Gut, 1991, 32, A553-A600 A553 British Society of Gastroenterology Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from

The 1991 Spring Meeting ofthe British Society ofGastroenterology was held from 10-12 April at the University ofManchester Institute of Science and Technology under the presidency ofProfessor Sir Robert Shields. Below are printed the 276 abstracts selected by the Programme Committee ofthe Society for oral and poster presentation in the scientific sessions.

tion. Therefore the aim of this study was to pared with sham operated animals (9-6 (0.6)). PORTAL HYPERTENSION AND CHRONIC LIVER investigate the effects of haemorrhage and The PS was negligible in the sham operated DISEASE reperfusion on portal pressure and collateral animals (range 0-10%) and ranged from 11-3- blood flow in cirrhotic rats. 74-3% in PPVL animals. There was a signifi- Rats with dimethylnitrosamine induced cir- cant correlation between PS measured by con- Gastric acid output in portal hypertension: rhosis were bled at a constant rate from a secutive injections of MAA and AM and the effect of gastropathy and treating oesopha- femoral artery. Arterial blood pressure and classic method using non-degradable '7Co varices portal pressure were monitored continuously. microspheres (r=0-91, p<0 001 Pearson's cor- geal Splanchnic and hepatic haemodynamics relation coefficient). F GRANAI, H HOOD, J T WALSH, H L SMART, (microsphere technique) and collateral blood These results suggest that consecutive intra- D R TRIGER (University ofSheffield Department of flow (consecutive intrasplenic injection of splenic injections of MDP and AM correlate Medicine and Pharmacology, Royal Hallamshire ""Tc-methylene diphosphonate (MDP) and well with the classic method using non-bio- Hospital, Sheffield) Conflicting data exist 'Tc-albumin microspheres) were measured degradable microspheres. Furthermore, since regarding acid output in portal hypertension before and after haemorrhage and following the computer adjusts the background radio- (PH) with little information in portal hyperten- reperfusion. activity to zero after each determination, sive gastropathy (PHG). We evaluated acid Haemorrhage resulted in a significant multiple measurements of PS can be made in secretion by pentagastrin stimulation in 63 decrease (p<0 001; Student's paired t test) in both experimental animals and man. patients with PH; 24 subjects without PH or portal pressure (mean (SD) 12-1 (0.31)-64 gastric pathology and of comparable age acted (0 6)mmHg) butcollateral bloodflowremained as controls. unchanged (1-3 (0.2)-11 (0.2) ml/min). After Basal acid output (BAO) was similar in both reperfusion portal pressure was returned to Are Child's grade C patients with bleeding groups (PH 1-6 (0 0-19 2), control 2-8 approximately prehaemorrhage values (11-3 oesophageal varices worth treating? (00-8.3); values median (range) mmol HCI/ (0.6) mmHg) but collateral blood flow was hour). Maximum acid output (MAO) was signi- significantly reduced (0.53 (0.07) ml/min). F J MULLAN, E F A SPENCER, G W JOHNSTON ficantly (p<0.05) lower in PH patients (16-3 The results of this study suggest that (a) the (Royal Victoria Hospital, Grosvenor Road, 0-57 than in controls maintenance of collateral blood flow after Belfast) In the 10 year period January 1980 to (0 0)) (23-4 (3 9-35.8)). http://gut.bmj.com/ In PH, BAO and MAO did not differ between haemorrhage may account for the persistent December 1989, 102 patients with Child's those with (n=44, BAO 1-6 (0 0-19 2), MAO bleeding observed in some patients and (b) that grade C liver disease (Pugh's modification) 17-5 (0 0-57 0)) or without PHG (n= 19, BAO resuscitation does not contribute to early were admitted with acute variceal bleeding to 1-8 (0 1-7 0), MAO 13-1 (1-2-35-6)). There rebleeding. one surgical unit with a policy of early sclero- was no difference in acid output between therapy. There were 56 men and 46 women; patients with untreated oesophageal varices the average age was 55 years (range 28-77). (n=28, BAO 1-3 (0-0-15-1), MAO 16-8 Fifty three suffered from alcoholic cirrhosis. (0 0-57 0)) or those who had received injection Novel method ofdetermining portalsystemic Four patients died before definitive treat- sclerotherapy (n=31, BAO 2-4 (0 0-19 2), shunting using biodegradable Tc albumin ment could be carried out, three from liver on September 24, 2021 by guest. Protected copyright. MAO 19-3 (0 0-48.5)). Both BAO (0.3 microspheres failure and one from uncontrolled bleeding. Of (0 0-0 8)) and MAO (5.4 (0 0-8.2)) were signi- the remaining 98 patients, eight had urgent ficantly (p.0O05) lower in patients who had J YATES, D M NOTT, D BILLINGTON, R SHIELDS, oesophageal transection, with three deaths undergone oesophageal transection/gastric S A JENKINS (University Department ofSurgery, from hepatorenal failure; 90 had sclerotherapy, devascularisation (n=4) compared with those Royal Liverpool Hospital, Liverpool) Portal with 19 hospital deaths, nine from recurrent with untreated or injected varices. hypertension is associated with the develop- bleeding, eight from liver failure often coupled In summary (1) MAO, but not BAO, is lower ment of portosystemic shunting (PS), which with renal failure, and two from respiratory in patients with PH compared with controls; can be measured in animals by intrasplenic complications. Of the 76 who survived to leave (2) unlike injection sclerotherapy, oesophageal administration of non-biodegradable radio- hospital, 55 entered a chronic injection pro- transection/gastric devascularisation pro- labelled microspheres. The number of deter- gramme, 10 had elective oesophageal transec- foundly reduces acid output; (3) altered acid minations ofPS in any one animal, however, is tion, and 11 did not have further intervention secretion plays no part in PHG. limited by the availability of the number of for various reasons. Surviving patients have isotopes with sufficiently different energies to been followed up at a special liver clinic for a facilitate counting of the radioactivity after minimum of one year. removal of the organs. This technique is not Although no patient has yet survived 10 Effects of severe haemorrhage and reper- applicable to man, and hitherto PS has been years, the two, five, and eight year survival fusion on coliateral blood flow and portal estimated indirectly by measuring azygous rates of 39%, 21% and 13% suggest that salvage pressure in the cirrhotic rat blood flow. We describe a method for repeated of these patients is worthwhile. measurements of PS that is also applicable to man. J YATES, D M NOTT, S ELLENBOGEN, D BILLING- TON, R SHIELDS, S A JENKINS (University Depart- Male Wistar rats underwent partial portal ment of Surgery, Royal Liverpool Hospital, vein ligation (PPVL) or sham operation. Three Seroprevalence of anti-core hepatitis C virus Liverpool) Approximately 30% ofpatients with weeks later PS was determined in all animals by antibodies in chronic non-A, non-B liver acute variceal haemorrhage are actively bleed- consecutive intrasplenic administration of a disease ing at the time oftheir diagnostic endoscopy. It small non-diffusible marker 9Tc-methylene is not known, however, why variceal bleeding diphosphonate (MDP) and 9Tc-albumin S DOURAKIS, J BROWN, R GOLDIN, P KARAYANNIS, persists despite massive haemorrhage or microspheres (AM). Immediately after com- H C THOMAS (Liver Unit, St Marv's Hospital, whether rebleeding is resuscita- pletion of these studies all rats received an London) The serological responses to C100--3 precipitated by intrasplenic administration of 17Co micro- and a new 22 kD recombinant protein (P22) spheres, and the PS was calculated from the encoded by the nucleocapsid region of the ratio of these isotopes in the liver and lungs. HCV genome were studied in patients with a The was chronic liver diseases and in The accuracy of the data in these abstracts is the portal pressure significantly greater variety of healthv responsibility of the authors since the abstracts have not (p<0*001 Mann-Whitney U test in PPVL blood donors. The study comprised 97 patients been subject to peer review. animals (mean (SD) 13-4 (0.5) mmHg) com- with non-A, non-B (NANB) hepatitis (60% A554 British Society ofGastroenterology sporadic and 40% parenteral), 87 patients with renal impairment in 73 patients with decom- S Y IFTIKHAR, R J C STEELE, P D JAMES, defined chronic liver disease, and 96 voluntary pensated chronic liver disease and sepsis, J D HARDCASTLE, M ATKINSON (Department of blood donors. randomised to receive treatment with either Surgery, University Hospital, Nottingham) In a Overall in the NANB group, 85-5% were ceftazidine or mezlocillin and netilmicin (38 15 year prospective study of surveillance of positive for anti-P22, 56-7% for anti-C100-3, cef, 35 amino). Renal impairment was defined columnar lined oesophagus (CLO), 102 Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from and 14-4% were negative by both tests. In as an increase in serum urea or creatinine, or patients with a mean (SD) follow up of 54 chronic post-transfusion liver disease, 84-6% both, during or after treatment. Severity of (12-5) years and total follow up of 462 years were positive for anti-C10-3 and 94 9% for liver disease was similar in the two groups: have been evaluated. The minimum acceptable anti-P22 (not significant). In the chronic Pugh's score cef mean (SD) 9-6 (2.5), amino length of CLO was 5 cm and the mean (SD) sporadic patients, 37-9% were positive for anti- 9.3 (2.6). Before treatment renal impairment length of the whole group was 6-9 (2.8) cm. C100-3 and 79-2% for anti-P22 (p<0-001). All was present in 15 of 38 patients in the cefgroup Of 373 sets of biopsy specimens analysed by 98 healthy blood donors were seronegative for (39%) and in 12 of35 in the amino group (34%). one senior pathologist, 59 individual specimens both of the HCV antigens. Renal function declined in five of 38 patients in 21 patients showed dysplasia or intramucosal The results confirmed that the new ELISA receiving cef (13%) compared with eight of 35 carcinoma. According to Riddle's classification test for anti-P22 is a more sensitive indicator of receiving amino (23%:p=NS). In patients with nine were considered indefinite negative, five chronic hepatitis C virus infection than the normal serum urea and creatinine values before indefinite positive, and three had low grade existing commercial test, suggesting a useful treatment, evidence of renal impairment dysplasia. Four subjects, all men, had intra- diagnostic role in both patients with sporadic developed in only one of 23 in the cef group mucosal carcinoma of the oesophagus, indicat- NANB liver disease and for the screening of (4%) and in two of23 in the amino group (8%). ing a 30 times increased risk of developing blood products for prevention of post-trans- In this study aminoglycosides were not carcinoma in CLO. fusion hepatitis. associated with a significant increase in renal Of the four patients with intramucosal car- impairment compared with ceftazidime in cinoma, three were offered surgery while a patients with chronic liver disease. fourth patient was denied this because of concomitant prostatic carcinoma. One subject Hepatitis C in chronic active hepatitis and died as a consequence ofoesophagectomy, two primary biliary cirrhosis in the UK - aetio- Assessment of chronic liver disease by mag- oesophagectomy subjects are alive and disease logical agent or artefact? netic resonance relaxation times free three years after operation, and the fourth patient died six years after diagnosis without B ROWAN, D GLEESON, A SMITH, T W WARNES E M ALSTEAD, S F KEEVIL, G DOLKE, F H MOURAD, any dysphagia. (Liver Unit, University Department of Gastro- A P BROOKS, P ARMSTRONG, M J G FARTHING To date, £47 688 has been spent on the enterology, Manchester Royal Infirmary) Hepa- (Department of Gastroenterology, Whipps Cross project. This gives a cost of £7427 per cancer titis C (HCV) antibody values (anti-HCV, Hospital, London and Departments of Gastro- diagnosed, which compares favourably with Ortho ELISA) were measured in 26 patients enterology andAcademic Radiology, St Barthole- other screening programmes. with chronic active hepatitis (CAH) (22 auto- mew's Hospital, London) A non-invasive immune, four idiopathic), 77 with primary method of assessing liver morphology and biliary cirrhosis (PBC) and 25 control subjects. disease progress is potentially attractive. In contrast to previous reports, anti-HCV Numerical data derived using low field mag- Bile reflux in Barrett's oesophagus was normal in all 26 CAH patients. However, netic resonance (MR) relaxation times may in PBC, anti-HCV was positive in 26% of provide such information, although early S Y IFTIKHAR, D F EVANS, R J C STEELE, patients; further study showed positive results studies using MR to measure T1 relaxation S LEDINGHAM, M ATKINSON, J D HARDCASTLE http://gut.bmj.com/ in only one of 46 patients in whom serum had times in small numbers of patients have been (Department of Surgery, University Hospital, been stored for <18 months but in 19 of 31 in inconclusive. We have compared TI and T2 in Nottingham) In this study, 30 patients with whom serum had been stored for ¢ 18 months. 42 normal individuals (21 women) and 20 histologically diagnosed columnar lined In both CAH and PBC anti-HCV correlated patients with biopsy proved liver disease (12 oesophagus (CLO), 15 age and sex matched positively with serum globulin (CAH p<0 02; women). Using an MD800 MR imager, operat- patients with oesophagitis, 15 healthy volun- PBC p<0-001, two-tailed Pearson's test) and ing in a field strength of 0-08 tesla, TI and T2 teers, and two patients with partial gastrectomy IgG values (CAH p<0-01; PBC p<0-001); in were derived from relaxation maps. T1 was were studied for bile reflux over an 18 hour

addition in CAH anti-HCV correlated with measured using an interleaved saturation period. Oesophageal aspirate from these sub- on September 24, 2021 by guest. Protected copyright. serum AST values (p<0-01). recovery/inversion recovery sequence and T2 jects was collected at two hourly intervals by a Multiple logistic regression analysis in the using a four echo Carr-Purcell-Meiboom-Gill replogal tube placed 5 cm above the mano- PBC group showed independent effects of IgG sequence. The system had previously been metrically demonstrated lower oesophageal and storage time on anti-HCV values. In nine calibrated to ensure accurate and reproducible sphincter and samples of oesophageal aspirate PBC patients in whom serial samples were results. were analysed by high performance liquid available (stored for up to nine years), anti- Results are expressed as mean (SD) relaxa- chromatography (HPLC). HCV rose with increasing storage time, with no tion time (ms) and comparisons made using the Total bile acid concentration in the oesopha- corresponding changes in serum globulin or Mann-Whitney U test. All nine alcoholic cir- geal aspirate in the CLO group (mean (SD) IgG. rhosis patients had increased TI, 287 (30.3), 2342-9 (2837.9) Iimoll1) was significantly In conclusion, we find no evidence for a six of whom also had increased T2, 76 (4.7) higher than that in the control subjects (613-8 significant aetiological role for HCV in auto- compared with controls, (TI, 213 (14-0) and (5552) imol/1) (p=0.05) but was not different immune CAH or PBC in the UK. We suggest T2, 66 (4.6); (p<0-0001)). In normal subjects, from the oesophagitis group (1484-7 (1862-7) that many of the positive results reported there was greater variation in T1 and T2 in ,umol/l). However, a significantly higher elsewhere may reflect raised serum IgG values women than men. In chronic active hepatitis, number of CLO patients than oesophagitis and storage effects. TI, 238 (32.5) and T2, 74 (3-1) were also patients were considered to be bile refluxers increased (p<0.03). Patients with iron over- when 95th centile value of bile acid concentra- load tended to have lower T1, 210 (30 9), (NS) tion in control subjects was taken as the cut off and reduced T2, 59 (6.9), (p<0 03). T2 was level (Fisher's exact test p=0 05). Aminoglycoside nephrotoxicity in chronic low in all non-venesected patients (n=5) but In conclusion, Barrett's patients seem to liver disease; a controlled clinical trial was within the normal range (mean+2SD) in reflux bile more commonly than oesophagitis one patient who had been fully venesected. patients, and this may have some role in the P A McCORMICK, L GREENSLADE, N McINTYRE, Thus MR relaxation times can differentiate development of columnar oesophageal epi- A K BURROUGHS (Hepatobiliary and Liver Trans- normal liver from iron overload and other thelium. plantation Unit, Royal Free Hospital School of parenchymal liver diseases and is worthy of Medicine, London) Aminoglycoside antibiotics further evaluation in clinical practice. are frequently used in patients with liver disease for treatment of severe infection. It has Novel epidermal growth factor secreting cell been suggested, however, that these drugs are OESOPHAGEAL MALIGNANCY AND lineage and pathogenesis of Barrett's colum- associated with a greater incidence of renal PREMALIGNANCY nar lined oesophagus dysfunction in cirrhotic patients than in those without liver disease. The only controlled trial M R GRAY, C K HOYLE, A N KINGSNORTH performed to date did not confirm this associa- (University ofLiverpool, Department ofSurgery, tion. Surveillance of Barrett's oesophagus: is it Liverpool) A novel epidermal growth factor We prospectively studied the incidence of worthwhile? (EGF) secreting cell lineage (Wright NA et al, British Society ofGastroenterology A555

Nature 1990; 343: 82-5) is induced at the site of localisation in Barrett's columnar lined Fifteen year retrospective study of oesopha- mucosal ulceration throughout the gastrointes- oesophagus geal carcinoma presenting to an endoscopy tinal tract. This cell lineage contains cyto- unit

plasmic EGF immunoreactivity, neutral M R GRAY, PA HALL, D LANE, J NASH, Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from mucin, and is non-proliferating. A N KINGSNORTH (Departments of Surgery and B J JOHNSTON, M J HILL, P I REED (Lady Sobell The key role of EGF is to stimulate cellular Pathology, University ofLiverpool; Department Gastrointestinal Unit, Wexham Park Hospital, proliferation at the site of mucusal injury, of Histopathology, Royal Postgraduate Medical Slough, Berks) Publications from the USA and facilitating healing. School, London and Department ofImmunocyto- UK have reported an increasing proportion of Barrett's columnar lined oesophagus (CLO) chemistry, ICRF, Clare Hall, Herts) Nuclear oesophageal adenocarcinoma (AC) (from follows mucosal ulceration in the lower expression of the 36 kD nuclear protein pro- <10% pre 1965) relative to squamous carci- oesophagus of man and dogs, both of whom liferating cell nuclear antigen (PCNA) is obli- noma (SC). As our preliminary data from have submucosal oesophageal glands. gatory for cellular proliferation and is 1981-85 showed that 60% of endoscopically We have sought evidence of EGF immuno- associated with cycling cells in normal tissues. detected carcinomas were adenocarcinomas, a reactive cells in oesophageal glands and Barrett's columnar lined oesophagus (CLO) 15 year analysis was carried out. In 27789 metaplastic CLO using a polyclonal rabbit carries an increased risk of adenocarcinoma. consecutive endoscopies during 1976-90, 194 antihuman EGF (Oncogene science Ab-3) and We studied the distribution ofPCNA immuno- casesofoesophageal carcinoma werediagnosed. distaste periodic acid Schiff as described by staining in 150 sections taken from 25 patients These were subdivided by histological type, Wright et al. with CLO and eight with adenocarcinoma location, age, and sex. Most oesophageal gland cells contained arising in CLO, utilising the murine mono- The overall proportion of male and female acidic mucin; a minority subpopulation con- clonal antibody PC1O using the avidin-biotin patients with AC was as expected (69 M:28 F) tained neutral mucin and these cells also con- complex immunoperoxidase method on for- but almost equal numbers presented with SC tained cytoplastic EGF immunoreactivity. malin fixed wax embedded tissue. Nuclear (39 M:43 F). In women, the proportion of SC EGF positive cells were present in profusion immunoreactivity was assessed by quantitative rose from 29% in 1976-80 to 77% in 1986-90, in small glands within the Barrett's mucosa, the microscopy and the spatial distribution of with a corresponding decrease in AC (71% staining was granular and cytoplasmic as pre- positive cells was noted. 1976-80: 14% 1986-90). In men, 70% of all viously described. EGF positivity was Altogether 80% of intestinal type metaplasia tumours were endoscopically low oesophageal abolished by prior absorption of the antibody crypt cells were positive for PCNA, signifi- (below 32 cm) compared with 47% in women. with EGF 100jIg/ml. Nuclear staining with the cantly greater than junctional and fundic types More AC and SC were low (AC 76%; SC 44%) proliferating cell nuclear antigen was absent. (50% and 40% of crypt cells respectively) but 23 (24%) of AC were above 32 cm. There Oesophageal submucosal glands contain a (p<005). In severe dysplasia and frank was no significant average age difference subpopulation of EGF containing cells which tumour up to 98% of cells were positive. between the sexes (M 680:F 69-1 years), but may proliferate in response to ulceration and Superficially sited columnar cells were PCNA women with AC were significantly older than acid exposure. Paracrine action of EGF may positive in some cases. Ofgreat interest was the men (F 73-5:M 65 4:p<005) with increasing lead to columnar regeneration from sub- observation of nuclear PCNA expression in female SC age (1976-80 65-2:1986-90 72-1 mucosal glands playing a key role in the smooth muscle, perineural cells, and fibro- years). pathogenesis of Barrett's columnar lined blasts associated with adenocarcinoma. This There has been a definite change in the oesophagus. was not seen in cases without dysplastic pattern ofoesophageal cancer in women during changes. Our results concur with thymidine the past 15 years. labelling techniques. PCNA may be an adjunct in assessment of malignant potential in Bar- http://gut.bmj.com/ Autocrine growth regulation in Barrett's rett's oesophagus. oesophagus - mitogenic or oncogenic? Combined Nd:YAG laser phototherapy and external beam radiotherapy for the palliation J JANKOWSKI, D HOPWOOD, J G PENSTON, of advanced malignant dysphagia K G WORMSLEY (Departments of Clinical Pharmacology and Pathology University of I R SARGEANT, L A LOIZOU, J TOBIAS, G BLACK- Dundee) We assessed 30 patients with Barrett's Length of columnar lined oesophagus, sex, MAN, D GRIGG, M TULLOCH, S G BOWN (National oesophagus. Ten had adenocarcinoma in Bar- age, smoking and drinking habits and risk of Medical Laser Centre and Department ofRadio- on September 24, 2021 by guest. Protected copyright. rett's mucosa and 20 had different histological adenocarcinoma in Barrett's oesophagus therapy, University College Hospital, London) A types ofBarrett's mucosa (10 intestinal type, 10 range of endoscopic techniques is available for fundic or cardiac type). Three biopsy speci- M B E MENKE-PLUYMERS, W C J HOP, J DEES, palliation of malignant dysphagia. NdYAG mens were removed from the area of Barrett's M VAN BLANKENSTEIN, H W TILANUS, THE ROT- laser therapy offers good palliation with few mucosa or the areas ofneoplasia and compared TERDAM OESOPHAGEAL TUMOUR STUDY GROUP complications, but repeat treatments are with specimens from normal gastric mucosa. (University Hospital Rotterdam-Dijkzigt, Rot- required monthly. In an attempt to reduce the Serial sections were analysed immunohisto- terdam, The Netherlands) The significance of number of follow up endoscopies, 22 patients chemically for expression of epidermal growth the length of columnar lined oesophagus (15 M, 7 F) with advanced oesophageal carci- factor (EGF), transforming growth factor a (CLO), sex, age, and smoking and drinking nomas and a good result after initial laser (TGFa), epidermal growth factor receptor habits as risk factors for malignant degenera- recanalisation were given palliative external (EGF-R) and Ki-67 labelling index. tion were evaluated by comparing data from 98 beam radiotherapy. The mean (SD) patient age The expression ofTGFa, EGF, EGF-R, and patients (53 men, 45 women, mean age 61 was 67 (11) years. Nine patients had squamous Ki-67 labelling was increased in Barrett's years) with a benign CLO and 62 patients (47 cell carcinomas and 13 adenocarcinomas, 15 mucosa compared with normal gastric mucosa. men, 15 women, mean age 62 years) with tumours crossed the cardia and six were The 'intestinal type' Barrett's mucosa had the adenocarcinoma in CLO, diagnosed over the thoracic. The mean (SD) tumour length was greatest expression of EGF, TGFa, EFG-R, same period (1978-1985). A distribution of 6-9 (3-1) cm. Five patients had documented and Ki-67 labelling compared with other types frequency for each length of CLO was made. metastases. Five patients received 40 Gy and 17 ofBarrett's metaplasia. Five cases of 'intestinal Statistical analysis was performed by logistic patients 30 Gy in 10-20 fractions. Dysphagia type' Barrett's oesophagus had high Ki-67 regression. was graded from 0-4 (0=normal; 4=dysphagia labelling indices and these patients also over The mean length of CLO was 6-6 cm (range for liquids). Mean dysphagia grade improved expressed both TGFa and EGF-R. 3-14) in the benign group, and 7-7 cm (range from 2.5 to 1-4 after laser treatment. There was The Barrett's adenocarcinomas over express 3-19) in the malignancy group (p=0.03). The a further small improvement in dysphagia in TGFa and EGF-R (p<0 05), but not EGF length of CLO was significantly related to patients receiving 30 Gy but a marked when compared with gastric mucosa. carcinoma using multivariate analysis: a deterioration in patients receiving the higher In conclusion, both normal gastric mucosa doubling of the length resulted in a 1-7 risk dose during the median follow up of 30 weeks and Barrett's mucosa have potential autocrine increase. Male sex and smoking were also (to death). Further endoscopic procedures regulatory mechanisms (expression of ligand significant risk factors. Adjusted for length of were required only once every 20 weeks on and receptor in the same cell) but Barrett's CLO, sex, and smoking, no relation between average to maintain improved swallowing. In mucosa has increased expression of both pep- carcinoma and age or alcohol consumption was patients treated previously with laser alone four tide (TGFa) and receptor (EGF-R). found. of 43 (9%) survived one year but in those given In conclusion, the risk of developing adeno- 30 Gy as well, five of 16 (32%) survived one carcinoma increases with the length of CLO. year. There were no endoscopy related com- Male sex and smoking are also significant risk plications. Proliferating cell nuclear antigen immuno- factors. In conclusion, combined treatment with laser A556 British Society ofGastroenterology and palliative radiotherapy (30 Gy) seems to 47.5% (3 0)% (NS). Cimetidine shifted the 28-0 years (range 21-81). None were smokers reduce the need for follow up laser endoscopies histamine response curve in a parallel manner or taking NSAIDs. Dyspeptic symptoms were and may improve survival. A randomised study in both groups. Analysis of the individual data present in 135 of 197 (68.5%). H pylon was is underway to test these conclusions. points (by ANOVA) showed no significant dif- detected in 74-6% ofsubjects. The point preva- ference between NUD and DU patients. lence of active peptic ulcer was 6-6% (13 of Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from These in vitro studies failed to show any 197). All ulcers detected were either prepyloric, difference in isolated PC to acid secretion pyloric, orduodenal. Afurther 6-6% ofsubjects PATHOGENISIS OF DUODENAL ULCER stimulation and inhibition by histamine and had definite evidence of scarring or deformity cimetidine in DU and NUD patients. It sug- indicative of previous ulceration. H pylon was gests that the acid hypersecretion in DU may present in all subjects with active ulcers and in occur as a result ofPC neuro-endocrine control 92% of those with scarring and there was a Depression of salivary epidermal growth rather than an inherent cellular abnormality. strong correlation between symptoms and factor by smoking ulcer (p<001). However, there was no correla- tion between dyspepsia and the presence of P D E JONES, N HUDSON, C J HAWKEY (Department H pylori. of Therapeutics, University Hospital, Notting- Effect of Helicobacter pylon on gastric The prevalence ofpeptic ulcer in this popula- ham) Epidermal growth factor (EGF) emptying of liquids and solids in duodenal tion is high. However, neither the high preva- deficiency leads to gastroduodenal ulceration in ulcer patients lence of ulcer disease nor H pylori infection experimental animals. Salivary EGF is explains the high prevalence ofdyspepsia in this depressed in rheumatoid patients, who are A M EL NUJUMI, G M FULLARTON, G F CUTHBERT, population. prone to peptic ulceration. Since smoking R G BESSENT, H W GRAY, K EL McCOLL (Univer- predisposes to peptic ulceration we investi- sity Department of Medicine and Therapeutics, gated salivary EGF in smokers and non- Western Infirmary, and Department of Nuclear smokers and in patients with idiopathic Medicine, Royal Infirmary, Glasgow) The COLORECTAL:CLINICAL duodenal ulceration and gastric ulceration. mechanism by which Helicobacter pylori infec- ASPECTS We studied patients attendingforendoscopy. tion ofthe gastric antrum predisposes to ulcera- Some 196 who were not taking drugs affecting tion ofthe duodenum is unclear. As the antrum salivary flow had normal endoscopic findings. is important in regulating the delivery ofgastric Importance of mild dysplasia in surveillance Fifty five had active duodenal ulceration, 33 contents into the duodenum, we have investi- ofulcerative colitis healed duodenal ulcers, 23 active gastric gated the possibility that H pylon predisposes ulceration, and 22 healed gastric ulcers. Saliva to duodenal ulceration by interfering with D A F LYNCH, G M SOBALA, A J LOBO, M F DIXON, was stimulated by citric acid and EGF was gastroduodenal motility. A T R AXON (Gastroenterology Unit and University measured by a radioreceptor assay. Eight patients confirmed endoscopically to Department ofPathology, The GeneralInfirmary, Among control patients, current smokers have duodenal ulcer disease but whose ulcer Leeds) Surveillance for colonic carcinoma in secreted significantly less EGF than non- was currently healed were examined before and patients with longstanding extensive ulcerative smokers (median (range) 56-1 (2.5 - 173-5) v one month after eradication of H pylon infec- colitis (UC) is widely advocated but of un- 31-1 (5.5 - 383.9); p=0-0174, Mann-Whitney). tion with four weeks' treatment with tripotas- proved benefit. Weight has been placed on the EGF secretion in patients with active duodenal sium dicitratobismuthate, metronidazole, and predictive value ofdysplasia. In our experience ulceration (44.9 (8-3-163)) healed duodenal amoxycillin. The presence and eradication of of 728 annual screening/surveillance colonos- ulcers (44.9 (8 3-280) ng/10 min), active the infection were confirmed by examination of copies in 159 patients with longstanding exten- http://gut.bmj.com/ gastric ulceration (58-4 (7-9-132) ng/10 min), antral biopsy specimens and the '4C-urea sive UC in whom routine biopsy specimens or healed gastric ulcers (37.5 (6-5-197-3)) did breath test. All patients stopped any medica- were taken from nine colonic sites, we have not differ significantly from control values. tion two weeks before the study. Gastric been able to follow up 40 patients with 201 Smokers tended to have lower values than non- emptying was assessed scintigraphically using a further examinations after the first diagnosis of smokers but not significantly so. meal with its liquid phase labelled with indium- mild dysplasia (total 2677 patient months In conclusion, smoking may predispose to III and its solid phase labelled with technetium follow up). peptic ulcer by reducing salivary EGF output. 99. Twenty patients (50%) had no further dys-

The mean (range) t½, gastric emptying for plasia (mean 4.0 colonoscopies, 55.9 months on September 24, 2021 by guest. Protected copyright. solids was 202 (53-55) minutes pretreatment follow up per patient) and 19 continued to and significantly quicker after eradication at exhibit mild dysplasia (mean 6.3 colonoscopies, Failure to show parietal celi hyperactivity in 105 (69-151) minutes (p<0 05). The t½/, gastric 81-4 months). One ofthese patients went on to duodenal ulcer patients emptying for liquids was 40 (25-66) minutes develop an adenoma six years later. This was pretreatment and unchanged after eradication removed at colonoscopy and the patient has S ENGLAND, M J DALY, S JACOB, K D BARDHAN at 39 (21-61) minutes. subsequently been free of dysplasia for six (District General Hospital, Rotherham; Astra This study shows that H pylori modifies further years. One patient went on to develop Clinical Research Unit, Edinburgh; and Bio- gastroduodenal motility and provides a severe dysplasia on the next colonoscopy 14 medical Science Department, University of mechanism by which it may predispose to months later and underwent total colectomy at Sheffield) We investigated if acid hypersection duodenal ulceration. which two Duke's A carcinomas were found. in duodenal ulcer (DU) disease is caused by a Life table analysis on all UC patients under- fundamental disorder of the perietal cells (PC) going surveillance showed that 25% and 50% by comparing the responsiveness to histamine manifested mild dysplasia at 17 and 25 years and cimetidine of isolated PC obtained from Prevalence ofHelicobacter pylon and peptic after the onset ofdisease respectively. Thus, in patients with non-ulcer dyspepsia (NUD) ulcer and relation to symptoms in a Tibetan our experience 'mild dysplasia' is a common (n=21) and DU (n= 19). refugee population in southern India finding in ulcerative colitis surveillance which Biopsy specimens were collected from the has little adverse prognostic importance. fundus, and in each experiment tissue pooled P H KATELARIS, G TIPPETT, R BRENNAN, from two to three patients was used. All drug P NORBU, M J G FARTHING (Department of therapy had been stopped >14 hours before Gastroenterology, St Bartholomew's Hospital, endoscopy. Dispersed mucosal cells (17% PC) London and Doeguling Tibetan Hospital, Karna- Does prolonged colonic transit impair the were prepared by sequential pronase and col- taka, India) The prevalence of Helicobacter efficacy of oral 5-aminosalicylic acid formu- lagenase digestion. Cells showed >85% pylori and peptic ulcer was determined in a lations? viability by trypan blue. Aliquots of cells population known to have a high prevalence of (300 il total volume) were incubated for 140 dyspeptic symptoms. A sample population was S A RILEY, I A TAVARES, A BENNETT, V MANI minutes in 96 well microfiltration plates (Milli- selected randomly from a rural monastic settle (Department of Medicine, Hope Hospital, Sal- pore) and maintained at 37°C in an oxygenated ment in southern India. Each subject was ford;King'sCollegeHospital, London; andLeigh chamber. The 14C-aminopyrine uptake (APU) interviewed using a standardised symptom Infirmary, Leigh) 5-Aminosalicylic acid (SASA) technique was used as an indirect measure of questionnaire followed by endoscopy and has a predominantly topical mode of action on acid production by the PC. antral biopsy for histology and CLO rapid inflamed colonic mucosa. As N-acetyl-5ASA APU increased with rising concentrations of urease test. has no therapeutic activity, intracolonic SASA histamine (1, 10, 100 FtM), the maximum Altogether 197 subjects were studied from a acetylation may influence clinical efficacy. We uptake at 100 FM above basal values (mean population of 1499 (13-1%). All were male have therefore studied the relation between (SE); n=6) being: NUD 46.6% (15-7)%; DU monks and ethnically Tibetan with median age steady state faecal drug concentrations and British Society ofGastroenterologyA A557 indices of colonic function in patients with logical prognostic indicator ofcolorectal cancer can be induced in patients by an anti-idiotypic ulcerative colitis maintained on oral 5ASA (CRC), however, long term survival ofpatients antibody without exogenous carrier deter- formulations. with early lesions as staged by this system is by minants. Ten patients with quiescent colitis were no means assured. Some 70% ofpatients under- studied. Faecal 5ASA and N-acetyl-5ASA con- going surgery for Duke's B CRC can expect to Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from centrations varied widely between patients but be alive at five years. Identification of the 30% correlated well in those studied repeatedly of patients destined to die of recurrent disease Increased intestinal transit times potentially (5ASA: r=0-83, p<001, N-acetyl-5ASA: would help target these for adjuvant therapy. increase absorptive capacity after restorative r=0-64, p<0 05). N-acetyl-5ASA accounted The histological specimens of 123 patients proctocolectomy for 10 to 87% of the total faecal drug excretion. with newly diagnosed Duke's B CRC admitted Concentrations were unrelated to stool pH to hospital between 1983 and 1988 were sub- K B HOSIE, A B MOSTAFA, N J TULLEY, A NOTGHI, (range 5-1 to 7.6), faecal mass (range 121 to jected to detailed analysis by a single histo- M R B KEIGHLEY, L K HARDING (Department of 380 g/day), or dietary fibre intake. pathologist. Histological variables studied in- Surgery, Queen Elizabeth Hospital, and Depart- Total faecal drug excretion was unrelated to cluded the overall grade and extent of tumour, ment of Physics and Nuclear Medicine, Dudley whole gut transit time. The percentage offaecal type of tumour front, presence or absence of Road Hospital, Birmingham) After pouch drug output excreted as N-acetyl-5ASA, how- inflammation, mucin, vascular invasion, formation the frequency of defaecation is vari- ever, correlated with transit during periods of neural invasion, necrosis, stromal reaction, able and may be related to the speed at which low fibre intake (r=0-77, p<0 01) and high Crohn's reaction, peritonitis, the presence of a food passes through the intestinal tract. In fibre intake (r=0-70, p<0 05). These findings papillary pattern to the tumour, signet ring addition, the time food spends in contact with suggest the progressive intracolonic acetylation pattern, and the number of negative lymph the intestinal mucosa affects its absorption. of 5ASA as it passes through the colon. nodes in the specimen. Follow up was between Parameters ofgastric, small bowel, pouch, and In patients with ulcerative colitis, prolonged 19 and 87 months. The end point was taken as whole gut transit were measured in 14 pouch intestinal transit may impair the efficacy oforal total mortality. patients and 10 ileostomy control subjects. 5ASA formulations by promoting intracolonic Using a stepwise Cox regression model both After an overnight fast, patients consumed a 5ASA acetylation. neural invasion and necrosis were found to be solid meal consisting of mince (70 g), potatoes independent variables related to survival. (25 g), and peas (15 g) labelled with 'Tc- Patients with neural invasion had an increased DTPA (40 MBq). Paired posterior and anterior relative risk of 3-02 (p<0-01), while those images were collected on a gamma camera at Resection of liver metastasis from colorectal whose tissues displayed necrosis had an in- regular intervals for eight hours. These were cancer: prognostic factors creased relative risk of 2-5 (p<0 01). No other corrected for background movement, decay, parameter added to these could predict an and scatter and the geometric mean of paired M JAMES, D KUMAR, j W L FIELDING, G D OATES unfavourable outcome. Neither age nor sex images was calculated. The frequency of (Department of Surgery, Queen Elizabeth were significant variables. defaecation was recorded and stool samples Hospital, Birmingham) Hepatic resection is In conclusion, the finding of neural invasion were collected for a total of 24 hours from the generally carried out for metastatic disease in or tissue necrosis in patients with Duke's B start of the study, during which time patients the absence of metastatic disease elsewhere. CRC heralds a poor prognosis and these ate a standardised diet. Despite an extensive search for prognostic patients should be considered for adjuvant The mean (SD) whole gut residence time was factors, the five year survival rates show con- therapy. longer in pouch patients 12-5 (2.5) meal hours siderable variation (20% to 35%). We have than ileostomy patients 6-6 (2.2) (p<0 002) analysed the results of 46 patients who have (Mann-Whitney). Because the gastric empty- http://gut.bmj.com/ undergone hepatic resection for metastatic ing t,/2 (pouch=54 (20) minutes, ileostomy 40 disease and 96 patients who had a palliative Cell mediated response in vitro after (12) minutes) and small bowel residence time resection ofthe primary tumour in the presence immunisation of colorectal cancer patients (pouch 4-4 (2-1) meal hours, ileostomy 5-4 ofhepatic metastasis. The mean age ofpatients with a human monoclonal anti-idiotypic anti- (2 1) meal hours) are similar, the increased in the two groups was 63 and 59 years body whole gut residence time is due to time spent in respectively. the pouch. There was no correlation between The five year survival for curative resection G W L DENTON, R A ROBBINS, L G DURRANT, frequency of defaecation and any of the para- group was 86% (one year), 54% (two years), E B AUSTIN, J D HARDCASTLE, R W BALDWIN meters of intestinal transit. on September 24, 2021 by guest. Protected copyright. 36% (three years), 29% (four years) and 20% (Department of Surgery and Cancer Research The longer residence time in patients who (five years), whereas the rates for the palliative Campaign Laboratories, Nottingham University, have undergone restorative proctocolectomy resection group were 36 5%, 18-8%, 6-3%, Nottingham) 105AD7 is a human monoclonal potentially increases absorption. 3-1%, and 1-0% respectively (p<0.01). IgG' antibody produced by hybridisation of Analysis of various prognostic factors lymphocytes from a colorectal cancer patient showed that a clear resection margin was injected with mouse monoclonal antibody, associated with a better survival (p=0-01) and 791T/36, for tumour imaging. 105AD7 human Fistula complicating restorative procto- an improved recurrence free survival anti-idiotypic monoclonal antibody binds colectomy (p=0-001). The other favourable factor was specifically to 791T/36 and blocks its binding to CEA both for improved survival (p=0 05) and gp72 antigen, suggesting that 105AD7 is an M R B KEIGHLEY, J ASPERER, K HOSIE, S GROBLER disease free survival (p=0.01). Deposits of internal image anti-idiotype of 791T/36. (Department of Surgery, Queen Elizabeth Hos- <3 cm (n= 12) and >9 cm (n= 10) had a A phase 1 clinical trial has been initiated in pital, Birmingham) Fourteen patients have significantly worse median survival (15 and 21 which five patients with advanced colorectal developed an enterocutaneous fistula and eight months) than those with deposits of >3 cm and carcinoma have been immunised with 105AD7 have had a pouch vaginal fistula after 114 <9 cm (n=24, 37 months) (p=0.05). Serum human anti-idiotypic monoclonal antibody as restorative proctocolectomies. Of those with alkaline phosphatase values of <300 mg were an aluminium hydroxide precipitate. enterocutaneous fistula, the underlying diag- associated with an improved survival (p=0 01). Clinical and laboratory evaluation has shown nosis was thought to be Crohn's disease in four, Age, sex, and nodal status and type ofresection no evidence of toxicity or the formation of ulcerative colitis in eight, and megarectum in had no correlation with improved survival. antibodies to the anti-idiotypic antibody, either two. Four enterocutaneous fistulas were from These data show that clear resection margin on initial exposure or repeated dosage with the ileostomy closure site (one diabetic), none \CEA, deposits between 3 and 9 cm, alkaline 105AD7 human anti-idiotypic monoclonal required pouch excision. Five cutaneous phosphatase >300 mg are associated with antibody. fistulas were from the ileoanal anastomosis to improved overall and recurrence free survival. Mononuclear cells were prepared from blood the abdominal wall (four Crohn's disease), only samples taken before and at weekly intervals one has been successfully managed by pouch for six weeks after immunisation. An in vitro reconstruction, two patients have a loop ileos- proliferative response, measured by incorpora- tomy, and two have had their pouches excised. Histological predictors of poor outcome in tion of tritiated thymidine, was seen in four Five cutaneous fistulas were from the pouch, Duke's B colorectal cancer patients, to both the anti-idiotypic antibody one being associated with a distal pouch stric- and to gp72 positive tumour cells. No response ture, two arose from a J pouch appendage, one H MULCAHY, M TONER, L DALY, S PATCHETT, was present before immunisation and a peak patient has required pouch excision, the D P O'DONOGHUE (Departments of Gastro- response was observed at three weeks after remainder have had their fistulas excised and enterology, Pathology, and Epidemiology; St immunisation with 105AD7 human anti- have good pouch function. Of the eight Vincents Hospital, UCD, Dublin, Ireland) idiotypic monoclonal antibody. patients with vaginal fistulas, three are thought Duke's classification is a widely used histo- These results suggest that cellular immunity to have Crohn's disease. All four high fistulas A558 BritishSocietyofGastroenterology

(one Crohn's disease, two from pelvic sepsis, These results provide evidence of oxidative the original basal growth (p=0.0166 from basal one from retained rectal mucosa) and have been stress early in the course of AP and indicate and p=0-0109 from gastrin-stimulated growth, successfully treated by pouch reconstruction. that it persists well after the attack is over, and Mann-Whitney U test on tumour cross sec- Four low fistulas from the ileoanal anastomosis in patients with recurrent acute and chronic tional areas at termination of the experiment, to the vulva (two Crohn's disease) were success- pancreatitis. day 24, n= 10 animals/group). Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from fully managed by seton division. GR antagonists with such favourable Fistulas are an uncommon complication of pharmokinetics may be a viable therapeutic restorative proctocolectomy, but many can option for GR positive GI tumours. usually be successfully managed without pouch Treatment with high dose octreotide excision. improves the clinical course of acute pan- creatitis Transforming growth factora is trophic to N BEECHEY-NEWMAN, W LEE, M WILKINSON, pancreatic cancer in vivo Perineal excision ofthe rectum for prolapse - J GROGONO, G A D McPHERSON (Department P KAPUR, N DAVIES, J GILLESPIE, G J POSTON, P J a minimally invasive technique to improve of Surgery, Wycombe General Hospital, High GUILLOU (Academic Surgical Unit, St Mary's functional outcome Wycombe, Bucks) High dose octreotide (SMS Hospital, London) Pancreatic cancers over 201-995) prevents the onset of acute pancreat- express epidermal growth factor (EGF) recep- I G FINLAY, M AITCHISON (INTRODUCED BY itis and reduces mortality of established pan- tors, a product of the erb oncogene. In addi- J McKENZIE) (Department of Surgery, Royal creatitis in rats, but no convincing study in tion, in vitro, pancreatic cancer cell lines Infirmary, Glasgow) The anatomical anomalies humans has been published. The present study produce transforminggrowth factora, (TGFct), in rectal prolapse include: patulous anus, dias- was designed to determine whether high dose the alternate agonist of the EGF receptor, tasis of the levator ani muscles, loss of sacral octreotide improves the course of acute pan- which ifstimulated promoted cell division. It is attachment, and a deep peritoneal reflection. creatitis in man. hypothesised that this may constitute an auto- We describe a perineal operation that aims to Nineteen consecutive patients with acute crine growth cycle. correct all these anomalies, thereby improving pancreatitis (amylase >1000 IU/l) were allo- The purpose ofthis study was to determine if functional outcome. cated to receive octreotide 250 [tg (sc) and TGFa is trophic to pancreatic cancers in vivo. In the prone position an anal canal mucosec- 0.5 pg/kg/hour (iv) (n=9) or to be controls Eighteen Syrian golden hamsters were inocu- tomy is performed; the rectal wall is divided (n= 10). In all other respects treatment was lated in both cheek pouches with H2T hamster above the sphincter until the rectum is free to standardised and identical. Analgesia was by pancreatic cancer and randomised to three protrude at the anus. The levator/sphincter patient controlled continuous infusion. The equal groups to receive immediately saline, muscles are plicated both anteriorly and pos- groups did not differ with regard to the Ranson EGF (10 rig/kg) or TGAa (10 ,ug/kg), given teriorly. The redundant rectum is amputated or Glasgow scales on admission. The clinical three times a day by intraperitoneal injection and anastomosed to the dentate fine. course was assessed by monitoring blood gases, for seven weeks. Tumour areas were measured The operation has been performed in 26 haematology, biochemistry, clinical signs, weekly. At sacrifice tumours were weighed and patients (median age 82 years, range 58-92). radiology including computed tomogram mor- analysed for DNA content. Statistical analyses Operative mortality was 4%. There has been phology, and clinical milestones. Although no were by ANOVA, p<0 05 significant. one recurrence of prolapse (4%). At six patients with severe pancreatitis were admitted From week four until sacrifice, both EGF months, 19% of patients had severe incon- during the study period, prognostic reductions and TGFa significantly promoted tumour tinence, 60% were completely continent, and in serum calcium (to <2-00 mmol/l), albumin growth. At sacrifice, tumour areas (mean

21% had minor leakage. (to <32 g/l), and haematocrit (> 10%) and falls (SEM) mm2) were: control 99 (6), EGF 145 http://gut.bmj.com/ These data suggest that a satisfactory func- in haemoglobin (of >2 g/dl) and P02 (to (12), and TGFct 140 (6); both the latter tional outcome may be achieved by a minimally <10 kPa) were significantly less frequent in significantly greater than control. Although invasive operation. the octreotide treated group (p<005 Fisher's tumour weights were not significantly differ- exact test). Analgesic requirements were also ent, both EGF treated (266 (22) and TGFa significantly less (p<005, Mann-Whitney treated (168 (9)) tumours had significantly U test). Every other variable without excep- greater DNA contents (mg) than control PANCREATIC DISEASE tion, including computed tomogram morph- tumours (101 (13)). This is the first finding ofa

ology, showed a non-significant improvement trophic effect of TGFt on a gastrointestinal on September 24, 2021 by guest. Protected copyright. in the octreotide treated group. No deaths cancer in vivo. This study shows the comple- occurred in either group. tion of an autocrine growth cycle which may Increased lipid isomerisation in acute pan- These preliminary results suggest that explain pancreatic cancer's bad prognosis. creatitis - evidence ofoxidative stress octreotide may beneficially affect the course ofacute pancreatitis. P M KAY, C CHALONER, J MADDISON, J M BRAGANZA (Manchester Royal Infirmary, Man- chester) Free radical attack on endogenous COLORECTAL linoleic acid (9,12-LA) yields a distinctive Therapeutic effect of the gastrin receptor 9,1 1-isomer(9,1 l-LA')whichcanbeseparated antagonist, CR2093, on gastrointestinal from the parent compound by HPLC. Results tumour cell growth Can fundoscopy identify patients with the are expressed as 9,11-LA' x 100/9,12-LA gene causing familial adenomatous (%MR). We have previously reported S A WATSON, J F ROBERTSON, J D HARDCASTLE polyposis? increased amounts of this marker in both (Cancer Research Campaign Laboratories and duodenal juice and serum of patients with Department of Surgery, University of Notting- W J CAMPBELL, T G PARKS, R A J SPENCE, N C recurrent pancreatitis. This was interpreted ham, Nottingham) Gastrin is a known growth NEVIN (Departments of Surgery and Medical as being the result of increased free radical factor for gastrointestinal (GI) tumour cell Genetics, BelfastCity Hospital, Belfast) Sixty six production from induced cytochromes P450. growth. Gastrin receptor (GR) antagonists may members of 21 families with at least one This study compares the %MR in blood therefore be a therapeutic option for the treat- member histologically confirmed as suffering samples taken at admission from 18 patients ment ofgastrin sensitive GI tumours. from familial adenomatous polyposis (FAP) suffering a first attack of acute pancreatitis The GR antagonist, CR2093 (kindly pro- and 40 control subjects were examined by (AP) with values in the quiescent phase some vided by Rotta Labs, Milan, Italy) competed indirect ophthalmoscopy to ascertain the pres- three months after the last attack in 10 patients with 12511[] gastrin-17 (5x 10-"M) for binding to ence of congenital hypertrophy of the retinal with acute pancreatitis (post-AP) and 20 GR on the rat pancreatic tumour cell line, pigment epithelium (CHRPE). Twenty eight patients with chronic pancreatitis (CP), and in AR42J (the concentration inducing 50% of of 37 patients diagnosed as having FAP were 20 healthy controls. '25[I]-gastrin-17 binding was 8x 10-5M for noted to have CHRPE lesions compared with Patients with AP had significantly higher CR2093, compared with 6x 10-'M for the three of the 29 at risk subjects and two control ratios than controls (mean (range) 3.53 natural ligand, gastrin-17). subjects. The separation between those (1-08-7-76) v 2-24 (0-81-3-90) 2p<0005) but Due to favourable pharmokinetics, CR2093 affected by FAP and control subjects was these ratios did not differ from those in post-AP was administered intravenously (40 mglkg/ significant (p=0-0001). or CP groups (3-22 (1 98-6.89) and 4 04 (1-63- day) to male nude mice bearing AR42J xeno- The failure to detect CHRPE in all patients 6 92) respectively. A fourth group of patients grafts. CR2093 had no significant effect on the affected by FAP and the difficulties in defining with (non-pancreatitis) acute abdomen had basal growth of AR42J xenografts but reduced the normal variation in retinal pigment epithe- ratios similar to controls. gastrin-17 stimulated growth to below that of lium make this an unsuitable screening test for British Society ofGastroenterology A559

