Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

Gut, 1986, 27, A 1234-A 1285

The British Society of Gastroenterology

The 1986 Autumn Meeting of the British Society of Gastroenterology was held in Cardiff on 24-26 September 1986 under the presidency of Dr G P Crean. Below are printed the abstracts+of the oral and poster com- munications selected by the BSG Programme Committee for presentation at the meeting.

term. (ii) redissolution of recurrent stones Nuclear uptake of [3H] thymidine signifi- PANCREATICO-BILIARY is highly successful but rerecurrence is cantly increased in the cholecystokinin Wi-5 usual. supplemented human gall bladder epithelial culture when added on initial day of culture WI (p<0.05) or after three days of culture Success and failure in the medical (pultrasound examination was tion (three) and development of symptoms cholecystokinin induced a significant in- arranged plus any other investigations that requiring surgery (five). crease in the cellular uptake of [33Hi thy- were clinically indicated. Gall stone disease By life table analysis the cumulative midine by the guinea pig gall bladder was diagnosed in 26 patients (12% of the recurrence rates±SE were 13±5% at one epithelial cells. 2234+205 to 3011±370 population studied). Other diagnoses in- year, 22±7% at two years, 33±8% at three (mean±SE) (p<0c0l) DPM/,ug DNA six cluded peptic ulcer (n=46), gastro-oeso- years and 48± 10% at four years. Thereafter hours after subcutaneous cholecystokinin. phageal reflux (n=49), irritable bowel syn- recurrence rate levelled out, being 56±11% The significant growth promoting effect drome (n=61) and other diseases (n 38). at nine years. Redissolution was achieved seen at six hours after injection of chole- The only symptom which, in association in all seven patients who had a second cystokinin was maintained up to 48 hours. with upper abdominal pain, significantly course of therapy but the rerecurrence rate Similarly the labelling index rose signifi- increased sensitivity (SS) and specificity was 73±19% at two years. cantly throughout the study period from (SP) in the diagnosis of gall stones was We conclude that (i) about 50% of 0(67±0+24% to 4-01±1 24% (mean±SE) radiation of the pain to the back (20/26 dissolutions remain stone free in the long (p<001) at 48 hours post cholecystokinin. patients, SS=77%, SP=74%, p<0005).

* Because of the time lag between acceptance of abstracts A1234 and the meeting, the data presented at the scientific sessions may not correspond exactly to the information contained in the abstracts. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A1235

Only six of 26 patients had classical biliary D DURRANS, T V TAYLOR, H B TORRANCF activity and dose response studies, using an colic (SS=23%, SP=98°/O). AND H J TESTA (Departments of Surgical ex vivo rat gastric chamber model, on the We conclude that radiation of upper Gastroenterology and Nuclear Medicine, effect of BA's+HCI, on gastric mucosal abdominal pain to the back is a more Manchester Royal Infirmary, Manchester) histology, PD and the 'release' of nucleic sensitive, though less specific, characteristic Diarrhoea is a recognised complication of acids (NA) and acid phosphatase (AP) into of gall stones than is classical biliary colic; both truncal vagotomy and cholecystectomy. the gastric chamber. The sodium salts of that this symptom complex is present in The underlying mechanism is unclear but the prototypic BA, deoxycholic acid (DCA) about 75% of such patients; and that it may relate to the deposition of excessive (0-2, 0.5, 1-0, 2-0 and 5 0 mM) and its should therefore be regarded as an indica- quantities of bile acids on the colonic glycine conjugate (GDCA) (0.5-5.0 mM) tion for abdominal ultrasound examination. mucosa. In this study the SeHCAT retention were studied in groups of six rats, with test, which examines the active terminal 9x 10 min study periods (two equilibration, ileal absorption of cholic acid, was used to one baseline, one BA challenge and five W4 compare bile acid absorption in the follow- postchallenge). The results show that 5 Effect of gastric distension on gall ing six groups, each with 10 subjects: mM DCA induced prompt (5-7 min) loss bladder emptying in man normal controls, patients with and without of transmucosal PD from -30±SEM 4-0 diarrhoea after truncal vagotomy, patients mV (baseline) to -3-6±2 3 mV, followed S ELLENBOGEN, J S GRIMF., M CRIHCIILEY, with and without diarrhoea after chole- by recovery over 40-50 min. The APD C R MACKIE, S A JFNKINS AND J N BAXTER cystectomy, patients after vagotomy and values with 5 mM DCA were 26±3-0 mV, (University Department of Surgery, Royal cholecystectomy. Statistical analysis was by 23±1 3 mV with 2 mM 23±2-8 mV with Liverpool Hospital, Department of Nuclear the Mann Whitney U test. No significant 1 mM, 16±2-5 mV with 0 5 mM, 3-6±0-9 Medicine, Royal Liverpool Hospital) We difference was found in cholic acid retention mV with 0-2 mM, and 1-1±0-7 mV with have investigated a 'gastric' phase to gall between the control group and those follow- saline. A dose dependent increase in NA bladder emptying (GBE) in man using ing either vagotomy or cholecystectomy and AP loss was seen, 5 mM GDCA 99Tcn'-EHIDA cholescintigraphy and bal- without diarrhoea. Bile acid malabsorption produced a loss of PD similar to that loon distension of the stomach. of a degree sufficient to cause bile acid produced by DCA-APD 22±0-7 mV with 5 The gastric stimulus was achieved by induced diarrhoea was seen in all other mM GDCA, 14+1-6 mV with 2 mM, distension of a nasogastric balloon tube groups when compared with both controls 3-5±1 3 mV with 1 mM and 2 0±1-4 mV with 500 ml water at 37°C over a 20 minute and the uncomplicated operation groups with 0-5 mM. period. The study was done on nine fasted (p<0.001 all groups). We conclude that studies with this model healthy volunteers (group I), and repeated These results support the idea that bile (i) show its suitability for systematic studies in six healthy volunteers with prior admin- acids are of importance in the aetiology of of the gastrotoxicity of duodenal contents, istration of atropine, 0 6 mg iv and 0)9 mg postvagotomy and postcholecystectomy and (ii) indicate the gastric mucosal toxicity sc (group II). Blood samples were taken diarrhoea. The specificity of the test in of DCA and GDCA. for gastrin radioimmunoassay. Comparison examining terminal ileal absorption of bile http://gut.bmj.com/ has been made with a group of healthy acids indicates an abnormality of small volunteers observed for a variable period bowel function or motility rather than a W7 (134-298 minutes) with a nasogastric tube colonic motility problem. of C-terminal in place and without any form of stimulation Expression flanking (group 111). peptide of human progastrin in human In a 10 minute period, the probability of gastroduodenal mucosa, G cell hyper- spontaneous GBE in group III was 0-09. plasia and islet cell tumours producing

Gall bladder emptying occurred in six of gastrin on October 2, 2021 by guest. Protected copyright. nine (67%) group I volunteers (p<0.(01, BASIC SCIENCE group I vs group III, Poisson Test) and W6-11 M HARA, I M VARNDELL, A E BISHOP, J RODE, none of six (0Oo) group II volunteers S R BLOOM AND J M POLAK (Departments (p=0.03, group II vs group I, Fisher's exact W6 of Histochemistry and Medicine, RPMS, test). In group I, GBE started 8 2±1 9 Ducane Road, London, and The Bland- minutes from the start of gastric distension, Are bile acids gastrotoxic in duodeno- Sutton Institute of Pathology, The Middlesex and from the start of GBE the 20 minute gastric reflux? Dose response and Hospital Medical School, London) gall bladder ejection fraction was 41±6.9%. structure activity studies using an ex Recently, the structure of human progastrin Serum gastrin was significantly raised after vivo rat gastric chamber model was deduced from the nucleotide sequence gastric distension (basal=19 9±3-3 ng/l, of mRNA cloned from human pancreatic post gastric distension=25-2±4-2 ng/l) D ARMSTRONG, M FARRELL, G M MURPHY gastrin producing tumours. In this study, (0O02

A1236 The British Society of Gastroenterology G34. In the gastric antrum, PSN-immuno- lium was mostly restituted in the De-Nol benzimidazole, were investigated against reactivity was colocalised with gastrin in group, but not in the ethanol treated gastric acid and pepsin secretions in con- antral G cells. At the EM level, PSN- controls. We conclude that De-Nol, like scious, gastric fistula cats. Gastric acid immunoreactivity was associated with each prostaglandins, protects the gastric mucosa secretion was stimulated by equisecretory granule type in the antral G cells - that is, by preventing ethanol induced deep (approximately half maximal) doses of both electron-lucent and electron-dense mucosal necrosis and by promotion of pentagastrin, histamine and insulin. granules. Hyperplastic G cells, in endo- mucosal restitution. This is in accordance (Omeprazole, 0-1-2-0 mg/kg, was a potent, scopic biopsies from pernicious anaemia with the postulated role of prostaglandins dose dependent, inhibitor of acid secretion patients, also showed PSN-immuno- in the cytoprotective activity of De-Nol. in the cat. The effects of omeprazole were reactivity. In the duodenum, PSN- and sustained; significant inhibition was still G34-immunoreactive cells were scattered, evident 2-5 hours after a single injection. in contrast with the large number of gastrin W9 Omeprazole was equipotent against acid immunoreactive cells detected by a C- Different mechanisms for gastric secretion stimulated by pentagastrin and terminal reacting gastrin anti-serum. In the mucosal injury by aspirin and sodium histamine (ID50-0 2 mg/kg=0-58 imoUkg). pancreatic tumours, the antisera to PSN, C- salicylate Insulin-stimulated acid secretion required terminal gastrin and G34 revealed a similar, five times the omeprazole dose for equiva- variable pattern of localisation. Thus, we P H ROWE AND W SILEN (INTRODUCED BY lent inhibition (ID50-l10 mg/kg). Pepsin report the existence of C-terminal flanking I MCCOLL (Department of Surgery, UMDS, output stimulated by pentagastrin, and to a peptide of human progastrin in normal Guy's Hospital and Harvard Medical lesser extent insulin, was reduced by ome- gastroduodenal mucosa, G cell hyperplasia School, Beth Israel Hospital, Boston, USA) prazole, probably indirectly as a result of and islet cell tumours producing gastrin. Aspirin (ASA) is rapidly hydrolysed to inhibition of acid secretion. salicylate (SA) in vivo, but both intravenous The hypokalaemic activity of insulin, in- W8 ASA and SA cause haemorrhagic lesions in creasing intracellular K' concentration, or the rat gastric mucosa. The effect of a omeprazole stimulation of K+ secretion, Light microscopic and ultrastructural vascular injury in the development of the may explain the reduced responsiveness of evaluation of rat gastric mucosa protec- haemorrhagic lesions in the gastric mucosa insulin to inhibition by omeprazole. tion by De-Nol by ASA and SA has been investigated using the extravasation of Evans Blue (EB) D W R HALL AND W E VAN DEN HOVEN as an indicator of vascular permeability, (INTRODUCED BY P R SALMON) (Gist- and Monastral Blue (MB) to label dam- Wil Brocades NV, Postbox 1, 2600 MA Delft, aged vascular endothelium. Anaesthetised Gastric mucosal damage by pepsin The Netherlands Visually De-Nol protects pyloric ligated rats were given a bolus of rats gastric mucosa against ethanol damage 100 mM HCI via a nasogastric tube. A LEONARD AND A ALLEN (Department of (cytoprotection), though light microscopic Autopsy was carried out 20 minutes after Physiological Sciences, Medical School,

and ultrastructural features of this protec- an intravenous bolus of ASA, SA or saline University of Newcastle upon Tyne, http://gut.bmj.com/ tion have yet to be documented. Conse- (control). An intravenous bolus of EB or Framlington Place, Newcastle upon Tyne) quently the morphological changes in the MB was given before autopsy. Salicylate Anaesthetised rat stomachs, after oeso- mucosa after De-Nol and ethanol adminis- but not ASA caused an increase in EB phageal cannulation and pyloric ligation, tration were examined. Groups of 10 Wistar concentration in the gastric mucosa com- were instilled with 1 ml buffer pH 2-2 for rats (130-150 g) received De-Nol (120 pared with control (p<005). Salicylate but five successive 30 minute periods. Infusion mg/kg po) or vehicle, and one hour later not ASA or control produced monastral of pepsin (0.5-2 mg/ml) in periods two 1 ml absolute ethanol (ig). At one and six stained blood vessels and this area of the to five resulted in a dose dependent in- hours after ethanol the rats were killed and gastric mucosa correlated with histological creased mucus glycoprotein release (maxi- the stomachs excised. These were then surface injury. Haemorrhagic lesions in the mal mean 1-26 mg) compared with buffer on October 2, 2021 by guest. Protected copyright. filled with buffered formalin and ligated. gastric mucosa caused by SA, but not ASA control pH 2-2 (mean 0-44 mg) over two After 0 5 hour the stomachs were dissected are associated with vascular permeability hours (n>6 all experiments). The adherent along the greater curvature and the mucosa with morphological evidence of an endo- mucus layer on unfixed mucosal sections assessed visually, and by light and scanning thelial injury. This implies different mech- was continuous and unchanged by exposure electron microscopy (SEM). Macroscopi- anisms for the haemorrhagic lesions caused to buffer at pH 2-2 but severely disrupted cally almost complete protection was noted by ASA and SA. and discontinuous after 60 minutes exposure in the De-Nol groups at both times, while to pepsin (2 mg/ml). Mucosal damage by the control groups showed severe necrotic, pepsin (after two hours), visible as lesions, haemorrhagic lesions. Although light W10 was quantified by mean luminal iron con- microscopy and SEM at one hour after Omeprazole is less potent against acid tent 0-05 Ftmol/ml to 0-12 himol/ml in ethanol revealed disruption and desquam- secretion stimulated by insulin periods two and five respectively; no iron ation of the epithelium extending into the was detectable in pH 2-2 controls. Pepsin 2 gastric pits of both groups, De-Nol pro- B H HIRST, E ARILLA, B SHAW AND mg/ml for 30 minutes released means of tected deep pit surface mucus cells and J C WILLIAMS (Department of Physiological 320 ig and 146 ,g mucus glycoprotein from gastric gland cells against injury. Necrotic Sciences, University of Newcastle upon perfused stomach and duodenum respec- lesions were virtually absent after De-Nol, Tyne, Medical School, Newcastle upon tively, in vitro. Smectite, (aluminium: in contrast with mucosa treated with Tyne) The effects of acute, intravenous magnesium:silicate) an anti-ulcer agent ethanol alone. By six hours surface epithe- injections of omeprazole, a substituted administered in vivo two hours previously, Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A1237 significantly reduced this degradation of W13 urea. High gastric juice ammonia concen- gastric mucus by pepsin by 46%. Gastritis associated with campylobacter- trations have been documented in the past These results show: (i) mucosal damage by like organisms in patients with rheu- and been noted to be particularly raised in excess luminal pepsin; (ii) digestion of the matoid arthritis patients with peptic ulcers, the majority of adherent mucus barrier by pepsin in vivo taking non-steroidal whom we now know to be colonised with (normally balanced by mucus secretion); anti-inflammatory drugs Cpyloridis. The possible role of Cpyloridis (iii) an animal model for studying mucosal urease in causing this has been studied by protection against damage by pepsin. R UPADHYAY, A HOWATSON, A MCKINLAY, ammonia genesis studies. Unlike Proteus R D STURROCK, AND R I RUSSELL (Depart- spp, C pyloridis urease requires no inducing ments of Gastroenterology and Pathology, by the presence of urea. Experiments Royal Infirmary, Glasgow) Forty four where live organisms (1-7x 109/ml) were patients with rheumatoid arthritis were incubated with 10 mmol urea at 37°C questioned about upper gastrointestinal resulted in >3 mg/ml ammonia produc- symptoms (and scored). All underwent tion within three minutes of the bacteria endoscopy at which the macroscopic ap- being added. This was associated with a pearance of stomach and duodenum was mean pH rise from 7-2 to 9-6. These data GASTRODUODENAL recorded and two antral biopsy specimens show that C pyloridis produces consider- W12-21 obtained. The presence and severity of able amounts of ammonia. The ammonia gastritis and of campylobacter-like organ- produced beneath the mucus layer may W12 isms (CLO) (using Cresyl Violet Stain) directly or by the resultant pH changes be A new potent cholecystokinin (CCK) were recorded using a scoring system. the mechanism by which these organisms antagonist Campylobacter-like were present in 23 damage the gastric epithelium. of 44 (52.2%) patients. Fifteen of these A MCDONALD, J C BOJARSKI, AND J CALAM patients (65.2%) had significant (score five (Department of Medicine, Royal Post- or more) gastrointestinal symptoms as com- W15 graduate Medical School, Hammersmith pared with six or 21 (28.5%) patients Effect of duodenal ulcer surgery on Hospital, Ducane, Road, London) Chole- without CLO (p<0-05). There was no campylobacter-like organisms (CLO) - cystokinin antagonists could be valuable in correlation between the presence of organ- the role of enterogastric reflux (EGR) pancreatic and biliary disease but pro- isms and the macroscopic appearances at glumide, which has been the best available endoscopy, or with ingestion of any par- ticular non-steroidal anti-inflammatory drug H J O'CONNOR, M F DIXON, J I WYANT, A T R drug, is not sufficiently potent for clinical AXON, D C WARD, E P DEWAR, AND D JOHNSTON use. We have assessed the specificity and (NSAID). Histological evidence of gastritis (Gastroenterology Unit and University potency of CR1392 (Rotta, Milan) - a new was present in 36 patients (81.8%). All Departments of Pathology and CLO positive patients had acute gastritis Surgery, CCK antagonist. http://gut.bmj.com/ in addition to General Infirmary at Leeds, Leeds) The CR1392 (100 ,uM) inhibited responses of (polymorph response) chronic effect of duodenal ulcer surgery on gastric dispersed rat pancreatic acini to CCK gastritis. Only two patients with acute CLO has not been previously assessed. In octapeptide (CCK8). ED50 values were; gastritis were not associated with CLOs. this study 35 DU patients and 54 who had control (C) 15±8 pM, and with drug (D) The results show two subgroups of gas- tritis with undergone surgery underwent gastric biopsy 683±290 pM (mean+SE, n=6, p<0-05, (in patients rheumatoid arthritis and measurement of total bile acid concen- Student's t test). CR1392 (100 FtM), how- taking NSAID) - either positive or negative tration (BAC) in their fasting gastric ever, had no effect on respones to carbachol for CLOs. These cannot be differentiated aspirate. Biopsies were blindly assessed by appearances at endoscopy, and thus for

(C: 190±40, D: 300±100 nM), bombesin the presence of CLO and also scored for on October 2, 2021 by guest. Protected copyright. (C: 230+80, D: 340±150 pM) and vaso- biopsy and staining for CLO is required. severity of reflux gastritis (RG). We have active intestinal peptide (C: 9 6+4-2, D: Gastrointestinal symptoms are strongly previously shown that RG has a character- 12±6-3 nM). Proglumide (100 ,M) had associated with CLO positive patients and istic histology comprising marked foveolar no significant effect on respones to CCK8 this may have therapeutic implications. hyperplasia, oedema, and vasodilatation of (C: 16±7, D: 19±5 pM). the lamina propria, and a paucity of acute CR1392 (10 ,M) also inhibited the direct and chronic inflammatory cells. These five effect of CCK8 on guinea pig gall bladder W14 histological features were each graded muscle (C: 5±2, D: 42±26 nM, n=10, Gastric ammonia production by from 0 (normal or absent) to 3 (severe) and p<0-01) and its nerve mediated effect on Campylobacter pyloridis the sum of the grades used to assign each longitudinal muscle of guinea pig ileum (C: patient a 'reflux score' (0-15). Thirty four 0-9±0-3, D: 21+14 nM, n=6, p<0.05). B J RATHBONE, A W JOHNSON, D TOMPKINS, of 35 DU patients and 15 of 16 after highly Proglumide had no significant effect at R V HEATLEY, AND M S LOSOWSKY (Depart- selective vagotomy (HSV) were CLO- concentrations less than 1 mM. Responses ment of Medicine, St James's University positive compared with only two of nine after to these tissues of carbachol were un- Hospital, Leeds and Department of Micro- Billroth I partial gastrectomy (BIPG), eight affected by CR1392 (10 FM). biology, University of Leeds, Leeds) of 17 after Billroth II PG (BIIPG) and six We conclude that CR1392 is > 100 Campylobacter pyloridis has been isolated of 12 after truncal vagotomy and gastro- times more potent than proglumide and from the majority of patients with chronic enterostomy (TV&GE). Absence of CLO selectively inhibits the responses of pan- gastritis. Although biotypically resembling correlated (p<0001) with high reflux scores creatic acini, gall bladder muscle and other campylobacters, one marked dif- (>10) and increased BAC's (>1 mmolIl). myenteric nerves to CCK. ference is its marked ability to hydrolyse Reflux scores and BAC's were higher Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1238 The British Society of Gastroenterology (p<0-01) after BIPG, BIIPG and TV&GE patients with chronic gastritis. No highly amongst the 20% of patients whose Vagorec compared with both DU and HSV. selective media are available and attempts test suggested total gastric denervation We conclude that DU patients may revert to isolate the organism from sites other could be because of failure of the stimulus from being CLO-positive to CLO-negative than the gastric mucosa have proved unsuc- or failure to detect the intragastric pressure and undergo a transition from CLO-related cessful. A monoclonal antibody specific for rise. We are currently investigating modifi- chronic gastritis to RG after operations C pyloridis would provide an invaluable cations of the test as until it has been made that increase EGR. HSV may protect means for further study of this organism. more reliable it cannot be recommended against these changes in the gastric mucosa. To raise monoclonal antibodies eight strains for wider usage in surgical training. of whole Cpyloridis were innoculated into 10 male Balb/c mice together with B per- W16 tussis vaccine. Sonicated organisms were W19 Campylobacter-like organisms in 'non- used for subsequent booster immunisations. Late complications of partial gastrec- ulcer dyspepsia' Splenocytes from two mice with high serum tomy antibody responses by ELISA were used for the generation of hybridomas. Subse- R P BECHI, U ARENA, G T ROKKAS, C PURSEY, N A SIMMONS, MAZZANTI, M I FILIPE, AND G E SLADEN (Gastroentero- quent screening for Cpyloridis and Cjejuni ARCANGELI, AND P GENTILINI (Istituto di logy Unit, Division of Medicine, Depart- reacting antibodies was carried out by Clinica Medica IV and Istituto di Clinica ments Clinical Bacteriology and Histopatho- ELISA and immunofluorescence on bac- Chirurgica Universita' Degli Studi di logy, UMDS Guy's Hospital, London) terial smears. Antibodies from the hybri- Firenze, Firenze, Italy) This study was Gastric campylobacter-like organisms domas reacting with C pyloridis antigen undertaken to investigate the role of bile (CLO) have recently been identified as a were predominantly non-reactive with Cje- reflux in determining the 'alkaline reflux possible cause of gastroduodenal pathology. juni antigens. It is likely that the specific gastritis syndrome' and to test whether gall The purpose of this study was to determine antibodies produced will be a useful tool stone incidence is increased after partial the prevalence of CLO in non-ulcer dys- in identifying the environmental reservoir gastrectomy. We studied 173 patients who pepsia (NUD) and to related this to histo- and mode of transmission of C pyloridis. had had gastric surgery 10-2() years before logical abnormalities. Forty consecutive pa- hand. All underwent gastric endoscopy, tients (23 men 17 women, mean age 40 yr, nasogastric aspiration and liver ultrasound range 18-65) with upper GI dyspeptic W18 or biliary radiograph. Fasting bile acid symptoms and no recent history of NSAID reflux (FBR), bacterial charge of gastric Limitations of the Vagorec electromoter aspirates and a remnant histology were consumption were studied. All had normal test in assessment abdominal ultrasound and in all upper GI the of proximal gastric assessed in all. Bile acid pattern in gastric endoscopy revealed no significant GI path- vagotomy (PGV) aspirates was determined in 57 randomised ology. Antral biopsies were taken for patients by gas liquid chromatography. http://gut.bmj.com/ bacteriological and histological examination. J DRUMM, I A DONOVAN, J Al EXANDER- Sixty three patients (36%) had developed CLO was cultured in 16 (40%) of the WILLIAMS, P LASARIDES, D BURKETT, gall stones after gastric surgery; the male/ patients. Sixteen (100%) of CLO positive N T DORRICOIrr, AND J G TEMPLE (Dudley female ratio was one. Secondary bile acid patients had gastritis in contrast with only Road Hospital, Birmingham and The were higher than normal (lithocholic and five (20-8%) of the CLO negative patients General Hospital, Steelhouse Lane, Bir- deoxycholic acid were 7% ± 1% and (p<0-001). Positive culture was also asso- mingham) The incidence of recurrent 51%±4% respectively) whether gall stones ciated with sex (60-9% of men were CLO ulceration reported after PGV varies con- were present or not. Bacterial change was positive compared with 117% of women, siderably from one centre to another and increased in gastrectomised patients in on October 2, 2021 by guest. Protected copyright. p<001). Positive cultures were not asso- consequently intra-positive tests for com- comparison with normal. The 110 patients ciated with smoking, alcohol consumption pleteness of vagotomy are being advocated. without gall stones were divided in two or endoscopic evidence of gastritis. We We have been evaluating the Vagorec groups according to the presence of the conclude that there is a strong association electromotor test of the proximal and distal 'alkaline reflux gastritis syndrome' symp- between antral CLO and gastritis in patients stomach. All operations were carried out toms. Fasting bile acid reflux and bile acid with NUD, and a male preponderance by consultants experienced at PGV and no pattern did not show any significant cor- among the CLO positive patients. The further dissection was done irrespective of relation with the severity of symptoms, relevance of these findings to symptoms the test result. Fifty patients were studied endoscopical pictures and histological and to treatment is being explored. and follow up (including endoscopy) has aspects of the remnant mucosa. Moreover, been for a median of 27 months (range a provocative test (Warshaw) did not dis- 13-32). There are six patients with recur- criminate between the two groups. These rent duodenal ulceration, three from 21 results show that gall stone incidence is W17 patients with incomplete vagotomy on test- higher in gastrectomised patients that in a Preparation of monoclonal antibodies ing and three from 10 patients who ap- normal population with a change in the to Campylobacter pyloridis parently had a totally denervated stomach. male/female ratio. Secondary bile acid There are no recurrences in 19 patients increase may contribute to the increased B J RATHBONE, R V HEATLEY, M S LOSOWSKY, with confirmed PGV. In our hands the risk of gall stone. In addition, the concept AND L K TREJDOSIEWICZ (Department of Vagorec test has shown a high incidence of of the 'alkaline reflux gastritis syndrome' Medicine, St. James's University Hospital, incomplete vagotomy (42%). Only half the must be questioned as symptoms were not Leeds) Campylobacter pyloridis has been recurrent ulcers occurred in this group, related with endoscopical and histological isolated world wide from gastric biopsies of however. The misleading responses in pictures. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A1239 W20) treatment on serum gastrin has to be asses- alone so, in the present study, 52 patients Can a poor pharmacological response to sed. We have studied the effect of weekly with autoimmune CAH in remission on P were randomly allocated to receive A cimetidine be overcome by higher dosing three day courses of 20 mg/day omeprazole followed by a four day period without medi- alone (27 patients) or continue on P+A (25 or combination with pirenzepine? cation for four weeks on serum gastrin in 10 patients). At the start, 17 of the A group patients with duodenal ulcer in remission. and 15 of the P+A group were anti-LSP M DEHAKIN, J K RAMAGE, D G COLtIN-JONES, Basal and postprandial serum gastrin con- negative. During a two year follow up, only AND J G WILLIAMS (Departments of Gastro- A RNH Haslar and Queen centrations were measured before (day 1) one patient (in the group) relapsed. enterology, and immediately after the three day course Liver biopsies were carried out in 39 of the Alexatndra Hospital, Portsmouth) In with omeprazole (day 4), and further on 51 patients showing, at worst, features of order to assess the efficacy of high dose day 6 and day 8. immediately before the chronic persistent hepatitis, three on A cimetidine or a cimetidine/pirenzepine next course of omeprazole. In the fourth alone had granulomata. There were no combination in controlling gastric secretion week basal and postprandial serum gastrin significant changes in anti-LSP status in the in refractory duodenal ulcer we have studied concentrations were measured at similar P+A group whereas 21 of the 26 A group the evening and nocturnal intragastric intervals that is, on day 22, 25, 27 and 29. patients who remained in remission showed acidity, nocturnal acid, and pepsin outputs Omeprazole did not induce significant large increases in serum anti-LSP levels, (0030-0730) of nine patients who had a changes in basal serum gastrin concen- from a median of 1:200 (range 1:100- poor pharmacological response to cime- trations. Postprandial increments in serum 1:1400) to 1:1100 (range (1:100-1:2600). tidinc 400 mg (C400) and failed to heal gastrin on day 6 (119±24 pg/ml), day 8 The findings suggest that P acts by sup- duodenal ulcers after six weeks on this (110±21 pg/ml), day 22 (114±20 pg/ml), pressing the autoantibody response while treatment given bd. The patients were day 25 (123±18 pg/ml), and day 27 (141+ A may act directly on K-cells. studied on no treatment, C400 mg, com- 27 pg/ml) were significantly higher than on bination of C400 mg with pirenzepine day 1 (90+22 pg/ml). There was a tendency 50 mg (C40(P5(), or cimetidine 1600 mg to higher basal and postprandial serum gas- W23 (C1600) all given at 2300. Control of hepatitis B virus infection in Median nocturnail pH (25-75th %iles) trin concentrations in the fourth week compared with the first week. It is con- a high prevalence country: a cost was 1-4 (14-7-8) on no treatment, 4-7 cluded that this schedule of intermittent effectiveness study -4 C400 mg, 5.3 (18 8) (3.9-7 8) C40(P50 omeprazole therapy does not result in and 7 2 (6.4-8.1) C1600 mg. Noctural marked basal or postprandial hyper- I N ROSS, P K DASS, A S THAVARASAH, AND pepsin output was: 24-2 (230-95 0) IU on gastrinaemia and may therefore be suitable S S NOOR (University Hospital (Universiti no treatment and 20(7 IU (3.6-37.3) on maintenance with this Sains Malaysia, Kubang Kerian, Kelantan, C400 mg (a non-significant change), 2-1 IU for future therapy drug. Malaysia) Control measures for hepatitis (0-5.25) after C400'P50) (p £250/HBV case prevented compared ance therapy of ulcer patients. Before withdrawal of P, relapse is preceded by a with HBe Ag screening. We conclude that maintenance therapy with omeprazole can rise in anti-LSP. Recent studies suggest (i) prevention of vertical transmission is be advocated, however, the effect of such that remission can be maintained with A unlikely to eradicate HBV in Malaysia, Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1240 The British Society of Gastroenterology because of a large, pre-existing pool of Response was defined as a sustained loss of W27 carriers and a mainly horizontal transmis- the HBe and HBV-DNA. None of the Screening diabetics for haemochroma- sion, (ii) if maternal screening is done, then control patients spontaneously sero- tosis use of HBe Ag is preferrable and, (iii) converted. None of the treated patients resources allocated to screening could be with HTLVIII antibodies responded and six JJ A MCALEER, L INGLES, DR HADDEN, AND transferred to a mass vaccination pro- of the HTLVIII negative patients (33%) M E CALLENDER (Royal Victoria Hospital, gramme when the vaccination cost becomes responded (p<004). The response rate Belfast) One thousand consecutive dia- £3/neonate. was greatest (44%) in the HTLVIII negative betic outpatients had blood taken for serum patients who received 10 mp/m2 of rIFNaA. iron and ferritin and percentage transferrin W24 In the HTVIII positive patients there was saturation. Clinical assessment and repeat Reducing the incidence of non-A non-B no significant difference in HBV-DNA blood samples were carried out on 63 levels after three months when compared patients who had either serum ferritin (NANB) hepatitis in haemophiliacs with pretreatment levels. In contrast, there above the 95th percentile (438 tg/l in men M L FLETCHER, C R RIZZA, AND J M TROWELL was a significant reduction in HBV-DNA and 280 sg/l in women), serum iron above (Oxford Haemophilia Centre and Nuffield levels in the HTLVIII negative patients 35 [tmol/l or percentage transferrin satur- Department of Clinical Medicine, Oxford) after three months of treatment (p<0.05). ation above 70% in men or 60% in women. Fifty patients who had received no blood We conclude that homosexual men are Four were unavailable for review. products in the preceeding year were an important 'at risk' group for hepatitis B For 20 patients repeat results were followed after treatment with factor VIII infection 44% of these patients without normal. Raised results were attributed to or factor IX with serum aspartate trans- HTLVIII infection respond, men with alcohol excess in 17 patients, oral iron aminase estimations at two weekly intervals HTLVIII antibodies are non-responsive to ingestion in two, neoplasm in three and for at least 12 weeks. Twenty patients had interferon. miscellaneous causes in three. received no previous treatment with factor Liver biopsy was carried out on 12 patients and two had precirrhotic hae- VIII or factor IX concentrate. W26 Twenty two of the 50 patients were mochromatosis on histology, supported by treated with factor VIII prepared from Developmental changes in a novel low spectrophotometric iron assay. Of six others small donor pools (373 to 1322 donor units) molecular weight copper binding pro- with raised results, liver biopsy was not with five batches in all. Thirteen had not tein (LMWP) in guinea pig liver clinically justified in four, and two declined previously received factor VIII treatment. biopsy. A further patient had treated hae- Eleven of the 22 patients developed NANB S K S SRAI, C D BINGLE, AND 0 EPSTEIN mochromatosis. hepatitis including six of the 13 previously (Department of Medicine, Royal Free Thus, screening for haemochromatosis untreated patients. This followed treatment Hospital School of Medicine, London) yielded two new cases in 1000 diabetic The evidence that Wilson's disease (WD) patients (95% confidence limits 0-7/1000) with three of the five batches. http://gut.bmj.com/ Twenty eight of the 50 patients were reflects failure to switch from the fetal to with an overall prevalence of 3/1000 studied after transfusion of factor VIII or adult mode of copper metabolism has (1-9/1000), which is in the range reported factor IX heated to 80°C for 72 hours. prompted us to study its ontogeny. We from studies of non-diabetic populations. Seven of the 28 patients were previously have previously reported that the neonatal guinea pig has a copper profile similar to untreated. None of the 28 patients devel- W28 oped hepatitis. WD and that the particulate fraction of An earlier study showed that nine pre- newborn guinea pig liver has a LMWP that Praziquantel - an active scolicidal is not present in adults. This study reports agent viously untreated haemophiliacs all devel- on October 2, 2021 by guest. Protected copyright. oped NANB hepatitis after factor VIII the pre- and postnatal changes in copper treatment. Although reducing the pool size proteins from the particulate fraction of D L MORRIS, D TAYLOR, AND K S RICHARDS reduced the incidence of NANB hepatitis, guinea pig liver. After gel chromatography, (Department ofSurgery, University Hospital, the method of heat treating used appears to copper in the 2-mercaptoethanol solublised Nottingham and Department of Biological have reduced it even more effectively. particulate liver fraction resolves into three Sciences, University of Keele, Keele) There peaks; (i) void volume (VV); (ii) metallo- are as yet few compounds with systemic thionein (MT); (iii) LMWP. Before birth activity against E granulosus. We have W25 LMWP is the dominant copper binding previously used an in vitro culture system Diminished responsiveness of homo- peak with a smaller amount associated with to evaluate the activity of mebendazole sexual HBV carriers with HITLVIII MT and little in the VV. On the day of and albendazole. Live scoleces (E granu- antibodies to recombinant alpha inter- birth LMWP is markedly reduced but MT losus) from ovine pulmonary and hepatic feron is unchanged. In the first 12 postnatal days cysts were maintained in tissue culture, LMWP and MT decrease in parallel with Praziquantel (PRZ) in concentrations of J MCDONALD, L CARUSO, P KARAYANNIS, falling liver copper concentrations. By day 10-1000 ig/l was studied together with L SCULLY, W HARRIS, G FORSTER, AND 28, once adult copper levels are reached, untreated controls. Viability of scoleces H C THOMAS (Academic Department of LMWP and MT are undectable, and copper was assessed by microscopy/eosin exclusions Medicine, Royal Free Hospital, London, is associated exclusively with the VV. The at seven day intervals and confirmed by and St Mary's Hospital, London) Forty parallel disappearance of liver copper and gerbil innoculation. Praziquantel in con- one homosexual men with chronic hepatitis LMWP indicates that this protein may have centrations of 50 [sg/l and above produced a B were randomised into three different a role in copper retention during fetal rapid (three days) reduction in viability of doses of rIFNaA, and one control group. development. scoleces. Almost all treated scoleces were Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A1241 dead by 10 days. Even at concentrations increased but the faecal water content plexus assumes a more regular appearance. below 50 [tg/l significant activity was seen remained unchanged; without Cisapride There have been few reports about the but a dose/speed of action relationship was 61-7%, with Cisapride 63-8% H20. This distal internal anal sphincter, but it is seen. Penetration of PRZ into intact cysts compound has an advantageous effect in commonly stated to be aganglionic. was studied by immersing cysts harvested paraplegic subjects because it increases Smooth muscle from the internal anal from gerbil peritoneal infections in media frequency of defecation, reduces transit sphincter was examined histochemically for containing 2000 [tg/l PRZ, intra cyst con- time, improves rectal tone and does not ganglion cells, using acid phosphatase and centrations were measured by HPLC. Entry cause diarrhoea or sphincteric obstruction. non-specific esterase staining. Ganglion of PRZ was detected within one hour and cells were present in distal sphincter in all equilibration occurred shortly thereafter. specimens examined, scattered in small Electron microscopy of scoleces treated W30 groups, associated with large nerve trunks with PRZ revealed gross damage to the Endoscopic balloon dilatation of colonic running longitudinally along the rectum. tegument. Praziquantel is a very active anastomotic strictures Occasional larger ganglia were found lying scolicidal agent which acts more rapidly between the internal and external anal with sphincters, as apparent continuations of than benzimidazoles. This together N 0 ASTON, W J OWEN, AND D IRVING the rapid cyst entry and known pharmaco- (Lewisham Hospital, London) Anasto- the myenteric plexus, and were also associ- trunks. The kinetics suggest that praziquantel may have motic strictures occur most often in the left ated with large nerve hypo- zone to the anal valve a role in hydatid disease for perioperative colon. Most are caused by ischaemia or ganglionic proximal prophylaxis. anastomotic leakage. Obstructive symptoms line was present in all specimens examined. of distal internal anal develop after surgery or the stricture is Ganglion cells the of enteric neurones seen on a distal loop enema done before sphincter were typical closure of a protective colostomy. The on ultrastructural examination. conventional treatment is resection. Balloon It is concluded that ganglion cells are dilatation is an alternative to surgery. present in the distal internal anal sphincter, are in Using a flexible sigmoidoscope or colono- and that they enteric origin. scope of 0-038 is COLORECTAI, inch guidewire passed W29-34 through the stricture. A 20 mm diameter by 8 cm dilatation balloon is passed over W32 W29 the guidewire. The balloon is filled with Influence of non-steroidal anti-inflam- dilute contrast and the stricture dilated Action of Cisapride on the chronic con- under image intensifier control. A second matory drugs on faecal occult blood tests stipation of paraplegics balloon may be used simultaneously. Seven anastomotic strictures have been dilated. G PYE, K C BALLANTYNE, N C ARMITAGE,

