Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from

Gut, 1981, 22, A414-A444

The British Society of Gastroenterology

The Spring meeting of the British Society of Gastroenterology took place in Bristol on 9 and 10 April 1981 under the Presidencies of Professor A E Read and Dr P B Cotton (Endoscopy) and Professor C G Clark (President Elect). Following the Teaching Day and splinter groups, 104 papers were read to the Society and 12 posters were on display. Dr N W Read delivered the Research Medallist lecture 'Waves, wind and a tricky passage'. The abstracts of the papers follow.

actively spurting), those without a vessel tumour, tube migration, or disintegration. ENDOSCOPY (11), and those with an overlying clot In three patients, after radiotherapy to T1-T5 persisting after washing (four). With squamous lesions, it was possible to visible vessel 9/19 treated and 9/20 remove the tube without recurrence of untreated rebled. Without a vessel or dysphagia. Median survival time after with clot, 2/7 treated and 0/8 untreated intubation was three months, and 28 have rebled. No significant benefit from laser survived for six months. It would appear (T1) treatment has been shown. In its present that this is a safe and effective method of Controlled trial of argon laser photo- form, there is little prospect of argon palliation of oesophagogastric neoplasms. coagulation for haemorrhage from peptic laser photocoagulation playing a useful

ulcers role in the endoscope treatment of major http://gut.bmj.com/ upper gastrointestinal haemorrhage. S G BOWN, D W STOREY, P SWAIN, J S (T3) KIRKHAM, T C NORTHFIELD, AND P R Prosthetic tube function after palliative SALMON (The Rayne Institute, University endoscopic intubation of oesophagogastric College Hospital and The Norman Tanner (T2) neoplasms Gastroenterology Unit, St. James' Hos- Outcome of endoscopic intubation in 100 pital, London) We present the results of patients with oesophagogastric carcinoma F J BRANICKI, A L OGILVIE, M WILLIS, AND a controlled clinical trial from two M ATKINSON (University Hospital and on September 27, 2021 by guest. Protected copyright. centres in London of the efficacy of argon A L OGILVIE, M W DRONFIELD, R FERGUSON, Department of Physical Chenmistry, Uni- laser photocoagulation in the endoscopic AND M ATKINSON (University Hospital, versity ofNottingham, Nottingham) One control of haemorrhage from peptic Nottingham) Inoperable carcinoma of hundred and eighteen prosthetic tubes ulcers. From an unselected series of 231 the oesophagus or cardia causes progres- were inserted at fibreoptic endoscopy consecutive admissions for upper gastro- sive relentless dysphagia and an effective across oesophagogastric neoplasms. These intestinal haemorrhage, all patients seen means of palliation is important in man- were followed up for a total of 428 tube at emergency endoscopy to have a peptic agement. We describe the results of months. Food blockage occurred on 24 ulcer were included in this trial if they successful insertion of prosthetic tubes at occasions and this was related to the showed stigma of recent haemorrhage fibreoptic endoscopy in 100 patients with length of the tube. Thirteen tubes dis- and if it was possible to aim the laser at oesophagogastric neoplasms. Fifty pa- placed proximally, eight of which had no the source of haemorrhage. One hundred tients had adenocarcinomas and 41 had distal shoulder. Distal displacement oc- and eight ulcers were seen, 79 had stigma squamous carcinomas. Their ages ranged curred once, requiring laparotomy and of haemorrhage and 53 were included in from 50 to 91 years. Five fatal, and nine two tubes disappeared without trace. the trial. Identification of the exact non-fatal oesophageal perforations were Structural deterioration resulted in dis- bleeding points was achieved using sustained in 118 intubations. Another integration and fragmentation in two standard endoscopes with meticulous seven patients died within a week of tubes, three and eight months after washing of the ulcer bases. The laser intubation, giving an overall mortality of insertion. Using the Instron method, power, exposure time, and aiming were 12%. Eighty-five patients survived to tensile strengths of virgin latex and sili- optimised in accordance with our previous leave hospital, with marked improvement cone rubber tubes were measured in vitro animal and clinical experience. in dysphagia. Tube function was good, after accelerated ageing by intubation in Stratification was in three groups: but occasionally problems arose from varying concentrations of hydrochloric ulcers with a visible vessel (39 total, six blockage with food or overgrowth of the acid and bile. After incubation in 01 M A414 Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A415 hydrochloric acid for one month at (T5) oesophageal reflux alone (controls). Pul- 40°C, the breaking force of latex fell by An overtube concept in upper gastro- monary function tests were performed 31 % (48 Newtons), while there was no intestinal endoscopy during the course of an acid infusion significant change for silicone rubber (Bernstein) test. Respiratory symptoms tubes. Neither the addition of bile nor P B COTTON (Gastrointestinal Unit, The were also recorded during overnight prior irradiation of the tubes had a Middlesex Hospital, London) Overtubes monitoring of oesophageal pH. significant effect. There was no change in have previously been advocated for pro- Significant bronchoconstriction was the breaking strength of silicone rubber tection of the oesophagus during endo- observed after oesophageal intubation in tubes after three months in vivo. It is scopic removal of foreign bodies. We nine asthmatic patients and four controls. suggested that prosthetic tubes should have designed a new tube and greatly Infusion of N/10 hydrochloric acid into have a distal shoulder to minimise dis- ~extended the range of applications. A the lower oesophagus caused broncho- placement and be fabricated of silicone plastic sleeve 40 cm long is placed over constriction in five asthmatic patients and rubber for improved durability. the proximal shaft of the fibrescope; once four controls. Those with asthma were the fibrescope is in the oesophagus, the affected to a greater degree. A second sleeve is advanced until its tip lies beyond acid infusion was done in the asthmatic the cricopharyngeus. The sleeve allows patients after instillation of 4% ligno- (T4) repeated removal and reintroduction of caine into the lower oesophagus. Bron- New disinfecting apparatus for gastro- fibrescopes without patient discomfort choconstriction was absent or reduced on intestinal fibre endoscopes and therefore greatly facilitates retrieval this occasion. of polyps, gastric suction and lavage (by Overnight pH monitoring revealed H J O'CONNOR, J ROTHWELL, C LINCOLN, replacing the scope temporarily with a frequent episodes of reflux with related S MAXWELL, AND A T R AXON (The large bore rubber tube), changing the episodes of cough and wheeze. Gastroenterology Unit and Department of type of fibrescope, and the endoscopic These results are consistent with the Microbiology, The General Infirmary at carriage of jejunal biopsy capsules. The hypothesis that acid reflux into the lower Leeds, Leeds) Bacterial contamination sleeve permits the use of muzzle-loaded oesophagus induces reflex bronchocon- of gastrointestinal endoscopes is a poten- 'jumbo' biopsy forceps, and can provide striction. In asthmatic subjects this may tial source of clinically significant infec- a gas-venting system during laser photo- be associated with episodes of wheeze. tion. Activated 2% alkaline glutaralde- coagulation. It can also be used in an hyde effectively disinfects fibre endoscopes entirely new method for introducing in the short time available between patient fibrescopes, which may be easier and (T7) procedures. Unfortunately, up to 37% of safer for the inexperienced. The patient Comparison of surgical and medical man- swallows the tip of a 36 French gauge British endoscopy units using glutaralde- agement of bleeding peptic ulcers http://gut.bmj.com/ hyde are experiencing serious staff hyper- rubber lavage tube, with the sleeve at its sensitivity reactions, especially contact hilt; the sleeve is advanced over the tube, K D VELLACOTT, M W DRONFIELD, M dermatitis. which is then replaced by the fibrescope. ATKINSON, AND M J S LANGMAN (Depart- In response to this problem we have Patient toleration is excellent and there ments of Surgery and Therapeutics, designed a 'closed system' disinfecting have been no adverse effects. University and City Hospitals, Notting- apparatus that ensures minimal staff ham) There are conflicting opinions as exposure to glutaraldehyde. The appara- to what the indications for surgery should tus consists of two Perspex chambers be in patients with bleeding peptic ulcers on September 27, 2021 by guest. Protected copyright. connected to suction apparatus and mains as illustrated by answers to question- water. The endoscope is disinfected for CLINICAL MEDICAL naires sent to gastroenterologists both in 30 minutes before the endoscopy session, T6-T20 the United Kingdom and the United for two minutes between patient pro- States. Of 1373 patients admitted to cedures, and for 10 minutes before Nottingham hospitals with upper gastro- storage. Tap water flushes the endoscope (T6) intestinal haemorrhage in a 4j year free of glutaraldehyde. Intra-oesophageal acid studies and pH period from mid-1975 to the end of 1979, Samples were taken for bacteriological monitoring in asthma 699 (51 %) were found to have peptic study from the channels and exterior of ulcers. Two hundred and ninety-eight had the endoscope before and after each D N COOPER, A PIERRY, M MARPLE, A gastric ulcers and 401 had duodenal disinfection cycle. Gross bacterial con- BERNSTEIN, AND J BANCEWICZ (M H IRVING) ulcers. The ulcer mortality was 74 tamination of the endoscope was found (Departments of Thoracic Medicine and (10-5%), 32 with gastric ulcers (10.7%) after each patient procedure. The wash- Surgery, Hope Hospital, Salford) A and 42 with duodenal ulcers (10-4%). ings and swabs from the endoscope were number of reports have suggested a rela- There has been a decline in the annual virtually sterile after two, 10, or 30 tionship between gastro-oesophageal re- mortality rate for gastric ulcers from minutes' disinfection by our method. flux and asthmatic symptoms. This might 18-7% in 1976 to 9.4% in 1978, and also Therefore, this relatively simple dis- be due either to pulmonary aspiration of for duodenal ulcers from 11-9% in 1976 infecting apparatus offers rapid and refluxed acid or to reflux bronchocon- to 4-6% in 1978. In addition, the percent- adequate disinfection of fibre endoscopes, striction induced by stimulation of the age of patients being operated on has while protecting endoscopy staff from the oesophagus. We have studied 12 patients steadily fallen from 38-8 % in 1975 to potentially toxic effects of contact with with asthma and gastro-oesophageal re- 16-5 % in 1979. Of the total 699, 196 glutaraldehyde. flux and nine patients with gastro- (28 %) had operations, 85 for gastric Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A416 The British Society of Gastroenterology ulcers and 111 for duodenal ulcers, with intestinal and Liver Service, Royal In- with cimetidine 200 mg three times a day mortality of 41 (209 %). The surgical firmary, Edinbutrgh) The accuracy of with meals and 400 mg at bedtime, and mortality each year has remained rela- urgent endoscopy in acute upper gastro- up to six days afterwards. All other tively constant. intestinal bleeding was investigated by medication remained unchanged. In each We conclude that a more conservative comparing the findings at endoscopy with patient cimetidine treatment resulted in attitude towards emergency surgery has those at surgery and/or necropsy per- statistically significant rises in plasma resulted in a reduction in the mortality formed on the same admission. Of 308 phenytoin (P< 002), which fell towards for both bleeding gastric and duodenal consecutive endoscopies (performed by a pretreatment levels when cimetidine was ulcers. number of endoscopists with varying withdrawn. The mean increase in each degrees of experience) 99 (32%) under- patient was 13%, 20%, 20%, and 33% (T8) went surgery alone and 23 (23 %) of these over pretreatment phenytoin levels. Dur- Experience of an upper gastrointestinal died. Five patients had necropsy alone. ing cimetidine treatment one patient bleeding management team The mean age of the 65 males and 39 developed symptoms of mild phenytoin females was 58 years (range 16-88 years). intoxication which resolved when cime- G G BIRNIE, F KENNEDY, C MACKAY, AND Endoscopy correctly identified the bleed- tidine was withdrawn. Urinary output of G WATKINSON (Departments of Surgery ing lesion in 79 (76 %) cases, and identified phenytoin and its metabolite pHPPH and Gastroenterology, The Western In- the site of bleeding correctly in another 11 increased during cimetidine administra- firmary aiid Gartnavel General Hospital, (11 %) cases. Excess blood prevented an tion. In another patient receiving pheny- Glasgow) As an agreed hospital policy adequate endoscopy in three (3 %) cases. toin intravenously, plasma levels also all patients admitted with upper gastro- Endoscopy was incorrect in 11 (11 %) increased during cimetidine treatment. intestinal bleeding are managed by a duty cases; four of 24 (l7 %) gastric ulcers, Thus cimetidine may reduce hepatic team consisting of a gastroenterologist five of 43 (12 %) duodenal ulcers, one metabolism of phenytoin and caution is and a surgeon. oesophageal ulcer, and gastric erosions necessary when adding cimetidine to Ninety-four per cent of 769 patients in one patient being missed. Three of the phenytoin therapy. admitted in 1978-79 and here reported four gastric ulcers were misdiagnosed as were endoscoped, 96% within 24 hours. erosions. Emergency endoscopy within six hours In 31 patients the endoscopy and was necessary in only 14%. barium meal findings were correlated (T11) Bleeding chronic peptic ulcers accoun- with those of surgery/necropsy. The two Retrograde cholangiogram after cholecys- ted for 36-2% of the series, gastritis for investigations agreed in 32 % of cases, tectomy 15.10%, and varices for 3 9%. The man- endoscopy only was correct in 580%, the agement team ensured a much lower barium meal only was correct in 7 %, and I HAMILTON, W S J RUDDELL, D J LINTOTT, recourse to surgery than in other series- both were incorrect in 3%. C J MITCHELL, AND A T R AXON (Gastro- http://gut.bmj.com/ namely, 21 % for gastric ulcer and 91 % This study shows that in acute upper enterology Unit and Department of for duodenal ulcer-a selection which did gastrointestinal bleeding urgent endo- Radiology, Gener.al Infirmary at Leeds, not increase the risk of exanguination, scopy may miss or misdiagnose 10-150% Leeds) Intrahepatic and extrahepatic which accounted for the death of only of gastric and duodenal ulcers. bile duct diameter was measured at ERCP one patient of 279 bleeding chronic ulcers in 50 patients without biliary, hepatic, or treated. The surgical mortality was cor- pancreatic disease (normal subjects), and respondingly increased in the highly in 109 patients after cholecystectomy, of selected group of 36 patients requiring whom 39 had biliary stricture or retained on September 27, 2021 by guest. Protected copyright. emergency surgery, reaching 42% for (T1O) stone and 19 were jaundiced. gastric ulcers and 21 % for duodenal Cimetidine interaction with phenytoin Common bile duct diameter in normal ulcers. Such patients had rebled, were subjects was 6.5 ±20 mm (mean ±SD) usually elderly, suffering from associated D J HETZEL, F BOCHNER, J HALLPIKE, AND and common hepatic duct diameter 6-0 disease, and had ulcers presenting difficult D J C SHEARMAN (Royal Adelaide Hos- 2-0 mm. In post-cholecystectomy patients technical problems. pital, Adelaide, South Australia) Cime- without biliary stones or strictures com- The overall mortality for the series was tidine has been shown to inhibit the mon bile duct diameter (10-0±3.0 mm) 81 %, half the deaths being attributable hepatic microsomal enzyme oxidation and common hepatic duct (9.0 ±30 mm) to malignancy or hepatic failure. Con- system, and drug interaction with cime- were greater than in normal subjects servative approach to surgery ensured an tidine resulting in an increase in the effect (P=< 0-001), and in post-cholecystectomy acceptably low overall mortality at the of warfarin and diazepam has been patients with stones or stricture common expense of a high operative mortality in reported. Phenytoin, a commonly used bile duct diameter (14-5 ±4 mm) and poor risk patients. anticonvulsant with a narrow therapeutic common hepatic duct diameter (15.55 I4.5 index, also undergoes hepatic microsomal mm) were greater than in post-cholecys- metabolism. We therefore investigated tectomy patients with no stones (P= (T9) the effect of cimetidine on steady state < 0.001), but all groups overlapped. Accuracy of urgent endoscopy in acute plasma phenytoin concentrations in four Ducts of jaundiced patients with stones upper gastrointestinal bleeding patients with long-standing epilepsy. were not more dilated than those of non- Serum phenytoin was measured daily jaundiced patients with stones. J A H FORREST, C ZAMBARTAS, R J CREGEEN, in the week preceding cimetidine adminis- Intrahepatic bile ducts were more AND N D C FINLAYSON (The Gastro- tration, then during six days' treatment dilated in post-cholecystectomy patients Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A417 without stones than in normal subjects evaluating protein synthesis by external malabsorption. However, they have not (P=< 0001), and, in post-cholecystec- detection. been compared together, nor against tomy patients with stones, intrahepatic measurements of faecal fat excretion. ducts were more dilated than in those These tests were evaluated against without stones (P=<0-05), with con- (T13) adjusted faecal fat using non-absorbable siderable overlap between groups. Glucose tolerance after acute pancreatitis- radio-opaque markers in 52 patients. In The bile ducts after cholecystectomy short-term and long-term studies eight healthy staff faecal collections were are dilated compared with normal and omitted. After a 60 g fat meal containing duct dilatation does not imply the pres- P BRADLEY, M J MCMAHON, AND J K WALES 10 ,uCi glycerol tri I-14C oleate followed ence of retained stone. Diagnostic (University Departments of Surgery and by a slice of toast, blood was collected methods relying on determination of duct Medicine, The General Infirmary, Leeds) hourly for six hours and plasma trigly- calibre-for example, ultrasound-may Diabetic states are occasionally encoun- ceride and optical density measured. be misleading in the investigation of tered in patients with acute pancreatitis; Breath 14CO2 was measured hourly for patients after cholecystectomy. yet glucose tolerance after acute pancrea- nine hours. After 48 hours' equilibration, titis has not been the subject of extensive stools were collected for three days and study. fat content adjusted using marker Glucose tolerance tests were carried recovery. (T12) out on 88 patients who were convalescent There was no discrimination between Pancreatic incorporation of '1C-L-methio- from their first attack of acute pancrea- subjects with normal and raised faecal nine evaluated by external detection and titis, at a mean time of 19 days after fat (adjusted) using maximal increases in duodenal aspirate in normal subjects and admission to hospital. By WHO criteria, optical density or plasma triglyceride. 36 (41%) were diabetic, 45 (51%) were and hour cumu- patients with chronic pancreatitis normal, and seven (8 %) showed inter- However, the seven eight mediate values. None had a past or lative % 14C02 breath excretion provided M CERF, M DOP-NGASSA, AND A SYROTA excellent separation, with four apparent (Service de Gastroenterologie, Hopital family history of diabetes. false positives and no false negative In a prospective study of 38 of these and Bichat 75018 Paris, SHFJ Departement patients, none of whom had received results. The simplicity, convenience, de Biologie, Commissariat a l'Energie reliability of breath analysis make it an treatment for diabetes, a second glucose faecal collection Atomique 91400 Orsay, France) The tolerance test was carried out between attractive alternative to uptake of a natural L-amino acid by the four and 60 months later (mean 37 in screening for fat malabsorption. pancreas has never been evaluated in months). Of the 19 patients whose man. L-methionine labelled with "1C, a convalescent test showed a diabetic