FAP. The authors recommend that all those at Using conventional cytology, two patients carefully to remove non-adherent cells and risk continue to attend for regular sigmoid- were considered to have malignant cells and counted in a gamma counter. The numbers of oscopy for screening. four other patients atypical cells. However, adherent cells were calculated according to the after immunocytochemistry only one of the formula: atypical patients was positive and the other Cell no/cm suture= Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from three clearly negative for malignancy. None of radioactivity of suturex 10 Cell proliferation in colorectal cancer studied these patients had detectable liver metastases. radioactivity of 107 tumour cells with in vivo administration of bromode- This study confirms that circulating malig- The median number ofadherent cells per cm of oxyuridine nant cells can be identified in patients without suture in mono- or multifilament steel was overt evidence of metastases, and shows the significantly less than in protein based or other M PONZ DE LEON, A SCALMATI, L RONCUCCI, value of immunocytochemistry as an essential multifilament sutures. G CALZOLARI, A MANENTI, C DI GREGORIO, adjunct to conventional cytology. This study suggests that in the presence of W GIARETTI, A RAPALLO (Ist Patologica Medica, free malignant cells steel is a safe suture Clinical Chirurgica, Anatomia Patologica, Uni- material but protein based and multifilament versita di Modena, Istituto Scientifico Tumori, sutures should be avoided. Genova, Italy) Bromodeoxyuridine is a non- Photoimmunotherapy: a potential treatment radioactive thymidine analogue that can be for residual colorectal cancer? given intravenously and is incorporated into the DNA of proliferating cells. Monoclonal J W DAWSON, J MORGAN, H BARR, B R DAVIDSON, Mitogenic response of normal colonic epi- antibodies against bromodeoxyuridine allow F SAVAGE, R MACROBERT, C DEAN, P B BOULOS thelium to peanut lectin correlates with lectin the identification of S phase cells by immuno- (Departments of Surgery and Haematology, histochemistry histochemistry. We evaluated cell kinetics in UCMSM and Department of Biochemistry, 20 patients with colorectal malignancies after Imperial College, London; andInstitute ofCancer S D RYDER, D ECCLESTON, M HAGANNI, J M an intravenous injection of 500 mg bromode- Research, Sutton) Local recurrence occurs in RHODES (Department of Medicine, University of oxyuridine two to four hours before surgery. a third of patients undergoing resection for Liverpool and Departments of Gastroenterology Tumour fragments were taken and processed colorectal cancer. Adjuvant therapies have and Pathology, Walton Hospital, Liverpool) The with standard techniques. In five patients been unsuccessful in eradicating residual cells T blood group antigen is commonly over- bivariate flow cytometry was used to measure after 'curative' resection. By targeting a photo- expressed in colorectal neoplasia and is the ploidy, S phase duration, and potential sensitiser to cancer cells using a monoclonal acceptor for PNA. We have previously shown doubling time. The labelling index (LI, frac- antibody, photoimmunotherapy offers an ad- that PNA stimulates crypt cell production rate tion of bromodeoxyuridine labelled cells) was vantage over photodynamic therapy which is in normal colonic explants. We have now mean (SEM) 20-7 (1-4)% with small differences limited by the poor uptake of photosensitiser studied the correlation between mitogenic re- between peripheral and central areas of the by tumour. sponse to PNA and PNA lectin histochemistry. tumour. The LI increased progressively from A conjugate of the photosensitiser phthalo- Colonic explants were obtained from 36 normal mucosa (6-0 (1-1)%), to adenomatous cyanin and monoclonal antibody UCH-39.4 histologically normal colons (14 irritable areas (11-6 (3 0)%), to carcinoma (F: 27, has been synthesised and tested in vitro and in bowel, five anaemia, 17 prior adenomatous p<001), whereas it was unrelated to stage, vivo using a rat colorectal cancer (RCC5). polyps). Biopsy specimens were cultured for 16 grade, site, and size of the neoplasm. Four of In vitro cytotoxicity was assessed using the hours, with or without PNA (25 mg/ml) and five tumours were aneuploid, while DNA MTT reduction assay after incubating cultured crypt cell production rate (CCPR) was deter- synthesis time was in the order of five to RCC5 cells with conjugate or free photosensi- mined. A biopsy specimen from each patient http://gut.bmj.com/ six hours. Potential doubling time was 50-53 tiser and exposure to 18J/cm2 red light. was snap frozen, 6 mm sections were cut, hours for the aneuploid and 60-72 hours for The uptake of photosensitiser by tumour and endogenous peroxidase blocked, the tissue the diploid populations. normal tissue was assessed in a nude mouse was incubated for four hours with peroxidase Thus, cell kinetics can be studied in xenograft model using quantitative photo- tagged PNA and was developed with DAB/ colorectal tumours with in vivo bromode- metric fluorescence analysis. H202. oxyuridine by immunohistochemistry and flow In vitro cytotoxicity of the conjugate was CCPR increased by mean (SD) 25% overall cytometry. These preliminary results show a 1000x greater than free phthalocyanin (90% in the presence of PNA. Biopsy specimens progressive increase of cell replication from cell kill using conjugated phthalocyanin at showing PNA binding on the epithelial cell on September 24, 2021 by guest. Protected copyright. normal colonic mucosa to dysplastic and neo- 10` M compared with free phthalocyanin at (n=9) showed an increase in CCPR of 57% (9) plastic tissues. 10`6 M). Uptake of photosensitiser using the (from 6-5 to 10-2 cells/crypt/hour) compared conjugate showed tumour:normal ratios of with a 14% (7) rise (from 6-9 to 7.9) in PNA 1000:1 (photodynamic therapy using free dye negative specimens (n=27), p=0-01. Only one achieves ratio of only 2:1). biopsy specimen was positive for PNA in Value of immunocytochemistry in the detec- Truly selective tumour ablation is therefore formalin fixed tissue. This study shows that tion of circulating malignant cells in feasible and could have useful practical altered blood group antigen expression detec- colorectal cancer application. ted by lectin histochemistry in frozen tissue may have functional importance, even in A J M LEATHER, N GALLEGOS, G KOGAN, F SAVAGE, normal colon, and implies that interactions C SMALES, W HU, P B BOULOS, J M A NORTHOVER, between epithelial carbohydrate epitopes and R K S PHILLIPS (ICRF Colorectal Cancer Unit, Adherence of colorectal cancer cells to dietary lectins may have important effects on St Mark's Hospital, Department of Cytology, suture materials - is stapling safe? the development of colorectal cancer. Middlesex Hospital and Departments ofSurgery, University College and St Bartholomew's C R UFF, C Y YIU, P B BOULOS, R K S PHILLIPS Hospital, London) Occult hepatic metastases (Professorial Surgical Unit, St Bartholomew's may be present in 24% of patients undergoing Hospital, London, and Department of Surgery, Metabolic patterns in normal human ileum laparotomy for colorectal cancer. It may be University College, London) Tumour cell adher- and colon hypothesised that these patients are identifiable ence to suturing material may contribute to by the perioperative detection of circulating anastomotic recurrence as free malignant cells P GIAMUNDO, M F GRAHN, P R O CONNELL, W malignant cells. To determine if these cells are present in the bowel lumen during WOODS, N S WILLIAMS (The Surgical Unit, could be detected the following study was colorectal surgery. Concern has been expressed London Hospital Medical College, The Royal initiated. about the risk of anastomotic recurrence after London Hospital, Whitechapel, London) The Eighteen consecutive patients undergoing resection and stapled anastomosis. We have aim of this study was to investigate the patterns colorectal cancer surgery were studied. Blood therefore compared tumour cell adherence to ofmetabolic activity along the colon and ileum. samples were collected preoperatively from the steel with other suturing material using the rat This was made possible by the development of antecubital fossa. Leucocytes and tumour cells colorectal cancer cell line RCC5. a simple technique that utilises the specimens were isolated with a Ficoll density gradient and One cm lengths of silk, nuralon, ethilion, obtained from colonoscopic biopsy forceps. cytospin preparations made. The slides were chromic catgut, coated vicryl, multifilament This method is the first that allows sequential stained by conventional cytology (May Grun- steel, monofilament steel, and PDS were added measurements to be made in humans. wald) and an indirect immunoperoxidase tech- to 107 radiolabelled RCC5 cells. The sutures Eight patients undergoing colonscopy for nique using the anticytokeratin 8.13 mono- and labelled cells were agitated together in non-inflammatory bowel disease were in- clonal antibody. All slides were assessed by a serum containing medium for 90 minutes at cluded. Three replicate biopsy specimens were consultant cytologist blindly. 37°C. The suture materials were then washed taken from the ascending, transverse, descend- A560 British Society ofGastroenterology ing, sigmoid colon and rectum of each patient. mucosa were sampled from 44 patients with their inhibitor, tissue inhibitor of metallopro- Six biopsy specimens ofdistal ileum were taken colorectal cancer immediately after excision, teinases (TIMP). In vivo evidence for this from each of a further three patients under- and samples were stored at -20°C until interaction is, however, lacking. going colectomy. The metabolic fluxes to "CO2 assayed. Protein extracts were prepared by Therefore, an immunolocalisation study of from radiolabelled glucose (10 mM), glutamine boiling in water, homogenisation, and centri- TIMP and the MPs: stromelysin (SL), gelatin- Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from (5 mM) and butyrate (5 mM) were expressed as fugation. Supernatants were subsequently ase (GL), and interstitial collagenase (CL) was mean (SEM) pmol/tg DNA/hour, p values by assayed for biologically active gastrin (antibody performed on biopsy specimens of tumour, unpaired t test. L2), for the immediate, glycine extended pre- tumour mucosal junction (TMJ), and normal Preliminary results show no significant dif- cursor (Gly-X) and for progastrin (L289; and mucosa from 20 consecutive resected speci- ferences in the pattern of utilisation of the LW60 which includes a C terminal tryptic mens ofcolorectal adenocarcinoma. metabolites between the various sites within fragment). Concentrations of gastrin and its None of the MPs were identified in normal colon. In colon as a whole, the utilisation of immediate precursor did not differ between mucosa, and only SL and GL were present in butyrate was greater than that of glutamine normal mucosa and tumour. However, there malignant tissue. In tumour biopsy specimens (479 (51) v 279 (30), n=35, p=0-01). Glucose was a significant excess of peptide (pmol/g-'; SL, GL, and TIMP were detected in 12, nine, was utilised to a lesser extent (54 (3), n= 30, mean (SEM) detected by both LW60 (7.53 and eight cases respectively and at the TMJ in p<0-01). In ileum, the utilisation of glucose (0.69) v 3-99 (0.42); p<0-001. Student's un- seven, nine, and 15. MPs without their asso- (72 (18), n=5) is somewhat higher than that in paired t test) and by L289 (1-54 (0.20) v 0.54 ciated inhibitor TIMP were seen in signific- colon (p<0 1), whilst that of butyrate (584 (0-12); p<0-01) in tumours compared with antly fewer biopsy specimens from the TMJ (92)) is not significantly different. Glutamine normal mucosa respectively. (one) than tumour (nine) (x2=5.01, p<0 05) utilisation is much greater in ileum (1202 (124)) These findings support the hypothesis that which suggests that TIMP is important in than in colon (p<0-01). the gastrin gene is expressed in colorectal regulating MP activity at the TMJ. It seems that while preferential glutamine cancers, and suggest that if gastrin has an These results support an in vivo role for SL, utilisation is specific to the ileum, the capacity autocrine role, it is exerted by a minority GL, and TIMP in colorectal tumour invasion for butyrate metabolism is not different in product ofposttranslational processing. and indicate a potential use for recombinant these organs. TIMP as a therapeutic agent.

Mucosal proliferation in patients with mRNA for oestrogen receptor in the large adenomas - a suitable biomarker for inter- bowel and large bowel tumours vention trials Does betelnut chewing protect Asians against ulcerative colitis? S SINGH, C J SHORROCK, M C SHEPPARD, M J S N C ARMITAGE, P CLARKE, K-A GIFFORD, L G LANGMAN (Department of Medicine, University DURRANT (Department of Surgery, University C N LEE, V JAYANTHI, B McDONALD, C S J of Birmingham) A strong positive correlation Hospital, Nottingham) Proliferation in normal PROBERT, J F MAYBERRY (Gastrointestinal Re- exists in international mortality data between colonic mucosa has been postulated as a marker search Unit, Leicester General Hospital, the incidences of breast cancer and colonic for neoplasia in high risk people and as a bio- Leicester) A questionnaire survey to study the cancers, and in individual women both cancers marker for trials of intervention. Most studies roleofsmokingin 223 Asianswithinflammatory occur together more often than expected. Sex have used 'H-thymidine labelling. We mea- bowel disease in Leicester was undertaken. Of steroids may therefore have an aetiological role sured mucosal proliferation in 70 patients the 122 who responded there were 116 patients in colorectal cancer. Ifoestrogens exert a direct undergoing colonoscopy because of new with ulcerative colitis (UC). Similar data were http://gut.bmj.com/ effect in the colon, appropriate receptors must adenomas, as adenoma surveillance or family collected from 79 healthy control subjects. The exist. We have therefore sought to show the risk or with symptoms. Proliferation was mea- mean age for male colitis patients was 41-8 presence of mRNA for oestrogen receptors in sured in colonoscopic caecal or rectal biopsy years and that for control subjects was 39-3 the large bowel. RNA extracted from freshly specimens, or both, using the metaphase arrest years. For the female patients and control collected tumours, polyps, and adjacent technique - crypt cell production rate (CCPR). subjects the mean ages were 41-1 and 35.3 years normal mucosa was analysed by dot blot There was close correlation between CCPR in respectively. Twenty three of the 69 male hybridisation to a full length human oestrogen the caecum and rectum (n= 18), r=0-72, patients with UC were either past or present receptor cDNA probe. Specificity of hybrid- p=0-001. In six patients CCPR was similar in smokers compared with 22 of the 47 control on September 24, 2021 by guest. Protected copyright. isation was shown by the presence of a single biopsy specimens taken at eight to 40 weeks subjects (X2= 1-6, NS). However, only eight band of approximately 6 Kb on northern apart. The median (range) CCPR for patients were smoking at the time of the survey com- blotting. Oestrogen receptor mRNA results with adenomas at the time of biopsy (n=22) - pared with 13 controls (X2=2O-9, p=0.05). were corrected for the amount of total mRNA 17 (6-26) crypt cells/crypt/hour - was signifi- There was no significant difference in smoking present. Oestrogen receptor values of 0-5-3.0 cantly higher than for patients under surveil- between female patients and control subjects arbitrary units were found in breast tissue lance (n=25) or with a family history (n= 16) in (X2'-= 11). Indeed, only two women admitted (positive control). High values (< 1 unit) were whom no new adenomas were found - CCPR to smoking. The relative risk of smokers with found in seven carcinomas, one polyp, and five 12 (6-26) crypt cells/crypt/hour and 11 (8-19) colitis developing UC was 0.4 (X2=2-5; 95% CI normal mucosae; moderate values (0.2-1.0) crypt cells/crypt/hour respectively or seven 1.2-0.2) while for a non-smoker the relative were found in two cancers and four normal subjects with normal colonoscopy - 13 (5-25) risk was 1-2 (XI= 12; 95% CI 2-2-0) clearly mucosae, and lower levels (<0 2) in seven crypt cells/crypt/hour. Mann-Whitney - suggesting a similar role for smoking in UC to carcinomas, six polyps, and seven normal W= 1520, p=0 02). that suggested in other European studies. Nine mucosae. Mucosal proliferation, as measured by of 69 men with colitis were regular betelnut In conclusion, the finding of oestrogen CCPR, is consistent between the right and left chewers compared with 14 of 147 control receptor mRNA in colonic mucosa and sides of the colon, is 'stable' in subjects over subjects. The relative risk of betelnut chewers tumours is evidence for the presence of oestro- time, and is higher in patients with adenomas. developing UC was 0.4 (X2=2-5; 95% CI 1-2- gen receptors, and is consistent with a role in Crypt cell production rate in rectal biopsy 0 2) which was the same as that for tobacco carcinogenesis. specimens may be used as a biomarker in smokers. Is there a common underlying dietary intervention trials in patients with mechanism? adenomas. Human colorectal cancers contain gastrin precursor Metalloproteinases and TIMP in colorectal Fluticasone propionate versus prednisolone J NEMETH, B A TAYLOR, G J DOCKRAY (Physio- tumour invasion in the treatment of active ulcerative colitis: a log;ical Laboratory and Department of Surgery, multicentre study University ofLiverpool, Liverpool) Cell culture N C CALLEGOS, C SMALES, R M HEMBRY, F J experiments and animal models have suggested SAVAGE, P BOULOS (Department of Surgery, A B HAWTHORNE, CO RECORD, C D HOLDSWORTH, a possible role for gastrin as a stimulatory University College and Middlesex School of M I KEECH, C J HAWKEY (University Hospital, growth factor in colorectal neoplasia. We have Medicine, London and Strangeways Research Nottingham; Royal Victoria Infirmary, New- assayed for gastrin and its immediate bio- Laboratory, Cambridge) In vitro studies suggest castle; Royal Hallamshire Hospital, Sheffield; synthetic precursor peptides in colorectal that tumour invasion is regulated by the inter- Glaxo Group Research Ltd, Greenfield, Middle- cancers using a battery of specific antibodies action of matrix degrading enzymes known as sex) Fluticasone propionate is a new poorly in radioimmunoassay. Tumour and normal the interstitial metalloproteinases (MP), with absorbable corticosteroid with extensive first British Society ofGastroenterology A561 pass metabolism. We evaluated its use as oral Laboratories, Wien, Austria) Trace elements AT R AXON (Gastroenterology Unit and University treatment for active ulcerative colitis (UC) in a metabolism is altered in ulcerative colitis (UC) Department ofPathology, The GeneralInfirmary, four week, double blind, multicentre trial. but their concentrations in intestinal mucosas Leeds) From 1978 to 1990 a colonoscopic

Altogether 205 patients with active UC, left are unknown. We measured trace elements in screening surveillance programme for patients Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from sided or total (taking 10 mg prednisolone or colonic mucosa and the influence of inflam- with longstanding (¢ eight years), extensive less), received fluticasone (5 mg four times a mation. (¢ splenic flexure) ulcerative colitis was under- day for four weeks) (n= 100), or prednisolone Biopsy specimens were taken at colonoscopy taken, consisting of annual colonoscopy with (n= 105) (40 mg (week 1), 30 mg (week 2), then from the right and the left colon of seven pancolonic biopsy. We have retrospectively 30 mg/20 mg or 20 mg/10 mg (weeks 3 and 4) patients with moderately active UC, five with identified 201 eligible patients who should have depending on disease activity on day 14). quiescent UC, and seven with irritable bowel been entered. Twenty three failed to be Intention to treat analysis: physicians con- syndrome (IBS). Zinc (Zn), iron (Fe), recruited, of whom 11 remain well, eight are sidered fewer fluticasone patients to be in selenium (Se), rubidium (Rb), cobalt (Co), and unaccounted for, and four developed colonic remission at two weeks (fluticasone v predniso- chromium (Cr) concentrations (ppm) were cancer. Four patients refused colonoscopy, all lone; 9% v 17%, p=0 007), but with similar assayed in colonic biopsy specimens by NAA. ofwhom remain well, and 15 await entry to the numbers (26% v 29%, p=NS) at four weeks. The mean mucosal Zn concentration in IBS programme. The remaining 159 patients had Sigmoidoscopy favoured prednisolone at two was 105 (5) with no significant variation 728 colonoscopies (4*6/patient; 692 patient weeks (grade 0 or 1: 37% v 50%, p=0O008) and between the right and the left colon. Zn years follow up). Eighty eight per cent colon- four weeks (49% v 62%, p=0028), as did four concentrations were significantly lower in oscopies reached the right colon with no mor- week patient assessment of remission (20% v active UC compared with UC in remission tality. Thirty nine patients (25%) who began 39%, p=0003) and histology (p=0O004). (84 (5) v 102 (4); p<0 02). The mean mucosal surveillance defaulted. Of these, 21 remain Efficacy analysis (n= 159) was similar. Plasma Fe concentration was 174 (21) in IBS; it was well, 17 are unaccounted for, and one died cortisol values fell significantly on prednisolone increased significantly in active compared with of colonic cancer. Surveillance detected one (mean (SEM) 310 (41) to 57 (21) nmolIl) inactive UC segments (284 (45) v 174 (28); Duke's A cancer. During this period there compared with fluticasone (306 (31) to 303 (24) p<005). The Se mucosal concentration in IBS were three other cases of colonic cancer in nmol/l) by week four, p<0-001. Prednisolone was 1-2 (2), Rb 28 (4), Co 0 04 (0-01) and Cr 2-0 association with ulcerative colitis at this centre, caused more steroid side effects (seven v one) (0.3) with no difference being found in UC two in patients erroneously believed to have and significantly higher blood pressure than mucosa. only proctitis and one in a patient with colitis fluticasone. In conclusion, the trace elements profile in ofonly seven years' duration. Thus only one of In conclusion, fluticasone, 5 mg four times a different segments of human colon can be nine colitis related cancers were detected by the day, is less effective than prednisolone in active determined in less than 3 mg tissue. Active UC surveillance programme. UC, but has minimal steroid side effects. A is associated with low Zn and high Fe mucosal The results of this large study cast serious higher dose may have a greater effect, without values: Zn depletion can affect mucosal repair doubts on the effectiveness of colonoscopic producing adrenal suppression or steroid side while Fe accumulation may have scavenger screening/surveillance programmes in detect- effects and merits further study. protective effects. ing colonic cancer in patients with ulcerative colitis.

Incidence of ulcerative colitis in Leicester, Defunctioned rectum in ulcerative colitis - a antibodies in inflammatory 1972-89 source of diagnostic confusion Lipocortin-1 http://gut.bmj.com/ bowel disease C S J PROBERT, V JAYANTHI, J F MAYBERRY B F WARREN, N A SHEPHERD, D C C BARTOLO, (Gastrointestinal Research Unit, Leicester J W B BRADFIELD (Departments ofHistopathology, T R J STEVENS, S F SMITH, T SMITH, R J FLOWER, General Hospital) A retrospective study of all Bristol Royal Infinnary, Bristol; Gloucestershire D S RAMPTON (GI Science Research Unit, London potential cases ofulcerative colitis in the city of Royal Hospital, Gloucester; and Department of Hospital Medical College, Department ofMedi- Leicester was performed. Cases were identified Surgery, The Royal Infirmary of Edinburgh, cine, Charing Cross and Westminster Hospital from registers held by hospitals, pathology and Edinburgh) Patients with acute ulcerative and Department of Biochemical Pharmacology, endoscopy departments, general practitioners colitis frequently undergo total colectomy with St Bartholomew's Hospital Medical College, and personal indexes were reviewed. Only ileostomy and preservation of a rectal stump. London) Antibodies to lipocortin-l (LC-1), a on September 24, 2021 by guest. Protected copyright. cases diagnosed in the city during the study This is a study of 15 of these patients who corticosteroid inducible protein that inhibits period were included. Proctitis and other forms subsequently had the stump resected. The phospholipase A2 activity, and therefore eioco- of colitis were excluded. Population data were macroscopic and microscopic features of the sanoid synthesis, have been detected in active taken from the 1983 Survey ofLeicester and the total colectomy specimens have been reviewed systemic lupus erythematosus and steroid City Council projection for 1989. and all showed classic acute fulminating treated rheumatoid arthritis. We have now Altogether 181 cases occurred in indigenous chronic ulcerative colitis. In none of the sought antibodies to LC- 1 by ELISA in Europeans and 100 in Asians, 77 ofwhom were patients was there any clinical, radiological, patients with inflammatory bowel disease first generation migrants. The incidence in or pathological evidence of Crohn's disease. (IBD). Europeans from 1972-80 was 3.94/105/year Microscopically, all the rectal stumps showed Sera positive for IgM LC- 1 antibodies (95% CI 3-4 8) and that for Asians was 6-7/105 predominant mucosal disease. The mucosa occurred in 10 of 29 ulcerative colitis patients year (95% CI 4.5-8 8). Asians again had sig- showed crypt distortion, crypt abscess form- (mean (SEM) 30-1 (3.1) ELISA units com- nificantly more ulcerative colitis than Euro- ation, mucin depletion, and diffuse inflam- pared with positive standard; p<001) and peans (z=2.7, p<0-01, relative risk 1.7, 95% mation - all the hallmarks ofchronic ulcerative seven of21 Crohn's disease patients (31-2 (3.4); CI 1-2-2-5). From 1981-9 the incidence for colitis. There were, however, additional find- p<0005) compared with one of 17 healthy Europeans increased a little to 4.6/105/year ings, including lymphoid follicular hyperplasia controls (18-6 (1-8)). There was no relation (95% CI 3-6-5.6) and to 9.3/105/year (95% CI in 12 patients, transmural inflammation in the between LC-1 antibody values and disease 7-11-5) for Asians. Asians still have signific- form of lymphoid aggregates (nine), gran- activity, site, or treatment with sulphasalazine antly more ulcerative colitis than Europeans ulomas (four), and fissures (eight). Pseudo- or topical steroids. However, antibody values (z=4.3, p<0-001, relative risk 2, 95% CI membranous exudates were seen in four. The were lower (21-6 (2.7); n=9) in IBD patients 1-5-2-8). results of this study indicate that Crohn's requiring oral prednisolone (median 15 mg) for The high incidence of ulcerative colitis in disease like features are very commonly found >two months (median 11 months) because of Asian people in Leicester is unexpected and in the defunctioned rectum ofulcerative colitis. continued disease activity or repeated relapse may lead to a better understanding ofaetiology. Biopsy specimens and resections of the stump on steroid withdrawal, than in patients may lead the unsuspecting pathologist to an responding promptly to this treatment (median erroneous diagnosis ofCrohn's disease, and the dose 20 mg) (34.9 (7.3); n-7, p<0O005) or not patient may therefore be denied the advantages taking steroids at all (36-7 (3.9); n=21; Trace elements in ulcerative colitis mucosa: of a subsequent pelvic ileal reservoir. pstomach and the response compared with J R M VAN DER SIJP, J M D NIGHTINGALE, M A UC, one CD) judged by concurrent contrast that of a standard 1000 kcal meal. Twelve KAMM, E WALKER, M GRANOWSKA, K BRITTON, radiology or colonscopy, or both (sensitivity normal men (mean (SD) age 22-4 (1.0) years) L M A AKKERMANS, J E LENNARD-JONES (St 82%, specificity 100%). All of four scans were were studied on two separate occasions. After Mark's Hospital, London) Upper gastro- positive in acute colitis (two UC, two CD) when an overnight fast a 4 lumen perfused tube intestinal symptoms are frequent in women contrast radiology/colonoscopy were deemed assembly was inserted into the unprepared with severe idiopathic constipation (SIC). unsafe. Of five scans done to assess disease sigmoid colon and a gastric balloon into the After subtotal colectomy these patients often activity, four were true positives and one true antrum ofthe stomach. Colonic pressures were still experience pain and may develop recurrent negative compared with clinical and laboratory analysed for activity index (AI - area under constipation or diarrhoea. We assessed gastric studies. No scans were done to look for CD curve, mmHg/minute) for the study segment emptying rate and small bowel transit for solids related abscess. In 14 patients with symptoms (sum of all four channels) by computer. and liquids in these patients. suggestive of IBD, nine scans were ultimately Balloon distension and meal stimuli were ran- We studied 12 women with SIC (mean age shown to be true negatives, one false positive; domly allocated and given after a 30 minute 35, range 24-46 years, stated bowel frequency four patients with negative scans had no other basal period, and recordings continued for a <1/week) and 12 healthy control subjects imaging. further 90 minutes. AI during balloon disten- (eight women and four men, mean age 33, In conclusion, 9Tc-HMPAO scanning in sion did not significantly (p=0.59) increase range 19-49 years). Solid phase transit was known or suspected IBD was uniquely useful above basal mean (SEM) 627-7 (151.4) mmHg/ measured using a 560 kcal pancake containing http://gut.bmj.com/ in 10% patients, all of whom had active colitis. minute v 557-7 (109-6)), whereas there was a 20 MBq "'In microspheres and liquid transit In 10% patients, scans were misleading, and in significant (p<0.02) increase in AI after the using 195 ml orange juice with 40 MBq 9Tc- most, although less unpleasant, scans gave standard meal (1432-0 (226.4) v 864-6 (147-9)). EDTA. Time activity curves were constructed little further information than conventional These data show that gastric distension has no for gastric emptying. Small bowel transit was tests. effect on colonic pressure activity, and plays no the difference beween head of column ("'In) part in the gastric phase ofthe colonic pressure entry into duodenum and into caecum. The response to food. first "'In in stool indicated colonic transit time.

While early gastric emptying was normal, on September 24, 2021 by guest. Protected copyright. Renal toxicity tests in patients with quiescent patients with SIC had a residue up to 48% of colitis solids and 40% of liquids at six hours (liquid Alteration ofviscosity in the ascending colon median 9 v 0%, p<0-01 median (Mann- S A RILEY, D LLOYD, V MANI (Department of by different dietary substances: effect of Whitney U test); solid 11 v 0% p<0-01 retained Medicine, Hope Hospital, Salford and Depart- lactulose induced accelerated colonic transit at six hours). Small intestinal transit time was ment of Chemical Pathology and Gastroenter- slower in SIC (75 v 55 minutes, p<0-01). Four ology, Leigh Infirmary, Leigh) Mesalazine has L BARROW, K P STEED, P J WATTS, C D MELIA, M C patients had a residue for liquid and solid of structural similarities to aspirin and phenacetin DAVIES, C G WILSON, R C SPILLER (Departments of <3% left at six hours, which coincided with and in high doses is nephrotoxic in rats. We Physiology and Pharmacology, Pharmaceutical small bowel transit times at the upper limit of have therefore studied sensitive indicators of Sciences and Therapeutics, University ofNotting- our normal range. Colonic transit was slow in renal toxicity in patients taking long term ham, Nottingham) Ispaghula husk and guar all patients (30 v 96 hours, p<0-01; three mesalazine. gum are gelling agents that increase the vis- patients passed no stool in seven days. Sixty two patients (32 men, aged 28 to 82 cosity of gut contents and enter the colon In conclusion, patients with severe idio- years) with quiescent colitis were studied. unaltered. Subsequent loss of viscosity by pathic constipation have a motility disorder of Thirty four had been maintained on oral bacterial degradation is, however, more rapid the stomach and small bowel and the colon. mesalazine 1-6 (0 8-2 4) g/day for 2-9 (0 5-6.9) for guar. Using a non-invasive gamma scinti- Upper gastric symptoms can be explained by years and 28 had been maintained in sulpha- graphic technique, we have previously shown the large gastric residue found in some of these salazine (2-3 g/day). Groups were comparable that lactulose accelerates transit through the patients. for age, sex, and disease duration and extent. ascending colon (AC) (GE 1989; 98: A394) Creatinine clearance and the excretion of providing a model for diarrhoeal diseases. We markers of (i) glomerular dysfunction: albu- now report the effect on colonic transit of men and transferrin, and (ii) tubular dysfunc- altering the viscosity of the AC with ispaghula Pelvic floor causes of obstructed micturition tion: ot-1-microglobulin and N-acetyl-,B-D- (3.5 g three times a day after meals) or guar (5 g in women glucosaminidase were measured in each three times a day before meals) for four days, patient. using the same technique, in 16 healthy volun- A C THORPE, D F BADENOCH, N S WILLIAMS Creatinine clearance values correlated neg- teers in whom stool frequency was doubled by (Departments ofSurgery and Urology, The Royal atively with age (r=-0 44 p<0 01) but were ingesting lactulose (20 ml three times a day) for London Hospital, Whitechapel, London) Of comparable in the two groups. Abnormal four days. On day four fasting volunteers also numerous hypotheses advanced to explain excretion of at least one marker was found ingested IMBq of "'In labelled 180-250 tim retention of urine in women, proctological in nine of 28 (32%) patients maintained on particles contained in two enteric coated cap- causes have seldom attracted attention, sulphasalazine and five of 34 (15%) on mesala- sules which disintegrated in the ileocaecal although rectocele is commonly observed in zine. Marker to creatinine excretion ratios, region. Serial anterior and posterior scintiscans women with voiding dysfunction. however, were not significantly different. No were obtained at 30 minute intervals for 16 We have developed a new method whereby correlations were found between markers of hours and at 24 hours. Time activity curves the rectum and bladder can be studied simul- British Society ofGastroenterology A563 taneously during defaecation and micturition. normal coordinated activity. A refractory (B2>B3=B4). A clone of B3 (B3c) gave a The study allows synchronous radiographic period with absent neurotransmission can be different DNA fingerprint to B3 indicating that visualisation of the bladder and rectum, intra- induced by excess stimulation. B3 was a mixed culture. Isolate B4 and a guinea rectal and intravesical pressure monitoring, pig isolate, GP, showed different fingerprint and electromyographic surveillance of the patterns with and without bile, suggesting that Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from puborectalis muscle activity. These combined changes in environmental conditions gave a studies have unexpectedly shown that many of PAEDIATRICS subdominant strain a growth advantage over these women have inappropriate contraction the others. ofthe puborectalis during micturition. Thus, human infection with Giardia may Sixteen female patients, average age 45 years consist of multiple strains with variable anti- (range 21-83 years) suffering with chronic Optimising the efficacy of polymeric oral biotic and bile sensitivities. This may explain constipation have been investigated by simul- rehydration solutions: studies in a model of the failure of previous studies to identify viru- taneous dynamic integrated Emg proctography rotavirus diarrhoea lence markers. and cystometrography. Six were able to mic- turate normally. Ten were either unable to A V THILLAINAYAGAM, J A DIAS, A F M SALIM, micturate or micturated by abdominal strain- MJ G FARTHING (Department ofGastroenterology, ing, and of these all but two had an inapprop- St Bartholomew's Hospital, London) Complex Modulation of expression of an immuno- riate contraction of puborectalis during mic- carbohydrate oral rehydration solutions (ORS) dominant Giardia antigen by components of turition compared with only one in the group diminish stool output and total ORS require- the gastrointestinal tract who micturated normally (p=0-02, Fisher's ments, but the optimal size and concentration exact test). Eight of the 10 abnormal mictura- of glucose polymer are not established. We S CHAR, A M CEVALLOS, M J G FARTHING (Depart- ters had a rectocele, compared with four of the have investigated the effects on water absorp- ment ofGastroenterology, St Bartholomew's Hos- six normal micturaters (p=0.5). However, in tion of varying the concentraton of a glucose pital, London) We have described previously a the abnormal micturating group, seven of the polymer of mean chain length G5. Three 57 kDa immunodominant Giardia antigen. As eight women with a rectocele also had polymer (P) ORS (9, 18, 36 mmol/l; 159, 168, it is becoming apparent that heat shock pro- inappropriate contraction of puborectalis, 186 mOsm/kg respectively) were compared teins are prominent antigens in the immune compared with none of the four women who with ORS of identical electrolyte response to a variety of infections, we have were able to micturate normally (p=0 02). (Na 60 mmol/l) content containing equivalent explored the possibility that this antigen is a These results suggested that in women with amounts of free (G) glucose (45, 90, heat shock/stress protein. obstructive voiding, in whom there is no 180 mmol/l; 195, 240, 320 mOsm/kg) by small Giardia trophozoites colonise the hostile obvious urological abnormality, a proctological intestinal perfusion in normal and rotavirus environment of the upper small intestine and or pelvic floor abnormality should always be infected neonatal rats. hence the expression of the 57 kDa antigen was considered, and a combined study may help to In normal (P9-ORS mean (SEM) 291-4 studied at the level of protein synthesis after elucidate the underlying condition. (16-4) G45-ORS 220-8 (8.4); P18-ORS 331-9 exposing cultured Giardia trophozoites in vitro (13-1), G90-ORS 240 (21); P36-ORS 284-3 to a variety of conditions (pH, increased (11-8), G180-ORS 79.4 (14-5) dl/g/minute; temperature, bile, duodenal fluid) closely p<002) and rotavirus infected intestine resembling the environment of the human Simulated defaecation: demonstration of (P9-ORS 232-8 (6), G45-ORS 116-7 (25 5); gastrointestinal tract. Trophozoites were colonic peristalsis with anal relaxation and P18-ORS 277-2 (20.5), G90-ORS 68-7 (12-4); metabolically labelled with ("5S)-methionine rectal contraction P36-ORS 166 (18-2), G180-ORS 21 (11-6) lil/g/ and proteins analysed by SDS-PAGE, immuno http://gut.bmj.com/ min; p<0005), P-ORS promoted greater blotting with Mab to the 57 kDa antigen, and J R M VAN DER SIJP, M A KAMM, J E LENNARD- water absorption than equivalent G-ORS. In fluorography. Shifting trophozoites to medium JONES (St Mark's Hospital, London) Although rotavirus, increasing the polymer concentra- containing 10% human duodenal aspirate mass movements are known to be responsible tion from 18 to 36 mmol/l resulted in a relative (normal and immune) depressed normal for colonic transport, it is not known whether fall in water absorption (p<0.01). The hyper- protein synthesis but enhanced synthesis of the anal relaxation occurs as part of colonic tonic G180-ORS promoted least water absorp- 57 kDa antigen. A temperature shift from 37'C peristalsis. It is also not known whether the tion (p<0-01). None of the ORS could reverse to 42°C also increased expression ofthis antigen rectum contracts during defaecation. In severe rotavirus induced net secretion of sodium, showing that it is a heat shock/stress protein. on September 24, 2021 by guest. Protected copyright. constipation, is the colon capable of coordi- which was similar from all ORS. When trophozoites were transferred from a pH nated peristaltic motor activity? We have These findings: (i) emphasise using glucose neutral to alkaline environment expression of addressed these questions using a combined polymer as substrate in ORS greatly enhances the 57 kDa antigen was again enhanced. colonic manometric and radioisotope study. efficacy; (ii) confirm the adverse consequences The in vivo regulation of expression of the Five severely constipated women (age 30-45 of high solute concentration; (iii) indicate the 57 kDa antigen by these factors suggests that years, <1 bowel action per week) and one optimum concentration for this polymer may this antigen plays an important role in host- normal man (age 58 years) were studied. Two lie between 9 and 18 mmol/l. parasite interaction. women were studied twice. An eight channel perfused manometric tube was colonoscopic- ally inserted to lie in the whole or left colon, with three pressure ports in the anal canal. The Genomic evidence for multiple strain in- STOMACH patient was positioned under a gamma camera. volvement in Giardia lamblia infection Bisacodyl 5 mg colonic infusion was used to initiate motor activity, and transport was S CARNABY, T D McHUGH, P H KATELARIS, observed using two isotopes: Tc99m and "'In. MJ G FARTHING (Department ofGastroenterology, Chemical gastritis and Helicobacter pylori in In all subjects, bisacodyl caused high pres- St Bartholomew's Hospital, London) It has been patients receiving non-steroidal anti- sure (up to 130 mmHg) colonic waves which postulated that Giardia lamblia is a species inflammatory drugs - correlation with peptic progressed distally, included early anal relax- complex consisting of several morphologically ulceration ation which is characteristic of true peristalsis, identical cryptic strains present in the same and resulted in defaecation. Rectal contrac- infection. To investigate this we have S D TAHA, I NAKSHABENDI, P BOOTHMAN, F D LEE, tions were seen to be part of this peristalsis. developed a DNA fingerprinting technique C G GEMMELL, R D STURROCK, R I RUSSELL Simultaneous movement of radioisotope con- using the M 13 bacteriophage genome and (Departments of Gastroenterology, Pathology, firmed transport. Stimulation at two colonic examined sequential Giardia isolates and their Microbiology, and Rheumatology, Royal In- sites showed unresponsiveness on the second clones from a patient with chronic infection. In firmary, Glasgow) Non-steroidal anti-inflam- stimulation; a repeat study which produced a addition we have used bile, a growth stimulant, matory drugs (NSAIDs) have been linked to response proved that this was due to a colonic to enhance strain heterogeneity by environ- the development of a distinctive histological refractory period. The test was painful in the mental selection. picture known as chemical gastritis. We aimed normal man - therefore no more normal sub- The three sequential isolates from the same to study the importance of this entity in jects were studied. infection in the same patient, B2 (pretreatment) comparison with gastritis found in association In conclusion, during simulated defaecation, and B3 and B4 (following two consecutive with Helicobacter pylon' in patients taking anal relaxation occurs as part of colonic treatments with metronidazole) had unique NSAIDs. peristalsis which transports colonic contents M13 DNA fingerprints, indicating that they Patients were included if they took NSAIDs and includes rectal contraction. In severely are different strains. A decrease in sensitivity to for a minimum of four weeks and excluded if constipated women the colon is capable of metronidazole supported this observation they had had antiulcer therapy or antibiotics. A564 British Society ofGastroenterology

H pylon' was detected in antral biopsy speci- H pylonr infection stimulates mucosal ROS Prevalence of IgG, IgA, IgM to Helicobacter mens by histology and bacteriology. Chemical production, we compared 75 FM luminol- pylori in 1018 blood donors gastritis was studied in antral tissue and defined dependent chemiluminescence (CL) in Hpylon' as the presence of foveolar hyperplasia, vaso- positive and negative endoscopic biopsy speci- D VAIRA, M MIGLIOLI, J HOLTON, M VERGURA, dilatation, oedema, paucity of inflammatory mens taken from antra mildly, or less, inflamed V MODUGNO, A NANNE-rrI, L BARBARA (lst Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from cells, and the presence of muscle fibres in the (Lanza grade <3). Mucosal inflammation was Medical Clinic, University ofBologna, Italy and lamina propria. All assessments were double also scored microscopically (routine histology Department of Microbiology, The Middlesex blind. and myeloperoxidase staining for neutrophils); Hospital, London) The aim of this study was to A total of218 patients were studied: 174 took H pylori was sought by a urease dependent assess the levels of IgG, IgA, and IgM to NSAIDs and 44 did not. Chemical gastritis was indicator system. Helicobacter pylori in Italian blood donors and found in 46 patients in the NSAID group (26%) H pylori positive biopsy specimens produced correlate the results with the age, sex, and and in three (7%) subjects not on NSAIDs more CL (median 8.73x 103 photons/minute/ blood group of the subject. The levels of the (x2=7 95, p<0-01). Ulcers, at least 5 mm in mg (range -2-8 to 544), n=27) than negative IgG only in 545 subject have been previously diameter, were identified in 68 patients on mucosa (-0 49, (-2-4 to 2.9), n=18, reported. NSAIDs, and were distributed according to p<0-001). Macroscopic grading was similar in A total of 1190 blood samples were collected the following histological findings: ulcers were the two groups (Hpylori positive median Lanza from 1018 blood donors (M/F: 559/459) from found in 16 of 72 (22%) patients without grade 1, (0-3); Hpylori negative 1, (0-2), NS). the Emilia-Romagna region of Italy. The sub- H pylori or chemical gastritis, in 27 of 56 Although there were no histological dif- jects were grouped into group I: 18-25 years patients (48%) with H pylori gastritis x2=9.09, ferences, myeloperoxidase staining to date (189:M/F:112/77), group II: 26-35 years p<0-01), and in 25 of 46 (54%) patients with showed significantly more neutrophils in posi- (216:M/F: 122/94), group III: 36-45 years chemical gastritis x2= 12-72, p<0-001). tive (260 arbitrary units (156-400), n= 11) than (243:M/F:123/120), group IV: 46-55 years NSAID related peptic ulcers occur more in negative antral mucosa (93, (68-123), n=3, (209:M/F:101/108), and group V: 56-65 years commonly in patients with chemical gastritis or p=O-Ol). For Hpylori positive but not negative (161:M/F:101/60). A standard ELISA tech- H pylori. patients, antral CL was related to duodenal nique was used to assess the IgG, IgA, and IgM macroscopic grading (Spearman's R= +0-4, levels to H pylori. p<0 05), which itself correlated with duodenal No correlation was found between blood CL (R= +0-89, p=0-0001). groups and seropositivity or sex. An increase in Helicobacter pylori in the aetiology of non- Production of ROS is increased in H pylori IgG levels correlated with age was observed ulcer dyspepsia infected antral mucosa, in part at least, because (group I:17%, group II:34%, group III:47%, of neutrophil infiltration. H pylor enhanced group IV: 55%, and group V:50%). A similar C HOLCOMBE, C THOM, J KALUBA, S B LUCAS ROS production could mediate damage in the trend was observed for the IgA levels in the five (INTRODUCED BY P SMITH) (University of antrum and in metaplastic gastric mucosa groups: 20%, 19%, 31%, 32%, and 35% for Maiduguri, Nigeria and University College and associated with duodenal ulceration. groups I to V respectively. No difference Middlesex School of Medicine, London) Non- between sexes was observed. The number of ulcer dyspepsia is common in Africa, but is subjects with high IgM levels to H pylori was Helicobacter pylori infection aetiologically im- found to decrease in the five age groups: 64%, portant in an environment in which most ofthe 46%, 45%, 36%, and 33% for groups I to V population are infected? Western blotting analysis of mucosal and respectively. In an endoscopic study ofpatients with non- systemic immune responses to Helicobacter In conclusion, (1) no correlation was found ulcer dyspepsia in northern Nigeria, 120 of 138 pylon with blood groups according to the age or sex or http://gut.bmj.com/ patients (87%) had H pylori infection. This did seropositivity; (2) above the age of 55 the not, however, differ significantly from the level J E CRABTREE, J D TAYLOR, T M SHALLCROSS, seroprevalence of H pylon as detected by IgG of infection in 40 asymptomatic controls, 32 of J I WYArT, B J RATHBONE, R V HEATLEY (Depart- does not seem to increase; and (3) the number whom (80%) were infected. ments of Medicine and Pathology, St _James's of subjects with high IgM seems to decrease Altogether 138 patients entered a thera- University Hospital, Leeds) Mucosal and sys- with increasing age. peutic trial of antacid (Gelusil, 1 tablet four temic humoral responses to Helicobacter pylori times a day) v bismuth and amoxycillin (De have been investigated by western blotting to