AND J D HARDCASTLE (Department of http://gut.bmj.com/ N R BINNIE, G CREASY, P EDMOND, AND Four have developed postoperative ob- A N SMITH (Wolfson, Gastro-intestinal Re- struction and in three symptoms have Surgery, University Hospital, Nottingham) search Unit, Western General Hospital, resolved completely. There has been only Non-steroidal anti-inflammatory drugs (NSAID) are a well recognised cause of Crewe Road, Edinburgh and Spinal Unit, partial improvement in a patient with a Edenhall Hospital, Musselburgh, Edin- rectal stricture and further dilatation is upper gastrointestinal mucosal damage. burgh) Paraplegic patients have intract- had successful More recently they have been implicated in planned. Three patients the aetiology of small bowel and colonic able constipation. Prolonged intestinal of a stricture dilatation before closure haemorrhage and perforation. Our aim transit and altered rectal compliance may colostomy. There has been no complication be associated with this. The action of Cis-4- from the procedure. Endoscopic balloon was to investigate the effect of NSAID on October 2, 2021 by guest. Protected copyright. - - - - - ingestion on the predictive value of a amino 5 chloro n 2 methoxyhexamide- dilatation of anastomotic strictures is a monohydrate (Cisapride) has been exam- positive faecal occult blood test (FOBT). simple, safe and repeatable procedure that Twenty five thousand asymptomatic indi- ined in six paraplegic subjects, give both may obviate further colonic resection. intravenously (single 10 mg dose) and viduals aged 50-75 years have been screened orally (10 mg 8 hourly). Colonic transit was by FOBT for colorectal neoplasia. Four estimated by subtracting orocaecal time hundred and fifty five patients have had (lactulose and expired H2 method) from W31 positive tests and undergone full colonic oroanal time (radio-opaque markers). The Ganglion cells in the human internal investigation. Fifty of these were taking mean colonic transit time without Cisapride anal sphincter NSAID at the time of the FOBT. In the was 284-5 h; with Cisapride orally this was 405 not taking NSAID, 129 (32%) were reduced to 148-25 h. Rectal compliance N D HEATON, J R GARRE-ir, AND E R HOWARD found to have neoplastic pathology (23 c pressure/d volume (cm H20/ml H20) was (Department of Surgery and Department of carcinomas, 106 adenomas). In the 50 measured in the same six patients using a Oral Pathology, King's College Hospital, patients taking NSAID 11 (22%) had neo- reproducible proctogram method (ref 1). London) The distribution of ganglion cells plastic pathology (three carcinomas, seven The mean was 7-5 with a mean maximum in the internal anal sphincter has been adenomas, one ileocaecal lymphoma). rectal volume of 338 ml; this was reduced investigated in 30 subjects considered to These detection rates are not significantly to 2-8 with a volume of 233 ml after have a normal innervation. Previous studies different (X2=2 03, p=NS). The predictive Cisapride intravenously. There was no have shown that there is a hypoganglionic value of FOBT for colorectal cancer in the significant change in anal sphincter pressure zone extending proximally from the anal non-NSAID group was 5-7% and in the profile. The frequency of defecation was valve line for 1-2 cm, before the myenteric NSAID group 6-0%. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1242 The British Society of Gastroenterology

We therefore conclude that a positive Surgery, University Hospital, Nottingham) pH (Synectics probe) and myocardial per- FOB test in patients receiving NSAID Population screening for colorectal neo- formance in 20 patients with effort angina treatment cannot be attributed to upper GI plasia requires a simple acceptable test and angiographic evidence of coronary mucosal bleeding but should prompt a which is specific and sensitive. Immuno- artery disease. Myocardial performance thorough lower GI examination. logical tests have been developed in an was evaluated by heart rate, blood pressure attempt to improve performance over product (RPP), ECG changes and maximal established chemical tests. Faecal occult effort tolerance. All patients were studied W33 blood tests (FOBT) were offered to 7233 under basal conditions (fasting, no therapy). Evaluation of faecal occult blood tests individuals as part of a screening pro- All had a repeatstudy; 10 (group A) - 30 in symptomatic patients in general gramme for colorectal neoplasia. They minutes after ingestion of a standardised practice were randomly allocated into three groups meal (1078 Kcal, 45% fat); and 10 (group to receive either an immunological FOBT B) immediately after intragastric infusion or a of 300 ml NHCI. No had effort N C ARMITAGE, R LEICESTER, AND J D (Fecatwin/Feca EIA) chemical FOBT 0-1 patient IIARDCASTLE (Departments of Surgery, (Haemoccult) for three or six days. Indivi- induced reflux under basal conditions University Hospital Nottingham and Haslar duals with a positive FOBT were offered whereas reflux occurred in seven of 10 Hospital, Gosport, Hampshire) Faecal colonoscopy. patients in group A, and five of eight occult blood tests (FOBT) in symptomatic Fecatwin/Feca EIA achieved greater patients in group B with acid exposure time of 22% and 28% Mean patients may reduce the time to diagnosis compliance (60(%/) than either three-day respectively. pH or fell from 7 2 to 5 6 of colorectal cancer and adenoma without (54%) six-day (50%o) Haemoccult significantly (basal) group A (p<002) to 4 5 group B (p<001). altering the stage of the cancers diagnosed. (p<0001). The positive rate for three-day Eight hundred and sixty six symptomatic Haemoccult (1-25%) was less than for six- Myocardial performance was similar to or in both groups patients (355 men, 511 women) in general day Haemoccult (2.83%) Fecatwin/Feca- basal levels (Wilcoxon's practice were randomised into test and EIA (3-12%) (p<0-01). Fecatwin/Feca- test). cardiac status is control groups. Test patients were given EIA had the lowest predictive value for These data suggest that three day FOBT and positive cases investi- colorectal neoplasia (carcinomas, adenomas unaffected by large food intake or acid meal gated by lower GI endoscopy and barium > 1 cm) (Feca=19%, three-day Hae- and that myocardial ischaemic threshold is unaltered acid reflux. enema control patients were managed moccult=72% six-day Haemoccult=61 %) by oesophageal routinely by the family doctor. (p

and pH monitoring has not hitherto been on October 2, 2021 by guest. Protected copyright. false negative rate - 27%. The family doctors' provisional diagnoses reported. Conventional manometry and OESOPHAGUS pH monitoring with a combined glass for large bowel neoplasia were correct in W35-38 only eight of 27 (30%) FOBT positive and electrode (GK 2801C) and Synectics digital pH meter were undertaken in 41 globus six of 33 (18%) control group. A positive W35 men, 31 women) aged 28-72 FOBT in a symptomatic patient increases patients (10 the likelihood of neoplastic pathology being Angina pectoris: is oesophageal acid years, in 31 controls (14 men, 17 women) present four-fold and should prompt reflux a factor? aged 21-75 years and in 28 patients with thorough investigation. histologically confirmed oesophagitis (14 B J O'CONNOR, J R LENNON, AND J CROWE mild, 14 moderate/severe) of similar age. (Department of Gastroenterology, Mater The controls were 11 asymptomatic volun- W34 Misericordiae Hospital and University teers and 28 chest pain patients with College Dublin, Ireland) Oesophageal normal manometry, radiology, and distal Comparison of three day Haemoccult, disease is suspected to aggravate angina. oesophageal biopsy. Globus patients also six day Haemoccult and Fecatwin/FECA Recent studies showed that oesophageal underwent videobarium radiology, direct EIA tests for the detection of faecal acid perfusion includes myocardial ischaemia laryngoscopy, rigid oesophagoscopy and occult blood in screening for colorectal and lowers exercise angina threshold in biopsy. Lower oesophageal sphincter pres- cancer patients with coronary artery disease. sures and oesophageal peristalsis were This study examines the effect of normal in the globus group and pH results G PYE, KC BALILANTYNE, N C ARMITAGE, maximal treadmill exercise (Bruce Protocol, (mean % total time pH<4=5-48) did not AND J D HARDCASTLE (Department of 12 lead ECG) on both lower oesophageal differ significantly from the controls (mean Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A 1 243

4.51), nor with age. In oesophagitis patients, Hospital, Liverpool) It is conventional significantly better in group C (-0(26±0+06)t values were significantly greater (mean to position the probe used in oesophageal when compared with groups B (-0(54+±005) 18-55, p<0(0005, Student's t on log trans- pH recording 5 cm above the lower oeso- and A (-0.64+±.04) which were not dif- formed data) and were positively correlated phageal sphincter (LOS). The aim of this ferent. Postoperatively, group B had lower with age (r= 057, p<0 01). Biospy revealed study was to investigate whether probe lactate*, pyruvate*, glucose*, insulin*, and mild laryngitis in two globus patients and position effects the results of 24 h pH higher branched chain amino acidst, total distal oesophagitis in six. Previous reports monitoring, as this may have implications ketonest and urea* than groups A and C. appear to have overestimated the impor- for reproducibility and trials of therapy. Additionally alaninet was lower and free tance of distal oesophageal dysmotility and We studied 10 patients and five controls. fatty acidst and total triglyceridest were GOR in globus pharyngis. All patients had symptomatic gastro- higher in group B than group C. Thus oesophageal reflux and above normal acid group B mobilised endogenous fat but reflux as measured using a standard single failed to spare nitrogen when compared W37 probe technique. Two microelectrode pH with group A. Group B had higher ure- Vertical gastric plication in the treat- probes connected to ambulatory recorders agenesist than group C which produced a ment of gastro-oesophageal reflux - an (Ormed system) were positioned in the better nitrogen balancet for a similar nitro- assessment in the dog and man oesophagus, one at 5 cm, the other at 10 gen intake. This evidence demonstrates the cm above the manometrically determined beneficial effects of TPN and does not T V IAYILOR AND R A KNOX (Department LOS. The recording period was 22 hours. support the use of IAA alone as a post- of Surgical Gastroenterology, Manchester Percentage reflux times (total period. erect operative nutritional regimen. Royal Infirmary, Oxford Road, Manchester) period, supine period) were analysed at the *p<0.05, tp<0001. An operation in which a vertical partition is 5 and 10cm levels for pH 35, pH 4, pH 45 made 5 5 cm in length and parallel to the using two-way analysis of variance for non proximal gastric lesser curvature has been orthogonal data. There was no significant devised to prevent gastro-oesophageal difference between the results at 5 and W40 reflux. The technique which can be simply 10 cm, for either patients or controls. This study has shown that the positioning New serotonin antagonist (ac5HT-M and rapidly done increases the effective blocks length of the 'intra-abdominal oesophagus', of the probe at either 5 or 10 cm above the receptor) diarrhoea in carcinoid the crural sling and mucosal flap valve LOS does not effect the results of oeso- syndrome effect, and the sharpness of the angle of phageal pH monitoring. entry into the gastric reservoir. The ef- M COUPE, J ANDERSON, M BARNARD, ficiency of the lower oesophageal sphincter E ALSTEAD, S R BLOOM, AND H J F HODGSON (LOS) is enhanced by the Bernouille effect. (Departments of Gastroenterology and The gastric cross sectional area along which Enidocrinology, Royal Postgraduate Medi- reflux can occur is markedly reduced by the cal School, Ducane Road, London) The http://gut.bmj.com/ creation of the partition. The stomach is pathophysiology of diarrhoea in the carci- SMALL BOWELNUTRITION noid syndrome is complex, and treatment neither opened nor divided. W39-45 The scientific basis of the operation was frequently unsatisfactory. Serotonin (5HT) established in six dogs which had their has been implicated in this condition. Two W39 classes of 5HT receptor are recognised. lower oesophageal sphincter excised by Intravenous nutrition (IVN) and circular myomectomy before vertical gastric the The SHT-D receptor is the predominant plication; oesophageal pH and manometry metabolic response to surgery form on smooth muscle, and is blocked by studies were carried out and vertical gastric classical serotonin antagonist such as on October 2, 2021 by guest. Protected copyright. plication prevented reflux. The operation H T KHAWAJA, J M JACKSON, S T I'ALBOT, methysergide. The other (5HT-M) is the was done in 17 patients over a two year P C WEAVER, H A LEE (INTRODUCED BY predominant form on enteric neurones, period who were assessed clinically, endo- D G COLIN-JONES) (Departments of Surgery and is unaffected by methysergide. It is, scopically and by 24 h ambulatory pH re- and Metabolic Medicine, St Mary's Hospital, however, blocked by the recently developed cording. Sixteen were classified Visick I Portsmouth) The purpose of this study drug ICS 205-930. or II and ambulatory pH recordings showed was to investigate the effect of short term We studied the effect of 5HT-M receptor IVN on the metabolic response to surgery blockade in three patients with diarrhoea a marked reduction in reflux. The operation with is technically as simple, quick and safe as particular reference to the controversial associated with disseminated neuroendo- inserting an Angelchik prosthesis, early nitrogen sparing effect of peripheral isotonic crine tumours. In one case ot diarrhoea results are encouraging. amino acids (IAA). Forty six patients associated with high circulating VIP con- undergoing elective abdominal surgery were centrations, and normal serotonin metab- randomised into three groups. Group A olism, diarrhoea was unchanged. In contrast (n= in W38 16) received 4% dextrose-saline de- two patients with longstanding carcinoid livering 6 kcal/kg/day. Group B (n= 15) syndrome there was a profound improve- Does the position of the probe effect the received IAA delivering 0()15 g nitro- ment in diarrhoea with both frequency and results of oesophageal pH monitoring gen/kg/day. Group C (TPN, n= 15) received total volume being decreased. Withdrawal a central venous infusion delivering 0 15 g of ICS 205-930 resulted in a return of S J WALKER, S IIOLT, C J SANDERSON, nitrogen and 24 non-protein kcal (50% fat. diarrhoea. This new SHT-M blocker offers C J STODDARD, AND R SIIELDS (University 50% glucose)/kg/day. The cumulative six promise in the treatment of diarrhoea Department of Surgery, Royal Liverpool day nitrogen balance (g/kg±SEM) was associated with carcinoid syndrome. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1244 The British Society of Gastroenterology W41 The effect of autologous peripheral glucosidase activity increased, but there Home parenteral nutrition in children blood T lymphocytes on the Ig secretion of was no difference whether GFIII was with small bowel failure isolated small intestinal mononuclear cells present or not. (IMC) has been examined. Intestinal Gluten toxicity for fetal rat intestine was D A KELLY, J ARMITSTEAD, AND J A WALKER- mononuclear cells were isolated from detected using morphological, but not bio- SMITH (Queen Elizabeth Hospital for endoscopic duodenal biopsies by enzymatic chemical, means. Morphological assess- Children, Hackney Road, London) Home digestion with collagenase (125 IU/ml) and ment was difficult, however, because of parenteral nutrition (HPN) has been suc- density gradient centrifugation. Isolated considerable variability within sections. We cessfully implemented in adults in this IMC were cultured for six days at a do not consider this type of culture to be country but not yet established in young concentration of 2x 105/ml and secreted Ig sufficiently reliable for routine investiga- children. Two children with small bowel was measured by ELISA. Mean values tion of cereal toxicity, and advise caution in failure are reported who have been main- ([ig/106 cells) for IgG, IgM and IgA were the interpretation of the results. tained on HPN for six months. JT (24 0 21±0 08, 3-82±0 83 and 10 33±2-4 months) has microvillous atrophy and out (n=20) respectively. of 20 months of TPN has spent the last six Coculture of IMC with autologous peri- W44 at home. RD (23 months) has a small pheral blood T cells (PBT) in the absence Histological changes in rat small bowel intestinal enteropathy and has had nine of mitogen resulted in enhanced secretion transplants treated with Cyclosporin A months of TPN with six at home. While in of both IgM and IgA, but had no effect on IgG production. The mean percentage hospital nutritional indices (height, weight, A J M WA1SON, P A l EAR, A M P MONTGOMERY, ratio of MAC/HC) improved with caloric increases in IgM secretion at 1:1, 1:5 and 1:10 ratio of IMC:PBT were 71%, R F M WOOD, AND M J G FARTHING (Depart- intake in both children but their psycho- 49%, ments of Gastroenterology and Surgery, St social development was delayed by the and 84% respectively. The percentage increases in IgA secretion were 59% Bartholomew's Hospital, London) We necessary hospitalisation. Before discharge (1: 1), have previously shown that water, elec- developmental delay was assessed at four 109%M (1:5), and 137% (1:10) (p<0.05). Indirect trolyte and glucose transport is reduced in months (JT) and nine months (RD). Com- immunofluorescence showed that rat small bowel transplants. The aim of the plications in hospital included: septic- the T4:T8 ratio of isolated IMC was 1-02:1. These results show that T lymphocytes present study was to establish whether aemia x 5; catheter occlusion x 5; the catheter mucosal damage could account for these was dislodged once and replaced eight exert an immunoregulatory influence on changes. times in a total of 17 months of TPN. At immunoglobulin production by human small intestinal lymphocytes. Jejunal grafts from (LewxBN)Fl donor home, both children have maintained their rats were transplanted into parental strain somatic growth while their psychosocial Lewis rats using microsurgical techniques. development improved dramatically with Control rats had a Thiry-Vella loop con- both children now being developmentally W43 structed from their own jejunum. Both normal for their age. Complications at Organ culture of fetal rat small intestine transplanted and control loops were isolated http://gut.bmj.com/ home included a single episode of sepsis for testing gluten toxicity: a reappraisal from the native gut and so did not receive and two catheter occlusions in 12 months of intraluminal nutrition. Both groups received TPN. There were no major problems with P D HOWDLE, G M WOOD, AND M S LOSOWSKY a seven day course of Cyclosporin A (15 electrolyte disturbance or hepatic dysfunc- (Department mg/kg/day). At nine days there was no tion. In of Medicine, St James's conclusion, HPN should be con- University Hospital, Leeds) Recent difference in villous height or crypt depth, sidered for children with small bowel failure reports of organ culture of animal fetal compared with Thiry-Vella controls despite their limited long term prognosis small intestine to detect cereal toxicity (335-7±17-1 vs 361 9±18 9 and 136 4±8+4 not only because complications are less but have proposed its use for screening the vs 140(2±8+2 ,um, respectively; n=6). Nor on October 2, 2021 by guest. Protected copyright. also because of the dramatic improvement toxicity of cereal peptides for coeliac was there any difference in the number of in psychosocial development and quality of mucosa. Some authors assessed toxicity intraepithelial or lamina propria lympho- life for both parents and children. morphologically, others by more objective cytes (162±1 3 vs 12 3±0+8 cells/100 biochemical means; the results were vari- enterocytes and 8346+816 vs 7800+410 cells/mm-; n=6). At 21 days villous height W42 able. We have used foetal rat small intestine organ cultures to test the toxicity of gluten in Thiry-Vella loops was reduced compared In vitro immunoglobulin production fraction III (GFIII), assessing the effect with nine days (260 0+±83 tim, p<0.05), by isolated human small intestinal morphologically and biochemically. but transplants remained similar to controls. mononuclear cells: evidence for T cell Small intestinal segments from 18 day We conclude that (i) mucosal damage immunoregulation old rat fetuses were cultured with and cannot account for the transport defects in without GFIII for 48 hours. Segments transplants; (ii) defunctioned gut mucosa, J E CRABTREE, R V HEATLEY, AND M S before and after culture were observed as expected, atrophies with time in this LOSOWSKY (Department of Medicine, St histologically and significantly more seg- model and (iii) Cyclosporin A is a potent James's University Hospital, Leeds) Iso- ments developed definite tall villi after inhibitor of rejection in rat small bowel lated human intestinal mononuclear cells culture in the absence of GFIII (p=0-009), transplants. secrete immunoglobulins (Ig) when cul- associated with significantly less stratification tured in vitro. Factors that control intestinal (p=0-014) and more columnar epithelial immunoglobulin secretion, however, are cells (p=0-024). Alkaline phosphatase W45 largely unknown. activity fell during culture, whereas a- Glycine and glucose polymer in oral Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology, A1245 rehydration solution (ORS): efficacy in cells, antibodies were found in serum from dismutase (SOD) contents by an ELISA an animal model of secretory diarrhoea Crohn's patients which reacted with cyto- method (expressed in ng SOD/4g DNA). plasmic antigen; they were shown by Disease activity of the patients was scored R (UNHA FERRERIA, E J EILIO'l-l'. J A immunofluorescence. Antibody was de- by the CDAI. WALKER-SMI'I'Hi AND M J G FARTHING tected in 50% of 71 Crohn's, 16% of 49 Neutrophils of CD patients showed a (Departments of Gastroenterology and with ulcerative colitis, none in 30 with significantly diminished maximum 02 pro- Child Health, St Bartholomew's Hospital, carcinoma colon, none in 30 with pneu- duction (430±23, p<0.05) compared with London) It has been suggested that sup- moconiosis and in 9% of 58 healthy controls. controls (516+25) whereas in UC the plementation of oral glucose-electrolyte Subsequent work showed antigen in 14% overall 02 production was markedly solutions with amino acids improves sodium of 94 normal controls, 5000 of 102 with decreased (range 30±4 to 404±31, and water absorption and that the substitu- Crohn's and 32% of 76 with ulcerative 0(05

Net glucose absorption was greater from level contributing to the inflammatory http://gut.bmj.com/ WHO-ORS (29±1 vs 15±1 stmol/min/g W47 process. dry wt; p<0.01), despite residual free glu- cose (17.3±1.9 mmol/l in the effluent of Impaired activation of the neutrophil gly-ORS rats. Gly-ORS was superior to oxidative metabolism in Crohn's disease WHO-ORS and other commercially avail- (CD) and ulcerative colitis (UC) W48 able ORS tested previously; its apparent Macrophage subpopulations in inflam- beneficial effect on water absorption may HI W VERSPAGFT, J ELMGREEN, A S PENA, I I matory bowel disease be related to mixed solute composition and WETERMAN, AND C B 1i W LAMERS (Depart- on October 2, 2021 by guest. Protected copyright. low osmolality. ments of Gastroeniterology and Hepatology, Y R MAHIDA, P GIONCHETrIT, D VAUX, University Hospital, Leiden, The Nether- S PATEL, AND D P JEWELL (Gastroenterology lands and Department of Gastroenterology, Unit, Radcliffe Infirmary, Oxford) Macro- Herlev Hospital, Copenhagen, Denmark) phages of the intestine are a heterogenous Phagocytosis associated oxygen metabolism population with respect to morphological is crucial in the killing and complete break- and histochemical criteria. This study down of microorganisms by neutrophils. characterises them further using a panel of We have previously shown that neutrophils monoclonal antibodies, both in normal and IBS POSTERS of untreated CD patients produced less diseased colon. The effect of cell isolation W46-50 hydrogen peroxide than controls. In the on the proportion of subpopulations is also present study we determined the neutrophil investigated. W46 oxidative capacity of 30 CD, 14 UC patients Tissue was snap frozen and sections were Does a retrovirus play a role in Crohn's and 18 controls. Cells, obtained by density stained using the peroxidase technique. disease? gradient centrifugation, were incubated with Antibodies:- RFD 1 (interdigitating cells), 5 oxidative stimuli (PMA, con A, zymosan, RFD7 (mature macrophages), RFD9 J SKELLY, M REES, J F WATKINS, AND f-MLP and C5a) and the superoxide anion (epithelioid cells and tangible body macro- J RHODES (University Hospital of Wales, (02) and hydrogen peroxide (HO,) pro- phages), 3G8 (Fcyreceptor on neutrophils Cardiff) In a preliminary study using a duction were measured (expressed in and some macrophages), 3C10 (monocytes cell line (55ME8) which was a hybrid of nmoles/3 x 10)' cells/30 min). Lysates of the and macrophages). For normal colon human rectal carcinoma and mouse embryo neutrophils were analysed for superoxide (n=10), the mean percentage (±SEM) of Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 1246 The British Society of Gastroenterology positive cells in the lamina propria were:- should be evaluated prospectively in in- D WESTABY, P C HAYES, A E S GIMSON, RFD1 - 19% (±1-0), RFD7 - 20% (+1.9), flammatory bowel disease. R POLSON, AND R WILLIAMS (Liver Uniit, RFD9 - 1% (±0.6) 3C10- 26% (±2.2), King's College Hospital and Medical 3G8 - 1% (±0+6). In active ulcerative School, Denmark Hill, London) The colitis (n = 10) and Crohn's disease (n=6), W50 therapeutic alternatives for the use of there was a significant increase in RFD9t Immunological findings in jejunal injection sclerotherapy in the management cells (11% (+1-1) and 8% (±2.0) respec- secretion of patients with Crohn's of variceal bleeding lies between its use tively) and 3G8+ macrophages (8% (±1+5) during active haemorrhage or after tem- and 11% (±2.7) respectively). The RFD9' disease (CD) porary control has been established by cells were largely aggregated in 5 out of 10 conservative methods. In a prospective UC and in all Crohn's tissue, occurring J F COLOMBEL, D DELACROIX, M HALPHEN, randomised trial injection sclerotherapy more frequently in the deeper layers of the C DIVE, AND J C RAMBAUD (INSERM U54, was compared with treatment by a combined lamina propria. Saint-Lazare Hospital, Paris, France and infusion of vasopressin (VP: 0)4 IU/min) These findings were confirmed in mono- Gastroenterology Unit, Catholic University and nitroglycerin (NG: 4t-4t)() tg/min) in nuclear cell isolated from colon of Louvain, Brussels, Belgium) Abnormal 40 patients with 49 episodes of endoscopy suspensions in vitro immunoglobulins (Ig) synthesis and by enzymatic digestion. secretion by intestinal plasmocytes have proven active variceal haemorrhage. been reported in patients with CD. The Patients were observed over a 12 hour aim of this study was to compare jejunal period after randomisation, after which W49 secretion rates of polymeric control of bleeding was assessed endo- IgA(p-IgA), scopically. Patients in the VP+NG group Oral and rectal permeability in monomeric IgA(m-IgA), IgM, IgG and secretory component in 11 were then treated by sclerotherapy as were patients with inflammatory bowel (SC) healthy those in the sclerotherapy group who con- disease volunteers and six CD patients free of lesions of jejunal biopsies and having no tinued to bleed. At 12 hours bleeding was active treatment. controlled in 21/27 (78%) of episodes R T JENKINS AND J K RAMAGE (INTRODUCED jejunal was carried treated by sclerotherapy compared with BY R H HUNT) (Intestinal Disease Research Segmental perfusion 12/22 (56%) in the VP+NG group (p<(0)5). Unit, McMaster University Medical Centre, out using a four lumen tube. The infusion was located near the Definitive control of bleeding during the Hamilton, Ontario, Canada) Increased point duodenojejunal admission was achieved in 26/27 (96%) of urinary excretion of 5'Cr-EDTA after oral junction above an occlusive balloon. Distal the sclerotherapy group and 19/22 (866%) of administration has been found in patients collection point was 40 cm below. The intestine was with a 115 mM the VP+NG treated episodes (NS). with Crohn's disease (CD), but studies of perfused Admission mortality was 6/27 (22%) and patients with ulcerative colitis (UC) have NaCl, 10 mM KCI and 35 mM mannitol 7/22 (32%o) respectively (NS). Although results. We solution with PEG 4000 (1 g/l) as a dilution yielded conflicting investigated http://gut.bmj.com/ marker. After a 60 min the overall control of bleeding and admis- whether the inflamed colon shows increased equilibration period sion mortality did not significantly differ permeability. Groups studied were: (a) 12 four 20 min samples were collected. Con- centrations of Ig and SC were measured for the two regimens sclerotherapy as a controls, (b) 12 patients with small bowel by single measure during active variceal bleed- CD, and (c) 15 patients with colitis (eight immunoradiometric assay and proportions of p-IgA and m-IgA by a sucrose den- ing proved highly successful and consider- CD colitis, five total UC and two left sided ably reduces the need for other measures. UC). 5'Cr-EDTA (25 [tCi) was given on sity gradient ultracentrifugation. Results: separate occasions either orally in a bland jejunal secretion rates (p.g 40 cm-') fruit drink or rectally in normal saline via (mean± SEM 1) controls (n = li ); p - IgA W52 on October 2, 2021 by guest. Protected copyright. 30 cm 8F catheter. Urine was collected for 220+44; m-IgA: 18 4+3; IgM 25+4; 24 h, and the total volume was counted. IgG 40+6-2; SC: 363+69 2 CD (n=6); Prospective randomised trial of Excretion (median, range) after rectal p-IgA 152±24 (p<001 vs controls at chronic sclerotherapy to prevent vari- administration to each group was: (a) Student's t test); m-IgA 18±3; IgM ceal rebleeding using the same protocol 0.7%/24 h (0.1 1-6), (b) 0 9%/24 h 37+10; IgG 53+11; SC 379±80. to treat bleeding. Interim analysis (0.2-3-5; p=NS); and (c) 6.6%/24 h (1 2- We conclude that polymeric IgA secretion is lowered in patients with CS. As p- IgA is 21 6; p<00001). After oral dosing, excre- A K BURROUGHS, F D IIFYGERE, A PhIlLLIPS, the main component of intestinal Ig tion was: (a) 1-2%/24 h (06-2-8), (b) secre- J DOOLEY, 0 EPSTEIN, AND N MCINTYRE 288%/24 h (0-8-14-0; p<0l0001), and (c) tion, our study supports the hypothesis of (Academic Department of Medicine and 6 1%/24 h (0.9-28.3; p<00001). No sig- an abnormal intestinal immune response in Clinical Epidemiology, Royal Free Hospital, nificant difference was found between CD CD. London) All but one of the controlled colitis and UC groups either orally or rec- trials of chronic sclerotherapy (CS) have tally. We conclude that in colitics abnormal used different emergency treatments at permeability is shown by both oral and varying time points for variceal rebleeding rectal tests. This indicates the colon is an in the control and sclerosis groups. Different important site of increased permeation. BSG/BASL treatments can cause different early mor- The oral test discriminates patients with W51-62 tality and early rebleeding rates. The effects colitis from controls as well as the rectal CS may be obscured by therapy used for test (accuracy 93%). The rectal test dis- W51 acute bleeding. From January 1984 we criminates between small bowel disease Injection sclerotherapy for active randomised 92 cirrhotics after control of and colitis (accuracy 89%). A combined test variceal bleeding: a controlled trial acute bleeding to CS (n=43) or no chronic Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A 1 247 sclerosis (n=49), who werc given sucralfate forming para-oesophageal varices. These small controlled study. We evaluated pro- (SU). Using a standardised protocol for all data may have implications for the develop- spectively intravenous glypressin (2 mg qds variccal bleeding if triansfusion and glypres- ment and rupture of gastrooesophageal for 24 hours) for active variceal bleeding in sin did not control bleeding then emergency varices. cirrhotics during the first 24 hours of sclerosis or oesophageal staple transection admission using a standardised protocol. were used in a randomised order. Charac- Study population: 208 admissions: Pugh's teristics of the index bleed and time to W54 grade A (47), B (82), C (79). Glypressin randomisation were well matched between Placebo controlled trial of glypressin in was not used in 132 admissions: eight due the two groups but mean Pugh's score was the management of acute variceal to terminal disease, seven balloon tampon- different: CS=7-95, SU=9 14. Fifty six bleeding ade used first, and in 117 glypressin was not episodes of variceal bleeding occurred in required. In 76 admissions (41 alcoholics) the SU group versu.s 45 in the CS group. J G FREEMAN, I COBDEN, AND C 0 RECORD glypressin controlled bleeding at 24 hours There was no difference between the sur- (Gastroenterology Unit, Royal Victoria In- is only 35 (46/O): 63'% of eight grade A, vival curves analysed by log-rank analysis: firmnar and University of Newcastle uipon 38% of 29 grade B, and 21% of 39 grade C both were very similar to those of sclerosed In the whole Tvne) In an open study we have shown patients. group, control of patients in the controlled trials. These that glypressin is significantly better than bleeding at five days was only 29%, balloon results suggest that if the same management vasopressin in controlling acute variceal tamponade was required in 37%, and 30 day is used for all episodes of bleeding the haemorrhage. The aim of the present study mortality was 22°%. All patients had therapeutic value of adjunctive chronic was to confirm the efficacy of glypressin abdominal colic, two developed heart sclerotherapy may prove to be small. and by means of a double blind placebo failure which in one was secondary to a fatal controlled trial compare therapy with the myocardial infarction. The efficacy of gly- natural history of variceal bleeding episodes. pressin appears no different from vasopres- W53 On entering the study all patients were sin, and is related to the severity of liver Venous drainage of the normal gastro- actively bleeding from varices confirmed disease. These results suggest that ran- by endoscopy. Patients were transfused domised studies of glypressin should be oesophageal junction: a route to under- undertaken to assess its efficacy taking into standing varices and randomised to either 2 mg glypressin or an identical placebo injection, intra- account the severity of liver disease. venously every four hours until bleeding A VIANNA, P hIAYES, CG MOSCOSO, M DRIVER, D WFSiABY, AND R WIl LIAMS (Liver Unit was considered to be controlled followed and Department of Morbid Ancatomy, King's by a further four I mg doses. A Sengstaken W56 College Hospital atId School of Medicine tube was passed if bleeding continued Effects of a somatostatin analogue and Dentistry, Loncdoni) A study into the despite two doses of the drug. Thirty one SMS 201-995 on endotoxaemia in the bleeding episodes in 29 patients were treated.