short half life isotope (20.4 minutes) (TI 5) http://gut.bmj.com/ response, five (26 %) remained diabetic, after produced in a cyclotron was injected in 10 (53 %) were normal (including the only Small bowel transit gastric surgery 25 normal subjects and in 16 patients with patient to have had a second attack of chronic pancreatitis. Data were recorded C L CORBETT, S THOMAS, N HOBSON, AND for 90 minutes with a gamma camera. acute pancreatitis), and four (21 %) were C D HOLDSWORTH (Gastroenterology Unit, Duodenal intubation was simultaneously intermediate. None of the 19 patients Royal Hallamshire Hospital, Sleffield) performed in 14 patients using an infusion whose convalescent test was normal (16) Small bowel transit time (SBTT) measure- of secretin (1 CU/kg/h) and coerulein or intermediate (three) showed a diabetic ment can contribute to an understanding (70 ng/kg/h) for 30 minutes. response, but two (12.5 %) previously of the pathophysiology of diarrhoeal normal now showed intermediate values. on September 27, 2021 by guest. Protected copyright. In normal patients time-activity-curves After the first attack of acute pan- states. This transit time is decreased in obtained in areas of interest selected over to be diarrhoea due to the irritable bowel the pancreas showed a plateau or a slight creatitis islet cell damage appears syndrome and can be increased by increase of activity with time. In contrast, common, and may be of long duration in constipating drugs. in patients with chronic pancreatitis the a few patients. Small bowel transit time was deter- plateau was preceded by a peak lasting mined by serial measurement of end- 10 to 20 minutes. (T14) expiratory breath hydrogen after inges- A similar peak of radioactivity was not Simple screening tests for fat malabsorp- tion of 10 g lactulose in 100 ml water detected in the duodenal aspirate suggest- tion: comparison of plasma triglyceride, until a rise in hydrogen excretion oc- ing that the peak seen by external detec- optical density and 14CO2 breath excretion curred. In seven post-gastrectomy patients tion was not due to a passive leakage of after fat meal containing 14C-triolein with no diarrhoea, small bowel transit L-methionine from the blood into the time was 85.0 1i0 min (M ± SE), simi- pancreatic ducts. The fraction of the G E GRIFFIN, P S WEST, G E LEVIN, AND lar to that of 20 normal subjects (930 ±L amino acid incorporated into proteins J D MAXWELL (Departments of Medicine 6-6 min). In eight post-gastrectomy pa- was low during the first 20 minutes and and Chemical Pathology, St. George's tients with diarrhoea small bowel transit then increased with time in normal Hospital, London) Three simple screen- time was significantly faster (44.3 ± 5.7 subjects (51 ±23 % at 70 minutes). It was ing tests-measurement of changes in min, P< 0.01), but in 10 patients with significantly lower in pancreatitis (6±10, plasma triglyceride, and optical density post-vagotomy diarrhoea it was slightly, P< 0.001). Concentration and output of after a standard fat meal, and 14C02 though not significantly, slower than in bicarbonate and amylase were also breath excretion after ingestion of 14C normal subjects (1 12.5 ±130 min). significantly lower. triglyceride-are claimed to discriminate Small bowel transit time is clearly not 11C-L amino acids could be used for between healthy subjects and those with reduced in post-vagotomy diarrhoea, in Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A418 The British Society of Gastroenterology contrast with both the irritable bowel D G MACDONALD, F D LEE, K M COCHRAN, course of faecal excretion of labelled syndrome and post-gastrectomy diarrhoea. M M FERGUSON, AND R I RUSSELL (Gastro- white cells was compared with that of The demonstration that there is premature enterology Unit, Victoria Infirmary, Glas- labelled plasma transferrin in two patients post-prandial return of jejunal fasting gow, Department of Oral Medicine and to compare the kinetics of white cell and motor complexes after vagotomy has led Pathology, Glasgow Dental Hospital, and protein loss. to the inference that small bowel peri- Gastroenterology Unit, Royal Infirmary, All patients showed normal uptake of stalsis may be increased by vagotomy. Glasgow) Crohn's disease can affect any labelled cells in liver, spleen, and bone Our data do not support this and addi- part of the gastrointestinal tract. A few marrow. Abnormal intra-abdominal local- tional studies of jejunal motor function patients have granulomatous lesions in isation of radioactivity (positive scan) after vagotomy are clearly needed. the mouth, suggestive of Crohn's disease. was found in all the patients with Crohn's The prevalence of intestinal involvement disease. Faecal counting showed mean in these patients is unknown. recovery of 9-21 ±SD 9-8% (range 1.9- We have studied 20 patients (age range 34%) of the dose. All patients with the (T16) 3 to 64 years; mean 25.5 years) who irritable bowel syndrome had negative Single dose gluten challenge in treated presented with swelling of the lips and/or scans and mean faecal isotope excretion coeliac disease: the first 24 hours face, thickening of the buccal mucosae, was 04±SD 0.4% (range 0-1-1.0%). mucosal tags, and oral ulcerations. There The rate of faecal excretion of labelled M G BRAMBLE, C 0 RECORD, AND N A were no gastrointestinal symptoms at the white cells was much more rapid than WRIGHT (Department of Gastroentero- time of presentation. Oral mucosal biopsy that of labelled transferrin. logy, Royal Victoria Infirmary, Newcastle in all patients showed granulomatous Indium labelled white cell scanning upon Tyne) Changes in brush border changes suggestive of Crohn's disease. with measurement of faecal recovery may enzymes and morphology in the early Gastrointestinal assessment included allow regional localisation of Crohn's period after gluten challenge are poorly tests of haematological, biochemical, and disease and provides an objective mea- documented, although a rapid fall in nutritional status, sigmoidoscopy and surement of white cell loss into the enzyme concentrations has been observed. rectal biopsy, jejunal biopsy (in most intestine. Using a Quinton biopsy tube we were patients), small and large bowel radiology. able to biopsy the distal duodenum of 10 Seven of the 20 patients (35%) were patients with treated adult coeliac disease found to have evidence of intestinal (T19) every hour for the first four hours, after involvement. Rectal histology was ab- A new look at the cancer risk in ulcerative instillation of gluten fraction III (=25 g normal in five patients. Six had low colitis gluten) into the proximal duodenum. albumin, five low haemoglobin, three low Additional biopsies were obtained at serum folate, and three low serum zinc. S GYDE, P PRIOR, J A H WATERHOUSE, AND http://gut.bmj.com/ eight and 24 hours. Low serum iron, calcium, magnesium R N ALLAN (Gastroenterology Unit, The Lactase, maltase, and alkaline phos- were also found, and five had a raised General Hospital, Birmingham, and Cancer phatase concentrations fell rapidly during ESR. Epidemiology Research Unit, University the first three to four hours. Lactase Patients presenting with these oral of Birmingham, Birmingham) The mag- appeared to be the most sensitive, falling features may have intestinal Crohn's nitude and pattern of risk of colorectal from (mean ±SEM) 23±6 ,umol/min/ disease and should undergo a full gastro- cancer in ulcerative colitis is uncertain, g X 103 to 14 ± 3 at three hours (P< 0.02). intestinal assessment, even in the absence the apparent risk varying greatly from Alkaline phosphatase fell from 531 66 of symptomatic or clinical evidence of one reported series to another. In this ,umol/min/mg to 337 i47 during the intestinal disease. analysis several models have been used to on September 27, 2021 by guest. Protected copyright. same period (P< 0.05). Villous cell popu- show how selection factors, operating in lation counts fell from 3310 ± 145 to most reported series, may alter the 2633 ±135 cells per villus at four hours (T18) apparent cancer risk and the pattern of (P< 002) and to 2525 ± 182 cells per IndiumII labelled autologous leucocytes in risk over time. These models have been villus at 24 hours. Crohn's disease applied to a hospital series of 676 patients This change was not reflected by direct under long-term review with ulcerative measurement of villous height, which S H SAVERYMUTTU, A M PETERS, J P LAVEN- colitis. The number of colorectal and remained unchanged. At 24 hours a DER, H J HODGSON, AND V S CHADWICK hepatobiliary cancers observed in the significant increase in the crypt population (Royal Postgraduate Medical School, series was significantly in excess of that count was observed (P< 0.05). London) The distribution and fate of expected in a comparable general popula- The rapid fall in brush border enzymes autologous IndiumIII labelled leucocytes, tion. The colorectal cancer risk varied paralleled a similar fall in the villous after intravenous injection, was investi- from six to 17 times that in the general population count. Toxic effects of gluten gated in 11 patients with active sympto- population according to which model was appear earlier than is generally matic Crohn's disease and in 11 patients used for analysis. This variation helps to appreciated. with the irritable bowel syndrome. After explain the widely differing estimates of intravenous injection of the labelled cells, colorectal cancers in published series. (T17) scans were obtained at two to four hours The model which seems to most closely Crohn's disease of the mouth as an early and 18 to 28 hours. Stools were collected resemble the natural history of the indicator of intestinal involvement for four days and Indium content mea- disease suggests that the risk of develop- sured to determine the percentage of ing colorectal cancer increases in the first P B MACINTYRE, M A K GHOURI, C SCULLY, administered dose excreted. The time 15 years after onset of ulcerative colitis Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A419