Nol 125 mg four times a day for four weeks and compare isotype responses and antigen recog- on September 24, 2021 by guest. Protected copyright. amoxycillin 500 mg four times a day for the first nition patterns. In vitro culture supernatants Eradication of H pylori reduces hypergas- 14 days). Symptom resolution occurred in 28 of from endoscopic antral biopsy specimens (48 H trinaemia due to proton pump inhibitor 86 patients given bismuth and amoxycillin and pylori associated gastritis, 12 histologically therapy in one of 32 given antacid (p<0-01). Of those normal, five with reflux gastritis) and concur- originally infected by H pylori, the organism rent sera were immunoblotted for IgG, IgM, K E L McCOLL, C DORRIAN, A EL NUJUMI, was cleared in 29 of 61 patients who had and IgA Hpylori antibodies. A MACDONALD (Department of Medicine and received bismuth and amoxycillin and in none A strong mucosal IgA (but little IgM) res- Therapeutics, Western Infirmary, Glasgow) ofthose given antacid. However, in those given ponse to H pylori was observed in all patients Serum gastrin concentrations increase during bismuth and amoxycillin, symptom resolution with H pylori associated gastritis. Mucosal IgA treatment with proton pump inhibitors was not related to H pylori clearance. recognition of 120, 90, 61, and 31 KD proteins because of increase in intragastric pH. Helico- In northern Nigeria H pylori infection is very occurred in 77%, 79%, 98%, and 69% of bacter pylori infection also raises serum gastrin. common in patients with non-ulcer dyspepsia positive subjects respectively. H pylori positive We have investigated the effect of H pylori and asymptomatic control subjects. The lack of patients showed astrongsystemic IgGresponse, status on the gastrin response to the proton symptomatic improvement related to H pylori but only 17-6% were positive systemically for pump inhibitor SK&F 96022. clearance suggests that it does not play a IgA Hpylori antibodies. Comparison ofantigen Thirteen duodenal ulcer (DU) patients with significant aetiological role in non-ulcer dys- recognition patterns ofserum IgG and mucosal H pylori infection were studied. Seven of them pepsia in this environment. IgA in individual patients showed common received triple anti-H pylori therapy, resulting recognition of many H pylori antigens (that is, in eradication of the infection, and this was 120, 90, and 61 KD) but also showed mucosal associated with a mean fall of30% in their basal IgA responses to proteins not recognised sys- gastrin concentration and a 41% fall in their Enhanced production of reactive oxygen temically. To confirm the local origin of peak post prandial gastrin concentration. All species by gastric antral mucosa infected H pylori IgA antibodies, gastric mononuclear patients then had their 24 hour intragastric pH with Helicobacter pylori cells purified from endoscopic biopsy speci- and basal and meal stimulated gastrin measured mens from 24 patients were cultured in vitro before and after five days' treatment with G R DAVIES, N J SIMMONDS, T R S STEVENS, for six days and the supernatants immuno- SK&F 96022, 40 mg/day. A GRANDISON, D S RAMPTON (Departments of blotted. All 17 patients with H pylor associated The percentage increase in gastrin con- Gastrointestinal Science, Histopathology, and gastritis were positive in IgA immunoblots. centrations on SK&F 96022 was similar in the Microbiology, The London Hospital Medical Western blotting analysis is a highly sensi- H pylori positive (84%) and H pylori eradicated College, London) The mechanisms by which tive means of examining mucosal immune res- (81%) patients, resulting in higher gastrin Helicobacter pylori infection causes antral gas- ponses to H pylori. A specific mucosal humoral values in the former (median basal= 109 ng/l, tritis and duodenal ulceration are unknown. response has been characterised and we have prandial=159) than in the latter (basal=71, We have previously shown generation of reac- identified that the major IgA response to prandial=90) (p<0 05). The intragastric pH tive oxygen species (ROS) by inflamed and H pylori infection results from mononuclear on SK&F 96022 was similar in the two groups. ulcerated duodenal mucosa. To see whether cells within the gastric mucosa. This study shows that eradication ofHpylori British Society ofGastroenterology A565 infection provides a means of limiting hyper- Mean in vivo urease activity, expressed as specimens. It was not inhibited by oligomycin, gastrinaemia and its potential adverse effects excess 6 "CO2 excretion, was 27-9 (2.6), (range sodium azide, or vanadate nor was it dependent during proton pump inhibitor therapy. It also 8-63)/mi. Specific in vivo urease activity (mean upon potassium or oxalate. It was inhibited by indicates that H pylori induced hypergastri- (SEM) was 74 (3.6) (range 34-116), and did not trifluoperazine, a calmodulin antogonist. Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from naemia is unlikely to be the result of an increase correlate with in vitro urease activity, while Topographical determination of this enzyme in antral surface pH by bacterial ammonia. total in vitro urease activity was dependent on through the purification of the brush border the concentration of bacteria (r2=0.76). membrane (BBM) showed a 13 fold enrich- Therefore in vitro urease activity is depen- ment in leucine aminopeptidase (BMM mar- dent on the number of organisms present and ker), and a 5 7 fold enrichment in Ca-ATPase. Helicobacterpylori serology or endoscopy in the variation of the 3C-UBT is due to variation Glucose-6-phosphatase, an endoplasmic reti- young dyspeptic patients? in the number ofHpylori, showing that the "3C- culum marker, was only enriched threefold and UBT is a quantitative measure of the extent of there was a 0-8 fold reduction in sodium- J S A COLLINS, K B BAMFORD, J M SLOAN, H pylori infection. potassium dependent ATPase (basolateral B J COLLINS, R J MOOREHEAD, A H G LOVE (Royal membrane (BLM) marker). This suggests that Victoria Hospital, Belfast and Departments of Ca-ATPase is probably not located on the Microbiology, Pathology, Medicine, andSurgery, endoplasmic reticulum and is not confined to The Queen's University of Belfast) Serological Effect on omeprazole in Helicobacterpylori the brush border. screening for Helicobacter pylori antibodies has This low affinity Ca-ATPase was measured been suggested as a method to reduce endo- J SHARP, R P H LOGAN, M M WALKER, in biopsy specimens taken from nine patients scopy workload. In this study, serology results P A GUMMETT, J J MISIEWICZ, J H BARON (Central before and after gluten free diet. Clinical were compared with endoscopy/biopsy speci- Middlesex and St Mary's Hospitals, London) response was confirmed histologically and by a mens in dyspeptic patients under 45 years of Omeprazole is a potent inhibitor ofgastric acid significant increase in alkaline phosphatase age. secretion and may affect Helicobacter pylori. (p<0-01), an enzyme disproportionately found Gastric biopsies from all patients were This study prospectively examines the effect of on the enterocyte plasma membrane (70% examined for H pylon associated gastritis. omeprazole on H pyloni in 25 patients (15 men, BBM, 30% BLM). There was no significant Serum antibodies were measured using an median age 43 years, range 22-65). Indications concomitant increase in Ca-ATPase activity. ELISA assay with positive cut off of for endoscopy and omeprazole were grade We conclude that this low affinity Ca-ATPase >10 ,ug/ml. Of 87 patients, 30 had duodenal I/III reflux oesophagitis (n= 13) or duodenal is unlikely to be related to active calcium ulcer (DU), three oesophagitis, one gastric ulcer (DU) not healed by H2 antagonists absorption across the enterocyte plasma mem- ulcer, and 53 non-ulcer dyspepsia (NUD). (n= 12). H pylon was detected by "3C-UBT brane since improvement in morphology and H pylon was detected in biopsy specimens of (positive=expired breath excessb63CO2 of >5) enzyme structure of the brush border is not 93-3% and 49-1% of DU and NUD patients and at endoscopy by antral histology matched by an increase in Ca-ATPase activity respectively. Serological positivity was found (H&E/Gimenez stains, with grading (grades in patients with coeliac disease. in 93% of DU and 49% of NUD patients. The 0-3) ofdensity ofHpylori, other bacteria (OB), sensitivity ofserology for Hpyloni infection was and gastritis (Whitehead) before, after four 94.8% and specificity 89 7%. However, the weeks omeprazole 40 mg mane, and two weeks predictive value for a positive test for DU was after stopping treatment ("C-UBT only). Reduction of duodenal folds seen at endo- only 48%, while the predictive value of a Fifteen of 25 (60%) patients had H pylon scopy is predictive ofcoeliac disease negative test for DU was 93%. before treatment diagnosed by histology and We conclude that serological screening is a "C-UBT (mean excess b "CO2=25.3 per mil D P K NG, A S McINTYRE, J SMITH, J AMOAH, http://gut.bmj.com/ highly sensitive test for H pylori infection. (sem 2.3). After four weeks omeprazole the R G LONG (Medical Research Centre, City Hos- While a positive test discriminates poorly density of H pylon on antral histology had pital, Nottingham) Loss of Kerkring's folds in between DU and NUD patients, a negative test decreased, with 4/15 becoming negative the upper small bowel has been observed has a high predictive value. Combined with (p<005). However, all 15 remained positive during barium meal studies in patients with clinical findings, serological screening could by 3C-UBT, excess 6 "3C02= 19-2 (sem=2-56, coeliac disease. Recently, similar changes have reduce workload in young patients. pO0 1). All seven patients with isolated lactase is not possible without assessing the extent of other bacteria. deficiency had normal folds. Two patients with H pylori infection. Endoscopic biopsy, of less giardiasis had folds that looked normal endo- than 0-1% of the gastric mucosa, is liable to scopically. Fifteen patients had coeliac disease, sampling error, whereas the "C urea breath test 11 ofwhom had abnormal macroscopic appear- ("C-UBT) assesses the entire gastric mucosa. SMALL BOWEL ances as compared with two of 60 patients with The aim of this study was to correlate in vitro partial villous atrophy (p<0-001 Fisher's and in vivo urease activity, thereby verifying exact test). The positive predictive value of the 'C-UBT as a quantitative measure of macroscopically abnormal folds indicating H pylori. Low affinity ATPase calcium compared in coeliac disease was 85%. The appearances were Twenty eight patients (16 men, median age coeliac patients before and after gluten with- specific (value: 95% confidence interval) (97%: 45 years) with duodenal ulcer (n= 15), non- drawal 89-100%) with good sensitivity (73%:45-92%). ulcer dyspepsia (NUD) (n= 10) and H pylori Similarly, the predictive value of macroscopi- detected by antral culture (microaerophilically, D P K NG, R G LONG (Medical Research Centre, cally abnormal folds indicating histological Oxoid SR147, for seven days) and histology City Hospital, Nottingham) Active calcium abnormality (total or partial villous atrophy), (H&E and Gimenez, with Whitehead grading absorption occurs through enterocytes of duo- which occurred in 10 of 17 compared with three of gastritis) were studied. In vivo urease denum and upper jejunum. Coeliac disease is of 38 patients (p<0-0001), was 77% with a activity was determined by standard 3C-UBT complicated by calcium malabsorption, which specificity of95%:86-98% and sensitivity 59%: within 24 hours of endoscopy. The in vitro improves with a gluten free diet. We have 34-81%. Thus, the endoscopic appearance of urease activity of H pylori was determined by compared low affinity calcium ATPase reduced or absent duodenal folds is a relatively assaying the rate of ammonia formation using (Ca-ATPase) activity in biopsy specimens sensitive and specific indicator of coeliac the Berthelot method ([mol/min) during in- taken from patients before and after treatment. disease. Biopsy of the duodenum if folds look cubation ofstandardised pure bacterial suspen- We have characterised a low affinity reduced or absent should increase the rate of sions with excess urea. Ca-ATPase from human duodenal biopsy detection of coeliac disease. A566 British Society ofGastroenterology

Small bowel enteroscopy in undiagnosed in superior mesenteric artery blood flow and bile salt retention scan is a useful diagnostic gastrointestinal blood loss cardiac output tool in patients with 'post infective' chronic diarrhoea. A J MORRIS, L WASSON, J F MACKENZIE (Gastro- A F MULLER, A J COWLEY (INTRODUCED BY intestinal investigation unit, Royal Infirmary, C J HAWKEY) (Department ofMedicine, Univer- Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from Glasgow) We have used a 2:7 m Sonde type sity Hospital, Nottingham) The digestion of a enteroscope (Olympus Co XSIF-SW) to per- meal is a metabolically active process, the Effects of chronic ethanol intake on small form small bowel enteroscopy in 60 patients. energy requirements of which are met by both intestinal and hepatic monoamine oxidase in The procedure took a median (range) of 6 an increase in gut blood flow and cardiac the rat (4 5-7 5) hours and a median (range) of 195 output, although the mechanisms responsible (90-260) cm from the nares was examined. We are unclear. This study assessed the relation N P KENNEDY, G T M HENEHAN, G S A McDONALD, have introduced the technique of continuous between the postprandial changes in superior K F TIPTON, D G WEIR (Department of Clinical water insufflation and have preserved small mesenteric artery blood flow (SMABF) Medicine, Trinity College Medical School, St bowel motility to improve mucosal views measured by Doppler ultrasound (Doptek James's Hospital, Dublin and Department of during withdrawal. We found jejunal or ileal Ltd), and cardiac output (CO) by an indirect Biochemistry, Trinity College, Dublin, Ireland) lesions in 17 of 28 (60%) patients with rheuma- Fick principle monitoring respiratory Chronic ethanol consumption causes both toid arthritis and unexplained iron deficiency gases (VG Medicals). Fourteen volunteers ultrastructural and functional change in the anaemia. Out of four patients with Crohn's (21-42 years) were studied supine after an small intestinal mucosa and the liver. Mono- disease, lesions were found in two in whom overnight fast before and at 15 minute intervals amine oxidase (MAO), an outer membrane small bowel enema was normal. In four of five for one hour after an 800 kcal meal. Eight mitochondrial enzyme present in these tissues, patients with subacute gastrointestinal bleeding subjects acted as controls. Heart rate was is responsible for the first pass metabolism of and normal upper gastrointestinal endoscopy, measured by electrocardiography and blood dietary amines. Male Wistar rats were fed a jejunal ulceration was found. Jejunal or ileal pressure by auscultation. Lieber-deCarli diet for four weeks. The test lesions were found in four of 14 patients with Controls showed nochangein anyparameter. group (C, n= 16) received ethanol containing iron deficiency anaemia of unknown cause. An Postprandially, both mean (SEM) SMABF and (5% w/v) feed ad libitum, the pair fed control unsuspected small bowel lesion was found in CO increased, peaking at 30 minutes (SMABF: group (B, n= 16) a diet with isocaloric substitu- one of the remaining five patients with miscel- 463 (35) ml/niin to 854 (110) m/min; CO:4 8 tion of dextrin-maltose for ethanol. Another laneous disorders. The procedure was ter- (0.3) VImin to 6-1 (0.5) 1/min (both p<0.001), control group (A, n= 16) took ethanol free feed minated or failed in four patients. although the magnitude of the increase in CO ad libitum. Our early results suggest that this technique was twice that of SMABF. This was matched Duodenal and liver samples (n= 8) from each has considerable potential in the detection of by a fall in both mesenteric vascular resistance group were examined histologically and by small intestinal sources ofblood loss. and total systemic vascular resistance (both transmission electron microscopy. Protein, p<0-001). At 15 minutes postprandially, there MAO-A, and MAO-B were determined in was a relation between the increase in SMABF small intestinal (SI) mucosal cell homogenates Comparison of percutaneous endoscopic and CO (r=0-62, p<0 02), although at 30 and in liver mitochondrial (LM) preparations. gastrostomy with nasogastric tube feeding in minutes this just failed to reach significance SI lactase was estimated also. It is noteworthy the management of patients with oropharyn- (r=0-46, p=0.09). There was no overall rela- that, although LM protein was lower in the geal dysphagia requiring long term enteral tion between the change in SMABF and CO alcohol fed group (n=8, mean (SD) 0 93 (0.09) nutritional support (r=0-24, p=0-07). mg prot/ml/mg liver (wet wt)) than in the pair The early postprandial increase in SMABF fed controls (n=8, 1-66 (0.32), p=0-00015), it http://gut.bmj.com/ may account for the increase in CO, although was similar to LM protein in the ad libitum R H R PARK, M C ALLISON, J LANG, J MORRIS, B DANESH, R I RUSSELL, P R MILLS (Gastroenter- the magnitude ofthe change is much greater for controls (n=8, 1.10 (030), p=0.16). Despite ology Units, Western and Royal Infirmaries and CO than SMABF. The precise mechanism for hepatitis and ultrastructural changes in intes- Stobhill Hospital, Glasgow) This prospective the late postprandial increase in CO is unclear tinal epithelial cells and hepatocytes in the study compared nasogastric (NG) tube feeding, but may result from increased sympathetic alcohol fed group, MAO activities (group, the standard method of providing longterm nervous system activity or the action of gut n=8, mean (SD), cpmxl10'/mg prot) were enteral nutrition, with percutaneous endo- derived peptides. similar in the three groups: SI MAO-A (C, 8-2 scopic gastrostomy (PEG). Twenty four (2.4); B, 7.5 (1-4); A, n=7, 7-5 (1-9)), SI on September 24, 2021 by guest. Protected copyright. patients were randomly allocated to receive MAO-B (C, 9.5 (2.8); B, 5.7 (2.4); A, n=7, 5-1 enteral nutrition (Ensure 2-4 1 per day) for a (1.9)), LM MAO-A (C, 95 0 (14-5); B, 85-8 study period of 28 days, either by NG (n= 12) Chronic diarrhoea, bile salt malabsorption, (12-1); A, 84-5 (8X1)), LM MAO-B (C, 67-2 or PEG (n= 12) tube feeding. All patients had and previous enteric infection (18-0); B, 74.2 (14-8); A, 67-0 (19.3)), as were longstanding oropharyngeal dysphagia secon- lactase activities (Group, n, mean (SD), U/g dary to motor neurone disease (14), cerebro- K SANDRAGESARAN, B J M JONES (Russells Hall prot) (C, n=4, 1-5 (1-0); B, n=7, 1-3 (1-0); A, vascular disease (8), Parkinson's disease (1), Hospital, Dudley, West Midlands) Bile salt n=6, 1. 1(0.9)). and multiple sclerosis (1). The mean age was 63 malabsorption is a cause of chronic diarrhoea We conclude that although the specific years, range 29-88 years. and may be diagnosed using a "SeHCAT scan. activity ofMAO in the small intestine and liver Treatment failure (blocked or displaced In many cases no underlying cause can be is not altered by chronic ethanol intake in rats, tubes on three or more occasions, or patient found and these are termed 'idiopathic'. In a reduced hepatic amine metabolism may result refusal to continue treatment) occurred in 10 of survey of 78 patients undergoing a 75SeHCAT from decreased liver mitochrondrial protein the 12 NG patients and all were changed to scan in our district in 1986-1990, 37 (50%) had and thus reduced MAO content. PEG feeding. One patient in each group died a positive test with seven day retention of during the study period. The other 11 patients <12% (Crohn's (5); post ileal resection (13); in the PEG group completed 28 days of feed- radiation enteritis (5); gastric surgery (3); and ing. No complications occurred in the NG ulcerative colitis (1). Of the 10 remaining BILIARY TRACT group but two of the PEG group developed 'idiopathic' cases, five dated their chronic delayed gastric emptying (2), pneumonia (1). diarrhoea (mean (range) 3-32 (0.75-8) years) PEG patients received a significantly greater back to an acute gastroenteritis (shigella (1), percentage of prescribed feed (mean (SEM) 97 Helicobacterjejuni (1), unknown (3). Eighty per Three dimensional ultrasound imaging of the (2)%) compared with the NG group (70 (7)%) cent had raised faecal fat excretion (mean biliary tree (p<0-01), and there was a significantly greater (SEM) 33-7 mmol (9.4)) and 20% a low serum weight after 14 days, 1-7 (0.5) v 0 5 (0.6) vitamin B12 concentration. Small bowel D FINE, S PERRING, J HERBETKO, N HACKING, gain enema, distal duodenal biopsy specimens and J BAMFORTH, K DEWBURY (Departments of kg (p<0 05). Analysis at days 21 and 28 was not touch smears, stool culture and microscopy for and possible due to small numbers in the NG Medicine, Radiology, Physics, Southampton is an and parasites, pancreatic, hepatic, and thyroid General Hospital) We have developed com- group. PEG tube feeding effective function were all normal. All five patients puterised three dimensional reconstructions of safe method of providing longterm enteral responded well to cholestyramine or biliary ultrasound images to aid their inter- nutrition and offers significant advantages over aluminium hydroxide. pretation by clinicians. Using a Toshiba Sono- standard tube feeding. We postulate that absorption of bile salts by layer VSSA 100A real time scanner with a the terminal ileum may become chronically 3.75 MHz linear array transducer, images were impaired after a bout of infective gastro- obtained from patients with dilated bile ducts. Relation between the postprandial increase enteritis. We would suggest that the 75SeHCAT Sample B scan frames from ultrasound British Society ofGastroenterology A567 examinations of the gall bladder and dilated perfusion (PCP), MTBE dissolution, and extra- diagnostic and therapeutic endoscopic retro- biliary tree were digitised using a recursive corporeal shockwave lithotripsy (ESWL) aid grade cholangiopancreatography (ERCP) must video processor. Images were compressed to clearance of common duct stones QCDS) after be at the highest risk of sedation related 256 by 256 pixel format and processed on a sphincterotomy. Over the past 30 months 217 cardiorespiratory complications. Immediate DEC VAX 11-730 minicomputer running a patients (124 female and 93 male, age mean reversal of the benzodiazepine sedation after Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from locally developed PICS general image process- (range) 76 (27-99) years) had endoscopic retro- the procedure by flumazenil might therefore be ing software. Individual frames were smoothed grade cholangiopancreatography (ERCP) for advantageous. In a double blind prospective using a large kernal, histogram based median CDS. In nine patients (4%) ERCP failed. Duct trial, 30 consecutive patients aged over 60 filter and a corresponding sobel gradient image clearance was achieved at the first ERCP in 129 undergoing ERCP were randomised to receive created. Bile ducts were highlighted by pro- (59%), aided by PCP in 18 and ML in three. either iv flumazenil 500 ptg or normal saline on ducing a negative image and weighting pixel Forty two (19%) had ducts cleared at repeat extubation. Patients were monitored clinically intensity according to proximity to maxima in ERCP, aided by PCP in six and ML in four. and by pulse oximetry before, during, and for the corresponding sobel image. Bile ducts were Thirty patients underwent ESWL with frag- two hours after ERCP. Of 30 patients ran- imaged using a voxel based three dimensional mentation and clearance in 22. Four patient's domised, results on 25 were compared - five projection and rendering technique. Series of stones showed no response to ESWL, but two patients needing oxygen during the procedure three dimensional image frames were displayed were subsequently cleared using MTBE or were excluded. Midazolam dosage (2-5 mg), at video rates to provide a realistic impression ML. Four patients showed fragmentation, but age, sex, pathology distribution, and pro- of object rotation. Results from 10 scans show clearance could not be achieved. Thirteen cedure length were similar in both groups. realistic three dimensional images ofthe biliary patients in whom duct clearance failed had Results showed that flumazenil treated tree. To assess the accuracy of ultrasound biliary stents inserted and remain well. Overall patients were significantly more alert within reconstruction, the bile ducts ofa cadaver liver duct clearance was achieved in 195 (90%). minutes of the injection but there was no were perfused with dilute contrast under Complications occurred in 11 patients, two difference in alertness at four, eight, and 24 pressure. Projections from computed tomo- needing urgent laparotomy. Two patients died hours. Twenty saturation was significantly gram and ultrasound images were compared within 30 days of ERCP. higher (p<0.0005) in the flumazenil group and found to be similar. These additional methods of clearing CDS 10-15 minutes into the recovery period and We conclude that three dimensional ultra- seem to improve the success of endoscopic mean values were higher for the first 45 sound of the biliary tree is a viable technique treatment, without increasing risk. Surgery for minutes of the recovery period but not dif- meriting further development. failed duct clearance is virtually never needed ferent thereafter. There was no evidence of when these adjunctive methods are available. resedation within two hours. This study showed an immediate but short lived benefit on 20 saturation with flumazenil Cheno plus ursodeoxycholic acid combina- sedation reversal after ERCP in high risk tion therapy: dose response effect and Abolition ofhypoxia during endoscopic retro- patients. The clinical importance ofthis benefit factors affecting gall stone dissolution rate grade cholangiopancreatography with pre- is at present uncertain. oxygenation D FACCHINETTI, G PIGOZZI, L BETTINI, P GUARIENTI, A LANZINI (Medicine 1. Spedali J RIGG, T WATT, D E F TWEEDLE, D F MARTIN Civili, Brescia, Italy) A combination of cheno (Withington Hospital, University Hospital of Bile duct exploration through the intact plus ursodeoxycholic acid (C+U) therapy has South Manchester, Manchester) Compared with papilla been reported to be better than urso alone for upper gastrointestinal endoscopy, patients http://gut.bmj.com/ treatment of gall stones. No information is undergoing endoscopic retrograde cholangio- W DICKEY, R G P WATSON, K G PORTER (Depart- available on the dose response effect and on pancreatography (ERCP) are likely to be less ment of Gastroenterology, Belfast City Hospital, factors affecting dissolution rate during C+U fit. The procedure may be lengthy and the Lisburn Road, Belfast) Endoscopic retrograde therapy. To obtain this information we patient lies prone and requires analgesics as cholangiography (ERC) may fail to show measured the dissolution rate (% change in well as larger doses ofsedative. All these factors choledocholithiasis even when other evidence stone area on standardised cholecystography) will aggravate the risk of hypoxia. is strongly suggestive of this. Based on our at six months in 88 patients matched in quartets We allocated 50 patients alternately to experience of ERC later shown to be falsely for stone size (within 5 mm diameter) and body receive 4 5 1 of intranasal oxygen per minute, negative, and our reluctance to proceed on September 24, 2021 by guest. Protected copyright. weight (within 10%), and treated with either (a) five minutes before sedation or (b) when routinely,to sphincterotomy (with its attendant 4.3, 8-6, or 12-8 mg/kg/day C+U or 9.0 mglkg/ turned prone after duodenal intubation. risks) in such cases, we attempted bile duct day urso. Cholesterol saturation index (SI) of Arterial oxygen saturation was measured exploration through the intact papilla using a gall bladder bile was also measured during before and every 2.5 minutes during oxygen Dormia basket. C+U (n=20). Gall stone dissolution rate was administration using a Critikon Oxyshuttle Basket insertion has been successfully faster with 8.6 mg/kg/day C+U compared with pulse oximeter. The two groups of patients achieved in 32 of 47 (68%) patients to date. Of 4.3 mg/kg/day (mean (SEM) 43 (1 1)% v 28 were similar with regard to sex, age, weight, 26 patients with no bile duct lucency on initial (9)%, p<0 05), and did not increase with indications for ERCP, American Society of ERC, exploration by this technique disclosed 12-8 mg/lkg/day C+U (34 (9)%, NS). There Anesthiologists grading, and dose of analgesic one or more calculi in five patients and none in was a strong tendency for dissolution to be and sedative (nalbuphine and midazolam). In 21. In four patients with vague lucency on faster with 8-6 mg/kg/day C+U compared with the preoxygenated group (a) median basal ERC, calculi were found in two. In two 9.0 mglkg/day urso (44 (10)% v 24 (7)%, NS). saturation (at rest before oxygen administra- patients, bile duct exploration showed that Dissolution rate was inversely related to pre- tion) was 95%, with a minimum saturation lucencies were caused by polypoid lesions and treatment stone diameter (n=66 C+U, during ERCP of 96%. No preoxygenated not calculi. r=-0-344, p<0 004), and was affected by SI patient had an oxygen saturation of less than Thus, bile duct exploration through the duringC+U (39 (8)% v 12 (7)% for SI <0-8 and 90% during ERCP. In group (b) median basal intact papilla was instrumental in showing >0 8 respectively). oxygen saturation was 95% falling to a lowest calculi in seven (22%) and polypoid lesions in We conclude that there is a dose response median of 90% during ERCP; nine of 25 two of the 32 patients. This technique clearly effect on gall stone dissolution rate during patients had oxygen saturation below 90% improves diagnostic accuracy and helps avoid C+U therapy with maximum effect at 8-6 mg/ during the procedure, always within 15 the need for sphincterotomy. kg/day C+U. In order to speed dissolution rate minutes ofsedation. it is worth aiming at a low SI in addition to We conclude that hypoxia during the early selecting patients with small stones. stages of ERCP is common and should be avoided by preoxygenation. NEW DIMENSIONS IN BILIARY TRACT THERAPY

Management of common bile duct stones - can we avoid surgery? Does sedation reversal by flumazenil benefit Experience with 97 laparoscopic cholecys- elderly patients after endoscopic cholangio- tectomies: prediction of difficult operations D A NICHOLSON, D MAXTON, D E F TWEEDLE, pancreatography? and management of common duct stones D F MARTIN (Departments ofRadiology, Medicine and Surgery, Withington Hospital, University D J HAINES, D BIBBEY, J R B GREEN (Gastroenter- R JAGO, I McCOLL (Departments ofSurgery, Royal Hospital of South Manchester, Manchester) ology Department, North Staffs Hospital Centre, Bournemouth Hospital, and Guy's Hospital, Mechanical lithotripsy (ML), pernasal catheter Stoke-on-Trent) Elderly patients undergoing London) Our first 97 laparascopic cholecystec- A568 BritishSocietyofGastroenterology tomies are described. One patient of 77 years General Surgery, Western General Hospital, pital, London) Extracorporeal shock wave litho- died after six days at home following an undiag- Edinburgh) Patients suffering from gall bladder tripsy combined with oral bile acid therapy is nosed acute cardiorespiratory event. Six disease come in all shapes and sizes and are effective treatment for radiolucent gall bladder patients had non-fatal complications. No re- often elderly and at high risk from surgery. The stones. However, repeat lithotripsy is often operations were necessary (total complications local gall bladder pathology varies technically required, reducing convenience and cost effec- Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from seven). In nine patients the procedure was from extremely simple to very demanding. tiveness. We report preliminary results with a converted to open operations: two urgently for This study addresses the crucial question of new electromagnetic lithotripter, the Storz uncontrolled haemorrhage; four for other diffi- whether the new technique of laparoscopic Modulith SL10/20, that delivers higher energy culties. The operation was classed as 'difficult', cholecystectomy can successfully manage the shock waves without the need for general due to adhesions or induration in 32 patients. whole spectrum ofpatient and pathology. anaesthesia. Most of these presented with either serious An unselected series of 100 patients suffering Twenty seven symptomatic patients with biliary sepsis, acute cholecystitis, a history of from acute or chronic gall stone disease were solitary (n= 12) or two to four radiolucent having passed a stone, or exceptional biliary submitted to laparoscopic cholecystectomy. stones (maximum diameter 3 cm) in a function- pain. The predictive value for difficulty of Suspected common bile duct stones were man- ing gall bladder were treated. Stones were serious sepsis was 100%. Eleven patients had aged by preoperative endoscopic retrograde targeted using ultrasound or x ray imaging. common duct stones, identified preoperatively cholangiopancreatography/papillotomy in 25 Intravenous analgesia and sedation were in seven. In five of the 11, the stones were patients. Only one ofthe 95 elective operations required in 13 cases (42%). Patients received removed endoscopically preoperatively and in required conversion to an open procedure, as ursodeoxycholic acid (10 mg/kg/day). Frag- two postoperatively In one, a large stone was did only one of five acute procedures for mentation and gall stone clearance were held in the common hepatic duct by narrowing gangrenous cholecystitis/empyema, giving an assessed by ultrasound or oral cholecystogram ofthe common bile duct due to pericholangitis: overall conversion rate of 2%. The major at one and three months. A maximum of two this stone was removed at laparoscopy by direct complication rate of 1% was due to a patient lithotripsy sessions were performed. incision into the duct and subsequent place- who required a laparotomy on the 10th day for The mean number ofshocks per session was ment of a t tube. In two, small stones (remain- biliary leakage. The mean postoperative in 2156 (range 1000-3500) at an energy of 16-1 kv ing after sphincterotomy in one) were flushed patient stay was only 1-8 days. (range 12-18). Stone disintegraton was into the duodenim during laparoscopy after It is concluded from this initial study that achieved after one lithotripter session in 23 dilating the sphincter with an angioplasty laparoscopic cholecystectomy should be patients (85%). Lithotripsy was repeated in balloon catheter passed through the cystic duct offered to all patients suffering from sympto- four, disintegration occurring in two. Frag- under screening control, with subsequent matic gall stone disease. mentation to less than 5 mm diameter was choledochoscopy in one. achieved in 18 patients (67%), with complete dissolution at three months in six (22%). The only significant complication was cholangitis in one patient. Patient selection for new techniques of gall Laparoscopic cholecystectomy - a district The Storz Modulith provides one session stone management general hospital service fragmentation and allows efficient, outpatient therapy ofgall bladder stones. S CHESLYN-CURTIS, S LAKE, A GILLAMS, T LEESE, R SANTOSCOY, W P MORGAN, J K BRIGG, W R LEES, A R HATFIELD, R C G RUSSELL J F KELLY (Department of Surgery, The Royal (Pancreatobiliary Unit, The Middlesex Hospital, Lancaster Infinnary, Lancaster) Laparoscopic London) With the introduction of several new cholecystectomy was introduced at a district http://gut.bmj.com/ techniques for managing symptomatic gall general hospital in September 1990. All four stones and the emphasis on greater choice for general surgeons offer the service. An 'all Treatment of symptomatic cholecystolithia- patients, selection is necessary as the new comers' policy was adapted. Patients with sis under local anaesthesia using the percu- techniques cannot be performed successfully in suspected common bile duct stones underwent taneous rotary lithotrite every patient. initial endoscopic retrograde cholangiopan- During the past two years, 281 patients with creatography. Previous upper abdominal sur- A GILLAMS, S P LAKE, S CHESLYN-CURTIS, gall stones have been assessed. Selection gery or second intra-abdominal abnormalities W R LEES, A R W HATFIELD, R C G RUSSELL depended on patient choice, the clinical requiring open laparotomy were the only con- (Departments ofRadiology and Gastroenterology, on September 24, 2021 by guest. Protected copyright. features, and a detailed ultrasound assessment traindications to the laparoscopic technique. The Middlesex Hospital, London) The manage- of stone number and size, of gallbladder posi- Fifty laparoscopic cholecystectomies were per- ment ofgall stones is changing rapidly particu- tion, well thickness, and function, and of the formed in the first three months. During the larly with the advent of laparoscopic chole- bile ducts. Thick walled contracted gall same period five other patients underwent cystectomy. However, there remains a group of bladders were accurately identified in 63 (22%) conventional open cholecystectomy. The patients who are unsuitable for this treatment patients. These were found to be suitable only median age of the laparoscopic group was 58 because general anaesthesia is contraindicated. for minicholecystectomy or the more difficult years (range 32-71). Median operating time An effective method of treating cholecystoli- laparoscopic cholecystectomy. The remaining was 80 (range 35-120) minutes. Six patients thiasis under local anaesthesia would thus be 218 (78%) patients had thin walled, mostly (12%) required conversion to open cholecystec- extremely useful. functioning gall bladders with fasting volumes tomy during the procedure because of dense The rotary gall stone Lithotrite (Baxter, CA) of >15 ml, and 185 of these patients have adhesions (3), haemorrhage (2), and minor consists of a rotating metal arm (impeller) held undergone treatment. Percutaneous chole- injury to the right hepatic duct (1). Postopera- within a rigid basket. Rotation (<30000 rpm) cystolithotomy failed in six of 111 patients tive complications were CO2 surgical generates a vortex sucking the stones into the because of a floppy gall bladder undetected by emphysema (1), symptomatic common bile basket where they are fragmented by the ultrasound. Four patients underwent percu- duct stone requiring endoscopic removal (1), impeller. The basket holds the gall bladder taneous rotary lithotripsy successfully and 24 and readmission with non-specific abdominal mucosa clear of the rotating impeller. The patients with one to three non-calcified stones in pain which settled on conservative treatment instrument is introduced in compressed form functioning gall bladders preferred extracor- (2). There were no deaths. Ninety per cent of through a 10 FG percutaneous catheter. The poreal shockwave lithotripsy, of which five are patients were discharged home within 48 hours lithotrite is suitable for any number of stones, stone free at a mean 11 months. Laparoscopic of surgery and most returned to full activity of any composition, <3 cm in diameter and cholecystectomy has been successfully per- within two weeks. occupying <75% of the total gall bladder formed in 47 of 51 patients using the above These early results suggest that laparoscopic volume. criteria but excluding largely intrahepatic gall cholecystectomy is suitable as a district general Five women, median age 81 (range 63-88) bladders. hospital service. years have been treated. Complete stone des- We conclude that the above criteria can truction and removal of all stone debris was accurately assess the optimum treatment and achieved in all patients. There were no compli- enable the surgeon to avoid technical problems. cations and the patients tolerated the procedure well. Percutaneous cholecystoscopy (via Early experience with a new electromagnetic catheter tract) was performed at 10 days in two gall stone lithotripter patients and showed normal gall bladder Laparoscopic cholecystectomy - the results mucosa. in an unselected series of 100 patients A P JENKINS, R J EDE, J PEMBERTON, This new treatment offers great potential for R P H THOMPSON (Gastrointestinal Laboratory treating symptomatic gall stones in patients J H SAUNDERS, R G WILSON (Department of and Department ofRadiology, St Thomas's Hos- unfit for general anaesthesia. British Society ofGastroenterology A569

Thus, only 18 (2 5%) out of the 736 patients minutes after ingestion of a standard liquid BILIARY TRACT FUNCTION referred over a five year period, or three-four/ meal (Ensure; 250 ml, 250 kcal), or until the 147 ERCP referrals, were candidates for SO gall bladder started to refill. The smallest manometry each year. To run an SO mano- volume obtained is termed the residual volume Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from Effects of instillation of nutrients into the metry service there should be at least 40-50 (RV). A single dose of erythromycin signifi- duodenum on gail bladder in man referrals per year. When taking into account cantly reduced fasting and residual gall bladder emptying that the provision ofgastrointestinal endoscopy volumes (FV 27.5 (SEM) 3-1) v 20-2 (2.9) ml; in the UK S ELLENBOGEN, S A JENKINS, S GRIME, (BSG 1990) is 50 ERCPs per 100 000 RV 9-1 (1-0) v 4-7 (0.9) ml, p<0-01) and this C R MACKIE, J N BAXTER (Departments ofSurgery of population per year, it is extrapolated that effect was maintained over four weeks; (FV andNuclearMedicine, RoyalLiverpoolHospital, such a unit should serve a population of at least 18-6 (6.4) ml; RV 3-7 (1.5) ml, p<0-01). Liverpool) The gall bladder emptying response four million. Intermittent erythromycin is therefore effec- to duodenal instillation ofnutrients ofdifferent We conclude that gastrointestinal endoscopy tive in reducing gall bladder FV and RV composition and osmolalities and varying rates units established in areas with a population of medium term and is worthy of trial in the of infusion was studied in normal subjects more than four million may obtain the experi- prevention of stone recurrence in those who using cholescintigraphy. Nutrients were in- ence and warrant the expenses of an SO have undergone dissolution therapy or litho- stilled into the duodenum via a nasoduodenal manometry service. tripsy. tube, and comprised; oleate (n=6), amino acid (n=6), dextrose (n=6), and saline (n=6). Nutrients were iso-osmolar, pH 7-0, 30°C and delivered at the rate of 5 mllminute for 20 Effect of nicardipine and ceruletide on Gall bladder function after percutaneous minutes. Iso-osmolar oleate was also instilled sphincter ofOddi finction cholecystolithotomy into the duodenum at 1 ml/minute for 50 minutes (n=6) and also administered as a bolus G M FULLARTON, S FALCONER, A CAMPBELL, S CHESLYN-CURTIS, A GILLAMS, S LAKE, of 50 ml (n=6). Finally, hypo-osmolar oleate W R MURRAY (University Department ofSurgery, W R LEES, R C G RUSSELL (Pancreatobiliary Unit, (10%) was instilled into the duodenum of 10 Western Infirmary, Glasgow) Pharmacological The Middlesex Hospital, London) Non-opera- subjects. relaxation of the sphincter of Oddi (SO) may tive methods used in the management of Gall bladder emptying occurred in all sub- have a beneficial effect, particularly in SO cholelithiasis, including percutaneous chole- jects given oleate - hypo-osmolar, iso-osmolar, dysfunction where basal sphincter pressure is cystolithotomy (PCCL), have been criticised 5 ml per minute, 1 ml per minute, and bolus; in high. The aim of this study was to investigate not only because there is a risk of developing five of six subjects given dextrose (p= 1); in the effects of a calcium channel blocker (nicar- recurrent stones but also becauseofthe undesir- three of six subjects given amino acids; and dipine) and synthetic cholecystokinin (cerule- ability of leaving an abnormally functioning three of six subjects given saline (p=0-1818). tide) on SO pressures. gall bladder in situ. Gall bladder function after Emptying was most rapid (p=0.0036) and Nineteen patients (median age 49 years; stone clearance byPCCL has not been reported. prolonged (p<0.05) following oleate infusion, range 21-75) attending for routine endoscopic We have determined gall bladder contrac- less rapid with amino acid and saline, and retrograde cholangiopancreatography tility using ultrasound, by measuring the slowest (p=0-0010) and of shorter duration examination were randomly allocated to change in gall bladder volume (emptying) after (p<005) with dextrose. A slow rate of oleate receive either a three minute iv infusion of a fatty meal stimulus. Eighty of 100 patients infusion delayed onset of emptying (p<005), nicardipine 3 mg (n=6), ceruletide 5 ng/kg who have undergone successful PCCL have (n=7), or placebo (n=6). Endoscopic biliary been assessed before and at a mean (range) of9 whereas a bolus infusion delayed onset empty- http://gut.bmj.com/ ing (p=0.0486). Gall bladder emptying with manometry was performed with recording of (3-36) months after treatment. Gall stone hypo-osmolar oleate was of slower rate (p= basal, amplitude, and frequency of phasic SO patients before PCCL had significantly greater 0.0181) and shorter duration (p<0 05). pressures before and after iv infusions. In the fasting (40 (3.4) ml) and residual (21 (3.5) ml) These results suggest that the type of duo- nicardipine group patients showed a decrease volumes than healthy controls (n= 10) (25 denal nutrient, its rate of delivery, and in both basal and phasic amplitude SO pressure (6.2) ml, 10 (0.9) ml respectively). After stone osmolality are important in determining gall (mmHg) from the mean (SEM) preinfusion extraction, the greater fasting volume persisted bladder response. values of 24-7 (3.6) and 112-3 (13-4) to 12-9 (38 (3.0) ml). Gall bladder emptying (% reduc- emptying (2.9) (p<0-01) and 89-9 (12-4) (p<0 03) after tion in volume) was similar in gall stone infusion respectively. Ceruletide produced a patients before PCCL (47 (3.4)) and in controls on September 24, 2021 by guest. Protected copyright. decrease in SO amplitude phasic wave fre- (49 (6.4)) but seemed to increase after PCCL quency (c/min) from 3-4 (0.3) before infusion (54 (2.6)) although this was not statistically Clinical needs for sphincter of Oddi mano- to 2-6 (0.5) after infusion (p<005). significant. Gall bladder function was restored metry in gastrointestinal endoscopy units We conclude that nicardipine effectively after stone extraction in 15 of 18 patients who decreases sphincter of Oddi pressure. This presented with non-functioning gall bladders S D LADAS, P S TASSIOS, J KATSOGRIDAKIS, drug may therefore be ofvalue in the treatment due to acute cholecystitis or a mucocoele. K GIORGIOTIS, T TASTESMIROGLOU, S A RAPTIS of SO dysfunction where raised sphincter In conclusion, most gall bladders in gall (Gastroenterology Unit, 2nd Department of pressures are thought to be the primary patho- stone patients have normal contractility but Internal Medicine-Prodeadeutic, Athens Univer- genic feature. have greater fasting volumes than healthy sity, Evangelismos Hospital, Athens, Greece) To controls. Function can usually be restored in investigate the clinical need for sphincter of the non-functioning gall bladder by stone Oddi (SO) manometry, we have analysed the extraction. results ofendoscopic retrograde cholangiopan- Effect of intermittent oral erythromycin on creatography in 736 consecutive patients the gall bladder is maintained medium term (1985-89). One hundred and eighty four patients (65 M/119 F, age mean (SD) 66-3 S M CATNACH, E PARKER, P D FAIRCLOUGH HELICOBACTER PYLORI: PATHOGENISIS, (11.8) years) referred because of postcholecys- (Departments ofGastroenterology and Radiology, DIAGNOSIS AND THERAPY tectomy symptoms had had simple cholecys- St Bartholomew's Hospital, London) A single tectomy performed mean (SD) 7-9 (8.6) years oral dose of erythromycin reduces fasting and (range 1-50 years) before their referral. Endo- postprandial residual gall bladder volume. If scopic retrograde cholangiography (ERC) was erythromycin is to have a clinical role in gall Helicobacter pylon raises the pH in the obtained in 154 (83.7%) and duodenoscopy or bladder disease this effect must be maintained, juxtaepithelial region of the mucus layer of endoscopic retrograde pancreatography were to aid fragment clearance after extracorporeal the gastric antrum and body diagnostic in an additional 19 (10-3%) patients. shock wave lithotripsy, or prevent stone recur- In 78 (50.7%) of them ERC showed bile duct rence after dissolution therapy. We therefore K BEARDSHALL, D ADAMSON, J GILL, R UNWIN, stones. In 44 (28 6%) patients various biliary or studied gall bladder motility by ultrasound J CALAM (Department of Medicine, Royal Post- pancreatic diseases were diagnosed. According after a single oral dose of 500 mg erythromycin graduate Medical School, Hammersmith Hos- to standard criteria (delayed contrast medium or placebo given two hours before scanning in pital, London) Helicobacter pylori might excretion >30 minutes, common bile duct 16 normal subjects and also after four weeks of increase gastrin release by increasing the pH diameter >12 mm, abnormal liver function erythromycin 500 mg taken three times a week around gastric G cells. Results obtained using a tests), 14 (9-1%) of the remaining 32 patients in six of those subjects. 1 mm pH electrode in vivo support this, but the suffered from SO dysfunction type 1 syn- Fasting gall bladder volume (FV) was deter- mucus layer is <0 5 mm thick so we used drome, but biliary manometry was necessary to mined after an overnight fast and volumes were 10 jim tip microelectrodes to measure the pH establish a diagnosis in 18 (9.8%) patients. then measured at five minute intervals for 40 more precisely in the juxtaepithelial region of A570 British Society ofGastroenterology the mucus layer of the antrum and also the gradual loss in mucus viscosity and an in- A G MORGAN, J E CRABTREE, R V HEATLEY, gastric body, where the organisms are located. creased permeability to hydrogen ions. These P G R GODWIN (Endoscopy Unit, Airedale Biopsy specimens collected at endoscopy findings could be responsible for a change in GeneralHospital and Department ofMedicine, St were immediately mounted in oxygenated, juxtamucosal pH in patients colonised by J3ames's Hospital, Leeds) To investigate the role urea free, modified Ringer solution (pH 7.5, H pylori. of Helicobacter pylorn serology as a preliminary Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from 37°C). Calibrated pH microelectrodes were The aim of this study was to investigate the screen for acute dyspepsia, we undertook a lowered into the mucus layer of the specimen relation between the presence of H pylon and prospective study on 979 consecutive patients using a micromanipulator until a plateau pH the pH mucosal gradient of the stomach in referred for endoscopy to a district general was reached. Three recordings were made for subjects with no endoscopically detectable hospital. In all patients, serum was assayed each specimen. Biopsy specimens were also abnormalities. blind for H pylori IgG antibodies by ELISA, collected for urease test. pH was measured in 20 subjects by means of and in most antral biopsy specimens were taken The mean (SEM) pH in the antral mucus a flexible microelectrode passed through the for urease detection (97%) and bacterial culture layer was 7-13 (0.06) in Hpylonr +ve (n= 8) and biopsy channel of an endoscope during an (75%). On endoscopy, 141 had duodenal 6-95 (0.04) in H pylon -ve patients (n=9, upper gastrointestinal endoscopy. Measure- ulceration; 120 were ELISA positive (85%). Of p<005). The mean (SEM) pH in the mucus ments were performed in the gastric body along the remaining 21, 10 were receiving NSAIDs. layer of the gastric body was 7.14 (0.04) (n=4) the greater curvature - first in luminal fluid and Fifty six had gastric ulceration. Forty five were in H pylon +ve and 6-96 (0.05) (n=5) in then on the underlying epithelial surface. seropositive (80%) and 11 (20%) seronegative. Hpylori -ve patients p<0 05). H pylon was detected by cultures, biochemical Five of the latter were on NSAIDs. Adenocar- In conclusion, the pH in the juxtaepithelial tests, and Gram staining of biopsy specimens cinoma was found in 12 patients, of whom 11 region of the mucus layer of the gastric antrum taken at the same sites ofpH measurements. were seropositive. and body are significantly raised in H pylon Gastric mucosal pH was mean (SD) 6-58 Of 252 patients under 40 years, 51% were infection. This would tend to increase gastrin (0 55) in 13 subjects negative for H pylon and seropositive. Twenty seven of 30 patients with release. 5.78 (0.49) (p<0 001) in seven with positive duodenal ulcers and five of seven with gastric cultures. Luminal fluid pH was 1-70 (0.78) in ulcer were seropositive. There were no gastric negative v 1.95 (0.75) (NS) in positive subjects. cancers. Forty per cent of normal endoscopies The pH gradient was 4-73 (0.67) in H pylon' were seropositive. Two of the three patients Helicobacter pylori related hypergastri- negative compared with 3-83 (0.80) (p<0 02) were seronegative duodenal ulcers were culture naemia is not due to elevation of antral in positive subjects. or urease negative, or both. Most physicians surface pH This study shows that the presence of H would perform routine endoscopy in new dys- pylon is associated with a lower juxtamucosal peptics aged over 45. Our results in younger R S CHITTAJALLU, W D NEITHERCUT, pH in the gastric body. The alterations in patients indicate that with an 86% detection of K E L McCOLL (University Department ofMedicine mucus observed in H pylori positive patients ulcers by H pylori serology, 123 endoscopies and Therapautics, Western Infirmary, Glasgow) may explain these findings. The reduced pH could have been avoided if only positive The mechanism by which Helicobacter pylon mucosal gradient in positive subjects may patients had been examined. infection of the gastric antrum increases basal indicate an increased mucosal susceptibility to and meal stimulated plasma gastrin concentra- acid injuries. tions is unclear. It has been proposed that it may be the result of the ammonia produced by Field trial of a simple, modified rapid urease the organism raising antral surface pH and thus Evaluation of the new Helico-G ELISA for test for the detection ofHelicobacter pylori

preventing acid inhibition of gastrin release. If serological diagnosis of Helicobacter pylori http://gut.bmj.com/ true, the infection should not affect gastrin infection P H KATELARIS, D LOWE, P NORBU, release at neutral intragastric pH. To test this M J G FARTHING (Department Gastroenterology, we have studied the gastrin response to a C K CHING, S THOMPSON, C BUXTON, C HOLGATE, St Bartholomew's Hospital, London, UK and peptone meal with and without gastric alka- P HILL, J G FREEMAN, GK T HOLMES (Derbyshire Doeguling Hospital, Karnataka, India) A modi- linisation, before and after eradication of Royal Infirnary) We have recently evaluated a fied rapid urease test (MRU test) was evaluated Hpylon in six patients. The pH was maintained new enzyme linked immunosorbent assay under field conditions during an endoscopic at 7 throughout the alkalinised meal by con- (ELISA) for aiding serological diagnosis of survey in rural India. It was compared with tinuous intragastric infusion of citrate buffer. Helicobacter pylon infection. histology and a commercially available urease The median integrated gastrin response to the Seventy five patients (45 men and 30 women) test (CLO test) with a published sensitivity of on September 24, 2021 by guest. Protected copyright. meal without alkalinisation was 2325 ng/l/ with a mean age of 52.35 years (range 22-81 95% and specificity of 100%. Preparation ofthe minute (range 550-5175) before and 600 ng/l/ years) have been studied. All patients were MRU test is simple. One drop of 1% phenol red minute (range 250-1850) after eradication of endoscopically proved to have antral gastritis. (as free acid) is added to 0 5 ml 10% (w/v) urea H pylon (p<0 05). The corresponding values H pylon infection was confirmed by the cyto- in distilled water (unbuffered). Four antral for the meal at pH 7 were 3163 (1900-14100) logical brushing urea breath test (CBBT) or biopsy specimens were taken 2 cm from the and 1025 (400-2350) (p<0 05). The median histology or both. ELISA (kit obtained from pylorus in 195 subjects, one for MRU test, (range) reduction in gastrin after eradication of Porton, UK) was performed on these patients' another for CLO test, and two for histology. H pylon was thus similar when the meal was sera by an independent investigator who had no Urease tests were assessed independently and taken alone (68% range 0-97) or at pH 7 (63% prior knowledge ofthe patients' Hpylori status. the time to positive was recorded. range 36-90). Thirty nine of the 75 patients were proved A total of 153 of 195 subjects (78 5%) were The fct that H pylon infection alters gastrin H pylori +ve by the conventional tests (CBBT H pylon positive by histology/or CLO test, or similarly in the presence or absence of intra- of histology, or both). Raised antibody titres both. Compared with this the sensitivity and gastric acid indicates that the hypergastri- were found in 32 of 39 Hpylori +ve (sensitivity specificity of the MRU test were 98% and 93% naemia is not due to the organism blocking the 82.05%) and in six of 36 H pylori-ve patients respectively. The MRU test was positive in 77, inhibition ofgastrin release by gastric acid. (specificity 83.33%). The H pylon +ve group 88, 93 and 96% of cases at 1, 5, 20, and 60 had a significantly higher mean Helico-G anti- minutes respectively compared with 3, 14, 49, body titre (44-21 (41-06) U/ml) than the and 71% of cases for the CLO test at the same H pylon -ve group (7.07 (3.35) U/ml) times. Gastric mucosal pH gradient and Helico- p-0 0000, Mann-Whitney U test). The assay Thus, the MRU test had comparable bacterpylori was highly reproducible with a mean intraplate accuracy to the CLO test and yielded a positive and interplate variation of 9% and 15% respec- diagnosis more rapidly, in most cases before G FRIERI, A AGGIO, G DE PETRIS, D SANTARELLI, tively. the subject left the endoscopy suite. The MRU E LIGAS, R ROSONI, R CAPRILLI (Cattedra di These preliminary results suggest that the test costs £0-04 per test compared with £2- 10 Gastroenterologia, Dipartimento di Medicina In- new Helico-G ELISA is a simple and useful test for the CLO test, is simple, rapid, reliable, and terna, Universita de l'Aquila, P'Aquila, Italy) A for diagnosing H pylon infection. It may have a robust. It may be ofuse in clinical or epidemio- pH gradient across the gastric mucus layer has role in aiding management of young dyspeptic logical work, especially where cost factors are been shown both in vitro and in vivo. It has patients without recourse to diagnostic gastro- critical. been suggested that the maintenance of the scopy. juxtamucosal pH is partly dependent on the integrity of the epithelial surface mucus layer. A one week eradication regime for Helico- Recent observations have shown that Helico- bacter pylori bacter pylon exerts a detrimental effect on the Role of Helicobacter pylon serology in the mucus integrity of the stomach consisting of a initial assessment ofpatients with dyspepsia R P H LOGAN, P A GUMMETT, J J MISIEWICZ, British Society ofGastroenterology A571