venous circulation of the GOJ using 52 rat http://gut.bmj.com/ cadavers and three techni- Nine patients were controlled by glypressin complementary (60%), whereas six patients were controlled ques (cast corrosion, and J N BAXTER, S A JENKINS, D W T)AY, radiology by placebo exact AND morphometry) allowed the demarcation of (37%; p> 0(05 Fischer's R SHIFTLDS (Department of Surgery aiTd four distinct venous zones: (a) gastric zone, test). Only two of nine Child's grade B/C were controlled Pathology, University oJ Liverpool, Liver- where the veins lie deep into the submucosa; patients by placebo com- pool) We have recently demonstrated (b) palisade zone, composed of numerous pared with five of seven by glypressin. Deaths were in the that a long acting analogue of somatostatin, narrow parallel longitudinal vessels in the higher placebo group SMS 201-995, markedly stimulates reticu- lamina (25% compared with 13% ). In conclusion, propria; (c) perforating zone, on October 2, 2021 by guest. Protected copyright. one third of loendothelial system (RES) activity in rats. characterised by treble clef shaped veins, bleeding episodes will cease As RES activity is an important defensive which collect and channel laterally blood spontaneously; glypressin appears to be of benefit to patients with mechanism against infection, the aim of the from ascending and descending intrinsic the more severe present study was to investigate if SMS vessels to the extrinsic veins; and (d) hepatic dysfunction. 201-995 could protect against endotoxaemia truncal zone, composed of four or five in rats. Eight male Wistar rats (250 g) deep lying descending large veins, which received 2 tg SMS 201-995 sc 30 minutes drain into the perforating zone. Venous W55 before administration of 20 mg E coli flow appears to be bidirectional at the Prospective evaluation of glypressin endotoxin (026 B6 Bovine) ip. A further palisade zone, a watershed betwcen the for variceal bleeding in cirrhotics 2 p.g of the analogue was given four hours portal and azygos systems. In portal hyper- after endotoxin administration. Control tension this venous system has to accom- F D HEYGERE, A K BURROUG,iS, S SHERIOCK, rats received similar doses of isotonic saline modate an increased cephalad portal venous ANI) N MCINTYRi (Academnic DIepartments sc and endotoxin ip. All rats were bled flow. Preparations from cadavers with of Medicinle anld Surgers', Royal Free Hos- from the tail artery eight hours after gastro-oesophageal varices showed the pital, London) The value of vasopressin endotoxin administration, killed, the livers consequences of this adaptation. Three in controlling aictive variceal bleeding has and kidneys removed, weighed and fixed in avenues of venous drainage were demon- been questioncd recently; its efficacy is formol saline. The livers and kidneys of strated: (1) from the stomach, through the about 50%o in both controlled and un- SMS 20(1-995 treated animals were relatively gastric and palisade zones; (2) from extrinsic controlled studies. Glypressin, a synthetic normal in appearance. In the control veins, through the perforating zone; and long acting analogue of vasopressin was animals, however, the livers were markedly (3) via extrinsic veins alone, thereby more effective than vasopressin in a single congested with conspicuous extravasation Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1248 The British Society of Gastroenterology of red blood cells from capillaries. More- to produce fibrosis and cirrhosis in baboons S IWARSON, R GERFTY, ANI) 1i C TIIOMAS over, the hepatocytes showed marked de- given large amounts of ethanol. Our results (Acadeinic Department of' Medicine, Royal generative changes. Similarly the kidneys suggest that nutrition is important in the Free Hospital, Lonidoni) Using an auto- of control animals displayed lobular necrosis genesis of such changes. logous cytotoxicity system to study 18 and capillary stains. The liver weights, HBsAg/cAg positivc paticnts (CAH) and kidney weight and serum levels of bilirubin nine control subjects (HBsAg/eAg negative and alanine amino transferase with no were signifi- W58 patients significant inflammatory cantly less (p<0)05, Student's t test) in liver disease). Fifteen out of 18 piatients SMS 201-995 treated animals than in Abnormal haem biosynthesis associated showed cytotoxicity indices above the controls. with unconjugated hyperbilirubinaemia normal rainge. By blocking techniques with The results of this study suggest that in the Gunn rat monoclonal antibodies, to HBc (RFHBc17), SMS 201-995 may be of value in protecting HBe (RFHBel), HLA class t (W6/32), Leu against hepatic and renal damage in K EL MCCOLL, F BONI), GG THOMPSON, AND 2 (T8) T cell cytotoxicity was significantly endotoxaemia. M R MOORE (University of Glasgow, inhibited. RFHBcl7 and RFHBel together Department of Medicinle, Westerni Inifirm- resulted in greater inhibition than with ary, Glasgow) Following the observaition either antibody alone. We have also in- of abnormal haem biosynthesis in Gilbert's vestigated the effect of passive administra- W57 syndrome we have studied this process in tion of monoclonal antibodies to HBc and Studies with alcohol in the baboon Gunn rats which have severe unconjugated HBe, on HBV infection in chimpanzees. hyperbilirubinaemia resembling thait in Two animals received the HBV inoculum C AINLEY, A SENAPAII, I M Hi BROWN, Crigler-Najjar syndrome type I. (1(), CID) preincubated with either C A ILES, B M SLAVIN, D R DAVIES, P W N The activities of the enzymes of haem RFHBc17 or RFHBel, and two chimpanzees KEELING, AND R P H THOMPSON (The synthesis, excretion of porphyrins and pre- received HBV alone. Passive immunisation Gastrointestinal Laboratory, Departmenit of cursors, and blood porphyrins were did not protect agiainst intection and in Dietetics, Department of Chemical Patho- examined in eight Gunn raits (mean serum both cases led to an unusually prolonged logy and Department of Histopathology, St bilirubin= 142 FtM, range 95-16(1) and eight hepatitis (> 6 months duration). Thomas's Hospital, London) Lieber and controls (mean serum bilirubin=5 [tM, These data suggest that two populations coworkers have produced alcoholic liver range 3-8). The activity of the penultimate of T cells exist recognising HBe and HBc disease in adolescent baboons, with steatosis enzyme of the haem pathwaiy proto- antigens on the hepatocyte membrane. in all animals and cirrhosis in 33%/. They porphyrinogen oxidase (PROTO.G) was High titre anti-HBc in the serum of piatients gave the Lieber-DeCarli liquid diet with reduced with a mean value of 38%/ of with chronic HBV infection will modulate 50%/ of calories as ethanol, but their controls in liver (p<0'001) and 24% of T cell lysis by cells sensitised to HBc. Thus animals only maintained their weight and controls in kidncy (p<0)001). In keeping HBe is the important target aintigen for did not grow. To examine the role of with an enzymatic partial block in haem cytotoxic T cells mediated liver damage http://gut.bmj.com/ nutritional factors we have attempted to synthesis there was a two-fold increase in during the phase of HBV replication and reproduce these findings. hepatic and seven-fold increase in renal HBeAg/Ab seroconversion. Ten adolescent baboons (colony 1) were activity of the rate controlling enzyme of divided into three groups: two controls; the pathway 5-aminolaevulinate synthase. four ethanol (E); four ethanol+zinc (E+Z). The Gunn rats also had increased urinary W60 All animals received the Mazuri primate porphyrin excretion (mean=302 [tg/24 h vs diet; E and E+Z were started on ethanol - control mean 17(0 sg/24 h, p<0(05) and Influence of epidermal growth factor increasing to 25 g/kg/day (70(% of calories), increased blood porphyrin concentration (EGF) on liver regeneration after on October 2, 2021 by guest. Protected copyright. and E+Z were supplemented with 5() mg (mean 1,167 nM vs control mean 719 nM, partial hepatectomy in rats zinc/day. They were monitored by regular P<0((1). weighing, blood ethanol concentrations, This pattern of enzymatic defect is P SKOV OLSEN, S BOESBY, R KIRKEGAARD, liver blood tests and liver biopsy. Four identical to that found in Gilbert's syndrome K THERKEISEN, SS POULSI-N, AND E NEXO further adolescent baboons (colony 2) were and provides further evidence that uncon- (Department of Surgery C, Rigshospiialei, given the Lieber-DeCarli diet in which the jugated bilirubin impairs haem synthesis by Department of Anatomv B, C'openhagen ethanol content was progressively increased inhibiting PROTO.O activity. This effect and Departmentt of Clinical Chemistry, to 10 g/kg/day. of unconjugated bilirubin may explain its Hiller0d Hospital, Denimark) Epidcrmal Colony 1 have been studied for up to 6(0 neurotoxicity. growth factor stimulates DNA synthesis in months. All animals gained weight normally. cultures of adult rat hepatolcytes. This Blood ethanol concentrations ranged from effect is enhanced in the presence of insulin 63 to 342 mg/dl, and changes in liver blood W59 and glucagon. The effect of EGF on liver tests were small. Two E and four E+Z regeneration after 700o hepatectomy in developed steatosis, which was severe in Cytotoxic T cell responses to the nucleo- rats was investigated. Eight to 32 hours two E+Z, but no fibrosis or cirrhosis was capsid proteins of HBV in chronic after partial hepatectomy the concentration seen in any animal. Colony 2 stopped hepatitis: evidence that antibody of EGF in portal venous blood was un- growing with the introduction of ethanol to modulation may cause protracted in- changed compared with unoperated controls. the diet, and then lost weight as the dosage fection Brunner's glands and the submandibular was increased. glands secrete EGF. Extirpation of Brun- We conclude that we have been unable M PI(iNAIILIl1, J WAIERS, A M L LEVER, ner's glands reduced the median liver Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A1249 regeneration significantly from 3.0(2% tropin has many similarities to peptide the value of propranolol in congestive (2.69-3-37) to 2 45% (2.13-2-72) (wet growth factors but its physico-chemical gastropathy of portal hypertension weight of the liver remnant five days after characteristics are those of a high molecular partial hepatectomy expressed as percent- weight protein. Further study should offer S W HOSKING, H KENNEDY, I SEDDON, AND age of total body weight), while extirpation new insight into control of liver regeneration D TRIGER (University Departments of of the submandibular glands had no effect. after partial hepatectomy. Surgery, Pathology and Medicine, Royal Antibody to rat EGF (ab 3124, 100 1d twice Hallamshire Hospital, Sheffield) Histo- daily (sc) for five days) also reduced liver logical studies have suggested that gastritis regeneration. Oral or sc administration of W62 in portal hypertension is due to submucosal synthetic human EGF (5 nmol twice daily Modulation of hepatitis B virus protein congestion rather than to inflammation; for five days) had no effect on liver expression by interferon (IFN): hom- this has been termed congestive gastropathy. regeneration, but simultaneous sc adminis- ology between the precore region of Because it does not respond to antacid tration of EGF and insulin (15 IU twice HBV-DNA and a sequence regulating therapy we have assessed the effect of daily) or glucagon (100 Ftg twice daily) D-propranolol on the lesion. Twenty four increased liver regeneration significantly to the cellular interferon induced antiviral patients (Child's A 15: B nine) with endo- 5-31% (4 86-6.30) and 4 04% (3.57-4.64) system scopic evidence of chronic gastropathy after five days. Insulin increased liver (present for at least six weeks without regeneration to 3 54% (3.15-4.39) and M PIGNATELLI, A M L LEVER, AND H C evidence of improvement) were given pro- glucagon to 3.35% (2X80-3-95). The results THOMAS (Academic Department of Medi- pranolol (160 mg Inderal LA daily) or suggest that endogenous EGF in combin- cine, Royal Free Hospital, Lonidoni) The placebo, with crossover to the other drug ation with insulin and glucagon enhance viral proteins recognised by cytotoxic after six weeks. The order of drug admin- liver regeneration after partial hepatectomy T cells have been shown to be HBe' and istration was randomly chosen. Endscopic in rats. HBc2. We have investigated the effect of assessment and gastric biopsies were taken (Synthetic human EGF was supplied by IFN on the expression of these proteins in at the start, crossover (six of 52) and end of G.D. Searle Co. Ltd. and Imperial Chemical HBV infected hepatocytes by screening trial (six of 52). Industries, PLC, UK). liver biopsy specimens from 16 untreated Twenty two patients completed the chronic HBV carriers (HBeAg positive) study; two withdrew (one propranolol: one and 13 patients given 7.5-1() PIm2 of placebo). Histology confirmed congestive W61 lymphoblastoid IFN (Wellferon) from two gastropathy in all patients, but consistent to 78 days. changes in response to propranolol were Further characterisation of high mole- Interferon produced an increase in not seen. Macroscopic appearances of mild cular weight hepatotropin induced by HBcAg and a reduction in HBeAg expres- gastropathy (snake-skin and scarlatina) did hepatic resection sion in the cytoplasm and reduced mem- not alter with the active drug, but severe

brane expression of HBsAg in infected changes (cherry red spots) disappeared in http://gut.bmj.com/ CLARE SELDEN, A BALSILI.E, H DARBY, AND hepatocytes. We then sought evidence of four of five patients on propranolol and H J F HODGSON (Department of Medic inle, sequences in the virus genome which might only one of five on placebo. Clinical Royal Postgraduate Medical School, be homologous with IFN sensitive sequences bleeding from gastropathy was seen during Hammersmith Hospital, London) We which have been identified upstream of the trial in only one patient (receiving recently described a high molecular weight several genes encoding for cellular proteins placebo). Because cherry red spots indicate hepatotrophic factor in the blood of man which can be induced by interferon. Such a high risk of gastrointestinal haemorrhage and rats 24 hours after hepatectomy, and sequences were identified in the coding in portal hypertension propranolol may report here further characterisation of the strand of HBV within the precore region play a role in preventing such bleeding. on October 2, 2021 by guest. Protected copyright. rodent substance. SDS-polyacrylamide gel (1821-1834 in adw subtype) and also in the electrophoresis demonstrated two major non-coding strand upstream from the DNA bands, MW 78 000 and 79 000. The pos- polymerase gene (2234-2245 in adw T2 sibility that these were high molecular subtype). Induction weight precursors of Somatomedin peptides We conclude that it is probable that the of remission in primary liver (IGF I and II) was dismissed by the use of HBV sequence showing homology to the cell cancer (PLC) with a new thymi- specific antisera. The radiolabelled hepato- IFN sensitive regulatory sequences of the dylate synthase inhibitor, CB3717. A tropin bound to rat hepatocytes in vitro. cellular genome are responsible for the phase II study Selectivity for stimulation of DNA synthesis effects of HBV protein expression, pro- in hepatocytes, in comparison with fibro- duced by alpha interferon. M F BASSENDINE, N J CURTIN, A L HARRIS. blasts or peripheral blood mononuclear AND 0 F W JAMES (Departments of Medi- cells, was demonstrated in vitro. Primary cine and Clinical Oncology, University of cultures of rapidly regenerating hepatocytes Newcastle uipon Tvne) CB3717 is a new were strikingly more sensitive to the stimu- ,non classical' antifolate which acts by latory effects of hepatotropin than were inhibiting thymidylate synthase (TS), a primary cultures of resting cells ( 1-5 fold at BSG/BASL BASIC SCIENCI pivotal enzyme in the biosynthesis of 27 [tg/ml. 3 5 fold at 67 tg/ml, and 8 fold at TI-12 DNA. We have already shown inhibition 160 Ftg/ml), a phenomenon similar to that of growth of two human PLC cell-lines previously reported for epidermal growth TI both in culture and xenograft models by factor. In its biological et'f'ects this hepato- A double blind crossover trial to assess CB3717. The cytotoxic dose of CB3717 to Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 125() The British Society of' Gastroeniterology PLC cells in vitro lies within that achieved tritiated sodium cyanoborohydride. Ace- 0(9-4-7, p<000 1). Similarly, adrenaline in plasma after intravenous infusion in taldehyde (1 mM) was incubated alone or was greater in ascites (median 0(74 nmol/l, phase I clinical studies. The activity of in the presence of equimolar, or excess range 0-3-2-5) versus either no ascites CB3717 lead to a phase 11 trial. (-5:1 molar ratio) cysteine or penicillamine. (median 0(41, range 0 1-1-6, p<0)005) or We treated 14 consecutive unselected Equimolar cysteine decreased the percent- controls (median 0(29, range t)1-0 9, patients with PLC with 300 mg/m2 IV every age binding from 100±4 8 (mean±SEM) p<0.001). Methionine enkephalin was not three weeks (three died after only one to 589± 108, n=6, p<0 02, and equimolar significantly correlated with either cate- course, max nine courses). There were penicillamine decreased the percentage cholamine. In conclusion. ME was raised eight men, six women, aged 27 to 74 years binding to 55-6±10 2, n=3, p<0 05. When eight-fold in ascites and we suggest that this (mean 56 years); 1 I had cirrhosis, six were both were in excess the binding was com- may be a causative factor in the fluid grade A (expected survival > 14/52, eight pletely inhibited. N-acetyl cysteine and retention of cirrhosis. were grade B (expected survival <14/52). s-methyl cysteine in equimolar amounts Six patients showed objective response caused no inhibition of binding. Therefore (four grade A, two grade B) with both the presence of a free amino and sulphydryl T5 decrease in tumour size (CT scan) arid group are necessary for an inhibitory effect. > 50%° reduction in alphafoetoprotein The inhibition of acetaldehyde binding by A new mechanism of hepatocyte injury (AFP) three of these had > 1 log fall in penicillamine and cysteine could have poten- in acute alcoholic hepatitis AFP; five of six of these were cirrhotic, five tial therapeutic importance in alcoholic liver of six were women; a further male grade B disease. A J K WILLIAMS AND R E BARRY (Depart- patient showed static disease (ST scan, ments of Medicine and Biochemistry, Uni- AFP) during nine courses. Thus of 11 versity of Bristol, Bristol) Acetaldehyde patients receiving >two courses seven T4 binds non-enzymatically with liver mem- showed clinical benefit. The median sur- brane proteins. Acetaldehyde modified vival of the grade A responders from start Is ascites caused by impaired hepatic in- liver membranes stimulate neutrophils in of therapy was 52 weeks, two still alive; the activation of circulating endogenous rat, and activate complement in man. The grade B responders (plus the static patient) opioid peptides? effect on the neutrophil in man has not was 40 weeks. Unwanted effects included been reported. Neutrophilic infiltration of malaise plus nausea (seven), hepatotoxicity J R THORNTON, H DEAN, AND M S l.OSOWSKY the liver is characteristic of alcoholic hepa- (five), stomatitis (two), rash (two), and (Department of Medicine, St Jame.s's Uni- titis. We have studied the effect of renal toxicity (two). Significant myelosup- versity Hospital and Department of Pharm- acetaldehyde-altered liver membranes on pression and alopecia were not encoun- acology, University of Leeds, Leeds) We neutrophil superoxide production in man. tered. TS inhibition is a rational and propose that the liver has a major role in Liver membrane vesicles were prepared effective target in PLC. the inactivation of circulating endogenous from operative biopsies from six patient http://gut.bmj.com/ These results suggest that CB3717 will be opioid peptides. These peptides are potent volunteers who also provided the neut- a useful new therapeutic agent in this vasodilators, and we suggest that ascites rophils. The liver membranes were ex- tumour. Further control trials are indicated. may be a consequence of an imperfect posed to 1 mM acetaldehyde, pH 7-4 for homeostatic attempt to maintain systemic two hours at 37°C with or without reduction blood pressure in response to this vasodi- of the resultant adducts. Identical mem- lation, sodium and fluid retention being branes not exposed to acetaldehyde but T3 mediated by secondary activation of the reduced or left non-reduced were controls. Penicillamine and cysteine protect sympathetic nervous and renin/angiotensin/ The effect of the adduct on neutrophil on October 2, 2021 by guest. Protected copyright. hepatocyte membranes from acetalde- aldosterone systems. superoxide production was assessed by hyde As an initial investigation of this hypoth- measuring cytochrome reduction before esis, we carefully collected plasma samples and after the addition of superoxide dis- A J K WILLIAMS AND R E BARRY (Depart- and measured methionine enkephalin mutase. Acetaldehyde preincubation signifi- ments of Medicine and Biochemi.stry, Uni- (ME) by specific radioimmunoassay and cantly increased superoxide production versity of Bristol, Bristol) AcetaIldehyde catecholamines radioenzymatically, in 20 in response to both the reduced (from binds to liver plasma membranes via the cirrhotics with ascites, 20 cirrhotics without 35-5±7-1 nmol O/IO cells/min to 128+25, formation of an intermediary Schiff base ascites and 15 healthy controls. All subjects mean±SEM, p<0.0l) and non-reduced with the free amino groups of lysine re- had normal plasma creatinine. Methionine membranes (from 17-2+4-3, to 81+17, sidues in membrane proteins. The resulting enkephalin was invariably raised in ascites p<0-() 1). Acetaldehyde alone caused no alteration in the hepatocyte surface inem- (median 299 pg/ml, range 135-755) versus superoxide production. Neutrophil free brane has been shown to activate comple- either non-ascites (median 40, range 3()- radical generation in response to ace- ment in man, cand stimulate the neutrophil 165, p<0(001. Mann-Whitney U test) or taldehyde altered hepatocytes is an impor- in rat. Mercaptans can react readily with controls (median 37, range 3(t-55, p<00())l). tant potential mechanism of injury in aldchydes. We have studied the effect of In three further patients who developed alcoholic hepatitis. two such potential therapeutic agents, cys- ascites, Methionine enkepalin rose on teine and penicillamine on the binding of average 3-7 fold. Noradrenaline (a measure acetaldehyde to the hepatocyte membrane of sympathetic tone) was greater in ascites of the rat. The binding of atcetaldehyde to (median 5 5 nmol/l, range 18-20( 1) versus T6 hepatocyte membranc vesicles wias studied either no ascites (median 2-8, range 16-46, Absorption of biliary cholesterol by using the incorporiation of tritum from p<0).0)()l) or controls (median 1 7, range human gall bladder Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The Briti.sh Society o1 Gastroenterologv A1251

P E ROSS, M R JACYNA, P F A BERRY, M BAKAR, free Ca in gall bladder bile - that is, which may assist cholecystokinin in D HOPWOOI), AND I A D BOUClIIi.R (Depart- [CaT]-[Ca`' ]: [Ca"'], rose exponen- emptying the gall bladder contents during a ments of Medicinie anid Patholoog, Ninewells tially with increasing [BA]. The gradient meal. In addition, gall bladders which Hospital aid Medical School, Dtunidee) (0(081) of this relationship (r=0.79, n=34; secrete Na' appear to have a functional Biliary cholesterol absorption by human p<0.OO1) was much higher than that rather than a structural defect which gall bladder, possibly involved in the acti- (0-032) of T-tube (hepatic) bile (r=0-65, appears to be mediated by chemical factors ology of gall stones and/or cholestcrolosis, n=133, p<0.1) indicating a greater Ca and can be reversed by the addition of was investigated using modified flux binding capacity of gall bladder bile. Poss- indomethacin. chambers. Sodium transport, metabolic ible explanations include the secretion of a rate and ATP levels were measured to Ca binding agent (possible mucus) by the assess viability in over 50 gall bladders gall bladder, thus decreasing the risk of Ca T9 studied. salt precipitation during the concentration Assessment of oesophageal function All gall bladders studied absorbed of bile. Gall bladder bile from patients with using scintiscanning after erradication cholesterol from the mucosal surface at calcified stones (n= 11) did not differ from of varices by chronic sclerotherapy rates ranging from 1-6 nmol/cm'/min and that from patients with radiolucent stones proportional to the cholesterol concentra- to (n=41) with regard [BA] (87.8+SD 51 2 R A J SPFNCE, J A SMITH, S ISAACS, AND Model biles showed a tion. maximal rate of vs 100-3+55-0), [CaT] (5-45±1.9 vs J TERBLANCHE (Department of Surgery, absorption when the lithogenic index 7-1±5-7), [Ca '+] (0-91±0+16 vs 0-88±0-30) University of Cape Town and Department reached 1 -0 although real biles gave in- or the relationships between [CaTI and of Nuclear Medicine and Statistics, Groote creased rates of absorption at lithogenic [BAI. Schuuir Hospital, Cape Town, South Africa) indices greater than 1. Model biles demon- We conclude that these data suggest that Oesophageal function has been assessed in strated differences between the individual disturbances of Ca-BA interactions per se a group of patients with varices who have bile acids but not the glycine - taurine do not play a major role in Ca gall stone had no sclerotherapy (n=15); a group of conjugates. Chenodeoxycholate bile gave formation. patients with erradicated varices (n=29), the highest rae of absorption (2 nmol/cm2/ and a group of age and sex - matched min) compared with 1 nimol/cm2/min for asymptomatic controls. Assessment was cholate biles. done with oesophageal scintiscanning using These results show that human gall T8 Sodium transport in the human gall 17 5 MBq (500 ROCi) Tc"9m tin colloid. Total bladder absorbs cholesterol at rates pro- transit times and individual transit times portional to the cholesterol concentration, bladder: effects of secretin for each one third of the oesophagus were reaching a limit when the model bile measured and compared in the three reached saturation. Real biles allowed M R JACYNA, P E ROSS, C GALLACHER, D IIOPWOOD, AND I A D BOUCIiER groups. When the erradicated group was greater absorption when bile was super- (Depart- compared with the control group total

ments of http://gut.bmj.com/ saturated and may reflect biliary consti- Medicine atnd Radiology, transit time (p=0-0001); upper third tuents not present in model biles. The Ninewells Hospital and Medical School, Dundee) Sodium transport, a principal (p=0-019); middle third (p=0.007) and biliary bile acid composition also affects lower third (p=0-0001) were all significantly rate of cholesterol absorption suggesting function of gall bladder epithelium, was studied by measuring the of 22Na greater in the erradicated group (Wilcoxon- that chenodeoxycholate feeding may alter flux Signed Rank). When the untreated varices gall bladder absorptive function. across isolated human gall bladder mucosa maintained in a modified Ussing' flux group was compared with the control group chamber. Tissue was obtained from total transit time (p=0-022) was significantly cholecystectomy specimens in symptomatic greater in the varices group compared with T7 on October 2, 2021 by guest. Protected copyright. patients with cholelithiasis. In 69 gall blad- the controls but the individual times for Relationships between bile acid (BA), ders studied, 52% had a net sodium (Na ') each one third did not reach statistical total, and ionised calcium (Ca) concen- significance. Fifteen of the 29 patients in flux from mucosa to serosa (Nat absorp- the trations in human gall bladder bile: tion: mean 3.4±0.2 .tEq/cm2/h) whilst 25% erradicated group had all their scler- role in Ca gall stones had a net Na' flux from serosa to mucosa otherapy sessions performed via the flex- secretion: ible scope and their transit times were (Na' mean 4-2±0+6 [tEq/cm2/h). compared with those erradicated uisng the 1) C GLEESON, Y QUERESIII, G M MURPIIY, The 23%o showed no net Na' remaining rigid oesophagoscope (n=14). Transit time AND R 11 DOWLING (Gastroenterology Unit, flux. Net Na' flux correlated with intra- in the lower one third was significantly Guys Campus, UMDS, London) Ca salts luminal bile salt concentration. Indometha- longer in the flexible group. (p=0035) are important constituents of gall stones cin (0-25 mg/ml) added to the serosal (Mann-Whitney U). There was rno signifi- but there are few data on Ca concentra- bathing solution reversed the direction of tions in human gall bladder bile. We found net flux in Na' secreting gall bladders and cant difference in the other transit times. that total [CaT] range 1-8-28 mM and [BA] caused an absorption of Na' Secretin (1 range 12-228 mM concentrations were U/ml) added to the serosal bathing solution significantly correlated (y=2-69e"-'H'", reversed the net flux in Na' absorbing gall T1O r=0-71; p<0)01; n=53), probably because bladders and caused a secretion of Na '. No Controlled trial to assess the patency of of water absorption by the GB. In con- change in sodium flux was induced by these oesophageal varices during maintenance trast, ionised [Ca '] fell slightly with agents in those gall bladders with no initial sclerotherapy increased [BA] (y=1- le"0e0 r -55; net Na' flux. Secretin appears to induce a p<001; n=34). Thus the ratio of bound: secretion of Na' in human gall bladders S W HOSKING, P ROBINSON, AND A G JOHNSON Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1252 The British Society of Gaistroetnterology' (University Surgical Unit, Royal Hallam- 'fibre' (purified wood cellulose) except in T13 shire Hospital, Sheffield) During main- the distal colon where it increased CCPR Cellular basis for impaired colonic Na+ tenance sclerotherapy inadvertant injection (p<001). A more readily fermentable absorption in ulcerative colitis of a thrombosed varix may cause ulceration 'fibre' (purified wheat bran) caused a largc and failure to inject a patent varix, by proliferative response throughout the G I SANDILE ANt) F MCGLONE (Departtnent believing it to be thrombosed, may allow colon and in the distal small intestine of Medicinie (University of Manchester further bleeding. In a pilot study, inter- (p<0.05-p<000l). There was no correla- School of Medicinie), Hope Hospital, Sal- observer variation in diagnosing patency or tion between CCPR and plasma gastrin ford) Diarrhoea in ulcerative colitis is thrombosis was 20%. Using an objective concentrations, but plasma enteroglucagon partly due to impaired colonic Na' and method of assessing patency by measuring levels were significantly correlated with water absorption, but the precise epithelial variceal pressure, we performed a controlled CCPR in almost all the sites studied defect is unclear. Intracellular micro- trial to determine whether this method (p