and thereafter becomes a constant in- Free Hospital, London) Many of the biliary cirrhosis were evaluated separ- creased risk. This pattern suggests that toxic effects of ethanol may be mediated ately. Patients with and without granu- cancer may be initiated and colitis by its metabolite, acetaldehyde. Alco- lomas closely matched clinical, labora- induced by a common aetiological agent holics given ethanol develop high blood tory, and histological features other than at or near the onset of colitic symptoms. acetaldehyde levels. This could be secon- granulomas. Although 23 of these patients dary to liver damage, increased formation showed granulomas, only one of 14 who (T20) related to induction of ethanol oxidation, died did so (P< 0-01). Thus the presence Reticuloendothelial function in coeliac or a primary defect of acetaldehyde of granulomas in primary biliary cir- disease and ulcerative colitis removal. Using a sensitive and repro- rhosis seems to be of prognostic signific- ducible assay, we have studied ethanol ance independently of previously re- K R PALMER, D C BARBER, S SHERRIFF, AND clearance and blood acetaldehyde in nine ported prognostic indicators. C D HOLDSWORTH (Gastroenterology normal subjects and 17 recently drinking Unit and Department of Medical Physics, alcoholic patients. Royal Hallamshire Hospital, Sheffield) Ethanol clearance did not differ be- It is still not known whether the hypo- tween the two groups (199 ± 3-5 (SD) and (T23) splenism which may occur in coeliac 21.4±5l1 mg/100 ml/h), but the mean Aryl hydrocarbon hydroxylase in alcoholic disease and ulcerative colitis is an isolated acetaldehyde was higher in the alcoholics cirrhosis and primary biliary cirrhosis phenomenon or is part of a more general- (17-8 ±6 FM and 10.4±4 FM, P< 001). ised reticuloendothelial atrophy. We have Thus, the defect is one of acetaldehyde K W WOODHOUSE, P H CHAPMAN, 0 F W therefore assessed circulatory clearance removal rather than increased formation. JAMES, A F MACKLON, AND M D RAWLINS of 1251-micro-aggregated albumen (MAA), Aldehyde dehydrogenase activity, mea- (Departments of Medicine (Geriatrics) which is almost exclusively cleared by sured on liver biopsies from nine of the and Clinical Pharmacology, The Univer- Kupffer cells, in 13 patients with coeliac alcoholic subjects, inversely related to sity, Newcastle upon Tyne) Aryl hydro- disease and 17 with ulcerative colitis. blood acetaldehyde levels. Those with the carbon hydroxylase (AHH) is involved in Four and six of these respectively were least damage (fatty liver-nine) showed the tratsformation of polycyclic hydro- hyposplenic as assessed by clearance of higher levels than those with more severe carbons to carcinogenic metabolites. In heat damaged red cells. Control groups liver disease (alcoholic hepatitis and animals, hepatic AHH activity is a major were six normal subjects and five patients cirrhosis). determinant of the carcinogenicity of after surgical splenectomy. Although raised blood acetaldehyde polycyclic hydrocarbons. Because the The splenectomised patients had slower and reduced aldehyde dehydrogenase occurrence of primary liver cancer in clearance of 1251-MAA than any other activity may be a consequence of liver patients with primary biliary cirrhosis is group (P< 005). As splenic uptake of damage, the lack of correlation with strikingly lower than in alcoholic cir- http://gut.bmj.com/ MAA is negligible, this implies that a histological severity suggests that this rhosis, we have compared hepatic micro- factor produced by the spleen enhances may not be the whole explanation. somal AHH activity in these two groups, MAA phagocytosis by Kupffer cells. and in histologically normal liver tissue Hyposplenic patients with ulcerative obtained during diagnostic workup. Both colitis or coeliac disease had normal or (T22) basal and induced (after 18 hours' incu- only slightly impaired clearance of MAA. Granulomas in primary biliary cirrhosis: bation with benzanthracene) AHH activi- The data suggest that hyposplenism in a prognostic feature ties were measured. both coeliac disease and ulcerative