R J POLSON, M M WALKER, Q N KARIM, J H BARON organism. This finding may be of importance blood or ulcer); and (C) ulcer, was assessed. (Departments of Gastroenterology, Microbiology in the pathogenesis of gastroduodenal disease. These were: group 1 on M (n=99) v P (n= 106) and Histopathology, Central Middlesex and St (p value) in: (A) 16% v 31% (0.007), (B) 3% v Mary's Hospitals, London) Eradication of 10% (0-071), (C) 2% v 7% (0.21); group 2 on M Helicobacter pylori infection may be indicated (n= 35) v P (n= 32) (p value) in: (A) 46% v 68% Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from even for young patients with severe duodenal Does gold therapy reduce non-steroidal anti- (0-1), (B) 3% v 24% (0-14), (C) 3% v 19% ulcer. However, the presently used lengthy inflammatory drug peptic damage in rheuma- (0.056); and group 1+2 on M (n=134) v P triple therapy regimens of bismuth and anti- toid arthritis? (n= 143) (p value): (A) 24% v 41% (0.005), (B) microbials are not ideal, with risks of side 3% v 14% (0.002), (C) 2% v 10% (0-018). M was effects, drug resistance, and poor toleration by A S TAHA, R D STURROCK, H CAPELL, R I RUSSELL also superior in healing/improving lesions patients. In addition, since one week of bis- (Departments of Gastroenterology and Rheuma- (M80% v P46% p=0.006). There was no clear muth treatment is as effective as four weeks, tology, Royal Infirmary, Glasgow) The com- correlation between endoscopic damage and there is no apparent rationale for these lengthy bination of second line agents (SLAs) and non- abdominal symptoms. Diarrhoea occurred in regimes. The aim ofthis study was to evaluate a steroidal anti-inflammatory drugs (NSAIDs) is M 13%, P 4%, but no patient was withdrawn one week eradication regimen consisting ofone frequently needed and used by rheumatoid for adverse effects. week bismuth subcitrate (120 mg qds) and arthritis patients. Little is known about the In conclusion, damage occurred early in the amoxycillin (500 mg qds) with metronidazole effect of this combination on the gastro- course of NSAID treatment and where minor (2 gm daily) for the last three days. duodenal mucosa despite the multitude of damage pre-existed it rapidly worsened; but Forty seven patients (30 men, mean age 45 studies relating NSAIDs to peptic ulceration. cotreatment with misoprostol significantly pre- years, range 16-80 years) with duodenal ulcer Using endoscopy, we tested the hypothesis that vented or reversed these changes. (n=24) non-ulcer dyspepsia (n=22), and the prevalence of NSAID induced peptic gastric ulcer (n= 1) and H pylon' detected by damage can be influenced by the intake of histology (H&E/Gimenez), culture (Oxoid SLAs. SR147), and a positive "C-urea breath test Patients were recruited if they had taken Misoprostol does not prevent the gastro- ("3C-UBT) (pooled excretion b"CO2 >5 per NSAIDs for a minimum of four weeks and duodenal mucosal effects of the non- ml) were entered into the study. Erythromycin SLAs for at least six months. SLAs included steroidal anti-inflammatory drug, diclofenac (500 mg qds) was used in patients allergic to intramuscular aurothiomalate (gold), amoxycillin (n=2). Follow up was with hydroxychloroquine, penicillamine, and sul- D ARMSTRONG, M NICOLET, G DORTA, `C-UBT at weekly intervals for one month, phasalazine. The endoscopist was not aware of J F SCHNEGG, D VOUILLAMOZ, E SARAGA, then at three, six, and twelve months, and by patients' medications. A L BLUM (Divisions of Gastroenterology and endoscopy at one month. Eradication was A total of 281 patients were studied and Pathology, CHUVIPMU, Lausanne, Switzer- defined as negative culture, histology, and classified according to whether they took land) The hypothesis that new mucosal lesions `C-UBT one month after finishing treatment. NSAIDs only or NSAIDs plus SLAs. Peptic and delayed biopsy site healing seen with the H pylon was successfully eradicated in 40 of ulcers, at least 5 mm in diameter, were found in soluble non-steroidal anti-inflammatory drug 47 (87%) patients (median follow up two 33 of 96 patients (34%) on NSAIDs only, eight (NSAID), diclofenac (DIEP) can be prevented months, range 1-7 months). In four of seven of33 on hydroxychloroquine (24%), 10 of30 on by the oral prostaglandin, misoprostol (M) was patients in whom eradication failed, pretreat- penicillamine (33%), 13 of46 on sulphasalazine tested in a placebo controlled crossover study ment metronidazole resistant strains were sub- (28%), and 11 of 76 on gold plus NSAIDs in 10 healthy volunteers with a normal initial sequently isolated. The most frequent side (14%, x2=7.95, p<0-01 compared with endoscopy. They received two treatment effect was taste disturbance (six of 47, 11%) NSAIDs only, p<0 05 using Bonferroni cor- courses of two weeks, four weeks apart, of M http://gut.bmj.com/ while taking metronidazole. No patients rection for multiple comparisons). Patients (200 ig bd) or placebo (P1). DIEP (50 mg tid) experienced diarrhoea. median ages were 59 years (NSAIDs only), 46 was given only during the second week. Before The results suggest that a one week eradica- years (hydroxychloroquine), and 57 years (the DIEP, three endoscopic biopsy specimens tion regime is a safe, effective, cheap, and well remaining groups). Female/male ratio was were taken from each of the corpus, antrum, tolerated treatment for H pylori. greater than 2:1 in all groups. Baseline and duodenum. After DIEP, endoscopy was NSAIDs and smoking habits were also com- repeated to assess biopsy site healing and new parable in all groups. lesion development and to repeat all biopsies. In conclusion, unlike other SLAs, gold Volunteers recorded symptoms in a diary. on September 24, 2021 by guest. Protected copyright. TREATMENT OF GASTRIC MUCOSAL DAMAGE therapy seems to be associated with a lower Results (statistics: Fisher's exact test) were prevalence of peptic ulcers in patients taking as follows: after DIEP, only petechiae or NSAIDs and its apparently beneficial effect erosions were seen: M+DIEP, two of 10, may have therapeutic implications. P1+DIEP, three of 10. M did not modify the Eradication of Helicobacter pylori: effect on proportion of unhealed, fibrin covered biopsy the antral mucus pH sites in the corpus (M+DIEP: 10 of 30, PI+DIEP: eight of 30), antrum (M+DIEP: 25 S M KELLY, S J MIDDLETON, J CRAMPTON, Misoprostol protects against and reverses of 30, P1+DIEP: 25 of 30) or duodenum J 0 HUNTER (Department of Gastroenterology, early non-steroidal anti-inflammatory drug (M+DIEP: 10 of 30, PI+DIEP: nine of 30). Addenbrooke's Hospital, Cambridge) The exact induced mucosal damage Epigastralgia was more frequent during DIEP mechanisms in the links between Helicobacter (18 of 140 days) than before (six of 140 days: pylori, chronic gastritis, and duodenal ulcera- KD BARDHAN, W M GRIFFIN, G C FENN, p=0-01) but was diminished by M (five of 140 tion remain unexplained but may involve the M J SHIELD, I T BJARNASON, ON BEHALF OF THE days) compared with P1 (19 of 140 days, organism's ability to produce urease, produc- UK/EIRE NSAID WORKING PARTY (District p=0-0028). ing ammonia from urea, and so altering the pH General Hospital, Rotherham; Medical Depart- In conclusion, M does not prevent produc- of the mucosal microenvironment. ment, Searle UK; and Northwick Park Hospital, tion of new lesions or delayed healing of biopsy We measured juxtamucosal pH in 47 Northwick Park) We investigated if the prosta- sites by diclofenac, whose effects may not, patients using a flexible pH microelectrode that glandin analogue misoprostol (M) protects therefore, be due to decreased prostaglandin can be passed down the biopsy channel of against and reverses early major and minor production. (Support: SNF 32-26369.89 & standard endoscopes. Nineteen patients who non-steroidal anti-inflammatory drug Searle.) were positive forHpylori had a pH of6-8 (0-16) (NSAID) induced gastroduodenal mucosal compared with 6-40 (0.24) in 28 negative damage; an unexplored area. A total of 328 patients (p<0-01). Seven positive patients arthritic patients underwent endoscopy one agreed to repeat endoscopy and pH measure- week after stopping NSAIDs: 51 (16%) had Randomised double blind controlled trial of ment after treatment to eradicate the organism ulcers and were excluded; 205 (62%: group 1) intravenous famotidine infusion in 1005 (six weeks bismuth subcitrate 240 g bd and two had no visible damage; 72 (22%; group 2) had patients with peptic ulcer bleeding weeks metronidazole 400 mg tds). erosions/or mucosal petechiae, or both, but no Eradication of the organism was achieved in ulcer. Patients in groups 1 and 2 were randomly R P WALT, J COTTRELL, S G MANN, N FREE- six patients and the mean juxtamucosal pH fell allocated to receive M 400-800 [tg daily or MANTLE, M J S LANGMAN (FOR GI BLEEDING from 6-81 (0-17) to 6-08 (0-16) (p<0-01). One placebo (P) with an NSAID and were endo- STUDY GROUP) (Department ofMedicine, Univer- patient remained positive and did not show scoped again after two weeks. The incidence sity ofBirmingham and Merck Sharp and Dohme such a fall (pH 6-8 initially, 7.0 post treatment). of: (A) all mucosal damage; (B) significant Pharmaceuticals, Hoddesden) Rebleeding after H pylori produces an increase in juxtamucosal damage (¢ 10 erosions or petechiae or coales- peptic ulcer haemorrhage can be disastrous. pH which is reversed by eradication of the cent intramucosal blood or free intraluminal Maintaining gastric pH close to neutrality A572 British Society ofGastroenterology could influence platelet function and plasma patients who had not received prior NSAID the elucidation of the role of mycobacteria in coagulation, which are pH sensitive, and might medication. inflammatory bowel disease and other gastro- limit pepsin induced clot lysis thus decreasing intestinal diseases. rebleeding. Previous individual trials with H2 antagonists have been inadequate but a meta- Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from analysis supported an important clinical effect. PATHOGENESIS OF CROHN'S DISEASE A total of 1005 patients admitted to any of 67 Serological and immunohistochemical study hospitals (UK and Eire) with haemorrhage offactor XIIIa subunit in Crohn's disease from peptic ulcer (including stigmata of ooz- ing, fresh clot, or visible vessel received either Polymerase chain reaction detects myco- M HUDSON, R A HUTTON, A P DHILLON, famotidine (10 mg bolus followed by 3-2 bacterum paratuberculosis in Crohn's E A SANKEY, L MORE, R SIM, A J WAKEFIELD, mg/hour intravenusly (F) n=497) or match- disease tissue extracts PB A KERNOFF, R E POUNDER (Inflammatory ing placebo ((P) n=508) for 72 hours. Treat- bowel disease study group, Academic Departments ment groups were similar in respect of age J D SANDERSON, M MOSS, Z MALIK, M TIZARD, ofMedicine and Histopathology and Department (range) 67 years (21-93) (F), 66 years (19-93) E P GREEN, J HERMON-TAYLOR (Department of of Haemophilia and Haemostasis, Royal Free (P); sex 37-6% women (F), 36-6% women (P); Surgery, St George's Hospital Medical School, Hospital School of Medicine, London) It has ulcer site 55 5% duodenal, 39-8% gastric (F), London) DNA was extracted enzymatically been suggested that thrombotic microvascular 55.9% duodenal and 40% gastric (P). Mortality from full thickness intestinal resection samples inflammation may be central to the patho- (6-2%, 5.0%), rebleeding (23-7%, 25 6%), and from 40 patients with active Crohn's disease genesis of Crohn's disease. The final com- surgical intervention (15-3%, 17-1%) in F and P (CD) and 27 cancer or diverticular disease ponent of the clotting cascade, factor XIII, is groups respectively did not differ significantly. control subjects. Polymerase chain reaction responsible for cross linking fibrin into stable Deaths were most common in the elderly (1-1% (PCR) was performed using oligonucleotide clot. Plasma factor XIII is composed of two <65 years, 9-1% ¢65 years) irrespective of primers amplifying a 400 base-pair portion of subunits denoted a and b (a2, b2), the active treatment. Death rates from duodenal (5.0%) IS900, a DNA insertion element specific for subunit ofwhich is factor XIIIa. and gastric (6.6%) ulcers were similar. Mycobacterium paratuberculosis. Stringent pre- The plasma level of factor XIIIa was com- Inhibition of acid secretion does not in- cautions were taken to exclude artefact due to pared with activity of Crohn's disease, quanti- fluence outcome from severe gastrointestinal contamination. A single M paratuberculosis fied by C reactive protein and Crohn's disease bleeding caused by peptic ulcers. genome could be detected in each PCR reac- activity index (CDAI) in 16 patients, in a tion. A 100% yield in the DNA extraction longitudinal study from relapse (CDAI>150) would enable detection of 1000 M paratubercu- to remission. Immunohistochemistry for factor losis genomes per lg of intestinal tissue. XIIIa was performed on formalin perfusion Misoprostol versus placebo in prevention of M paratuberculosis DNA was detected in 26 of fixed specimens of resected Crohn's disease recurrence of acute upper gastrointestinal 40 (65 0%) CD tissues and in four of27 (14-8%) bowel. haemorrhage: a randomised double blind control tissues. The proportion among small Factor XIIIa plasma values were signifi- study. and large bowel samples was the same. All cantly lower in active Crohn's disease (median buffer only controls were negative. 63 (95% CI 46-72) U/dl) than in remission G C ROBINSON, M J SHIELD, G C FENN (INTRO- Mparatuberculosis is long known as a cause of (median 90 (95% CI 60-112) U/dl), p=0002; DUCED BY D G THOMPSON) (GD Searle & CoLtd, chronic enteritis in animals. Its presence in a there was a significant negative correlation with High Wycombe, Bucks) The effect of miso- low proportion of control human gut tissues is CDAI (p=0 005) and platelet count (p=0 003), prostol (M) or placebo (P) on rebleeding was consistent with an environmental prevalence. and a significant positive correlation with http://gut.bmj.com/ assessed in 307 patients with acute upper Its presence in a high proportion of CD tissues serum albumin (p=0 006). Immunohisto- gastrointestinal haemorrhage confirmed endo- is consistent with a role for this organism in the chemistry showed that gut mucosal and sub- scopically with 24 hours of admission. Patients pathogenesis ofchronic enteritis in humans. mucosal macrophages stained strongly for satisfied rigorous admission criteria (presence factor XIIIa, even in macroscopically normal of adherent clot or visible vessel at endoscopy areas of mucosa; capillary thrombi underlying and a requirement for at least two units of superficial mucosal erosions showed immuno- packed red blood cells or whole blood) and Detection of Mycobacterium paratuber- staining for factor XIIIa. received 275% ofprescribed study medication culosis in inflammatory bowel disease In conclusion low factor XIIIa values in on September 24, 2021 by guest. Protected copyright. over a period of four days after admission. active Crohn's disease and the finding of capil- In this multicentre study patients received M P QUIRKE, D DOCKEY, G R TAYLOR, F A LEWIS, lary thrombi (and factor XIIIa positive macro- 200 ig qds (n= 160) or P (n= 147) on a P HAWKEY, D GRAHAM, M F DIXON (Gastroenter- phages) in non-ulcerated mucosa, suggest that randomised double blind basis. Endoscopy or ology Group, UniversityDepartment ofPathology microvascular injury is an early event in surgery was used to confirm suspect rebleeding and Yorkshire Regional DNA Laboratory, Leeds Crohn's disease. (vasomotor collapse, haematemesis, melaena, General Infirmary Trust, Leeds; Department of fresh blood in stools). Microbiology, University of Leeds; and Depart- The rebleed rate was 14-4% on M v 23-8% on ment of Gastroenterology, Baylor College of P (p=0-016). In the M group, 27% of rebleeds Medicine, Houston, Texas, USA) The role of Specific inorganic microparticles in gut occurred from gastric ulcers compared with mycobacteria in Crohn's disease remains an tissue may initiate Crohn's disease 40% of rebleeds from gastric ulcers in patients enigma. Polymerase chain reaction (PCR) treated with P. amplification of specific mycobacterial genes J J POWELL, C C AINLEY, M D KENDALL, Patients on M were discharged earlier than overcomes many of the difficulties previously A P DHILLON, E A SANKEY, R P H THOMPSON patients on P, and fewer required surgery encountered. We have developed a PCR to 16S (Gastrointestinal Laboratory, Rayne Institute, St (13-8% v 18-6%). This difference was not rRNA which identifies Mycobacterium para- Thomas's Hospital; Cell Biology Unit, Bio- statistically significant. At four days, the 98 tuberculosis and M avium-intracellulare and two chemistry Department, UMDS, St Thomas's patients who had received non-steroidal anti- PCRs to the 5' and 3' ends ofthe IS900 gene of Hospital; and Department of Histopathology, inflammatory drugs (NSAIDs) in the 30 days M paratuberculosis that are specific for the Royal Free Hospital, London) Mucosal intes- before entry were more prone to rebleeding latter. The specificity of the PCRs were con- tinal lymphoid aggregations (ILA) scavenge (28.6%) than patients who had not received firmed by positive amplification of mycobac- particles and macromolecules from the gut prior NSAIDs (16-9% rebleeds). The treat- terial cultures ofM paratuberculosis strains Ben lumen to carry out immunological surveillance. ment difference between M and P was, how- and Dominic and failure to amplify M avium- Pigmented macrophages, consistently found at ever, seen in both groups (NSAID takers and intracellulare and M tuberculosis. Five cases of the base of ILA, contain scavenged material non-NSAID takers). Johne's disease amplified successfully. DNA that is resistant to cellular breakdown. The Diarrhoea was reported by 5% of M treated extracted from surgically resected specimens physicochemical characteristics of this patients and 2% of P patients. Overall, the from 10 cases of histologically and clinically material is unknown, but it contains alumi- incidence of adverse events, reported in each documented inflammatory bowel disease were nium, silicon, and titanium. We have now group, was similar. amplified with IS900 primers with detection of further examined these macrophages by laser In conclusion, M significantly reduced M paratuberculosis in two of five cases of scanning microscopy (LSM), electron micro- rebleeding rates particularly from gastric ulcer Crohn's disease and one of five cases of ulcera- scopy, x ray microanalysis, and electron energy and reduced the need for surgery in patients tive colitis. loss spectroscopy. Wax sections (10 Am) were with a recent upper gastrointestinal haemor- This work confirms the presence ofM para- prepared for LSM (n= 10 Crohn's, five colitis, rhage. Patients with a recent history ofNSAID tuberculosis in both types of inflammatory five bowel cancer) and areas ofILA reprocessed treatment were more likely to rebleed than bowel disease. This type ofapproach will allow for electron microscopy and analysis. British Society ofGastroenterology A573

Distinct intracellular particles were consis- its morphogenesis and growth factor tively) and with ulcerative colitis patients tently found in all patients. Stepwise (1 lim) expression. (p<00001 and p<0*0006 respectively), and sectioning through these macrophages allowed Cells in the mid-region of the duct were lgG antibodies were significantly higher in reconstruction of three dimensional images, positive for the proliferating cell nuclear small bowel than in colonic Crohn's disease showing that the particles were clustered in antigen (PCNA; a protein maximally expressed (p<0 01). Titres were no higher in two patients Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from discrete areas of the cells, found to be vesicles in S phase of the cell cycle) suggesting the with clinical intolerance to yeast. The antibody by electron microscopy. Analysis showed the establishment of a proliferative compartment titres in ulcerative colitis were not different to presence of titanium dioxide and generally rod within the lineage. Abundant immunoreactive those ofnormal controls. High titres oflgG but shaped semicrystalline aluminosilicates. transforming growth factor a (TGFa) was not lgA isotypes were present in patients with These inert, inorganic particles may cause found in cells in both the gland area and in the coeliac disease, the antibody responses being chronic inflammation in tissues, as they do in ducts of the lineage. Immunoreactive EGF indistinguishable from those found in Crohn's susceptible individuals in the chronic inflam- receptor was found predominantly on the disease. matory disease, podoconiosis, in Africa. An microvillar membrane of the non-lineage We conclude that the presence of lgG anti- abnormal reaction to such modern dietary enterocytes of the villous. By comparison no body to S cerevisiae is not specific to Crohn's particles, initiated at the base of ILA's, could cell surface expression of EGF receptor was disease. Although lgA antibody titres seem to explain the pathological, epidemiological and seen on cells ofthe lineage. be more specific to Crohn's disease, their clinical basis ofCrohn's disease. These observations suggest that the lineage pathogenic importance remains to be is self renewing and that it is capable of established. producing multiple growth factors that can interact with receptors on adjacent enterocytes. Distribution of collagen types in Crohn's disease GROWTH AND REPAIR IN THE SMALL INTESTINE

J-L FAUCHERON, A ALEXANDER, M IRVING Metalloproteinases in the intestine of (Department ofSurgery, Hope Hospital (Univer- patients with Crohn's disease sity ofManchester School ofMedicine), Salford). Effects of bolus doses of fat on release of In previous studies we have shown abnormal C J BAILEY, R M HEMBRY, A ALEXANDER, enteroglucagon, peptide tyrosine, tyrosine, concentrations ofvitamin C, an essential factor C A SHUTTLEWORTH, M E GRANT, M H IRVING gastrin, and cholecystokinin in collagen metabolism, in bowel affected by (Departments of Biochemistry and Surgery, Crohn's disease (CD). We have also shown University of Manchester and Strangeways A P JENKINS, M A GHATEI, S R BLOOM, abnormal accumulation of collagens in macro- Research Laboratonres, Cambnrdge) Crohn's R P H THOMPSON (Gastrointestinal Laboratory, scopically normal and diseased segments of disease is associated with significant connective Rayne Institute, St Thomas's Hospital, and bowel affected by CD. In the present studies tissue remodelling and deposition within the Department ofMedicine, Hammersmith Hospital, we have used immunofluorescence and intestinal wall. Alterations in connective tissue London) Compared with divided doses, bolus immunoperoxidase techniques to show the levels at these sites represents a change in the doses of long chain triglycerides increase rat anatomical distribution of these abnormally balance between collagen synthesis and small intestinal mucosal mass and cell pro- accumulated collagens. degradation. Connective tissue is degraded by liferation. It is possible that this effect is All collagen types (I, III, IV, V, and VI) the matrix metalloproteinases, collagenase, mediated by an enterotrophic peptide, perhaps seemed increased in CD throughout the whole stromelysin, and gelatinase, whose activity is enteroglucagon. thickness of the bowel (n=18). In 65% of regulated by tissue inhibitor of metallopro- There were four replicate studies, each in- http://gut.bmj.com/ macroscopically diseased bowel samples we teinases (TIMPs). Immunolocalisation has volving two groups of 12 female Wistar rats observed patchy deposition of type V collagen shown gelatinase and stromelysin to be con- (185-220 g) isocalorically fed identical diets in the muscularis propria. This finding was fined to a few isolated inflammatory cells in giving 48-2% total calories as the essential fatty reduced to 25% in macroscopically normal normal intestine. In Crohn's diseased intestine acid rich oil Efamol. To one group the oil was bowel, but was not observed at all in the bowel the inflammatory infiltrate is associated with a given in bolus doses twice daily by gavage, of patients without CD (n=4). The same dramatic increase in these two enzymes. while for the other group it was mixed with the pattern of collagen deposition was also seen Stromelysin is also detectable on the extracel- remainder of the feed and therefore consumed with types I and III. The increase in type IV lular matrix in regions of mucosal degradation over the course of 24 hours. After 21 days, one on September 24, 2021 by guest. Protected copyright. collagen could be related to the increased and smooth muscle cell proliferation. TIMP is animal from each group was killed every two vacularity associated with active CD. shown to be synthesised and secreted by the hours by exsanguination, thus providing In conclusion, these studies confirm the intestinal mucosa and to be present in blood regular plasma samples over 24 hours for abnormal accumulation of collagen in patients vessel endothelial cells. The distribution of subsequent measurement of enteroglucagon, with CD and have shown the exact distribution TIMP is not related to the diseased state of the peptide tyrosine, tyrosine (PYY), gastrin, and of each type. The accumulation of collagens in tissue. In contrast, the consistent finding of cholecystokinin (CCK). the muscularis propria seemed specific to active raised levels of gelatinase and stromelysin in Bolus dosing with Efamol significantly in- CD. Future studies must be directed towards Crohn's diseased tissue strongly implicates a creased the area under the curve of plasma identifying the factors stimulating proliferation key role for these enzymes in connective tissue concentrations of enteroglucagon (mean 3211 of collagen. remodelling in Crohn's disease. (SEM) (155) v 1618 (182) pmolhour/l, p<0 05, Wilcoxon's test) and also of PYY (1728 (75) v 1014 (86) pmolhour/l, p<005). However, plasma concentrations of gastrin and CCK Morphogenesis ofand growth factor produc- Yeast antibodies in patients with Crohn's were unaffected. tion by the cell lineage induced by mucosal disease In conclusion, the enhanced enterotrophic ulceration in Crohn's disease effects ofbolus doses oflong chain triglycerides M H GIAFFER, C D HOLDSWORTH, A CLARK may be mediated by enteroglucagon. D J AHNEN, W GULLICK, N A WRIGHT (Denver (Departments of Gastroenterology and Clinical Department of Veterans Affairs Medical Center Immunology, Royal Hallamshire Hospital, Shef- and The University of Colorado School of field) It has recently been suggested that Medicine, Denver CO, USA; Imperial Cancer Saccharomyces cerevisiae (baker's yeast) may Effects of interferon-y and tumour necrosis Research Fund Oncology Group, Hammersmith play a significant role in the pathogenesis of factor a on HLA class II expression on Hospital; and Histopathology Unit, Imperial Crohn's disease. We have therefore assessed jejunal mucosal biopsy specimens cultured in Cancer Research Fund, London) We have the prevalence of lgG and lgA antibodies vitro recently described an epidermal growth factor against three S cerevisiae strains (NCYC 77, (EGF) producing cell lineage that is induced by NCYC 79, and NCYC 1108) in 49 patients with R P STURGESS, J SPENCER, C-H HUNG, ulceration of the gastrointestinal tract. The Crohn's disease, 43 with ulcerative colitis, 14 J M NELUFER, L B HOOPER, P J CICLITIRA (The lineage appears as buds from the base of with coeliac disease, and 21 healthy control Rayne Institute, St Thomas's Hospital and intestinal crypts and grows locally to form subjects. The Department of Histopathology, University small glands in the lamina propria which lgG and lgA antibody responses to each of College and Middlesex School ofMedicine, Lon- converge to form a duct that emerges onto the three strains were similar. lgG and lgA anti- don) HLA class II molecules present antigen to villous surface. We have used immuno- body titres were significantly raised in patients the immune system. Aberrant enterocyte HLA peroxidase immunohistochemistry of serial with Crohn's disease compared with healthy class II expression has been shown in coeliac sections through the lineage to examine further controls (p<0 0001 and p<0 0001 respec- and inflammatory bowel disease, and on A574 British SocietyofGastroenterology colonic cell lines and fetal intestine after culture E LIEHL, F-E MALY (Gastrointestinal Unit and suggests intraluminal growth factors are with the cytokines interferon y (IFN y) and Institute of Clinical Immunology, University important regulators ofintestinal growth. tumour necrosis factor a (TNF a). Hospital, Berne, Switzerland, and Sandoz AG, Seven patients subsequently shown to have Vienna, Austria) Cytokines, products from normal jejunal histology underwent small inflammatory or immune reactions, influence Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from intestinal biopsy for diagnostic purposes. The functions of many cell types outside the CONSTIPATION AND INCONTINENCE expression of HLA-DR, DP and DQ was immune system: tumour necrosis factor (TNF) investigated by immunohistochemistry of regulates gastric acid secretion and 116 has been frozen sections cut from biopsy specimens that found in human intestinal epithelial cells had been cultured for 24 hours with IFN y, (IEC), but its relevance to their functions is Abnormal visceral autonomic sensation in TNF a, or both, at concentrations of 10, 100 unknown. We investigated whether IL 6 and neurogenic faecal incontinence and 1000 IU/ml. Specimens cultured with TNF modulate the growth of a rat small medium alone, or 0 1, 1 and 10 mg/ml of intestinal epithelial cell line (IEC18) and if this CT M SPEAKMAN, M A KAMM (Physiology Unit, phytohaemagglutinin (PHA), a T cell mitogen, would be modified by the growth factor EGF. St Mark's Hospital, London) Neurogenic faecal served as negative and positive controls respec- Cells from semiconfluent cultures in Dul- incontinence may involve both sphincter tively. becco's modified Eagle's medium (DMEM) denervation and a visceral autonomic distur- Increased expression of HLA class II anti- with 5% fetal calf serum (FCS) were plated to bance. To investigate this we have studied gens in all biopsy specimens cultured with microtitre wells (15 x 10' cells/well) in DMEM rectal and anal sensation using balloon disten- PHA was observed. Five patients exhibited containing 0.5% FCS with or without rat sion and the more quantifiable electro- increased HLA class II expression after culture recombinant epidermal growth factor (EGF), sensitivity. Patients with neurogenic incon- with both IFN y or TNF a. No synergism was 20 ng/ml. After 42 hours ofculture with human tinence were contrasted with healthy control observed between IFN y and TNF a. recombinant Il 6 or TNF (2-50 ng/ml), 'H subjects and patients with direct sphincter DR>DP>DQ staining patterns were thymidine (1 ,uCi/well) was added and incor- damage. observed. poration was measured six hours later. Twenty six women (mean age 49 years, range We have shown that cytokines induce in- Il 6 and TNF. both modulated growth of 22-67) with neurogenic incontinence as shown creased HLA class II expression in jejunal IEC18: II 6 dose dependently enhanced by prolonged pudendal nerve latencies and an mucosal biopsy specimens. This in vitro pro- thymidine incorporation (cpm, mean (SD), intact spincter, 16 women (age 44 years, 30-66) duction of a small intestinal abnormality n=6) from 5989 (422) (control) to 7050 (431) with obstetric sphincter tear but normal inner- observed in coeliac disease provides further (50 ng/ml), p<0*005. This effect was even vation, and 17 healthy control women (age 37 evidence ofa local T cell mediated pathogenetic more pronounced in the presence of EGF years, 26-61) were studied by one investigator. mechanism in this condition. (15553 (1295) v 21950 (2109), p<0 0005). Maximum resting and contraction pressures TNF alone stimulated cell proliferation at were recorded, rectal sensation was tested smaller doses (2-10 ng/ml). However, it dose using balloon distension (noting volume for dependently inhibited EGF stimulated pro- threshold, urgency, and pain) and a bipolar Epithelial celi height in nornal subjects and liferation (15553 (1295), control v 12332 (1592) ring electrode (noting sensory threshold). Mid- in patients with coeliac disease 50 ng/ml, p<0 01). anal canal sensory threshold was tested. Thus, these cytokines may contribute to Mean resting and contraction pressures were M G TABBA, M F DIXON, A T R AXON (Gastro- regulation of intestinal epithelial cell regenera- significantly lower in both groups of inconti- enterology Unit and University Department of tion; II 6 particularly may act as an autocrine nent patients (p<005). Patients with neuro- Pathology, The General Infirtnary, Leeds (The growth regulator. (Supported by SNF No genic incontinence showed raised rectal sensa- http://gut.bmj.com/ characteristic histological abnormality in 32-26478.89). tion to threshold (54-1 v 31.5 ml, p<0-05) and coeliac disease is villous atrophy associated urgency (94.9 v 65 ml, p<0-05) when com- with crypt hypertrophy. In addition, however, pared with control subjects. Pain threshold was epithelial cells change from a tall columnar normal. Electrical sensory threshold in these morphology to a cuboidal appearance. The aim Pancreatic biliary diversion increases patients was also raised in both the rectum of this study was to measure cell height and luminal growth factor activity proximal to the (25-7 mA v 16 mA, p<0 05) and anal canal (7-8 width to determine whether these abnor- entry ofpancreatic juice mA v 4-2 mA, p<0 05). Patients with malities can be used objectively. sphincter tears showed normal distension and on September 24, 2021 by guest. Protected copyright. Using an eyepiece micrometer, epithelial R J PLAYFORD, A C WOODMAN, P WATANAPA, electrical sensitivity. height (EH) was measured in four compart- M ALLISON, P H DEPREZ, R C N WILLIAMSON, In conclusion, there is a disturbance of ments of the jejunal mucosa; top, middle and J CALAM (Department ofMedicine, Royal Post- visceral autonomic sensation in patients with bottom third of the villi (VEH) and in the graduate Medical School, London) Pancreatic- neurogenic incontinence as shown by two crypts (CEH). In addition epithelial cell width obiliary diversion (PBD) causes increased different techniques. However, women with was measured in the villus (VEW) and the growth of the proximal segment of intestine incontinence because of a sphincter tear have crypts (CEW). In patients with normal histo- which is not perfused with pancreatic juice. reduced anal pressures but normal anorectal logy (n=25) the mean VEW was 5-8 lim and The mechanism of this effect has not been sensation. Neurogenic faecal incontinence CEW 6-3,um compared with 5-75 and 6.0 in the established. We recently showed that epider- therefore involves a disturbance ofthe innerva- coeliac group (n= 10) respectively (not signifi- mal growth factor and transforming growth tion of proximal bowel as well as the sphincter cant). Normal subjects had a mean VEH at the factor a can be digested by pancreatic enzymes mechanism. bottom of the villi of 28-6 tim, in the middle in vitro. This led us to speculate that increased 34-3 rim, and at the top 29-1 rim. The mean growth in the proximal segment is the result of VEH was 30.7 [sm. Coeliacs had a mean VEH diminished digestion of lumenal growth of 19-5 [im (p<0 001). Conversely, the crypt factors. We therefore examined intralumenal Spina bifida occulta: is it of any relevance in cells in coeliacs were taller than in normal growth factor activity above and below the the pathophysiology of constipation due to subjects, with a mean CEH in coeliacs of22-9 v entry ofdiverted pancreatic juice. outlet obstruction? 19-8 in normal subjects (p<0 001). The ratio of Six rats had a Roux-en-Y operation to pro- villous to crypt epithelial cell height was 1-55 in duce PDB six months before the study. Eight A C THORPE, R EVANS, N S WILLIAMS (Depart- normal subjects compared with 0-82 in coeliac cm of intestinal lumen above and below the ments of General Surgery and Radiology, Royal patients. diversion were washed with Williams medium London Hospital, London) Spina bifida occulta This investigation shows that changes occur E+antibiotics. The growth factor activity of (SBO) is an abnormality usually found in the in the height ofepithelial cells during migration washings was assessed using (H3) thymidine posterior arch formation of the upper sacrum. from crypt to villous tip in the normal jejunum uptake into primary rat hepatocytes as a Since it has been implicated in the aetiology of and that VEH provides an objective assessment bioassay. Intraluminal growth factor activity urinary voiding problems, we have investi- of epithelial changes which arise in coeliac was 2100 (900) DPM below the diversion gated its incidence in constipated patients with disease. which was not significantly different from non- outlet obstruction. stimulated hepatocytes (2600 (200) DPM) but Plain abdominal radiographs of 52 female growth factor activity was 4900 (700) DPM) patients with chronic constipation were (p<002) above the diversion. reviewed by one radiologist. Abnormalities in Cytokines: mediators of intestinal epithelial In conclusion, these results are consistent both the posterior sacral archi and the level of cell growth with the idea that diversion of pancreatic juice opening of the posterior art were assessed. increases growth proximally by decreasing Abdominal radiographs of 48 age matched C-C SCHURER-MALY, F HALTER, A URWYLER, digestion of lumenal growth factors. This women attending hospital for intravenous British Society ofGastroenterology A575 urography as an investigation of haematuria pancake and the next two days. A single offer a better result? Does a simple stoma were similarly assessed to act as controls. radiograph was obtained at four and seven days relieve symptoms? We have explored these two SBO was seen in 17 patients (32 6%) and 11 (radiation 10 mSv). Regions of interest were: alternative managements. of All patients had 50% of the radioisotope mean age 19 years, mean follow up one year) - gorised as having anismus, slow transit, or a at 72 hours. In patients at 24 and 48, and 120 with rectosigmoid dilatation. (B) Colostomy mixed picture. Three of seven patients (42 6%) hours the COM of radioisotope and markers eight patients (three women, mean age 35 with anismus had SBO. Of 19 patients with was not different (24 hours: 4-2 v 3-8, 48 hours: years, mean follow up three years). (C) Ileos- slow transit, five (26.2%) had SBO and of seven 4.5 v 4.9, 120 hours 6-6 v 6-3, p>0 05; tomy - four patients (two women, mean age 35 patients with a mixed picture, three (42.6%) medians, Wilcoxon test). At 72 and 96 hours years, mean follow up one year) with previous had SBO. There was no statistical significance (the time of optimum importance) there was a colectomy. on comparing the incidence of SBO in these significant difference (72 hours: 5.2 v 5-6, 96 (A) Coloanal anastomosis restored normal groups with the control group. hours: 5-6 v 5.9, p<0-01). A time activity bowel frequency in five patients but one patient In conclusion, these results suggest that SBO curve, to demonstrate sites of delay, could be died of cardiorespiratory failure and another plays no role in the pathophysiology of con- constructed only with the isotopes. needed further surgery for constipation. stipation due to outlet obstruction. In conclusion, resin bound isotope ingestion (B) Colostomy improved wellbeing in four allows accurate regional colonic transit deter- patients but three proceeded to a later colec- mination with a low radiation. To obtain these tomy. (C) Ileostomy improved the wellbeing in data using markers and x rays requires a daily x all four patients but abdominal pain and disten- What is outlet obstruction constipation? - a ray and high radiation; we have shown that sion remained unchanged. pathological and biochemical study of the infrequent radiographs, even with three dif- In conclusion, coloanal anastomosis involves pelvic floor musculature ferent markers, are not accurate in constipated a lesser resection than colectomy but is more subjects. complex and requires careful patient selection. - I G FINLAY, M AITCHISON, S GORAM, D DOYLE Preoperative motility studies are necessary in (INTRODUCED BY J McKENZIE) (Department of one coloanal patient non-dilated colon was still Surgery, Royal Infirmary, Glasgow) Patients poorly propulsive postoperatively. Colostomy with idiopathic faecal incontinence (IFI) have Dynamic proctography in constipated and ileostomy are satisfactory reversible alter- an antecedent history of straining at stool, subjects natives which may produce symptomatic relief. similar to that reported in patients with outlet obstruction constipation (OOC). Histology of M PAPACHRYSOSTOMOU, T M J GRIFFIN, the pelvic floor musculature in IFI shows C M FERRINGTON, M V MERRICK, A N SMITH neuropathy and collagen depositions but has (Departments ofSurgery, Nuclear Medicine, and Anal anaesthesia is a common cause of not been studied in OOC. We compared Medical Physics, Western General Hospital and failure after surgical treatment of neuro- traditional neurohistology and biochemical University of Edinburgh, Edinburgh) Twelve pathic faecal incontinence http://gut.bmj.com/ quantification ofcollagen content ofthe levator patients with longstanding constipation were ani (LA) and puborectalis (PR) muscles in examined by radioisotope proctography. Tech- J ORTIZ, M OYA, A ROBSON, J ASPERA, B PANA- patients with (a) IFI (n=9) (b) OOC (n= 10), netium labelled potato mash was inserted rec- GAMURA, D KUMAR, M R B KEIGHLEY (Depart- and (c) normal control subjects (n=7). tally to provoke the urge to defaecate. Counts ment of Surgery, Queen Elizabeth Hospital, On histology, neuropathy with reinnerva- were recorded during periods of squeezing, Birmingham) Anal anaesthesia is common in tion was found in seven patients with IFI; in coughing, straining, and evacuation. The neuropathic faecal incontinence. To investi- seven patients with OOC, and in one control stored data were used to produce computer gate whether anal anaesthesia improves after subject. imaging of the effects of these manoeuvres. surgical repair of the pelvic floor, if it is In IFI, the collagen content was increased in The changes observed were as follows: associated with motor deficiency in the anal on September 24, 2021 by guest. Protected copyright. both PR and LA muscles compared with (1) Pelvic floor movements (imparted to the canal, and whether it can predict a group who control subjects, p<0-01. In OOC only the LA isotopically labelled 'faecal' bolus) - movement are unlikely to be improved by operation, we muscles had an increased collagen content was consistently upwards on squeezing (range have studied 49 patients who underwent anal compared with control subjects, p<0-01. 5.5-48.5 mm), less so on coughing, and was manometry, rectal sensation, and mucosal elec- These data show that a similar pelvic floor downwards on straining and maximal at trosensitivity before and three months after neoropathy occurs in both OOC and IFI. IFI evacuation (range -2 to -48). (2) Alteration in operation. Complete anal anaesthesia was differs from OOC only in the degree of damage the anorectal angles - the anorectal angle at rest recorded in 33 patients (66%), eight had some to PR, suggesting that OOC may preceed IFI. (range 91-133°) became more acute on squeez- impairment of sensation, and only eight were ing (range 55-119°), less so on coughing; it judged to have normal sensation preoperatively. became wider than at rest on straining (range There was no correlation between anal mucosal 94-149°) and maximal on evacuation (range electrosensitivity (mA) and max resting or max Assessment of regional colonic transit in 105-165°). (3) The expulsion time of the squeeze anal canal pressures (cm H2O). There severe idiopathic constipation: superiority of 'faecal' bolus (the duration and adequacy of was no correlation between anal sensation and radioisotope compared to radio-opaque this was estimated) - in five of the 12 patients either rectal sensation or the rectoanal inhibi- markers expulsion was noticeably delayed or evacuation tory reflex. Of the 33 patients with complete incomplete. anaesthesia, only 10 had a good result, whereas J R M VAN DER SIJP, J M D NIGHTINGALE, This method allows measurable visualisation 1 1 of the remaining 16 patients who either had M A KAMM, E WALKER, M GRANOWSKA, of simulated defaecation without the discon- slight impairment or normal electrosensitivity G P MORRIS, J E LENNARD-JONES, L M A AKKER- tinuity which accompanies the radiological had a good result (p<0 05). MANS (St Mark's Hospital, London) Radioiso- one. These data indicate that anal anaesthesia tope bound to a non-absorbable resin bound in may identify a group of patients who are as a meal has been used to assess accurately unlikely to benefit from pelvic floor repair. regional colonic transit and was compared with simultaneously ingested radio-opaque markers Alternative surgery for idiopathic mega- and x rays to assess their accuracy. rectum and megacolon Twelve women with severe idiopathic con- Cisapride in severe chronic constipation: a stipation (mean age 35 years (range 24-46) G STABILE, M A KAMM, P R HAWLEY, double blind study bowel frequency <1 per week) and 12 control R K S PHILLIPS, J E LENNARD-JONES (St Mark's subjects (eight women, mean age 33 years Hospital, London) Colectomy for idiopathic L BENINI, S CALIARI, E BARDELLI, S PILATI, (range 19-49)) ate a pancake containing "'In megarectum or megacolon offers the best F BONFANTE, G CASTELLANI, C SEMBENINI, labelled resinmicrospheres (radiation 0 8 mSv). results, but some patients remain constipated. I VANTINI (Divisione di Gastroenterologia, COC Scans were obtained three and six hours after the Those with a very dilated rectum may require a di Valeggio siM, University ofVerona, Italy) The meal and then three times daily for seven days. Duhamel procedure, but with a variable out- aim of this study was to test the efficacy of Radio-opaque markers were ingested with the come. Does excision of the dilated segment cisapride in constipation refractory to bulk A576 BritishSociety ofGastroenterology forming agents. Forty patients referred for pathogenetic role of AECA, if any, requires oncogene c-n-ras. This report indicates, how- severe constipation underwent a one month further investigation. ever, that overexpression of HGF is unlikely to basal period with bran supplements; they were be an integral part of the malignant process of admitted to the study if bowel frequency was established liver cancer, it may be although Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from less than three per week. Only fifteen entered involved in hyperplastic states predisposing to the four month study; all underwent a H2 Secretion of circulating ICAM-1 into bile malignancy. breath test for mouth to caecum transit time, duct during human liver allograft rejection mouth to anum transit time with radio-opaque markers, and completed a diary card with D H ADAMS, E MAINOLFI, J M NEUBERGER, number ofmovements, consistency, severity of E ELIAS, R ROTHLEIN (The Liver Unit, Queen constipation, and subjective efficacy of treat- Elizabeth Hospital, Birmingham and Boehringer Inhibitory effects on hepatocyte DNA syn- ment. The Fisher's and Friedman's tests were Ingelheim Division of Immunology, Ridgefield, thesis of conditioned medium from liver non- used for statistical evaluation. Eight patients USA) The leucocyte- adhesion molecule parenchymal celis after partial hepatectomy received cisapride (C) and seven placebo (P1). ICAM-1 is strongly expressed on structures Five patients dropped out after one to three such as bile ducts during human liver allograft A J WOODMAN, H J F HODGSON (Royal Post- months for inefficacy (four P1, one C). Age, rejection where, it may play a role in targeting graduate Medical School, Hammersmith Hos- bowel frequency, stool consistency, severity of immune damage. Lymphocytes secrete a func- pital, London) Liver regeneration is initiated by symptoms, and transit times were equal at tionally active circulating form of ICAM-1 growth stimulators and terminated by growth in the two A inhibitors. TGF 3 is the best characterised of entry groups. significant improve- (CICAM-1). We have developed an ELISA the ment in bowel frequency and severity of symp- using two monoclonal antibodies recognising inhibitors of growth. We have shown toms compared with the basal was previously that conditioned media from period found different epitopes on CICAM-1 and used it to cells in all the studied patients (p<003). Ifstratified measure levels of ICAM-1 in blood and serum hepatic non-parenchymal (NPC) isolated for treatment, this improvement was from livers 24 hours after partial hepatectomy signifi- after liver transplantation. CICAM-1 was inhibited EGF stimulated DNA in cant in the C group overall and at two and three detected in serum from 17 patients with acute synthesis months (p<0 05), in the PL group it was rejection (median (range) 744 (424-1458) normal rat hepatocytes, and now report the significant only in the first two months time course of production of this inhibitor. (Fried- ng/ml) and 14 patients with graft dysfunction Conditioned man's). C was considered effective by seven of caused by bacterial cholangitis or cytomegalo- media from NPC cultures isolated eight patients, P1 by two ofseven (p<0 05). No vinis hepatitis (median (range) 644 (305-1426) at intervals after 70% hepatectomy were added difference in stool consistency was found. ng/ml). to EGF stimulated (10 ng/ml) primary rat In conclusion, in severe constipation bran is Median values from both groups were signi- hepatocyte cultures, assessing DNA synthesis often effective, the placebo effect is relevant, ficantly greater than those from patients with by 3-H thymidiie incorporation. Results were and cisapride represents an effective and well stable graft function (250 (75-810) ng/ml; compared with EGF alone (82101 (1912) dpm/ tolerated treatment. p<0025) and outside the range for healthy well). Significant inhibition of DNA synthesis controls (100-200 ng/ml). CICAM-1 was was obtained with conditioned media from detected in bile in 14 of 15 patients with acute NPCs 24 and 48 hours post hepatectomy rejection (490 (0-1850) ng/ml) and the median (24519 (2019), p<0-01, and 49715 (2197), value was greater than in patients with infective p<0 05, respectively, paired t test). However with conditioned media 10 and 72 hours post LIVER DISEASE complications (0 (0-282) ng/ml; p<0 025) and in patients with stable graft function in whom hepatectomy (80192 (1791) and 83181 (2517)) biliary CICAM-1 was not detected. no significant inhibition was found. http://gut.bmj.com/ In conclusion, CICAM-1 is released into the This time course differs from that reported Antiendothelial celi antibodies in primary circulation during both allograft rejection and for expression of TGF 1P mRNA, which pro- biliary cirrhosis infective complications gressively rises for 96 hours, and supports the of liver transplanta- presence of another NPC derived growth in- tion. The high biliary levels in acute rejection hibitor after P A McCORMICK, A SAWYERR, M HUDSON, might reflect local secretion of CICAM-1 from partial hepatectomy. A J WAKEFIELD, M R BIAGINI, B E POTTINGER, lymphocytes infiltrating the portal tracts. The J D PEARSON, N McINTYRE, A K BURROUGHS role of CICAM-1 during graft rejection

(Hepatobiliary and Liver Transplantation Unit, remains unknown but raised levels in bile on September 24, 2021 by guest. Protected copyright. Royal FreeHospitalSchool ofMedicine, London, might enable infective complications to be Detection of antibodies to acetaldehyde- and MRC Clinical Research Centre, Harrow, distinguished from graft rejection. albumin conjugates in alcoholic liver disease Middlesex) Antiendothelial cell antibodies (AECA) have been described in a number of J P TEARE, A J CARMICHAEL, F BURNETT, pathological states in which vasculitis is the M 0 RAKE (Gastrointestinal Laboratory, Rayne principal pathogenic mechanism. Primary Expression of hepatocyte growthfactor Institute, St Thomas's Hospital, London; Kent biliary cirrhosis (PBC) is a chronic granulo- associated with hepatocellular cancer and Canterbury Hospital, Canterbury; and Kent matous condition like Crohn's disease, in University) The principal metabolite ofethanol, which vasculitis has also been described. We C SELDEN, S F DING, N HABIB, H J F HODGSON acetaldehyde, conjugates with various proteins investigated the presence of AECA in PBC. (Royal Postgraduate Medical School and The that form antibody inducing neoantigens. We Sera were obtained from 20 patients with Royal Free Hospital, London) Hepatocyte have analysed sera from patients with biopsy AMA positive PBC (predominantly Pugh's growth factor (HGF), a high molecular weight proved alcoholic liver disease (hepatitis=10, grade A), from 15 patients with autoimmune growth factor capable of stimulating DNA cirrhosis=11, steatosis=2) and control sub- chronic active hepatitis (CAH), and from six synthesis in hepatocyte cultures, was recently jects= 13 (normal teetotallers and non- patients after orthotopic liver transplantation purified and its nucleotide and amino acid alcoholic liver disease). (OLT). IgG AECA were measured using a sequence established. We have shown in- Sera were examined with an enzyme linked human umbilical vein endothelial (HUVEC) creased expression ofa 6 kb mRNA for HGF in immunoabsorbent assay (ELISA) for anti- cell based ELISA, with horseradish peroxidase regenerating rat liver and in human fetal liver. bodies binding preferentially to an acetalde- conjugated rabbit antihuman IgG. Sera were We have studied the expression of HGF hyde-albumin conjugate. Reactive sera from tested at 1/1000 dilution. Sera with AECA mRNA in liver tissue taken from within hepa- alcohol abusers were then purified using an binding activity greater than the mean +3 SD tocellular cancer and from the adjacent area. amino-hexyl sepharose affinity column. of 54 healthy volunteers were designated as Total RNA was prepared, and resolved on Antibodies binding to the acetaldehyde- positive. AECA were identified in 15 of 20 1-5% agarose/formaldehyde gels, before trans- albumin epitopes were significantly raised patients with PBC (75%), in eight of 15 patients fer onto nylon membranes. Parallel gels were (p less than 0.005) in all groups of alcohol with CAH (53%), in one of six patients post stained with ethidium bromide to ensure RNA abusers, and present in greatest titre with (OLT), and in one of 54 normal volunteers integrity. Northern blots were probed firstly alcoholic hepatitis. These antibodies were suc- (2%). with a 560 bp cDNA to human HGF and then cessfully purified using the gel affinity column. In conclusion, AECA are common in with a cDNA to glyceraldehyde-3-phosphate We conclude that alcohol abusers have patients with autoimmune liver disease and dehydrogenase (G3PDH). significant titres of antibodies reacting to the particularly so in patients with PBC who have HGF mRNA was over expressed in tissue aceteldadehyde-albumin complex. The role of very high levels compared with other vascular taken outside the tumour as compared with these antibodies remains unclear, but may be disease. The presence of AECA in PBC raises involved liver tumour, as estimated from the related to the initiation of an inflammatory the possibility that endothelial injury may be ratio of signals for HGF and G3PDH. Anala- response and tissue damage following ethanol important in the pathogenesis of PBC. The gous findings have been reported for the proto- consumption. British Society ofGastroenterology A577