The British Society of Gastroeniterology A1253 rically for nine hours during fasting and for upright reflux only. Twelve had a poor four hours after a 540 kCal meal. Duo- result because of persistent reflux in nine, Omeprazole versus ranitidine in the denocaecal transit (lactulose-breath H. severe dysphagia in two, gas bloat in one treatment of reflux oesophagitis: a method) was assessed 30 min after the first and intractable post-thoracotomy pain in double blind multicentre trial duodenal migrating motor complex one. In all 12 cases the poor results were (MMC) and 30 min after the meal. This because of technical factors: disrupted or slipped fundoplication in nine, overtightened E C KLINKENBERG-KNOl, J B M J JANSEN, H P protocol was repeated on day 2 during M FESTEN, S C M MEUWISSEN, AND C B H W which a balloon was inflated in the rectum hiatus in two and post-thoracotomy neuralgia LAMFRA (Departments of Gastroentero- for one hour of fasting and for one hour in one. logy, Free University Hospital, Amsterdam, postprandially, starting immediately before In the absence of a gross failure of University Hospital, Nijmegen, University transit determinations. Rectal distension oesophageal peristalsis, pre-operative Hospital, Leiden, Groot Ziekengasthuis, had no significant effect on blood pressure oesophageal manometry and pH studies are not helpful in predicting failure of the s-Hertogenbosch, Holland) Omeprazole or heart rate. During fasting, MMCs were (OME) is the most potent inhibitor of more frequent after the period of rectal Nissen fundoplication. The 15%o incidence gastric acid secretion currently available distension (cycle length 81±34 vs 123±60 of poor results in our study was largely because of technical failures. and may therefore be superior to H,- min; p<0.01). Transit was delayed, how- receptor antagonists in the treatment of ever, (99±30 vs 71±25 min; p<0.05) in reflux oesophagitis. The effectiveness of association with a reduction of duodenal OME in a single, oral morning dose of phase II motility index (66±45 vs 100±48X 60 mg or ranitidine (RAN) 150 mg bd was p<0-0 1). Postprandially, the duodenal T16 studied in a randomised, endoscopically motility index was reduced (24±12 v.s pH Profile of Barrett's oesophagus and controlled, double blind trial. 100±59; p<0-01) during the period of its implications Fifty one patients with macroscopic rectal distension and transit was again oesophageal erosions or ulcerations were delayed (113±22 vs 80±17 min; p<0.01). included: symptoms were recorded daily Proximal GI motor activity, the effector of P GIl LEN, P KEEl INGi, P J BYRNE, A B WEST, and endoscopy was repeated after four AND T P J IIENNESSY (Departments of luminal transit, is profoundly influenced by weeks and, if patients were not healed, distal sensory stimuli. Surgery anid Pathology, St James's Hospital, Dublin) Barrett's oesophagus is generally after respectively eight, 12, and 16 weeks accepted as secondary to gastro-oesophageal with a blind switch to the other modication reflux and may present with strictures, after eight weeks. The healing rate after ulcers or malignant change. Twenty four four weeks of treatment was: 19/25 OME- hour ambulatory pH monitoring was used patients (76%o) versus 7/26 RAN-paticnts to assess the severity of reflux in 21 patients (27%, p=0-002), and after eight weeks three 22/25 OME-patients (88%) versus 10/26 with Barratt's (seven strictures, http://gut.bmj.com/ OESOPHAGEAL-GASTRODUODENAI, ulcers) and the results compared with 25 RAN-patients (38oO, p=0.003). Omepra- T15-28 patients undergoing antireflux surgery for zole was more effective in severe oesopha- severe oesophagitis. All Barrett's patients gitis than RAN. Fifteen patients, not T15 had histological proof of specialised healed with RAN, changed medication to Can failure of the Nissen fundoplication columnar epithelium > 2 cm proximal to OME: 10 patients healed after four weeks be predicted? the gastro-oesophageal junction. The 0o time and 13 after eight weeks. Alternatively, (mean±SEM) pH was <4, was significantly one of three patients, not healed on OME, healed four weeks after switch-over to M M MUGHAL, J BANCEWIC7, AND M MARPLES greater in Barrett's patients than the (INTRODUCED BY M H IRVING) (University oesophagitis group (25,05+3,8 vs 13 0±2 1, RAN. Omeprazole was superior in the on October 2, 2021 by guest. Protected copyright. Department of Surgery, Hope Hospital, p<0(005), as were the number of reflux relief of heartburn (p=0-00(1). There were Salford It is stated that troublesome dys- episodes >5 min duration (11-1±1-5 1'S no side effects of clinical importance. phagia and 'gas bloat' after Nissen fundo- 6-5±1 2, p<0.01). Neither lower oeso- The results of this double-blind study plication is more common in patients with phageal sphincter pressure (12-8+1-6 vs show that OME is superior to RAN in the disordered oesophageal motility, those 14.8±1.8) nor the total number of reflux short term treatment of reflux oesopha- with a mechanically competent cardia and episodes (60,5±10,6 vs 46-1±6-4) differed gitis. the 'air swallowers' who characteristically significantly between the two groups. In only reflux in the upright position. We patients with Barrett's oesophagus acid have tested this concept by analysing clearance is impaired and leads to prolonged according to these three attributes the acid/mucosal contact time. Oesophageal T18 results of the floppy Nissen fundoplication strictures and ulcers and the extent of Laser therapy and intubation for gastro- in 79 patients with proven gastro- columnar change in the Barrett's patients oesophageal malignancy: practicalities oesophageal reflux. was related to the degree of abnormality in and problems At a median follow up period of 32 oesophageal acid clearance. In conclusion, months (range six to 84 months), 66 pa- paticnts with Barrett's mucosa demonstrate N KRASNER, 1I BARR, A I MORRIS, AND R J tients (85%O) had a good result (Visick 1 marked acid reflux and atbnormal acid WALKER (Gastrointestinal Unit, Walton and 2). This included 24/27 (89% ) with clearancc and should be managcd by anti- Hospital, Liverpool) A combination of disordered motility, 19/24 (79%o) with a reflux surgery to avoid potential complica- endoscopic Nd-YAG laser therapy and competent cardia and 20/24 (83%S) with tions. oesophageal intubation was used in the Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 1254 The British Society of Gastroenterology palliation of 25 patients. There were 15 Responsiveness to carbachol returned after (Department of Medicinie, Nationial Uni- men and 10 women of mean age 71 years removal of pepsin. So far, only those com- versitv of Singapore) We have previously (range 65-85). In nine patients severe pounds that stimulated PG secretion, were shown that perfusion of duodenal ulcer dysphagia was encountered after endosco- found to stimulate PG synthesis. (DU) craters with 1()0 ml 0.1, N HCI pic intubation and the laser was required to We conclude that PG synthesis is stimu- reproduced ulcer pain in one third of remove tumour overgrowth in six at the lated after sufficient PG is released; PG symptomatic patients - that is, the last upper end and in one at the lower end of synthesis is under both positive and nega- episode of pain within 24 hours. In the the tube. In an additional two cases, tive feedback control. In vivo, therefore, present study we investigated (1) the effect repositioning of the tube was possible after the chief cell may maintain a constant of acid perfusion on non-symptomatic DU laser treatment. These patients survived, concentration of pepsin, when gastric juice and (2) the effect of an anti-spasmodic on swallowing well, for a further 14 weeks flow is increased by pentagastrin and ex- acid-induced DU pain. Four groups of DU (range 7-26). Another group of 16 patients plain partly in vivo stimulation of PG patients were studied (a) untreated symp- was treated initially with the laser and then release by pentagastrin. The in vitro studies tomatic (b) untreated non-symptomatic (c) subsequently intubated because of the indicate however, that other factors such as unhealed after a course of treatment (d) length of oesophageal stricture (four), vagal tone, are also involved. treated healed. During routine endoscopy rapidity of tumour growth (six) or extrinsic under local anaesthesia, 100 ml 0( 1 N HCI tumour compression (three). Attempted was infused onto the ulcer crater or scar intubation after prior laser therapy resulted using a washing tube. By random allocation, in oesophageal perforation in three pa- T20 group (a) patients were sub-divided into tients. Two died and these had had a Evidence for cholinergic modulation of group (a)l (40 mg buscopan given intra- fibrous stricture. duodenal bicarbonate secretion venously prior to acid infusion) and group Laser treatment is the management of (a)2 (no buscopan). Patients were asked to choice for exophytic tumours and for re- J R CRAMPTON, L C GIBBONS AND, W D W indicate if ulcer pain developed, the person moval of tumour overgrowth of the tube. REES (Department of Gastroenterology, assessing the pain being unaware of the Also, the laser is preferable to intubation Hope Hospital, Salford) Electrical field group each patient was in. The numbers of when the tumour occurs high in the stimulation (EFS) is a technique used to patients developing pain were as follows: oesophagus. Intubation is best applied in provoke release of neurotransmitters of the (a)1 13/33=39'%.,; (a)2 9/26=35%; (b) extrinsic tumour compression, rapidly enteric nervous system. We have recently 2/14=l14%; (c) 1/6=17%; (d) 0/16=0%Yo. growing tumours and poor response to described a new method where EFS is (Group (a)2 versus groups b+c+d-p<0 05; lascr treatment. The combination may used to examine the effect of enteric nerves Group (a)1 versus (a)2-NS. Ninety five prove helpful provided intubation is per- on duodenal bicarbonate secretion and per cent confidence limits=29% in favour formed before the oesophagus is rendered established that EFS is a potent stimulant of (a)2 to 21 % in favour of (a)1). We con- inelastic by laser induced fibrosis. of alkali secretion. A 2 cm segment of bull cluded that (1) acid infusion seldom induced frog (Rana catesbeiana) proximal duodenum pain in patients with non-symptomatic DU http://gut.bmj.com/ is mounted on cannulae so that bicarbonate (2) pain production by acid infusion secretion can be measured by stat titration probably involved a mechanism other than T19 and EFS applied longitudinally by platinum spasm. Pepsinogen synthesis and secretion in electrodes. The response to EFS (50 V, chief cells monolayers 5 Hz, 1 TPS, 0(5 s) consists of a 50±28%/O (n=5, p<0.05) increase in the rate of T22 J DEFILE AND R 1i HUNT (Intestinal Dis- alkalinisation. This response was blocked eases Research Unit, McMaster University by 1( 4 M dinitrophenol (95+13(Yo basal Functional dyspepsia on October 2, 2021 by guest. Protected copyright. Hamilton, Ontario, Canada) To deter- rate, n=6, p<005) indicating its depen- mine whether modulation of pepsinogen dence on oxidative cellular metabolism. It G P CREAN, R J lHOLDEN, RP KNILL-JONES, (PG) synthesis occurs after stimulation of was also abolished by the neural depolaris- AND D SPIEGEIIALTER (The Diagnostic PG secretion, we have studied PG syn- ing agent veratrine, 1() 4 M (95± 18% basal Methodology Research Unit, Southern thesis in canine chief cell monolayers, rate, n=6, p<0(05) and atropine, 10-5 M General Hospital, Glasgow) Functional cultured in 4C labelled amino acid medium. (70±77% bastal rate, n=5, p<0.05) indicat- disorders of the alimentary tract account Stimulation of PG secretion by carbachol ing the existence of enteric cholinergic for as many as 500% of patients seen in our or dbcAMP resultd in a 400=500"o/ in- neurones capable of modulating duodenal clinic, the conditions including irritable crease and caused a 10 fold increase in PG bicarbonate secretion. Further study of the bowel syndrome, abdominal pain for which synthesis. Synthesis returned to basal level response may provide additional infor- no cause can be discovered, and patients after addition of atropine during carbachol mation on the neural control of bicarbo- with upper alimentary symptoms variously stimulation. Pentagastrin enhanced PG nate secretion. classified as functional dyspepsia (FD), or secretion only in the presence of sub- non-ulcer dyspepsia. The symptoms of FD threshold doses of carbachol (165%), but may resemble those of peptic ulcer (PU) had no significant effect on synthesis. and patients are often referred for endo- Histamine did not further increase T21 scopy on this account. Two hundred and pentagastrin/carbachol stimulated release. Further studies on the pathogenesis of ninety three patients with proven PU, and Carbachol stimulated PG secretion and acid induced pain in duodenal ulcer 191 patients with FD are compared. Symp- synthesis were also inhibited by high con- toms which tend to separate FD from PU centrations of pepsin (> 0.5 mg/ml). J Y KANG, R GUAN, H H TAY, AND I YAP include short history, female gender, age Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A 1255 under 30, and pain that is not episodic, not tion and plasma gastrin concentration present study therefore examined directly relieved by belching or by food, and which during omeprazole treatment the response of the H, receptor to stimula- occurs rarely at night. tion by the specific H, agonist, improm- Scores obtained from out extensive data T LIND, M AXELSON, AND 1. OLBE (INIRO- idine (IMP). Five male patients (age 38-62 base on dyspepsia allow the probability of DUCED BY M J DALY) (Department of years) with DU in remission underwent PU to be calculated using 19 indicants. Of Surgery II, Sahlgrenska Hospital, Gothen- IMP stimulated gastric acid studies before 254 patients reaching a probability greater burg, Sweden and Hdssle Gastrointestinal (study day 1) and after (study day 2) three than 3-7 for peptic ulcer, 70% proved to Research Laboratories, Mol1ndal, Sweden) months' RAN 150 mg nocte. Gastric acid have PU, and 12% FD. Of 172 patients Omeprazole (OME), a gastric proton was collected for one hour basal, and reaching very low probabilities for PU (less pump inhibitor, markedly suppresses acid during sequential IMP infusions of 2 5, 5-0 than 0 05), 3% proved to have PU, and secretion over a 24 h period in doses of and 10 0 mcg/kg/h for 9(1 min each. During 23% FD. Of 496 patients reaching in- 20 mg and higher. The purpose of this high dose IMP, 50 mg of RAN was given iv termediate probabilities (p 0(05-p 0-73), study was to investigate the relationship over 5 min, and gastric acid collected 22% had PU and 25% FD. It is suggested between acid secretion and gastrin release during a further two hours of high dose that endoscopy be reserved for this group during OME treatment. IMP. only. In a randomised, double blind, crossover Maintenance RAN treatment resulted in study seven healthy men received placebo, an increase in basal acid output compared T23 5, 10, 20 and 40 mg OME once daily for with pre-treatment from 1. 1±0.5 to Twenty four hour five days. Pentagastrin stimulated (9(1 ,g/h 3-1±1 1 (mean±SE) mmolUh (p=(0 13). intragastric acidity iv) acid secretion (PAO) and fasting Impromidine resulted in a stepwise in- and plasma gastrin concentration be- plasma gastrin concentrations were studied crease in gastric acid secretion to a maxi- fore and during treatment with either six and 24 h after the last dose in each mal of 40-45 mmolUh during IMP 100 ranitidine or omeprazole period. Before the first period, the subjects mcg/kg/h infusion. At each IMP dose, took part in a meal stimulated gastrin test. there was a significant increase in acid S LANZON-MILLER, R E POUNDER, S BALL, M R Omeprazole resulted in a dose depen- output on study day 2 compared with study HAMILTON, N A F CHIRONOS, AND F RAYMOND dent inhibition of acid secretin. 40 mg day 1 -for example, during IMP 10-0 (Academic Department of Medicine, Royal OME inhibited mean PAO by 94 and 61% mcg/kg/h, acid output on study day I was Free Hospital, London) The object of six and 24 h after dose, respectively. 39 3+5-1 mmolUh compared wtih 46-6±7-0 this study was to relate drug induced Gastrin concentrations were not affected mmol/h on study day 2 (p=0-02). Addi- changes of intragastric acidity and plasma until PAO was suppressed by about 80%. tionally, the response to iv RAN 50 mg was gastrin concentration. Twelve patients with This was only observed six hours after accentuated by three months' RAN treat- a history of duodenal ulceration were dosing with 20 and 40 mg OME. Gastrin ment, causing a reduction in acid output to studied under identical conditions for four concentrations during omeprazole treat- 9 1±1 4 mmolUh on study day 1 compared 24 hour periods- before and on the 28th with 4-4±1 8 mmol/h on study day 2 ment were within the same range as those http://gut.bmj.com/ day of oral treatment with either ranitidine observed during meal stimulation. In no (p=0.06). 150 mg bd or omeprazole 20 mg om. After case was massive hypergastrinaemia or In summary, three months' treatment two to six weeks without treatment, the achlorhydria observed. with maintenance RAN 150 mg nocte patients were restudied before and on the We conclude that there is a relationship results in a significant increase in IMP 28th day of treatment with the other drug. between the degree of inhibition of acid stimulated gastric acid output. The ac- Treatment was in a predetermined, ran- secretion caused by OME and the degree centuated response to iv bolus of RAN dom order: morning and evening doses of increase in fasting plasma gastrin con- suggests an increased sensitivity of Ho were taken at 0900 and 2215 h. centration. A level of acid inhibition higher receptors during maintenance H,RA treat- Both drugs were well tolerated: no side than about 80% must be achieved before ment. on October 2, 2021 by guest. Protected copyright. effects were observed. The two before gastrin levels are affected. treatment studies showed virtually identi- cal 24 hour intragastric acidity and plasma gastrin profiles. During treatment with T25 T26 ranitidine 150 mg bd median 24 hour intra- Alteration of H2 receptor sensitivity Tissue oxygen tension measurement in gastric acidity decreased from 48-2 to 21 3 during maintenance ranitidine treat- the human gastrointestinal tract mmol/l and mean plasma gastrin rose from ment 33.7 to 52 4 pmol/l. During treatment with W G SHERIDAN, R LOWNDES, AND H L YOUNG omeprazole 20 mg om, median 24 hour D B JONES, C W HOWDEN, D W BURGET, (University Departmetnt of Slurgery, Uni- intragastric acidity decreased from 51 4 to C SILLETTI, AND R H HUNT (Division of versitv of Wales College of Medicine, Heath 1 6 mmol/l and median plasma gastrin rose Gastroenterology, McMaster University Park, Cardiff) Experimental determina- from 20 5 to 99 8 pmol/l. Medical Centre, Hamilton, Ontario, tion of gastrointestinal tissue oxygen tension Drug induced hypoacidity does raise Canada) Despite maintenance H, receptor (PtO2) has previously been confined to plasma gastrin concentration in duodenal antagonist (H,RA) treatment, 20-30% of animals. In 27 patients undergoing laparo- ulcer patients. duodenal ulcers may relapse per annum. tomy, PtO. was measured at various pre- Although compliance is a major factor in determined sites on the serosal surface of such relapse, it has been suggested that the the gastrointestinal tract using a specially T24 sensitivity of the H, receptor may change constructed modification of a Clark type Relationship between gastric acid secre- during maintenance H,RA treatment. The oxygen electrode. This electrode, incor- Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1256 The British Society of Gastroenterology porating a thermistor for temperature T28 A, hepatitis B, Chlamydia and HTLV III compensation, has been shown to have a Effects of truncal vagotomy and pyloro- antibodies: rectal swab cultures for N gon- linear response to oxygen tension (r=0(995, plasty and highly selective vagotomy on orrhoea, chlamydia and herpes simplex: p<0-001). The patients (age range 26-85 antroduodenal motility and transpyloric stool culture and rectal biopsy. Five pa- years) had an inspired oxygen concentration tients were homosexual, one with HTLV of 30% with a mean arterial PO, of fluid movement III antibodies. Serology was positive for 128±32 9 mmHg (mean±SD). The mea- syphilis (one), hepatitis B (three), hepatitis sured PtO. values (mmHg, mean±SD) P M KING, A PRYDE, AND R C HEADING (De- A (33), Chlamydia (28). Rectal swabs and were: stomach 44.6+13 7, mid ileum partment of Medicine, Royal Infirmary, stool cultures were all negative. Stool 35-4±10-4, terminal ileum 33-5+12-8, Edinburgh) Using real time ultrasound microscopy showed Giardia lamblia (one) caecum 29-3±7-6, transverse colon imaging, the pattern of contractions and and cryptosporidium (one). 36-7±9 8. PtO, measurements at the above fluid movement at the gastroduodenal A random sample of 50 known homosex- sites correlated with arterial PtO. (r=0-70, junction were examined in 10 patients after uals attending the genitourinary depart- p<0(001). Temporary arterial occlusion truncal vagotomy and pyloroplasty (TVP), ment showed positive results for HTLV III resulted in a gradual decrease in measured 10 with highly selective vagotomy (HSV) antibodies (four) serology for syphilis (14), PtO. reflecting the onset of tissue hypoxia. and in 1i) healthy controls given a fluid hepatitis B (13), hepatitis A (one) and In conclusion, tissue oxygen tension mea- meal. Antral peristaltic cycle times were Chlamydia (21). Rectal swab culture was surement in patients using a modified similar in each group, but proximal positive for gonorrhoea (one), herpes Clark electrode is feasible and may have duodenal contractions were seen to follow (three), Chlamydia (three). Stool micro- clinical applications in the per-operative terminal antral contractions less frequently scopy showed cryptosporidium in two. assessment of tissue and organ viability. after TVP (34%0) than HSV (60%0) or Homosexuals with sexually transmitted dis- controls (59%/) (p

The British Society of Gastroenterology A 1257 patients were reviewed, showing a very cells may be implicated in UC. Tobramycin three days incubation with ultrapure human similar age and sex distribution, but 70% has been studied for its ability to remove IL-2 (50 pIml). of the polyps were distal to the splenic these organisms. E coli from 58 patients The results demonstrate that while pa- flexure. with UC were sensitive to Tobramycin. tients with advanced GI cancer possess We conclude that colonic adenomatous Frequency of in vitro mutational resistance only minimally impaired levels of LAK pre- polyps are common in our postmortem to Tobramycin was < 10' . Safety of in cursors (basal NK), lymphocyte prolifer- population and if this incidence is reflected vivo treatment with Tobramycin 120 mg tds ation and the ability to generate cytotoxic in the general population, logistical prob- for seven days and prednisolone 60 mg/day cells (stimulated NK) they remain unable lems will be enormous. was assessed in six patients with severe to generate adequate LAK cell activity. UC. Peak and trough serum levels of We conclude that this may explain the T31 Tobramycin remained 0(5 tg/ml. Mean failure of LAK cell therapy to cause Is the diarrhoea in ulcerative colitis percentage dose urinary excretion at seven regression in some cases of advanced GI related to a failure of colonic salvage of days was 2 56%. HeLa and buccal epithelial cancer and prompts the search for further cell adhesion of patients' E coli were means of augmenting this activity in these carbohydrate assessed before and after treatment. Sero- patients. type of five, and plasmid profiles of the S S C RAO, N W READ, AND C D HOLDSWORTH sixth patient's E coli were determined T34 (Clinical Research Unit, H Floor, Royal before and after treatment. One patient's Hallamshire Hospital, Sheffield) The Is colonic pH important in colorectal serotype and adhesion index did not cancer? normal colon salvages unabsorbed carbo- change. Of those treated one required hydrate by bacterial conversion to short surgery, one had azathioprine and remitted, chain fatty acids, which are rapidly absorbed the remainder responded. No side effects, D F EVANS, G PYE, R BRAMLEY, T J DYSON, T W along with water. In order to determine BALFOUR, AND J D HARDCASTLE (Depart- emergence of Clostridium difficile or ment of Surgery, University Hospital, whether failure of colonic salvage of carbo- Tobramycin resistant E coli were noted. hydrate could contribute to the diarrhoea Nottingham) It has been shown that Tobramycin can safely eradicate adhesive enzymes important in the breakdown of of unabsorbed carbohydrate we investigated E coli, is not significantly absorbed from the effect of a drink containing 20g bile salts to carcinogens in the colon are inflamed bowel, and is unlikely to result in inactivated below pH 6-5. Colonic pH may lactulose on stool output and breath hydro- Tobramycin resistance amongst E coli. gen production in 39 patients with un- therefore be important in the genesis of Eradication of adhesive E coli in UC using colorectal cancer. Intracolonic pH was absorbed carbohydrate subdivided accord- oral Tobramycin would appear to be a safe ing to disease activity and extent and in 13 measured in 21 patients with left sided means of determining their role in this colorectal neoplasia (14 adenoma, seven normal controls. Each subject took a stan- disease. dard diet for four days and stool output was carcinoma, (49-80 years)) and compared monitored throughout. Administration of with 23 normal volunteers (20-85 years) lactulose on day three increased stool pH was recorded for up to 48 hours using http://gut.bmj.com/ weight and frequency in patients with total T33 an ingested radiotelemetry capsule (RTC) colitis (265±143 vs 187±118 g/day, Lymphokine activated killer cell pro- (Remote Control Systems, London) and a mean±SD, p<0)01 and 3 9±2 0 vs 2-6+1-4 duction in with portable recorder (Oxford Medical Systems) patients gastrointestinal colonic transit. was motions/day, p<0O1) but not in patients cancer during pH consistently with distal colitis (137±113 vs 130±84 higher in both patient groups and controls g/day and 1-8±1-7 vs 1-7±1-1 motions/day) on the left compared with the right side of and in normal J R T MONSON, CAROI. RAMSDEN, G R GillES, the colon (p<0.001) (Mean pH left 7-34 subjects (195±103 vs T G BRENNAN, AND P J GUILLOU (Depart- (0.7 SD) right 6-52 (0-62) neoplasia left on October 2, 2021 by guest. Protected copyright. 190± 113 g/day and 1 46±0 5 vs 1-38±1 0 ment of Surgery, St James's University motions/day). The basal and peak hydro- pH 6-75, (0.88), right 6-2 (0.5) normal). Hospital, Leeds) The in vitro stimulation Colonic pH was higher in the cancer gen responses to lactulose in patients with with interleukin-2 of resting lymphocytes group colitis were similar to normal subjects. The (left colon pH 7 48 (0.19) p<0 04, right with natural killer (NK) cell characteristics colon pH 6-65 (0.49) p<0.06) when com- mouth-caecum transit was delayed (p<0-01) results in their proliferation. This sub- in all groups of patients when compared sequently results in the generation of pared with controls. In the adenoma group with normal subjects. Impaired colonic lymphokine-activated killer (LAK) cells, a similar trend was seen but this failed to salvage of carbohydrate could contribute to reach significance (pH left 7 2 (0-71), right which are strongly cytotoxic towards 6-4 the diarrhoea of total colitis but not distal tumour but not normal cells. Re-infusion (0.75). These results suggest that intra- colitis, and this is not due to rapid transit. of LAK cells has colonic pH may be important in the develop- autologous produced ment of colorectal neoplasia and may ex- regression of but not metastatic T32 some, all, plain why carcinomas develop more com- cancer. We have measured LAK precursors monly on the left side of the Eradication of adhesive E coli in ulcer- (NK activity), proliferative responses (Con colon. ative colitis (UC) A stimulated 3H-Thymidine uptake) and LAK cell generation by the lymphocytes T35 D A BURKE, S A CLAYDEN, R W LACEY, AND from 27 control subjects and 27 patients Pararectal lymph node involvement in A T R AXON (Gastroenterology Unit, and with gastric and colorectal cancer (nine rectal cancer assessed by endoluminal University Department of Microbiology, localised, 18 advanced). Cytotoxicity was ultrasound The General Infirmary, Leeds) E coli measured against the NK target K562 and capable of adhering to human epithelial LAK cell target DAUDI before and after J BEYNON, D M A FOY, J L CHANNER, N J Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 1 258 The British Society of Gastroeniterology

MCC MORTENSEN, AND J VIRJEE (Depart- ,non-responders' (<25% clinical or radio- (Department oJ Surgery and Department of ments of Surgery, Medical Physics, Pathol- logical tumour shrinkage). Survival was Oral Pathology, Kinig's College Hospital, ogy antd Radiology, Bristol Infirmary, Bris- significantly (p<0 (4) longer in non-res- Lonidon) Abnormalities of the myenteric tol) Assessment of pararectal lymph node ponders whose CEA fell (median 10(2 m) plexus are increasingly being recognised in involvement in rectal cancer continues to than in non-responders whose CEA did patients with severe bowel dysfunction. be a problem. Previous studies have shown not fall (media 8X0 m). A fall in serum The absence of ganglion cells in Hirsch- digital examination correctly identifies only CEA within two months of starting chemo- sprung's disease is well documented, but as 50% of involved lymph nodes while com- therapy for colorectal carcinoma is a sensi- a consequence the presence of ganglion puter tomography is also disappointing in tive and economical indicator of prolonged cells in colonic biopsies is often assumed to this field. Endoluminal rectal ultrasound survival. exclude significant neuronal abnormalities. has been used to assess the involvement of Fourteen patients presenting with neonatal pararectal lymph nodes in 66 patients with T37 bowel obstruction or severe constipation primary rectal cancer. Examinations have have been diagnosed as hyperganglionosis. been undertaken with a rotating endo- Restorative proctocolectomy: the four All had neonatal onset of symptoms, and prode and 5 5 MHz and 7-0 MHz transdu- Loop W reservoir boys predominated 2:1. Associations with cers. Subsequently 57 resections were done aganglionosis (three), enterocolitis (three), and histological assessment compared with R J NICHOLLS AND D LUBOWSKI (St Mark's anal atresia (one), and Sipple syndrome ultrasonic data. Sonographically, involve- Hospital, City Road, Lonidon) The four (one) were noted. Clinically the appear- ment was correctly predicted in 22 cases loop (W) ileal reservoir was developed ance of a distended abdomen, with palp- with seven false positives, while 24 cases with the aim of improving the functional able faecal masses may suggest agangliono- were negative with four false negatives. results of the J reservoir, and to avoid the sis. Barium enema examination reveals The coefficient of correlation between need for catheterisation often seen with the dilated colon and rectum, but most striking ultrasonic examination and histopathology S reservoir. Sixty four patients have under- are uncoordinated contractions occurring was 0(62 (p<0001). The accuracy for gone the procedure between March 1983 throughout affected colon. Pathological predicting lymph node metastases was and March 1986. There were 28 men and features include the presence of ectopic 810o, the sensitivity 85%, specificity 77% 36 women with a mean age of 31 years ganglia, hyperplasia of the enteric plexuses, and the predictive value 76%. Endolumi- (14-52 years). Fifty seven had ulcerative and increased acetylcholinesterase positive nal rectal ultrasound is an accurate method colitis, six familial adenomatous polyposis, nerves in the lamina propria. Twelve pa- of assessing pararectal lymph node involve- and one functional bowel disease. tients had surgical resections as emergencies ment in rectal cancer and its use pre- Mean hospital stay (including ileostomy or electively to relieve symptoms. Post- operatively enables a more accurate closure) was 24+8 days. Pelvic sepsis operative results were related to the cxtent staging to be carried out. occurred in four cases (6%) and obstruc- of disease and the innervation at the tion requiring laparotomy in eight cases resection margin. Hyperganglionosis is a

(13'%). Other complications included re- http://gut.bmj.com/ T36 recognisable abnormality of hindgut in- operation for bleeding (one), wound infec- nervation, presenting with severe bowel Does a fall in serum CEA after chemo- tion (eight), anastomotic stricture requiring dysfunction. Thus the presence of ganglion therapy for disseminated colorectal dilatation (four). The reservoir has been cells in colonic biopsies does not exclude cancer predict prolonged survival? removed in one patient (one week post- significant neuronal disorders. operatively) with a Dukes' B rectal carci- T G Al l EN-MERSII, D NIED7WIECKI, B SHUR- noma, giving an overall failure rate of GOT, N KEMENY, AND J M DAILY (Memnorial 1 6%. Six patients have not yet had the T39 ileostomy closed and in six it has been Sloan-Ketterinig Canicer Center, New York Autosomal recessive visceral myopathy on October 2, 2021 by guest. Protected copyright. USA) The majority of patients with dis- closed for x /week) 14%. Continence is Royal Postgraduate Medical School, London has assessed the value of a fall in serum completely normal in 92%, and 8% have and Rashid Military Hospital, Iraq) A CEA as a predictor of prolonged survival minor leakage. Twenty per cent use anti- kindred with chronic intestinal pseudo- after starting chemotherapy for dissemi- diarrhoeal medication. Compliance mea- obstruction affecting 11/54 members was nated colorectal carcinoma. CEA was sured in 12 patients (38X5 ml/cm H.O) was studied. Clinically, patients presented with measured in the sera of 329 patients with significantly greater than in 11 patients recurrent intestinal obstruction in childhood an elevated pretreatment CEA who were with J reservoirs (189 ml/cm H,O) or adolescence. Eight of the 11 affected treated with chemotherapy for dissemin- (p<0(01). All patients defecate spon- individuals died before the age of 30. ated colorectal carcinoma. The CEA fell in taneously. Pedigree analysis showed four consan- 7)0% of patients with two months of starting guineous marriages amongst the progeny chemotherapy. Survival in patients whose of the great-great grandparents of the CEA fell (median 12 m) was significantly T38 affected subjects in the fifth generation, (log rank test p<0()-)00l) longer than in Bowel dysfunction in the presence of and established an autosomal recessive patients whose CEA did not fall (X'X m). ganglion cells mode of inheritance. Barium studies Fifty three per cent (93/175) of patients demonstrated dilatation in both large and whose CEA fell after chemotherapy were N D IIE.ATON, J R GARREHI-1, AND E R HOWARI) small intestine. Histological, immuno- Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroetiterology A 1259 cytochemical and electron microscopic the therapeutic effect of anorectal myectomy than one weeks' abdominal pain were studies were performed on a colectomy is merely to reduce resting anal pressure recorded. Junior doctors' diagnostic specimen from one of the surviving aftected and we wonder if these findings might be accuracy with (65 cases) and without (7() family members. Light microscopy showed entirely because of the bivalved oval re- cases) structured computer history sheets fibre degeneration with replacement by tractor used in this procedure. were compared with 1st year clinical collagen and fibrous tissue in both layers of medical students using structured sheets the muscularis propria and the muscularis and a computer system (46 cases). These mucosa. Myenteric plexus ganglion cells T41 students had no previous clinical surgical were normal in number and morphology Postnatal repair and intersphincteric experience. on light microscopy and immunocyto- Ivalon sponge rectopexy for the treat- Doctors' diagnostic accuracy of 51% chemistry. Decreased numbers of epithelial ment of rectal prolapse rose significantly to 69% with the use of endocrine cells containing glucagon, PYY structured history forms (x2 =4-53, p three diagnosis by non-qualified medical staff annum in the two cohorts. Most of the stools per week after operation. There was alcohol associated patients (18 first cohort: a fall in maximal resting anal pressure after P C lAWRENCE, P C CLIFFORD, AND I TAYLOR 38 second cohort) were young or middle operation from 106' 1+±98 to 88X2±22 8 cm (University Department of Surgery, South- aged men. For gall stone and 'non-gall H.O (p=)-058) but the operation had no ampton General Hospital, Soluthampton) stone' associated groups the incidence rose influence on squeeze pressures, length of The aim of this study was to explore the sharply with increasing age for both sexcs. the high pressure zone or rectal sensation. role of computer aided diagnosis for pa- For both cohorts there were large (more The anorectal angle opened during attemp- tients with acute abdominal pain when than five-fold) statistically significant ted defecation by 22 4°+30(3 preoperatively applied by non-qualified personnel. (p<0(OOl) variations in the distribution of compared with 290± 17,3° after myectomy The clinical features of 153 patients pancreatitis within the defined population (NS). These results seem to indicate that (median 35. age ranige 16-92) suffering less area. Moreover, the spatial distribution Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1260 The British Society of Gastroenterology