Basal and induced AHH activity (pmol on September 27, 2021 by guest. Protected copyright. colitis is not associated with generalised 0 EPSTEIN, R G LEE, H 0 JAUREGI, S SHER- 3-OH-BP/mg protein/h) was 95.2 ±10 3 reticuloendothelial atrophy, but that LOCK, AND P J SCHEUER (Department of and 152±22 in normal biopsies (n= 8) Kupffer cell function can itself be de- Medicine and Pathology, Royal Free compared with 54.7±4 and 122±11 in pressed as a secondary effect of hypo- Hospital, London) In Crohn's disease, alcoholic cirrhotics (n=10) and 28.2 ±3 splenism. This could account for the Hodgkin's disease, and leprosy the pre- and 55±7 in primary biliary cirrhosis increased susceptibility to perioperative sence of granulomas is associated with (n=12). AHH activity in both cirrhotic Gram negative endotoxaemia, which improved prognosis. To evaluate the groups was significantly lower (p<0-01) appears to be present in patients with significance of granulomas in primary than in normal patients, and the activity ulcerative colitis complicated by hypo- biliary cirrhosis, 295 liver biopsies from in primary biliary cirrhosis was signifi- splenism. 100 patients with primary biliary cir- cantly less (p< 0001) than in alcoholic rhosis were reviewed. Granulomas were cirrhosis. These differences remained found in biopsies of 54 patients and were significant when smokers and women LIVER/IMMUNOLOGY less frequently noted as histological stage were considered as separate groups. T21 T35 increased. They often persisted in mul- These results suggest that (1) although tiple biopsies from individual patients. AHH may play a role in the pathogenesis Granulomas did not correlate with clini- of primary liver cancer in alcoholic cir- (T21) cal presentation or biochemical values, rhosis, other factors must be involved; Impaired acetaldehyde oxidation in alco- but were associated with better survival, (2) this potential impairment in produc- holism as, of the 18 patients who died, only two tion of carcinogenic metabolites in showed granulomas on biopsy. To test primary biliary cirrhosis may offer some K R PALMER, W J JENKINS, AND S SHERLOCK this finding in patients at a uniform stage explanation for the low incidence of (Academic Department ofMedicine, Royal of progression patients with late primary primary liver cancer in this group. Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A420 The British Society of Gastroenterology

(T24) In order to investigate possible beneficial alcoholic hepatitis and/or steatosis. Plate- Possible recurrence of primary biliary effects of vegetable protein in chronic let associated immunoglobulins were cirrhosis after orthotopic liver trans- portal systemic encephalopathy, eight measured by a modification of the anti- plantation patients with stable cirrhosis and a globulin consumption technique, and, in history of spontaneous portal systemic order to establish whether platelet asso- J NEUBERGER, B PORTMANN, B R D MAC- encephalopathy after shunt-surgery were ciated immunoglobulins were specifically DOUGALL, R WILLIAMS, AND R Y CALNE studied while they were off all antience- directed against the platelets, immune (The Liver Unit, King's College Hospital phalopathic therapy. Under metabolic complexes were measured with the Clq and Medical School, London, and The conditions for five consecutive one week binding assay. Department of Surgery, Addenbrooke's periods, equal amounts of mixed proteins Nine of 14 patients with alcoholic Hospital, Cambridge) Three patients were alternated with animal or vegetable cirrhosis and all five patients with non- surviving more than two years after protein in a crossover protocol. alcoholic cirrhosis had raised levels of orthotopic liver transplantation for pri- On admission only three patients had platelet associated immunoglobulins. Im- mary biliary cirrhosis were investigated signs of clinical portal systemic ence- mune complexes were measured in 18 2.6, 3.3, and 3-6 years after transplanta- phalopathy, while all had slowing of cases (14 cirrhotics). Nine of this sub- tion for possible recurrence. Two have a EEG, raised ammonia levels and abnor- group of 14 cirrhotics had raised platelet recurrence of jaundice, not due to biliary mal Trailmaking Test performance. associated immunoglobulin levels and obstruction, and one has developed During the vegetable diet the apparent five of these had normal levels of circu- pruritis. Postoperatively, antimitochon- nitrogen (N-) balance (2.1 ±0.66 g/day) lating immune complexes suggesting that drial antibody levels fell but, despite tended to be more positive than during in the majority platelet associated im- some fluctuation, have shown an overall the animal diet (1.1±063, n=017), munoglobulins were specifically directed rise since; only one has raised immuno- because a decrease in the urinary N- against the platelets. globulin M. Liver biopsy in one showed excretion (6.1 ±74 vs 7.4±0.87 respec- We conclude that platelet associated only fibrosis, but in others there were tively P=007) but no change in faecal immunoglobulins may be important in features of primary biliary cirrhosis, with N-output. The mean peak frequency of the pathogenesis of thrombocytopenia in reduced numbers of bile ducts, bile duct computer analysed EEGs was lower patients with chronic liver disease. destruction, lymphoid aggregates, granu- during the animal diet (6.58 ± 0.43 Hz) loma formation, and slight cholestasis than during the vegetable diet (7.10±0.44 with increased deposition of copper- Hz P=001). A high arginine intake (T27) binding protein. during the vegetable and a high methio- Jejunal biopsy and lymphocyte co-culture As a control group, eight other patients nine intake during the animal diet may in coeliac disease surviving more than two years after explain part of this effect. However, http://gut.bmj.com/ transplantation were investigated. None plasma levels of amino acids did not F G SIMPSON, P D HOWDLE, D A F ROBERT- had antimitochondrial antibody. Only in change. SON, AND M S LOSOWSKY (Department of one patient did liver biopsy show small Vegetable protein diets, rather than Medicine, St. James's University Hospital, bile duct damage, during an episode of simply protein restriction should be Leeds) It has been suggested that an Nocardial infection, but this was not considered in the management of chronic immunological reaction to gluten causes seen on subsequent biopsies. Cholestasis, portal systemic encephalopathy, especi- the jejunal mucosal damage in coeliac present in five, was not associated with ally if the patient is undemourished. disease. increased deposition of copper-binding Organ culture of jejunal biopsies has on September 27, 2021 by guest. Protected copyright. protein. demonstrated gluten toxicity in vitro in In chronic rejection, liver histology (T26) untreated coeliac disease by quantitative may be that of predominant bile duct Are platelet antibodies the cause of histology and biochemical techniques. damage, and in graft-versus-host disease thrombocytopenia in patients with chronic This contrasts with results of culture of the picture may resemble primary biliary liver disease? treated coeliac mucosa where gluten cirrhosis. However, recurrence of primary produces only minor histological changes. biliary cirrhosis is suggested by a rise in I G BARRISON, I D KNIGHT, L VIOLA, M One possible explanation is that treated antimitochondrial antibody and com- BOOTS, T MITCHELL, AND I M MURRAY- coeliac mucosa contains fewer effector patible biopsies only in those with LYON (Gastrointestinal Unit and Depart- lymphoid cells than untreated mucosa. primary biliary cirrhosis initially, although ment of Haematology, Charing Cross We have therefore cultured jejunal the disease is still at a mild and early Hospital and Medical School, London) mucosa from 10 treated coeliacs with and stage. Multiple platelet abnormalities, including without gluten and with and without thrombocytopenia, occur in patients with added autologous peripheral blood lym- chronic liver disease. Increased autoanti- phocytes. (T25) body activity is also well recognised in Biopsies cultured with gluten alone Dietary protein manipulation in mild (and this group of patients. The aim of this showed no reduction in mean enterocyte subelinical) portal-systemic encephalopathy study was to establish whether thrombo- height (mean 25.1 ,u, SD 2.2) compared cytopenia in patients with chronic liver with controls (mean 25.4 ,, SD 1.3) but KAREL M DE BRUIJN, MADELEINE F BEECHING, disease was due to platelet antibodies. those cultured with lymphocytes did CINDY LI, AND LAWRENCE M BLENDIS Twenty-five patients were studied, 14 show a reduction (mean 24.3 g, SD 0-8, (Toronto General Hospital and Addiction with alcoholic cirrhosis, five with non- P< 0.05), as did those cultured with Research Foundation, Toronto, Canada) alcoholic cirrhosis and six patients with gluten and lymphocytes (mean 23.1 gs, Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A42 1