Correlation of cytokine values with haemo- (p<0002) higher PMT than asymptomatic need for MBP before elective colorectal surgery dynamic and oxygen transport variables in patients (10-8 ng/ml (24-52-2), n=15 v in a prospective randomised trial. fuihninant hepatic failure 4-4 ng/ml (2-8-10-8), n=19; respectively). Patients undergoing elective colorectal

PMT from PBC patients in stage I (n=8) or II surgery were randomised preoperatively to Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from 1 A WENDON, N SHERON, P M HARRISON, (n=6) were similar to controls (3-8 ng/ml (2-5- receive either oral polyethylene glycol 4000 H KEANE, G J M ALEXANDER, ROGER WILLIAMS 5-4) and 3-3 ng/ml (2-8-4-8), respectively) (GoLYTELY) or no MBP. All patients (Institute of Liver Studies, King's College Hos- while most patients in stage III (n=9) or stage received standard perioperative intravenous pital and King's College School ofMedicine and IV (n= 15) disease had clearly raised PMT antibiotics and intraoperative saline lavage. Dentistry, London) Multiple organ failure is (4-8 ng/ml (3-2-7-8) and 9-4 ng/ml (44-52-2), Postoperatively, patients were examined for common in patients with fulminant hepatic respectively, both p<0-002 v controls, stage III wound infection (discharge of pus), intra- failure (FHF), and tissue hypoxia is of great v stage IV p<0-01). Follow up of six PBC abdominal sepsis, and anastomotic leakage importance in its pathogenesis. In these patients (median five years) showed that an (clinical and radiological). patients, when oxygen delivery is increased increase in stage was always accompanied by an A total of 115 patients have so far been oxygen consumption rises, indicative of an increase in PMT (p<005). studied, 56 of whom received MBP. The underlying tissue oxygen debt. Endotoxin and In conclusion, plasma metallothionein con- principal pathology (90%) was carcinoma, and a variety of cytokines have been postulated as centrations are significantly raised in patients 35% of patients underwent anterior resection. mediators of the microcirculatory abnormali- with PBC or PSC. In PBC, the increase in the There was no difference in wound infection ties (arterio-venous shunts, interstitial oedema, plasma MT concentration is symptom but rate, three of 56 with MBP compared with six white cell and platelet plugs) that result in this primarily stage related. of 59 without MBP (p=0-4913) and intra- tissue oxygen debt. In a prospective study of abdominal sepsis rate, two of 56 with MBP patients with FHF, admission values for sys- compared with one of 59 without MBP temic vascular resistance index (SVRI) (1305 (p=096). Anastomotic leakage occurred fol- (513) v 807 (374), p<0001), pH (7-45 (0-05) v Effect of transplantation and chemical lowing anterior resection only and was present 7-36 (0-12), p<005), oxygen consumption denervation of the liver on liver blood flow in in six with MBP and one without MBP (p= (131 (40) v 106 (36), p<0 05) and oxygen the rat 0-0948). extraction ratio (OER) (16 (3-6) v 12-6 (3.6), The results suggest that MBP does not pdopamine, 50 mg/kg, intraportally). Liver M R B KEIGHLEY, G TSANG, T BACELAR (Depart- measured haemodynamic or oxygen transport function was assessed in vivo by the amino- ment of Surgery, Queen Elizabeth Hospital, variable. pyrine and galactose breath tests. Under Birmingham) We have compared three methods These data suggest that IL 6, rather than sodium pentobarbitone anaesthesia, liver of mechanical bowel preparation before elec- TNF or endotoxin, may be the important blood flow was measured using the xenon tive colorectal surgery in 75 consecutive mediator of the haemodynamic disturbance in clearance method. Cardiovascular status was patients who were randomly allocated to http://gut.bmj.com/ fulminant hepatic failure. monitored and blood biochemical parameters receive CP100, a balanced commercially avail- measured at sacrifice. Blood biochemical able electrolyte solution for oral wholegut parameters were unaltered in transplanted and lavage; sodium picosulphate (Picolax); or denervated animals compared with control sodium sulphate. The relative costs ofprepara- Increased plasma metaliothionein values in animals, except for alkaline phosphatase tion per patient were CP100 £6, Picolax £0-61, patients with liver diseases associated with activity which was significantly lower in dener- and sodium sulphate £0-41. Satisfactory bowel increased liver copper concentrations vated animals. The rate constants for amino- preparation was recorded in 80% after CP100, pyrine N-demethylase and galactokinase were 88% after Picolax, and 92% after sodium on September 24, 2021 by guest. Protected copyright. T P J MULDER, A R JANSSENS, H W VERSPAGET, similar to control values. Liver blood flow was sulphate. The quantity of faeces per cm length C B H W LAMERS (Department ofGastroenterology not significantly different in the denervated or of resected bowel was 0-37 after CP100, 0-46 and Hepatology, University Hospital, Leiden, transplanted groups, although the mean after Picolax, and only 0-009 after sodium The Netherlands) In chronic cholestatic dis- arterial pressure and heart rate were signifi- sulphate (p<002). More patients found pre- orders the liver copper concentration often cantly lower in denervated animals compared paration unacceptable after CP100 (40%) than becomes raised during the course ofthe disease. with transplanted and control animals. after Picolax (16%) or sodium sulphate (8%). The accumulated copper is thought to be We conclude that hepatic denervation by There were no electrolyte disturbances among detoxified by inducing the synthesis of the orthotopic liver transplantation or chemical patients admitted to the study. copper binding protein metallothionein (MT). denervation does not compromise hepatic These data indicate that sodium sulphate is Studies in rats showed that increased liver MT haemodynamics or function in the rat. (This at least as good as Picolax and is cheaper. concentrations are reflected by increased work was supported by SNF grant No. 32- plasma MT concentrations (PMT). We there- 9528.88). fore determined the PMT in 20 healthy control subjects and in 105 patients with several types Predictive factors of colonoscopy findings in of liver diseases by a recently developed RIA open access endoscopy units for human MT. Patients with diseases associated with in- COLORECTAL G MASTROPAOLA, M G LUCA, S KUSSTATSCHER, creased liver copper concentrations - that is G C STURNIOLO, R D'INCA, D MARTINES, primary biliary cirrhosis (PBC, n=34) and A MARTIN, R NACCARATO (Cattedra Malattie primary sclerosing cholangitis (PSC, n=7) - Apparato Digerente, University ofPadua, Italy) had significantly (p<0-002) raised PMT Mechanical bowel preparation for colorectal The request for colonoscopies has been increas- (4-9 nglml (1-8-52-2) and 5-4 ng/ml (4-4-19-0), surgery - preliminary results of a prospective ing, affecting both health care costs and the respectively) and many of them (50% to 57%) randomised trial work load for endsocopy units. Because of the were above the maximum control concentra- often vague indications, the diagnostic yield is tion of 4-8 ng/ml (median controls 3-8 ng/ml). S ELLENBOGEN, P BROWNSON, D M NOTT, poor and a better selection of patients would be In contrast, patients with liver diseases without S A JENKINS (University Department of Surgery, desirable. The aim of this study was to assess copper accumulation - that is alcoholic cir- RoyalLiverpoolHospital, Liverpool)Mechanical which clinical data may suggest or exclude the rhosis (n=24), cryptogenic cirrhosis (n= 14), bowel preparation (MBP) before elective presence of lesions in the colon of patients acute hepatitis (n= 8), and chronic active hepa- colorectal surgery has become established sur- undergoing full colonoscopy. titis (n= 18) - had normal plasma MT concen- gical practice but this has recently been chal- In 277 consecutive outpatients (age 16-89 trations with medians of 3-6 to 3-9 ng/ml (range lenged (Irving AD, Scrimegoer D: Mechanical years, 149 men), the complaints leading to 2-4-8-8), and only a few (4% to 38%) were bowel preparation for colonic resection and colonoscopy were recorded by means of a 64 above the maximum control value. anastomosis. BrJ Surg 1987; 580-1). item questionnaire and related to the subse- Symptomatic PBC patients had significantly The aim of this trial was to determine the quent endoscopy findings. Findings were clas- A578 British Society ofGastroenterology sified as major (cancers, stenosis, polyps, symptomatic DD before and after four weeks' centre and Department of Medicine, Hope Hos- moderate/severe inflammatory bowel diseases treatment with 7 g IH per day. The capsule was pital, Salford) Somatostatin and the a2 (IBD)), minor (mild/quiescent IBD, diverticu- linked by a novel aerial to a computer pro- Adrenergic agonist, clonidine, inhibit intes- losis, etc), and on if and secretion but little negative, based histology grammed to give transit times, integrated tinal fluid electrolyte is Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from necessary. pressure, % activity, and peaks greater than 5 known about their sites and mechanisms of Colonoscopy was negative in 87 patients and 50 mmHg. action. Using the HT29 colonic cell line we (31-4%) but minor and major findings being IH reduced the mouth to rectum transit time examined the possibility that they can inhibit found in 105 (37.9%) and 85 (30 7%) patients from a mean of 46 (17) hours before to 25 (8) agonist stimulated Cl- secretion by a direct respectively. Out of the 64 clinical items, the hours after treatment, p<0 05. The corres- action on epithelial cells. Cl- secretion was ones significantly related (x2) to lesions were sex ponding values for mouth to mid transverse detected by the increase in short circuit current (108 men, p<001), age over 50 years (99 colon were 30 (13) and 16 (5) hours respectively, (Isc) across cell monolayers mounted in flux patients, p<001), diarrhoea (n=79 p<0-01), p 0.05. Left colonic transit was unchanged at chambers. Basolateral addition of the cAMP and blood in the stools (n= 104, p<0 05); while 10 (6) hours and 9 (5) hours respectively, agonist prostaglandin E2 (PGE2) (20 nmol/l) abdominal pain, in particular, was not. The p=NS. provoked a sustained increase in Isc above above data showed the following positive and IH had no significant effect on left colonic basal (Isc 21-3 (2-1) itA/cm2). The subsequent negative predictive values (PPV, NPV %): sex motility. In the right colon, % activity in- addition of either somatostatin (1 ,umol/1) or 72-5, 35 9; age 71-7, 34.5; diarrhoea 77.5, creased from a median (range) of 6% (3-20) clonidine (10 pumol/l) induced a rapid (t½/, 1-5 36-6; blood 72-7, 35.8; abdominal pain before to 15% (10-37) after IH, p<0 05. Cor- minutes) inhibition of Isc by 80-61 (1-6) and (present in 139 of 277 patients) 66-9, 29-7. responding values for peaks greater than 5 65-2 (3.3)% respectively. This was accom- In conclusion, some clinical features that are mmHg were 46 (14-132) and 105 (46-144), panied by a reduction in cAMP accumulation easy to collect from the patient's history carry a p<0.05. from 41-6 (2-1) to 9 5 (0.9) pmol cAMP/mg predictive value for colonoscopy findings Five of the seven patients who predomi- protein. Somatostatin and clonidine also greater than 70%. With the aid of these simple nently had abdominal pain and six of the nine attenuated the rise in Isc induced by the Ca2+ criteria, better priorities in patient waiting lists patients with altered bowel habit improved dependent cholinergic agonist, carbachol. could be established and the number of pro- after treatment. These data suggest that IH Somatostatin and clonidine activity could be cedures could even be reduced. may alleviate symptoms of left sided DD by blocked by pretreatment with pertussis toxin virtue of its action on the right colon. (PT 200 ng/ml; 18 hours) which inactivates inhibitory G proteins. These data suggest that (i) somatostatin and Experimental anal dilatation clonidine can inhibit CL secretion in HT29- Regulation of Caco-2 Na+/H+ exchange by 19A cells and (ii) these effects are dependent on A G MILES, T G ALLEN-MERSH, C WASTELL serum through a novel mechanism which is the activation of pertussis toxin sensitive G (Charing Cross and Westminster Medical School, dependent on actin proteins. Westminster Hospital, London) Dilatation of the anal sphincter in man, whether surgically or by A J M WATSON, M DONOWITZ, M H MONTROSE other means, is relatively uncontrolled and the (INTRODUCED BY L A TURNBERG) (Division of effects are unknown. Certainly, therapeutic Gastroenterology, Department of Medicine, The Oral tobramycin in ulcerative colitis: effect anal dilatation for chronic anal fissure results in J7ohns Hopkins Medical School, Baltimore, on maintenance ofremission a small percentage of patients with a degree of USA) We have previously shown that Caco-2 incontinence. cells possess a basolateral Na+/H+ exchanger A J LOBO, D A BURKE, G M SOBALA, M F DIXON, http://gut.bmj.com/ Four groups ofsix Sprague Dawley rats were which is not sensitive to cAMP, cGMP, Ca2 , A T R AXON (Gastroenterology Unit and University sedated with fentanyl fluanisone and the effect phorbol dibutyrate, or osmotic cell shrinkage. DepartmentofPathology, The GeneralInfirmary, of anal dilatation to 7, 9, and 11 mm diameter In this study the regulation of Caco-2 Na+/H+ Leeds) Oral tobramycin for seven days has been on anal pressure was observed. Pressures were exchange by fetal bovine serum (FBS) was shown to be of benefit as an adjunct to con- measured with a 2 mm diameter balloon before investigated. Na+/H' exchange (measured by ventional medication in acute ulcerative colitis. and 15 minutes after each dilatation, daily for BCECF fluorescence) was reduced by 60 (10)% A total of 81 patients (40 had received tobra- four days. Pressures were then remeasured but (n=41) when FBS deprived for at least four mycin; 41 placebo) who had been enrolled in a without further dilatation at one week and one hours. Readdition of FBS for four hours was double blind placebo controlled trial of this on September 24, 2021 by guest. Protected copyright. month. The diameters of the dilators were required to fully restore Na+/H+ exchange drug were subsequently followed to determine chosen since the median diameter of 100 fresh activity. Kinetic analysis showed that four hour whether this short term benefit persisted. rat stool pellets was 7 mm (range 6-0-8 5 mm). FBS deprivation reduced the Km of the Relapse was defined as a recurrence of colitic Single dilatation to 11 mm reduced anal exchanger for external Na+ from 21 to symptoms with a stool frequency ofthrice daily pressure 15 minutes afterwards (T=3-72, 6 mmol/l. The Vmax was reduced by 60% and blood in faeces. Results were analysed by p=0002) but not with dilatation to either suggesting that the number of exchangers in the log rank test on Kaplan-Meier survival 7 mm or 9 mm. In addition, three dilatations to the plasma membrane is reduced. Inhibition of curves. Treatment failure was defined as failure 11 mm resulted in a significant drop in anal protein synthesis with 5 itm cycloheximide did to enter remission by the end of the initial trial pressure which had not recovered by 24 hours not alter the effect of FBS deprivation or FBS period or subsequent relapse. Although at the (T=3-26, p=0-01). Anal pressures remained readdition on Na+/H+ exchange, suggesting start of the follow up period significantly fewer significantly lower than predilatation values FBS is acting at a post-translational level. patients in the tobramycin group had failed one month after four dilatations to either 7 mm Cytochalasin D (10 Fg/ml) blocked the reduc- (failed: tobramycin (9), placebo (24); not (T=2-40, p=0 03) or 11 mm (T=6-66, tion of Na+/H+ exchange activity after four failed: tobramycin (31), placebo (17); p=0 0006). hours FBS deprivation but did not block p=0-001), the failure free survival curves sub- These preliminary results indicate that restoration ofactivity when FBS was readded. sequently converged and did not significantly dilatation does produce some effect on We conclude (1) FBS deprivation reduces differ (p>O0 1). After one and two years respec- sphincter function consistent with the Na+/HI exchange activity by a mechanism that tively the mean (SEM) failure free survivals observed effect in man and will provide the is dependent on actin, (2) FBS readdition were 40 (7.8)% and 20 (6.3)% for the tobra- basis for further investigation. restores the Na'/H+ exchanger by a non-actin mycin group and 24 (6.7)% and 12 (5 1)% for dependent mechanism, (3) FBS deprivation is the placebo group. associated with an increase in the km of the Benefit from tobramycin is shortlived and exchanger for external Na'. This slow time may therefore relate to short term changes in How does ispaghula husk relieve symptoms course regulation may be explained by cycling the faecal flora. in diverticular disease? of the exchanger in and out of the plasma membrane. I G FINLAY H A THORBURN, K CARTER, J GOLD- BERG (INTRODUCED BY J McKENZIE) (Department Peptide based diet: an altemative to elemen- of Surgery, Royal Infirmary, Glasgow) Fibre tal diet in the treatment of acute Crohn's supplementation (for example ispaghula husk Somatostatin and clonidine inhibit Cl secre- disease (IH)) is used to treat symptomatic diverticular tion via G protein mediated pathways in a disease (DD) but the mode of action is colonic cell line (HT29-19A) S J MIDDLETON, A M RIORDAN, J 0 HUNTER unknown. Using an untethered pressure sensi- (Department of Gastroenterology, Addenbrooke's tive radiotelemetry capsule, we studied right G WARHURST, N B HIGGS, J GRUNDY, Hospital, Cambridge) Ninety per cent of and left colonic motility in 10 patients with L A TURNBERG (Epithelial membrane research patients with acute Crohn's disease (ACD) British Society ofGastroenterology A579 respond to an elemental diet (ED). Peptide diagnosed in the city during the study period had no trouble choosing a suitable diet and 96% based diets (PBD) are more palatable, but their were included. Population data was taken from were healthy with a steady weight. Answers to relative efficacy is unknown. We compared ED the 1983 Survey of Leicester and the City questions about consistency, frequency, pain,

with PBD (E028 and Pepdite 2+, both manu- Council projection for 1989. A total of 180 cases and odour after ingestion of 70 specific food Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from factured by Scientific Hospital Supplies, occurred in indigenous Europeans and 23 in items showed no consistent pattern. Symptoms Liverpool, England). A total of 29 patients Asians, 21 of whom were first generation were commonly associated with onions (56%), (median age 27 years) with ACD (14 colonic, 12 migrants. The incidence in Europeans from baked beans (52%), sprouts (52%), nuts (50%), ileal, three both) were randomised to the study. 1972-80 was 3.83/105/year (95% CI 2-96-4-71) beer (42%), and fizzy drinks (34%). In general, Activity was confirmed by a Harvey and Brad- and 0-87/105/year (95% CI 0-21-1-9) for foodstuffs with a high fibre content were more shaw index (HBI) >6, remission by a HBI <3. Asians. Europeans had significantly more likely to be associated with symptoms. Fifteen patients received PBD and 14 ED. Crohn's disease than Asians (z=3 5, p<0-001, Many patients described defaecation occur- Three patients in each group decided to with- relative risk 4 4, 95% CI 1 8-11). From 1981- ring at a regular time after eating a main meal. draw from dietary treatment. After 14 days, 11 89 the incidence for Europeans increased to Some 40% found that they could avoid defaeca- of 12 were in remission on PBD, (HBI at start 5-8/105/year (95% CI 4-6-669) and to 2.9/10/ tion interferring with work or sleep by control- 8-8 (3), at finish 2 (1-3), p=0 003) and all 11 on year (95% CI 1-4-3-9) for Asians. Europeans ling the meal quantity and times. ED (HBI 8 5 (2.7) and 1-75 (1-2), p=0O002). still have significantly more Crohn's disease This study suggests that pouch function may Alpha 1 antichymotrypsin fell on ED from 1-0 than Asians (z=3.2, p<0-001, relative risk 2-2, be partially controlled by dietary manipula- (0 42) to 0 7 (0-31) (p=0 05) and on PBD from 95% CI 1-3-3-6), although the incidence in tion. There is no evidence that any one food- 0.79 (0-17) to 0 77 (0.24) (NS). The ESR fell Asians is increasing more rapidly. The stuff always produces problems. Pouch from 51 (35) to 35 (28) on ED (p<0 05) and 36 explosion in cases of Crohn's disease in Asians patients should endeavour to maintain a (27) to 32 (24) on PBD (NS). C reactive protein suggests an environmental factor may yet be healthy mixed diet and only avoid specific food fell only on ED from 55 (40) to 20 (29) identified. if they personally find it upsets them. (p<005). Haemoglobin and albumin concen- trations were unchanged. PBDs induce symptomatic remission in ACD, but are less effective than ED in reduc- Abnormal pulmonary function in non- Is a loop ileostomy desirable in restorative ing parameters of inflammation. smokers with ulcerative colitis and primary proctocolectomy? sclerosing cholangitis M R B KEIGHLEY, J ASPERER, S GROBLER, K HOSIE A T COLE, G L CULLINGFORD, D D VARA, (Department of Surgery, Queen Elizabeth Stoma anxieties of Asian and European M D L MORGAN (INTRODUCED BY C J HAWKEY) Hospital, Birmingham) The use of loop ileos- patients (Department of Therapeutics, University Hos- tomy (LI) for restorative proctocolectomy may pital, Nottingham; Leicester Royal Infirmary; not be desirable particularly with stapling P BHAKTA, C S J PROBERT, V JAYANTHI, and Glenfield General Hospital, Leicester) Pul- techniques and increasing experience with the J F MAYBERRY (Gastrointestinal Research Unit, monary abnormalities have been described in operation. Although LI may protect against the Leicester General Hospital) A total of 167 stoma ulcerative colitis, usually in groups including consequences of anastomotic dehiscence, it therapists were asked to comment on their smokers. A similarity has been reported involves two hospital admissions and may experience, if any, of Asian patients. Each between the histological features of primary cause increased morbidity after closure. LI was used in 53 anas- week 1941 ostomists were reviewed including sclerosing cholangitis and the peribronchial patients (11 stapled ileoanal http://gut.bmj.com/ eight Asians. Europeans were seen three times fibrosis seen complicating ulcerative colitis. tomosis). No covering stoma (NS) was used in more often than Asians. Twenty five per cent of We therefore assessed pulmonary function in 32 patients (18 stapled ileoanal anastomosis). stoma therapists had no access to translators lifelong non-smokers with ulcerative colitis, Pouch excision or persistent loop ileostomy has and only 28% felt patients would prefer an both uncomplicated (n= 18, age 23-66 years) been necessary in nine LI and one NS patients, Asian therapist. Only half believed Asian and with sclerosing cholangitis (n=6, age 29- leakage from the ileoanal anastomosis was patients wished to see a fellow ostomist. All 63 years), and examined whether additional recorded in 10 LI and two NS, pelvic abscess claimed to discuss the stoma site with regard to abnormalities could be detected with sclerosing was recorded in 17 LI and two NS, pouch ethnic dress. Of the 36 European and 24 Asian cholangitis. Lung function was assessed by vaginal or pouch cutaneous fistula was ileostomists studied, Asians were less likely to flow volume loop, body plesthysmography, recorded in 12 LI and three NS, and intestinal on September 24, 2021 by guest. Protected copyright. have inflammatory bowel disease (X2=ll .3, and single breath carbon monoxide gas trans- obstruction occurred in 12 LI and one NS. The p<0-001) or know the reason for surgery fer. All values were compared with accepted incidence of wound sepsis, anal stricture, and X2=5-2, p=<005). Only 35% of all patients reference standards. pouchitis was the same in both groups as was saw an ostomist, compared to the 61% who Maximal mid expiratory flow was reduced the functional outcome. wished to (X2=8-5, p=<0. 005). Fifty per cent (p<001 Wilcoxon) by mean 1-28 1/second, to These data suggest that intestinal obstruc- ofAsians thought Asian therapists were needed, 73-3% predicted (range 50% to 98%) in un- tion, fistula, and pelvic sepsis are more com- compared with 28% of stoma therapists complicated ulcerative colitis and 1-08 I/second mon ifa loop ileostomy is used. Thirty patients (x2=4.5, p<003). Few patients were coun- to 68-1% (32% to 103%) in sclerosing cholan- have now entered a randomised trial of loop selled about employment, education, or gitis. Other measurements were within the ileostomy in stapled restorative procto- marital problems. Postoperatively, 32% normal range; there were no significant dif- colectomy. remained concerned about their body image ferences between uncomplicated ulcerative and 28% about their partner's view. Sexual colitis and with sclerosing cholangitis. worries were expressed equally; but these In conclusion, lifelong non-smokers with improved more in Europeans than Asians, uncomplicated ulcerative colitis have evidence Biochemical and histochemical analysis of (x2=7.7, p<001). of small airways disease but those with com- mucin in ileoanal pouches Stoma therapists think they are aware of plicating primary sclerosing cholangitis have Asian patients needs, but the service received no additional abnormality. A P CORFIELD, B F WARREN, D CC BARTOLO by both ethnic groups was significantly lacking (University Departments of Medicine, Histo- in many areas and needs critical re-evaluation. pathology, and Surgery, Bristol Royal Infirmary, Bristol) Cellular and secreted mucins in the Diet after restorative proctocolectomy ileal, rectal pre- and post closure pouch tissue of 14 patients undergoing restorative procto- Incidence of Crohn's disease in Leicester, K B HOSIE, J BUSBY, H FERGUSON, M KUO, colectomy were monitored after metabolic 1972-89 M R B KEIGHLEY (Departments of Surgery and labelling with (3 5S)-sulphate and ('H)-glu- Nutrition and Dietetics, Queen Elizabeth cosamine. A mucin histochemical analysis of V JAYANTHI, C S J PROBERT, J F MAYBERRY Hospital, Birmingham) Patients often ask for the same tissue was carried out. The quality of (Gastrointestinal Research Unit, Leicester advice on diet after restorative proctocolec- the isolated mucins was reflected in the ratio General Hospital) A retrospective study of all tomy, yet there is very little detailed informa- (3'S):(3H). potential cases of Crohn's disease was per- tion available. The experience of 50 (20 men, Cellular mucins showed no difference formed. Cases were identified from registers 30 women) well adapted patients at least 6 between proximal, distal ileum, and rectum. held by hospitals, pathology and endoscopy months (range 6 months-6 years) after restora- Higher ratios were found in pre- and post- departments, general practitioners and per- tive proctocolectomy was recorded using a closure pouch tissue relative to ileum and sonal indexes were reviewed using Lennard- detailed questionnaire. Some 66% of patients rectum. The secreted mucins showed no Jones criteria of case definition. Only patients felt that their diet affected pouch function, 82% change in the ratio for any tissue. Significant A580 British Society ofGastroenterology increases were detected for the turnover of five to nine and 10 to 14 years after gastrectomy per cent of ODC activities in operated secreted mucins in distal ileum rectum, and were fewer than expected: RR (95% CI) 0.62 stomachs were above the upper limit of normal postclosure relative to proximal ileum and also (0.42-088), 0-60 (04-0 87) respectively, (mean+2SD). Two gastrectomy patients had a for pre to post closure tissue. A decrease was p<001. At 15-19 years after operation the RR carcinoma and ODC activity was higher in seen in preclosure tissue relative to rectum. was 0-92 (0-66-1-23), but after 20-24 and >25 tumour than surrounding mucosa. There was Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from The combined results show clearly the years the values were 1 -55 (1 14-2-05) and 1 -68 no correlation between an increase in ODC reduction in rectal relative to ileal sulphated (1 14-2-32) respectively, p<001. The cumu- activity and histological evidence of dysplasia mucin in ulcerative colitis and progressive lative RR was 1-08. or inflammation. There was no relation changes in pre- and postclosure pouch tissue Partial gastrectomy leads to a reduced risk of between an increase in ODC activity and time consistent with a reversion to colonic type gastric carcinoma for the first 15 years, and since surgery, type of operative procedure, or mucosa with more sulphated mucins. after 20 years the increased risk is minimal. Hpyloristatus. Increasedmucosal ODC activity This sensitive method is used as a reliable Screening is not justified. in 50% of operated stomachs is consistent with indicator for the onset of colonic metaplasia. It increased cell turnover. Prospective studies are is ideally suited as a routine control method for required to establish whether mucosal ODC the characteristic mucin changes seen in in- activity has a role in the selection of individuals flammation and neoplasia. Failure of R3 radical gastrectomy in serosa for surveillance. positive gastric cancer

S A RAIMES, S C C CHUNG, L McGUIRE, A K C LI Enterocutaneous fistula c mplicating res- (Prince of Wales Hospital, Chinese University of Prognosis of adenocarcinoma of the gastric torative proctocolectomy HongKong) Most gastric cancer patients do not cardia according to TNM classification present until the tumour has breached the S GROBLER, K HOSIE, M R B KtIGHLEY (Depart- serosal surface (S+). The aim ofthis study was J G A M BLOMJOUS, W C J HOP, ment of Surgery, Queen Elizabeth Hospital, to determine whether R3 radical total gastrec- B L A M LANGENHORST, F J W TEN KATE, Birmingham) Thirteen patients have developed tomy is an effective treatment for S+ gastric W M H EYKENBOOM, H W TILANUS (INTRODUCED enterocutaneous fistulas in a series of 114 cancer. Between 1984 and 1990 we operated on BY M VAN BLANKENSTEIN) (Departments of restorative proctocolectomies (12%). Six 226 patients with T3 or T4 tumours. A total of Surgery and Pathology, Erasmus University Hos- occurred in the first 30 patients of the series. 105 had resections that left no macroscopic pital Dijkzigt; Departments ofEpidemiology and The underlying diagnosis was thought to be residual disease (Ro) with no peritoneal, Biostatistics, Erasmus University; and Rotterdam Crohn's disease in three, ulcerative colitis in hepatic, or distant metastases - 70 had an R3 Radiotherapeutic Institute, The Netherlands) We eight, and megarectum in two. Four entero- resection and 35 a lesser procedure. The 30 day reviewed survival and recurrence rates in 93 cutaneous fistulas were from the ileostomy mortality for R3 resection was 7-1% and the patients operated on between 1 January 1983 closure site (one diabetic); none required survival rate was 57 9% at one year, 22-9% at and 1 January 1989, with a follow up until 1 pouch excision. Four fistulas have been from three years, and 11-1% at five years. Forty July 1989. Adenocarcinomas of the gastric the ileoanal anastomosis to the abdominal wall three patients died during follow up, 38 as a cardia were classified as gastric carcinoma (three Crohn's disease); only one has been result of recurrent gastric cancer. The median according to the 1987 IUAC TNM criteria, successfully managed by pouch reconstruc- time to death was 11 months (interquartile including the following histopathological grad- tion, one patient has a loop ileostomy and two range 8-20 months). Seventeen of 38 died from ing (G): well (G1), moderately (G2), poorly have had their pouches excised. Five fistulas multiple peritoneal deposits and 13 of 38 from (G3), and undifferentiated (G4) tumours. were from the pouch, one being associated with gastric bed recurrence; only seven patients had Recurrence rates (local, metastases, and over- http://gut.bmj.com/ a distal pouch stricture, two arising from a long hepatic or distant metastases. There was no all) and survival curves were calculated on an J pouch appendage. Only one of these patients significant difference in survival between node actuarial basis using the Kaplan-Meier has required pouch excision, the remainder positive and node negative patients. Although method. The cumulative five year rate for local have had their fistulas excised and have good not randomised, there was no significant sur- recurrence was 36%, for metastatic recurrence pouch function. vival benefit of R3 compared with R1/2 64%, and for overall recurrence 69%. Five year Aggressive surgical treatment of pouch gastrectomy. survival according to the TNM classification cutaneous fistulas is worthwhile since in many We conclude that R3 gastrectomy is not an and its different subgroups showed for T1/T2 v patients a satisfactory functional outcome is effective treatment for S + gastric cancer and T3/T4 tumours: 31% and 21% (p=0.08), for on September 24, 2021 by guest. Protected copyright. achieved. that early failure is common and caused by NO v N1/N2 status: 31% and 17% (p<0 001), intraperitoneal recurrence in most cases. for MO v M1 status: 28% and 0% (p=0 03), for stage (S) IISII v SIII/SIV: 38% and 8% (p<0002) and for G1/G2 v G3/G4: 31% and STOMACH 17% (p=0.001). Stage of disease correlated to Increased mucosal ornithine decarboxylase histopathological grade showed that patients activity in the operated stomach: a potential with SI/SII and G1/G2 simultaneously had a biomarker for malignant risk better survival than all the other subgroups Gastric stump carcinoma: does the risk (p<0-001) X2 (3 df)= 17.0. Five year survival justify screening? E M ALSTEAD, K PRZYTULSKI, M L CLARK, for this group was 53% against: SI/SII-G3/G4: M J G FARTHING (Department ofGastroenterology, 19%; SIII/SIV-G1/G2: 0%; SIII/SI-G3/G4: N J V BELL, j W RADEMAKER, R H HUNT (Division St Bartholomew's Hospital, London) There is an 13%. of Gastroenterology, McMaster University increased risk of gastric cancer 15-20 years Medical Centre, Hamilton, Ontario, Canada) after gastric surgery for peptic ulcer. Mucosal The association between partial gastrectomy ornithine decarboxylase (ODC) activity is in- for benign peptic ulcer and subsequent gastric creased in gastric cancer and may be a useful Incidence and mortality of gastric and pan- carcinoma and endoscopic surveillance remain marker for premalignant change. Eighteen creatic cancer in England and Wales 1961- controversial. In a meta-analysis a com- patients (three women), median age 70 years 1988 puterised and full recursive bibliography (range 27-82) were studied. The median time search of the English language published after surgery was 18 years (range 2-51). Seven M ASHTON-KEY, S HAMMERSLEY, C D JOHNSON reports yielded 93 papers and case reports and patients had had vagotomy and pyloroplasty (University Surgical Unit, Royal South Hants six abstracts. Critical assessment identified 11 and 11 partial gastrectomy. Patients underwent Hospital, Southampton) Recent reports indicate studies with varying time intervals which met gastroscopy and gastric biopsy specimens were a falling incidence of gastric adenocarcinoma, predetermined criteria of a defined surgically taken for ODC activity, histology, and a rapid and (in north America) a rise in pancreatic treated cohort with a minimum follow up urease test for Helicobacterpylori. ODC activity adenocarcinoma to exceed gastric cancer. In- >80%, and in which gastric carcinoma mor- was measured using a radiometric bioassay. formation for England and Wales is lacking. tality was compared with that expected from ODC activities were compared with those in 10 We have examined age and sex related inci- age and sex matched national mortality figures. patients with sporadic gastric cancer and 30 dence and mortality (OPCS data) for gastric Four papers met all criteria and provided normal subjects. and pancreatic cancer in order to determine analyses in five year periods. Information on Median ODC activity in operated stomachs current trends. 18 082 patients was pooled and relative risk was 1004 pmol C02/mg protein/hour, range Registrations for gastric cancer have (RR) was calculated from the ratio ofobserved/ (198-13914) compared with 337 (81-1033) in remained unchanged, between 25-30/105 expected deaths. Significance was determined control subjects (p<0-0001, Mann-Whitney) (men) and 16-20/10' (women). Registrations by X2 analysis. Deaths from gastric carcinoma and 2550 (419-9916) for carcinoma (NS). Fifty have fallen in both sexes aged <75 years and British Society ofGastroenterology A581

increased in those >74 years. Gastric cancer controls. This was increased by 400% to 1-6 (p<0-01), but no effect is observed on binding mortality has fallen for all ages, from 34/10' crypt cells per hour in omeprazole treated rats to HGM membranes. In the presence of 5 (men) and 25/10' (women) to 22/10' and 14/10' (p<0-01 Student's t comparison of linear mmolIl MgCI2, the sodium dependent decrease respectively. Pancreatic cancer registrations regression gradients). in specific binding in RCC membranes is still rose from 7/105 to 12/105 (men) and 6/10' to 11/ The hypergastrinaemic response seen in observed, whereas in HGM under the same Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from 105 (women) up to the mid 1970s. Since then, rats and man is associated with a marked conditions, NaCI does not increase the specific registrations have been stable, with a small fall proliferative response in the gastric mucosa of binding. Scatchard analysis at 80 mmoL/l NaCl in those under 75 years. Mortality figures are the rat which is not confined to ECL cells and and 5 mmolIl MgCl2 showed that receptor almost identical to registrations. may facilitate ulcer healing. The impact on density (Bmax) remained unchanged despite Mortality from gastric cancer has declined, dysplastic gastric intestinal metaplasia and ionic manipulations. In HGM, 80 mmol/l NaCl while the incidence remains stable, suggesting dysplastic Barrett's oesophagus has yet to be produced an approximately threefold increase improvements in treatment results. Age related determined. However, an acceleration of the in receptor affinity (Kd) compared to binding changes suggest a population cohort at highest proliferative rate may be expected in gastrin in the presence of MgC12. risk aged over 65 in the 1970s. Pancreatic sensitive tissues. In conclusion, HGM and RCC have different cancer registrations and mortality have not ionic requirements for optimum specific bind- increased since the 1970s, and the sex ratio is ing. These data confirm that at least two equal, in contrast with experience elsewhere. distinct receptor subtypes exist and in HGM Gastric mucosal adaptation to continued the SS2 subtype predominates. non-steroidal anti-inflammatory drug administration: role of epidermal growth Post gastrectomy follow up of 159 patients factor with early gastric cancer SMALL BOWEL S M KELLY, R J DICKINSON, J R JENNER, S GUADAGNI, M CARTARCI, M CARBONI, BELINDA JO HUNTER (Departments ofGastroenterology and J JOHNSTON, P I REED (2nd Surgical Clinic, Rheumatology, Addenbrooke's Hospital, Cam- University 'La Sapienza', Rome, Italy and Lady bridge and Hinchingbrooke Hospital, Hunting- Evidence for accelerated thrombogenesis in Sobell Gastrointestinal Unit, Wexham Park don) The mechanisms by which the gastric Crohn's disease Hospital, Slough, Berks) The cumulative sur- mucosa adapts to damage by non-steroidal anti- vival rate (Kaplan-Meier method) at the end of inflammatory drugs (NSAIDs) are unknown. M HUDSON, R A HUTTON, A J WAKEFIELD, 1989 was 0.906 (excluding operative and other Epidermal growth factor (EGF) present in A M SAWYERR, PB A KERNOFF, R E POUNDER causes of mortality), or 0.863 when operative gastric juice and saliva is known to contribute (Inflammatory Bowel Disease Study Group, mortality was included. There was a significant to mucosal defence and repair. Salivary and Academic Department of Medicine and Depart- difference in the survival rates (p=0.02 Mantel gastric juice EGF concentrations were ment of Haemophilia and Haemostasis, Royal Cox and Breslow tests) between cancers con- measured before and after two weeks' treat- Free Hospital School of Medicine, London) fined to the mucosa and those with submucosal ment with NSAIDs in 10 patients with arthritis Chronic mucosal ischaemia, mediated by a invasion and between patients with and with- whose initial gastroscopy was normal. Gastric granulomatous vasculitis, could be augmented out lymph node metastases (p=0 05), between juice was collected at endoscopy. After two by a hypercoagulable state. intestinal and non-intestinal type cancers weeks, three patients had developed gastric We measured markers of accelerated coagu- (p=002) and also between patients under and erosions. There was no change in salivary EGF lation (fibrinopeptide A (FPA), prothrombin over 50 years (p=002). Resection type had no concentrations (3-02 (169) v 2-84 (1-30) ng/ml, fragments 1+2 (F1+2)); fibrinolysis (cross http://gut.bmj.com/ influence on survival. NS) but gastric juice EGF increased from 0-42 linked FDP's); and the physiological inhibitors Using Cox's multivariate analysis and a (0.38) to 0-69 (0.45) (p<0 05). of coagulation (antithrombin III (AT III), stepwise procedure for eight variables (sex, In a further study five different patients protein C, protein S, PAI-1, and Exner's test age, depth ofinvasion, lymph node metastases, followed the same protocol but were given for lupus anticoagulant). Results were com- presence of ulceration, location, histological Misoprostol (Searle) as well as the NSAID. In pared with Crohn's disease (CD) activity (C type and operation) age, depth ofinvasion, and this group no mucosal damage was seen at reactive protein, Harvey-Bradshaw score intestinal type cancer had the most significant endoscopy and no changes in EGF were (HBS), and Crohn's disease activity index effect on survival. detected in saliva (2-8 (1-68) v 2-87 (1-62)) or in (CDAI)). Sixteen CD patients were studied on September 24, 2021 by guest. Protected copyright. Eleven patients died from recurrent cancer, gastric juice (0.33 (0 28) v 0.32) (0-18)). In- from relapse (HBS>4, CDAI>150) into one is still alive with a stump recurrence. Other creased gastric juice EGF after NSAIDs may remission. causes of death were metachronous primary be an important factor in mucosal adaptation. High levels of FPA (median 5.35 ng/ml) and cancer (6), cardiovascular disease (2), F1+2 (median 2-3 nmol/l) were found in active pneumonia (3), AIDS (1), and car accident (1). disease but they did not differ significantly Although the prognosis of early gastric from the inactive phase; F1+2 correlated in- cancer is relatively good in western countries, Effects of ionic concentration on somato- versely with HBS (p=0 047) and serum patients should be carefully followed over a statin receptor affinity and specific binding in albumin (p=0-010), whereas FPA correlated long period for late recurrences and the high human gastric mucosa only with serum albumin (p=0 008). There incidence ofmetachronous cancers. was no significant difference in the ATIII, G V MILLER, I WOODHOUSE, S M FARMERY, protein C activity, protein S, Exner ratio, or J N PRIMROSE (Department ofSurgery, StJames's PAI-1 in active or inactive disease. However, University Hospital, Leeds) High (SS,) and low the protein C antigen was significantly lower Proliferative response of gastric body (SS2) affinity somatostatin receptors with dif- (p=0-011) in the active phase; two (13%) mucosa to short term administration of ferent ionic requirements for optimum binding patients had free protein S values below the omeprazole are found in rat cerebral cortex (RCC). This lower limit of normal. Despite activated coagu- study evaluates the ionic requirements ofsoma- lation, all cross linked FDPs were <250 ng/ml, M R GRAY, A N KINGSNORTH (University Depart- tostatin receptors in human gastric mucosa suggesting impaired fibrinolysis. ment of Surgery, Royal Liverpool Hospital, (HGM) in comparison to RCC. In conclusion, there is evidence of Liverpool) Omeprazole causes achlorhydria and Plasma membranes were prepared from accelerated thrombin generation in CD which hypergastrinaemia in man and rats. Long term normal gastric body mocusa (seven patients) shows little correlation with disease activity. administration is associated with entero- and RCC (five female Wistar rats). Competitive With low fibrinolytic activity, thrombin chromaffin like (ECL) cell hyperplasia and the radioligand binding assays were performed in generation may be of importance in the patho- induction ofcarcinoid tumours in rats. the presence or absence ofeither NaCI (20-120 genesis of Crohn's disease. We studied the response to 30 days adminis- mmol/l) or MgCl2 (1-25-10 mmol/l). Results tration of omeprazole 400 [tmol/g/day in 20 are expressed as percentage of binding in the rats. In omeprazole treated rats the mean absence of salts. At 60-100 mmol/1 NaCI, serum gastrin rose 19 fold from 45-45 fmol/ml specific binding to RCC membranes is reduced Detection of Mycobacterium paratuber- (range 29-89 fmollml) to 831 (29) fmol/ml by up to 60%. By contrast, the addition ofNaCl culosis in long term cultures of Crohn's (range 625-1400 fmollml) (p<0-01 Mann- in HGM increases binding in a dose dependent disease by polymer chain reaction amplifica- Whitney U test). manner, maximal at 80 mmol/l NaCI (170 tion Gastric body crypt cell production rate (22)% (mean (SEM)) n=7, p<0-001). Signifi- measured by vincristine metaphase arrest cant increase in specific binding to RCC mem- M MOSS, J D SANDERSON, M TIZARD, J HERMON- 1 mg/kg was 0.4 crypt cells per hour in vehicle branes is produced by addition of MgC92 TAYLOR, F EL-ZAATARI, D MARKESICH, A582 British Society ofGastroenterology

D GRAHAM (Department of Surgery, St George's have been characterised in ileal biopsy speci- elemental diet (ED) or prednisolone (P), pros- Hospital Medical School, London Digestive mens from patients with ulcerative colitis pective follow up and comparison of these Disease Section, VAMC and Baylor College of (n=11), colonic Crohn's disease (n=6) and remissions warrants further study. Thirty of42 Medicine, Houston, Texas, USA) In vitro myco- control groups patients with cancer (n=7) and patients with active CD completed four weeks' bacterial cultures of intestinal tissue obtained constipation (n=8). The ileum was macro- randomly allocated treatment with either ED Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from at resection (R) or biopsy (B) from 18 Crohn's scopically and microscopically normal in all (Vivonex TEN 21/day for one month) or disease (R=13, B=5), five ulcerative colitis cases. Ileal mucosa from the distal 2 cm of P (0.75 mg/kg/day for two weeks and subse- (R=2, B3), and six non-inflammatory bowel ileum resected at surgery was stripped of quent reducing doses). The remaining 12 disease patients (R=2, B=4) were incubated at underlying muscle layers and mounted in a patients were withdrawn, nine being intolerant 37°C for between two and six years. Culture small flux chamber. Using `4C labelled TA in a of ED and three requiring early surgery. At pellets were tested blind for the presence of standard buffer absorption was shown to be four weeks, both groups showed similar signi- Mycobacterium paratuberculosis using a highly active because (i) it occurs predominantly in ficant improvements in disease activity index, sensitive polymer chain reaction assay based on the mucosa to serosa direction, (ii) it occurs ESR, and albumin. IS900, a DNA insertion element specific to this against a concentration gradient, (iii) is In those who had remitted on ED (n=i1, organism. Extreme precautions were taken to reduced in the presence of inhibitors, (iv) is five newly and six previously diagnosed CD), avoid contamination. sodium dependent and (v) demonstrates the site of disease was small intestine in four, M paratuberculosis was present in six of 18 saturation with an estimated Km of 10 [tmol/1-'. colon in two, and ileocolonic in five. In the (33%) CD and one of 11 (9%) non-CD cultures. A standard 10 [tmolll-' TA was used to compare P treated group (n=19, 10 newly and nine All UC specimens were negative and the single clinical groups. The TA uptake (mean (SD)) in previously diagnosed CD), disease site was positive control was a mucosal biopsy specimen pg/g wet weight/45 minutes was 13-4 (3-1) for small intestine in six, colon in six, and ileo- taken at follow up for colonic polyp. Media and ulcerative colitis, 8-2 (4.0) for Crohn's, 13-1 colonic in seven. The 30 patients were prospec- buffer only control samples were consistently (4.2) for cancer and 12-9 (3.9) for constipation. tively followed for one year. ED treated negative. The intensity of the polymer chain The ileal mucosal absorption is not signifi- patients had a higher relapse rate, with just one reaction signal in the CD positive samples was cantly different in patients with cancer, consti- patient still in remission at 12 months. The consistent with an abundance of M paratuber- pation, and ulcerative colitis. Patients with cumulative probability of maintaining remis- culosis approximating to 5-30 genomes per colonic Crohn's disease have a reduced ability sion at six months was 0-67 after P, and 0-28 culture pellet. All but one of the positive CD to absorb TA despite a macroscopically and after ED, and at 12 months was 0.35 after P, cultures were from resections. microscopically normal ileum (p<0O05, Mann- and 0.09 after ED, (p<0 05; log rank test). Although the study may have been affected Whitney). Among the ED treated group, patients with by unequal R/B ratios, these results are consis- CD confined to the small intestine tended to tent with the presence of M paratuberculosis in relapse later than those with colonic involve- Crohn's disease affected tissue in a form which ment. replicates extremely slowly. Comparative study of "Tc HM-PAO and ED is as successful as P in inducing remis- indium 111 tropolone leucocyte scintigraphy sion in acute CD but the subsequent relapse in inflammatory bowel disease rate is higher.