was very similar for both cohorts with the A P MANNING, 0 R BULGIM-TOMLINSON, D J above 18 000 IU. This sharp pathophysio- highest rate wards clustering in a U shaped LINTO17, AND A T R AXON (Gastroenterol- logical threshold was not seen with similarly area east of the city centre. Investigation of ogy Unit, and Department of Radiology, administered subcutaneous caerulein, which environmental factors suggested that this The General Infirmary, Leeds) Endo- cause a linear progression in the severity of coincides with a particular domestic water scopic retrograde cholangiopancreatography pancreatitis with increasing doses of cae- supply. (ERCP) is a standard technique for the rulein in the range 1-2-74 nmol/kg/h. These This second 1977-83 cohort confirms the investigation of pancreatic disease. Changes findings show, for the first time, the experi- previously reported association with the seen in chronic pancreatitis (CP) are vari- mental induction of pancreatitis by CCK8 domestic water supply and this observation able, but usually include dilatation and in a critically dose-dependent manner with now applies to a 15 year period. The irregularity of the main pancreatic duct a sharp pathophysiological threshold, and incidence of the disease has increased (MPD); although there may be stenoses or suggest that the biological response to the during the study period. obstruction of the MPD its overall width is two peptides in vivo may differ from that greater than normal; side branch changes seen with isolated pancreatic acini in vitro. may include nipping at their origins and T44 dilatation beyond. Occasionally, however, T47 Assessment of pancreatic function there is diffuse and irregular narrowing of using Reduced biliary lipid secretion by nor- bentiromide and p-aminosalicylic acid MPD and side branches giving a 'shrunken' appearance. Of 3529 ERCPs done in this dihydroxy bile acids in rodents I M CHESNER, R A ALLEN-NARKER, N LAWSON, department, 362 have shown changes of G V H BRADBY, B M BUCKLEY, AND J D chronic pancreatitis with six having this J P NEOPTOLEMOS, A F HOFMANN, D GURANTZ, BERG (Department of Clinical Biochemis- 'shrunken' appearance. We present these K PALMER, L R HAGEY, AND A R MOOSSA try and Medicine, Sandwell District General six patients including representative radio- (Department of Gastroeniterology and Sur- Hospital, West Bromwich, West Midlands graphs to illustrate their characteristic fea- gerv, University of California, San diego, and The Metabolic Unit, East Birmingham tures: the MPD is irregular and narrowed USA) Gall stone dissolution by cheno- Hospital, Birmingham) The bentiromide throughout its length and may be shor- deoxycholate (CDC) and ursodeoxycholate test, widely used in the assessment of tened; side branches, often difficult to (UDC) involves reduction of cholesterol exocrine pancreatic function, is based on demonstrate, are narrowed and shortened, (CHO) secretion but the degree of de- the specific hydrolysis of orally adminis- never showing dilatation. All six patients saturation never exceeds 30}40%o and the tered bentiromide by pancreatic chymo- have other confirmatory evidence of CP; clinical results are poor. Biliary lipid secre- trypsin. The p-aminobenzoic acid (PABA) none is alcoholic, one had gall stones, and tion by bile acids (BA) is inversely related released is absorbed and may be measured two have idiopathic inflammatory bowel to the critical micellar concentration in either urine or serum. Its specificity can disease. No other aetiological factors were (CMC). As shortening of the C5 side chain be enhanced by concurrent administration identified. We conclude that there is mor- of natural C24 BAs increased the CMC, the of 14C-PABA, allowing an excretion index phological variant of CP demonstrated at effects on lipid secretion by CDC, UDC for PABA to be derived. We describe a ERCP as a 'shrunken' pancreas which and deoxycholate (DC) wcre compared http://gut.bmj.com/ modified test where p-aminosalicyclic acid usually has no common aetiological asso- with the synthetically prepared C,, nor-BA (PAS), a structural analogue of PABA, ciations. homologues. Studies in the hamster replaces the radiolabel. showed a dramatic reduction of CHO for In control subjects and patients with nor-DC, nor-CDC and nor-UDC when pancreatic disease we have compared ex- T46 compared with DC, CDC and UDC: 10(4 cretion indices for the bentiromide test Hyperstimulation pancreatitis induced vs 7(0, 19-1 vs 4-9 and 11 (0 vs 1-7 stmol using PAS and 14C-PABA. In controls the by CCK8: differing dose response CHO/mmol BA respectively (p<0.0l at mean excretion index PAS was x=90 a using characteristics to caerulein least). There was also marked reduction on October 2, 2021 by guest. Protected copyright. (SD± 12, n=19) and using 14C-PABA of phospholipid (PL) secretion: 66 vs 38, 60 x=94 (SD+ 18, n= 18). There was excellent K SHORROCK, B M AUSTEN, AND J H[ERMON- vs 28 and 57 vs 9-4 Ftmol PL/mmol BA correlation between the two excretion in- TAYLOR (Department of Surgery, St respectively (p<)-01 at least). When the dices (r=0-98, p<0-001, n=32). George's Hospital Medical School, Lon- taurine/glycine conjugates of the C,3 and These results suggest that PAS can re- don) Male CBA mice (19-21 g) were C.4 BAs were compared the reduction in place 14C-PABA in the bentiromide test. given seven, hourly, subcutaneous injec- biliary lipid secretion by the nor-BAs was The bentiromide/PAS test has important tions of sulphated CCK8 amide (Sigma) in maintained. In the rat, nor-BAs induced practical advantages. It does not require a doses from 10-9 nmol/kg/h to 262 nmol/ even less CHO secretion than PL secretion. radiolabel, it removes the necessity for kg/h. Mice were killed nine hours after the In conclusion, nor-dihydroxy BAs are measuring urine volume and only one first dose and blood for amylase (Phadebas) potent biliary cholesterol desaturation analytical technique is required. Also this and pancreas for histology were obtained. agents and warrant further study. approach makes the test more widely Mean nine hour serum amylase did not applicable. exceed twice mean control level at doses of T48 49 nmolUkg/h or less and without micro- scopic evidence of pancreatitis. Doses of Comparison of plasma cholecystokinin T45 CCK8 of 55 nmol/kg/h and higher caused responses to bombesin and food in The 'shrunken' pancreas: a morpho- apparently near-maximal pancreatitis with patients with pancreatic insufficiency logical variant of idiopathic chronic oedema, acinar cell necrosis, and inflam- pancreatitis matory infiltrate and mean serum amylase J B M J JANSEN AND C B H W LAMERS Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A1261 (Departments of Gastroenterology and rats by infection with the parasite, Nippos- 8-4± SD 4-3 fmol/ng protein (33-15.9%) Hepatology, University Hospital, Leiden, tronglyus brasiliensis. Preliminary studies and after adding 100 nmoles CCK.-SO4, The Netherlands) This study was under- by gavage showed an increased 24 hour reversible receptor binding was 41+12-8% taken to compare the stimulatory effects of excretion at eight to 10 days postinfection of total, but enrichment of the fraction with food and bombesin on plasma CCK in nine compared with controls (2.5 vs 1-6, mean 5'-NT was poor. With both 25 000 and patients with steatorrhoea due to pancrea- % of dose, p<0.05). Thus animals were 200 000 g ultracentrifugation, there were tic insufficiency and nine normal subjects. studied at three stages of infection: early membrane ribbons and vesicles by EM, Pancreatic enzyme supplementation was (seven days), acute (10 days) and post- a 3-5 fold enrichment of 5'-NT; 06- stopped at least three days before the inflammation (21 days). Controls were 2-8 fmol/mg prot. (13-23-2%) total CCK studies. Plasma CCK concentrations were non-infected littermates. Five tCi of 5'Cr- binding, of which 51-90% was reversible. measured by radioimmunoassay using anti- EDTA was injected into a 15 cm ligated These preliminary studies have shown for body T204, which binds to carboxy- loop of jejunum in anaesthetised rats. the first time in man, CCK binding by gall terminal CCK-peptides containing the sul- Hydration was maintained by iv saline, and bladder myocyte membranes similar to that phated tyrosine region. There were no at five hours the urine, one kidney and the reported in animals. These methods will be significant differences in basal plasma CCK intact loop were counted. Mean±SEM, % used to correlate CCK binding with in vivo levels (2.8±0.4 and 2-3±0 4 pM in pan- of administered dose in urine (n=6) were: and in vitro studies of gall bladder contrac- creatic insufficiency and 2-4±0 3 and controls 3-4+0-6, seven days 5 4±0 9, 10 tion in man. 2-9±0 5 pM in normal subjects). Ingestion days 6 1±0 6 (p<.)05 vs control), 21 days of a liquid test meal induced significant 2-4±0-3. Kidney counts followed the same increases in plasma CCK in both the trend, higher at 10 days (p<005); counts patients with pancreatic insufficiency and in the gut did not change significantly. the normal subjects. The integrated meal- Myeloperoxidase activity was increased in T51 stimulated plasma CCK secretion in jejunal mucosa in the acute stage whereas Mucus glycoprotein degrading enzymes patients with pancreatic insufficiency sucrase was decreased. Ligated loops of in inflammatory bowel disease detection (176±26 pM 150 min) was significantly ileum showed no changes in inflammation of a novel sialic acid 0-acetyl esterase lower, however, (p=0.001) than that in the or permeability to the probe (means 1 0% normal subjects (596±115 pM 150 min). vs 0-9%). We conclude that permeability A P CORFIELD, A J K WILLIAMS, S A WAGNER, In contrast, the integrated plasma CCK changes are related to active inflammation, J R CLAMP, AND R A MOUNTFORD (Uni- secretion during infusion of bombesin are reversible and are not seen distal to the versity of Bristol, Department of Medicine, (100 ng/kg 20 min) in the patients with pan- inflamed site. Bristol Royal Infirmary, Bristol) A sensi- creatic insufficiency (134±23 pM 20 min) tive physiological assay for sialidase activity was not significantly different from the in human faecal extracts, using the mucin to normal type disaccharide N-acteylneuraminyl-a (2-6) CCK response bombesin in the T50 subjects (146±28 pM 20 min). The de- N-acetylgalactosaminitol [3Hi, has been http://gut.bmj.com/ creased postprandial plasma CCK secretion Cholecystokinin receptor binding by developed and optimal conditions deter- in the presence of a normal CCK response human gall bladder myocyte mem- mined. The assay avoids artefacts arising to bombesin in pancreatic insufficiency branes with colorimetric and radioactive glyco- suggests that luminal factors, probably protein substrates. pancreatic enzymes, play an important role P PORTINCASES, A HOWARD, G M MURPHY, The activity of sialidase, acylneuramin- in the plasma CCK response to a meal. AND R H DOWLING (Gastroenterology Unit, ate pyruvate lyase, protease and non- Division Medicine, UMDS, Guy's Hos- specific esterase were assayed in 24 normal

pital, London) The first step in CCK- five Crohn's disease and five ulcerative on October 2, 2021 by guest. Protected copyright. induced gall bladder contraction is ligand colitic patients. Significant differences binding of the peptide by myocyte mem- were found between the two inflammatory brane receptors. This has been studied bowel disease groups and normal for the BASIC SCIENCE little in animals but never in man. Because lyase and protease, but no change in T49-53 gall bladder emptying in response to CCK sialidase or non-specific esterase actitives. is impaired in gall stone patients, we This confirms previous results with synthe- T49 wished to see if this was because of changes tic sialidase substrates but provides new Permeability of inflamed jejunum to in myocyte membrane receptor activity information regarding sialic acid metabol- 51Cr-EDTA in the in vivo rat (number and/or activity). To date we have ism with respect to lyase activity. homogenised fresh gall bladder muscle The degradation of colonic mucus glyco- J K RAMAGE, R T JENKINS, R H HUNT, AND M H (five pooled samples from 25 gall stone proteins rich in 0-acetyl sialic acids may be PERDUE (Intestinal Disease Research Unit, patients), prepared plasma membrane frac- governed by the release of these 0-acetyl McMaster University Medical Center, tions either by Percoll spontaneous density groups which block sialidase action. Hamilton, Ontario, Canada) Increased gradients or by ultracentrifugation Accordingly a novel esterase was detected urinary recovery of orally administered (25 000-200 OOxg), checked their purity in partially purified normal faecal extracts 5'Cr-EDTA may be related to activity and by measuring the membrane marker en- with a mucus glycoprotein substrate. The extent of intestinal inflammation. To ex- zyme 5'-nucleotidase (5'-NT) and by elec- ratio of this activity to that of sialidase was plore this, we measured changes in gut tron microscopy, and studied total and re- -1:100 and this may govern the initiation permeability to 5'Cr-EDTA in a controlled versible binding of 3H-CCK8-S04. Using of mucus glycoprotein breakdwon in the model of jejunal inflammation produced in Percoll gradients, total CCK binding was colon. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 1262 The British Society of Gastroenterology

T52 43-2% showed no mannose-resistant hae- the biopsies were taken from non-affected Luminal alkalinisation by rat caecum magglutination with any source of red sites. The lower level of normal was de- in vitro blood cell. No CFA/I or CFA/II type fined as the 10th percentile of the dyspeptic pattern was found in any colitic E coli. The patients (control group). S P CANFIELD (INTRODUCED BY B P CURWAIN salting out method was used to assess Abnormally low gastrin responses to (Department of Physiology, St Mary's hydrophobicity of E coli from 42 colitics bombesin were found in nine of 21 patients Hospital Medical School, London) This and 15 controls. The mean (+SEM) lowest with the intestinal type of gastric cancer study investigates the ability of rat caecum molar dilution of ammonium sulphate re- (p<0(05), in two of 12 patients with the to alkalinise a luminal solution under in sulting in autogglutination for colitic E coli diffuse type or cardiac cancer (NS) and in vitro conditions. was 0-93 M±0-16 compared with 2 45 M three of 17 patients with gastric ulcer (NS). The serosal surface was bathed in a ±0-25 for controls (p<0-0001). Buccal The antral gastrin content was abnormally HCO3 buffered saline gassed with 95% epithelial adhesion negatively correlates low in 10 of 21 patients with the intestinal 0/5% CO, (pH 7-4) at 35°C and the (p

The British Society of Gastroeenterology A1263 fore, of vitamin C) and the use of home trin and hypertrophied gastric mucosal aspiration cytology allows sampling of the made salt treated meat products were folds. These findings are relevant to the deeper layers of the stomach. We have registered. The brother affected by gastric pathogenesis of hypertrophic gastropathy developed a technique, using a flexible cancer, the two brothers in whose gastric and to potential effects of longterm therapy varices injection needle to obtain cell mucosa epithelial dysplasia was present with PGE2 analogues. aspirates, and have compared results with and, obviously, at least one of the parents, the two conventional methods. shared the same HLA haplotype (A3-B35). Initial studies confirmed that cells could Blood groups, PGI and gastrin did not T57 be aspirated at endoscopy. Sampling of an show peculiar features. Mean gastric juice Difficulties in the diagnosis of adeno- operative specimen was then carried out at pH was abnormally high in both siblings carcinoma of the stomach in routine multiple sites on and around a gastric and grandchildren (4.3±0.6) and detec- practice carcinoma and compared with subsequent table levels of nitrites were present in 33% histology. Needle aspiration obtained read- able samples at all sites and of gastric juices tested. High levels of M DEAKIN, D G COLIN-JONES, AND M VESSEY corresponded gastric juice CA 19-9 were present in three (Department of Gastroenterology, Queen in every case with histological findings. of four siblings and even in five of seven Alexandra Hospital, Portsmouth, and Comparative studies were therefore grandchildren who had no CAG or epithe- Department of Community Medicine and done on 19 benign or malignant gastric lial dysplasia. These data show that, at General Practice, Radcliffe Infirmary, lesions in 16 patients undergoing endo- least in the family studied, both genetic and Oxford) A detailed retrospective assess- scopy. Successful aspirates were obtained dietary factors (lack of vitamin C and use ment was made of 342 cases of adenocarci- from 19 lesions. The technique was quick of nitrate treated food) play an important noma of the stomach diagnosed in Ports- and easy. All three methods provided the role in gastric carcinogenesis. mouth and Oxford during 1979 and 1980. same diagnosis in 15 lesions. In two in- Stage 1 and 2 disease accounted for only stances cancer was shown on biopsy alone T56 46/342 (1333%) of tumours diagnosed and but not on cytology, but in two instances aspiration cytology alone correctly re- Hypertrophic gastropathy associated only nine patients (2.6%) had early tumours. vealed the presence of cancer. with overproduction of prostaglandin We conclude that endoscopic aspiration E2 in the carcinoid syndrome Most patients including those with early tumours presented with weight loss and cytology is a simple technique and its abdominal pain and in 72% within three addition to conventional sampling im- G HULKS, E J S BOYI), G LAFERLA, AND K E 1I proves diagnostic accuracy. MCCOLL (University of Glasgow, Depart- months of onset of symptoms. ment of Medicine, Western Infirmary, Glas- During the year up to diagnosis 232 gow) Hypertrophic gastrophy radiologi- patients underwent 247 barium meals with cally and endoscopically resembling a false negative rate of 26%o for cancer T59 Menetrier's disease was found in a 60 year detection and 125 patients underwent Post-trial surveillance of mortality in http://gut.bmj.com/ old man with dyspepsia. He was achlorhyd- upper gastrointestinal endoscopy on 141 ric with normal serum gastrin and normal occasions with a false negative rate of 13%. bleeding peptic ulcer disease The false negatives had different bases, vitamin B 12 absorption. Gastric biopsies K E WHEATLEY, S BREARLEY, P W DYKES, AND showed superficial gastritis but no evidence radiology missed lesions completely whilst M R B KEIGHLEY (The General Hospital, of tumour. endoscopy observed them only to conclude erroneously that they were Birminigham) Between October 1980 and Two years later he developed features of benign. September 1983 we conducted a random- the carcinoid and was confirmed Symptoms in gastric cancer do not de- syndrome velop early, so early diagnosis in symp- ised trial of the timing of surgery in to have hepatic metastases and grossly bleeding peptic ulcer disease. This demon- increased urinary excretion of 5-hydroxy- tomatic patients is essential. The false on October 2, 2021 by guest. Protected copyright. negative results contributed to strated no mortality in patients under 60 indole acetic acid (5HIAA). A search was delays in no with early or delayed surgery, but early made for a substance produced by the less than 20% of the cases investigated. surgery was associated with a significantly tumour which might explain the hyper- Awareness of the failings of the two dia- lower mortality in older patients. This trial trophic gastropathy. Raised prostaglandin gnostic modalities is important if more has, however, been criticised on statistical E2 (PGE2) concentrations were found in cases of gastric cancer are to be diagnosed grounds. Since the completion of the trial his gastric mucosa (50 pg/mg), gastric juice at a treatable stage. we have adhered to a policy of early (539 pg/ml), plasma 93 pg/ml and urine surgery in the over 60 group and delayed (38 pg/ml), being respectively 100, 50, 4 surgery in the under 60 group and surveyed and 2 times the mean control values. After T58 the mortality rates. hepatic artery embolisation, which reduced Endoscopic aspiration cytology of gas- In the 27 months to May 1986, 200 the 5HIAA excretion by 90%, there was tric lesions patients were admitted with definite return of gastric acid secretion and regres- haematemesis and/or melaena from peptic sion of the mucosal hypertrophy. C J H INGOLDBY AND R I HAiI. (Universitv ulcers. Eighty one patients were under 60 It is concluded that the tumour was Department of Surgery, St James's Hospi- years (56 duodenal ulcers (DU), 25 gastric secreting a circulating factor stimulating tal, Leeds) The limitations of endoscopic ulcers (GU)) and 119 were over 60 (64 DU, overproduction of PGE2 by peripheral biopsy in the diagnosis of gastric cancer are 55 GU). There were nine deaths overall tissues. The markedly raised PGE2 con- well recognised. The addition of brush (4.5%) with all deaths in the older group centration in the gastric mucosa can ex- cytology improves diagnostic accuracy but (766%). plain the achlorhydria, normal serum gas- only surface cells are sampled. Needle There were 41 emergency operations Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1264 The British Society of Gastroenterology with two deaths (4-9%), both in the over 60 B J Z DANESH, M L LUCAS, J M RAWLINGS, AND extirpation of the submandibular glands group (2/29 - 6-9%). R I RUSSELL (Institute of Physiology, Uni- and the effect of oral administration of We conclude that under our current versity of Glasgow and Gastroenterology synthetic human EGF on healing of chro- policy we continue to have a low mortality Unit, Royal Infirmary, Glasgow) It is nic gastric ulcers in rats were investigated. rate in bleeding peptic ulcer disease and an recognised that a neutral mucus-bicarbonate Removal of the submandibular glands de- acceptable postoperative mortality. Pa- gel layer protects gastric mucosal surface layed healing of chronic gastric ulcers when tients below 60 years of age continue to against luminal acid. This study examines examined after 50. 100, and 200 days. Oral show zero mortality. the relation of gastric antral mucosal sur- administration of synthetic human EGF face pH to luminal acid in 34 endoscopically increased gastric ulcer healing when ex- normal (controls), 22 gastric ulcer (GU) amined after 25 and 50 days of treatment. T60 and 25 duodenal ulcer (DU) patients. The effect of synthetic human EGF was Relief of gas bloat syndrome by gastro- Gastric (fundal and antral) mucosal and comparable with that of cimetidine. Com- intestinal stimulation luminal pH was measured, using a flexible bined administration of synthetic human electrode introduced through an endo- EGF and cimetidine further enhanced F C CAMPBELL, D H COOK, GERALDINE scope. The subjects were divided into those healing of gastric ulcers compared with the BLANCH, AND A CUSCHIERI (Department with high and low fundal and antral luminal effect of each substance. Neither synthetic of Surgery, Ninewells Hospital and Medical pHs. In subjects with fundal luminal pH human EGF nor removal of the subman- School, Dundee) In gas bloat syndrome higher than 2 5, (and antral pH greater dibular glands influenced gastric acid secre- (GBS), the retrograde passage of swal- than 4.0) the antral mucosal pH (mean± tion. This study shows that the subman- lowed air is prevented by the oesophago- SEM) was neutral and similar in the 3 dibular glands influence healing of chronic gastric 'valve' created by antireflux sur- groups; 7 17+±007 in controls (n=10), gastric ulcers and suggest that EGF partici- gery. Postprandial gastric distention and 7 05+0 05 in GU (n= 10) and 7(09±+0(04 in pate in healing of gastric ulcers in rats. discomfort result but there is no effective DU (n=9). In those with fundal luminal (Synthetic human EGF was supplied by treatment. While stimulation of stomach pH below 2-5, however, the antral mucosal G D Searle Co, Ltd. and Imperial Chemi- emptying and transit of contents through pH was again neutral (pH 7(00±0 20) in cal Industries, PLC, UK). small bowel could alleviate symptoms, this GU (n= 12) but not in controls (n=24) (pH method could theoretically cause 'dumping' 4.7±0.42) p<0)01) or DU patients (n= 13) T63 and reactive hypoglycaemia. (pH 5.90±0.46) (p>O0'(5). In the latter In 10 patients with severe gas bloat subgroup those who had antral luminal pH Clinical and ultrastructural studies in syndrome baseline symptoms were evalu- below 4 0, the antral mucosal pH was again duodenal pseudomelanosis ated by scored linear analogue scale - the higher (pH 6 49±0+41) in GU (n=4) than worse the symptoms, the higher the score. in controls (pH 3 18±0+43, n= 12) and DU J Y KANG, A Y T WU, J L S CIIIA, A WEE, In response to a solid meal, baseline gastric (pH 4 31±0+85, n=4). I E SUTHERLAND, AND R HORI (Depart- emptying and intestinal transit were evalu- This study has shown that in contrast ments oJ Medicine, Pathology atd Zoology, ated by isotope scintiscan and H2 breath with DU and control subjects, patients National University of Singapore and http://gut.bmj.com/ test respectively. Sequential blood glucose with gastric ulcer disease can maintain a Department of Renal Medicine, Singapore assays were taken for three hours after the neutral mucosal microclimate in the face of General Hospital, Singapore) The solid meal. All patients were then given a high fundal luminal acidity. presence of a spotty brownish-black pig- oisapride, a new stimulatory prokinetic mentation in the duodenal mucosa at endo- drug, 4 mg iv initially then 10 mg orally tds scopy, termed duodenal pseudomeclanosis, for one week. Symptomatic and objective T62 has been described in eight previous case reports. We have studied seven more pa- tests were repeated after treatment. Symp- Effect of submandibular glands and tom score fell from x±SEM=62 9±8-7 tients: four men and three women, aged on October 2, 2021 by guest. Protected copyright. before (B) to x±SEM=29-7±7'7 after (A) synthetic human epidermal growth 28-79 vears. Five were on maintenance treatment (*p<002). Transit times dimin- factor (EGF) on healing of gastric haemo- or peritoneal dialysis, one had ished from x±SEM=156+23 mins (B) to ulcers in rats undergone renal transplantation while the x±SEM=97±917 mins (A) (*p<006) and seventh was anaemic. Six of the seven were gastric emptying times fell from x+SEM= P SKOV OLSEN, S S POULSEN, K THERKEISEN, on oral iron supplementation. There were 44-4±6-2 (B) to x±SEM=38-6±4-1 (A) AND E NEXO (Department of Surgery C, no symptoms attributable to the pigmen- (*paired Student's t test). Blood glucose Rigshospitalet, Department of Anatomy B, tation. In five, the pigment was positive levels were unaffected by cisapride. University of Copenhagen and Department with the Perl's iron stain (P+ve) but We conclude that cisapride relieves of Clinical Chemistry, Hiller0d Hospital, negative by the Masson-Fontana method symptoms of gas bloat syndrome by gastro- Denmark) In rats sialoadenectomy de- for melanin (MF-ve); one was P-ve intestinal stimulation, but it does not creases the synthesis of DNA in gastric MF+ve; while in another, P+ve MF-ve induce reactive hypoglycaemia. mucosa and the resistance of the gastric pigment became P+ve MF+ve one year epithelium to damaging agents such as bile later. At electron microscopy MF+ve pig- salt solutions. Epidermal growth factor is ment comprised characteristic angular T61 secreted in an exocrine manner from the membrance-bound structures while MF-ve submandibular gland. We have previously pigment contained more rounded or ir- Relation of gastric mucosal surface pH shown that oral administration of EGF can regularly-shaped granules. Electron probe to luminal acid in gastric and duodenal prevent the development of experimental x-ray analysis demonstrated the presence ulcer patients gastric lesions in the rat. The effect of of iron in P+ve as well as P-ve pigment. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A1265

MF+ve pigment had high sulphur content P BANNISTER, J OAKES, P SHERIDAN, AND M S with histology; 28 confirmed rejection. but MF-ve pigment had little or no sul- LOSOWSKY (Department of Medicine, St Thirty eight cytological diagnosis did not phur. Duodenal biopsies from 32/46 uremic James's Hospital, Leeds) Men with liver suggest rejection. Ten were matched against patients (on oral iron but endoscopically disease are hypogonadal and feminised. histology. Six of these confirmed the ab- normal) contained iron compared with European workers consider the liver dis- sence of acute rejection, three suggested 22/12() non-uraemic subjects (p<0.001). ease and American workers consider alco- 'mild' or improving rejection. Two patients We postulate that, in uremic subjects hol consumption the major factor. We were not treated for rejection because of taking oral iron, duodenal pseudomelanosis studied sexual dysfunction and sex hor- mild biochemical changes and one incident may represent a disorder of iron transport mones in three groups of men; control was treated despite spontaneously improv- from the duodenal mucosa. Iron-containing (n=22), alcoholic liver disease (ALD) ing biochemistry. The 36 biopsies with no pigment with a high sulphur content (n=22); non-alcoholic liver disease histology, showing the absence of rejection may become MF+ve. (NALD) (n=24). The liver disease groups were done in the absence of clinical suspi- were matched for age, drug therapy, cion of active acute rejection. The presence disease severity and complications. Men of macrophages preceded or accompanied with ALD had significantly more sexual serious graft disease including chronic re- dysfunction. Androgen concentrations jection and graft ischaemia. lIVER POSTERS were changed in ALD and NALD, more so Cytological examination of liver grafts T64-70 in the ALD group. Data is mean±SD; carries a high sensitivity and specificity for Control vs ALD vs NALD. acute rejection. T64 Testosterone; 18.1±5.2 vs 6-6+4-8 vs Urban clustering of primary biliary cir- 12 9±6-0 nmol/l; NALD vs control p<0)01; T67 rhosis ALD vs control p<000(1; NALD vs ALD p<0005. Natural killer cell activity in hepato- J F MAYBERRY, J GIGGS, H L SMART, AND P J Androstenedione; 3-8+±17 vs 8 12±2-8 cellular carcinoma: in vitro and in vivo TOGHILL (University Hospital of Notting- vs 5-46±2-47 nmolUl; NALD vs control response to interferon ham and University of Nottinigham, p<0 (2; ALD vs control p<0)001; NALD Nottingham) Between 1970 and 1984 38 vs ALD p<0(005. AA DUNK, D NOVICK, AND H C THOMAS patients with primary biliary cirrhosis were Dehydroepiandrostrone-sulphate; 6 78+ (Academic Department of Medicine, Royal diagnosed in the greater Nottingham area 3-2 vs 1 27±1 6 vs 1 71±1 7 smol/l; NALD Free Hospital School ofMedicine, London) which has a population of 573 000. The vs control p<0001; ALD vs control Natural killer (NK) cells may be important diagnosis was accepted on the basis of p<0001; ALD vs NALD p<05. in the host defence against cancer and classical histological changes. During this Oestradiol concentrations were raised reduced NK activity has been found in period 14 additional patients were found to only in the ALD group; 96+5 vs 177±189 patients with a variety of different cancers. have positive antimitochondrial antibody vs 94±50 pmolUl. ALD vs control p<0O05. In a "tchromium release assay we have titres by their general practitioners, but no In this, the first controlled study, liver measured the in vitro NK cytotoxicity of http://gut.bmj.com/ liver biopsy was performed. These patients disease per se causes sexual dysfunction peripheral blood mononuclear cells were not included in the study. The overall and sex hormone changes but these (PBMCs) isolated from patients with hepa- incidence of primary biliary cirrhosis was changes are amplified by ethanol. tocellular carcinoma (HCC) against K562 0(44/105/year. Between 1970 and 1984 24 cells, and have examined the effects of a- patients died giving a prevalence for the interferon (IFN) on NK function both in disease of 4 2/1(05. The majority of the T66 vitro and in vivo. At all effector:target patients were women (ratio 19:1). The age Cytological diagnosis of hepatic dys- (E:T) ratios studied, NK cytotoxicity in specific incidence rose to a peak of 5-2/105/ function after liver transplantation HCC patients (n= 17) was significantly on October 2, 2021 by guest. Protected copyright. year in the 65-69 age group. lower than patients with cirrhosis (C: In all cases a detailed residential history R M KIRBY, J A YOUNG, S G HUBSCHER, W B n= 13) or normal controls (NC; n= 12 - was obtained from the patient or a close CUTHBERTSON, A B JAIN, AND P MCMASTER for example, at E:T=50:1, % cytotoxi- relative and this was analysed using data (Queen Elizabeth Hospital, Edgbaston, city (mean±SEM) HCC**=26-3±3.7, obtained from census enumeration dis- Birmingham) Sixteen patients have been C**=45.6±2 2, NC=53-8+4-6. *p<0 05 tricts. There was clear evidence of cluster- studied after 19 liver transplants by fine vs C, p<0-01 vs NC. **p>0.05 vs NC). ing of cases in the town and this was needle aspiration cytology in combination Natural killer activity in HCC did not significantly associated with the water with Menghini needle biopsies. Eighty correlate significantly with either serum supply in the two areas of Clifton and seven specimens have been examined. AFP concentration or patient performance Stapleford. Further studies may elucidate Thirty nine of these followed histological score. Natural killer activity in all groups an important environmental factor in the biopsy and allowed direct comparison once could be increased by prior incubation of development of primary biliary cirrhosis. the cytological diagnosis had been made. PBMCs with IFN but this was significant Eleven baseline aspirations were done im- only in HCC patients, where 10 IU/ml of T65 mediately after perfusion of the graft. IFN increased NK cytotoxicity from Rejection was diagnosed by a rise in liver 36 9±10-0 to 52-8±8-2% E:T=50:1, n=5, Sexual dysfunction and sex hormone aspirate lymphocytes, plasmablasts and mean±SEM, p<005. Further increases in changes in liver disease. A controlled plasmacytes compared with peripheral IFN concentration failed to further in- study of alcoholic vs non-alcoholic blood. There were 36 diagnoses of rejec- crease NK activity. Natural killer activity disease tion. Twenty nine of these were matched was measured before and 24 hours after Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1266 The British Society of Gastroenterology 2-5 mU/mr of IFN was given to four geal staple transection for acute vari- identical to colour, taste, pH, and osmolar- HCC patients. Natural killer cytotoxicity ceal bleeding. Single interim analysis ity containing either 75 g/100 ml lactitol or (mean±SEM) rose from 27 5±8 6 to 50-6 g/l00 ml lactulose. The initial dose of 60 9±522% (p=005). A K BURROUGHS, F D'HEYGFRE, A PHILLIPS, 0-75 ml/kg was adjusted to produce two We conclude that natural killer activity K E F HOBBS, AND N MCINTYRE (Academic semi-soft stools per day. Patients were is reduced in HCC. This is not explicable Department of Medicine, Clinical Epide- assessed 12 hourly for five days. Patient on the basis of underlying cirrhosis, or miology and Surgery, Royal Free Hospital groups were comparable on entry to related to serum AFP level or poor patient and Medical School, London) Emergency the trial. During the trial, significant im- condition. Natural killer cytotoxicity in sclerotherapy (ES) for variceal bleeding provements occurred in clinical and HCC can be increased in vitro and in vivo has relegated surgery to second line treat- psychometric performance and in the EEG by small doses of IFN. ment in many centres, although very few in the majority of patients in both groups. randomised studies exist comparing ES and At the end of the trial 67% of patients in surgical treatment. We randomised cir- the lactitol and 69%M in the lactulose group T68 rhotics to ES or oesophageal staple tran- were clinically normal. At 24 hours, Multiple logistic analysis of Pugh's section (OST) if bleeding was not controlled however, 33 0% of lactitol patients but criteria for early mortality from vari- with transfusion and glypressin at any time only 8-2% of lactulose patients had im- ceal bleeding. Comparison with other within five days of admission. There were proved significantly (p<0.05). Both drugs modified Child's classifications 200 admissions (125 patients): Pugh's grade are effective in the treatment of acute A (47), B (80), C (73). In 82 admissions hepatic encephalopathy, but patients F D'HEYGERE, A K BURROUGHS, A PHILLIPS, bleeding was not controlled: 12 not ran- treated with lactitol responded more AND N MCINTYRE (Academic Department domised (eight not eligible, four mori- quickly. of Medicine and Clinical Epidemiology, bund): 70 randomised (63 patients) - 35 to Royal Free Hospital School of Medicine, OST, 35 to ES: grade A (nine), grade B London) Modified Child's classifications (25), grade C (36). The two groups were (MC) in cirrhotics using grades A, B, and well matched as regards clinical status, C are commonly used to assess prognosis, severity and duration of bleeding. Mortality at 30 days was 34%M (12 of 35) in both COLORECTAL and 30 day mortality after variceal bleeds. T71-77 Component criteria of MC are statistically groups (1A, 4B, 19C) analysed by inten- a good index of overall prognosis', but tion to treat, and 27% (OST) and 31% have not been validated as prognostic (ES) related to treatment received. T71 Emergency sclerotherapy (. injections) indicators after variceal bleeding. More- Epithelial cell proliferation kinetics of over simple comparison of the same grades failed to completely control bleeding in

colorectal mucosa http://gut.bmj.com/ using different MC may be misleading 15% (five admissions - one survived); in patients with because of different systems of grading. OST in 3% (one admission - survived). polyps of the large bowel We compared prospectively in 132 cirrho- Fatal complications were similar. These tics bleeding three MC (Campbell, Pugh results show that OST has a similar mor- M PONZ DE LEON, P DI DONATA, L RONCUCCI, and Cello). There was great variation in tality to ES. Emergency sclerotherapy was M G AMORICO, C SACCHETTI, G MALAGOLI, grading: grade A 6% to 42%, grade B 28% less effective, and there was a high mor- M PERINI, L CODELUPPI, AND A FERRARI to 36% and grade C 210% to 66%, with tality in patient failures. Prediction of ES (Istituto di Patologia Medica, Istituto di similar differing proportions of deaths at 30 failures and/or early changes to alternative Radiologia, Cattedra di Gastroenterologia, days (n=29) in each grade. The prognostic therapy may improve survival in acute Universita di Modena, Modena, Italy) In on October 2, 2021 by guest. Protected copyright. value of several variables including Pugh's variceal bleeding. normal subjects the cytoproliferative activ- criteria (PC) for 30 day mortality after ity of colonic mucosa is limited to the lower variceal bleeding was analysed using mul- T70 portion of the crypts and almost absent in the surface. In subjects at high risk tiple logistic analysis. All PC correlated Randomised controlled double blind for univariately: bilirubin p<0O004, ascites colorectal cancer (such as members of trial of lactitol and lactulose in acute families with adenomatosis coli or Lynch p<00002, encephalopathy p<00005, hepatic in cirrhotic prothrombin time p<002, albumin p<008. encephalopathy syndromes) cell proliferation is observed in Only one other factor correlated: early patients the whole body of the crypt. It is not rebleeding p<0003. Bilirubin, ascites, known if this abnormal proliferative pat- encephalopathy, and early rebleeding had K HAWLEY AND M Y MORGAN (Academic tern is also observed in the more common independent prognostic value. Thus PC are Department of Medicine, Royal Free patients with solitary or multiple polyps. statistically valid prognostic indicators for Hospital, London) Lactitol is a non- Thus, we purposed to investigate the pro- 30 day mortality after variceal bleeds. A absorbable disaccharide available as a pow- liferative pattern of large bowel mucosa in uniform system of grading, however, must der which, in open comparison, is as subjects with adenomas. be adopted for clinical use. effective as lactulose in the treatment of Twenty eight patients with polyps and 15 chronic hepatic encephalopathy but is bet- healthy controls entered the study. During ter tolerated. Twenty five cirrhotic patients endoscopy small samples of mucosa were needing treatment for 28 episodes of acute taken at 10-15 cm from the anus and T69 hepatic encephalopathy were blindly incubated with 'H-thymidine (1-5 iCi/ml) Prospective randomised trial of endo- randomised to either lactitol (n= 15) or for one hour at 37°C. After exposition of scopic sclerotherapy versus oesopha- lactulose (n= 13) dispensed as solutions Kodak AR 10 films and histology, each Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A 1267 intestinal hemicrypt was divided into five Six of 13 adenomas (46% ) excised from compared with normal mucosa. The con- longitudinal compartments from the fun- men had positive receptor binding activity, tribution of u-PA to the total PA-activity dus to the surface. For each hemicrypt total whereas only one of 13 (7-7o) from (% u-PA) in normal colon mucosa was cells, cells for each compartment and label- women was positive (p=0.03), Fisher's 6 2±0 5, whereas in the adenocarcinomas led cells (in phase S of the replicative cycle) exact test). There was no significant cor- the % u-PA was significantly increased to were counted. relation between AR levels and patient age 48-7±2-5 (p<0-001) with a specificity and In total, 11 948 cells were counted in or between adenoma site, histological type sensitivity of respectively 98-8% and patients with polyps and 5471 in controls. or degree of dysplasia. In normal mucosa, 95-8%. Adenomatous polyps showed Labelling index (o/o of labelled cells) was AR levels ranged from 7-33 fmolUmg and values of % u-PA (20 2+1.3) which were 11-2+2-5% SDM in the polyps group and Kd's ranged from 0 243-1 x 10 - M. There intermediate as well as significantly dif- 9-5±+25% in controls (NS). In the first and was no significant difference between ferent (p<0.001) from those of normal in the second compartments the ratio either AR prevalence or levels in the mucosa and adenocarcinomas. between labelled and unlabelled cells was adenomas and the normal mucosa. The sex This study shows that the sequence of not different between the two groups. In difference was exclusive to the adenomas. normal mucosa-polyp-adenocarcinoma in the third compartment the ratio was higher These results suggest that endogenous the colon is associated with a parallel in the polyps group (0.107±0.13 vs androgen may play a role in the adenoma- increase in u-PA activity. Thus PA mea- 0090±+012, p<0(02) and even higher carcinoma sequence early in the pro- surements in intestinal tissue might be in the most superficial compartments motional process. helpful in the early detection of colorectal (0(040±0+07 vs 0 020±0+07. p<0.0 1). cancer. We conclude that a significant increase T73 of the cytoproliferative in the most activity Plasminogen activator activity in the superficial portion of the large bowel mu- T74 cosa (30, 40 and 50 compartments) has been colonic polypadenocarcinoma sequence found in patients with adenomatous Calcium has a protective role against polyps. These findings might be of rele- P A F DE BRUIN, H W VERSPAGET, G GRIFFIOEN, the development of colorectal tumours vance in order to define the predisposition J H VERHEIJEN, M NAP, AND C B H W LAMERS to colorectal cancer in this population at (Departments of Gastroenterology and G V N APPLETON, P W DAVIES, J B BRISlOL, risk. Hepatology, Department of Pathology, AND R C N WILLIAMSON (University De- University Hospital and Gaubius Institute partment of Surgery, Bristol Royal Itnfirm- TNO, Leiden, The Netherlands) Ma- ary, Bristol) Carcinogenesis in the large T72 lignant changes are often accompanied by intestine is promoted by both intrarectal Role for endogenous androgen in the alterations in activity and composition of administration of sodium deoxycholate and development of colorectal adenomas? the plasminogen activators (PA). To study small bowel resection. Oral supplements of the relation between PA expression and calcium reduce the mitogenic effect of fatty

