper-motility was present in only two of 20 IBSpatients, while in nine the MI was belowthe lower limit of normal. These resultssuggest that colonic hypermotility is not afeature of IBS.

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Fl 19Treatment of irritable bowel syndrome withdomperidone and pinaverium bromide

A MARTIN, R D'INCA, G C STURNIOLO, GGURRIERI, AND R NACCARATO (Cattedra diMalattie dell'Apparato Digerente,Universitd di Padova, Policlinico, Padova,Italy) We tested the therapeutic effect ofthe dopamine receptor antagonistdomperidone (D) and the antispasmodicpinaverium bromide (P) in a randomiseddouble blind crossover trial. Twenty twoconsecutive patients (11 men, 11 women,aged 19-54 years) with irritable bowelsyndrome (IBS) entered the study andwere prescribed bran 30 g/day for the twoweeks preceding and throughout the thera-peutic trial. In the first three weeks, 11randomly selected patients received D (10mg tid) whereas the others received P (50mg tid). After a seven day washoutinterval, the patients switched treatmentfor the second three week period. Patientsgraded the severity of their symptoms onan analogue scale before starting the study,after bran only and at the end of eachtreatment period. A higher score (range0-10) indicates a more severe symptom.Abdominal pain decreased from 3-07±0-50(x±SE) before treatment (B) to 1.12±0*37after D (p<001, Student's t test) and to1 89±0-57 after P. Abdominal distensionimproved from 4-39±0-61 (B) to2*01±0*41 after D (p<0.01) and to2*51±0*57 after P (p<0.05). Flatulencedecreased from 3 95±0*64 (B) to2-41±0-42 after D (p<0.05) and to2-23±0-61 after P. Treatment with branonly did not alter symptoms significantly,while D and P reduced symptoms to 48%(p<O001) and 60% (p<0.05) of the base-line scores respectively. Side effects wererare and generally mild for both drugs. Inconclusion D significantly improvedsymptoms of IBS; P was also found to beeffective, though to a lesser extent.

F120Fat and fibre restriction is not helpful in theshort bowel syndrome

P B MCINTYRE, M FITCHEW, E ROGERS, AND J E

LENNARD-JONES (St Marks Hospital, CityRoad, London) Patients with a shortsmall intestine have been recommended alow fat diet with the aim of reducing thevolume of diarrhoea and calcium andmagnesium losses but this practice hasrecently been challenged. To determine

whether the amount of fat or fibre in a dietwas an important factor in fluid, calorieand mineral balance three whole food dietswere constructed to contain (1) normal fat(68-106 g), high fibre (26-29 g), (2)reduced fat (42-51 g), high fibre (24-29g)and (3) reduced fat (39-46 g), normal fibre(11-15 g) daily while maintaining fluidinput constant, and with an oralsupplement of 12 mmol magnesium daily.Four patients with a residual jejunum of60-150 cm ending in a terminal stoma tookeach of the diets in random order for twodays. Twenty four hour collections weremade of stoma effluent and urine. The wetweights (mean ± SEM) of effluent on diets(1), (2) and (3) were 3093±658 g,3070±607 g, 3330±462 g and dry weights248-6±47-3 g, 224 1±37-4 g and233-4±26-7 g respectively. Calorie absorp-tin by bomb calorimetry as a percentage ofthose available was 42-7±6-8%,44-7±7-2% and 43 9±5-4% respectively,but absolute calorie absorption tended tobe greater on the normal fat diet. Fat lossestended to be higher on the normal fat diet,43-5±6-8 g compared with 21-9±3-2 g and22*8±3-7 g on the reduced fat diets.Magnesium excretion was similar on alldiets, 19-8±2-1, 19±1-5 and 16-2±1-9mmol/day respectively, and all patientsremained in positive balance. Calciumexcretion was more variable betweenpatients but three of the four maintainedpositive calcium balance on all diets. Thisstudy suggests that patients with a shortsmall intestine should be allowed to takefat normally to improve palatability of thediet and to increase total calorie intake.