SD 1.5, P< 002). Enterocyte height in (Intestinal Studies Group, Division of from 0-5 and 5-25 hours in the presence biopsies cultured with gluten and lym- Clinical Sciences, Clinical Research and absence of 1 mg/ml GFIII, with and phocytes was significantly lower than Centre, Harrow, Middlesex) In cows' without the addition of 15 ,ug/ml puro- those cultured with gluten alone (P=0-02) milk protein intolerance the local immune mycin. Leucocyte migration inhibition or lymphocytes alone (P< 0 05). reaction in the intestine includes a raised tests, using normal leucocytes, were These results demonstrate that the plasma cell count. To obtain more performed on the culture media, appro- combination of gluten and lymphocytes specific information we have looked for priately reconstituted with GFIII or is more toxic to treated coeliac mucosa cells in the jejunal mucosa producing puromycin. than either alone and support the sugges- antibody to milk proteins. Jejunal biop- Migration inhibition in the presence of tion that immune reactions to gluten may sies from children aged under 2 years, GFIII was demonstrated in the five produce jejunal mucosal damage in with and without such intolerance, were untreated coeliacs but not in the seven coeliac disease. examined for plasma cells containing treated coeliacs or three controls, con- antibodies to the bovine milk proteins firming previous findings. Puromycin did (T28) 3-lactoglobulin and bovine serum albu- not prevent this inhibition and was also Improved technique for the detection of min. A direct immunofluorescence tech- shown to have no non-specific effect on alpha gliadin sensitised cells in the peri- nique with fluorescein-labelled antigens leucocyte migration. pheral blood of untreated coeliac patients was used. Antibody-containing cells were These results confirm that a substance present in 10 of 14 patients intolerant of which inhibits leucocyte migration is CLIONA O'FARRELLY, C. FEIGHERY, J F cows' milk protein but only one of seven produced by untreated coeliac mucosa in GREALLY, AND D G WEIR (Immunology De- controls, all on a diet containing cows' the presence of gluten but suggest that partment, School of Pathology, Trinity milk, and in two of seven patients with active protein synthesis is not required College, Dublin) It has been shown that cows' milk protein intolerance on a cows' for its release. This casts some doubt upon leucocytes obtained from coeliac patients milk-free diet at time of biopsy. The the role of cell-mediated immunity in the will react with alpha gliadin, a purified antibody-containing cells comprised a pathogenesis of coeliac disease. wheat protein shown to be toxic to coeliac small, varying proportion of the total mucosa. However, using the direct or plasma cells, equivalent to up to 7% of (T31) one-step leucocyte migration inhibition the IgA count. In two patients, double Changes in the populations of mucosal factor (LMIF) assay, 100% of treated, immunofluorescence with rhodamine- immunoglobulin-containing cells preceding but only 500% of untreated, coeliac labelled antigens and fluorescein-labelled a relapse of ulcerative colitis patients (and 13 % of controls) responded class-specific anti-human immunoglobu- to the antigen, which confirms the lins showed the antibody-containing cells E LOPES PONTES, J PIRIS, D P JEWELL, AND observations of Haeney and Asquith. In to be 64-80% IgA cells and 20 400% IgE S C TRUELOVE (Gastroenterology Unit, http://gut.bmj.com/ order to reduce the incidence of false cells. No IgM antibody-containing cells The John Radcliffe Hospital, Oxford) negative results in untreated coeliac have yet been identified. Our results Previous studies have shown an increase patients, a more sensitive indirect or two- provide direct evidence of local produc- in immunoglobulin-containing cells in step LMIF assay has been developed. tion of specific antibody to milk proteins the colonic lamina propria of patients Peripheral blood lymphocytes are exposed in the jejunal mucosa in cows' milk with active ulcerative colitis. In the to the antigen to be tested for 72 hours. protein intolerance. present study, serial observations have The cells are separated from the tissue been made of the immunoglobulin- super- containing cell populations in patients in culture medium and the resultant on September 27, 2021 by guest. Protected copyright. natant is assayed for the presence of (T30) remission in order to determine whether lymphokines using normal leucocytes as Further studies in cell-mediated immunity changes in these populations precede a indicator cells. By this method, 100%0 of (CMI) to gluten fraction III (GFIII) in relapse. untreated and 930% of treated coe!iac the small intestinal mucosa in coeliac Twenty patients with ulcerative colitis patients reacted to alpha gliadin as com- disease in clinical and sigmoidoscopic remission, pared with 150% of control groups who were on no treatment, have had comprising normal subjects and patients P D HOWDLE, A W BULLEN, F G SIMPSON, sigmoidoscopy and rectal biopsy per- with other gastrointestinal diseases. The AND M S LOSOWSKY (Department of formed at monthly intervals for a period technique is highly sensitive, requiring Medicine, St. James's University Hospital, of six months. Normal rectal tissue was one thousandth the amount of antigen as Leeds) The demonstration of cell- obtained from 20 patients with the irrit- the direct method. This study indicates mediated immunity to gluten in the small able colon syndrome. Biopsies were fixed there are lymphocytes sensitised to alpha intestinal mucosa of untreated coeliacs in formol sublimate and stained with gliadin in the peripheral blood of all provided further evidence of the import- antisera to lgA, lgG, and IgM by an coeliac patients. This may be of aetio- ance of immune mechanisms in coeliac immunoperoxidase technique. Point logical as well as of diagnostic importance. disease. This suggested that sensitised counting was used to quantify the lymphocytes produce a substance in immunoglobulin-containing cells. (T29) response to gluten, but other explanations IgA-, IgG-, and lgM-containing cells Specific antibody production to milk are possible. To provide additional were significantly increased in patients in proteins in the jejunal mucosa of children information about such a substance we remission compared with the control with cows' milk protein intolerance have extended our previous work using group. Nine patients relapsed and in puromycin, a protein synthesis inhibitor. most of these all three populations of J R PEARSON, D KINGSTON, AND M SHINER Small intestinal biopsies were cultured cells increased three to five weeks before Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A422 The British Society of Gastroenterology clinical relapse was apparent. The greatest tarda patients have antibodies reacting WRIGHT (Professorial Medical Unit, proportional rise was seen in the IgG- specifically with porphyric hepatocytes. Southampton General Hospital, South- containing cells which increased six-fold. ampton) Earlier studies have demon- These results support the hypothesis strated that macrophages recruited into that mucosal antibody production has a (T33) rat livers during an inflammatory reaction role in the pathogenesis of ulcerative Different mechanisms of lymphocyte- produce increased amounts of tissue- colitis. mediated liver cell damage in 'auto- damaging lysosomal enzymes. In order to immune' and HBsAg positive chronic study the influence of various drugs on (T32) liver disease this enhanced production, macrophages Specific antibody-dependent cell mediated have been isolated from rat livers using cytotoxicity (ADCC) against isolated por- G MIELI-VERGANI, D VERGANI, B PORTMANN, pronase digestion; these cells have been phyric hepatocytes in porphyria cutanea I MURRAY-LYON, R THOMPSON, 1 WOOLF, exposed to the appropriate drugs in vitro tarda A L W F EDDLESTON, AND R WILLIAMS for two hours and the production of an (The Liver Unit, King's College Hospital acid hydrolase (n-acetyl-B-glucosamini- E BARAVALLE AND J PRIETO (introduced by and Medical School, London) Mech- dase, NAG) measured at the end of an R E Pounder) (Department of Medicine, anisms of lymphocyte-mediated damage additional 24 hours in culture. Both University Clinic, University of Navarra, to hepatocytes have been investigated in normal liver macrophages and macro- Pamplona, Spain) The mechanism of 57 patients with chronic liver disease by phages recruited into the liver after an hepatic damage in porphyria cutanea incubating subpopulations of peripheral intravenous injection of Corynebacterium tarda remains unknown. Rats were made blood lymphocytes with the patients' own parvum have been studied. Drugs used porphyric by administering hexachloro- hepatocytes. In 10 of 16 patients with were prednisolone (200 ng/ml), levami- benzene. An ADCC test was carried out HBsAg negative chronic active hepatitis sole (10 -3 M), azathioprine (100 ng/ml), as follows: hepatocytes from normal and non-T cells showed increased cytotoxicity or 6 mercapto-purine (6 MP, 100 ng/ml). porphyric rats were isolated and used as but only one, with a previous history of These drugs did not influence normal targets; serum from normal subjects or non-A non-B hepatitis and no auto- macrophage NAG production. Signifi- patients was added, and normal peri- antibodies, had in addition cytotoxic cant decreases in the enhanced produc- pheral blood mononuclear cells were T-cells. In contrast, T-cell cytotoxicity tion by recruited cells were observed in used as effectors. LDH release was was found in seven of 12 patients with the presence of azathioprine (P< 0-05) measured as an indicator of cytotoxicity. HBsAg positive chronic active hepatitis. and 6 MP (P< 001). Total NAG (nmol The cytotoxicity index was obtained by Five also had non-T cytotoxicity. Aggre- activity/kg cell protein) for the respective the expression: gated IgG and liver membrane lipopro- groups at the end of the culture period