Assessment of the activity and extent of S J MIDDLETON, D LI, E P WRAIGHT, J 0 HUNTER Crohn's disease: a comparative study of (Departments of Gastroenterology and Nuclear indium III tropolone and "Tc HM-PAO medicine, Addenbrooke's Hospital, Cambridge) PANCREAS labelled leucocyte scintigraphy 'Tc HM-PAO leucocyte scanning (TLS) http://gut.bmj.com/ yields high quality scintigrams and leads to a S J MIDDLETON, D LI, E P WRAIGHT, J 0 HUNTER lower radiation dose and shorter imaging time (Departments of Gastroenterology and Nuclear than indium 111 tropolone leucocyte scanning Impact of technology on outcome in pan- Medicine, Addenbrooke's Hospital, Cambridge) (ILS). We compared their diagnostic accuracy creatic cancer patients Scintigrams were performed in 31 patients with in inflammatory bowel disease (IBD). A total of Crohn's disease using leucocytes labelled with 143 patients with known IBD or suspected A TOCCHI, L BASSO, L LEPRE, G LIOTTA, indium-III tropolone (ILS) (n= 16 - small IBD (SIBD) received either TLS (39 IBD, 16 G MIAZZONI, A GIULIANI (INTRODUCED BY bowel Crohn's (SB) =4, large bowel (LB) =8, SIBD) or ILS (61 IBD, 27 SIBD). Six received C o'MoRAIN) (lst Department ofSurgery, Univer- on September 24, 2021 by guest. Protected copyright. both (B) =4), or HM-PAO (TLS) (n= 15 - both. Age and sex were well matched in both sity ofRome, La Sapienza, Italy) We reviewed SB = 7, LB = 7, B = 1). Activity was assessed groups. The presence and extent ofactive IBD 207 consecutive patients admitted to our hos- separately in three segments (small bowel and were assessed from clinical, endoscopic, histo- pital for pancreatic cancer - 100 from 1960-74 caecum, ascending and transverse colon, logical, and radiological findings and para- (group A) and 107 from 1975-89 (group B). descending and sigmoid colon) and each meters ofinflammation in venous blood. These During this latter period there was progressive graded according to whether bowel activity was findings were compared with scintigrams introduction of ultrasound, fibreoptic endo- nil (0), less than bone marrow (1), less than graded 0-4 according to whether bowel activity scopy, ERCP, computed tomography, and liver (2), less than spleen (3), or greater than was nil (0), less than bone marrow (1), less than nuclear magnetic resonance into clinical prac- spleen (4). Grades were added to give the total hepatic (2), less than splenic (3), or greater than tice. Mean duration of symptoms before diag- activity index (TAI). Maximum segmental splenic activity (4). For TLS, specificity nosis was of 6-4 months in group A and 6-5 activity in ILS correlated with erythrocyte (SP)=95%, sensitivity (SEN)=94%, accuracy months in group B. Substantial differences sedimentation rate (ESR) (p=0 047), C reac- (ACC)=95%, positive predictive value were found only in the subset of patients who tive protein (CRP) (p=0.002) and al-anti- (PPV)=97%, negative predictive value had been symptomatic for pancreatectomy. All dard meals at 9.00 am and 5.00 pm. Blood 10-2 (5-2-15-7) jtg/ml, and 12-8 (6.8-16.9) the parameters were studied for five days with samples for PP and CCK were taken after the Fg/ml for TAA (p.0O001 for each), respec- the patient on an elemental (Nutrinaut, 2500 second meal - every 30 minutes for two hours. tively. For comparison, admission sera from cal/day, 1 cal/ml) or a polimeric (Nutrisond, Basal PP and CCK values did not change nine patients with non-pancreatitis acute 2500 cal/day, 1 cal/ml) diet, with or without PS significantly during the four week period. The abdomen gave values of 5.6 (0-8-14-5) Fg/ml (Pancreasmit, 70000 U/day of lipase, 12000 integrated meal stimulated PP response was for AA, and 7.0 (3-0-15-4) itg/ml for TAA U/day of trypsin). significantly decreased (p<0 05) on day 1, but (p<002 v controls, p<0 002 v pancreatitis in Without PS, malabsorption was found with not on days 15 and 29 compared with pre- each case). In the pancreatitis group, values both diets. A noticeable reduction in faecal entry. On days 30 and 31 the PP response was were equally low in patients predicted to have a weight and faecal loss was obtained with PS significantly increased (p<0.01) compared mild or severe course while serial sera, taken up both for the elemental (faecal weight from with pre-entry (mean (SEM) 9 40 (1-44), 8-10 to 12 months later in individual cases, showed mean (SEM) 193 (3.3) g/day to 41-4 (20.7) (1-63), 8-30 (1-38), 9-46 (1-85), 13-2 (2-41), little ofno change. Thus, it is unlikely that non- p<0005; fat from 29-1 (3.0) to 5-1 (2.7), 12-7 (2.20); nmol/l/minute; days 0, 1, 15, 29, specific efflux of the vitamin from serum into p<003; nitrogen from 2 (0-31) to 0-61 (0-31), 30, 31 respectively). The integrated meal blood cells and internal organs was the explana- p<003) and the polimeric diet (faecal weight stimulated CCK response was significantly tion. Instead it seems that: (a) premorbid from 165 (30.3) to 74 (48 0), p<0 005; fat from decreased on day 15 (p<0-01), but no signifi- dietary deficiency of vitamin C may facilitate 36-4 (8-1) to 6-5 (3.2), p<0-01; nitrogen from cant change was found on the other days acute pancreatitis when predisposing factors 2-2 (0.49) to 0-72 (0.34), p<0*05). No dif- http://gut.bmj.com/ compared with pre-entry (609 (77), 501 (33), exist; (b) pancreatic oxidative stress and the ference in faecal losses was found between the 372 (56), 473 (48), 667 (79), 596 (51); pmol/l/ elicited inflammatory response compounds the two diets with or without PS. minute; days 0, 1, 15, 29, 30, 31 respectively). problem; (c) suboptimal diets and consump- In conclusion, a digestive capacity is neces- In conclusion, during four weeks' treatment tion of AA during inflammation may also sary for the absorption of both elemental and with enprostil, postprandial PP and CCK rationalise changes in other patients with the polimeric diets. Pancreatic enzymes must be release were inhibited at two weeks but not at acute abdomen. added to enteral diets when pancreatic insuffi- four weeks. On the first two days after stopping ciency is present. treatment PP, but not CCK, values rose above on September 24, 2021 by guest. Protected copyright. the pretreatment values. Thus, the changes in plasma PP cannot be explained by changes of Scoring CT scans in severe pancreatitis CCK induced by PGS. DUODENUM J S O'NEILL, B SUC, L W TURNBULL, D C CARTER (University Departments of Surgery and Radiology, Royal Infirmary ofEdinburgh, Edin- burgh) To determine if contrast enhanced com- Duodenal ulcer bleeding and perforation - Endocrine sensitivity of the human pan- puted tomogram (CT) appearances correlate implications for long term management creatic tumour cell line with clinical outcome in severe pancreatitis, a simple scoring system has been devised to S A RAIMES, CC CHUNG, J W C LEUNG, J F ROBERTSON, S A WATSON, J D HARDCASTLE quantify CT abnormalities. S C S CHUNG, A K C LI (Prince ofWales Hospital, (Department of Surgery and Cancer Research Twenty three patients with severe acute Chinese University of Hong Kong) The aim of Campaign Laboratories University of Notting- pancreatitis underwent contrast enhanced CT this study was to determine the significance of ham, Nottingham) We have derived a human scanning, and the scans were scored for the acute bleeding or perforation in the long term pancreatic adenocarcinoma cell line (Pan 1). degree of pancreatic swelling/necrosis and in- management of patients with duodenal ulcer The growth response of Pan 1 to gastrointes- volvement of adjacent organs and tissues. (DU). Two groups of consecutively admitted tinal (GI) peptide hormones and sex steroids Five patients required urgent surgical inter- DU patients were compared: group A (n= 174) was compared in vitro by measuring cell pro- vention to drain/debride infected necrosis. A - acute bleed; group B (n= 100) - perforation. liferation by 75[Sel-selenomethionine incor- further five patients underwent elective drain- The groups were comparable for age, sex ratio, poration and direct cell counts. age of pseudocysts/collections. The remainder and proportion ingesting non-steroidal anti- The proliferation of Pan 1 was unaffected by were successfully managed conservatively. inflammatory drugs. A total of 47. 1% of group gastrin, bombesin, and the somatostatin CT scores ranged from 0-24. Significant A but only 4% of group B (p<0 001) had analogues; sandostatin and RC-160. Radio- correlations were noted between the CT score suffered a previous DU complication. Only ligand binding studies confirmed the prolifera- and length ofhospital stay (r=0-736, p<0-001) two of the patients in group A had had a tion assays as Pan 1 had no gastrin-17 or (linear correlation coefficient); duration of iv previous perforation, 80 had had at least one somatostatin-14 binding sites. fluid administration (r=0-667, p<0-001) previous bleed. The proliferation of Pan 1 was unaffected by (linear correlation coefficient). and APACHE Follow up ofpatients treated medically or by oestradiol but significantly enhanced by pro- II scores (r=0-549, p<0-01) (linear correlation non-definitive ulcer surgery was for 36-60 gesterone (10-'M, 135% of control, p<0 02, coefficient). CT scores were also higher in those months, at a time when we did not prescribe n= 8 expts). Conversely, the antisteroidal patients who underwent surgery (mean score long term maintenance H2 antagonists. Some agent, Danol, significantly reduced the growth 13 (4-24)) than in those managed conserva- 42-2% of group A but only 3-8% of group B of Pan 1 (10 [sg/ml, 20% of control, p<0-001, tively (mean score 8 (0-20)) (p<0 05) (Wil- (p<0-001) suffered a further ulcer complica- n=6 expts) which titrated out at 1 [sg/ml. coxon test). tion. The median time to a further complica- Immunohistology showed that Pan 1 was posi- Such a scoring system seems therefore to tion was 12 months in group A - only two A584 BritishSociety ofGastroenterology patients had perforated ulcers, the others had tion rate of H pylon). "C-UBT and endoscopy domly allocated to continue treatment (single further bleeds. were repeated at one, three, six, and 12 months blind) for 12 weeks on their existing dose of We conclude that DU patients who suffer an or at symptomatic recurrence. (H pylori posi- C (1 g (200 mg three times daily+400 mg at acute bleed are a high risk group for further tive on 'C-UBT=excess b9'CO2 >5 per ml.) bedtime), 2 g or 3 g daily, subdivided appro- bleeds but not for perforation. Patients who Thirty patients (20 men, median age 45 priately) or CBS 240 mg twice daily as follows: Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from perforate have a significantly lower risk of years, range 16-70 years, 10 smokers, 20 CBS v C, 1 g n=25; 2 g n=22; 3 g n=l1. The further complication. This has important healed on ranitidine) were randomised. There patients on CBS and on C were well matched implications for the long term treatment of were no significant differences between the two for demographic features including previous patients with DU complications. groups with respect to the usual variables or courses of ulcer treatment, number of relapses initial ulcer healing treatment. In the placebo on maintenance treatment, and previous group seven of 15 (50%) DUs have recurred at refractory episodes. Of the 47 patients who 10 (n=1), 21 (n=2), 30 (n=3), and 90 (n=-) completed the trial, the cumulative healing rate Duodenal ulceration during maintenance days. In the eradication group none of 15 DUs on CBS v C (taking all three strata together) ranitidine therapy: silent and deadly? recurred (median follow-up 12 weeks, x2=534, was: four weeks, 12 of 23 (52%) v 14 of 24 p<003). H pylon was eradicated in 12 of 15 (58%); eight weeks, 16 of 23 (70%) v 17 of 24 D ARMSTRONG, A L BLUM, R ARNOLD, M CLASSEN, patients, while in three the '3C-UBT values (71%); and 12 weeks, 20 of23 (87%) v 21 of 24 H GOEBELL, M FISCHER, THE RUDER STUDY were significantly lower than before (mean (88%). Healing rates within each stratum were GROUP (Division of Gastroenterology, CHUVI (SEM) excess 6"CO2=29-1 (3-1) v 13-2 (1-6) also similar on both drugs and at each time PMU, Lausanne, Switzerland) Maintenance per ml, p<005) treatment, suggesting a point, at 12 weeks being CBS v C: 1 g, 10 of 11 therapy for duodenal ulcer (DU) relieves symp- decrease in the bacterial load. (91%) v eight of 10 (80%); 2 g, seven of eight toms but the risk of asymptomatic relapse and These data suggest that a possible strategy (88%) v 10 of 11 (91%); 3 g, two offour (50%) v complications is unknown. After DU healing, for long term DU management could be initial three ofthree (100%). Pain was present in CBS 1899 patients entered a multicentre study of healing with H2 anatagonists, followed by one 22% and C 46% in the two weeks before entry risk factors for DU relapse during ranitidine week oftriple therapy. to the trial; and during the trial in 25% and 13% (150 mg at night) therapy. Endoscopy, obliga- respectively (NS). No patient had significant tory at 12 and 24 months, was also dis- side effects. cretionary if symptoms recurred. Overall, 432 In conclusion, in cimetidine refractory DU, (23%) patients relapsed, 107 (5.6%) repeatedly; Effect of eradication of Helicobacter pylori changing treatment to CBS did not confer any DUs were found at 205 of 3002 (6.8%) obliga- on acid secretion in duodenal ulcer patients advantage over continuing the same dose of tory endoscopies and 361 of 1168 (31%) dis- cimetidine; healing occurred with both drugs cretionary endoscopies. No relapse at dis- G M FULLARTON, R CHITrAJALLU, K EL McCOLL in most patients and at a similar rate. cretionary endoscopy but 87 of 432 (20%) of (Departments ofSurgery, Medicine, Therapeutics, initial relapses and 87 of 205 (42%) of relapses Western Infirmary, Glasgow) Eradication of at obligatory endoscopy were asymptomatic. Helicobacter pylori is associated with a OESOPHAGUS Risk factors for asymptomatic relapse include 50% decrease in circulating gastrin concentra- duodenal oedema (p=0037, Fisher's exact) tions. It has been hypothesised that this reduc- and erosions (p=0008) at healing, multiple tion in gastrin may be accompanied by DU (p=0022), tea (p=0-031), and poor decreased acid secretion which may explain the Acute dysautonomia: a rare cause of dys- motivation (p=0037) but not previous asymp- beneficial effect ofHpylor eradication on ulcer phagia and transient achalasic manometry tomatic recurrences or non-steroidal anti-in- relapse. To study this we have examined acid http://gut.bmj.com/ flammatory drugs. Haemorrhage (1-3% per secretion before and after eradication of L BENINI, S CALIARI, S PILATI, E BARDELLI, patient year before, 0.37% during main- H pylorn in eight patients (seven women, one C SEMBENINI, M T BRENTEGANI, F BONFANTE, tenance) and the individual relapse rate (1 7 per man) median age 55 years (range 38-60) with G CASTELLANI, I VANTINI (Divisione di Gastro- year before and 0- 16 during maintenance) inactive duodenal ulcer disease. Basal (BAO) enterologia, COC di Valeggio sIM, University of decreased. and pentagastrin stimulated maximal acid out- Verona, Italy) Acute dysautonomia is a rare In summary, maintenance ranitidine put (MAO) and meal stimulated output (MSO) disease that often follows viral infection and is therapy may be silent but is not deadly: 6.8% of were measured before and one month after characterised by functional derangements of patients, about 40% asymptomatic, will have a eradication ofHpylori. In addition, six patients the sympathetic/or parasympathetic nervous on September 24, 2021 by guest. Protected copyright. recurrence at routine endoscopy but relapse had pentagastrin studies one year after eradica- system, ofboth, similar to Guillain-Barre poly- and complication rates are reduced. Risk tion. H pylor status was confirmed by antral neuritis. Dysphagia may be present, but the factors for asymptomatic relapse may indicate biopsy, urease test and "4C urea breath test. The motor abnormalities involved have not been patients with severe disease who are accus- MSO was measured in response to a peptone described so far. Two cases were studied in our tomed to pain or patients who deny their meal using the double marker technique. Acid centre. The first, a 54 year old woman, disease. (Support: SNF 32-26369.89 & outputs (mmol/hour) were similar one month presented two weeks after an acute pharingitis, Cascan.) after eradication (mean (SEM), BAO 6-7 (1 -1), dysphagia, and mild dysuria. The second, a 37 MAO 30-1 (3.9), MSO 23.4 (6.6)) compared year old man, presented with sudden onset of with the respective pre-eradication values (10-7 accommodation problems, dysuria, and severe (2.4), 34.7 (4.7), and 22-8 (6 0)). BAO (10-1 dysphagia. Nuclear magnetic resonance A new strategy for long-term management of (3.8)) and MAO (30.9 (7.6)) were also similar excluded brain problems, and autonomic func- duodenal ulcer (DU) one year after eradication compared pre-eradi- tion testing showed a mild derangement mainly cation values. of the cholinergic system. In both patients, R P H LOGAN, R J POLSON, J J MISIEWICZ, We conclude from this study that eradication endoscopy and upper gastrointestinal investi- MM WALKER, Q N KARIM, J H BARON Departments ofH pylori is not accompanied by a decrease in gations were normal, apart from oesophageal of Gastroenterology, Microbiology, and Histo- acid secretion. The decreased ulcer relapse athony and delayed barium emptying in clino- pathology, Central Middlesex and St Mary's rates after eradication of H pylori cannot be static position. Manometry showed complete Hospitals, London) Duodenal ulcers (DUs) explained by reduced gastric acidity. aperistalsis and only partial relaxation of the healed by bismuth salts have lower recurrence lower oesophageal sphincter. Symptoms rates than those healed by other agents: this resolved in two weeks in both patients. After may be the result oferadication ofHelicobacter one month the manometry results had reverted pylori. A prospective placebo controlled trial of Colloidal bismuth subcitrate in the treatment to normal in the first patient only. Two years short term H pylon eradication therapy on DU of refractory duodenal ulcer later oesophageal scintigraphy and manometry recurrence after DU healing was performed. were normal in both patients. There were Patients with a DU (>5 mm) and H pylori KD BARDHAN, S SINGH, P CHERIAN, M THOMP- similar manometry and radiological findings in (diagnosed by13C urea breath test ('C-UBT), SON, P MORRIS, M GAMMIE, K F C HINCHLIFFE a third patient with chronic sympathetic dys- antral culture and, histology) were treated with (District General Hospital, Rotherham) We in- autonomia caused by medullary degeneration ranitidine 300 mg nocte for one month. DUs vestigated ifwhether refractory duodenal ulcer (esosaminidase deficit). not healed on ranitidine were treated with (RDU) - that is duodenal ulcer (DU) still active Accurate history and physical examination omeprazole 40 mg mane. Immediately after after -three months' treatment on cimetidine are necessary to exclude acute dysautonomia in endoscopically confirmed ulcer healing and (C) 3 1 g daily) would heal when treatment was patients with suspected achalasia. These cases repeat 3C-UBT, patients were randomised to changed to the mucosal protectant drug col- may also confirm a role of autonomic nervous either placebo or one week triple therapy loidal bismuth subcitrate (CBS). RDU patients system derangement in the pathogenesis of (which we have shown achieves 87% eradica- (n=58) without severe symptoms were ran- achalasia. British Society ofGastroenterology A585

Oesophageal transit before and after healing disease is common. Among our patients, alter conduction velocity (LOSs to LOS1O -0-8 ofoesophagitis weight loss is frequent but other complications to 0.3 mm/seconds). LOS tone was not are rare. The proportion of patients progress- changed by baclofen (-10 to 9 mmHg). Simi- P SINGH, A ADAMOPOULOS, R H TAYLOR, ing to achalasia from diffuse oesophageal spasm larly, no significant effect was seen on any D G COLIN-JONES (RoyalNavalHospital, Haslar, is higher than previously reported. parameter at one or four hours. Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from Gosport, and Queen Alexandra Hospital, We conclude that GABAB receptors do not Cosham, Hampshire) Several studies have modulate the hypertensive contractions in nut- shown that oesophageal transit is often slower cracker oesophagus. Any effect of benzo- in patients with reflux oesophagitis. This study Peristaltic propagation accelerated after diazepines (GABAA and GABAB agonists) in was designed to determine whether the pro- oesophageal stricture dilatation these patients is likely to be mediated by central longed oesophageal transit in this condition can mechanisms. be reversed with the healing ofinflammation. M DAKKAK, G K BUCKTON, J R BENNETT (Hull Twenty three patients with endoscopic Royal Infirmary, Hull) Abnormalities of oesophagitis were recruited. A 24 hour oesophageal motility occur in association with oesophageal pH test showed abnormal acid oesophageal strictures. Whether these peristal- Redox potential in the lower human reflux in 19 of 23 patients. The patients tic abnormalities would be altered after dilata- oesophagus swallowed a 10 ml bolus of water labelled with tion is unknown. Eleven patients with benign 1 mCi of 'Tc followed by dry swallows every peptic oesophageal stricture (seven men and R J C STEELE, S LEDINGHAM, S Y IFTIKHAR, 15 seconds. A total of 180 one second frames four women): mean age 64-9 years; range 39-67 J D HARDCASTLE (Department ofSurgery, Univer- were taken. Time versus activity curves were years) had oesophageal manometry before and sity Hospital, Nottingham) Redox potential generated for the proximal, middle, and distal three weeks after dilatation. In each case 10 wet reflects the ratio of oxidised to reduced species thirds ofoesophagus and thewholeoesophagus. swallows (5 ml of water) were studied measur- in a medium. A redox sensitive radiotelemetry Transit times were measured as the interval ing wave amplitude and duration at 3, 8, and capsule has recently been developed and, using between the initial appearance to the dis- 13 cm above the lower oesophageal sphincter. this device tethered 5 cm proximal to the lower appearance of more than 90% of the peak The percentage of swallows resulting in a oesophageal sphincter, the redox potentials in counts. The test was repeated after complete propagated peristaltic wave were calculated in the lower oesophagus have been measured in endoscopic healing of oesophagitis in all the each case and the velocity of peristaltic propa- five healthy volunteers over a 24 hour period. patients after a course of omeprazole (40 mg/ gation was measured over a 10 cm distance. Simultaneous pH monitoring was also per- day) for a median duration of 11 weeks. Thirty Wilcoxon's rank sum test was used to compare formed. healthy volunteers served as control subjects. the two series. Percentage ofswallows resulting During the day, the redox potential The patients had longer median total supine in a propagated wave was also not different remained within the range of0 to 100 mV apart transit times than controls (16 v 11 seconds; after dilatation, but there was a difference in from occasional rises up to 200 mV. These p<0025). This was because of prolonged the velocity of peristaltic propagation (mean increases usually, although not invariably, transit in the distal oesophagus (14 v 10 (SEM) 2-86 cm/second (0-15) before; 3-06 coincided with drops in pH. At night, how- seconds; p<0025). There was a strong positive (0-15) after dilatation) (p<0.05). Amplitude ever, dramatic cyclical falls in the redox poten- correlation between the grades of oesophagitis (mean (SEM) 67 cm H20 (7.0) before; 66 (5.5) tial which were not accompanied by changes in and total and distal supine transit times after dilatation) and duration (mean 3-2 pH were observed. These falls were gradual (r= +0-723; p<0.01). There was no correlation seconds (0-1) before; 3. 1 (0-1) after dilatation) and had a mean duration of 26 minutes, between the age and sex of the subjects and did now show significant difference. frequently reaching a value of - 500 mV. The their transit times. There was no significant In conclusion, we suggest that dilatation of episode always ended in a rapid rise in redox http://gut.bmj.com/ change in median total supine or distal supine strictures apart from widening the lumen may potential, usually back to the normal daytime transit times after the healing of oesophagitis improve peristaltic propagation velocity. This range, and was followed immediately by (16 v 14 seconds; and 14 v 13 seconds respec- may be one of the factors which explains another similar episode. Upon waking, the tively). amelioration ofdysphagia after dilatation. pattern reverted to that seen during the Results from this study suggest that pro- previous day. longed oesophageal transit in gastrooesopha- At night, therefore, there seems to be a geal reflux disease is a primary phenomenon cyclical redox reaction in the normal lower rather than a consequence ofinflammation. Double blind crossover study of a GABAB oesophagus, the importance of which is on September 24, 2021 by guest. Protected copyright. receptor agonist on the hypertensive contrac- unknown. tions ofnutcracker oesophagus Four year prospective study ofthe presenting A S McINTYRE, K KNOWLES, R G LONG (Medical features ofachalasia in Edinburgh Research Centre, City Hospital, Nottingham) Does prolonged ambulatory oesophageal pH The effect of gamma-aminobutyric acid monitoring influence clinical management? P J HOWARD, L MAHER, A PRYDE, R C HEADING (GABA) receptor agonists on oesophageal (Department of Medicine, University of Edin- motor function has not been investigated des- N I McDOUGALL, W DICKEY, J S A COLLINS, burgh) We have prospectively studied the clini- pite some authors advocating the therapeutic B J COLLINS, A H G LOVE (Royal Victoria cal presentation ofachalasia in patients referred use ofdiazepam (GABAA and GABAB agonist). Hospital, Belfast and Department of Medicine, to us during the last four years. With the Studies in guinea pig intestine and human The Queen's University of Belfast) Although increasing availability of manometry, we sus- jejunum suggest that enteric GABAB receptors prolonged ambulatory pH monitoring is the pected that the clinical presentation might now mediate relaxation while GABAA receptors standard research technique for acid reflux differ from classical textbook descriptions. The augment contraction. We have investigated the quantification, its relevance in clinical manage- diagnosis was established in 29 patients (17 effect of baclofen (20 mg), a selective GABAB ment is less clear. We have audited the results men; 12 women). Their mean (SD) age at onset agonist, on the oesophageal motility of seven and management outcome, defined as com- of symptoms was 40-1 (17-7) years (range 5 to patients with nutcracker oesophagus. Motor mencement, change, or cessation of medical 70) and at diagnosis was 43-3 (18) years (range activity was recorded at baseline, one, two, and therapy, diagnostic confirmation or surgical 15 to 71). The presenting symptoms were: four hours on each of two days at the lower referral, resulting from 85 clinical referrals to a dysphagia for solids 100% and for liquids 93%; oesophageal sphincter (LOS), and at 5 cm regional service for monitoring. Results of regurgitation 86%; chest pain 69%; weight loss (LOS5), 10 cm (LOSIo), and 15 cm (LOS15) monitoring were normal in 40 (47%), abnormal 59%; vomiting 38%; chest complications 0%. above the LOS. in 43 (5 1%), and two studies (3%) were unsuc- Endoscopy was normal in 12 patients; achalasia Baclofen's effect on contraction amplitude cessful. Sixty nine patients (8 1%) had under- was suggested from only 15 of 24 barium was maximal at two hours (24% reduction) with gone upper gastrointestinal endoscopy before examinations. Eleven of the patients had been no effect at one hour (3%) or four hours (6%). monitoring. Of 21 patients with normal endo- treated for gastro-oesophageal reflux disease. At two hours, however, baclofen showed no scopic findings, 19% had an abnormal monitor- Three patients progressed from diffuse statistically significant effect on the amplitude ing result compared with 34% of those with oesophageal spasm to achalasia during the of contraction (censored loge pressure) (95% endoscopic evidence of reflux disease. Manage- study period. confidence interval for mean change placebo- ment was influenced by monitoring in 67% of The results show that the clinical features of baclofen) (-35 to 55 mmHg LOSs, -3 to 73 patients with normal endoscopic findings and achalasia conform to textbook descriptions. mmHg LOS1O, and -11 to 20 mmHg LOS15), in 46% of abnormal patients. The results However, it is no longer exceptional for radio- or on the duration of contraction (-3 to 1.5 suggest that the role of ambulatory monitoring logy and endoscopy to fail to make the correct seconds LOS5, -0.5 to 0.7 seconds LOS1O, is primarily in those patients with normal diagnosis, and initial misdiagnosis as reflux -0-2 to 0-6 seconds LOS15). Baclofen did not endoscopic findings, although the overall yield A586 BritishSociety ofGastroenterology of abnormal results is low. Since management endoscopic 'gastritis'. There was no pattern of 1:100000 adrenaline and 0.5-2 ml of 5% in patients with abnormal endoscopic findings association between the endoscopic categories ethanolamine injected into the bleeding ulcer. is influenced in less than 50% of referrals, the and histological types of gastritis. However, if The two groups were well matched for known contribution ofmonitoring in this group seems erosions were seen endoscopically, histological risk factors offurther bleeding. to be of limited value. gastritis was present in 20 of 21 cases. There- Twenty five patients from the conservative Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from fore, we examined whether endoscopic 'gas- group and seven from the injected group rebled tritis' was related to degeneration ofthe surface during hospital admission (p<0-01). epithelium, assessed histologically. Thirty two A total of 20 patients underwent emergency Patients with reflux oesophageal strictures of 79 patients with endoscopically abnormal surgery and a further three patients died have reduced sensitivity to oesophageal acid mucosa, compared with five of 43 with normal without an operation. Seventy ofthe remaining mucosa, showed surface degeneration 86 patients underwent endoscopic follow up; P J WINWOOD, C MAVROGIANNIS, C L SMITH (p=O0002 x2). 42 from the injected group and 28 from the (Department of Medicine II, University of We conclude that endoscopy is unreliable conservative group. All receive standard ulcer Southampton) It has previously been suggested in detecting gastritis, that the endoscopic healing doses of H2 receptor antagonist drugs. that patients with strictures have reduced classification does not correlate with the histo- Ulcer distribution (gastric and duodenal), age, oesophageal mucosal sensitivity to acid. In this pathological changes, and suggest that endo- non-steroidal anti-inflammatory drug usage, study sensitivity to acid has been investigated scopic 'gastritis' reflects the presence ofsurface and severity ofbleeding were similar in the two in a larger group of both stricture and degeneration ofthe mucosa. groups. oesophagitis patients. Forty eight hours after the index endoscopy, Thirty five patients with a history of benign injection sites were oedematous but ulcers were peptic stricture and 30 patients with uncom- not enlarged. In both actively and conserva- plicated oesophagitis recorded symptoms of Endoscopic Nd-YAG laser ablation of bleed- tively treated patients endoscopic stigmata of reflux and indicated their severity on a visual ing vascular malformations in the upper recenthaemorrhagewereunchanged. Sixweeks analogue scale of0 to 10. Patients with Barrett's gastrointestinal tract: a long term follow up after presentation endoscopy showed that 41 oesophagus, other upper gastrointestinal ulcers treated by injection had healed (45%) disease and those taking non-steroidal anti- I R SARGEANT, L A LOIZOU, D GRIGG, and 26 ulcers treated conservatively (93%) had inflammatory drugs were excluded. Oesopha- M TULLOCH, S G BOWN (National Medical Laser healed. Percentage healing of gastric and duo- geal acid perfusion tests were performed dur- Centre, University College Hospital, London) denal ulcer were similar in the two groups. ing which the lower oesophagus was initially Vascular lesions of the upper gastrointestinal Endoscopic injection therapy given for acute perfused with water followed by 0-1 N HCI at a tract can cause recurrent haemorrhage of in- bleeding does not impair peptic ulcer healing. rate of 6 mI/minute (maximum 80 ml). At the creasing frequency and severity, often from onset of reflux symptoms, the perfusion was more than one site. We have treated 42 such stopped and the volume of acid infused patients endoscopically with the Nd YAG laser recorded. and followed them for a mediau of 27 months. Is your endoscopic retrograde cholangiopan- The mean symptom score in oesophagitis All patients required transfusion to maintain creatographic examination really necessary? patients was 4.95 compared with 3.75 in the haemaglobin before laser phototherapy. Four stricture group. Two of the stricture patients distinct groups of patients were identified. All J R THORNTON, A J LOBO, D J LINToTr, A T R AXON had experienced no reflux symptoms. The eight (100%) of those with single angiodys- (Gastroenterology Unit and Department of mean volume of0. 1 N HCI infused at the onset plasia, seven of eight (88%) patients with Radiology, The General Infirmary, Leeds) We of symptoms was 44-1 in the oesophagitis multiple angiodysplasia, 11 of 15 (73%) reviewed retrospectively the value of liver http://gut.bmj.com/ group compared with 61-8 ml in the stricture patients with diffuse antral ectasia (water function tests and ultrasound as screening tests group (p<005, Mann-Whitney). There was melon stomach), and six of 11 (55%) patients of the need for endoscopic retrograde cholan- no correlation between severity ofreflux symp- with hereditary haemorrhagic tielangectasia giopancreatography (ERCP) in patients with toms, severity of oesophagitis at endoscopy, (HHT) showed a noticeable reduction in trans- unexplained abdominal pain. In 1989 and age, or length ofhistory and the acid perfusion fusion requirement after treatment. Most of 1990, 1005 ERCPs were performed, of which results. these patients required minimal or no trans- 139 (14%) were for pain alone. The notes of 130 These findings confirm that patients with fusion after treatment but a few developed of the 135 patients (96%) were traced. Their

oesophagitis who develop strictures have recurrent bleeding from new lesions and median age was 56 years (range 22-87), 67% on September 24, 2021 by guest. Protected copyright. reduced sensitivity to oesophageal acid. required further laser therapy. This occurred were women and 34% were extradistrict refer- more frequently in those with multiple angio- rals. The pain was suspected to be biliary in dysplasia or HHT. Overall control of bleeding 58% (49% had had cholecystectomy), pan- was achieved in 32 patients (76%) with laser creatic in 23% (cholecystectomy 7%), and and in a further three (7%) patients in whom uncertain in 19% (cholecystectomy 20%). The ENDOSCOPY laser was ineffective, bleeding was controlled duct(s) ofinterest were delineated by ERCP in with surgery (total 83%). One patient with an 93% ofthose with suspected biliary pain, 100% extensive water melon stomach sustained a suspected pancreatic pain and 96% pancreato- treatment related perforation and died. Five gram, 92% biliary tree in pain ofuncertain site. Sydney classification of gastritis: the endo- patients continued to require similar rates of The lesions found were duct stones in 10 scopist's view blood transfusion to maintain haemaglobin. patients, chronic pancreatitis in five, pan- In conclusion endoscopic laser therapy is creatic carcinoma in one, and peptic ulcer/ P DUANE, P N FOSTER, J I WYATT, M S LOSOWSKY highly effective in reducing bleeding rate from duodenitis in four. Ultrasound had been under- (Departments of Medicine and Pathology, St upper gastrointestinal vascular anomalies; taken in 94% of cases. For duct stones, its James's University Hospital, Leeds) We have patients with single and multiple angiodys- sensitivity was 90% and specificity 86%. For examined the relation between the endoscopic plasias and water melon stomachs are most pancreatic disease, its sensitivity was 50% and features of gastritis proposed in the Sydney likely to benefit but most of those with HHT specificity 95%. Liver function tests were system (J Gastroenterol Hepatol Working Party are also well controlled. performed in 96%. Ofthese, alkaline phospha- Reports (1990), 1-10) and the presence and tase was the most sensitive (67%) and specific type ofhistological gastritis. Four endoscopists (95%) for duct stones. None of the 10 patients performed 122 unselected gastroscopies; with duct stones had both normal ultrasound biopsy specimens were examined by a single Healing after endoscopic injection therapy and alkaline phosphatase. Thus, normal ultra- histopathologist. A total of 79 patients had for bleeding peptic ulcer sound and normal alkaline phosphatase to- endoscopic gastritis (erythematous/exudative gether have 100% sensitivity in excluding duct (33), flat erosive (18), raised erosive (3), C RAJQOPAL, K R PALMER, A I AMIN (Gastrointes- stones. Using this knowledge might have atrophic (13), haemorrhagic (1), and reflux tinal Annexe, Western General Hospital, Edin- spared 52 ERCPs, saving £8320. (11)). There was agreement about the presence burgh) Endoscopic injection therapy is effective or absence of gastritis in 11 of 14 patients treatment for bleeding peptic ulcer but sclero- examined independently by two endoscopists. sants cause mucosal and submucosal inflamma- Altogether 106 patients had histological tion and could impair healing. Endoscopic biliary stenting in a district gastritis (Helicobacter pylori associated in 77). A total of 109 patients presenting with major general hospital Thirty six of 43 patients with endoscopically haemorrhage from peptic ulcers were ran- normal mucosa had histological gastritis; nine domised to conservative therapy (n=53) or K J M RAO, M VARGHESE, H BLAKE, A THEODOSSI of 16 with histologically normal mucosa had active treatment (n=56) comprising 3-8 ml of (Departments ofGastroenterology and Radiology, British Society ofGastroenterology A587

Mayday University Hospital, Thornton Heath, P J McKIERNAN, J F T GLASGOW, E J GUINEY, F H MOURAD, L J D O'DONNELL, M JAMES, Surrey) Between January 1987 and June 1990 J A DODGE, J M THOMSON, C M SCRIMGEOUR, M J G FARTHING (Department ofGastroenterology, biliary stents were inserted in 290 of 310 (94%) M J RENNIE (Department of Child Health, The St Bartholomew's Hospital, London) The deter- patients with obstructive jaundice, including Queen's University ofBelfast; Our Lady's Hos- minants for the development offood allergy are four requiring a combined endoscopic and pitalfor Sick Children, Dublin; and Department not well known although sensitisation to food Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from percutaneous procedure. The age range was of Anatomy and Physiology, University of antigens in children may follow an episode of 21-95 years; 57% had common bile duct stones Dundee, Scotland) Anorexia, malabsorption, gastroenteritis. We therefore attempted to in- and 38% had malignant biliary obstruction. and catabolism contribute to malnutrition and duce oral IgE sensitisation to ovalbumin in Endoscopic stenting failed in 20 patients (6%) - poor growth in extrahepatic biliary atresia. Our allergy prone, neonatal Hooded-Lister (H-L) 10 with malignant duodenal obstruction, six aim was to measure total energy expenditure rats infected with rotavirus. with Billroth II gastrectomy, and only in four (TEE) in this disorder using doubly labelled H-L rats aged 12, 15, 17, and 19 days were because oftechnical failure. water (2H2 180). We studied 10 patients, aged innoculated with 100 ig of ovalbumin ip, with The 30 day mortality was 3-2%. The pro- mean (SD) 3-4 (2-1) years, following hepato- alum as adjuvant. Further groups of similarly cedure related mortality was 0-6% including portoenterostomy. All had hepatic fibrosis/cir- aged rats infected 24 hours earlier with group B one death from sphincterotomy bleeding and rhosis and six persisting jaundice, one ofwhom rotavirus were innoculated with 100 itg of another from fulminant pancreatitis. Fifteen of had ascites. Standard deviation scores (SDS) ovalbumin by gavage; jejunal histology was 16 other early complications resolved with for height and weight were -1-36 (11) and also examined in parallel groups of rotavirus supportive treatment alone, the remaining -0-92 (1-0), respectively; in the jaundiced infected animals 24 hours after virus adminis- patient requiring cholecystectomy. The sur- group mean height SDS was significantly more tration. The primary and secondary IgE res- vival rates for patients with malignant hilar abnormal (p<0*05). In each patient, TEE was ponses were measured by passive cutaneous (n=30), mid (n= 18), and low (n=56) common greater than normal, the mean (SD) being 1295 anaphylaxis. Either primary or secondary IgE duct lesions were two, four, and nine months (504) kcal/day. TEE/unit body weight was 93-1 responses were elicited in 100% of 12 day respectively. In patients with benign lesions, (7.6) kcal/kg/day. TEE was correlated with (n=7), 63% of 15 day (n=8), 91% of 17 day 27 and 19 have been followed for more than both age and weight (r=+0-95 and +0-98, (n=11), and 100% of 19 day (n=7) animals three and two years respectively; 7% have respectively). Interestingly, TEE/kg did not given ip ovalbumin. All rats infected with developed recurrent cholangitis. differ significantly between those with jaundice rotavirus developed typical histological We conclude that in a district general hos- and those without (91.9 v 94-7, respectively). changes of villous shortening and syncytium pital biliary stenting is highly successful and TEE/kg was not correlated with the height or formation but these changes were less pro- associated with acceptably low morbidity and weight SDS or with any liver function test. minent in the older rats. No IgE response was mortality rates. With malignant lesions it pro- In our hands, TEE/kg was 38% higher than detected in any of the rotavirus infected rats vides good palliation and in selected patients previously reported and approximates to that given ovalbumin orally. with benign lesions it may be used as definitive found in younger patients with cystic fibrosis. Thus, parenteral IgE sensitisation to a food treatment. Account should be taken of these very in- allergen can be induced in neonatal H-L rats creased levels of TEE when calculating dietary but oral sensitisation during the acute phase of intake in extrahepatic biliary atresia. rotavirus infection could not be elicited. Intes- tinal damage occurring during rotavirus gastro- Colonoscopic follow up after resection of enteritis does not seem to be a determinant for colorectal cancer: a selective policy the development offood allergy. Chronic diarrhoea and giardiasis: a defect in A P BARLOW, M H THOMPSON (Department of specific IgA response? http://gut.bmj.com/ Surgery, Southmead Hospital, Bristol) The value of colonoscopy before and after resection of S CHAR, A M CEVALLOS, P YAMSON, P B SULLIVAN, Paediatric duodenoscopes in endoscopic colorectal cancer (CRC) is uncertain. We have G NEALE, M J G FARTHING (Department of retrograde cholangiopancreatography in adopted a policy of postoperative colonoscopy Gastroenterology, St Bartholomew's Hospital, children: indications and results in a selected group - patients under 70 years London and Dunn Nutritional Laboratory, with favourable histology. University ofCambridge, Cambridge) To inves- M L WILKINSON, E KATSIYIANNAKIS, P J MILLA Between 1981 and 1989, 269 patients under- tigate the importance of antibody response in (Gastroenterology Unit, UMDS, Guy's Campus went resection for CRC which was potentially the clearance ofinfection, we studied Gambian and Institute of Child Health, Great Ormond on September 24, 2021 by guest. Protected copyright. curative in 236 (88%). Preoperative barium children with chronic diarrhoea and giardiasis Street, London) The need for an endoscopic enemas showed one synchronous cancer and at one, three, and 52 weeks after presentation. retrograde cholangiopancreatography (ERCP) eight adenomas. Undiagnosed cancers were While total immunoglobulin concentrations service in children is not established. Below the found in five specimens and adenomas in 63. were increased in patients with giardiasis, the age of 1 year paediatric duodenoscopes (PD) Seventy nine patients have undergone post- concentrations of specific anti-Giardia anti- are necessary for the performance of ERCP. In operative colonoscopy at a median of 18 bodies by ELISA showed that only IgM was older children they may be desirable. We have months after operation. This was repeated in raised, whereas the concentrations of IgA and reviewed 77 ERCPs performed in 72 children 23 patients, 10 ofwhom had polyps at their first IgG anti-Giardia antibodies were similar in by one operator from 1981-90 to assess indica- colonoscopy. patients and controls. The antigenic deter- tions, results, and the impact of PD. From Postoperative colonoscopy showed adeno- minants of the serum IgG, IgA, and IgM 1981-6, adult duodenoscopes (AD) were used mas in 18 patients (23%) (multiple in six). They responses were determined by western blot and from 1987-90 PD (Olympus prototype). occurred more commonly when the original analysis. Patients' sera recognised, 57, 53, and Indications were: neonatal conjugated hyper- resection specimen contained polyps (p<0.01), 45 kDA antigens. All three antigens were bilirubinaemia 17 (PD), ?choledochal cyst 12 and with a family history of CRC. A second recognised by IgG, the 53 and 45 kDa antigens (PD 9), ?sclerosing cholangitis 12 (PD 2), colonoscopy showed polyps in nine patients were also recognised by IgA antibodies. There biliary trauma 6 (PD 3), miscellaneous biliary (39%) and an early metachronous cancer in one was no IgA response to the 57 kDA antigen problems 13 (PD 7), and pancreatic disease 11 patient. One patient developed an advanced while an IgA and IgG response to this antigen (PD 8). Procedures were carried out under metachronous cancer before screening was has been reported in children with acute infec- general anaesthesia (61) or sedation (11). The adopted. tion. A response to proteins of31, 100-170 kDa procedure was technically completely success- The detection of adenomas in a quarter of were also observed in patients and controls. ful in 64 children. In four the films were patients and the potential for the detection of The association of high concentrations of inadequate, in four cannulation of both ducts early metachronous cancer suggests that post- IgM anti-Giardia antibodies, low concentra- (2) or bd alone (2) were unsuccessful (all PD). operative colonoscopy is worthwhile in this tions of IgA anti-Giardia antibodies, and in- In 24 (PD 19) a new diagnosis was established select group but may not benefit the majority. ability to clear the infection suggest that there is by ERCP, in 24 (PD 13) the pre-ERCP diag- a failure to switch the IgM response to an IgA nosis was confirmed and in 16 (PD 8) rejected. response. The absence of specific IgA anti- In 12 (PD 4) further information was provided, bodies to the 57 kDa antigen suggests that their which was incorrect in one (PD). In 46 (PD 36) development is important for parasite the information influenced management. In PAEDIATRICS clearance. one sphincterotomy and stenting were per- formed (AD). Simultaneous opacification of biliary and pancreatic systems was the rule below the age of 1 year (10), except with biliary Total energy expenditure in extrahepatic Effect of intestinal infection on oral IgE atresia (6) or technical failure (1). In one patient biliary atresia sensitisation to a food allergen in this age group (26 weeks) the ducts filled A588 British SocietyofGastroenterology separately. Complications were few and minor. of non-EC patients and in aganglionic bowel of seven of 50 (54%) ulcerative colitis (UC) sera Indications for ERCP alter much with the all patients were similar to controls. were positive by indirect immunofluorescence availability of PD, and diagnostic yield is high, These data show that in addition to a general- for antibodies to ethanol fixed human neutro- suggesting that ERCP with PD should be ised immunocyte inflammatory response in with none of seven