F121Home parenteral nutrition

R H WHITE AND M H IRVING (Department ofSurgery, Hope Hospital, (University ofManchester School of Medicine), Salford)Between October 1978 and November1983 Hope Hospital home parenteralnutrition (HPN) programme treated 32patients, 17 women and 15 men. The meanage of the patients was 36-09 years andranged from 14-5 to 76-2 years. Theprimary disease was Crohn's disease in 19cases, mesenteric vascular disease in four,and radiation enteritis in one. A furtherseven patients had varied pathologies. Theprimary disorder was complicated by theshort bowel syndrome in 13 instances,enterocutaneous fistula in 13.

Apart from three patients who wereunemployed, all were involved in some

occupation before starting HPN, and onceon the programme two-thirds returned towork, 16 of these full time and six parttime.

Strict protocols are observed forinsertion and care of central feeding lines.Feeding catheters are inserted in theoperating theatre with full surgical aseptictechnique. Under the direction of the staffof the nutrition unit patients rapidlyacquire techniques for connecting anddisconnecting their nutrition, dressing thelines and heparin locking catheters. Usingthese methods only two patients have hadcatheter sepsis and metabolic problemshave been minimal. Sixteen patients havecompleted HPN, the mean duration oftherapy being 124-75 days (range 9-503days). Nine of these have returned to anormal diet, five due to adaptation of shortbowel and four to closure of fistula. Therewere five deaths (15-6%), three unrelatedto their disease or HPN and two related totheir disease alone. Mean duration of HPNfor those still on the programme was 326-63days range 20-1293 days. Home parenteralnutrition is a valuable treatment for bothshort and long term intestinal failure.

F122Body composition in ileostomy patients withand without ileal resection

J C COOPER, A LAUGHLAND, L BURKINSHAW,AND N S WILLIAMS (University Departmentof Surgery, The General Infirmary, Leeds)Recent evidence suggests that modest ilealresection (IR) during protocolectomy (PC)results in malabsorption of fat andnitrogen, in addition to water and electro-lytes. Serious nutritional deficits may thusensue.Body composition (BC) was therefore

studied in nine ileostomy patients (resectedgroup: mean ± SD: age 43± 17 yr; height172±14 cm; M:F 4:5) who had undergonesignificant IR (70±28 cm range 50-120cm), and nine ileostomy patients (controlgroup: age 43±13 yr; height 170±9 cm;M:F 4:5) who had undergone minimal IR(4±3 cm p<0-001). Time since operationwas similar (resected 5-6±4-9 yr, controls7-3±4-5 yr) Values were compared withpredicted values for normal subjects, basedon age, sex and height. All patients (17ulcerative colitis, one Crohn's disease) hadundergone PC and had a normal residualsmall bowel.Body weight and 24 hour ileostomy

volumes were determined. Total body

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nitrogen (TBN) and minerals were

measured using neutron activationanalysis. Total body weight was measuredusing tritiated water, and total body fat(TBF) was calculated using skin foldmeasurements. Twenty four hour ileo-stomy volume in the resected group

(1809±1614 ml) was significantly greaterthan the control group (570± 159 ml

p<0-01). Total body nitrogen in bothresected (1468±471 g) and control groups(1446±471 g) was significantly less thanpredicted (1677±484 g p<0-02; 1627±371g p<0-001 respectively). Body weight(60±9-5 kg) and TBF (12-8±4-4 kg) in theresected group were reduced comparedwith predicted (wt: 69-5±9 kg p<0 01,TBF: 17-5±6-0 kg p<0-02) and controls

(wt: 67*5±15 kg, TBF: 18-5±7-0 kgp<006).Thus the only serious nutritional deficit

shown in ileostomy patients without IR wasa reduction in TBN, which could in part beexplained by resection of the large bowel.Modest IR during PC however, causedsignificant loss of weight which wasprimarily because of loss of body fat.

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