tein blocked non-T cytotoxicity but did were: normal macrophages 0-25 ±004; http://gut.bmj.com/ LDH released LDH released not affect T-cell killing, results consistent recruited macrophages, RM 0-63 ±0.08; by patient serum - by normal serum with the proposal that non-T killing is RM after prednisolone exposure 0.55± x 100 antibody mediated and directed at a 0.06; RM, levamisole 0.53 ±004; RM, Total LDH content of hepatocytes normal membrane component. T-cell azathioprine 0.44±0-08; RM, 6 MP In six of eight porphyria cutanea tarda cytotoxicity was decreased but not com- 0.36±0-06. These changes may represent patients a high cytotoxicity index was pletely blocked by purified HBsAg and one mechanism of action for the bene- found with porphyric hepatocytes and in 41 patients with a wide range of ficial influence of azathioprine on chronic very low or null with normal hepatocytes. chronic liver disease due to HBV infection liver disease. The six sera with positive ADCC test be- the frequency of T-cell cytotoxicity was on September 27, 2021 by guest. Protected copyright. longed to patients with chronic active higher in HBeAg positive cases, findings hepatitis and/or cirrhosis. Sera from two consistent with a relationship between (T35) porphyria cutanea tarda patients without T-cell killing and active viral replication. Does proximity to colorectal carcinoma liver disease did not show positive ADCC The results show a clear difference in suppress the immunological competence of either with porphyric hepatocytes or with immune-effector mechanisms between lymphocytes? normal hepatocytes. Sera from patients 'autoimmune' chronic active hepatitis and with non-porphyric chronic active hepa- chronic active hepatitis associated with G H HUTCHINSON, D HEINEMANN, M 0 titis showed very low LDH release with persistent viral infection. While non-T SYMES, AND R C N WILLIAMSON (Depart- porphyric hepatocytes and a positive lymphocytes reacting with normal mem- ment of Surgery, Bristol Royal Infirmary, ADCC towards normal hepatocytes. brane components may be involved in Bristol) The finding that lymphoreticu- Alcoholic liver disease serum did not both sub-groups, T-cells, probably react- lar infiltration of solid tumours may exhibit ADCC with porphyric hepato- ing with viral determinants, are exclusive impart a favourable prognosis prompted cytes nor with normal hepatocytes. to those with viral infection. a study of lymphocyte immunoreactivity In immunofluorescence studies, por- in human colorectal cancer. Tumour phyria cutanea tarda serum from patients digests (collagenase/DNAse) from 16 with active liver disease showed an (T34) large-bowel carcinomas were passed intense immunofluorescence with isolated Drug influences on the enhanced produc- through a nylon-wool column to separate porphyric hepatocytes, and weak im- tion of acid hydrolases from macrophages neoplastic cells and tumour infiltrating munofluorescence with normal hepato- recruited into rat livers during liver injury lymphocytes. Lymphocytes were also cytes. obtained from the peripheral blood by We conclude that porphyria cutanea A R TANNER, A H KEYHANI, AND RALPH centrifugation on a Ficoll-Isopaque gra- Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A423 dient. The cytotoxicity of each population (20 mg/kg enteric). All rats were killed at intraductal infusion of a mixture of the of lymphocytes was assayed against six hours. bile salt sodium taurocholate (3.5%) and autoplastic tumour cells, using a two- Raised serum amylase levels occurred trypsin (6000 BAEE units per ml). hour 51Cr release assay. in all except the control group. The survival times of 15 rats given In 11 of 16 patients peripheral blood Lung compliance was reduced in the continuous intravenous leupeptin in lymphocytes showed moderate cytotoxi- pancreatitis group (0-61 _±008 ml/cm saline I ml per hour was 3444 --4.4 hours city, whereas tumour infiltrating lympho- H20/g) compared with the control group compared with 28 0 4 2 hours in 15 cytes showed similar cytotoxicity in only (0.73 -0 1 ml/cm H20/g, P< 005) and simultaneous control animals receiving five cases. The cytotoxicity of tumour in- this change was reversed by dexametha- saline alone (P< 0.001). We conclude that filtrating lymphocytes from 1 1 patients sone (072iO08 ml/cm H20/g, P< 002), the proteolytic enzyme inhibitor leupeptin was therefore compared before and after heparin (0.74-40.09 ml/cm H20/g, P< significantly prolongs survival in acute washing six times in medium 199. Reac- 0.01), and aspirin (0.77-0 07 ml/cm experimental pancreatitis. tivity against tumour cells was shown by H20/g, P< 0-001). unwashed tumour infiltrating lympho- Percentage lung weight was raised in cytes in three of 1 1 and by washed tumour the pancreatitis group (0.45 ±005 %) (T38) infiltrating lymphocytes in nine (P< 0.02). compared with the sham operation group Physiological actions of pancreatic poly- At effector: target ratios of 10:1 and 20:1 (037+±0.02O%, P< 001) and this change peptide on pancreatic exocrine secretion the level of reactivity was significantly was reversed by heparin (0.36±0 04%, greater for washed tumour infiltrating P<0 01) and aspirin (0.39+0.03o%, P< P G DEVITT, J LONOVICS, S GUZMAN, P L lymphocytes (P=005-0 001). 0.05) but not by dexamethesone (0.45 ± RAYFORD, AND J C THOMPSON (introduced The cytotoxicity of lymphocytes derived 0.07%, P>0 05). by R Shields) (Department of Surgery, directly from the tumour may be impaired 'Stiff' and heavy lungs occurred in University of Texas, Medical Branich, by a blocking factor (perhaps tumour- experimental acute pancreatitis. These Galveston, Texas, USA) Pancreatic associated antigen), adherent to the changes were completely reversed by polypeptide in pharmacological doses has lymphocyte membrane but removed by heparin and aspirin and partially reversed an inhibitory effect on pancreatic exo- washing. Proximity to the carcinoma may by dexamethasone, suggesting that pul- crine secretion. We have studied the action suppress the immunological competence monary intravascular coagulation con- of exogenous pancreatic polypeptide, in of lymphocytes. tributes to the pulmonary changes of doses which could be considered physio- acute pancreatitis. logical, on endogenously stimulated pan- creatic secretion. Five dogs with pancreatic fistulae were (T37) infused intraduodenally with either hydro- PHYSIOLOGY I Leupeptin, a low molecular weight trypsin chloric acid or an amino acid mixture. http://gut.bmj.com/ T36-T50 inhibitor, prolongs survival in acute Pancreatic secretion of water bicarbonate experimental pancreatitis and total protein, and plasma concentra- tions of secretin, cholecystokinin and (T36) PETER JONES, D A W GRANT, J HERMON- pancreatic polypeptide were measured. Effect of various drugs on the pulmonary TAYLOR (Department of Surgery, St. Pancreatic polypeptide (0.8 and 2-1 sg/kg/ changes occurring in experimental acute George's Hospital Medical School, Lon- h) was infused for 45 minutes during pancreatitis don) Acute pancreatitis has a mortality the period of stimulated pancreatic of about 1I1 and results in the liberation secretion. % on September 27, 2021 by guest. Protected copyright. A R BERRY AND T V TAYLOR (University of pancreatic enzymes into the circula- Hydrochloric acid stimulated secretion Department of Clinical Surgery, Royal tion. The mortality is higher in those with of water (59.7 - 15-8 ml/45 min), bicar- Infirmary of Edinburgh, Edinburgh) The the haemorrhagic form. The kallikrein bonate (764-1-7 mEq/45 min), and pro- respiratory complications of acute pan- and trypsin inhibitor Trasylol (aprotinin) tein (1837731-8 mg/45 min), while the creatitis are closely related to prognosis failed to reduce mortality or morbidity amino acid mixture increased secretion of and an undertanding of the mechanism in recent multicentre trials. This failure water (8.0±1.7 ml/45 min) and protein involved is vital to improve management. has been attributed to the inability of (183-3+14-3 mg/45 min). Hydrochloric With the use of a rat model of acute Trasylol to abolish catalytic activity of acid increased circulating concentrations pancreatitis lung compliance and lung trypsin in the circulation, where it is of secretin only, and the amino acid weight were studied and the effects of bound predominantly to ac2 macroglobu- mixture increased plasma concentrations dexamethasone, heparin, and aspirin on lin. Inhibition of the a2 macroglobulin- of cholecystokinin. These increases in these parameters in acute pancreatitis trypsin complex is complete in the pancreatic exocrine secretion were inhi- were investigated. Compliance was cal- presence of low concentrations of leu- bited by pancreatic polypeptide: low culated from lung inflation studies after peptin, a low molecular weight peptide dose figures for hydrochloric acid stimu- the rats had been killed. aldehyde proteinase inhibitor of micro- lation: water (24.4±6.4ml/45 min), bi- Five groups of eight rats were studied: bial origin. Its use in pancreatitis has not carbonate (3.3 4-11 mEq/45 min), pro- a control sham operation group, a pan- been reported. tein (50.8 128.8 mg/45 min) (P< 0 05). creatitis group, and pancreatitis groups We studied the effect of leupeptin on Pancreatic polypeptide did not affect the given dexamethasone (3 mg/kg intra- the survival of rats with experimental release of secretin or cholecystokinin. venously), heparin (150 IU/l subcutane- acute haemorrhagic pancreatitis. This We conclude that pancreatic polypep- ously and intravenously) and aspirin was induced by controlled, standardised tide inhibits pancreatic exocrine secretion, Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A424 The British Society of Gastroenterology and this action may be of physiological Long-term oesophageal pH monitoring years) were studied to ascertain the normal significance. This inhibition does not provides a measure of the duration of range and reproducibility of transit times. appear to be through interference with high oesophageal acidity and may thus A bolus of 500 ,1Ci/99mTc sulphur col- the release of secretin or cholecystokinin, help to identify patients at greatest risk loid in 10 ml of water was swallowed, with and may be mediated by direct action on of stricture formation. the patient positioned supine beneath a the pancreatic acinar cell. We have monitored gastro-oesopha- gamma camera linked to video-recorder. geal reflux occurring in hospitalised Computer processing allowed analysis of patients and in the same group at work time activity curves for the upper, middle, and in the home using a newly developed and lower thirds of the oesophagus. The (T39) radiotelemetry capsule (RTC average mean transit time in the normal Duodenal reflux oesophagitis in the rat pH sensitive 7006 Rigel) and a portable receiving subjects was 2-5 s (i SD 0.6), and the system. A three-aerial chestband detected average total transit time was 6.23 H J MUD, S E KRANENDONK, D L WESTBROEK, frequency modulated signals emitted by SD H OBERTOP, H VAN HOUTEN, AND M VAN (l 1.1). the tethered RTC positioned 5 cm proxi- The procedure was then undertaken on BLANKENSTEIN (Departments of General pres- 10 patients with the manometric features Surgery and of Internal Medicine II, mal to the lower oesophageal high sure zone. was moni- of diffuse spasm and who University Hospital pH continuously oesophageal Dijkzigt-Rotterdam) tored the receiver and a suffered from chest pains and dysphagia. We planned to study (1) the effect of by portable Nedilog 24 hour cassette recorder worn The total transit time, which proved the reflux of gastric juice, bile, or pancreatic on a waist belt, allowing the patient more discriminating measurement, was juice separately or in combination on the freedom of movement. prolonged in all cases (range 90-90 s) rat oesophagus; (2) the relation between complete Studies were performed in 10 patients and accorded with the degree of mano- the presence of active trypsin and/or bile with graded symptoms of gastro-oeso- metric abnormality. acids in oesophageal washout samples phageal reflux accompanied by oesopha- Radionuclide transit measurement is a and the occurrence and degree of oeso- phagitis. gitis graded at endoscopy and biopsy. quick, comfortable, and reproducible new The mean number of reflux episodes procedure which should prove useful in Male Wistar rats (n=88) of equal age per two hours' recording time for hos- identifying oesophageal motility disorders. and weight were randomly subjected to pitalised patients was 2-32 (+0 49 SEM) either one of seven different reflux- compared with 7-3 (±1-53 SEM) for inducing operations. An oesophageal outpatients-a significant difference (t= washout sample was obtained before the 3-08, P< 0.02). Similar analysis for the (T42) selected operation and seven days after total duration of episodes for both Effect of natural prostaglandin E2 (PGE2) the operation when the rats were killed hospitalised and outpatients gave mean and derivatives on aspirin-induced fall in for trypsin and bile acid determinations. durations of 15.88 minutes (±7.23 SEM) gastric mucosal electropotential differencehttp://gut.bmj.com/ In all rats the oesophagus was examined both macroscopically and microscopically and 39-62 minutes (±4 94 SEM) respec- in man for signs of oesophagitis. tively again significant (t= 2.7, P< 0.05). Ambulatory outpatient oesophageal pH H A CARMICHAEL, L M NELSON, AND R I Oesophagitis followed all operations is useful in that allowed pancreatic juice to reflux monitoring assessing patients RUSSELL (Gastroenterology Unit, Royal with atypical symptoms and may demon- Infirmary, Glasgow) We have investi- into the oesophagus, by itself or in com- strate significant gastro-oesophageal re- gated the effect of pretreatment by oral bination with either gastric juice or bile or flux when inpatient studies and endo- administration of several PGE2 com-