phils (NA), compared Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from available on a supraregional basis. patients with EC complicating HD there is a proctitis sera, five of 50 (10%) Crohn's (one of selective increase in NK cells in the ganglionic 18 Crohn's colitis) and none of 34 control sera segment ofexcluded bowel. A major functional (each p<001 v UC). In UC, NA prevalence role of NK cells is that ofan antiviral response. was not related to disease activity or oral steroid Serum interleukin 6: a marker for severity of The presence of such a response in the gan- therapy. Predictive values of a positive NA shigellosis glionic colon of patients with EC complicating were 96% for UC v Crohn's colitis, 100% for HD suggests that viral infection may have a UC v proctitis, and 100% for IBD v other bowel D G H DE SILVA, V DEVASIRI, J GOKA, U JAYANTHA, role in this condition. diagnoses (mainly bacterial diarrhoea and H KEANE, G ALEXANDER, D C A CANDY (Depart- irritable bowel). In the 32 positive sera, the ment ofChild Health, Institute ofLiver Studies, staining pattern was perinuclear (17), cyto- KCSMD andDepartment ofPaediatrics, Univer- plasmic (12), or nuclear (3). In contrast to sity of Ruhuna, Sri Lanka) The haemolytic INFLAMMATORY BOWEL DISEASE vasculitis associated ANCA, staining was uraemic syndrome (HUS) complicates Shigella usually (20 of32) abolished by formalin fixation dysenteriae in 5-10% ofaffected children. Endo- of neutrophils, and ELISAs showed that the thelial damage in HUS is attributed to shiga antibody was not directed against myeloper- toxin and endotoxins or both. Cytokines in- Displacement of the normal colonic macro- oxidase, elastase, or serine proteinase 3 cluding interleukin 6 (IL6), and tumour phage population by tissue histiocytes - antigens. necrosis factor (TNF), which are released in possible prerequisite for the development of In conclusion, (1) antineutrophil antibodies response to endotoxin, are also associated with inflammatory bowel disease occur commonly in UC and may be useful in endothelial damage and multiorgan failure. distinguishing it from Crohn's colitis, proctitis, To determine whether TNF or IL6 might M C ALLISON, L W POULTER (Gastroenterology and other diarrhoeal diseases; (2) the anti- mediate endothelial damage in shigellosis, Unit, Royal Infirmary, Glasgow; and Depart- neutrophil antibodies found in UC differ from serum from consecutive children admitted in ment ofImmunology, Royal Free Hospital School those in systemic vasculitis, appearing to react the first week of illness with dysentery during of Medicine, London) Most macrophage like against a formalin sensitive antigen of as yet an epidemic of S dysenteriae I infection, were cells in normal colonic mucosa are pheno- undetermined identity and intracellular assayed for TNF (by bioassay; n=39) and IL6 typically distinct from their counterparts else- location. (ELISA; n=32) respectively. where in the body in that they coexpress Serum TNF values were raised in the acute antigens recognised by the monoclonal anti- phase (10-3942 pg/ml; median 285 pg/ml), bodies RFD1 (an interdigitating cell marker) when compared with convalescence (10-1368, and RFD7 (a marker for tissue histiocytes). In Interactions and secretory effects of inflam- median 103) (p<0 05). There was, however, inflammatory bowel disease (IBD), the normal matory mediators in ulcerative colitis no correlation with the disease severity or dual positive macrophage population is largely complications. replaced by an infiltrate of cells staining with T D WARDLE, L A TURNBERG (Epithelial Mem- Serum IL6 was also higher in patients with either RFD1 or RFD7. The present study brane Research Centre and Department of acute disease (3.5-7748 pg/mI, median 203) compares findings in normal and IBD mucosa Medicine, Hope Hospital, Salford) Inflam- compared with convalescence (3.5-197 pg/ml; with those in ischaemic or infective colitis matory cells release a variety of mediators in http://gut.bmj.com/ median 22). In contrast with TNF, serum IL6 (disease controls). Cryostat sections of biopsy ulcerative colitis (UC) which may contribute to correlated with complications, including HUS, specimens from five patients with normal diarrhoea by stimulating secretion. Twenty convulsions, prolonged diarrhoea, and throm- mucosa, 15 patients with IBD, six with patients with UC had biopsy specimens taken bocytopenia (p<0 02). ischaemia, and three with pseudomembranous from inflamed mucosa. Control biopsy speci- colitis were examined using an indirect two mens were from patients with irritable bowel colour immunofluorescence technique. In syndrome. Biopsies were cultured: (a) control, normal mucosa, the median proportions of or with (b) indomethacin (cyclo-oxygenase Increased natural killer cell infiltration in cells recognised by RFD1 alone, RFD7 alone, inhibitor), (c) ICI 207968 (lipoxygenase in- on September 24, 2021 by guest. Protected copyright. enterocolitis complicating Hirschsprung's and both antibodies were 11%, 8%, and 80% hibitor), (d) combined (b) and (c), (e) mepa- disease respectively. Greater macrophage hetero- crine (phospholipase A2 inhibitor), or geneity was found in the disease control sec- (f) DABK (bradykinin antagonist). Culture A IMAMURA, P PURI, D S O'BRIAIN, DENIS REEN tions, in which the corresponding proportions medium was assayed for PGE2, and LTD4 and (Children's Research Centre, Our Lady's Hos- were 19%, 22%, and 57%. Significantly lower its effect on short-circuit current (Isc) across pitalfor Sick Children, Dublin, Ireland) Entero- proportions of dual positive cells were seen in rat distal colonic mucosa in vitro. Results colitis (EC) remains an important cause of IBD (median 6%, range 0-53%) than in disease show that inflamed mucosal medium contained morbidity and mortality in Hirschsprung's control mucosa (median 57%, range 14-85%, more PGE2 and LTD4 than normal and pro- disease (HD). The aetiology ofEC is uncertain; p<001). These were largely replaced by voked a greater Isc response. Indomethacin ischaemic and bacterial causes and recently RFD7+ tissue histiocytes (median proportions inhibited PGE2 production but enhanced rotavirus infection have been suggested. We were 71% in IBD and 22% in disease controls, LTD4 production; ICI 207968 had the reverse examined bowel from 12 patients with HD who pmepacrine and DABK. Phospholipase A2 in- possible immunopathologic mechanisms. development of a chronic inflammatory state. hibition caused the greatest reductions in Isc IgA, IgM, J chain containing plasma cells and eicosanoid production. (but not IgG) were significantly increased in the In conclusion, inhibition of either lipoxy- lamina propria along the entire length of genase or cyclo-oxygenase alone enhances resected bowel in enterocolitis patients com- Antineutrophil antibodies in inflammatory secretory responses; a reduction is only seen pared with non-enterocolitis patients and con- bowel disease: prevalence, diagnostic role, with a combination of these, or by inhibition of trol subjects (p<0-01). Luminal secretory and antigenic reactivity arachidonic acid release by either mepacrine or component staining of the aganglionic seg- bradykinin blockade. These data provide a ment of enterocolitis was reduced. Lamina G CAMBRIDGE, B LEAKER, T R J STEVENS, basis for potential therapeutic attack. propria CD68 positive monocyte/macrophages D S RAMPTON (Department ofNephrology, Insti- and CD45RO positive lymphocytes were in- tute ofUrology, University College andMiddlesex creased in all EC patients compared with non- School of Medicine, and Gastrointestinal Science EC patients (p<0 01). CD57 positive natural Research Unit, London Hospital Medical Col- Immunohistochemical evaluation of altered killer (NK) cells showed a unique distribution lege, London) Antibodies to cytoplasmic com- epithelial cell proliferation in patients with pattern compared with other cell types. ponents of neutrophils (ANCA) occur in sys- chronic ulcerative colitis Patients with enterocolitis showed a significant temic vaculitis and have recently been reported increase in CD57 positive NK cells in the in inflammatory bowel disease (IBD). We have M P SAUNDERS, M I FILIPE, M H JOURDAN lamina propia of ganglionic bowel only studied coded sera from 100 patients with IBD, (DepartmentofSurgery, Guy'sHospital, London) (p<005). NK cell values in ganglionic bowel 20 healthy and 14 gut disease controls. Twenty Large bowel epithelium of patients at risk of British Society ofGastroenterology A589 developing colonic cancer show increased cell L MORE, A M SAWYERR, A J WAKEFIELD, --H202). CL was directly related to myeloper- proliferation. The association of colorectal C THRASHIVOLOU, A P DHILLON, R E POUNDER oxidase activity (Spearman's Q=072, cancer in patients with longstanding ulcerative (Inflammatory Bowel Disease Study Group, p=0 0028) in biopsy specimens from controls colitis is well established. Using an in vitro Academic Departments of Medicine and Histo- (n=8) and patients with IBD (n= 10). CL was technique for labelling colonic mucosa with the pathology, and Department of Anatomy, Royal not apparently affected by smoking or oral Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from thymidine analogue bromodeoxyuridine Free Hospital School of Medicine, London) sulphasalazine or mesalazine. (BrdU), alterations in epithelial proliferation in Granulomatous vasculitis has been proposed as In conclusion disease activity related pro- patients with chronic ulcerative colitis were the cause of multifocal mural vascular damage duction of ROM by colorectal mucosa in IBD assessed and compared with normal controls. in Crohn's disease. To investigate this pro- and the relation of CL to myeloperoxidase Left sided colonic biopsy specimens from 18 posal, we have studied the types of lesion activity suggest that neutrophil derived hypo- patients with chronic ulcerative colitis and 18 produced by occlusion of blood vessels in the chlorite could play a pathogenetic role in IBD. matched normal controls were studied. Incor- wall of the ferret's small intestine. porated BrdU was visualised immunohisto- Combinations of 27, 50, and 90 ,um styrene chemically. The mean labelling index was microspheres were injected into the artery significantly higher (p<0-001) in colitic supplying a defined loop ofbowel. Thirty seven Effect of sulphasalazine and 5-aminosalicylic patients (12-5%) compared with controls injected loops and 18 control loops were acid on a1 acid glycoprotein synthesis in vitro (7.8%). Active disease was accompanied by studied in 32 ferrets. Animals were killed at 24, further elevation of the labelling index (mean 48, and 72 hours, and the loops of bowel were M Z MAZLAM, J CUNNINGHAM, H J F HODGSON 14-6%) and an expansion of the proliferative perfusion fixed with formol saline. (Department of Medicine, Royal Postgraduate compartment (p<0 005). Despite a reduced A combination of 27 and 90 im spheres, Medical School, Hammersmith Hospital, Lon- mean labelling index (1 1-3%), patients with injected at a density of up to 20 000 spheres per don) Sulphasalazine and 5-aminosalicylic acid extensive and longstanding (>10 years) colitis cm of bowel length, produced patchy macro- (5-ASA) are effective in the treatment of retain an upwards shift of the proliferative scopic erythema. Histologically, focal 'summit' inflammatory bowel disease. They are shown to compartment (p<0 005). mucosal lesions were observed over blood be potent inhibitors of cytokine production in Cell proliferation is increased in chronic vessels occluded by spheres, with an acute mononuclear leukocytes. The aim of this study ulcerative colitis, even when the disease is inflammatory cell infiltrate at 24 hours; at 48 was to investigate the ability of lipopolysac- quiescent. In extensive and longstanding hours lymphocytes predominated; and by 72 charide (LPS) stimulated monocyte con- disease an expanded proliferative compartment hours collateral vascular channels had opened ditioned medium from normal controls to continues independently of the labelling index and mucosal continuity was observed. Focal enhance release of a1 acid glycoprotein from and seems associated with an increased risk of ulceration was consistent with acute ischaemia. the liver cell line HepG2 in culture and the malignant change. In conclusion, this model represents an acute effects of sulphasalazine and 5-ASA. vascular insult, distinct from the chronic lesion Sulphasalazine or 5-ASA alone had no effect of Crohn's disease. It shows that acute vascular on the synthesis of a, acid glycoprotein. How- disruption to individual mucosal arteries or ever, LPS stimulated monocytes cultured for The 60 kDa stress (heat shock) protein submucosal vessels can produce focal mucosal 48 hours in the presence of sulphasalazine (HSP-60) in ulcerative colitis and Crohn's lesions with normal adjacent mucosa. In (without SASP: 296-1 (17-0) ng/ml; at disease Crohn's disease, with chronic recurrent granu- 0-1 [sg/ml SASP: 348-7 (47.7) ng/ml, p>0 05; lomatous vasculitis, the repeated vascular at 1-0 ig/ml SASP: 370-1 (33-1) ng/ml, V R WINROW, T R J STEVENS, G MOJDEHI, damage could produce ulceration, fibrosis, and p>005; at 10 jsg/ml SASP: 643-8 (43.2) ng/ml, D R BLAKE, D S RAMPTON (Gastrointestinal a patchy distribution of pathology. p<0OOl) or 5-ASA (without 5-ASA: 3308 http://gut.bmj.com/ Science Research Unit and The Inflammation (34.7) ng/ml; at 0-1 ig/ml 5-ASA: 380-6 Group, The London Hospital Medical College, (54 2) ng/ml, p>005; at 1-0 ptg/ml: 379-1 London) Stress proteins are highly conserved, (99 7) ng/ml, p>005; at 10 [tg/ml: 513-1 immunogenic intracellular molecules that can Colorectal mucosa in inflammatory bowel (47 9) ng/ml, p<005) resulted in an increase in be induced by inflammatory mediators and disease produces reactive oxygen meta- the synthesis of a1 acid glycoprotein. may provoke autoimmune phenomena in bolites, principally hypochlorite The mechanism by which this occurs is not vivo. We have (1) looked for HSP-60 in known but the functional consequence of this colorectal biopsy specimens using an indirect N j SIMMONDS, R E ALLEN, T R J STEVENS, increase may be to counterbalance the toxic on September 24, 2021 by guest. Protected copyright. immunoperoxidase technique with ML30 R N M VAN SOMEREN, D R BLAKE, D S RAMPTON actions of mediators of inflammation on tissue monoclonal antibody, and (2) measured serum (Inflammation Group, Gastrointestinal Science damage since this acute phase glycoprotein is antibodies to HSP-60 by ELISA, in patients Research Unit, The London Hospital Medical an immunosuppressor. This finding may have with ulcerative colitis (UC) and Crohn's disease College, London) Studies of peripheral blood a role in the anti-inflammatory action of (CD). monocytes and isolated intestinal macrophages sulphasalazine and 5-ASA. ML30 antibody produced specific, discrete have suggested increased production of reac- cytoplasmic staining of colonocytes between tive oxygen metabolites (ROM) in inflam- the nucleus and apical membrane. Serial dilu- matory bowel disease (IBD). We have used tion of ML30 showed more HSP-60 in UC, luminol (300 pmol)-amplified chemilumi- NEW CONCEPTS IN GASTRIC DISEASE unrelated to disease activity, than in CD or nescence (CL) to measure the production of controls (p<0-01 each). Serum IgA, but not such metabolites by colorectal biopsy speci- IgG or IgM, antibodies to HSP-60 were raised mens in vitro and the addition of various in active UC (mean (SD) 174 (81)% of a scavengers, enzymes, and enzyme inhibitors to Stimulatory effect ofhistamine on the growth standard control n= 17; p<0 05) and in CD, identify the ROM involved. of human gastric tumour cells: reversal by whether active (202 (112), n=11; p<0 05) or Median CL in ulcerative colitis (UC) was cimetidine inactive (178 (103), n= 11, p<0.05), compared related to disease activity assessed endoscopi- with controls (107 (72), n=2 1). cally: normal-looking mucosa (0), 0-8 photons/ S A WATSON, L WILKINSON, J F ROBERTSON, In conclusion (1) increased HSP-60 is in- mg wet weight x 103 (95% confidence intervals J D HARDCASTLE (Cancer Research Campaign duced in colonocytes in UC but not CD and (2) -0-2-5, n=21); hyperaemia (1), 16 (7-51, Laboratories and Department ofSurgery, Univer- raised IgA antibodies to HSP-60 in active UC n=35, p v 0=0.0008); contact bleeding (2), 72 sity of Nottingham, Nottingham) Histamine in- and CD may reflect release of stress protein (38-180, n=26, p v 1=0.0014); spontaneous creased the in vitro growth of two human from damaged gut epithelium, or increased bleeding (3),247 (94-628, n= 13, p v 2=0 019). gastric tumour cell lines, MKN45, and the mucosal permeability with generation of cross CL was also raised in active Crohn's disease gastrin producing derivative, MKN45G as reacting antibacterial antibodies. Raised anti- (CD), 28 (3-262, n=9) compared with inactive assessed by both 7(Se)-selenomethionine in- bodies in inactive CD could be explained by CD, (0I2-34,1 n=7, p=0*005) and controls, corporation and direct cell counts. The growth increased permeability, persistent cellular 0.4 (-0 04-13, n=41, p=0 0001). In UC, CL of MKN45 was increased to 140% of control stress, or abnormal immune regulation. was related to microscopic disease activity (p<0-02, n= 10 experiments) as assessed by (Spearman's p=0-62, p=0-0001) and label uptake and 167% of control (p<0-001, decreased on addition ofsodium azide, a myelo- n=2 experiments) as assessed by cell counts at a peroxidase inhibitor (-96%, n=6, p<0 05), histamine concentration of 10-'M. Cimetidine Ferret model of acute multifocal gastro- catalase (2H202-*2H20+02 (-23%, n=10, (10-'M) had no direct effect on the basal intestinal infarction p<005), and dimethyl sulphoxide, a hydroxyl growth of MKN45 but reduced histamine- radical scavenger (-29%, n= 10, p<0 05), stimulated growth to control values (p<0l001, M HUDSON, C PIASECKI, E A SANKEY, R SIM, but not of superoxide dismutase (02-+2H+ label uptake (one experiment); p<0-01, cell A590 British Society ofGastroenterology counts (two experiments)). With MKN45G the stimulates mucosal hypertrophy and ECL cell proximal stomach primarily controls liquid optimal growth response to histamine was proliferation which can result in production of emptying but the antrum may be more impor- achieved at concentrations of 10 6M and 10-7M. carcinoid tumours in the long term. tant than previously realised. A technique of With 75(Se)-selenomethionine uptake the res- Hypergastrinaemia has been shown to be sequential gastric emptying analysis in the rat ponse was 153% of control (10-6M, p<0 02, 10 associated with increased antral mucosal has been applied to assess the antrum's role in Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from experiments) and with cell counts, 139% of gastrin, gastrin mRNA, and antral G cell the emptying ofnon-nutrient liquids. control (107M p<0 05, six experiments). proliferation. 2,6 Difluormethyl ornithine Forty male Wistar rats underwent gastric Cimetidine reduced histamine stimulated (DFMO) is a specific inhibitor or ornithine emptying analysis using '9mTc-tin colloid in N growth to control concentrations (p<0 05, decarboxylase (ODC) the rate limiting saline. Twenty then had two thirds resection of label uptake (4 experiments); p<0 05, cell enzymes in polyamine biosynthesis. the glandular stomach with Polya-type recon- counts (four experiments)). Of 40 rats studied, in untreated controls the struction. Twenty were controls - 10 un- Histamine had no effect on the growth of a mean serum gastrin was 45.45 (2-1) fmol/ml. operated and 10 with a laparotomy alone. human colorectal cell line, LoVo. After one week of treatment with omeprazole Emptying was studied weekly for four weeks, If histamine does stimulate the proliferation 400 pmol/kg/day serum gastrin rose to 831 then monthly for four months. of some human gastric tumour cells, this may (29-1) fmol/ml, p<0-01 Mann-Whitney U test. Emptying was unchanged in unoperated play a role in the survival advantage observed However, concomitant treatment with DFMO controls. Laparotomy alone caused delayed with gastric cancer patients treated with cime- 2% in drinking water reduced the rise by 63% emptying until two months (p<0 05). After tidine. to 310 (18-8) fmol/ml p<0-01 Mann-Whitney gastrectomy emptying was delayed for four U test. months (p<0 01), with the initial delay being We concluded that the hypergastrinaemic greater than with laparotomy alone (p<0 05). response to achlorhydria is partly ODC depen- We conclude that a laparatomy alone delays dent. However, polyamines can be absorbed gastric emptying. The addition of an antrec- Effect of somatostatin analogues on the pro- from the intestine and blood bypassing ODC. tomy causes a greater emptying delay, which liferation ofgastric carcinoma cells in culture An assessment of antral mRNA and G cell persists for longer than that due to laparotomy numbers in this model will be of interest in alone. This supports the concept in man that G V MILLER, J N PRIMROSE (University Depart- elucidatingtheroleofODC ingastrin synthesis, the antrum may have an important role in ment ofSurgery, StJames's University Hospital, post-translational processing, and secretion. liquid emptying. Leeds) The aim of this study was to determine the in vitro growth responsiveness of human gastric carcinoma cell lines to somatostatin analogues. Established human gastric car- Intestinal metaplasia: relation to atrophy and Direct studies of human gastric fundal tone cinoma cell lines MKN45, ST42, and ST16 bile reflux and compliance were each cultured for 24 hours in 96 well microtitre plates with medium containing no G M SOBALA, R F G KING, AT R AXON, M F DIXON N K AHLUWALIA, D G THOMPSON, L TRONCON, fetal calf serum (FCS). The cells were then (Gastroenterology Unit, Professorial Department J BANCEWICZ, j BARLOW (University Department cultured for a further 72 hours with medium of Surgery and University Department of of Medicine, Hope Hospital, Salford) We containing 10% FCS and somatostatin Pathology, The General Infirmary, Leeds) To developed a device capable of independently analogue. At 24 hour intervals during this investigate the relations between intestinal recording both gastric fundal tone and com- period, cellular proliferation was quantitated metaplasia (IM), age, atrophy, and duodeno- plience using computer controlled volume and by '5selenomethionine incorporation as an gastric bile reflux, 657 antral biopsy specimens pressure monitors attached to a distending bag http://gut.bmj.com/ index of protein synthesis, and samples from six previous studies were collectively (maximum volume 1200 ml). counted on a gamma counter. Somatostatin reviewed and scored according to the Sydney After an overnight fast, the assembly was analogues RC-160 (Debiopharm, Switzer- classification of gastritis. Most patients were positioned in the fundus of 13 volunteers and land), BIM 23014 (Ipsen, France), and SMS unselected but a group of 70 had undergone compliance (volume-pressure) curves obtained 201 995 (Sandoz, UK) were used in the micro- reconstructive gastric surgery. The preva- by stepwise inflation. Tone was measured by molar to picomolar concentration range. lences ofIM were 1 6%, 10-5%, 11 5%, 25 4%, continuous recording of volume required to Values are expressed as mean (+SEM) isotope and 36-9% in patients aged under 30, 30-39, maintain a preselected pressure. The study was incorporation as percentage of control at the 40-49, 50-59, and over 60 years respectively. repeated after meal ingestion (250 ml; on September 24, 2021 by guest. Protected copyright. concentration for maximal growth inhibition. The corresponding prevalences of atrophy 250 kcal). Samples were processed in triplicate and from a were 17-5%, 316%, 40-6%, 48-9%, and 56 0%. In respect offasting: compliance, a triphasic series of three experiments. The prevalences of IM in the presence of curve occurred in all, with an initial phase Significant inhibition of proliferation of cell atrophy were 5.7%, 34 4%, and 58.2% in (mean (SEM) slope=0.60 (0. 1) mmHg/30 ml) line ST16 occurred with both RC-160 and patients aged under 40, 40-59, and over 60 to 185 (21) ml when the slope changed to a SMS 201 995, optimal at 10-'M (74.4 (+3.5)% years respectively. Fasting gastric juice bile steeper phase (slope=2-1 (1) mmHg/30 ml; and 70 9 (+1-8)% respectively; p<0.01). acid concentrations were available in 350 p<0 001 v initial phase) which continued to Similarly for MKN45, marked growth inhibi- patients (66 with reconstructive surgery). 385 (16) ml, then changing to a plateau phase tion was observed with RC-160 and SMS 201 There was an increased risk of IM with higher (slope=0.00; p<0 001 v other phases) to the 995, optimal at 10-CM (65.2 (+2.9)% and 60-1 bile acid concentrations: odds ratios relative to limit oftolerated distension (528 (21) ml). Tone (+3.5)% respectively; p<0.005). Analogue baseline were 2-24, 3-84, and 3.99 for bile remained static during the initial phase but BIM 23014 had no effect upon growth of any 0-51-1-00, 101-5.00, and >5.00 mmol/l res- during other phases, regular (1-1 (0 1)/5 cell line studied and ST42 cell line was not pectively; X2 for linear trend= 14-3, p=0.0002. minute) oscillations with an amplitude of 71 influenced by any of the agents tested. There- A bile acid concentration >0 5 mmol/l was still (5.8) ml were observed. After foods, a mono- fore certain somatostatin analogues may have associated with IM after controlling for age and phasic compliance curve replaced the triphasic therapeutic potential in the treatment ofgastric surgery (Mantel-Haenszel weighted odds pattern with a reduced slope (slope=0-4 (0 01) carcinoma and further evaluation is indicated. ratio=2-87, 95% CI= 1-54-5-37, p=0 001 1). mmHg/30 ml, p<0001 v fasting) indicating We conclude that, contrary to recent asser- fundal relaxation. With regard to tone, oscilla- tions, the occurrence ofIM is distinct from that tions in volume (65 (10) ml; p>005 v fasting) of atrophy. IM is associated with duodeno- remained but were slower (0.7 (0.2)/5 minutes; gastric reflux ofbile. p<0 05 v fasting). Role of ornithine decarboxylase in the hyper- In conclusion, the fundus shows substantial gastrinaemic response to achlorhydria in the oscillations in tone, unaltered by food or degree art of distension which seem to serve to mix and Importance ofthe antrum in gastric emptying distribute nutrients within the stomach. M R GRAY, A N KINGSNORTH, J NEMETH, of a non nutrient liquid in the rat G DOCKRAY, H M WALLACE (Departments of Surgery and Physiology, University ofLiverpool A D HOUGHTON, P LIEPINS, S CLARKE, R MASON and Department of Medicine, Therapeutics and (Departments ofSurgery, Nuclear Medicine, and Biochemistry, Aberdeen) The rat shows a notice- Radiological Sciences, Guy's Hospital, London) PHYSIOLOGY OF THE SMALL INTESTINE able increase in serum gastrin in response to Gastric emptying ofnutrient fluids is restrained achlorhydria induced by antral exclusion, high by feedback mechanisms involving small bowel dose H2 antagonists, and the proton pump osmoreceptors. Emptying is faster and volume Effect of cephalic stimulation on human inhibitor omeprazole. High serum gastrin dependant in the absence of nutrients. The smali bowel motility and intestinal flows British Society ofGastroenterology A591

A H RAIMUNDO, J ROGERS, J J MISIEWICZ, feeding, however, most manometric events are tomy or ultrasound subsequent to the last D B A SILK (Department of Gastroenterology and dissociated from propulsion and seem to serve a resection occurred in 12 of 31 (39%) EJ and 11 Nutrition, Central Middlesex Hospital, London) mixing function. of 29 (38%) JC patients at median times of 48 To investigate whether small bowel motility and 54 months. Most patients with 50-100 cm Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from and intestinal flows are affected by a cephalic residual jejunum can be maintained on an oral phase in response to food a food discussion regimen when the colon is preserved; similar (FD) stimulus was applied to six normal volun- Assessment of the effect of cisapride on patients with an end jejunostomy usually need teers (mean age: 26-1 years, range: 25-29). proximal small bowel motility by prolonged intravenous supplements. Subjects were intubated with a 9 lumen tube ambulator manometry and 3H-PEG was infused at 1 ml/minute over a 10 cm segment of duodenum. Flows were M J BENSON, F D CASTILLO, J DEEKS, D L WINGATE determined at 15 minute intervals for three (GI Science Research Unit and Department of A potential role for 5-hydroxytryptamine in hours before and three hours after a 30 minute Statistics, Royal London Hospital Medical mediating cholera toxin induced secretion in FD. Small intestinal motility was recorded at College, London) Previous studies using man six sites (10 cm apart) spanning 60 cm of stationary perfused tube monometry, show proximal jejunum. The effect of gastric acid that cisapride (Cis) stimulates proximal small A V THILLAINAYAGAM, J A DIAS, A SCHIRGI- secretion on the cephalic-small intestinal res- bowel (PSB) motility. Prolonged ambulant DEGEN, E BEUBLER, M L CLARK, M A GHATEI, S R ponse was also studied after pretreatment with manometry is a better method of defining BLOOM, M J G FARTHING (Department ofGastro- ranitidine 1200 mg (in four divided doses) or motor physiology: this technique was used to enterology, St Bartholomew's Hospital, London, identical placebo, in random order, given over study the effect ofCis on PSB motility in seven Institute for Experimental and Clinical Pharma- the 24 hours before study. Fasting type III healthy subjects (six men, one woman: age cology, Karl-Franzens University Graz, Austria; migrating motor complexes (MMCs) were 20-24 years). andRoyalPostgraduateMedicalSchool, London) present in all subjects before and after FD. The Cis was taken orally, 20 mg tid on day one While cholera toxin (CT) induced intestinal number of MMCs was not significantly and 10 mg tid on days two and three. On day secretion is classically attributed to activation (p>0.06) different between the basal and post two, following an overnight fast, subjects were of adenylate cyclase, recent work in rat FD periods either in the presence (basal, mean intubated with a three channel nasojejunal jejunum suggests that other mediator pathways (SEM): 9*5 (1-7) v FD: 7-7 (2 0)) or absence manometry catheter. A portable digital may be involved. We have investigated mucosal (8-0 (2-1) v 7-8 (1-2)) of gastric acid. However, recorder was used for data acquisition. Two 5-hydroxytryptamine (5-HT) and vasoactive there was a significant increase in flows com- weeks later, subjects were restudied without intestinal polypeptide (VIP) release from pared with basal during FD in both the the drug. healthy human jejunum, using a subclinical presence (basal: 25.3 (4.5) ml/15 minutes v Interdigestive motor activity was analysed model of cholera (paired, randomised, and FD: 50.0 (6.5), p<0 02) and absence (15.5 using repeated measures analysis of variance. double blind; n=4). After intestinal intubation (4-2) ml/15 minutes v 23-0 (5.1), p<003) of There was no significant change in nocturnal or an isolated segment of proximal jejunum was gastric acid. diurnal MMC cycle length or percentage dura- exposed to 30 jig of purified CT for two hours These data show (in the presence and tion of the constituent phases. The mean before closed segment perfusion with a plasma absence of gastric secretion) that there is a amplitude of contractions for nocturnal and electrolyte solution containing a non-absorb- cephalic phase of increased small intestinal diurnal phase II (p=0 004, p=0 034) and able volume marker. Plasma and luminal fluid flows in response to food, but that a cephalic nocturnal (p=0.04) mean 'area under the samples were collected at regular intervals. phase of small intestinal motility in response to curve' were increased. There was no significant 5-HT concentrations were measured by food does not exist. change ofcontraction frequency. reversed phase high performance liquid http://gut.bmj.com/ Our data show that the effect of Cis, in chromatography with amperometric detection normal subjects, is an increase in the force of and VIP by radioimmunoassay. All subjects PSB phase II contractions, indicating that the secreted fluid in response to CT (median -2-9 Relations between propulsion and pressure drug affects the contractile apparatus, but not (interquartile range -2-13 to -3.95) mI/cm/ activity in the human small intestine the circuitry that controls the timing of motor hour). 5-HT in the luminal perfusate samples events in the PSB. was below the limit of detection of our method N K AHLUWALIA, D G THOMPSON, J BANCEWICZ, (<4 ng/ml), but an increase in plasma 5-HT L HEGGIE (University Departments of Medicine concentration was seen 30 minutes after CT on September 24, 2021 by guest. Protected copyright. and Surgery, Hope Hospital, Salford) We have exposure (195 (98-348) v 243 (173-418) ng/ml; developed a new method for directly measuring After jejunoileal resection preservation ofthe 0 v 30 minutes, paired comparison; p<0 05), intestinal propulsive force using an ingested colon is equivalent to 50 cm of jejunum but unlike controls. VIP concentrations did not miniature strain gauge transducer with an increases the risk of renal stones change in either plasma (10-1 (5-3-13-1) v 11 5 attached 1.5 ml balloon, sited in the proximal (7-15-4) pmol/1) or luminal perfusate (3 (2-3- small intestine. J M D NIGHTINGALE, D J GERTNER, S R WOOD, 4.5) v 2-5 (2-45) pmol/l) after CT exposure. After an overnight fast, propulsive events C I BARTRAM, J E LENNARD-JONES (St Mark's This early, transient elevation of plasma were recorded continuously for 90 minutes Hospital, London) The case notes of 82 patients 5-HT after exposure to CT is supportive before, and for 30 minutes after, ingestion of a with less than 200 cm remaining jejunum and evidence that 5-HT is a mediator ofCT induced standard meal (360 ml; 200 kcal) in 14 healthy managed at this hospital over the past 10 years secretion but the specificity of this finding volunteers. An additional perfused multilumen were reviewed. The patients, who had no overt requires further confirmation. catheter system was employed to monitor disease in the remaining jejunum, were divided adjacent motility and determine pressure/pro- into two groups; end jejunostomy (EJ) or pulsion relation. jejunocolic anastomosis (JC). Crohn's disease With regard to fasting, during phase I no was the commonest diagnosis in each group. Inhibition of plasma membrane calcium propulsive or manometric events were detected. Among patients with a residual jejunal pump activity by gastrointestinal peptides During phase II, 2-1 (0.2) (mean (SEM)) length of0-100 cm, 12 of 16 with EJ and seven propulsive events/minute occurred generating of 21 with JC required iv supplements at six J R F WALTERS, A HOWARD (Department of 14-9 (3.2) g force/minute. Some 75% of mano- months. For those with a jejunal length of Medicine, Royal Postgraduate Medical School, metric events (3.94 (0. 13)/minute) were propul- 50-100 cm, nine of 13 with EJ and only one of Hammersmith Hospital, London) The secretion sion associated. During phase III, 92-7 (31-2) g 12 with JC needed long term intravenous and absorption of water and electrolytes by the force/minute was generated by regularly occur- therapy. All EJ patients with less than 85 cm intestine is regulated by the integrated actions ring propulsive events. Altogether 89% of residual jejunum and all JC patients with less of the many peptides produced by the enteric manometric events (11-3 (1-3) were propulsion than 30 cm needed long term intravenous neuroendocrine system. The intracellular associated. After food, 2-7 (0.26) propulsive nutrition. There was little change at two years mechanisms of these actions are still unclear, events/minute (p>0 05 v phase II) occurred, when 10 of 12 EJ patients and seven of 17 JC though some peptides affect the cyclic AMP generating 21-75 (2.2) g/minute (p>0 05 v patients with a jejunal length less than 100 cm dependent or the Ca2+ dependent protein phase II). Manometric events were signifi- still required intravenous supplements. kinases. The purpose of this study was to cantly increased (7-02 (2)/minute; p<0-001 v No patient in the EJ group developed symp- investigate whether any of these peptides phase II) but the majority were dissociated tomatic renal stones after their last small bowel affected the plasma membrane Ca2' pump from propulsive events (63% p<0-001 v phase resection; however nine of 39 (23%) of the JC which lower cytoplasmic Ca2' by extruding II). patients did after a mean time of 30 months Ca2' by an ATP dependent mechanism. Baso- In conclusion, fasting manometry predicts (2-67); analysis in three showed calcium lateral enriched membrane vesicles were pre- propulsion in all phases of the MMC. After oxalate. Gall stones found either at cholecystec- pared from rat proximal small intestine. These A592 BritishSocietyofGastroenterology were incubated at 37°C with various peptides, are depleted in HIV infection. Rectal biopsy woman, mean age 34-5 years) underwent usually at 0-1 [rmol/l concentration, for 10 specimens from 19 HIV positive male homo- surgery for acute abdominal symptoms. minutes to load the sealed inside out vesicles. sexuals (five asymptomatic, eight persistent The commonest indication was acute colitis

The rate of ATP dependent "Ca2l uptake into generalised lymphadenopathy (PGL), six (six patients) with toxic megacolon in four and Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from these vesicles was determined at one minutes AIDS) were stained with haematoxylin and colonic perforation in two. Treatment was by by millipore filtration using a buffered free eosin, modified Ziehl-Neelsen, PAS, and total colectomy and ileostomy. Cytomegalo- Ca2+ concentration of 0.5 [imoUl. Inhibition of Warthin-Starry to detect enteropathogens. virus (CMV) was identified in five colectomy ATP dependent Ca2+ transport activity was Stools were examined also for entero- specimens, CMV and ulcerative colitis produced by peptide YY, endothelin 1, sub- pathogens. NEC were detected with chromo- occurred together in two patients and sal- stance P, vasopressin, somatostatin, and granin monoclonal antibody (Biogenesis) using monella and Crohn's colitis in one. Findings in neurokinin A; these effects were significant indirect immunoperoxidase technique. The the remaining patients included intestinal (p<0O05), but relatively small (reduction to percentage of crypt basement membrane sup- lymphoma (four patients) atypical mycobac- approximately 90% of control) which may be porting NEC (BM) was calculated using a terial (MAI) infection (three patients), and partly due to suboptimal loading ofthe vesicles. linear intercept graticule under light micro- acute appendicitis (three patients, two with Other peptides including VIP and bombesin scopic examination in HIV biopsy specimens features ofCMV). were without effect. (H) and in eight specimens from age and sex This is the largest series reported in the UK. Thus, some gastrointestinal peptides pro- matched controls (C). Sufficient intercepts Postoperative survival was 89% at one month, duce an inhibition of the plasma membrane with crypt basement membrane were counted 75% at three months, and 54% at six months. Ca'+ pump which will raise intracellular Ca2+ in each specimen to obtain a value for BM with Lower operative mortality than previously values and so affect the cellular response. a confidence interval of 95%. Spirochaetosis reported may be the result of earlier surgical was found in four HIV positive specimens intervention with a lower incidence of perfora- (asymptomatic three, PGL, one). No other tion in toxic megacolon. Outcome was better in enteropathogens were detected. The cell the CMV colitis patients than in the lymphoma COLORECTAL density ofNEC in rectal crypts was reduced in or MAI subgroups. Carefully selected AIDS HIV positive subjects: mean (SD) BM (H) 2.5 patients can survive surgery and achieve worth- (1-14), BM (C) 4.5 (1-99), p<0-01, Mann- while palliation after major intra-abdominal Whitney U test). sepsis. Trial of essential fatty acids in the treatment Thus NEC are depleted in rectal biopsy of ulcerative proctocolitis specimens of HIV infected patients. This may be due to lysis ofHIV infected neuroendocrine A T GREEN, N A PUNCHARD, R P H THOMPSON cells. Decreased production of peptides by Enhancement of toxin production by vero- (Gastrointestinal Laboratory, Rayne Institute, St NEC which modify intestinal motility may cytotoxin producing Escherichia coli: appli- Thomas's Hospital, London) The synthesis of contribute to diarrhoea in HIV infection. cation of method to community acquired prostaglandin E2 and leukotriene B4 is in- diarrhoea creased in ulcerative proctocolitis (UC). To alter their production we supplemented D A BURKE, B AL JUMAILI, C 0 RECORD (Depart- patients with UC with Efamol (10% gamma- Microbiology ofanal fistulas ments of Gastroenterology and Microbiology, linolenic acid) or MaxEPA (20% eicosapen- Royal Victoria Infirmary, Newcastle upon Tyne) tanoeic acid, EPA) and assessed disease activity S CHOEN, A J HAY, S HEARD, RK S PHILLIPS (St A significant proportion ofstools from patients and red cell fatty acids. Mark's Hospital and Homerton Hospital, Lon- with diarrhoea yield no pathogens, current http://gut.bmj.com/ Thirty six patients with stable UC (un- don) Anal fistulas probably arise from crypto- methods may not recognise or be sensitive changed treatment >six weeks; <6 mg oral glandular infection of anal glands lying in the enough to identify all infective causes. Vero- prednisolone) were randomised to receive cap- intersphincteric space. The type and virulence cytotoxin producing Escherichia coli (VTEC) sules of Efamol (n= 16), MaxEPA (n= 10), or of the organism may determine whether a are known to cause haemorrhagic colitis and placebo (olive oil; n= 10) for six months with chronic abscess (fistula) then ensues. The the haemolytic uraemic syndrome but their their usual treatment. Each received 6 g daily microbiology of established fistulas has not role in community acquired diarrhoea is not for one month and then 3 g daily. Disease previously been reported. fully known. VTEC may be present in low activity was assessed monthly by symptom Twenty two consecutive anal fistulas were numbers during an infection making their on September 24, 2021 by guest. Protected copyright. score and three monthly by sigmoidoscopy and studied prospectively (men 15, women six: detection difficult. Using mitomycin C in cul- rectal biopsy. Red cell fatty acids were intersphincteric seven, transsphincteric 12, tures as an inducing agent VT production was measured three monthly by gas liquid chroma- suprasphincteric two, extrasphincteric one). shown to be increased up to 100 fold. This tography. Patients with Crohn's disease were excluded. method adapted to mixed faecal culture The groups were initially comparable. Bowel In 15 patients, 0-1 ml of granulation tissue enabled the detection ofVT when substantially frequency was improved in six of 16 patients on from the fistula track was obtained and pro- fewer VTEC were present in the faeces com- Efamol but not in the other groups (p<005). cessed within four hours using standard micro- pared with standard culture. Using the toxin There were two flare ups on MaxEPA, three on biological techniques. Fifty seven isolates with enhancement method 175 stools, culture nega- Efamol, and three on placebo (p=NS). All at least 18 species were obtained. The pre- tive for pathogens, and 25 normal controls were were mild and responded to local or oral dominant organisms were: Gram negative= tested for faecal cytotoxin against HeLa cells. steroids. There was no significant difference Escherichia coli; Gram positive=enterococci; Forty six (28%) were positive for a cytotoxin, between the groups on histology or sigmoido- anaerobe=Bacteroides fragilis. There was an nine neutralised by anti-VTl, 29 by anti-VT2, scopy. Red cell EPA and dihomogammalino- interesting paucity ofbacterial counts and most and eight by neither. lenic acid values were increased during treat- growths were obtained only from enriched or A proportion of cases of community ment in the MaxEPA and Efamol groups, neat dilutions. Only one patient grew bacteria acquired diarrhoea may be caused by VT or VT respectively. at 10' dilution. In 22 patients, granulation like producing organisms not detected by In conclusion, Efamol may improve symp- tissue was processed for mycobacterial culture conventional means. Use of the toxin enhance- toms in UC. and one patient grew Mycobacterium tuber- ment method may aid in the detection of culosis. No other mycobacteria were isolated. VTEC. The chronic inflammation in anal fistulas does not seem to be maintained either by excess Neuroendocrine cells in rectal biopsy speci- organisms or by organisms ofan unusual type. mens of male homosexuals infected with Microvascular injury associated with super- human immunodeficiency virus (HIV) ficial mucosal lesions in Crohn's disease

J B McCULLOUGH, P A BATMAN, A R 0 MILLER, Emergency laparotomy in AIDS E A SANKEY, L MORE, A P DHILLON, A J WAKE- P M SEDGWICK, G E GRIFFIN (Department of FIELD, R SIM, A M SAWYERR, M HUDSON, Histopathology, Bradford Royal Infirmnary and T DAVIDSON, T G ALLEN-MERSH, B GAZZARD, R E POUNDER (Inflammatory Bowel Disease Communicable Diseases, St George's Hospital, A J G MILES, C WASTELL (Surgical and HIV Study Group, Academic Departments ofMedicine London) HIV infection of intestinal neuro- Units, Westminster Hospital, London) We have and Histopathology, Royal Free Hospital School endocrine crypt cells has been postulated. We reviewed the experience with emergency of Medicine, London) The pathogenesis of have quantitated crypt neuroendocrine cells laparotomy in AIDS patients (CDC stage 4) mucosal ulceration in Crohn's disease (CD) is (NEC) in rectal mucosa of HIV infected over a three year period in one hospital. unknown. Examination of areas of apparently subjects to test the hypothesis that these cells Nineteen patients with AIDS (18 men, one non-inflamed bowel in patients with CD allows British Society ofGastroenterology A593 the identification of mucosal changes which M HUDSON, A M SAWYERR, A P DHILLON, for DAO in inflammatory bowel disease during precede ulceration and may lead to an under- R E POUNDER (Inflammatory Bowel Disease pregnancy. standing ofits pathogenesis. Study Group, Academic Departments of Histo- Resection specimens from 18 patients with pathology and Medicine, Royal Free Hospital CD were perfusion fixed at mean arterial School of Medicine, London) Constitutive Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from pressure with 10% formalin. Serial sections expression oftissue factor (TF) in the intestinal In vitro al acid glycoprotein synthesis in from areas of non-inflamed mucosa, identified lamina propria may be an important haemo- inflammatory bowel disease by haematoxylin and eosin, were immu- static barrier. Pathological expression ofTF by nostained for vascular endothelium macrophages and endothelial cells, a pathway M Z MAZLAM, J CUNNINGHAM, H J F HODGSON (QB-end-10), vascular basement membrane active in Crohn's disease (CD), is a prerequisite (Department of Medicine, Royal Postgraduate (collagen IV), and vessel constituents (fibrino- for fibrin deposition in the full expression of Medical School, Hammersmith Hospital, Lon- gen, platelets (platelet glycoprotein III), factor cellular immunity. We have examined, the don) et1 Acid glycoprotein ((t1-AGP) oroso- XIIIa, macrophages (KPl)). pattern of lamina propria TF expression in mucoid is an acute phase reactant synthesised These techniques identified small mucosal normal bowel and bowel from CD patients. by the liver. Production is enhanced by cyto- capillaries which would not otherwise have Sections from five resected specimens of CD kines notably interleukine 13 (IL-1,B), acting been apparent with conventional techniques. and two normal controls were snap frozen or on hepatocytes. Serum a1-AGP values are a In areas with intact mucosa, vascular immuno- perfusion fixed with 10% formalin. Serial correlate of inflammation in inflammatory staining identified damage and rupture ofthese sections from normal tissue and CD tissue that bowel disease (IBD), but are affected by both small capillaries, which preceded infiltration of included areas of both ulcerated and intact synthetic rate and protein loss. We assessed the lamina propria by inflammatory cells. A mucosa, were stained immunohistochemically relations between IL-10 production (ELISA plume of material arising from ruptured capil- for TF, vascular endothelium (QG-end-10) and assay ofconditioned medium (CM) from circu- laries, often deep within the lamina propria, fibrinogen. lating monocytes), the effects of those cyto- stained strongly for fibrinogen, platelet glyco- In frozen tissue sections lamina propria, TF kines on ae-AGP synthesis (ELISA assay of protein, and factor XIIIa. Loss ofthe overlying expression was prominent in both normal supernatant from HepG2 cells cultured with epithelium appeared to follow this vascular intestine and non-ulcerated CD intestine. In monocyte CM), and serum ct,-AGP values in damage. A similar pattern of staining was seen CD, as epithelial injury progressed, TF stain- 44 patients with IBD and controls. in areas of simple mucosal ulceration and also ing intensified and fibrinogen staining became Lipopolysaccharide (LPS) stimulated mono- in more advanced, aphthoid type ulcers. positive. With frank ulceration, mucosal cyte CM from patients with active IBD caused In conclusion, these findings support the macrophages and vascular endothelium greater al-AGP release from HepG2 cells hypotheses that vascular damage is an early adjacent to areas of ulceration stained strongly (545.6 (54 9) ng/ml) than CM from inactive event in CD and that aphthoid ulceration has for TF and fibrinogen. In formalin fixed tissues patients (414-5 (21) ng/ml) or controls (413.4 an ischaemic origin. from normal and CD mucosa, mucosal goblet (29.2) ng/ml), p<0 05. In IBD patients there cells exhibited a granular pattern of cyto- was a significant positive correlation between plasmic staining for both TF and fibrinogen. spontaneous and LPS stimulated IL-10 pro- In conclusion, these observations support duction and ca,-AGP synthesis, r=0-62, Distal ulcerative colitis; evidence of the role of TF as a haemostatic barrier which p<0 001 and r=0-25, p<0 05 respectively. abnormal mucosal immunity in the proximal may be activated by mucosal injury. The However, serum a,-AGP ofindividual patients colon mucosal goblet cell may be a source of TF or it did not correlate with in vitro cl-AGP syn- may act as an accessory cell in the assembly or thesis stimulated by control or LPS stimulated C J O'BRIEN, D M McKENNA, H HOLDEN, storage ofcoagulation factors. monocyte CM from that patient. http://gut.bmj.com/ C D HOLDSWORTH (Gastroenterology Unit and Thus IL-1,B from IBD monocytes is a signifi- Department of Pathology, Royal Hallamshire cant modulator ofae-AGP production by hepa- Hospital, Sheffield) In distal ulcerative colitis tocytes, but in vivo other influences such as (DUC) microscopic evidence of mucosal in- protein losing enteropathy affect circulating flammation may be more extensive than that Diamine oxidase activities in inflammatory values. visible at endoscopy, but the proximal colon is, bowel disease during pregnancy by definition, histologically normal. We used monoclonal antibodies to identify M HUDSON, S GREENFIELD, N A PUNCHARD, on September 24, 2021 by guest. Protected copyright. distal and proximal colon tissue macrophages G M MURPHY, R P H THOMPSON, R E POUNDER Peripheral blood monocyte cytokine profiles (LeuM5), interdigitating (antigen presenting) (Academic Department ofMedicine, Royal Free differ between Crohn's disease and ulcera- macrophage like cells (RFD1), and mature Hospital School of Medicine, Gastrointestinal tive colitis (resting) macrophages (RFD7) in eight Laboratory, Rayne Institute, St Thomas's Hos- patients with DUC and in five patients' normal pital, and Departments of Medicine and Bio- M Z MAZLAM, H J F HODGSON (Department of mucosa. In the DUC patients, inflamed distal chemistry, UMDS, London) Intestinal activity Medicine, Royal Postgraduate Medical School, mucosa contained a mean 39% (range 25-62) of the enzyme diamine oxidase (DAO), which Hammersmith Hospital, London) Cytokines LeuM5 positive cells, a mean 38% (range controls the levels of putrescine, a growth released from activated mononuclear leuco- 22-52) RFD1 positive cells, and a mean 25% regulating polyamine, correlates inversely with cytes are involved in triggering the acute phase (range 15-33) RFD7 positive cells. Histologi- clinical disease activity in Crohn's disease. response and many of the inflammatory mani- cally normal proximal mucosa from these Circulating levels of DAO are normally vir- festations ofulcerative colitis (UC) and Crohn's patients contained a mean 19% (range 11-31) tually undetectable, except during pregnancy disease (CD). We compared the ability of LeuM5 positive cells, a mean 17% (range 9-48) they rise to peak at 24 weeks' gestation, return- circulating monocytes from patients with UC RFD1 positive cells, and a mean 20% (range ing rapidly to baseline after term. We therefore (n=22) and CD (n=22), and 11 normal con- 12-32) RFD7 positive cells. In comparison measured 21 serum DAO samples in eight trols to generate the cytokines interleukine 1 P normal control proximal mucosa contained a pregnant patients with inflammatory bowel (IL-IB) and tumour necrosis factor ex mean 6% LeuM5 positive cells (p<0 05), a disease, and compared them with 15 samples (TNF-a), both spontaneously and in response mean 2% RFD1 positive cells (p<0 05), and from eight matched pregnant controls using 14C to stimulation by optimal doses of lipopolysac- a mean 3% RFD7 positive cells (p<0001). putrescine as a substrate. charide (LPS). IL-163 generation in response to These findings show a significant increase in DAO values (median; range) in Crohn's LPS in CD (592-3 (277.8) pg/ml; p<0 05) was the number of both scavenger and mature disease (171; 11-595 mU/l; n= 11) were signifi- significantly higher compared with UC (114-7 macrophages in apparently normal proximal cantly (p=0-017) lower than in ulcerative (26-1) pg/ml) and normal controls (101-2 colonic mucosa of DUC, indicating a more colitis (587; 96-1246 mU/l; n= 10), but neither (43 6) pg/ml), with a dramatic elevation in diffuse disease process than is histologically were different from those in normal pregnancy patients with active disease (1078-0 (536.7) perceived and suggesting a role for abnormal (239; 24-1302 mU/l). In the one pregnant pglml). For TNF-a, there was a significant immunity in the development of ulcerative patient with fulminant ulcerative colitis, the reduction in LPS stimulated TNF-a generation colitis. DAO value fell from 915 mU/l (25th week) to in UC (59.4 (23.9) pg/ml; p<0 05) compared 357 mU/l (32nd week) and rose again at 36 with CD (177-5 (66-1) pg/ml) and normal weeks (541 mU/l) when in remission. controls (196-3 (50 5) pg/ml). Il-1, and Patterns of mucosal tissue factor In conclusion, serum DAO activities were TNF-ct release correlated significantly with expression higher in ulcerative colitis than Crohn's disease serum CRP in CD (r=0-30 and r=0-31 respec- in normal intestine and Crohn's disease during pregnancy. The relevance of the preci- tively; p<005) but not in UC (r=0-22 and pitous fall in DAO activities in fulminant colitis r=0 18 respectively; p>005). A J WAKEFIELD, L MORE, A COX, E A SANKEY, is unclear but it may suggest a protective role The differences in cytokine profile in A594 British Society ofGastroenterology patients with CD compared with UC suggest an The first pass metabolism of ethanol was up hibitor of human stomach yy alcohol dehydro- intrinsic difference in the ability to produce to 90% (range 11-90%) at this low dose. This genase with a Ki of 1-93 (0.22) mmol/l and that cytokines in patients with these two forms of was significantly reduced in patients taking this inhibition is competitive with respect to

inflammatory bowel disease, and may explain ranitidine (median reduction 41%, 96% CI ethanol. A single dose (400 mg) would give a Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from features such as the enhanced ability to 6-61, p=0 02). There were no significant dif- local concentration of approximately generate a brisk CRP response in CD. ferences related to gastric histology nor to the 20 mmol/l. Such a concentration would cause age or sex ofsubjects. inhibitionofhumanyyalcoholdehydrogenases. In conclusion, ranitidine significantly We conclude that this inhibition is caused by reduced the first pass metabolism of ethanol the structural similarity of cimetidine with Serum alkaline phosphatase isoenzymes in leading to higher blood ethanol concentrations. pyrazole which is a known inhibitor of human inflammatory bowel disease Neither abnormal gastric histology nor female class I alcohol dehydrogenases. sex had a significant effect. A ABU-KHALAF, P KAY, L HUNT, A SMITH, T W WARNES (Liver Unit, University Department ofGastroenterology, ManchesterRoyal Infirmary) The effect of H2 blockade on plasma gastrin Serum alkaline phosphatase (ALP) normally Effect ofdestruction ofmyenteric neurons of in the achlorhydric stomach consists of bone, liver, and small intestinal (SI- rat stomach by benzalkonium chloride on ALP) isoenzymes. The appearance of SI-ALP gastric acid secretion and gastrin release G M FULLARTON, K E L McCOLL (University in serum is genetically controlled, varying with Departments of Medicine and Therapeutics and ABO blood group. We now report a distinc- L M F ROMANELLO, L E A TRONCON, S ZUCOLOTO, Surgery, Western Infirmary, Glasgow) It is not tive, slow moving 'colonic' band of ALP V C BORGHI, M G GINABREDA, R B OLIVEIRA known whether the hypergastrinaemia during (C-ALP) on polyacrylamide electrophoresis in (INTRODUCED BY D G THOMPSON) (Faculdade de H2 receptor antagonist (H2RA) treatment is 37% of 49 patients with ulcerative colitis and Medicina de Ribeirao Preto, USP, Brazil) We entirely secondary to acid inhibition or partly 26% of 23 with Crohn's disease compared with have previously shown that benzalkonium the result ofa direct effect ofthe drugs on antral 5% of 18 patients with other digestive tract chloride (BC) is effective to denervate the G cells. To investigate this we studied the effect diseases and 4% of 46 normal subjects myenteric plexus of the stomach causing of H2RA on plasma gastrin in nine patients (p<0o00l). appreciable gastric dilation delayed gastric with pentagastrin fast gastric achlorhydria SI-ALP was more common in patients with emptying. We aimed to study the effect of BC caused by pernicious anaemia (PA). The sub- pancolitis (63% of27) compared with 32% of22 on gastric acid secretion and plasma gastrin jects received in double blind randomised cross- with limited colitis and 37% of 46 normal values. Young male Wistar rates were laparoto- over fashion 28 day courses of ranitidine subjects (p<0 025). mised and the stomach was wrapped with 150 mg bd, ranitidine 300 mg qds, and placebo The genetic control of SI-ALP seen in gauze soaked in a 2-0% BC solution (n=8) or with one mouth 'wash out' between each. The normal subjects appears to be lost in IBD. In saline (n= 12) for 30 minutes. After three fasting and peptone meal stimulated gastrin contrast, we have shown, for the first time, that months, volume and acidity ofgastric contents concentrations were studied on the final day of a strong genetic control of C-ALP exists in were measured after one hour intragastric each course of treatment. The median fasting IBD; C-ALP was significantly more common instillation of saline and ligation ofpylorus and gastrin concentrations (ng/l) were similar fol- in patients with blood group 0 or B than in cardia. Plasma gastrin was measured by radio- lowing placebo (1132, range 27-2196), rani- group A (p<0 025). immunoassay. Intramural neurons were tidine 150 mg bd (1687, range 23-3158), and Thus, C-ALP is of diagnostic value in IBD. counted by a sampling histological method. In ranitidine 300 mg qds (1080, range 17-2655). SI-ALP appears to reflect the extent ofdisease, all BC rats the stomach was grossly enlarged, Despite the considerably raised basal values the http://gut.bmj.com/ being more common in pancolitis, suggesting intramural neurons were noticeably reduced patients still showed a further noticeable in- that there may be a functional abnormality of (median and range: 75; 0-425/mm v 2550; crease in response to the peptone meal. The the small intestinal mucosa in pancolitis lead- 550-4750/mm, p<0 01). BC rats showed median peak percentage rise over basal in ing to an increased secretion ofSI-ALP into the higher values for gastric acid secretion (101; response to the meal was similar after placebo circulation. 31-3708 [imol/hour v 44; 15-80 imol/hour, (87%, range 6-278), ranitidine 150 mg bd p<0O05) and plasma gastrin values (20; 12-30 (110%, range 0-250) and ranitidine 300 mg qds pmol/l v 10; 2-26 pmol/l, p<0 01). (111%, range 25-425) (all p<0 02). In conclusion, damage to gastric myenteric In conclusion, (1) hypergastrinaemia in PA on September 24, 2021 by guest. Protected copyright. STOMACH neurons by BC is associated with acid hyper- can be further increased by a peptone meal; secretion and hypergastrinemia possibly due to (2) H2RAs have no effect on plasma gastrin in chronic gastric distension or destruction of the achlorhydric stomach indicating that their inhibitory neurones acting on gastric parietal gastrin effect is secondary to acid inhibition. Ranitidine but not gastritis or female sex and G cells, or both. reduces the first pass metabolism of ethanol