W S 1. STEBBINGS, M J G FARTHING, J R the development of colorectal cancer, we acids and bile acids on large bowel mucosa, http://gut.bmj.com/ PUDDEFOOT, T E ANDFRSON, G P VINSON, J M A determined tissue-type plasminogen activa- and calcium is antitropic to human colon. NORTHOVER, AND R F M WOOD (Professorial tor (t-PA) and urokinase-type plasminogen The role of intraluminal calcium in pre- Surgical Unzit and Departments of Gas- activator (u-PA) activity in normal mucosa venting colonic tumour formation was troenterology and Biochemistry, St Barth- (n=78), polyps (n=76) and adenocarcino- tested in 60 male Sprague-Dawley rats olomew's Hospital Medical College, Lon- mas (n=70) of the colon. Tissue obtained weighing 185-6±9-2 (SEM) given a six don) Necropsy and colonoscopic studies from surgical resection or polypectomy was weeks course of azoxymethane 15 mg/kg/ have shown that colorectal adenomas occur homogenised and analysed for both PA- wk and then submitted to either an 80%'O

more frequently in men than women. To activities by (a) SDS-PAGE followed by jejunoileal resection, or simple transection on October 2, 2021 by guest. Protected copyright. evaluate the potential effect of androgens PA identification from lysis areas in a and resuture of the bowel. Within each on the development and growth of human fibrin-plasminogen gel overlay (zymogram- group half the animals had 24 g/l cal- colorectal adenomas, the prevalence and technique); (b) t-PA and u-PA activity cium lactate added to the drinking water. concentrations of cytosolic androgen re- measurements in an enzymatic assay using Twenty five weeks postoperatively the num- ceptors (AR) were analysed in 26 adeno- plasminogen, a chromogenic substrate and ber of colonic tumours per animal was mas and 19 samples of normal mucosa by a selective quenching with monospecific anti- recorded. Among rats with transection hybrid ligand receptor binding assay. bodies to determine both activators (ex- calcium supplements more than halved Scatchard analysis was used to determine pressed as enzymatic units, mean±SEM). tumour numbers from 43±+1 0 to 1 8±0+8 the binding specificity and tissue was con- Zymograms of normal mucosa revealed (p<002). As expected jejunoileal resec- sidered AR positive at receptor concen- PA-activity exclusively at MW=65 000 tion increased tumour yield - by 65% in trations -5 fmol/mg cytosolic protein. (t-PA) whereas in adenocarcinomas this rats drinking normal water (p<0.05), and Androgen receptors were detected in seven activity was decreased and a second 105% in the animals with added calcium of the adenomas (26-9/O) and in six of the stronger activity occurred at MW=50 000 (p<005 - but again calcium reduced the normal mucosa samples (31.6%). In the (u-PA). The enzymatic assay confirmed number of tumours from 6-9±1 6 to adenom.as, AR levels were low ranging these observations by a significant reduction 3-7±1-2, a fall of 46% (p<0.02). Increased from 6 to 31 fmol/mg cytosolic protein, and in t-PA activity (0(65±0+06 vs 2 22±0-16, dietary levels of calcium tend to blunt the dissociation constants (Kd) ranged from p<0-O(l) and a corresponding increase in carcinogenic effect of massive enterectomy, 0) 17-2*7x 10 " M, comparable with the Kd u-PA activity (0 55±0 05 vs 0 13±0 01, conceivably by binding tropic substances of AR in human prostate (0*4xl10 " M). p<000(1) in the adenocarcinomas when such as bile acids. Calcium protects against Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 1268 The British Society of Gastroenterology the development of colorectal neoplasia paraffin embedded material in 109 patients ploidy at routine histology. Nuclear size and this may be important in man. with between one and three years follow up. was determined using an eyepiece grati- DNA content was measured by flow cyto- cule, and DNA ploidy was correctly esti- metry on disaggregated tumour samples mated in 38/51 (740/) of the tumours. T75 using as fluorochromes ethidium bromide/ Tumour ploidy is related to nuclear size, Value of screening postcholecystectomy mithramycin (E/M) for fresh, and diaminido and this simple histological technique may patients for colorectal neoplasia phenyl indole hydrochloride (DAPI) for distinguish aneuploid tumours with im- paraffin embedded material. There was provement of subjective grading. R J MOOREHEAD, J 0 M MILLS, H K WILSON, 89/110 (81%) agreement between the two AND S T D MCKEIVEY (Department of methods with DAPI more accurate in Surgery, The Queen's University' of Belfast, identifying abnormal cell populations. and Department of Radiology, Royal Vic- Fifty seven (52'%) tumours had an toria Hospital, Belfast, and Ulster Hospital, abnormal DNA content - 52 (47%) aneu- Dundonald) Cholecystectomy may in- ploid, five (5%) tetraploid. There was no crease the risk of developing colorectal relationship with pathological stage or his- OESOPHAGUS adenoma and carcinoma. Patients over 60 tological grade. Of 59 patients whose T78-80 years of age who have undergone cholecys- tumours had no evidence of metastasis tectomy more than 10 years previously are (Dukes' stages A and B 11 (19%o) have T78 thought to be particularly at risk. developed local or distant recurrencc- Effects of ranitidine and of sleeping We are undertaking a prospective study 8/27 (3°0%) aneuploid, 0/4 tetraploid and of 100 patients to determine the incidence 3/28 (11%O) diploid tumours. posture on symptoms and endoscopic of colorectal neoplasia a decade after Prospective measurement gives at similair appearances in patients with severe cholecystectomy. To day 84 patients (mean proportion of tumours with abnormal peptic oesophagitis age 68.4+6.4 years, men 28, women 56) DNA content as found retrospectively. have been investigated by sigmoidoscopy Patients undergoing potentially curative C GORDON, N IIADIEY, D lONG, R MACPHER- and barium enema examination. The inter- surgery with aneuploid tumours appear to SON, B, BEATS, AND R F HARVEY (Gastroeni- val since cholecystectomy was a mean of have an increased risk of developing early terology Unit, Frenchay Hospital, Bristol) 12-8+SD 4-2 years. Control observations recurrence. After an initial symptomatic assessment were made on 84 age and sex matched and oesophagoscopy, 71 patients (43 men subjects undcrgoing hospital and non- and 28 women) with gastro-oesophageal hospital postmortem examination. reflux and severe peptic oesophagitis Thirteen postcholecystectomy patients T77 (defined as ulceration with slough forma- http://gut.bmj.com/ had tumours (nine with adenomas > 1 Can DNA ploidy be estimated histo- tion) were entered into a double blind trial cm, four wtih carcinoma). In the control logically in colorectal adenocarcinomas? of ranitidine 150 mg twice daily or placebo group three had adenomas > 1 cm and for a period of six weeks. The effect of none had carcinoma. The difference is J T KENT, J S LOWE, N C ARMIJlAGE, K C elevation of the head of the bed on 20 cm statistically significant (p<0.05 (X2 test). BALLANTYNE, AND J D HARDCASIIE blocks was tested separately by randomly The results to date confirm that (Department of Surgery and Department of allocating 36 of the 71 patients to this cholecystectomy increases the risk of de- Pathology, University Hospital, Notting- therapy, irrespective of whether they were veloping colorectal neoplasia. Further stu- ham) Subjective histological grading of on ranitidine or placebo. dies are needed to determine if younger colorectal carcinomas is not a powerful Thus there were four groups of patients on October 2, 2021 by guest. Protected copyright. patients and those with shorter postoper- indicator of patient survivail. Tumour cell (placebo, flat; placebo, blocks; ranitidine, ative intervals are at similar risk. Surveil- DNA content (ploidy) has been shown to flat; ranitidine, blocks). In these groups, lance for large bowel tumours is indicated be of independent prognostic value, but symptoms improved overall in 26 6, 58X8, in older postcholecystectomy patients. flow cytometry is limited in application to 76 5 and 86-7'% respectively, and healing specialist centrcs. Using computer aided of more than half the ulcerated area was morphometry, the mean nuclear profile seen in 46 2, 76 5, 70(6 and 93-30/o respec- T76 area (300 nuclei) was measured in 51 tively. All symptoms studied (retrosternal Tumour cell DNA content as an indica- moderately differentiated stage B colorec- and epigastric pain, reflux and dysphagia) tion of early recurrence in colorectal tal carcinomas. The results were compared were significantly improved by ranitidine, cancer with the evaluation of DNA ploidy made as were endoscopic appecarances. The addi- by flow cytometry. Twenty six (51%S) of tional beneficial effect of elevation of the N C ARMIIAGE, K C BAI.I ANTYNEI, JUDITH the tumours were DNA aneuploid. The head of the bed, independent of the effect WRIGHT, AND J D IIARDCASFLE (Depart- mean nuclear profile area for the aneu- of ranitidine, was statistically significant for 2 ment of'Surgery, University Hospital Not- ploid tumours was 62-9 m compared all symptoms except dysphagia. 2 tinigham) Tumour cell DNA content as with 48X3 !tm for the diploid (p<0(X)01, We conclude that: (1) ranitidine im- measured in paraffin cmbedded matcrial t=7-4, 49 dof). The mean nucleair profile proves the symptoms and promotes healing his been shown to influencc the survival of area was found to be greater than 53 5 VM 2 of severe reflux oesophagitis. (2) Eleva- patients with colorectal cancer, indepcn- in 24 (92%) of the aneuploid tumours. but tion of the head of the bed is beneficial dent of pathological stage and histological only four (16'%) of the diploid. in severe reflux oesophagitis. (3) These grade. We have meaLsured prospectively A simple algorithm was constructed two effects are independent and tumour cell DNA contcnt in both fresh and from these findings to estimate DNA complementary. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroeniterology A1269 T79 pain made worse on swallowing saliva, permeation 0-38, p=0-04; permeability Arterial vascularisation of the oeso- taking liquid, or solid food. In most pa- 0-72, p=0.02). In Crohn's disease, man- phagus tients odynophagia lasted for four to six nitol permeation was reduced (0(69, days, but dysphagia persisted for another p=0-02) but raffinose was unchanged. D LIEBERMANN-MEFFERT. U NEFF, U 1 USCHER, three to four days. In all patients symptoms Permeabilities to both sugars were normal. AND M ALLGOWER (Kantonsspital, Depart- disappeared within eight to 14 days. The results are compatible with trans- ment Chirurgie, Spitalstrasse 21 Basel, Oesophagoscopy carried out in 35 of cellular uptake of mannitol (surface area- Switzerland 4031; Creighton University, these patients showed; large serpigionous, dependent) and paracellular uptake of Omaha, Nebraska, USA) Blunt cervico- single or multiple ulcers involving part or raffinose (surface area-independent). oesophagectomy, an increasingly used op- the whole circumference of the mucosa. We conclude (1) transcellular uptake is eration for oesophageal cancer, caused Ulcers, usually 22-26 cm from incisors and reduced in untreated coeliac disease and only exceptional mediastinal bleeding. The for a length of 3-8 cm were biopsied. returns to normal on treatment; (2) para- oesophageal blood supply was studied in 16 Histologic examination of ulcer margins cellular uptake of both sugars is increased human cadavers by injecting plastic com- showed; basal cell hyperplasia and spon- in untreated coeliac disease and may re- pounds into the Aorta. Three-dimensional giosis of the sguamous cells, but acute main abnormal following treatment; (3) in corrosion casts showed: (1) the proximal inflammatory cell infiltration and necrosis Crohn's disease only the transcellular route third of the oesophagus was well supplied were present in ulcer bases. Ten of these is affected. by pairs of arteries branching from the patients underwent repeat endoscopy three inferior thyroid artery and by a bunch of to four weeks after their initial examination small tracheo-oesophageal arteries arising and no trace of lesions could be found. None of these patients had history for T82 from the aortic arch. (2) The middle Increased rates of trabecular oesophagus, a 16 to 24 cm long section, was reflux or previous history of dysphagia, and spinal supplied by only one and rarely two un- none developed symptoms after taking bone loss in patients with inflammatory paired small arteries arising directly from morning medication. A video tape of the bowel disease the thoracic aorta. This area was mainly ulcers, and after improvement at endo- supplied by minute collaterals coming from scopy is available. R MOTI EY, E 0 CRAWLEY, W D EVANS, C the proximal and distal oesophagus and EVANS, J RHODES, AND J E COMPSTON (De- located in the submucosa. (3) The distal partments of Gastroenterology, Pathology oesophagus and cardia were well supplied and Medical Physics, University Hospital of by a number of branches originating from Wales and University of Wales College of the left gastric and splenic arteries. Medicine, Cardiff, Glam) Low bone SMALL BOWEL/NUTRITION mineral content (BMC) in spinal trabecular Phrenic arteries did not supply the oeso- T81-87 phagus and intercostal branches only twice. bone and cortical bone in the radius has

been demonstrated in approximately one http://gut.bmj.com/ The poor extraparietal blood supply to the T8 1 thoracic oesophagus explains why 'blunt third of patients with inflammatory bowel oesophageal dissection' in smaller oeso- Mucosal permeability to sugars in vitro disease (IBD). We have carried out repeat phageal tumours caused no mediastinal in coeliac and Crohn's disease measurements of BMC after one year to bleeding and why oesophageal anastomotic determine the rate of bone loss in these leak is frequent. D J DAWSON, A M DUNNE, R W [OBLEY, patients. Bone mineral content was mea- J NOTMAN, M MAHON, AND R HOLMES (Uni- sured in spinal trabecular bone by quantita- versity Department of Gastroenterology, tive computerised tomography and a cor- Manchester Royal Infirmary and Depart- tical radial bone T80 by single photon absorp- on October 2, 2021 by guest. Protected copyright. ment of Anatomy, University of Manchester, tiometry. The reproducibility of both Oesophageal ulcers associated with Manchester) To differentiate surface area methods is 2-3%. doxycycline therapy effects from mucosal permeability changes Twenty seven patients (15 women) aged we have studied the total uptake, mucosal 23-78 years were studied. In 18 patients, SAEFD ADIB-BAGHERI (INTRODUCED BY R E permeation and mucosal permeability changes in spinal trabecular BMC were POUNDER) (Gastroenterologist, PO Box: (permeation corrected for surface area) of similar to those observed in controls: 71345-1443, Shiraz, Iran) Over a period mannitol and raffinose in jejunal biopsies however, nine patients, four men, aged of 16 months, 56 patients, 41 women and from controls (n=48), coeliacs in relapse 23-73 years (mean 41) showed accelerated 15 men, aged 17-47 years developed re- (13) and remission (11), and patients with rates of bone loss ranging from 8-50% of trosternal burning pain and odynophagia small intestinal Crohn's disease (12). the initial BMC (mean 22%). All but two after taking doxycycline hyclate. The drug In coeliacs in relapse, mannitol permea- of these had received steroids over the was used mainly for pelvic inflammatory tion was reduced vs controls (median 0-59 preceding year; seven of the nine patients disease, upper respiratory, urinary tract, vs 0 90 4/mg dry wt, p=0.0006), raffinose had small bowel IBD with resection. Only and skin infections. Hundred milligram permeation was increased (0-51 vs t)-31, one patient showed an increased rate of blue capsules in majority of patients taken p=0009; and permeability to both sugars cortical bone loss at the radial site. twice a day, the last dose, before retiring was increased (mannitol 2 54 vs 1-21, Our results show rapid spinal trabecular and usually with less than a glass of water. p=0-0()9; raffinose 2 38 vs 0(51, p=0(0X1). bone loss over a relatively short period of Within one to seven hours after one of the In coeliacs in complete remission, per- time in some patients with IBD and suggest evening doses the patients woke up with meation and permeability for raffinose but that steroid therapy may be an important severe low or midretrosteronal burning not mannitol remained abnormal (raffinose contributory factor. Further studies are Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1270 The British Society of Gastroenterology required to identify patients at risk and ileal cannula 50 cm from the ileocolonic sit time significantly faster than controls, establish effective prophylaxis. junction (I-CJ) at the following times (all in 51-1±4-4 minutes p<0Ol1, but after treat- duplicate); (a) during phase I of the inter- ment returned to normal (82(0±7+0 min). digestive myoelectric cycle (IDMEC), (b) In six patients with hypothyroidism the T83 10 min before a 400 kcal meal, (c) two OCTF was 96-7±13 3 mins, and in four Transport of bile salts (BS) by enteric hours postcibal (pc), and (d) four hours pc. retested after thyroxine replacement it did and non-enteric Gamma scans were obtained every 4 min not change. microorganisms and while simultaneous myoelectric activity Our results show that the OCIT (1) their effect on growth was recorded from serosal electrodes. measured by this breath test is reproduc- During phase I of the IDMEC isotope ible, (2) is significantly faster than normal C E W HALLIDAY, 0 D PREDOLAC, C CLARK, remained immobile while migration of in thyrotoxicosis and approaches normal AND M J G FARTHING (Department of Gas- phase III down the study segment was after treatment and (3) in hypothyroid troenterology, St Bartholomew's Hospital, associated with sudden movements, patients is similar to controls. It is likely West Smithfield, London) We have boluses of isotope entering the colon when that in thyrotoxicosis but not in myxoedema shown previously that BS stimulate growth phase III was 12±9 cm from the I-CJ. the OCTT is a major factor in the disturbed of Giardia and are taken up by an energy Phase Ills occurred every 113+7 min bowel habit. dependent, saturable process. The aims of (mean±SEM) and cleared 48+7% of ileal this study were to determine (1) if BS are isotope into the colon. The time for 50% of actively transported by Giardia and (2) isotope to enter the fasting colon (T50) was whether BS uptake and the effects of BS on T86 111± 11 min (n=6). Postprandially colonic growth are specific to Giardia. To deter- filling was similarly episodic; some boluses Critical rise in breath hydrogen in mine the intracellular concentration of BS, (six of 27) were associated with discrete evaluation of intestinal transit intracellular volume of Giardia was esti- clustered contractions but most (17/27) mated by ['4C]-urea diffusion. The effect occurred during irregular phase Il-like F C CAMPBELL AND A CUSCHIERI (Depart- of BS on growth of Giardia, Trichomonas concentrations. Immediately after eating ment of Surgery, Ninewells Hospital and vaginalis and E coli was assessed. Kinetics (study B) ileal activity rose transiently in Medical School, Dundee) The hydrogen of BS uptake were determined with sodium six of 10 studies but T50 was increased to [H,] breath test of intestinal transit relies glycocholate (GC) (0-1-5 mmol1l) and 207±16 min (p<002). T50 at four hour pc on caecal fermentation of an ingested tracer [I4C]-GC. Intracellular volume of was 91±31 min (n=8), significantly shorter non-absorbable saccharide with liberation x Giardia was 1-85±0-25 10- 41. Uptake of than at two hour pc, 162±25 min (n=8) or of H2 which is absorbed and exhaled in

GC from 2 mmolUl GC was 17 9±0-9 nmolU study B (both p<001). We conclude that breath. There is no uniform 'critical rise' in http://gut.bmj.com/ 108 trophozoites/30 min. The calculated episodic fasting ileal emptying is clearly breath H2 although values of three or 10 intracellular concentration was 9 7 mmol/l, related to the IDMEC; postprandially parts per million (ppm) have been sug- suggesting that GC was actively trans- emptying is also episodic but less clearly gested. This study investigates test reliabil- ported against a five-fold concentration related to propulsive motor patterns. ity according to the level of 'critical rise'. gradient. Ox bile stimulated growth of Fasting sample variation and correlation Giardia, inhibited Trichomonas but had no with disease state have been considered. effect on E coli. Glycocholate uptake by T85 In 26 healthy volunteers and 43 patients

Trichomonas and E coli was a saturable Orocaecal transit time in health and in with symptomatic diarrhoea (21 post- on October 2, 2021 by guest. Protected copyright. process, (Trichomonas Km 5 19 mmolUl, thyroid disease gastrectomy syndrome, 12 visceral auto- Vmax 4 10 nmolUmg protein/30 min; E coli nomic neuropathy, 10 irritable bowel syn- Km 0 154 mmol/l, Vmax 0-24 nmol/mg M V TOBIN, R A FISKEN, R T DIGGORY, A I drome) multiple fasting breath samples proteinl30 min) but was substantially less MORRIS, AND I T GILMORE (Gastroenterol- were taken before a liquid test meal of 10 g than uptake by Giardia (Km 1 11 mmol/l, ogy Unit, Royal Liverpool Hospital, Liver- isotonic lactulose. Breath samples were Vmax 18 04 nM/mg protein/30 min) (4-75 pool) The lactulose H2 breath test is a taken at 10 minute invervals afterwards for times). Thus BS stimulate growth and are simple, non-invasive method of determin- up to six hours. actively taken up by Giardia, but the ing the orocaecal transit time (OCTT) but Fasting variation increased in proportion biological relevance of intracellular BS its reproducibility and clinical application with initial fasting H2 value (Kendall accumulation remains to be determined. remain uncertain. After assessing its repro- au=0-42; p<0(001). Variation between ducibility by duplicate studies in 12 normal fasting samples exceeded 3 ppm in 15 of 35 T84 subjects using lactulose 30 g in a liquid subjects with initial fasting H2 >9 ppm. meal, we studied OCTT in 17 patients with No differences of transit time were Episodic nature cannine terminal ileal thyrotoxicosis, 14 of whom were retested observed between patients and volunteers emptying after being rendered euthyroid, and in six with a critical rise of 3 ppm. A rise of patients with myxoedema, four of whom 10 ppm distinguished the two groups, with R C SPILLER, M L BROWN, AND S F PHILLIPS were repeated after replacement therapy. shorter transit times in the patients (Gastroenterology Unit, Mayo Clinic, The mean OCTT in controls was (p<0).01 Mann Whitney). Rochester, Min, USA) The effect of pre- 86 7+15 9 (mean+SEM) minutes and after We conclude that a critical rise of 3 ppm viously described patterns of terminal ileal four weeks, 84 1±11 9 mins. The mean is inadequate to overcome fasting H2 motility have been quantified in the pre- coefficient of variation for transit time breath variation and has poor correlation sent study by means of gamma-scintigraphy. within individuals was 8-6%+±30 (range with disease state. A minimum rise or 0-3 mCi of '99Tc DTPA was injected via an 0-28%). Hyperthyroid patients had a tran- 10 ppm is suggested. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Castroenterology A1271 T87 Herts) Prednisolone absorption was stu- cronucleus (MN) formation in their lym- Is TPN related hepatobiliary dysfunc- died after a 20 mg oral dose, given as phocytes than age- and sex-matched con- tion secondary to deprivation of enteral uncoated tablets, in 13 normal subjects trols. This indicates that these patients (five women, eight men), eight patients have a raised frequency of DNA damage stimulation with ulcerative colitis, and 21 patients with and chromosome aberrations or chromo- various types of Crohn's disease, all receiv- some non-disjunction. In order to distinguish W P MORGAN, P TRUSKEIT, M ROSE, AND J M ing prednisolone therapy. Normal subjects between the disease and the drug in the HAM (Departments of Surgery, Royal showed a peak plasma level (PPL) of causation of this effect we have examined Hallamshire Hospital, Sheffield and Prince on diagnosis but before treat- Wales Hospital, Sydney, NSW) We 285±4 SE ng/ml, a time to peak (TTP) of IBD patients of 105±2 minutes, and an area under the ment and at intervals over a 21 month have previously reported a model of TPN or other ther- in which cholestasis and gall curve (AUC) of 1389+11. Corresponding period during sulphasalazine in the pig, categories apy. There is a progressive increase in both bladder 'sludge' occurred. The present values in the various disease (significance of differences from normal) SCE and MN frequency in patients receiv- study was to determine whether the but no increase in the administration of TPN by methods causing were as follows: Ulcerative colitis: PPL ing sulphasalazine 343± 11 ng/ml (NS), TFP=209±11 minutes other patients. This implies that sulphasa- enteral stimulation altered those findings. lazine is the cause of the increased level of Intravenous, intragastric and intravenous (p<005), AUC=1422±31 (NS). Colonic or ileocolic Crohn's (n=6): PPL=335+ genetic damage. Acetylation of sulphapy- plus cholecystokinin infusions of TPN were 23 ng/ml (NS), TTP=205±10 5 minutes ridine, a major metabolite of sulphasala- administered to young pigs. Their effect AUC=1546±90 (NS). Ter- zine, is under genetic control but 'fast' and upon bile flow, bile salt excretion, liver (p<0.05), minal ileal Crohn's, including anastomo- 'slow' acetylating individuals do not differ histology, the character of gall bladder bile of genetic and the lithogenic index of hepatic duct tic recurrence (n=5): PPL=312+13 ng/ml in their (raised) frequency (NS), TTP= 183±3 minutes (p<0'05), damage. The significance of this genetic bile was compared with controls. Bile flow AUC= 1368±22 (NS). Jejunoileal or ex- damage is as yet unclear but could be and salt excretion were asscssed by their tensive ileal Crohn's disease (n= 10, six related to cancer risk. Alternative therapies response to sequential intraportal infusions with previous resection): PPL= 255+ of taurocholic acid (TCA) and secretin. for IBD should now be similarly assessed in 10.5 ng/ml (NS), TTP=220+12 minutes order to minimise risk to patients. The pattern and magnitude of the bile flow (p<0 05), AUC=1216+22 (p<005). Pa- and salt excretion responses to TCA dif- tients with extensive small bowel disease fered in the TPN groups compared to had a significantly lower PPL (p<0 05), T90 controls, but not to one another. Regression the other patient bile and AUC (p<0.05) than of analysis of the relationship between groups. These results show delayed predni- Double blind controlled comparison flow and bile salt excretion suggested that solone absorption in all patient groups, and balsalazide and sulphasalazine in the bile salt independent fraction of canali- that decreased absorption is confined to maintenance therapy of patients with cular flow was significantly less in all three ulcerative colitis patients with extensive small bowel http://gut.bmj.com/ TPN groups compared with controls. Gall Crohn's disease. In eight patients with bladder bile was normal in controls but steroid dependent disease, similar absorp- P B MCINTYRE, C A RODRIGUES, J E LFNNARD- viscid and particulate in the majority of JONES, I G BARRISON, J G WALKER, AND J H TPN pigs. The livers of the TPN animals tion studies were done, with the mini- mum dose required to maintain remission. BARON (St Mark's, St Mary's, and St showed marked centrilobular fatty infiltra- Charles' Hospital, London) Balsalazide indices of hepatic duct Despite variation in this dose between tion. The lithogenic patients, the plasma prednisolone levels (BSZ) is a pro-drug which releases 5- bile were low in all groups. We have failed obtained were similar in all patients, and aminosalicylic acid (5ASA) and 4-amino-1- to show enteral stimulation alters hepato- benzoylalanine (an inert carrier) in the

a 20 on October 2, 2021 by guest. Protected copyright. biliary dysfunction in TPN. about half those obtained with mg dose. intestine in man. Balsalazide was com- pared with sulphasalazine (SSZ) (both 1 g bd orally) in the maintenance in remission of patients with ulcerative colitis (UC). T89 Seventy five patients (51 men, 24 women) Sulphasalazine causes chromosome mean age 43 yr (range 19-79 yr) with UC INFLAMMATORY BOWEL DISEASE changes in patients with inflammatory were randomly allocated to either treat- T88-92 bowel disease ment (41BSZ, 34SSZ) for six months. The groups were similar in respect of age, sex, T88 J M MACKAY, D P FOX, P W BRUNT, G M smoking, duration and extent of disease. Plasma prednisolone concentrations HAWKSWORTH, AND J E BROWN (Depart- Four patients defaulted (2BSZ, 2SSZ) after oral administration in inflam- ments of Genetics, Medicine and Therapeu- leaving 39 on BSZ and 32 on SSZ for matory bowel disease: correlation with tics and Clinical Pharmacology, University analysis. Two other patients on SSZ with- anatomic extent and therapeutic efficacy of Aberdeen, Scotland) Sulphasalazine drew with side-effects. Remission rates at remains the treatment of choice for the six months (59% (95O/O CI 42-74%) BSZ, C A RODRIGUES, E M NABI, C SPILIADIS, P B long term management of colonic in- 73% (95% CI 54-88% ) SSZ) were not MCINTYRE, V PHONGSATHOM, J E LENNARD- flammatory bowel disease (IBD). We have significantly different (x =10, p>0.05). JONES, A ROSFN, AND M J WILLOUGHBY (St shown that IBD patients treated with Seventeen patients previously experienced Mark's Hospital, London, King's College, sulphasalazine have a higher frequency of minor side-effects from SSZ. Nine of 32 London and Lister Hospital, Stevenage, sister chromatid exchange (SCE) and mi- patients on SSZ and three of 39 on BSZ Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 1272 The British Society of Gastroenterology reported side effects in this study (p=0-048 Clostridium difficle has been implicated in simultaneously using the lecturescope. The Fisher's exact test). One patient with a skin relapse of UC. Controversy exists, how- endoscopists were unaware of which group eruption on SSZ did not react subsequently ever, over the diagnostic and therapeutic each subject was in and recorded their to open BSZ. Mean haemoglobin concen- implications for its role in UC. Sixty two of results independently. The gastric body, trations, similar on entry, increased after 77 patients (42 men, 35 women age 19-75 gastric antrum, duodenal bulb and duo- six months with BSZ (0-2 g/dl) but de- years) with UC in relapse were able to denal second part were assessed as follows: creased with SSZ (0-5 g/dl) (p<0-(H1). provide stool before treatment and within normal - 0, erythematous patches or Balsalazide may be as effective as SSZ in 12 hours of attending hospital. One patient streaks - one, haemorrhages - two, and the maintenance of UC in remission and with typical pseudomembranous colitis erosions - three. For each subject, the four has fewer side effects. after antibiotics was not included. Four had grades were added to give a composite received antibiotics other than sulphasala- score. There was 950o agreement between zine (SS) before the onset of their symptoms. the two endoscopists. The total scores for T91 Thirty five were taking SS. One patient was each of the three groups were: chilli - two; Reversal of sulphasalazine induced culture positive, toxin negative, after anti- aspirin - 39; control - four. Chilli vs seminal abnormalities after substitution biotics; another with detectable toxin (one aspirin - p<0-01 by the Wilcoxon's rank in two) but culture negative had not received sum test; aspirin vs control - p<0-01; chilli with 5-ASA (Mesalazine) antibiotics. Six with no initial stool sample vs control - not significant. All six subjects were CD culture negative during treatment. who took chilli reported nausea while five S RILEY, V MANI, M GOODMAN, B MANDAL, Fifty seven (25 in patients) were assayed experienced abdominal discomfort. One of AND L A IUJRNBERG (University, Depart- during their treatment period; two had the six subjects who took aspirin experi- ment of Medicine, Hope Hospital, Salford received antibiotics and became culture- enced abdominal discomfort. We conclude and Leigh Infirmary, Bury General, Mon- positive, but toxin negative, the remainder that although chilli ingestion is associated sall Hospital, Manchester) Seminal ab- were all negative. Three patients required with gastrointestinal symptoms, it does normalities are commonly found during emergency colectomy, all of whom were not lead to macroscopic gastroduodenal sulphasalazine (SZP) treatment. Although CD negative initially. By undertaking mucosal damage. these changes are reversible after with- culture and toxin assay before treatment drawal of the drug this may result in and any significant hospital exposure, this T94 disease relapse. Animal studies suggest study shows that CD is not a cause of that 5-ASA, the active component of SZP, relapse in UC and is not secondarily Somatostatin analogue (SMS 201-995) does not impair fertility. acquired during relapse unless exposed to inhibits early rapid gastric emptying We have studied 16 patients with chronic antibiotics. SS does not predispose to after truncal vagotomy and drainage ulcerative colitis in clinical remission taking acquisition of CD. There is no role for 2-3 g SZP daily. Each patient produced routine screening or treatment of CD in N PARR, S GRIME, S A JENKINS, M CRITCHLEY, three samples of semen at weekly intervals UC. J BAXTER, AND C MACKIE (Departments of and of the 48 samples analysed 40%O