both. on September 27, 2021 by guest. Protected copyright. scopy findings show minimal abnormality. pounds on the fall in electropotential In the case of reflux of pancreatic juice difference induced in six normal human active trypsin was detected in the volunteers by 1200 mg aspirin in 50 ml oesophageal washout samples. The (T41) saline given orally. The dose of prostag- presence of active trypsin correlated well Radionuclide transit studies of the oeso- landin that prevented the electropotential with the occurrence, but not with the phagus difference falling by more than 50% of degree, of oesophagitis. the fall induced by aspirin alone was The presence of bile acids in the oeso- J N BLACKWELL, W J HANNAN, S HOLT, determined for each prostaglandin in each phageal washout samples was not associ- P TOTHILL, AND R C HEADING (Depart- subject. ated with the occurrence or the degree of ments of Therapeutics and of Medical Using the Kendall coefficient of con- oesophagitis. Physics, The Royal Infirmary, Edinburgh) cordance, there was a highly significant Current methods of investigating patients agreement between (a) the subjects with with motility disorders of the oesophagus regard to ranking of potencies of the (T40) are unsatisfactory. Contrast radiology is compounds and (b) the compounds on Ambulatory monitoring of oesophageal pH insensitive, and manometry is both time- ranking of the sensitivities of the subjects in reflux oesophagitis using a portable consuming and uncomfortable for the (p <001 in both cases). (a) The ranking radiotelemetry system patient. Our aim was to assess whether of the compounds in order of potency oesophageal radionuclide transit studies was: 15 (S) 15 Me PGE2 >15 (R) 15 Me F J BRANICKI, D F EVANS. A L OGILVIE, M might prove a satisfactorily sensitive, PGE2 > 16, 16 di Me PGE2 Natural ATKINSON, AND J D HARDCASTLE (De- objective, and non-invasive method for PGE2. (b) There was marked variation in partment of Surgery, University Hospital, identifying oesophageal dysfunction. the sensitivity of individuals to the Queen's Medical Centre, Nottingham) Ten normal volunteers (aged 24-74 protective effect of the prostaglandins, Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from

The British Society of Gastroenterology A425 with > 100-fold difference between cer- (T44) prostaglandins and prostaglandin synthe- tain individuals. The PGE2 compounds Motility patterns of the human antrum tase inhibitors on antral mucosal barrier alone did not reduce electropotential and jejunum and their association with damage induced by topical bile salts. difference. sleep: studies using a radiotelemetry Dogs were prepared with denervated Prostaglandin E2 compounds, including system antral pouches (n=4). Control studies natural PGE2, prevent breaking of the demonstrated that topical 20 mM sodium gastric mucosal electropotential difference D F EVANS, G E FOSTER, AND J D HARD- taurocholate (NaT) caused a transient barrier and may be useful cytoprotective CASTLE (Department of Surgery, Uni- but significant increase in net H+ loss agents in man. The marked interindivi- versity Hospital, Queen's Medical Centre, from -91 ± 15 ,umol/30 min to -372+ 51 dual sensitivity to the protective effect of Nottingham) Gastrointestinal pressures ,umol/30 min (p < 0.05) and a correspond- PGE2 compounds could be relevant in can be conveniently recorded using a ing increase in net Na+ gain from 145 ± the context of susceptibility to peptic tethered radiotelemetry capsule. However, 46,mol/30 min to 407±115 gimol/30 min disease. this does not permit the recognition of (p < 0.05). propagation of activity, essential if the Intravenous 15 (S) 15 methyl prostag- migrating motor complex and its phases landin E2 (PG; intravenous bolus dose are to be studied. We have used two 12,g/kg) reduced net H+ loss induced by linked radiotelemetry capsules, each tuned NaT from -372± 51 ,umol/30 min to -67 to a different frequency and receiver, to ±36,mol/30 min (p < 0.05) but caused a (T43) record activity in the antrum and jejunum significant increase in net Na+ gain from Motility of the denervated human stomach of 20 fasting volunteers, during the day 407±115 F±mol/30 min to 751 ± 130,mol/ and duodenum and during a night's sleep; during sleep 30 min (p < 0.05). heart rate and electro-oculogram were Intravenous indomethacin (IND; in- D L WINGATE AND A GORCHEIN (London recorded to identify REM periods. A travenous bolus dose 5 mg/kg) similarly Hospital, London, and St. Mary's Hos- correlation is seen between REM periods reduced net H+ loss induced by NaT pital, London) A 34 year old man, and a phase 111 activity front in the from -372±51 ,umol/30 min to -51±18 subsequently found to have acute inter- antrum (x2=19.9, P= <0 001), antral t,mol/30min (P<0-02) but had no signi- mittent porphyria, developed quadri- fronts always propagated to the jejunum, ficant effect on net Na+ gain. plegia, respiratory paralysis, and signs of the interval between successive jejunal We conclude that both exogenous autonomic denervation after a laparo- fronts being 136-4 minutes (±6-01 SEM). prostaglandin E2 and indomethacin re- tomy. After six months on a ventilator In 14 subjects fronts were recorded in the duce taurocholate-induced net H+ flux, with total parenteral nutrition, some jejunum only without preceding antral but may do so by differing mechanisms. recovery of neck and shoulder movement activity often occurring shortly before or Prostaglandin E2 may stimulate Na+ rich http://gut.bmj.com/ prompted a study of gastroduodenal after a propagated front; their inclusion secretion while decreasing the severity of motility in the hope of instituting enteral in migrating motor complex interval NaT induced damage, while indo- feeding. Motility was recorded for 72 analysis reduced the mean interval to methacin directly affects monovalent hours through three perfused lumens of 107-5 minutes (45.9 SEM). Isolated ionic permeability of the antral mucosa. a nasoduodenal tube with openings jejunal fronts were never associated with located in the distal, and mid-duodenum, preceding REM sleep periods and com- and in the antrum. prised 300% of all jejunal fronts recorded. (T46)

During the first 61 hours of study, the Two forms of activity front occur in the Histamine is not the final common pathway on September 27, 2021 by guest. Protected copyright. patient received intravenous dopamine, human jejunum: a propagated front for gastric acid secretion but, as the dose was diminished, antral associated with preceding REM sleep contractions at 3/min appeared and and therefore central influence, and W K MAN, C J H INGOLDBY, AND J SPENCER persisted, although varying in amplitude, isolated fronts apparently free of such (Department of Surgery, Royal Post- for most of the rest of the study. During central control. graduiate Medical School, Hammersmith the final 18 hours, some periods of low- Hospital, London) The relationship be- amplitude contractions at 10/min were tween gastric acid secretion and gastric noted (? antral tachygastria). There was (T45) and plasma histamine release, after penta- no evidence of duodenal contractile Effect of parenteral prostaglandin and a gastrin infusion, is so close as to suggest activity at any time during the study. prostaglandin synthetase inhibitor on antral that histamine is acting as a transmitter Neither the antral motility nor the duo- mucosal permeability to induce acid release. denal atony were in any way altered by We have attempted to discover whether oral feeding, intraduodenal nutrition H J E LEWI AND D C CARTER (University a similar pattern of histamine release (Isocal), or intraduodenal neostigmine. Department of Surgery, Royal Infirmary, follows insulin-induced gastric acid secre- The findings suggest that both the Glasgow) Exogenous prostaglandins re- tion. normal periodic fasting motor activity duce monovalent ion flux across fundic Nine patients with proven duodenal and the normal motor response to food is mucosa exposed to topical damaging ulcer were studied by a combined insulin/ neurally dependent, but that the neural agents, while prostaglandin synthetase pentagastrin gastric secretion test. Acid control of the stomach and duodenum inhibitors alter monovalent ion flux both output, gastric histamine output, and differ; in the antrum it is inhibitory, in the presence and absence of topical plasma histamine levels were measured. while the duodenum requires neural damaging agents. The present studies There were no significant changes in activation. were undertaken to explore the effect of gastric or plasma histamine levels during Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A426 The British Society of Gastroenterology insulin-induced acid secretion (median may be maintained beyond three hours Suirgery, Harvard Medical School, and basal 0-98; median highest fraction 0.93; and a significant effect for longer than Guy's Hospital, London) The effects of median basal plasma 4.06; median eight hours. Additional studies are re- indomethacin and 16-16 dimethyl PGE2 highest plasma 6.68). quired to examine these possibilities. (16 dm PGE2) on duodenal HCO3' After pentagastrin infusion there was secretion were studied in vitro. Stripped an immediate increase in gastric hista- amphibian duodenum was mounted in mine to a peak (median 2.66, P<0.05) (T48) Ussing chambers and HCO3' secretion followed by a fall and then a second peak Gut-glucagon and GIP may cause sufficient measured by pH stat. Indomethacin (median 4.89, p< 0.001). The biphasic hypoglycaemia in duodenal ulcer patients inhibited active HCO3' secretion by 36± nature of the gastric histamine release is to activate the vagus nerves 3 % at 10-5 M and 58±6% at 5 x 104M. unexplained. The occurrence of acid 16 dm PGE2 (10 -5M) stimulated active secretion without histamine release during N F KNIGHT, S ZAHEDI-ASL, D J SANDERS, HCO3' secretion by 151±8% of control insulin infusion suggests that the changes A P MARR, C W VENABLES, AND A MOODY valves, and completely reversed the induced by pentagastrin are not simply a (Departments of Phlysiology and Surgery, inhibitory effect of low-dose indomethacin passive 'washout' of histamine during The University, Newcastle utpon Tyne) (10- M). The effect of high-dose indo- acid secretion. We have previously reported to this methacin (5 x 10 4M) was significantly The lack of histamine release during society that after eating a standard break- mitigated by 90 minutes' pretreatment insulin infusion is not compatible with fast, a group of patients with endoscopic- with 16 dm PGE2 and was completely the theory that histamine is the common ally proven active duodenal ulcer had prevented by simultaneous addition of final transmitter to the parietal cell. significantly higher plasma insulin and 16 dm PGE2, but was not reversed if significantly lower glucose concentrations 16 dm PGE2 was added 90 minutes after than age and sex-matched controls. indomethacin. 16 dm PGE2 demonstrated (T47) The hypoglycaemia in duodenal ulcer protection only when given on the serosal SK&F 93479 is a long-acting inhibitor of patients may be very important because side of the tissue; mucosal administration gastric acid secretion in man it was recently shown that hypoglycaemia was ineffective. over the range 5-3 mM produces gastric We conclude that 40% of duodenal W L BURLAND, A C CLANCY R H HUNT, acid secretion. Our duodenal ulcer HCO3' secretion is driven by endogenous JANE G MILLS, DIANA VINCENT, AND G J patients went below 3 mM glucose from prostaglandins and this component is MILTON-THOMPSON (Smith Kline and about 75 to 180 minutes after feeding. abolished by low-dose indomethacin. French Research Ltd, Welwyn Garden We have now measured the plasma Exogenous prostaglandins on the serosal City, Herts; Royal Naval Hospital, Haslar, glucose-dependent insulinotrophic pep- side stimulate HCO3' secretion, reverse