J R FIATARONE, M K BENNETT, P KELLY, Antral progastrin concentrations after O F W JAMES (Departments of Medicine, Path- Kinetic analysis on the effects of cimetidine omeprazole ology and Medical Statistics, University ofNew- on human stomach alcohol dehydrogenase castle upon Tyne) Recent evidence suggests that activity A VARRO, J NEMETH, J BRIDSON, R WALKER, the first pass metabolism of moderate doses of G J DOCKRAY (Department ofPhysiology, Univer- oral ethanol occurs in the gastric mucosa and is E P CARR, P W N KEELING, K F TIPTON (Depart- sity of Liverpool, and Gastrointestinal Unit, mediated by gastric alcohol dehydrogenase ments of Biochemistry and Clinical Medicine, Walton Hospital, Liverpool) The achlorhydria (ADH). It has been suggested that gastric Trinity College, University ofDublin, Ireland) It produced by omeprazole in the rat leads to ADH activity is less in women and reduced by has recently been reported that cimetidine increased gastrin production reflected in raised cimetidine and in chronic alcoholics, leading to interacts directly with rat gastric and hepatic tissue concentrations of the gastrin precursor, higher blood ethanol concentrations and alcohol dehydrogenases and that this drug progastrin. We have examined concentrations possibly enhanced toxicity of this drug. significantly altered blood ethanol concentra- of progastrin in antral mucosal biopsy speci- To examine the effects of (a) abnormal tions in man after oral administration. mens from patients with oesophagitis (n=8) gastric mucosa and (b) ingestion of ranitidine In the present study we report the separation before and after treatment with omeprazole we have determined the first pass metabolism of the different alcohol dehydrogenase (20 mg daily) for six to eight weeks. Biopsy of ethanol in 18 adult subjects (10 men and isoenzymes from human stomach and in vitro specimens were extracted for estimation of eight women) undergoing routine upper gastro- kinetic analysis on the interaction ofcimetidine (a) biologically active (amidated) gastrins and intestinal endoscopy by measuring the dif- with the yy isoenzymes. Ethanol oxidation was (b) progastrin, by specific radioimmunoassays. ference in areas under the curves of blood monitored by a spectrophotometric assay and The progastrin assay (antibody L289) showed a ethanol concentrations after oral v intravenous the different alcohol dehydrogenase single peak of activity eluting in the region of ethanol (0. 15 gmlkg bodyweight). Gastric his- isoenzymes were visualised by activity staining progastrin when extracts were fractionated by tology, assessed by two to four random antral after starch gel electrophoresis. The yy iso- gel filtration on Sephadex G50. Basal plasma biopsy specimens, was as follows: chronic gas- enzymes are the main alcohol dehydrogenases concentrations of amidated gastrins were tritis n= 12, of which Helicobacter pylori +ve present in human stomach and are primarily slightly raised after omeprazole treatment (pre: n= 10 and chronic gastritis with atrophy n=6. responsible for ethanol metabolism in this 15 (3); post: 35 (9) pmol/l; mean (SE)), but Normal gastric histology n=6. Nine subjects tissue. tissue concentrations ofamidated gastrins were were taking ranitidine 300 mg/day. Our results show that cimetidine is an in- not changed (pre: 11 1 (2.9); post: 11-7 (2.6) British Society ofGastroenterology A595 nmol/g). Tissue progastrin immunoreactivity gastric instillation of pepsin 5 mg/ml, pH 1. determination was performed by the alcohol was 8-4 (1-1)% of the amidated gastrin con- Histamine significantly increased mucus dehydrogenase method (Sigma). A follow up centration before omeprazole treatment and erosion by pepsin (143% rise in luminal study with 24 subjects was performed using this increased to 19 1 (3.6)% after omeprazole degraded glycoprotein over control) and signi- similar study design, but dosing only with (p<0 05, t test). ficantly reduced (by 21%) pepsin induced ranitidine 300 mg or placebo, and 0-6 g/kg of Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from We conclude that after omeprazole treat- mucosal bleeding. alcohol was given one hour postprandially. ment there are relatively higher concentrations The results show that H2 antagonists There was no significant difference in the ofprogastrin in antral mucosa, which is consis- increase thickness of the adherent mucus gel mean integrated four hour blood alcohol con- tent with increased gastrin gene expression. barrier, and associated with this increased centration (AUC) in the placebo study (33.7 v protection is a reduction in mucosal bleeding 32-7 mg.h/dl) confirming the reproducibility of through pepsin damage. These effects are the method. There was no significant dif- independent of inhibition of endogenous acid ference in AUC between control studies and Persistent gastritis after ranitidine or antacid pepsin secretion. Histamine decreased mucus after seven days ofdosing with any ofthe three therapy predicts relapse of duodenal barrier thickness and increased its rate of H2 antagonists (ranitidine 35-1; cimetidine ulceration erosion by pepsin but produced a small reduc- 33-5; famotidine 32-6 mg.h/dl). There was no tion in mucosal bleeding, probably due to difference in AUC after dosing with 0-6 g/kg D ARMSTRONG, A L BLUM, H DAMMANN, vasodilatory effects. alcohol after seven days' treatment with M FISCHER, L GREINER, W HAASE, M LISZKAY, placebo or ranitidine (142 v 147 mg.h/dl). M STOLTE, M SULSER, B SIMON, THE TALCICAMP In conclusion, H2 receptor antagonists have STUDY GROUP (Division of Gastroenterology, no effect on the absorption of postprandial CHUVIPMU, Lausanne, Switzerland) Duo- Tolerance to H2 receptor antagonists - is alcohol in healthy subjects. denal ulcer (DU) healing after one month in hypergastrinaemia the cause? 127 of 164 patients receiving ranitidine (Ran: 300 mg nocte) and in 102 of 161 patients N PATEL, U M WARD, A K BROWN, J N PRIMROSE receiving an Al-Mg antacid (Ant: Talcid lg tid, (University Department of Surgery, St J3ames's Open access endoscopy - a nationwide Bayer) is independent of Helicobacter pylori University Hospital, Leeds) Pharmacological survey eradication, although subsequent six month tolerance to the acid inhibitory effects of H2 relapse rates, off treatment (36 of 90 Ant receptor antagonists is well established and an M G BRAMBLE (Middlesbrough General Hospital, patients; 48 of 115 Ran patients), are low in increase in the plasma gastrin value has been Cleveland) In a survey of BSG endoscopy H pylori negative patients (Blum, Gastro- implicated in its development. The aim of this members, 353 replies were received from 290 enterology 1990; 98: A21). study was to investigate further the temporal hospital units. Open access endoscopy (OAE) We tested the hypotheses that Ant heals DU relation between acid inhibition and plasma was offered by 46-7% of respondents (168), by improving antral gastritis and that persis- gastrin. A short term (24 hour), randomised, with virtually all offering gastroscopy, 17% tent gastritis provokes subsequent relapse. crossover study of placebo, ranitidine (Ran) offering flexible sigmoidoscopy, and 7-4% Antral biopsy specimens, taken at month 0, 300 mg nocte and Ran 300 mg bd daily was colonoscopy. Within this group one fifth month 1, and month 6, or earlier if symptoms performed on 12 healthy men, mean age 21 (21-4%) used a structured request form. 'Cen- recurred, were assigned a gastritis score (19-23) years. The 24 hour intragastric pH was sored' open access was widely used (61-3%- (GS-mild: 0-4, severe: 5-8), calculated from measured by radiotelemetry and acidity cal- 69.6%) on receipt of a letter from the general the density of lymphocytic (0-4) and granulo- culated from the area under the curve (AUC) of practitioner. Units performing OAE were cytic (0-4) infiltrates. The GSs at month 0 were (H+) versus time. The 24 hour plasma gastrin more likely to have a clinical assistant working http://gut.bmj.com/ similar (Ant: mild 9-6%, severe, 90.4%; Ran: (AUC) was calculated from hourly blood in them (50.5% v 37-1% p<0-01), with a mild 7-8%, severe 92.2%), and neither treat- samples. The 24 hour plasma gastrin (median greater number of endoscopists sharing the ment improved GS (Ant p=0 35, Ran p=0-28: (quartiles)) rose from 43 (40-57) mollminute workload (3-1 v 1-08). Very few centres were Wilcoxon: month 1 v month 0). At one month, before treatment to 59 (50-77) mol/minute on performing OAE because of restrictions on mild gastritis was not associated (p=060, Ran nocte (p<0 05) and 67 (59-91) mol/minute barium meal examination (7.2%) but 38% of Fisher) with a higher healing rate (13 of 17) on Ran bd (p<0 005 v placebo, p<0 05 v Ran units performing flexible sigmoidoscopy did than severe gastritis (200 of 265). Fewer nocte). However, there was no associated not have open access barium enema examina- patients relapsed with mild (two of 13) than attenuation in the inhibition of nocturnal tion (50% for open access colonoscopy). Sixty on September 24, 2021 by guest. Protected copyright. with severe gastritis (82 of 182; Fisher, acidity (95 (83-97)% v 91 (81-96)%). Thus, six consultants indicated they would like to p=0.044). even short term treatment with Ran led to an extend OAE to include large bowel endoscopy. In conclusion, neither Talcid nor ranitidine increase in the 24 hour plasma gastrin value, However, more than half had waiting times heals DU by improving antral gastritis. How- which significantly increased with the dose. which had exceeded six weeks at some time. ever, the risk of DU relapse is much greater Significant tolerance was not observed. Clinical assistants were endoscoping their own in patients with persistent severe gastritis. Tolerance to H2 receptor antagonists cannot patients in 68 out of 85 units (80%). (Support: SNF 32-26369.89 & Bayer). be solely attributed to the rise in plasma There has been a large increase in the gastrin. number of units offering OAE in the last 12 months (64) compared to the previous five years (49). H2 antagonists do have direct mucosal pro- tective actions Ranitidine, cimetidine, and famotidine have no effect on alcohol absorption in healthy M B COPEMAN, J MATUZ, A ALLEN, J P PEARSON volunteers SMALL BOWEL (Department of Physiological Sciences, The Medical School, University of Newcastle upon A G FRASER, E J PREWETT, M HUDSON, Tyne) There are conflicting reports on whether A M SAWYERR, S ROSALKI, R E POUNDER H2 antagonists have direct mucosal protective (Academic Department ofMedicine, Royal Free Is there specific glycoconjugate alteration in actions. This study describes in an anaesthe- Hospital School ofMedicine, London) Previous coeliac disease? tised rat model effects of H2 antagonists and studies have reported variable effects of H2 histamine on (1) integrity of the adherent receptor antagonists on postprandial alcohol C K CHING, S J STARMER, G K T HOLMES gastric mucus gel barrier and (2) mucosal absorption. The numbers have been small, (Derbyshire Royal Infirmary) We have evaluated resistance to pepsin induced damage. without placebo controls. the lectin binding activities of the small bowel Cimetidine (30 mg/kg ip), ranitidine Forty-eight healthy men were given either epithelium (SBE) from patients with adult (10 mg/kg ip), and nizatidine (10 mg/kg ip) ranitidine 300 mg (double blind and placebo coeliac disease (CD) and assessed their evolu- significantly increased gastric mucus thickness controlled), or cimetidine 800 mg, or famo- tionary changes after treatment with gluten (medians 157 [tm, 120 Vtm 130 im respectively) tidine 40 mg (single blind). Each subject was free diet in this study. compared with a saline (ip) control (median studied in a control experiment, and after seven Lectin histochemistry using six different 92 im); histamine (5 mg/kg ip) significantly days ofdosing with an additional dose one hour lectins PNA (gal 1-3 galNAc binding), UEA I decreased gastric mucus thickness (median before alcohol ingestion. Subjects were given a (L-fucose binding), WGA (glc NAc and sialic 60 ptm). Cimetidine, ranitidine, and nizatidine standard lunch and evening meal. 0 3 g/kg of acid binding), Con A (mannose binding), DBA significantly reduced mucosal bleeding (65%, alcohol was given one hour after the evening (gal binding), and GS2 (glc NAc binding) have 33%, and 62% respectively, measured as meal and blood samples taken at 10 to 20 been performed on formalin fixed, paraffin luminal haemoglobin bound iron) after intra- minute intervals for four hours. Blood alcohol embedded small bowel tissues obtained serially A596 British SocietyofGastroenterology

(before and six monthly after gluten free diet) replaced by host cells; the stroma and germinal positive subjects underwent small intestinal from patients with CD (n= 12) and normal (N) centres of the follicles remained of graft origin. aspiration and microbiological analysis. Four- controls (n= 12). In the Peyer's patches, the dome showed teen of the 19 had proved bacterial overgrowth

UEA I and PNA binding glycoconjugates maximal infiltration: 55%, day 28; 78%, day (total count ¢ 10' or strict anaerobes >103 Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from were strongly expressed in all parts of the SBE 56. In the parafollicular zone there was 40% CFU/ml), including counts of 10' in three, 10' in untreated CD when compared with N, infiltration at both time points with only 5% of in two, 10' in four, and 10' in two. A raised which was generally lacking in both UEA I and host cells in the follicles by day 56. The lamina fasting hydrogen frequently associated with PNA lectin binding. No difference was propria contained 54% host cells on days 28 and SIBO, was evident in only three of the 14. The observed between CD and N by other lectins, 56. There was no significant infiltration of the mean haemoglobin, folate, vitamin B12, cal- which bound strongly and diffusely to both intraepithelial compartment. cium, and alkaline phosphatase values did not groups. Progressive diminution of UEA I and Despite the absence of rejection host cells differ significantly between those with positive PNA lectin binding was observed in the serial infiltrate small intestinal transplants to a signi- and negative HBTs. Of the 14 proved SIBO biopsy specimens of the CD as villous height ficant extent. cases, all had normal haemoglobin, calcium, and morphology returned to normal so that the and vitamin B12. In five of these, there was lectin binding activity of the latter resembled previously documented weight loss and in the N controls. three, diarrhoea, which may have been attri- These results probably indicate increased Disturbed gastric emptying in short bowel buted to SIBO. Thus, we found a high fucosyl transferase activities and the presence syndrome: correlation with jejunal length and incidence of positive HBT (29 of 122) and of glycoconjugates bearing immature oligosac- evidence for a 'colonic brake' culture proved bacterial overgrowth (14 of 19) charide side chains of gal 1-3 gal NAc rather in elderly hospitalised patients. However, only than specific changes in regenerating SBE in J M D NIGHTINGALE, J R M VAN DER SIJP, a small proporion of these had any of the CD. M A KAMM, E R WALKER, S J MATHERS, classically described features of SIBO. K E BRITTON, L M A AKKERMANS, J E LENNARD- These data suggest that SIBO is relatively JONES (St Mark's Hospital, City Road, London) common in the elderly and that the indications Patients with short bowel have inadequate for treatment in this patient group requires Small bowel ultrasound to detect Crohn's absorption ofnutrients and fluids which relates careful evaluation. disease to a decreased absorptive surface. Is gut transit, in particular gastric emptying, rapid which D F MARTIN, D A NICHOLSON, M B SHERIDAN would contribute to poor absorption? Does (Department ofRadiology, Withington Hospital, preservation of the colon affect gut transit? Variation in pathogenicity between Giardia University Hospital ofSouth Manchester, Man- We studied 12 patients with a short intestine, lamblia isolates chester The need to exclude small intestinal six with end jejunostomies (EJ) (jejunal length Crohn's disease is a common cause of referral 50-160 cm) and six with jejunocolic anasto- A M CEVALLOS, M JAMES, S CHAR, M J G FARTHING for small bowel barium examination. Despite moses (JC) (jejunal length 25-75 cm), and 11 (Departments of Gastroenterology and Histo- attempts to select patients on clinical grounds, healthy subjects. Solid phase transit was pathology, St Bartholomew's Hospital, London) most small bowel barium examinations will be measured using a 560 kcal pancake containing We have shown that Giardia lamblia isolates normal. In an attempt to allow more selective 20 mBq of "'In microspheres and liquid transit differ in surface proteins, isoenzyme produc- use of small bowel barium examination and to using 195 ml oforange juice containing 40 mBq tion and DNA analysis when hybridised with a minimise radiation we have 9Tc-EDTA. Time activity curves for gastric G lamblia To determine if exposure, specific probe pGL2. http://gut.bmj.com/ evaluated the use oftransabdominal ultrasound emptying were constructed after making these differences in the genotypic and pheno- examination of the small bowel before barium geometic corrections. EJ patients had a signifi- typic profiles result in differences in biological examination in all patients referred with the cantly (p<0O05: Mann-Whitney U test) faster behaviour we compared five different G lamblia clinical suspicion of small intestinal Crohn's initial (25%) emptying rate ofliquids (median 9 isolates in a neonatal rat model. disease. To date, 64 patients (38 women, 26 minutes) compared with controls (median 25 Six day old Sprague-Dawley rats were men - age range 18 to 84 years, mean 43) have minutes) and JC patients (median 36 minutes). inoculated with 5-x 105 G lamblia tropho- been examined immediately before barium The emptying of solids for EJ patients was not zoites strains PO1, B2, B3, VNB3, or GP. examination performed by a radiologist who significantly different from controls or JC Animals inoculated with strain GP (isolated was unaware of the ultrasound findings. Ten of patients. The gastric emptying for liquids and from a guinea pig) did not develop infection. on September 24, 2021 by guest. Protected copyright. 13 patients with active Crohn's disease have solids in JC patients was normal. There was a Infection rates for the other isolates varied from been correctly identified by ultrasound, as have tendency for the rate of gastric emptying for 63-100%. The number of trophozoites in the 50 of 51 patients without disease. Clinical liquids and solids to correlate with jejunal small bowel of infected animals was similar in review at up to one year has showed no length in both groups ofpatients. all animals (Kruskal-Wallis p=-0 22). undected disease. Patients with a short bowel and no colon Mucosal damage was assessed histologically These results support the use of ultrasound have rapid gastric emptying of liquids. The and bydisaccharidase activities. On lightmicro- as a procedure which can select appropriate normal gastric emptying in JC patients may scopy there was no increase in intraepithelial patients for small bowel barium examination indicate the presence ofa 'colonic brake.' lymphojytes or evidence of villous blunting. and minimise radiation exposure in patients Mucosal disaccharidase activities were who do not harbour disease. decreased in all animals infected. However, there was a difference in the enzyme affected by Small intestinal bacterial overgrowth in the individual isolates. Sucrase activity was pre- elderly - an incidental finding? served in PO1, B2, and B3 but not in VNB3. Small intestinal transplant infiltration Lactase and maltase activities were preserved M MACMAHON, M KELLY, D NUNES, D G WEIR, in all but VNB3. C L INGHAM CLARK, B A PRICE, P W CRANE, R R 0 MOORE, J B WALSH, CT KEANE, D COAKLEY Thus, we have shown differences in biologi- P A LEAR, R F M WOOD (INTRODUCED BY (Departments ofMedicinefor the Elderly, Gastro- cal behaviour between G lamblia isolates in the R K S PHILLIPS) (Professorial Surgical Unit, St enterology, and Microbiology, St _James's Hos- absence oflight microscopic mucusal damage. Bartholomew's Hospital, London) Small bowel pital and Trinity College, Dublin) Previous transplants were performed between two fully studies have suggested that small intestinal allogeneic inbred strains of rat. All animals bacterial overgrowth (SIBO) is implicated in were given cyclosporin 15 mg/kg/day from the pathogenesis of anaemia, vitamin B 12 defi- DNA fingerprinting of Giardia lamblia with operation - a dose known to prevent histo- ciency, biochemical osteomalacia, weight loss, the M13 bacteriophage genome logical rejection. Host cell infiltration within and diarrhoea in the elderly. However, data these non-rejecting transplants was investi- regarding prevalence of SIBO in elderly with- S CARNABY, T D McHUGH, M J G FARTHING gated. Studies were performed at days 28 and out known nutritional deficiencies is conflict- (Department of Gastroenterology, St Bartholo- 56 post-transplantation. Graft tissues were ing. We prospectively screened 122 elderly (age mew's Hospital, London) Giardiasis is often harvested, snap frozen, sectioned, and stained range 70-92 years) hospitalised patients using a asymptomatic but may cause acute or chronic with strain specific monoclonal antibodies two hour glucose (50 g) hydrogen breath test diarrhoea. This may relate partly to host factors (OX27; anti-PVG, and MN4; anti-DA) using (HBT). Those taking antibiotics were ex- but intrinsic characteristics of the parasite are an indirect immunoperoxidase technique. In- cluded. A hydrogen rise 10 ppm (positive) also likely to be important. There are no filtrating cells were counted as a percentage of was considered evidence of SIBO and was satisfactory methods for identifying different the total cell number. The parafollicular tissue recorded in 29 (24%) subjects; the remaining isolates of Giardia lamblia and no markers of within the mesenteric lymph nodes was entirely 83 (76%) were negative. Nineteen of the 29 virulence. We have characterised our isolates British Society ofGastroenterology A597 using DNA fingerprinting with the M13 phage Department of Medicine and Phartnacology, M T HENDRICKSE, D R TRIGER (Department of genome which has been shown to identify Royal Hallamshire Hospital, Sheffield) To Medicine and Pharmacology, University ofShef- hypervariable minisatellites in a range of examine the natural history ofanorectal varices field) Although both peripheral and autonomic organisms. Total genomic DNA (4 rig) from (ARV) we have prospectively evaluated by neuropathy have been described in primary each of our 19 G lamblia isolates from different anorectoscopy a group of 100 cirrhotic patients biliary cirrhosis (PBC), their inter-relation has Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from host species and temperate locations was in whom we previously described a prevalence not been examined. Peripheral nerve function digested with one of several '4-base' cutting of ARV of 44%. After a median follow up of (PNF) was assessed by standard clinical and restriction enzymes. DNA separation and 40-6 months (range 31-5-47-7) 44 patients were neurophysiological techniques, and autonomic southern transfer was performed in the usual alive, three had undergone liver transplanta- function (AF) by standard cardiovascular tests manner and the resulting filters were tion, 42 had died, and 11 had been lost to follow as described by Ewing and Clarke, together hybridised with 32P-labelled M13 phage DNA, up. The presence of ARV had no effect on with the heart rate variation at rest and to washed and visualised by autoradiography. patient survival but a greater number of those intravenous atropine. Twenty seven patients Restriction enzymes Rsa I, Pvu II, and Sau IIIa with ARV (43%) than those without (28%) and 28 control subjects ofcomparable age were proved most useful as they allowed recognition subsequently suffered oesophageal variceal studied. Some 7% (two of 28) controls v 52% of up to 14 bands per isolate. Most isolates haemorrhage. Repeat anorectoscopy, planned (14 of 27) patients had cardiovascular showed distinct banding patterns, although the for two years after the initial assessment, was autonomic dysfunction (p=00008). Seven per number of bands and the presence of banding possible in 45 of 89 patients; of the remainder cent (two of 28) controls v 44% (12 of 27) pattern differences between each isolate was seven refused and 37 had died. ARV were patients had symptoms or signs, or both, plus not the same with each enzyme. Therefore, found in 28 (62%) of those re-examined. Com- nerve conduction abnormalities indicative of a further work will be necessary in order to pared with the initial anorectoscopy, ARV had peripheral neuropathy (p=0 004). Serum produce a definitive fingerprint to enable posi- developed in nine patients and become more albumin correlated with sural nerve conduc- tive identification of each isolate. This method extensive in two with the findings unchanged in tion velocity (NCV) (r=0-64 p=0.0007) but will provide a basis for the detailed analysis of 31. Three patients had ARV detected initially there was no relation between serum vitamin E isolate heterogeneity and study ofvirulence. but not subsequently; this was explained in two and autonomic or peripheral neuropathy. AF patients by successful reduction in portal was related to PNF with correlation between pressure. Overall, three patients bled de novo the valsalva ratio and peroneal NCV (r=0 51 from ARV and required surgical treatment. p=0 01); heart rate variation on deep breathing Small intestinal permeability in HIV positive Only one of these had ARV at initial assess- and sural NCV (r=0 522 p=0.007) and patients ment, the varices developed subsequently in peroneal NCV (r=0-67 p=0.0003); the lying the others. standing ratio and median sensory NCV S G LIM, I S MENZIES, C A LEE, M A JOHNSON, ARV are common, often develop, and may (r=0.51 p=0 007); and the response to iv R E POUNDER (Departments ofHaemophilia and bleed (cumulative risk 10% over follow up atropine and sural action potential (r=0-76 Medicine, Royal Free Hospital School of period) but do not confer excess mortality on p=O-00l). Medicine, and Department ofClinical Chemistry, patients with cirrhosis. These results indicate a high prevalence of St Thomas's Hospital, London) The aim of this peripheral and autonomic neuropathy in PBC study was to assess the incidence of abnormal and a significant correlation between AF and intestinal permeability in patients with HIV PNF in this disorder. infection. Tin-protoporphyrin combined with haem The urinary lactulose rhamnose (L:R) ratio arginate - an improved treatment for acute was measured in a five hour urine collection hepatic porphyria http://gut.bmj.com/ after drinking an oral iso-osmolar sugar solu- Graft versus host disease after reduced size tion (lactulose 5 g, rhamnose 1 g, xylose 5 g, S B DOVER, M R MOORE, A GRAHAM, K E L McCOLL orthotopic liver transplantation 3-0-methyl glucose 2.5 g). Forty four HIV (University Department ofMedicine and Thera- positive patients (25 asymptomatic, 5 ARC, peutics, Western Infirmary, Glasgow) In acute A S REECE, K C TAN, G MELI-VERGANI, and 14 AIDS; haemophiliacs 24, homosexuals porphyria there is overproduction of the haem AP MOWAT, M LEYTON, S HUMPHREYS, 20) and 14 controls were investigated. All precursors, aminolaevulinate (ALA) and por- R WILLIAMS (King's College Hospital, London) patients with gastrointestinal problems (eight phobilinogen (PBG). This can be suppressed Graft v host disease (GVHD) is a well recog- weight loss and three diarrhoea) had repeated transiently by administering haem, which in- nised problem in the transplantation of organs on September 24, 2021 by guest. Protected copyright. stool cultures and relevant investigations. hibits ALA synthase. We investigated the containing a considerable population of Patients on non-steroidal anti-inflammatory possibility of augmenting this effect by co- passenger lymphocytes such as bone marrow, drugs, alcoholics, and those with a history of administering Tin-protoporphyrin, which in- small bowel, and pancreaticosplenic blocks. bowel disease were excluded. Urine lactulose hibits hepatic breakdown of haem by haem- However, it is in general only occasionally and rhamnose were measured by thin layer oxygenase. Five patients were each treated in reported after transplantation of other solid chromatography and the results were three separate attacks with placebo, haem organs. Two patients with reduced size liver expressed as the ratio of the percentage of the arginate alone (3 mg/kg) and haem arginate transplants performed at this institution have oral dose oflactulose and rhamnose. with tin-protoporphyrin (1 imollkg), each developed this complication, which proved The 14 controls had a mean L:R of 0-029 given daily for three days. On day three of fatal in both. These patients are described, and (0-011); the upper limit of normal was 0-051 placebo the mean urinary excretion of ALA the occurrence of GVHD is discussed in the (mean (+2 SD)). An abnormal L:R ratio was and PBG were 86% and 73% of pretreatment light of the above mentioned classic conven- found in seven of 19 symptomatic HIV positive values, and 90% and 77% five days later. Haem tions and recent observations that the propen- patients (AIDS and ARC), and in four of 25 arginate alone lowered ALA and PBG to 15% sity for GVHD in these systems is related to the asymptomatic patients. The L:R ratio in- and 24% on day three, but five days later they burden of lymphatic tissue implanted with the creased significantly as the T4 lymphocyte had risen to 49% and 54%. The addition ofTin- graft. Paediatric patients, by virtue of their count decreased to <0-01 x 109/l, compared protoporphyrin gave similar third day values smaller body size would therefore be placed at with those with T4 counts >0.25 x 109/l (p= (ALA 11%; PBG 15%), but biochemical remis- greater risk of these problems than larger 0-001, unmatched t test) and was also signifi- sion was sustained five days later - ALA 14%, recipients. This early observation would seem cantly increased (n=8, p=0-029) in patients PBG 15%. This was seen in all the patients. to be of no little importance in a context in with weight loss (10 kg or 10% body weight). The ability of the combined treatment to which the use of reduced size organs is increas- Two of three patients with diarrhoea had prolong remission was further assessed in a ing for many applications in paediatric and abnormal L:R ratios. There was no difference patient experiencing frequent attacks. With general liver transplant practice. It is suggested in the mean L:R ratio between haemophiliacs placebo (n-4), Haem arginate (n-23), and that the technique of hilar lymphadenectomy and homosexuals. combination (n=3), the mean times from treat- would be a surgical technique which would ment to the next attack were 11, 23, and >64 allow this problem to be circumvented. days respectively. The coadministration of Tin-protopor- LIVER phyrin prolongs the beneficial effects of haem arginate therapy. Donation and liver transplantation: a survey of attitudes in northern Italy

Natural history of anorectal varices A MARTIN, L ROSSARO, A M MANGANELLI, Peripheral and autonomic neuropathy in D CAPOZZA, M SALVAGNINI, G C STURNIOLO, H L SMART, D R TRIGER (University ofSheffield primary biliary cirrhosis R NACCARATO (Division of Gastroenterology and A598 BritishSocietyofGastroenterology

Department ofGeneral Psychology, University of bile acids identify different defects in liver mechanisms. Hypocalcaemia due to multiple Padua, Italy) Liver transplantation is still disease factors was found in seven patients. limited by the shortage oforgans and only 25% R P ofpatients are transplanted. We aimed to assess JAZRAWI, J DE CAESTECKER, P GOGGIN, Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from the possibility of affecting people's attitudes A BRITTAIN, J D MAXWELL, A E A JOSEPH, towards organ donation. We developed a 25 T C NORTHFIELD (Departments ofMedicine and OESOPHAGEAL item, self administered questionnaire: 421 Nuclear Medicine, St Georges Hospital Medical adults were interviewed and feelings about School, London) After intravenous injection, brain death, organ allocation, and economic bile acids disappear from plasma in a biex- implications were explored. Statistical analysis ponential manner with an early rapid (K,) and Gas bloat syndrome after Nissen fundo- was performed by factor analysis, main axes, a late slow disappearance (K2). We have pre- plication the Dquartimax oblique rotation and the viously shown by hepatoscintigraphy that Crombach coefficient, the Student's t test, and patients with primary biliary cirrhosis (PBC) T O'HANRAHAN, A VALLI, J BANCEWICZ (Univer- Manova test. have a hepatic excretory defect but normal sity Departments ofSurgery and Radiology, Hope Three major factors were identified: scien- uptake of bile acids, in contrast to other types Hospital, Salford) Nissen fundoplication pro- tific and social responsibility of the physician of cirrhosis. Our aim was to study the relation vides good control of gastro-oesophageal (F1), equality of organ allocation and distribu- between K,, K2, hepatic uptake, and excretion reflux, but its effectiveness is said to be reduced tion (F2), and commercialisation of organs ofbile acids in liver disease. by a high incidence of gas bloat syndrome (F3). People trust the medical profession for We studied 12 patients with PBC before and (GBS). This is attributed to the production of a their decisions (F1: p<0-0001), are against during three months' treatment with UDCA supercompetent cardia. We have assessed the discrimination (F2: p<0 0001), and oppose and 10 patients with biopsy proved cirrhosis relation between gastric size on x ray and organ commercialisation (F3: p<0-0001). due to some other cause. After an intravenous symptoms attributable to GBS. A total of 89 Younger people and the better educated are bolus of they labelled bile acid75 SeHCAT, we patients (47 men, 42 women) were studied 15 more critical (p<001) of the responsibility of carried out simultaneous y camera scanning months (median; range 2-89) after fundoplica- physicians and have stronger views against and serial blood sampling for 90 minutes. We tion. Symptom assessment included leading discrimination (p<0-02). Insufficient know- measured plasma disappearance, hepatic up- questions about gastric fullness, abdominal ledge concerning regulations, criteria, and pro- take, and net excretory rate for 75SeHCAT. K1 distension, and bloat. The area (cm2) of the cedures was apparent. and K2 (%/min) were determined from early gastric gas shadow, detected on supine plain In summary, (1) people trust the medical (up to 12 minutes) and late (20-60 minutes) abdominal x rays, was measured using a trans- profession and oppose discrimination and com- decline in plasma activity of 75SeHCAT respec- parent grid. Twenty patients without gastro- mercialisation of transplant procedures; tively. There was no correlation between K1 intestinal symptoms undergoing intravenous (2) young and educated people are more critical; and K2 indicating that they identify different urography served as control subjects. The size (3) the individual is seen as the only one hepatic functions. K1 correlated with hepatic of the gastric shadow was significantly greater responsible for the decision to donate; uptake (r=0-54, p<0-01), but not excretory after fundoplication (79 cm2 median) than in (4) having met a transplanted individual rate (r=0-05, NS); while K2 correlated with control subjects (39 cm') (p=00004 Mann- strongly reinforces positive attitudes; and hepatic excretory rate but not uptake (r=0.54, Whitney U test). However there was no signifi- (5) an educational approach should be aimed at p<002, and r=0-04, NS respectively). Treat- cant difference after fundoplication between improving both knowledge and attitudes. ment with UDCA improved K2 (17 (0.2) to 2-0 those with (3) and without (86) the clinical (0.2); p<0 03) but not of v 81 K,. syndrome gas bloat (67 cm2; p=0.43). http://gut.bmj.com/ We conclude that K1 is related to hepatic Gaseous gastric distension is common after uptake and K2 is related to excretion; and that Nissen fundoplication but GBS is not. There is Combined heart-liver transplantation in a these measurements may offer a sophisticated no relation between symptoms of distension, patient with familial hyper cholesterolaemia and specific method of assessing pathophysio- fullness, or bloat and the size of the gastric gas logy and response to treatment in liver disease. shadow. A more likely explanation for the K C TAN, R MODRAGON, M YACOUB, S COTTAN, symptoms of GBS is abnormal sensory per- W GAVIN, R WILLIAMS (King's College Hospital, ception. London and Harefield Hospital, Middlesex) Familial hypercholesterolaemia (FH) is a Acid-base and electrolyte abnormalities in on September 24, 2021 by guest. Protected copyright. genetic disorder characterised by raised plasma alcohonic patients concentrations of low density lipoprotein Overnight stay or same day discharge after (LDL) and cholesterol, resulting in severe and M ELISAF, H LIAPIS, K C SIAMOPOULOS, oesophageal dilatation and variceal premature atherosclerosis. E V TSIANOS (Department of Internal Medicine, sclerotherapy? We report a 33 year old woman with FH who School of Medicine, University of Ioannina, had a successful combined heart and liver Greece) This study was undertaken to evaluate D BULLIMORE, P FOSTER (St James's University transplant. Although she had been diagnosed the pathogenetic mechanisms of acid base and Hospital, Leeds) Audit of management after since 18 months ofage and had received various electrolyte abnormalities in 50 alcoholic dilatation of benign oesophageal strictures and kinds of treatments, in 1988 she developed patients aged 21-78 years admitted to our long term endoscopic variceal sclerotherapy incapacitating angina and cardiac failure. department for causes related to alcohol abuse. (EVS) showed noticeable differences among 40 Examination showed tendon xanthomata and None of the patients had ascites, diabetes endoscopy units polled by postal questionnaire aortic stenosis. She had a cholesterol of mellitus, or renal insufficiency and none were (87.5% response). Details of methods used for 23 mmol/l and LDL of 11-5 mmol/l. Coronary receiving diuretics. Eighteen patients had res- each procedure also varied. All units dilated angiography showed severe ostial and aortic piratory alkalosis which was due to lung infec- strictures and 83% performed sclerotherapy. stenosis, diffuse coronary arterial insuf- tion, liver damage, and delirium tremens. In dilating strictures, 37% of centres never ficiency. Combined heart-liver replacement Metabolic acidosis was found in nine patients. used and 17% always used screening. Patients was carried out and within three months there Twenty three of the 50 patients had serum were routinely admitted overnight (29%), dis- was good function from both grafts. Her serum electrolyte abnormalities. Hypokalaemia was charged rapidly (34%), or within a few hours LDL and cholesterol are normal and she is found in 10 patients and was due to respiratory (37%). Some 31% performed routine CXR. asymptomatic. alkalosis or to hypomagnesaemia induced Fifty seven per cent had had no perforations Combined heart-liver transplantation was kaliuria, or both. Hypomagnesaemia was during past year. There was no correlation first successfully carried out in 1984 by Starzl detected in 15 patients and was attributed to between use of screening, duration of observa- et al in a 16 year old girl with FH. The first respiratory alkalosis as well as to alcohol in- tion, or use of CXR and detection of perfora- operation was fraught with difficulties and duced magnesiuria. Six patients had hypona- tion. Units undertaking EVS used ethano- subsequent attempts of such a procedure were traemia due to volume depletion which was lamine (50%) or STD (50%); 90% favouring met with universal failure. This was because of caused by the diuretic action of alcohol as well intravariceal injection. Injection volume/site the simultaneous implantation of the two as by the hypotonic replacement of isotonic was generally 0-5-1 ml (24%) or 1-2 ml (55%) organs or 'en bloc' engraftment. We described losses. Three patients had pseudohypona- and volume/session was 5-8 ml (48%) or 9-12 a new surgical technique whereby the organs traemia due to coexistent hyperlipidaemia. ml (31%). Forty five per cent used overnight were grafted with enormous success. Severe hypophosphataemia was found in 16 stay; 55% same day discharge. One unit patients who had also respiratory alkalosis or favoured overnight stay and gastrograffin phosphaturia due to metabolic acidosis, hypo- swallow. Twenty eight per cent reported pro- magnesaemia, phosphaturic effect of alcohol, cedure related bleeding during the past year. Early and late plasma disappearance rates for or to the combination ofthe above pathogenetic This occurred early and did not correlate with British Society ofGastroenterology A599 discharge policy. Bleeding was not reported 35%; hiatal hernia 6%; Barrett's gastric type saline (11-7 to 10-6 ml). There was no signifi- from units using 0-5-1.0 ml/site and seemed mucosa 12%; Barrett's intestinal type mucosa cant change in OP threshold after either fluid. more common in units using over 8 ml (dysplasia absent or mild) 14%; Barrett's intes- We conclude: (a) oesophageal nociceptors sclerosant/session. tinal type mucosa (dysplasia moderate-severe) can be sensitised by acid perfusion; (b) this is a receptor phenomenon, as pain threshold after We conclude that after either procedure 22%; and adenocarninoma 41%. Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from neither radiology nor routine overnight stay Expression of PCNA was positively cor- OP (which directly stimulates afferent nerve (except for social reasons) is required and may related with Lewis x expression in the fibres) is not affected by acid; and (c) the results represent a less than optimum use ofresources. squamous oesophageal tissue (p<0-01) and suggest oesophageal stretch receptors sensing TGFa expression in Barrett's mucosa and pain behave as polymodal nociceptors adenocarcinomas (p<005). Lewis x and TGFa may be a guide to proliferation indices of Radial and axial asymmetry ofthe pharynx oesophageal tissue in routine histological analysis. Influence of gestational age on pregnancy A PRYDE, J A WILSON, C C A MACINTYRE, heartburn R C HEADING (Departments of Medicine, Oto- laryngology andMedical Statistics Units, Univer- J M MARRERO, P M GOGGIN, J S DE CAESTECKER, sity ofEdinburgh) Widely differing values have Long term clinical review of patients with M PEARCE, J D MAXWELL (Departments of been reported for pharyngeal contraction oesophageal pain Medicine and Obstetrics, St Georges Hospital pressure on swallowing, and the likelihood of Medical School, London) Heartburn in preg- asymmetry has often been disregarded. We G L SWIFT, H ALBAN-DAVIES, H McKIRDY, nancy has been attributed to increased intra- have undertaken pharyngo-oesophageal mano- R LOWNDES, D LEWIS, J RHODES (University abdominal pressure. An effect of raised sex metry with an intraluminal strain gauge Hospital of Wales, Cardiff) Between eight and hormones has also been implicated. Our aim assembly (Gaeltec Research Ltd) linked to a nine years ago 36 patients with recurrent was to study by questionnaire the prevalence, computer recorder (GR800, Aspen Medical) in anginal chest pain, in whom cardiological severity, and time of onset of heartburn in 13 patients aged 39 to 85 years complaining of investigations were negative were found to women attending antenatal clinic. A total of globus sensation (6), cervical dysphagia (6) or have oesophageal dysmotility by manometry 625 were analysed. The prevalence of heart- hoarseness (1). The five sensors were orien- studies. We have completed a follow up study burn increased with gestational age (26% in the tated radially in posterior (P), right and left by a questionnaire and 11 have had repeated 1st, 31% in the 2nd, and 66% in the third posterolateral (RPL and LPL), and anterior manometry. Two could not be traced, three trimester; p<0-0001). Severity of heartburn (A) positions during a 1 cm station pull through had died (one ofmyocardial infarction) and one also increased with advancing pregnancy of the pharynx from station 0 (SO) just above no longer had episodes of pain. Thirty, how- (p<00001). Symptoms of heartburn rapidly upper margin of the upper oesophageal ever, continued to have chest pain which increased towards the end of the 2nd trimester sphincter (UOS) to station 6 (S6, base of limited activity in 21. The frequency and showing a close temporal relation with pub- tongue), with 3 x 5 ml water swallows at each severity of pain was the same or had increased lished values for 24 hour urine pregnanediol station. Significant axial asymmetry was identi- in 20, but there had been a significant reduction excretion (Shearman, J Obstet Gynaec 1959; fied with a pressure trough 3 cm above the UOS in hospital admissions from 60 in 21 patients 66: 1), while reported changes in uterine size (at SO, mean= 100 mmHg, S3, mean= before diagnosis to 18 in 10 patients during showed a different pattern with increasing 73 mmHg, S6, mean=95 mmHg). In the lower the nine years after diagnosis. In spite of the gestational age (Calvert, BMJ 1982; 285: 846). 3 to 4 cm of the pharynx, there was also advice given to family practitioners, 10 patients Furthermore, the decrease in heartburn tradi- significant radial asymmetry with greater had been told their pain was of cardiac origin. tionally expected during the last three weeks of pressures in the AP than the lateral planes (at Sublingual nitrates were found to be the most pregnancy (foetal head descent) was not Si, mean RPL=81 mmHg, mean A=120 helpful preparation for relief of pain in 16 observed. Logistic regression analysis showed http://gut.bmj.com/ mmHg, mean P= 165 mmHg). In conclusion, patients. Eleven had repeated manometry increased risk of suffering heartburn with the human pharynx shows (1) axial asymmetry which showed persistent abnormality up to increasing gestational age (p<00001), parity with a pressure trough at 3 cm, probably the nine years after diagnosis. (p<00003), and pre pregnancy obesity (pon- functional counterpart of Killian's dehiscence; In conclusion, oesophageal dysmotility is a deral index, p<005) but not with age, race, or (2) radial asymmetry, more marked in the chronic condition in which symptoms and weight gain in pregnancy. lower 3-4 cm, similar to that observed in the manometry abnormality may persist for many We conclude (i) heartburn increases in pre- UOS. These findings help to explain the wide years. valence and severity with gestational age and

range of reported pharyngeal contraction parity; (ii) temporal changes in heartburn on September 24, 2021 by guest. Protected copyright. pressures. reflect changes in progestagen secretion more closely than changes in fundal size. These Cross modality sensitisation of oesophageal results suggest pregnancy heartburn depends pain receptors more on hormonal changes than uterine Proliferating cell nuclear antigen in oeso- expansion. phageal diseases; correlation with ligand A J MEHTA, J S DE CAESTECKER, T C NORTHFIELD expression (Department of Medicine, St Georges Hospital Medical School, London) Polymodal cutaneous J JANKOWSKI, D HOPWOOD, K G WORMSLEY nociceptors can be sensitised by repeated BILIARY TRACT (Departments of Clinical Pharmacology and noxious stimuli. Such effects have not been Pathology, University of Dundee) We assessed described in the gut. We studied the effect of 88 patients who had proved oesophageal oesophageal acid perfusion on oesophageal disease and who also had had an oesophago- sensitivity to distension. Fifteen patients with Microlithiasis ofthe gail bladder - a challeng- scopy. Oesophageal biopsy specimens showed non-cardiac chest pain underwent a double ing diagnostic problem a range of oesophageal disease - seven normal, blind randomised crossover oesophageal per- 12 oesophagitis, eight oesophageal squamous fusion (10 ml/minute) with 300 ml 0-1 N HC1 or P KAR, A GOGNA, N R ACHARYA (INTRODUCED BY cancer, six gastric mucosa in hiatal hernia, 44 0.9% saline on separate days. A latex balloon on J B DILWARI) (Department ofMedicine (Gastro- Barrett's oesophagitis, and 11 oesophageal a multilumen catheter was placed 5 cm above enterology Services), Maulana Asad Medical adenocarcinoma. the lower oesophageal sphincter and a pacing College, New Delhi, India) The causes of Biopsy specimens were processed immuno- electrode at the same level. Graded balloon repeated right hypochondrial pain when all histochemically to show proliferating cell distension (BD) was followed by oesophageal conventional investigations such as oral choly- nuclear antigen (PCNA). A minimum of 2000 pacing (OP) at increasing current strengths cystography (OCG) and ultrasonography are cells were counted. We assessed the expression with ECG monitoring. Threshold for discom- unrewarding have always remained elusive. of two potential markers of differentiation - fort during BD or OP were recorded as volume This study was designed to screen such patients Lewis x and transforming growth factor a (ml) or current (mA). Repeat procedure at 10 for the presence of microlithiasis (CMC or (TGFa). minutes was followed by oesophageal perfusion CBG, or both) using polarised microscopy of PCNA stained mainly the basal cells in the and BD/OP pain thresholds measured. Basal the bile obtained by duodenal intubation after squamous oesophagus and the epithelial cells of pain threshold was similar on both days (mean stimulating the gall bladder with CCK. The Barrett's glandular tissue. (SE) 11-8 (0.8) and 11-5 (1-0) ml; 12-6 (2-1) and study group comprised of 20 patients with Expression of PCNA for each tissue was as 12-2 (1-2) mA). Mean BD pain threshold biliary colic who had normal OCG and ultra- follows; normal oesophagus 8% of cells; in- decreased from 11-7 to 9.1 ml (p<0O02) after sound, a control group of 10 healthy subjects, flamed oesophagus 16%; squamous carcinoma acid, with a small non-significant drop after and 15 patients with symptomatic gall stones A600 British SocietyofGastroenterology who had undergone cholycystectomy (bile Southampton General Hospital, Tremona Road, alone and in model preparations in Tris buffer obtained by intraoperative needle aspiration of Southampton) Selecting symptomatic patients (20 mmol/l, pH 8.2) and 2D spectra confirmed gall bladder). Eleven of 20 patients (55%) with without gall stones who may benefit from the assignments of individual resonances. biliary colic (with normal OCG and ultrasound) cholecystectomy is often based on bile crystal Model vesicles were prepared from chol had microlithiasis in the form of CMC and or analysis. The standard technique, by duodenal (5 mmol/l) and PL (5, 10, and 20 mmol/l) in Gut: first published as 10.1136/gut.32.5.A553 on 1 May 1991. Downloaded from CBG. All patients with proved gall stones had intubation and bile aspiration, is lengthy and Tris buffer. Fresh human bile was studied microlithiasis but there was none in healthy sometimes unsuccessful. We report our without preparation. subjects. There was no correlation between the development and validation of percutaneous Assigned peaks from Na taurocholate, PL, cholesterol saturation index and the presence of bile aspiration from the gall bladder (GB) with and chol were identifiable in both model and microlithiasis. special reference to its safety. A total of 44 human biles. 2D COSY spectra confirmed the In conclusion, examination of bile for micro- patients about to undergo cholecystectomy for position of the 26, 27 chol methyl groups at lithiasis by polarised light microscopy in symptomatic gall stones underwent preopera- 0.9 ppm. The PL choline head group was patients with a history suggestive of biliary tive percutanous bile aspiration. Using ultra- assigned at 3 25 ppm and the CH2 tail groups at colic but who have normal OCG or ultrasound sound guidance, a 21G needle was aimed 1-25 ppm. PL and chol resonances from is a useful diagnostic procedure. transhepatically into the gall bladder and up to vesicles were broad due to short T2 relaxation 10 ml of bile were aspirated. At cholecystec- times reflecting constrained molecular motions tomy (the same day) any blood or bile leakage in the vesicle. It was possible to quantify was noted and a further sample of GB bile was resonances with an external reference. Gall stones - a disease ofnon-smokers? collected. This was compared microscopically In conclusion, chol and PL can be more with the first sample to ensure GB bile had been confidently identified using 2D COSY NMR M RHODES, C W VENABLES (University Depart- aspirated preoperatively. and their distribution in the vesicular and ment of Surgery and Freeman Hospital, New- Thirty six patients had an uncomplicated micellar phases of human bile in vitro can be castle upon Tyne) Smoking depresses prosta- transhepatic GB puncture. In four patients determined. glandin synthesis in human gastric and rectal aspiration was unsuccessful. At surgery these mucosa. Such an action in the gall bladder had shrunken thick walled gall bladders would inhibit mucus secretion and this might packed with stones. In another four patients Allele loss of chromosomes 1, 5, and 17 in be expected to reduce gall stone formation. complications occurred - transperitoneal GB cholangiocarcinoma Comprehensive postal questionnaires were puncture and bile leak (3) and liver bleed- sent to 221 cholecystectomy patients (157 ing (1). S-F DING, J DOOLEY, J DELHANTY, L BOWLES, women, 64 men) who were asked to give a We conclude that unless patients have a C WOOD, N A HABIB (Departments ofSurgery and similar questionnaire to a 'buddy' control ofthe thick walled shrunken gall bladder (unlikely in Medicine, Royal Free Hospital School of same sex and age group. those with acalculous biliary symptoms), per- Medicine; Department ofSurgery, Hammersmith The two groups did not differ significantly in cutaneous aspiration of bile is quick and very Hospital; Department of Genetics and Biometry, their weight, past medical history, drug usage, successful. Provided a transhepatic aspiration University College London, London) The aim of or alcohol consumption. Female patients had a is attempted complications occur rarely (3%). this study was to identify consistent changes in mean (SD) of 2-34 (1.8) pregnancies, female Percutaneous bile aspiration may be a valid DNA (allele loss) in cholangiocarcinoma (ChC) controls 2-0 (1-5), (p<0 05, paired t test). alternative to duodenal intubation techniques. which might represent tumour suppressor gene Analysis of smoking habits showed that 32% of loss. We have prepared DNA from tumour and female patients had smoked on average 18-4 non-tumour material from nine patients with cigarettes/day for a mean of 29-9 years whereas ChC. Southern analysis was performed with 27 http://gut.bmj.com/ 54% of female controls had smoked 16-7 Use of one and two dimensional 'H nuclear selected probes assigned to chromosomes 1, 2, cigarettes/day for a mean of37.0 years (p<0-01, magnetic resonance spectroscopy to deter- 3, 4, 5, 7, 9, 11, 12, 13, 14, 16, 17, 18, and 20, McNamars test for matched pairs). Some mine the distribution of cholesterol and and the pattern of banding in tumour DNA 37.5% of male patients smoked (21-7 day for phospholipid between the miceliar and vesi- compared with that in non-tumour DNA. 44-7 years) as compared with 60-9% of male cular phases ofhuman bile in vitro Three probes for chromosome 1 showed allele controls (231l/day for 46 years), (p<0 05, loss in two of five informative cases with McNamars test). J P M ELLUL, H PARKES, G M MURPHY, kMS32; two of two with PB3; and one of five It is concluded that smoking is significantly R H DOWLING (Gastroenterology Unit, UMDS, with kMS1 respectively. Probe kMS8 from on September 24, 2021 by guest. Protected copyright. less common among cholecystectomy patients Guy's Campus, and Department of Chemistry, chromosome five showed allele loss in two of than in asymptomatic 'buddy' controls. This Birkbeck College, London) Cholesterol (chol) in seven informative cases. Allele loss was also supports the hypothesis that gall stones are a gall stones is thought to arise from the vesicular shown with two probes near the locus of p53 disease of non-smokers. rather than the micellar phase of gall bladder tumour suppressor gene on the short arm of bile but conventional analytical techniques chromosome 17 (pl44-D6: two of three; modify the distribution of chol and phos- pYNZ.22: two of five). Screening with other pholipid (PL). To ensure differentiation probes had not shown any consistent allele loss Percutaneous ultrasound guided aspiration between chol and bile acids (similar resonances to date. of bile for crystals in ID NMR) we used 2D COSY NMR. In conclusion, this study suggests that there The 'H spectra of chol (5-15 mmol/l), Na is allele loss in ChC using probes for chromo- S HOSKING, N HACKING, J HERBETKO, K DEW- taurocholate (20 mmolIl), and phosphatidyl- somes 1, 5, and 17 which may play a role in the BURY (Departments of Surgery and Radiology, choline (5, 10 and 20 mmol/l) were studied development ofthis tumour.