SurgerY and Nuclear Medicine, University http://gut.bmj.com/ showed oligospermia, 40(% an increased oJ Liverpool and Royal Liverpool Hospital, number of abnormal forms and 90%° im- Liverpool) Somatostatin infusion, while paired motility. improving symptoms of early dumping in Eight patients substituted enteric coated pCatients, has been reported to accelerate 5-ASA (Mesalazine) tor SZP (dose equiva- DIET AND TJHE GUI gastric emptying (GE) of liquids in healthy lence 400 mg 5-ASA= 1 g SZP) for a T93- 104 volunteers. We have investigated the minimum period of three months. One effects of a long acting analogue of soma- patient developed a salmonella associated T93 tostatin, SMS 201-995. on GE in five dogs colitis relapse while the others remained Effect of chilli ingestion on the gastro- after truincal vagotomy and pyloroplasty on October 2, 2021 by guest. Protected copyright. well. Improvement in sperm count duodenal mucosa and in four patients suffering from dump- (p<0(05), motility (p<0 02) and morphol- ing or diarrhoea after truncal vagotomy ogy (p<0-02) occurred in all cases. J Y KANG, I YAP, AND I cC lIM (Department with drainage. Suboptimal improvement of motility of Medicine, National University of Sing- Gastric emptying was assessed using prompted re-evaluation in two patients apore and the Department of Medicine gamma camera imaging of 15°/ dextrose after 12 months 5-ASA and in these further IIl, Singapore General Hospital, Sing- labelled with ")')'Tc-DTPA. Studies were improvement occurred. These studies de- apore) Chilli ingestion may lead to dys- done with and without prior administration monstrate that treatment with 5-ASA pepsia. The aim of the present study was to of SMS 201-995 (0(05 mg SC). Each animal allows the recovery of seminal abnormali- determine whether acute ingestion of chilli study was duplicated. ties induced by SZP in patients with colitis. causes macroscopic gastroduodenal muco- In both dogs and patients GE without sal damage. Eighteen healthy male subjects prior administration of SMS 201-995 was were studied after a normal control endo- biphasic with an early rapid component. T92 scopy one week previously. By random Gastric emptying at 10 min was 35+6%Yo Clostridium difricile (CD) and ulcerative allocation, six subjects took 20 g ground (mean±SEM) for dogs and 84±5% for colitis (UC) dried chilli (Capsicum annlum), another six patients. Administration of SMS 201-995 2 tablets of aspirin 300 mg each, while the significantly inhibited GE during this D A BURKE AND A T R AXON (Gastroenterol- last six acted as controls. Endoscopy was period, being 13±3'Yo for dogs (p<0)-2, ogy Unit, The General Infirmary, Leeds) done six hours later by two endoscopists Student's paired t test) and 44+±10(o for Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A 1273 patients (p<0(05). By the end of the test pital Medical Physics Department, New- in untreated coeliacs were strongly positive period, however, (dogs- 60 min, patients - castle upon Tyne) It is generally believed for all antigens. Crypt enterocytes were 30 min) the differences in GE between that postvagotomy diarrhoea is caused by DQ and DP and weakly DR in controls studies with and without SMS 20)1-995 gastric incontinence. This is based on the and treated coeliacs, but strongly DR' and administration were not significant (dogs: results of intubation studies and outdated weakly DO' DP' in untreated coeliacs. with=25±5%, without=35±6°/o; patients: radioisotope techniques which may have The intensity and extent of distribution was with=62+ 14%, without=88±6%). These underestimated the early emptying phase. DR> DP> DO. Intra-epithelial lympho- results show that SMS 201-995 inhibited We have re-investigated this hypothesis cytes (IELs) were negative for class II rapid early GE of liquids after truncal using a computerised gamma camera sys- antigens in controls and treated coeliacs vagotomy. Inhibition of this magnitude has tem to measure emptying of a 50% glucose with a T4:T8 ratio of 2:3. In untreated not previously been achieved, except by drink. Plasma volume changes (haemato- patients > 80% of IELs were DR' DP' revisional surgery. crit method) were also measured. Fifteen with a T4:Ts ratio of 1:1. patients 3+ years after truncal vagotomy In conclusion, untreated patients have T95 and pyloroplasty were studied, divided into increased class II expression on enterocytes two distinct clinical groups - seven with and IELs. This has implications for gliadin Blood glucose, plasma motilin and gas- postvagotomy diarrhoea (A) and eight presentation, in vivo activation (only acti- tric emptying without (B). vated T-cells express class II) and autoim- The drink provoked diarrhoea attacks in munity. S L GRAINGER, I SCOBIE, J PETRANYI, J I seven of seven in group A but only one in GAUNT, AND R P H THOMPSON (Gastrointes- eight in group B (p<0-t)01). Early gastric T98 tinal Laboratory, The Rayne Institute, St emptying was rapid in both groups (median Thomas' Hospital, Londoni) Gastric T1/2: 6 minutes vs 8-8 minutes; p=NS). Six Mucosal permeability to gliadin is motility is enhanced by hypoglycaemia and of seven in group A and six of eight in normal in treated coeliac disease diminished by hyperglycaemia; the mechan- group B emptied more than half of the glu- ism might be because of altered levels of cose within 10 minutes (p=NS). The maxi- D J DAWSON, A M DUNNE, R W LOBLEY, J peptides that modulate motor activity of mum fall in plasma volume was greater in NOTMAN, M MAHON, P M RAWCLIFFE, AND R the gut. group A (median fall: 13% vs 8%; p<0(00l) HOLMES (University Department of Gas- We have measured plasma motilin and This fall did not correlate significantly with troenterology, Manchester Royal Infirmary gastric emptying of radiolabelled poached any parameter of gastric emptying. We and Department ofAnatomy, University of egg white twice in eight diabetic patients on conclude that gastric incontinence does not Manchester, Manchester) Abnormal in- different days at blood glucose levels of 3 necessarily lead to diarrhoea. These results testinal permeability to gliadin may be and 11 mmol/l, maintained by dextrose/ suggest that therapy should be aimed at implicated in the aetiology of coeliac dis- insulin infusion for at least two hours. reducing fluid shift into the intestine rather ease. We have measured the 10 minute Vagal tone was assessed from heart rate than attempting to uptake and mucosal permeation of 3H- slow gastric emptying. http://gut.bmj.com/ variations during deep breathing and plas- labelled peptic tryptic fragments of gliadin ma motilin was measured immediately and bovine serum albumin (BSA) into before the labelled meal. T97 jejunal biopsies from treated coeliac pa- Vagal tone was unaffected by blood tients (n=9) and controls (n=-l). The glucose level. At the lower level, however, Expression of class II antigens in coeliac acute effects of the proteins on sugar gastric transit was faster in every patient jejunal mucosa permeability were also measured. Peptic (median area under emptying curve 5360 vs hydrolysis during incubation was inhibited 5639, p<00t)l), chiefly because of the A M P MONTGOMERY, C NAVARRETE, AND P J by a combination of aprotinin, bestatin, and shorter gastric lag times (median 23 vs 34 KUMAR (Department of Gastroenterology, on October 2, 2021 by guest. Protected copyright. St captopril. min, p<0)10), and plasma motilin levels Bartholomew's Hospital and Department Mucosal permeation of gliadin was tended to be higher (mean (SE) 28 (9) vs 16 of Immunology, The London Hospital, greater than that of BSA in controls (4) pmol/l, p=0-08). London) Class II antigens have distinct 0-66 wt functions [median lIUmg dry (interquartile Therefore ambient blood glucose con- in immunoregulation (DR in range 0-604-0688) vs 0-421 (0-350-0521), centration influences gastric transit of food stimulation, DO in suppression), whilst but not in coeliacs their p=0o016)] [0.520 and may thus regulate food intake. Gen- expression on non-immunological (0-516-0-556) vs 0-4611 (0-361-0-634), eral changes in vagal tone are not involved; cells has implications for antigen presenta- p> 0-5). Mucosal permeability to gliadin changes in motilin level may be causal or tion and autoimmunity. These functions (permeation corrected for mucosal surface simply secondarily reflect enhanced gastro- suggest a role for these antigens in the area) was not significantly different from duodenal motility. immunopathogenesis of coeliac disease. that for BSA in either group, but BSA Serial sections of jejunal mucosa from permeability was increased in coeliacs controls T96 (six), treated coeliacs (six) and (p<003). Neither gliadin nor BSA had a untreated coeliacs (six) were used in three significant effect on the permeation or Postvagotomy diarrhoea is more than stage immunoperoxidase techniques using mucosal permeability for mannitol or gastric incontinence new monoclonal antibodies to DP and DQ raffinose. and monoclonals to DR and T-cell subsets. These results provide no support for S A RAIMES, V SMIRNIOTIS, F HAWKINS, C W In controls and treated coeliacs villous en- abnormal peptide permeability or for a VENABLES, AND I D A JOHNSTON (University terocytes were DQ negative (DO ), weakly selective mucosal defect in gliadin per- Department of Surgery and Freeman Hos- DP positive (DP') and strongly DR' but meability in treated coeliac disease. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 1274 The British Society of Gastroenterology Gliadin has no acute effects on the per- disease in remission on a gluten free diet. better results cannot be achieved with meability of other solutes in vitro. Control studies were undertaken at 33 more energy alone (1 5 kcal/ml), but also sg/ml using eight healthy controls matched substantially more N (9 4 g/l) is required. for age and sex and a group of patients with T99 inactive ulcerative colitis or Crohn's dis- Coeliac disease and malignancy ease who were not receiving immunosup- T102 pressive therapy. At 33 tg/ml the migration Small intestinal response to 'elemental' M R LANE, P PRIOR G K T HOLMES, AND R N index (MI) was 0-74 (SD 0(09) for coeliacs and 'complete' liquid feeds ALLAN (General Hospital, Birmingham) compared with 0-97 (SD 0()12) for healthy The increased risk of malignancy in coeliac controls (p<0(00 1). No significant differ- D G MAXTON, E U CYNK, AND R P H disease is now well accepted, whether this ence was found between healthy controls THOMPSON (Gastrointestinal Laboratory, risk is reduced with the use of gluten free and patients with inflammatory bowel dis- The Rayne Institute, St Thomas's Hospital, diets remains unknown. The longterm out- ease (p> 0.05). A dose response effect was London) Liquid amino acid elemental come among 210 patients studied in 1976 seen in coeliacs. At 33 [tg/ml MI was 0(74 diets may be effective in Crohn's disease by who presented with biopsy proven coeliac (SD 0-09), at 11 tg/ml MI was 0-87 (SD producing bowel rest. Substitution with disease before 1973 has been reassessed. 0-06, p

feeds reduce ileal weight more profoundly. on October 2, 2021 by guest. Protected copyright. 12 gen. Forty three patients requiring naso- This property may be important for the gastric feeding were randomised to receive therapeutic effect of elemental diets in J A KARAGIANNIS, J D PRIDDLE, AND D P 2 I/d of one of three diets supplying the inflammatory bowel disease, and is prob- JEWELL (Gastroenterology Unit, Radcliffe following total energy (kcal) and N (g): ably due to the availability of luminal Infirmary, Oxford) A sequence analogy 2000 and 12 6 (gp I, n= 13); 3000 and 15 6 nutrients. has been reported between a region (re- (gp II, n=14); 3000 and 18 8 (gp III, sidues 206-217) from A-gliadin of Scout 66 n= 16). Groups compared well for duration wheat and the early protein Elb of human of feeding (gp 1, 10-8±SD 6 2 d; gp II, T103 adenovirus type 12 (residues 384-395). 11 6+6 2; gp III, 11-9+6.6). There was no Bicarbonate in oral rehydration solu- Cross-reactivity was shown between Elb, significant difference in average daily N tions (ORS): a double blind controlled A-gliadin and a synthetic heptapeptide balance between gps 1 (-4.0±9.8 g) and trial in children with gastroenteritis in comprising A-gliadin residues 211-217. II (-1X8±7.2). In contrast, significantly the United Kingdom Cell mediated immunity to a peptide better daily N balance was achieved in gp comprising A-gliadin residues 206-217, III (+116±5-6) compared with gps I E J ELLIOTr, J A ARMISTEAD, M J G FARTIIING, prepared by solid phase synthesis, was (p<0.001) and II (p<0-003). AND J A WALKER-SMITH (Academic Depart- studied at 33, 11 and 5-5 ,g/ml using a These findings confirm that in routine ment of Child Health, Queen Elizabeth two-stage migration inhibition assay. clinical practice, widely used 'standard' Hospital for Children, London and Depart- Peripheral blood mononuclear cells were diets supply insufficient energy and nitro- ment of Gastroenterology, St Bartholomew's prepared from eight patients with coeliac gen for positive N balance. Significantly Hospital, London) Bicarbonate is added Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Societv of Gastroenterology A1275 to ORS for (i) correction of acidosis and infusion (2 ng/kg/min) and 40 patients nium. The increase in disease at all sites (ii) promotion of sodium and water absorp- placebo (P) infusion administered on the suggests that the figures are not distorted tion. Nevertheless, there is little objective first postop day. The two groups were by inclusion of patients who would pre- clinical evidence to support its inclusion. similar in respect of age, sex, operation, viously have been labelled ulcerative colitis. Forty children < 5 years old with acute extent of bowel handling and serum elec- The figures show that the incidence of gastroenteritis for

would simplify production, increase stability pares with the buccal epithelial cell index http://gut.bmj.com/ and reduce cost of ORS, without apparent J D R ROSE, J RHODES, G WILIIAMS, G M of 470o for the enteropathogenic EC impairment of efficacy. ROBERTS, AND J F MAYBERRY (University E851/7 1. Hospital of Wales, Cardiff and City Hos- The buccal epithelial cell assay offers a T10)4 pital, Nottingham) The incidence of simple and rapid screening technique that Crohn's disease in the City of Cardiff has differentiates between inflammatory bowel Pharmacological manipulation of post- been recorded from 1934 and has risen disease and control EC due to the expres- operative ileus: results of a placebo from 0.18/105/year for the period 1931-35 sion of a potentially pathogenic characteris- controlled double blind clinical trial to 4 92/10S/year for the period 1976-80; a in the EC of tic patients with inflammatory on October 2, 2021 by guest. Protected copyright. total of 281 patients were identified between bowel disease. Eighty six per cent of S A SADEK, C ERIKSEN, C A CRANFORD JR, 1934 and 1980. From diagnostic records in patients with inflammatory bowel disease AND A CUSCHIFRI (Department of Surgery, the Departments of Pathology, Radiology, carry EC with a buccal epithelial cell index Ninewells Hospital and Medical School, Outpatient Clinics and from the Area >25% compared with 0% controls. Dundee) Postoperative ileus after abdo- Health Authority 115 new patients with This observation supports the hypothesis minal surgery contributes to hypoxaemia Crohn's disease resident within the City at that EC have a role in the pathogenesis of and chest infection, and may delay recov- the time of the diagnosis were identified inflammatory bowel disease. ery after abdominal surgery. Attempts at between 1981-85. The individual yearly pharmacological manipulation have in- incidences/105 of the population were 6-4 cluded adrenergic blockage and chol- in 1981, 7 1 in '82, 9 3 in '83, 6-4 in '84 and T107 inesterase inhibition. The synthetic peptide 11-8 in '85 with a mean for the 5-year Plasmid profiles in E coli isolated from ceruletide has been shown to reduce post- period of 8-2/105/year. IBD patients operative intestinal paralysis. The effect of Analysis of the distribution of disease at this agent on the postoperative course was the time of diagnosis showed all forms were M R LANE, P E PEASE, AND R N Al.LAN (De- investigated in a placebo controlled double increasing. Of the 115 patients, 42 had partment of Medicine Microbiology, Medi- blind randomised clinical trial involving 82 ileocaecal disease, 43 ano-colo-rectal dis- cal School, Birmingham and The Gastro- patients undergoing elective abdominal ease, six small bowel and 21 a combination enterology Unit, General Hospital, Birming- surgery. of small and large bowel disease. This ham) Plasmids, extrachromosomal DNA On completion, 42 patients were found distribution of disease does not differ elements, found in bacteria mediate many to have received ceruletide (Cer) as an iv significantly from the previous quinquen- functions including virulence. We have Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 1276 The British Society of Gastroenterology examined plasmid profiles of E coli from artefacts of the six salt steps used. Further- RICHARD F A LOGAN, CLIFFORD R KAY, AND patients with inflammatory bowel disease more, comparison with ion-exchange LOUISE SCOTT7 (Department of Community to search for a putative 'disease-related' chromatographs of highly purified bovine Medicine and Epidemiology, The Univer- plasmid. submaxillary mucin suggests that at least sity of Nottingham Medical School and the Forty three isolates from 27 patients with two of the six subclasses may not be Royal College of General Practitioners, ulcerative colitis (UC), 17 from 12 with mucins. Manchester Research Unit, Manchester) Crohn's disease (CD) were compared The previous findings may therefore Recent studies have suggested that con- with 44 isolates from 25 control patients. simply reflect mucus depletion and further traceptive pill use is associated with a two Plasmids were extracted using alkaline lysis work is needed to elucidate colonic mucus to four-fold increased risk of Crohn's at 56°C, cellular protein precipitated with glycoprotein abnormalities in ulcerative disease (CD) and Vessey et al have also phenol and removed by centrifugation and colitis. found a two fold increased risk of ulcera- the plasmids separated by electrophoresis tive colitis (UC). We have examined pros- in 0-7% agarose. T109 pectively collected data on pill use, smoking The average number of plasmids per and the development of CD and UC isolate were controls (4 2), UC (3.12) and Can rectal biopsy distinguish acute self- available from the RCGP contraceptive CD (2.35) (p<0-05). These reductions in limiting colitis from early inflammatory study which has recorded all new morbidity plasmid number were due to significant bowel disease occurring in 46 ()0) married women followed loss of small plasmids (<3-6 Kb pairs). since 1968. After excluding 13 cases where Within the UC group isolates from active M C AlIISON, S J IIAMILTON DUTOFF, P the diagnosis was not confirmed CD had colitis contained more plasmids than those DHII-LON, AND R E POUNDER (Academic developed in 42 and UC in 78 women. with inactive disease (4.09 vs 2-09 p<0 05). Departments of Medicine and Histopathol- Annual incidence of CD (10/100 000) and Sulphonamide resistance did not affect ogy, Royal Free Hospital School of Medi- UC (19/100 000) were in keeping with plasmid numbers, but did seem to account cine, London) It can be hard to distin- expected figures. There were small in- for the presence of plasmids common guish acute self-limiting colitis (ASLC) creases in rates of both CD and UC in to several isolates. The increased number from inflammatory bowel disease (IBD) in current pill users compared with non-users of plasmids found in active UC when a patient presenting for the first time with (Ratio of rates (RR)) for CD=1 6. compared with inactive UC supports the diarrhoea and/or rectal bleeding. We iden- p>0(05, RR for UC= 1-5, p>0.05). Rates concept of plasmid mediated factors influ- tified 72 such patients who presented in of CD and UC in ex-users were similar to encing the activity of ulcerative colitis. one health district between 1978 and 1983, never users. Analysed by smoking habit, in whom biopsy of inflamed rectal mucosa recorded at entry, the incidence of CD was had been T108 performed. Follow up informa- higher in smokers and that of UC lower. tion was obtainable for 64 patients of The incidence in non-smokers, smokers of Colonic mucin subclass defect in ulcer- whom 37 had definite IBD. The other 27 <20/day and smokers of >20/day of CD ative colitis: real or artefact? had had no further symptoms or treatment, was respectively 8, 13 and 18/100 000 and and were considered to have had a single of UC respectively 22, 16, 13/100 000 - http://gut.bmj.com/ M RHODES, N PARKER, P PATEL, AND C K episode of ASLC. All original biopsies results consistent with previous studies of CHING (University Department of Medi- were evaluated blindly by two independent smoking in CD and UC. In this the largest cine and Walton Hospital, Liverpool) It observers for the presence of eight criteria study of pill users there were only small has been suggested that ulcerative colitis reported to be highly discriminant between increases in risk of CD and UC in pill users results from defective colonic mucus. ASLC and IBS. Crypt distortion and lym- which were not statistically significant and Podolsky and Isselbacher recently reported phocytic infiltration were commonly seen, disappeared after stopping the pill. a selective depletion of one of six mucin but were only 75-80%0 predictive of IBD.

subclasses defined by discontinuous gra- Epithelial surface erosions, crypt atrophy on October 2, 2021 by guest. Protected copyright. dient ion-exchange chromatography of or lymphoid aggregates beneath the crypts Tl 1 1 purified colonic mucus obtained from pa- each had 82-90% specificity for IBD. Mucosal T lymphocytes and HLA-DR tients with ulcerative colitis in remission Isolated basal giant cells or epithelioid expression in ulcerative colitis (Gastroenterology 1984; 87: 991-8). The granulomata, although present in only 11 significance of this finding depends on the biopsies, had 100% predictive value for L K TREJDOSIEWICZ, S BADR-EI-DIN, D J interpretation of the ion-exchange chroma- IBD. OAKES, R V IEAITIEY, G JANOSSY, AND M S tography. The discriminant features recorded in LOSOWSKY (Department of Medicine, St We have analysed mucus obtained from this study can distinguish ASLC from IBD James's University Hospital, Leeds and colon resected for carcinoma (n=6). Mucin in rectal biopsies from most new patients Academic Department of Immunology, was purified by homogenisation, centri- with colitis. Only the presence of basal Royal Free Hospital, London) Mucosal fugation, Sepharose 4B gel filtration and giant cells or epithelioid granulomata, immunoregulatory T lymphocytes are caesium chloride density gradient centri- however, is diagnostic of IBD. thought to play a major role in ulcerative fugation. Discontinuous gradient ion- colitis (UC), although their subset distribu- exchange (DEAE cellulose and Pharmacia TI 10 tion and relationship to MHC antigens has mono 0) with six salt steps yielded six not been extensively studied. We have mucin fractions but continuous gradient The pill, smoking and inflammatory used double label immunofluorescence of ion-exchange yielded only three major bowel disease - results from the Royal cryostat sections of colonoscopy biopsies fractions. This shows that the six mucin College of General Practitioners with combinations of monoclonal anti- subclasses previously reported are largely (RCGP) Oral Contraception Study bodies in 21 UC patients (10 with total Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A1277 colitis) and 30 controls. Although large architecture is normal. Plasma cell num- showed good correlation with mucosal individual variations in both groups were bers in small bowel did not differ between relapse on challenge a high count at di- observed, there were no statistically signifi- IL (IgG 5-5±0 1; IgA 94-2±9-9; IgM agnosis was of insufficient specificity to cant differences between patient and con- 53-1±5-1 per 1000 random points, obviate the need for gluten challenge. trol groups in either intraepithelial or mean+SEM) and the other two groups. In- lamina propria compartments in terms of traepithelial lymphocytes were, however, CD4:CD8 (T4:T8) ratio, nor of co- significantly reduced in IL (1t)-2±1-9, per T1 14 expression of CD5 (TI) antigen by CD8' 1(X) epithelial cells) compared with normal Restorative proctocolectomy J pouch (T8 suppressor/cytotoxic) cells. However, (18(0±0+8, p<0 (1). Thus patients with IL ileoanal anastomosis: a single surgeon's there was increased expression of the CD7 have morphological evidence of normal experiences over two and a half years (T2 'T blast') antigen by CD4' (T4 helper/ humoral immunity in the gut, but a reduc- inducer) cells in those patients where the tion in intraepithelial lymphocytes. It is of M R B KEIGHI EY (The General Hospital, epithelium was strongly positive for ex- interest that this latter abnormality, a loss Birmingham) Thirty two patients have pression of MHC Class II antigens (HLA- of suppressor-cytotoxic lymphocytes, is not had a J pouch ileoanal anastomosis since DR and HLA-DO). Moreover, whereas associated with gut infections. October 1983 (three polyposis, 25 ulcera- the epithelium of control patients was tive colitis, four megacolon): 20 had a invariably negative for Class II antigens, in previous colectomy and 12 a single stage the majority (58%/) of UC patients, the T1 13 proctocolectomy (five had no stoma). epithelium was strongly HLA-DR+ and There were no deaths: 12 patients (370o) HLA-DQ+, especially in patients with Predictive value of intraepithelial lym- counts in entero- had surgical complications (pelvic sepsis total colitis (87%), irrespective of treat- phocyte childhood six, bleeding one, rectovaginal fistula one, ment or duration of illness. Class I MHC pathies high fistula-in-ano one, intestinal obstruc- antigens (HLA-A, B, C) were expressed tion two, electrocutaneous fistula three). apparently equally by enterocytes in UC C J TAYLOR (Department of Child Health, The pouch has been removed in two and control groups. These data suggest that Alder Hey Children's Hospital, Liverpool) (sepsis, bleeding) and a loop ileostomy local immunostimulation of CD4+ helper/ Changes in intraepithelial lymphocyte raised in three (rectovaginal fistula, short inducer cells may be linked to the possible (IEL) numbers have been found to correlate bowel syndrome, sepsis) three patients are antigen-presenting capabilities of MHC with active coeliac disease. If specific, IEL awaiting ileostomy closure. Class II+ enterocytes, especially in total counts may be of value in childhood entero- Of 25 whose intestinal continuity has colitis, and thereby result in the mainte- pathies, where subtotal or severe partial been restored the median frequency of nance of the chronic inflammatory state. villous atrophy is not infrequently seen defecation is 5 7 during the day, and only with cow's milk protein intolerance (CMPI) eight rise at night. Only one patient wears or after gastroenteritis. To evaluate the use TI 12 pads (only at night). Fourteen patients take of IEL counts a supervised gluten challenge antidiarrhoeals and 11 require dietary res- http://gut.bmj.com/ Local mucosal immune system in intes- was performed on 116 children initially triction. None have sexual dysfunction. tinal lymphangiectasia diagnosed as coeliac on the basis of charac- Three patients have features of Crohn's teristic jejunal biopsy and an apparent disease in the colectomy specimen. Median M MYSZOR, THE LATE ANGELA DAVIDSON, AND response to gluten exclusion. Counts were duration of convalescence is 6 2 months H J F HODGSON (Departments of Medicine performed blind by a single observer on (2-18 months). Improvements in surgical and Pathology, Royal Postgraduate Medi- routinely processed 4 ftH+E sections. technique which seem to have reduced cal School and Hammersmith Hospital, Results were expressed as IELs/100 morbidity include: stapling leaving a long Immunodefi- enterocytes. Ducane Road, London) rectal stump at the original colectomy, on October 2, 2021 by guest. Protected copyright. ciency, affecting either cell mediated or Forty nine per cent of patients failed to mucosectomy from above, extensive vascu- humoral immunity, is often associated with relapse on challenge with only one late lar mobilisation of the ileal blood supply, chronic intestinal infection. Intestinal lym- relapse on two year follow up. Reappraisal preservation of the ileocolic artery and phangiectasia (IL) is sometimes associated of these cases suggested alternate di- removal of the entire rectal cuff. with marked immunodeficiency, due to agnoses, of which CMPI (16%) or post loss of immunoglobulins and T cells into enteritis (20%) were the most common. the intestinal lumen, but not with obvious Intraepithelial lymphocyte counts in con- TI 15 susceptibility to gut infection. We investi- firmed coeliacs were high at diagnosis gated this paradox by studying local intesti- [67±(16)] (mean (+SD)) fell on diet Treatment of Crohn's disease with nal immunity in IL. We compared lamina [28±(13)] and rose on challenge [64+(20)J. Cyclosporin-A: a report of 11 cases propria plasma cell counts, and intra- These changes were significant (p<0-01 epithelial lymphocyte counts (IEL) in using paired t test). Raised IEL counts at H R PARROTT, R M R TAYLOR, C w VENABLES, jejunal tissue from six patients with IL, diagnosis were also found in patients with AND C 0 RECORD (Gastroenterology Unit nine normal biopsies, and nine with un- CMPI and giardiasis but a significant fall and Department of Surgery, Royal Victoria treated coeliac disease. In well orientated on diet only occurred in CMPI patients Infirmary and University of Newcastle upon sections, plasma cells stained for IgG, IgA (p<0(05). Only patients showing mucosal Tyne) It has been suggested that and IgM were counted using a random relapse - that is, confirmed coeliacs, Cyclosporin-A may be effective in the dispersed points grid. Intraepithelial lym- showed a significant increase in IELs post treatment of active Crohn's disease. Its phocytes were expressed per 100 epithelial challenge compared with counts on a clinical utility in a series of 11 patients with cells, a procedure valid when villous gluten free diet. While an increase in IELs active disease as shown by a raised activity Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1278 The British Society of Castroenterology index, ESR or mucoproteins, or depressed B 16). The 178 patients who completed the T1 18 serum proteins or haemoglobin is therefore trial without incident complied well with Total pancreatectomy - diabetes and reported. All of the patients except one the diets prescribed (Median change in enzyme replacement were started on a dose of 15 mg/kg/day for sugar intake A -76 G/week (NS): B -372 two weeks after which the dose was pro- G/week (p<0-001). Median change in fibre I P lINEHAN, D C BROWN, A B KURTZ, AND gressively decreased until termination intake A -3 G/week (NS): B +48 G/week R C G RUSSEI.I (Departments of Surgery after a maximum of one year. Only five of (p<0-001) at two years. The clinical score and Medicine, The Middlesex Hospital, the patients responded to treatment, the deteriorated in 52 (A 24: B 28), was London) Total pancreatectomy will remainder having shown no clinical improve- unchanged in 12 (A 11: B one) and relieve the symptoms of end-stage chronic ment, deteriorated or failed to absorb the improved in 114 (A 55: B 59). pancreatitis but it reputedly results in drug. Two of the patients who initially Thus, a greater number of patients failed dangerous 'brittle diabetes'. This has not appeared to respond relapsed during main- to continue with diet B and no clear been our impression, therefore we have tenance treatment and one required surgery. difference in the clinical course was observed reviewed our experience in relation to Two further patients required surgery but in patients who accepted the two different diabetic control and enzyme replacement. the remainder responded to corticosteroids types of dietary advice. Twenty two patients are under review sometimes dramatically. The most common after undergoing total pancreatectomy for side effect has been hyperaesthesia, which benign disease (follow up 4-80 months); occcured in most patients, but this improved eight standard total pancreatectomy (TP) when the dose of the drug was decreased. PANCREATICO-BILIARY and 14 duodenum-preserving total pan- One patient developed mild nephrotoxicity, TI 17-128 createctomy (DPTP). They were compared which was dose dependent and reversible. with age and sex matched insulin- In conclusion, in our experience Cyclosporin- T1 17 dependent diabetic controls for HbAl, A appears to be of low efficacy and has percentage ideal body weight (0%/IBW) only a limited place in the treatment of Raw soya flour produces a marked in- and insulin requirement/kg/day. Bowel Crohn's disease. crease in cholecystokinin (CCK) release frequency and enzyme requirement was in man assessed. T1 16 Total pancreatectomies weighed less J C BOJARSKI, C J SPRINGER, AND J CALAM than controls (median %IBW 89-7, 115 6, Controlled multicentric therapeutic (Department of Medicine, Royal Post- p=0 004) and had lower insulin require- trial of an unrefined carbohydrate, graduate Medical School, Hammersmith ment (medians 0(49, 0-64, p=0.024). fibre rich diet in 'Crohn's disease' Hospital, London) Rats fed on raw soya DPTPs did not differ from controls. HbAI meal develop increased plasma CCK and did differ in any group. There were five JEAN K RITCHE, JANE WADSWORTH, J E pancreatic hypertrophy and cancer. severe hypoglycaemias in the TPs (three LENNARD-JONES, AND ELIZABETH ROGERS Cholecystokinin stimulates pancreatic during periods of profound steatorrhoea)

(St Mark's Hospital, London) Between growth and soybeans contain trypsin in- compared to one each in DPTPs and http://gut.bmj.com/ 1.9.80 and 31.8.83, 352 patients with in- hibitors which remove inhibition of CCK controls. Twelve patients had normal active or mildly active Crohn's disease but release by trypsin. The relevance of this bowel action and have stable diabetes: two on no drug therapy apart from sulpha- effect to man, however, has been ques- on Pancrex V Forte (30 and 150 tabs/day) salazine were entered from 39 hospitals tioned on the basis that soybean trypsin and 10 on Creon (median 52 5/day, range into a prospective trial to assess the effect inhibitors are partially inactivated by hu- 18-80). Ten are increasing their enzyme of two different diets on disease activity. man gastric juice and react less with human dose. The clinical condition was assessed at three trypsin compared with rat trypsin. Adequate pancreatic enzyme replace- monthly intervals using a scoring system Eight normal subjects ate scrambled egg ment is essential to prevent diabetic insta- on October 2, 2021 by guest. Protected copyright. and dietary intake recorded every six on two occasions plus 5 g of soya flour in bility, and if attained diabetic management months. One hundred and sixty two patients apple sauce every 30 min. On one occasion is straightforward. were randomly allocated to diet A (un- flour was raw and on the other it had been restricted sugar low fibre) and 190 diet B heated resulting in a fall from 34 to 3 mg in (ideally no sugar high fibre). trypsin inhibited/gram of flour. Cholecys- T1 19 During the two year trial period 21 tokinin was measured in C18 Sep-pak patients required surgical treatment (diet extracts of plasma using a bioassay on Endoscopic biliary prostheses in 102 A 14: diet B seven). Thirty nine patients dispersed rat pancreatic acini. poor risk patients with carcinoma of were admitted to hospital (A 21, anal Raw flour produced a substantial and the pancreas surgery only two: B 18, anal five) and 36 sustained increase in plasma CCK with a required out patient treatment with anti- two hour integrated CCK response of A G SPEER, P B CO1'rON, L P DINEEN, AND R P inflammatory or antibacterial drugs (A 15: 21 1+6-6 pM (mean±SE) compared with A'HERN (Department of Gastroenterology, B 21). Seventy w eight patients withdrew/ 6-6+2-6 pM during ingestion of cooked The Middlesex Hospital and Cancer Re- were withdrawn before completion of the flour (p<0-01, Wilcoxon matched pairs search Campaign Centre, King's College trial. The withdrawal was caused by test, p also <0-05 at four time points). Hospital, London) Between May 1983 worsening of symptoms (including weight This result is of interest because a recent and March 1986 102 patients with low loss) in 22 (A two: B 20), dietary non- rise in the incidence of pancreatic cancer biliary obstruction caused by carcinoma of compliance in 24 (A four: B 20) or for coincidcs with a massive increase in soya the pancreas were considered for palliation unknown or irrelevant reasons in 32 (A 16: products in our diet. with an endoscopic biliary prosthesis. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A 1279

These were high risk patients judged un- Ten patients were studied (seven men, prospective trial of fresh frozen plasma suitable for surgery - median age 76 years three women). All had a laparotomy di- in the treatment of acute pancreatitis (35-95); median bilirubin 378 stmolIl (27- agnosis of pancreatic cancer, five had 907); 25 patients (25%) had renal impair- metastases and the diagnosis was con- T LEESE, M HOLLIDAY, D HEATH, T HUNT, ment and 17 patients (17%) had previous firmed histologically in a further three. J SCOU, D WITHERS, M C A BREUT, AND A W unsuccessful attempts at surgical (14) or Serum CEA and Ca 19-9 levels were HALL (Departments of Surgery and percutaneous (3) relief of obstruction. measured, 7t) MBq of radiolabelled anti- Pathology, University of Leicester, Leices- Three patients had such advanced disease body administered, and imaging performed ter) An uncontrolled clinical study and that endoscopic intervention was judged after 48-72 hours. Positive tumour uptake animal work suggests fresh frozen plasma not indicated and all three died within was demonstrated in eight of 10 patients; (FFP) reduces mortality in acute pancreati- seven days. Stenting was attempted in 99 four primary cancers, one of three liver tis, possibly by replenishing the plasma patients and was successful in 88 (899%). metastases and three of three abdominal antiproteinase system. A prospective con- The external diameter of the prostheses metastases. In two patients with ascites trolled randomised clinical trial is under- used was 11 5 Fr gauge - 9, 10 Fr - 71 and diffuse intra-abdominal uptake was also way to explore this possibility. 8 Fr - 8. The serum bilirubin fell satisfac- seen. Serum Ca 19-9 levels were particu- Patients with acute pancreatitis have torily in 87 patients (89'Yo of attempted larly raised in patients whose cancers were prognostic markers measured and are procedures). The 30 day mortality for successfully imaged. randomised to receive either FFP (2 units successfully inserted prostheses was eight This study suggests that immunoscin- per 24 hours for 72 hours) or purified patients (9% ). Complications occurred tigraphy using Imacis-1 may have a role in protein fraction (1 bottle per 24 hours for within two weeks of the procedure in nine the investigation of patients with suspected 72 hours) as part of the intravenous fluid patients (9%O) mainly cholangitis. The med- pancreatic cancer. therapy. Serum cc, antiproteinase and (i2 ian survival of patients with successfully macroglobulin levels are measured on days inserted stents was 21 weeks (mean 25 1, 3, and 7. weeks). Prosthesis blockage requiring en- T121 To date 113 attacks of acute pancreatitis doscopic replacement occurred in 26 pa- Results of an aggressive surgical ap- have been randomised - 56 FFP and 57 tients (29-5% of those at risk). Duodenal proach to hilar cholangiocarcinoma colloid control. The two groups are well obstruction requiring surgical bypass de- matched in all clinical criteria including veloped in two patients. A Cox regression N S HIADJIS, I S BFNJAMIN, AND L H BLUM- prediced severity of pancreatitis. No signi- analysis identified increased age and high GART (Department of Surgery, Royal ficant difference has yet been shown be- white cell count as having a significantly Postgraduate Medical School, London) tween the two groups in clinical outcome adverse effect on survival. Age <80 years Of 128 patients admitted with hilar (five deaths in each group). Both show a median survival 24 weeks (mean 28-6), age cholangiocarcinoma, 27 underwent cura- significant rise in a, antiproteinase levels > 80 years median survival 18 weeks (mean tive resection. There were 11 local resec- from days 1 to 3 and this is not influenced 18) (p=0-006). White cell count <6-5 of FFP. ct, tions of the ductal confluence and 16 liver by administration macroglobulin http://gut.bmj.com/ cells/ml median survival 24 weeks (mean resections (extended right lobectomy 12, levels show a significant fall in the colloid 31.3), white cell count >6-5 median sur- left lobectomy three, extended left lobec- control group from days 1 to 3 (p<0).02) vival 20 weeks (mean 21 2) (p=0-04). En- tomy one). The 30 day hospital mortality but remain substantially unaltered in pa- doscopic insertion of a biliary prosthesis is was 7.4%. None of the 11 patients submit- tients receiving FFP (p=0 91, two-tailed an effective technique in high risk patients ted to local excision, and only one of 18 Mann-Whitney Ranking Test). Relatively with low malignant strictures. patients who did not have previous surgery low volumes of FFP have been shown to or preoperative biliary drainage, died in prevent the usual depletion of serum a, macroglobulin in acute pancreatitis and T120 hospital. The mean survival for the 24 on October 2, 2021 by guest. Protected copyright. patients who left the hospital is 22 5 this may have therapeutic implications. Monoclonal antibody imaging of pan- months. Sixteen patients died at six to 80 creatic cancer months, with a mean survival of 24 months; 13 of them had local recurrence. Eight T123 K C BAL LANTYNF, A C PERKINS, G PYF, AND J D patients are alive, with a mean survival of HARDCASTLE (Departments of Surgery and 20 months (range 10-45). The quality of Do postcholecystectomy symptoms im- Medical Physics, University Hospital, Not- life according to defined criteria was much prove? tingham) The first commercially available improved. monoclonal antibody preparation for The results show that radical resection T BATES AND M HARRISON (The William tumour imaging is ImaQis-I (International can be accomplished with a low mortality Harvey Hospital, Ashford, Kent) In a CIS). It is a combination of fragments and can be expected to significantly pro- prospective study of 170 consecutive F(ab)2 of two monoclonal antibodies, anti- long survival. It appears, however, that cholecystectomy patients, symptoms werc CEA and 19-9 radiolabelled with Iodine- current surgical methods alone cannot con- recorded pre-operatively and again after 131 and it is recommended in the detection trol the disease locally, and a study of the one and two years. All patients had right of recurrent gastrointestinal cancer. As place of adjuvant radiotherapy after a upper quadrant (RUQ) pain pre-operatively both of these antibodies are frequently curative resection is suggested. and when asked to rate the success of their expressed by pancreatic cancer, we have operation 90 (53%) regarded this as com- evaluated the ability of this antibody cock- plete. Fifty patients (29%), however, had tail to image previously diagnosed pancrea- T122 RUO pain in the first year and, whilst half tic cancer. Preliminary results of a multicentre of them then improved, 17 patients (10%) Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A1280 The British Society of Gastroenterology developed their first recurrence of pain T125 graphy. Passage of stones into the duo- more than a year postoperatively. Endoscopic removal of stones from the denum was documented in 12 patients At two years, pre-operative flatulence common bile duct: the whole truth (52% ) with complete clearance in eight was reduced from 67% to 42%, distension (35%). The radiological stone size ranged from 58%o to 36%, reflux type indigestion M E LAMBERT, D F MARTIN, AND DE F from 3-15 mm. There was no correlation from 60% to 42% and nausea from 63% to TWEEDLE (Departments of Surgerv' and between a successful outcome and size of 21%. There was little change, however, in Radiology, University Hospital ofa South retained stones. The flow rate of the saline the incidence of these symptoms at one and Manchester, Manchester) There is still T-tube infusion during ceruletide treat- two years and in at least a third of the doubt about the morbidity and mortality of ment was 55 3 mlUmin, SD 21 1. There was patients they were new. Exploration of the endoscopic removal of gall stones, largely an inverse correlation between the CBD bile duct (19%) did not appear to affect because of concern about the accuracy of pressure during ceruletide controlled saline symptomatic outcome and of 15 patients audit. Three hundred and fifty six patients T-tube infusion and successful stone passage. referred back to hospital with persistent with proven stones were referred during When the pressure remained below 25 cm symptoms none has yet been shown to have 1981 and 1985 for endoscopic treatment H,O, a successful outcome was obtained in a retained stone. which was carried out by two clinicians. In all the cases as opposed to two of eight It is concluded that apparently non- 26 patients (7.3%) a cholangiogram could patients in whom the pressure exceeded specific symptoms are less common after not be obtained, in three because of failure this level (27-45 cm H,O). Ampullary cholecystectomy. Early postcholecystectomy to intubate the second part of the duo- impaction of the stone was encountered in symptoms may improve with time but some denum (0.88%) and in five because of two patients. These results are superior to patients only develop symptoms after an failure to locate the papilla (1-.4%). Twenty those obtained by mono-octanoate and interval. of these patients underwent operations; indicate that this simple method of treat- three of them dying. In seven of the 330 in ment should be tried before more invasive T124 whom a cholangiogram was obtained, the methods for this problem. Outcome of endoscopic sphincterotomy stones were too large for endoscopic for papillary stenosis removal (2% of the 356). Three hundred and fifteen (88% ) underwent successful T127 D CARR LOCKE, I BAILEY, J NEOPrOLEMOS, endoscopic sphincterotomy and in 281 Prospective trial of pre-operative endo- T LEESE, AND D HEATH (Departments of (79%) all stones were eventually removed scopic sphincterotomy (ES) Surgery and Gastroenterology, Leicester after a mean of 1-98 ERCPs (range 1-7). There were four deaths directly attributable Royal Infirmary, Leicester) The benefits D L CARR-LOCKE, J P NEOPTO! EMOS, AND D P of endoscopic sphincterotomy for pre- to the procedure (1. 1%) and 43 complica- FOSSARD (The Leicester Royal Infirmary, sumed papillary stenosis are controversial. tions (6,4% of ERCPs but 12l1% of pa- Leicester) In a prospective study, 120 Out of 454 ERCPs for postcholecystectomy tients). The results continue to improve; patients were randomised to ES followed between 1981 and 1985 the proportion of symptoms, 32 patients with persistent bili- by surgery (group 1) or to surgery alone http://gut.bmj.com/ ary pain have undergone endoscopic patients in whom stones were successfully (group II). The groups were well matched sphincterotomy (ES) for 'papillary steno- removed rose from 79% to 91%, the with respect to age, sex and biochemical sis'. There were 28 women and four men number in whom the procedure failed, and clinical risk factors. Five were incor- with a mean age of 51 years (range 31-72 resulting in operation, fell from 21% to 8% rectly entered into the trial and six were years). The outcome has been indepen- and the complication rate fell from 13% to subsequently withdrawn because surgery dently reviewed at one to six years and 7% per patient. was refused in five (group I) and one had compared with diagnostic factors. In two ES alone following a myocardial infarct patients ES was not possible because of (group II). There remained 50 patients in severe fibrosis. After ES, 18 patients were T126 group I and 59 patients in group 11. The on October 2, 2021 by guest. Protected copyright. significantly improved (group A), 11 un- Efficacy of ceruletide treatment for re- overall mean age was 61 years (range 2(-83 changed and one worse (group B). Signifi- tained common bile duct stones years) and the mean serum bilirubin was cantly different individual criteria between 120 [tmoUl (range 5-474 [tmol/l). patients in group A and group B were, S A SADEK AND A CUSCHIERI (Department Failure to carry out ES or clear the CBD CBD diameter > 10 mm (15 vs 1, p<0-0()1) of Surgery, Ninewells Hospital and Medical of stones occurred in seven patients in delayed drainage of contrast, > 30 minutes School, Dundee) The synthetic peptide group I (14%), whereas retained or recur- after ERCP, (11 vs 2, p<0.01) but not ceruletide induces maximal relaxation of rent stones occurred in six patients in group abnormal LFTs, (6 v 1, NS). Two or more the sphincter of Oddi and has been re- 11 (10%). Major complications in group I factors were present in 13 patients in group ported to be effective in the management occurred in seven patients (14%) including A and only one patient in group B of retained CBD stones after cholecystec- two deaths compared with five patients (p<0.01). Manometric studies were per- tomy. The treatment which entails an (8 5%) including one death in group II. formed in nine patients, five in group A intravenous infusion of ceruletide (2 ng/kg/ Nine other patients had minor complica- and four in group B, all showing abnormally min in saline for one hour) during pressure tions in group I (18%) and nine patients in high sphincter of Oddi pressures. controlled saline infusion through the long group II (15%). We conclude that duct dilatation and limb of the T-tube, was evaluated in 23 In conclusion, these results do not sup- delayed drainage of contrast appear to be patients treated in several district general port the routine pre-operative use of ES in good indicators of outcome, but the place hospitals. The success of the procedure was patients with CBD stones who are other- of manometry is unclear. assessed by repeat T-tube cholangio- wise suitable for biliary surgery. Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A1281

T128 at 250 000. Data were obtained from ne- admissions. Subdividing the region into Morbidity and mortality of common cropsy reports, hospital, and general prac- five geographical areas revealed compar- bile duct exploration titioner records. Ninety one at home deaths able trends in all areas except that the rise occurred accounting for 37% of all ulcer in emergency GU admissions did not occur related deaths. Patients were grouped into in Cumbria. W G SHERIDAN, H 0 L WILLIAMS, AND M H three five year periods: 1972-76 (21), These findings confirm a continuing im- LEWIS (Department of Surgery, East the intro- Glamorgan General Hospital, Pontypridd, 1977-81 (32) and 1982-86 (38). The mean pact on admissions for PU from ages were similar at 70-8, 70(7, and 73-4 duction of histamine H, antagonists. S Wales) Only limited data exist on the years respectively. Men were in the major- morbidity of common bile duct (CBD) exploration in UK surgical practice. We ity in the first period whereas women were more common in the last five years. T131 have therefore carried out a retrospective review of 257 patients who had CBD Duodenal and bleeding ulcers predomin- Which ulcer patients are likely to pre- ated in the first period in contrast with exploration in one hospital over a 15 year sent with bleeding? period. One hundred and eighteen patients gastric and perforated ulcers in the last five years. Non-steroidal anti-inflammatory (45.9%) developed one or more complica- K MAYTHEWSON, S PUGH, AND T C NORTH- drug use increased from 37% to 46% and tions as follows: septic complications FIELD (Gastroenterology Units, St James then to 87% in the last five years. (19-5%) (includes a 15.9% wound infec- Hospital, Balham and University College tion rate), cardiorespiratory complications These figures emphasise the previously Hospital, London) The factors which de- unrecognised importance of including all at (16 7%), wound dehiscence or incisional termine whether a peptic ulcer presents hernia (3.9%), T-tube complications home deaths in future studies of peptic with pain or bleeding are unknown. We (3-5%), haemorrhagic complications (2.3%), ulceration. In the study period there have have prospectively evaluated patient fea- urinary tract problems (2.3%), prolonged been marked epidemiological changes. Pa- tures (age, sex, smoking, alcohol, and ileus (1.9%), postoperative pancreatitis tients dying at home from peptic ulceration analgesic consumption, and previous his- (1 9%), renal failure (1 2%), hepatic failure are now more likely to be women with a tory of peptic ulceration) and endoscopic perforated gastric ulcer. Most of the sub- (0-4%). Thirty seven patients (14.4%) had features (ulcer number, site, diameter, retained stones, discovered before dis- jects are now using anti-inflammatory depth and nature of ulcer base) in 106 charge from hospital in 20 (7-8%) and later drugs which we believe are responsible for unselected patients presenting with acute in the remainder. Postexploratory chol- these changes. bleeding and 58 presenting with pain who angiography did not significantly reduce were found to have peptic ulcers at endo- the incidence of retained stones. Of 12 scopy. As patients with bleeding were older patients who had choledochoscopy, none T130 (median age 65 vs 51, p<0O001), other had retained stones. Five patients (1-9%) Impact of histamine H2 receptor anta- statistical comparisons were age corrected. Patients with bleeding were more likely to died, death being because of postoperative gonists upon admissions for peptic anti-inflammatory http://gut.bmj.com/ pancreatitis in two and to septicaemia, bile ulceration within the Northern region have taken non-steroidal peritonitis and myocardial infarction in the drugs (NSAIDs) within the previous four remainder. In conclusion, CBD exploration (1971-84) weeks (59% vs 20%, p<0.001) and to have has a high associated morbidity, particularly an ulcer greater than 20 mm in diameter C W VENABLES, K DENHAM, AND R A because of septic complications and a high (27% vs 6%, p<0-01), but there were no MCNAY Surgery, Freeman retained stone rate, for which choledocho- (Department of significant differences regarding sex, Hospital, Newcastle upon Tyne and Northern scopy may offer the best solution. smoking, alcohol intake, incidence of Regional Statistics Section) Early studies multiple ulceration, ulcer depth, ulcer site, showed a reduction in gastric surgery after

or nature of ulcer base. Although there was on October 2, 2021 by guest. Protected copyright. the introduction of cimetidine but there no significant difference in the overall have been no longer term studies or data incidence of a previous ulcer diagnosis, on medical admissions. bleeding patients were more likely to have We have analysed all discharges or GASTRODUODENAL had a previous ulcer complication (bleed- deaths (of over 48 hours admission) for T129-138 ing or perforation) (20% vs 0%. p<0001). peptic ulcer (PU) in the northern region for We have therefore shown for the first time the period 1971-84. These have been sub- T129 that ulcer patients who present with bleed- divided by type, treatment, ulcer category ing rather than pain are three times as Sudden deaths at home from peptic and area. Trends have been analysed by likely to have taken NSAIDs recently; they ulceration - a hitherto unrecognised comparing three time periods (1971-75, tend to be older, are more likely to have phenomenon 1977-80, and 1981-84). had a previous ulcer complication and are The results show that there is a con- more likely to have a large ulcer. A L BLOWER AND C P ARMSTRONG (Leighton tinuing reduction in all surgical admissions Hospital, Crewe, Cheshire) There are (Elective DU 70%: GU 50%: emergency over 4000 deaths annually from peptic DU 37%: GU 19%: perforated DU 20%) T132 ulceration in this country. Many die be- except perforated GU (+60%) when 1981- Occurrence of pain in peptic ulcer hae- fore medical treatment is possible. All 84 was compared with 1971-75. There was morrhage: relation to age and non- sudden deaths from peptic ulceration since a similar trend in medical admissions (elec- steroidal anti-inflammatory drugs 1972 have been studied in South tive DU 61%: GU 25%; emergency DU Cheshire; population approximately stable 23%) with a 61% rise in emergency GU I M CHESNER, L E RHODES, AND R D MONT- Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

A 1282 The British Society of Gastroenterology GOMERY (Department of Medicine, East or absent) to 3 (severe) and the sum of the gastrin secretion was inhibited by Enprostil Birmingham Hospital, Birmingham) It grades used to assign each patient a 'reflux in all subjects (228±316 to 709±154 pg/ml has been claimed that haemorrhage from score' (0-15). Forty three patients (74%) 2 h in antral G-cell hyperfunction, 4544+1774 peptic ulcer tends to be painless in the were CLO-positive and 15 CLO-negative. to -578±342 pg/ml 2 h in Zollinger-Ellison elderly, and also in patients taking non- Of the CLO-negative GUs, nine had a syndrome and 660±128 to 199±50 pg/ml aspirin non-steroidal anti-inflammatory reflux score >10 compared with only five 2 h in normal subjects). The percentage drugs (NANSAIDs). We have reviewed of those CLO-positive (X2. p<0'00(l(). inhibition was slightly higher in Zollinger- the records of 254 consecutive cases of Furthermore, CLO-negative GUs showed Ellison syndrome (1 13+45%Y) than in antral endoscopically proven bleeding ulcer, con- significantly higher reflux scores G-cell hyperfunction (69±13'%) and normal cerning abdominal pain on presentation (mean±SD) than CLO-positive GUs subjects (70+19%). It is concluded that and during the preceeding six months and (10-9+2.4 vs 8-1±2-3; p<0O0(1). Enprostil inhibits postprandial gastrin also the ingestion of NANSAIDs as re- These results suggest that there may be secretion not only in normogastrinaemic corded on positive questioning. With in- fundamental differences between CLO- subjects but also in patients with antral G- sufficient data in 18 cases, 236 were analy- positive and CLO-negative GU. The cell hyperfunction or Zollinger-Ellison sed (38 taking NANSAIDs). Overall 58% evolution of GU in CLO-positive patients syndrome. had no pain on presentation and 36% had may be related to CLO-induced gastric no pain then or in the preceeding six mucosal injury whereas in CLO-negative months. There were no differences be- subjects enterogastric reflux may be the tween GU and DU or between the sexes. prime aetiological factor. T135 Pain was unrelated to NANSAID ingestion Highly selective vagotomy (HSV) and in DU or GU or in any age group. Of duodenal ulcers resistant to H2-blockers patients with no pain during the six months T134 21%, were taking NANSAIDs and of those Effect of enprostil on basal and post- J N PRIMROSE, A T R AXON, AND D JOHNSTON with pain 20%o were taking NANSAIDs prandial serum gastrin levels in patients (University Department of Surgery and De- (44%o and 40% respectively in patients over with antral G-cell hyperfunction, partment of Medical Gastroenterology, The 70 years old). Ulcers tended to be painless Zollinger-Ellison, syndrome and General Infirmary, Leeds) Our aim was over the age of 70 compared with under 50 normal subjects to establish whether HSV provides effective (X2 =3934, p<0'05). treatment for the DU which fails to heal on NANSAIDs do not reduce pain in ulcers L F S J CROBACH, J B M J JANSEN, AND C B H W H2-blocker (H.B). which bleed. Hence the previously con- LAMERS (Departments of Gastroenterol- In a prospective study of HSV (1978- firmed tendency for NANSAID-associated ogy and Hepatology, University Hospital, 83), 141 patients were operated on for ulcers to present with haemorrhage indi- Leiden, The Netherlands) Enprostil, a uncomplicated DU and had satisfactory cates a genuinely increased bleeding risk in synthetic dehydro-prostaglandin E., in- pre- and postoperative acid studies. In 52, such ulcers, rather than a selective under hibits serum gastrin levels in normal sub- the DU had failed to heal despite six weeks

estimation of their prevalence. jects and patients with duodenal ulcer. The on full dose H2B (group R), 14 patients http://gut.bmj.com/ present study was undertaken to assess the relapsed on maintenance therapy (RM), 63 effect of Enprostil on basal and postpran- remained healed on H.-B (H) but relapsed T133 dial serum gastrin concentrations in pa- frequently off therapy and 12 did not Campylobacter positive and campylo- tients with hypergastrinaemia and gastric receive H.B (N). bacter negative gastric ulcers (GU) - acid hypersecretion of antral (antral G-cell The overall recurrence rate was 7-5% at have they a different aetiology? hyperfunction) or tumour (Zollinger- two years and 15% at four to five years. Ellison syndrome) origin. Basal and post- There were eight recurrent ulcers (RU) H J 0 CONNOR, M F DIXON, J I WYATT, AND prandial serum gastrin concentrations were among 45 of 52 group (R) patients who on October 2, 2021 by guest. Protected copyright. A T R AXON (Gastroenterology Unit and measured after 70 ,ug Enprostil or placebo attended for follow up at two years (17%) University Department ofPathology, General orally in five patients with antral G-cell and 10 RU among 25 of 40 patients at four Infirmary at Leeds, Leeds) About 30"% of hyperfunction (four men, one woman, to five years (40%). In the 'RM' group, GU patients are Campylobacter (CLO)- 22-44 years, BAO 11-0-19 3 mmol/h), in there was no RU (0%) either at two years negative on gastric biopsy. The significance three patients with Zollinger-Ellison syn- among 13 of 14 patients or four to five of this finding is at present unclear and drome (three men, 19-52 years, BAO 284)- years among nine of 10 patients. In the 'H' possible differences between CLO-positive 45-0 mmol1h) and in five normal subjects group, there was one RU among 63 pa- and CLO-negative GUs have not been (five men, 33-65 years). tients at two years (2%) and one among 40 evaluated. In this study, gastric biopsies Enprostil reduced basal serum gast- of 48 patients at four to five years (3%). In from 58 patients with untreated GU were rin concentrations in all five patients with the 'N' group, there was one RU in 10 of 12 blindly assessed for the presence of CLO antral G-cell hyperfunction (230+52 to patients at two years (1()%) and one in and also scored for severity of reflux 145±34 pg/ml), in two or three patients seven of eight patients at four to five years gastritis (RG). We have previously shown with Zollinger-Ellison syndrome (1269±427 (14%). that RG has a characteristic histology to 1048±445 pg/mg), and in all normal sub- Recurrence was more common in the 'R' comprising marked foveolar hyperplasia, jects (51±9 to 41±7 pg/ml). The percentage than in the 'H' group, both a two year oedema, and vasodilatation of the lamina reduction in antral G-cell hyperfunction (p<002) and at four to five years propria, and a paucity of acute and chronic (37+12%) was slightly higher than in (p<001), and was independent of surgeon inflammatory cells. These five histological Zollinger-Ellison syndrome (17±19%) and and preoperative BAO and PAO. An ulcer features were each graded from 0 (normal normal controls (19±7%). The postprandial that fails to heal on H2-blockers represents Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of GastroenterologyA A 1 283 a more severe ulcer diathesis, for which T137 ments of BAO and PAOPg before and after HSV is less effective. Simple and effective treatment for operation. postvagotomy diarrhoea Bile acid output and the responses to insulin and pentagastrin were measured in T136 S A RAIMES, V SMIRNIOTIS, E WHEILDON, C W 38 patients with RU after HSV for DU, and VENABILES, AND I D A JOHNSTON (University in 101 patients without RU more than Famotidine, a new H2 receptor anta- five after HSV for DU. In Department of Surgery, Newcastle upon years each gonist, restores levels of cytoprotective patient BAO and PAOPg were measured prostaglandin E2 in the peripheral blood Tyne) The treatment of postvagotomy diarrhoea is often unsatisfactory. before HSV; and BAO, PAO' (except in a of patents with ulcer Choles- peptic disease. tyramine has been reported to be effective few unfit people) and PAOPg one week after but is unpleasant to take and may have HSV. J P WALSH, W J MAXWELL, FP HOGAN, AND undesirable long term effects. In this study The IT (Hollander) was 'positive' in 34%O P W N KEELING (Department of Clinical cholestyramine has been compared of the RU patients compared with 8% of Medicine, Trinity College Medical School, with non-RU. The best discriminant using St James' Hospital, Dulbin 8) Prostaglan- loperamide in treating this condition. Thirty three patients with persistent diar- BAO/PAO was a reduction of <50%MO in the din E2 (PGE2) has been shown to play an PAO This was rhoea were studied: group A - truncal following operation. 'posi- important role in the maintenance of the tive' in 53% of RU but also in 28(Yo of non- vagotomy+drainage (n =22); group B - gastroduodenal defense mechanisms. A RU. Other discriminants were even less deficiency of PGE, has been shown in truncal vagotomy+drainage plus cholecys- tectomy (n= 11). Patients were randomised specific. mucosal biopsies, gastric juice and peri- the IT was less sensitive than to receive a course of either cholestyramine Although pheral blood of patients with duodenal other indicators of recurrence it is much 4 g bd or loperamide 4 mg mane, after ulcer disease (DUD). The aims of this more If the incidence of recur- which treatment was stopped for one week specific. study were to examine the effect of a new and the patient crossed-over to the alter- rence after HSV is low the insulin test has Ho receptor antagonist (H,RA), Famotidine better value than or nate drug. Diary records of diarrhoea were predictive BAO (FAM), on PGE, biosynthesis by peri- PAOPg: it would be premature to abandon pheral blood mononuclear cells (PBMC) of kept throughout the study. After reassess- ment patients received their it. patients with DUD. Twenty patients with preferred treatment for a further four weeks, endoscopically proven dosage active DUD entered being adjusted for best control. a double blind, placebo controlled ran- In group A only one of 22 found domised trial of FAM (40) mg nocte) or cholestyramine effective and 11/22 com- placebo for six weeks with repeat endo- plained that it was intolerable or made Pl ENARY SESSION scopic examination to assess ulcer activity. diarrhoea worse. In group B eight of 11 Fasting peripheral were FI-6 blood samples found cholestyramine effective (p<0.001; taken before and after six weeks treatment. Freshly isolated PBMC (Hypaque-Ficoll) Fisher Exact Test). Loperamide was effec- Fl http://gut.bmj.com/ tive in 16/22 of group A and nine of 11 were stimulated with opsonised zymosan Development of colonic transport pro- group B, the latter patients preferring it to for 30 mins at 37°C. Prostaglandin E, cholestyramine. cesses in infancy: the influence of aldo- concentration in the supernatants were sterone measured by radioimmunoassay. We conclude that the prophylactic use of The results from both active and placebo low dose Loperamide given once daily is a simple, safe and effective treatment for H R JENKINS, T R FENTON, M 0 SAVAGE, M J treatment DUD groups were compared post-vagotomy diarrhoea. Cholestyramine DILLON, AND P J MILLA (The Hospital for with those from healthy controls and it was Sick Children. St and is useful in patients who have also had a George's Hospital on October 2, 2021 by guest. Protected copyright. found that PGE. levels in the pretreated cholecystectomy, but is their second line The Institute of Child Health, Lonidon) DUD were groups depressed significantly treatment. Aldosterone is of critical importance in the compared with that found in control sub- regulation of Na+ conservation by both jects. Placebo 15 4±2 6; FAM 14 3+1-7, kidney and colon. Little is known, however, (n=10) vs Control 27X8±3 3 (n=43); T138 of the ontogeny of these processes in the ng/10' monocytes, X±SEM, p<0-01 human infant. Using the of non- Insulin test as a technique Student's t test. After six weeks treatment (IT) predictor of recur- equilibrium rectal dialysis we have investi- 62-5'Yo of the placebo and 90% of the FAM rent ulceration (RU) after highly selec- gated rectal Na+ absorption in 25 pre- group had healed. Despite healing PGE, tive vagotomy (HSV): comparison with mature infants and neonates (N, 30-44 biosynthesis by PBMC remained depressed the value of measurement of BAO and weeks gestation), 15 infants (I, 1-12 in the placebo group (12 9±2 7), however, PAO months) and 14 older children (C, 1-7 but were normalised in the FAM treated years). Na4 absorption was highest in N patients (27-5±4-6). In a previous study we J N PRIMROSE AND D JOHNSTON (University (274 nmoUcm2/min±ISD) compared with I found that in 20 DUD patients treated with Department of Surgery, The General In- (200±56) and C (149±42). Plasma aldo- Cimetidine (800 mg nocte for four weeks), firmary, Leeds) Though the IT is widely sterone was markedly elevated in N all healed but PGE. levels remained de- used as an indicator of incomplete vago- (7570±2500 pmol/l) compared with infant pleted. In conclusion, FAM in contrast to tomy and future RU, it is tedious and reference levels (790±210). Urinary Na' other H2RA appears to restore peripheral unpleasant. The aim of this study was to wasting was apparent in the preterm in- blood cell biosynthesis of cytoprotective determine whether similar information fants in group N. Plasma aldosterone and PGE. at six weeks in patients with DUD. could be derived from simpler measure- Na+ absorption was also studied in infants Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from A1284 The British SocietY( of Gastroenterology with end-organ unresponsiveness to aldo- F I LEE ANI) P M SMITH (Departments in lower oesophagus, fundus, corpus, sterone (7200±210, Nat 90+42), aldoster- of Gastroenterology, Victoria Hospital, antrum, duodenal cap and duodenal loop one deficiency (0, Na+ 60±46) and secon- Blackpool and Llandough Hospital, Cardiff) using a flexible microelectrode passed dary hyperaldosteronism (1300+346, Na' Twelve men have developed angiosarcoma through the biopsy channel of an endo- 281±52). These data suggest that colonic of the liver (ASL) in association with scope. Studies were donc in 23 normal Na' transport processes are efficient in occupational exposure to vinyl chloride subjects, and in patients with reflux oeso- early infancy and that aldosterone is a monomer (VCM) in two factories in the phagitis (n= 10), antral gastritis (n= 10), major regulatory hormone. In the preterm UK. Presenting clinical features included duodenitis (n=6) and duodenal ulceration infant prior to 34 weeks gestation renal abdominal pain (six), malaise (five), jaun- (n= 01U). tubular Na' reabsorptive mechanisms are dice (two), haemorrhage from oesophageal In normal subjects mucosal pH in the poorly developed and the colon is the varices (two), ascites (five) and hepa- fundus, corpus and duodenum remained major organ of Na' conservation. The tomegaly (10). The men were aged 37-71 stable above pH 4 over a range of intra- consequences of diversionary surgery and years at the time of diagnosis. In two, non- luminal pH from 1 to 7-4. In the lower colectomy should be carefully considered cirrhotic portal hypertension had been oesophagus and antrum, however, mucosal in this age group. recognised 13 and 5 years previously. pH dropped sharply when intraluminal pH Hypercalcaemia was a persistent feature in levels fell below 2-5. In comparison with F2 one case. In general. disease progressed both controls and the other disease groups Endoscopic biliary prosthesis in the rapidly without remission, death occurring patients with duodenitis and DU demon- palliation of malignant biliary obstruc- in a few weeks due to hepatic coma in strated significant deficients in mucosal pH tion - a randomised trial association with gastrointestinal or intra- in the duodenal cap once luminal pH fell peritoneal haemorrhage. One man showed below 3. At other sites the mucosal pH limited response after intermittent to low luminal was similar in H A SHEPHiERD, A DIBA, A P ROSS, M ARTHUR, chemo- response pH G ROYLE, AND D COLIN-JONES (Winchester, therapy and survived longest - seven all patients groups. Southampton and Portsmouth Hospitals) months. Clinical, laboratory and angio- While the juxtamucosal neutral zone Plastic endoprostheses, inserted trans- graphic features may bc typical but open lining ftundus, corpus and duodenum in hepatically or endoscopically into the bile liver biopsy is the safest and most certain normal man can resist low luminal pH that duct, are alternatives to surgical bypass for method of proving the diagnosis. At lining lower oesophagus and antrum is the relief of malignant biliary obstruction. necropsy the livers of these patients showed more easily dissipated. Duodenal ulccr We considerable, sometimes massive, replace- patients have a specific deficit in mucosal report an ongoing randomised trial in the which compares endoscopy with surgery in ment by tumour, apparently multifocal, pH duodenal cap. the palliation of malignant obstruction of with necrosis and hacmorrhage. Only one the distal bile duct. man, who died from a cerebrovascular F5 Eighty three patients have been referred accident due to a cerebral deposit, had 'Real' cancer risk in ulcerative colitis and 46 (55-4%0) have been randomised. evidence of metastases. In view of the long latency period observed in some cases S N (GYDE, A STEVENS, P PRIOR, J A 11 Exclusions were, preferred treatment http://gut.bmj.com/ (59-2%0), duodenal obstruction (11 O), world wide, the full extent of ASL occur- WA I ERIIOUSE, D P JEWIEIt, 0 BROSIROM, porta block (18E%), and disseminated rence may not be known for 20 years or so. R L0OFBERG, G I{I.LERS, AND R N AllAN malignancy (1 1%o). Treatment failures In summary, ASL is a rare, highly malig- (Gastroenterology Unit, General Hopsital, were crossed into the other treatment nant tumour seen after several years expo- Birmingham) While there is conclusive group surgery 1). Proof of sure to medium/high concentrations of evidence that ulcerative colitis carries an (stent 3, malig- VCM. cancer nancy was obtained in 61% and 89%/ of the Metastases arc uncommon. increased risk, estimates of the endoscopic and apparent cancer risk vary widely between surgical groups respect- series probably because of selection bias ively. Analysis to date (stent n= 18, surgery F4 and small sizes. on October 2, 2021 by guest. Protected copyright. n=19), shows a significant difference in sample Can the mucus bicarbonate barrier The ideal study would identify a large hospital stay between endoscopy and withstand low intraluminal pH - surgery, md 6 and 11-5 days respectively, representative group of patients at the studies in health and gastroduodenal onset of their disease (inception cohort) p<)-05. No significant differences were with found between and mucosal disease complete long term follow up. endoscopy surgery We the results of a in relief of icterus vs report such collabora- (respectively) (78-9% E M M QUIGLEY AND L A 1URNBERG (Depart- tive between 73-60o), 30 day mortality vs study Birmingham, Oxford, (5'Yo 21%), ment of Medicine, Hope Hospital (University and Stockholm. Patients were diagnosed at complications (22% vs 36(Yo), overall sur- of Manchester School of the vival 176 vs Medicine), Salford) referral centre within five years of (md 128 days), and total Recent studies show the ability of an onset of hospital stay vs 286 disease between 1945-65 drawn (225 days). Readmissions gastroduodenal mucosa to protect itself from a defined only occurred in the geographical area and endoscopy group from acid-peptic followed for a minimum (n=7) and were for with digestion by maintaining a of 20 years. cholangitis zone of near neutral pH immediately The series comprised 822 patients of blocked stents. Endoscopic prosthesis adjacent compares with to the mucosa. In vitro, this zone whom 485 had extensive colitis. The relative favourably surgical bypass. is dissipated at very low luminal pH. Our risk of developing colorectal cancer was 7-7 aim F3 was to assess, in vivo, the integrity of in the whole series and 17-1 for those with the juxtamucosal neutral zone in the face extensive colitis. The cumulative colorectal Occupationally related angiosarcoma of of low luminal pH in health and disease. cancer risk in patients with extensive colitis the liver (ASL) in the United Kingdom Luminal and mucosal pH were measured was 0-6+±0-1-3-2% at 10 years from onset, Gut: first published as 10.1136/gut.27.10.A1234 on 1 October 1986. Downloaded from

The British Society of Gastroenterology A 1285

7 1+3 411 1% at 20 years and 164±8+6- Institute for Cancer Research, Cambridge) 'y' staining at the crypt base with moderatc 24 0% at 30 years. These results provide Cellular oncogenes occur both in normal exclusive (17/21) or predominant (four of the best estimates as a basis for the clinical tissue and in tumour cells and, although 21) cytoplasmic staining at the mucosal management of patients with ulcerative they may induce cellular transformation in surface. Staining was similar in quicscent colitis at risk of developing colorectal vitro, the importance of their expression in UC. By contrast, in the cancers, while cancer. human cancers is unclear. We have studied intense predominantly nuclear staining was c-myc oncogene expression in the develop- seen at the crypt base, in six of eight ment of cancer F6 colorectal by immuno- tumours there was heavy mixed nuclear histological detection (using monoclonal and cytoplasmic staining at the surface. Abnormal expression of C-MYC on- antibody: 6E-10) of the abundance and Although no consistent pattern emerged in cogene product in dysplasia and neo- distribution of the protein product of c- mild dysplasia, in the seven most severely plasia associated with ulcerative colitis myc, p62k-myc, in archival histopathological dysplastic tissues, the distribution and samples of normal colonic tissue (n=21), intensity of staining paralleled that of the I C FORGACS, V SUNDARESAN, G EVAN, D G D quiescent ulcerative colitis (UC) (n= 10), carcinomas. WIGHT, G NEALE, J 0 HUNTER, AND J V UC with dysplasia (n=17) and UC with Thus in the transition from chronic UC WATSON (Departments of Gastroenterol- invasive carcinoma (n=8). In normal tissue to malignancy, there is evidence of abnor- ogy and Pathology, Addenbrooke's Hospi- there was light-to-moderate exclusive mal expression of the protein product of tal, Cambridge and MRC Centre and Ludwig (13/21) or predominant (8/21) nuclear p62c- the c-myc oncogene. http://gut.bmj.com/ on October 2, 2021 by guest. Protected copyright.