Gosport, Hants) The H2-receptor anta- tide (GIP) and shown that control and the inhibitory effects of low-dose indo- http://gut.bmj.com/ gonists cimetidine, oxmetidine, and rani- duodenal ulcer basal are not significantly methacin, and protect HCO3' secretion tidine differ in potency but not in duration different. There is a significantly greater against high-dose indomethacin. Such of action. SK&F 93479, a non-imidazole GIP response in duodenal ulcer patients observations provide a possible explana- H2-antagonist, is 16 times more potent on from 15 to 120 minutes after feeding and tion for the observed but unexplained a molar basis and longer acting than this probably accounts for the high ulcerogenic effects of indomethacin and cimetidine. insulin response in these patients. prostaglandin 'cytoprotection' in animal We studied the effect of oral cimetidine In addition, the significantly higher and human duodenum. 3 and SK&F 93479 on plasma gut-type glucagon concentrations mg/kg 0-25 mg/kg on September 27, 2021 by guest. Protected copyright. the gastric secretory response to meals seen in duodenal ulcer patients from 15 given 30 minutes or one hour and six to 120 minutes after feeding may also (T50) hours after dosing using a modified help to account for the hypoglycaemia in Nicotine-induced relaxation of the ampulla intragastric titration technique. these patients. It is known that gut-type of Vater Mean two hour acid output in six glucagon can bind to liver cell glucagon healthy men during the first meal was receptors and this may prevent the action HELEN L LEATHARD AND T G ALLEN-MERSH reduced from 64.6 mmol (placebo) to of pancreatic glucagon in stimulating (Departments of Pharmacology and of 21-2mmol (67%) by cimetidine and to glucose release from the liver. Surgery, Charing Cross Hospital Medical 23.7 mmol (63%) by SK&F 93479. A The increased release of gut-type School, London) Nicotine, at levels sustained response to SK&F 93479 oc- glucagon and GIP in duodenal ulcer comparable with those caused by cigarette curred in all subjects but in four this was patients may be secondary to the ulcera- smoking, stimulates duodenal motility achieved only after the first hour. Mean tion or it may be a primary change. It in vivo. To investigate the possible acid output after the second meal was would appear to produce sufficient hypo- influence of nicotine on bile and pancrea- reduced from 59-2 mmol to 46-7 mmol glycaemia to activate the vagus. tic juice propulsion we have recorded its (21 %) by cimetidine and to 34-0 mmol effects on strips of bile duct, pancreatic (43 %) by SK&F 93479. The difference duct, and longitudinal and circular between drugs was significant (p < 0.05). (T49) duodenal muscle from the dog. Our re-sults suggest that the antisecre- Indomethacin inhibits duodenal HCO3 The ducts were dissected free of duo- tory effect of SK&F 93479 is prolonged secretion: protection by prostaglandin denal muscle and cut spirally to record and that on a molar basis it is approxi- sphincter muscle responses. Thin strips of mately 20 times more potent than cime- J N L SIMSON AND W SILEN (introduced by duodenum were cut parallel to the longi- tidine. The maximum antisecretory effect Professor I McColl) (Department of tudinal or circular muscle fibres. The Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A427 strips were suspended in Krebs' solution (73 %, and 860% respectively). Parenteral After mean follow-up of 3-7 years six had at 37°C and responses recorded isotonic- drug abuse was more common in the developed complications of portal hyper- ally (1 g load). non-A, non-B group than in the hepatitis tension, three died. Group 4: eight patients Preparations from five dogs yielded a B virus group (55 % vs 36%). None of the (10%) presented with complications of consistent pattern of responses to nicotine non-A, non-B group was homosexual in portal hypertension. After mean follow-up (100 ng/ml, 10 t±g/ml): the bile duct contrast with the hepatitis B virus group of 2.5 years three died. sphincter was predominantly relaxed; where 18% were homosexuals. None in We conclude that many patients with duodenal circular muscle gave a biphasic either the non-A, non-B or hepatitis B primary biliary cirrhosis (46% here) are response of weak relaxation and then virus groups worked in health-related asymptomatic, an unknown proportion contraction; duodenal longitudinal muscle occupations. Twenty-eight per cent of the (14% here) have normal LFTs but signi- contracted strongly; pancreatic duct non-A, non-B hepatitis patients had ficant liver pathology. Asymptomatic failed to respond. These responses re- evidence of past infection with hepatitis patients have an excellent prognosis. flected those caused by stimulating the B virus. intramural nerves electrically at 4 Hz In London, acute non-A, non-B hepa- (1 ms pulses, supramaximal voltage). titis accounts for 16% of all acute viral These results suggest that the bile duct, hepatitis. An important risk factor is (F3) but not the pancreatic duct, can respond parenteral drug abuse. Sexual transmis- Advantages and disadvantages of percu- independently of the surrounding duo- sion was not noted. There was no associa- taneous transhepatic biliary drainage as denal muscle. By relaxing the bile duct tion with health-care occupations. Hepa- part of a staged approach to obstructive sphincter, nicotine could cause premature titis A virus is commonly transmitted jaundice flow of bile into, or promote reflex from among male homosexuals. the duodenum, depending on prevailing G A D MCPHERSON, I S BENJAMIN, B NATH- pressures. ANSON, I B BLENKHARN, N B BOWLEY AND L H BLUMGART (Departments of Sur- (F2) gery, Bacteriology, and Radiology, Royal Primary biliary cirrhosis-a frequently Postgraduate Medical School, London) asymptomatic disease A two-stage approach has long been advocated for high-risk patients with

O F W JAMES, A F MACKLON, AND A J obstructive jaundice. The recent introduc- PLENARY WATSON (Departments of Medicine tion of percutaneous transhepatic biliary F1-F9 (Geriatrics) and Pathology, University of drainage as a non-surgical first stage has

Newcastle upon Tyne) Primary biliary been reported as a significant advantage http://gut.bmj.com/ cirrhosis is thought to be a disease in in the preoperative management of the (F1) which virtually all patients have marked jaundiced patient. No reports, however, Prospective study of acute non-A, non-B rises in serum alkaline phosphatase. Only have provided a critical assessment of hepatitis in a London population a small proportion of patients are thought percutaneous transhepatic biliary drain- to be asymptomatic. We present 84 age based on defined criteria for selection. M BAMBER, A MURRAY, B BANNISTER, H C patients with primary biliary cirrhosis We have treated 26 patients by percu- THOMAS, AND S SHERLOCK (Department (seven males), all histologically confirmed, taneous transhepatic biliary drainage (19 Free 83/84 had antimitochondrial antibody with high bile duct tumours, and seven ofMedicine, Royal Hospital, London, on September 27, 2021 by guest. Protected copyright. and Coppetts Wood Hospital, Muswell (AMA) titre > 1/40. There were four with low bile duct or pancreatic tumours), Hill, London) The epidemiology of groups. Group 1: 12 patients (14%) of whom 23 came to second-stage surgery. non-A, non-B hepatitis unrelated to asymptomatic of liver disease having Satisfactory changes in plasma bilirubin transfusions, was studied in 70 consecu- normal alkaline phosphatase, bilirubin, (T1/2= 10-4 days) and renal function tive cases of acute viral hepatitis admitted aspartate aminotransferase (LFTs). All were obtained, but the incidence of com- to a London infectious diseases hospital. were detected on review of +ve anti- plications rose with increasing duration Non-A, non-B hepatitis was diagnosed if mitochondrial antibody found during of drainage. Infection was the main serological markers of recent hepatitis A investigation of an unrelated problem problem. Seven (27%) had infected bile (IgM anti-HAV) and B (HBsAg, HBcAb), (usually thyroid or joint disease). All had at the time of drainage. This high inci- Epstein-Barr virus, and cytomegalovirus abnormal liver biopsies, seven were diag- dence for malignant obstruction may were absent. Twenty-nine (41 %) of the nostic of primary biliary cirrhosis, five have been related to previous surgery. cases were due to hepatitis A virus, 28 had raised serum gamma GT, five raised Serial bile sampling showed that the (40%) due to hepatitis B virus, two (3 %) serum IgM. After mean follow-up 4.0 incidence of colonisation of the drainage due to Epstein-Barr virus, and 11 (16%) years two had developed abnormal LFTs, system increased progressively after the due to non-A, non-B hepatitis. none had symptoms of liver disease. first four days. This colonisation signifi- In the hepatitis A virus group nine Group 2: 28 patients (33 %) asymptomatic cantly affected the operative outcome. (31%) of the patients were homosexual of liver disease but with abnormal LFTs. There were two deaths in the post- males. After mean follow-up of 2-5 years five operative period which were secondary to The non-A, non-B and hepatitis B patients had developed symptoms of infection arising in the drainage system. virus groups were similar in their average liver disease, one died of liver failure. Exogenous infection, common in the age (31 years, and 28 years respectively) Group 3: 36 patients (43 %) presented early patients, was later excluded by and predominant occurrence in males with symptoms suggesting liver disease. adding povidone iodine to the system. Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from

A428 The British Society of Gastroenterology

(F4) intravenous infusion of secretin (1 clinical ergometrine. Twelve patients had neither Duodenoscopic sphincterotomy in patients unit/kg/h) and cholecystokinin (1 Ivy Dog pain nor oesophageal spasm. with gallbladders unit/kg/h). Se75-methionine (3.0 micro- In 10 of the 29 patients with either curies/kg) was added to the infusion. proven or suspected oesophageal spasm, A G VALLON AND P B COTTON (Gastro- Pancreatic juice was collected in 15 this problem was not considered until intestinal Unit, The Middlesex Hospital, minute batches and assayed for pH, ergometrine was given. Ergometrine pro- London) Duodenoscopic sphincterotomy bicarbonate, and enzymic activities. Each vocation alone saved many patients from is widely used in patients with duct stones sample was immediately mixed with 0-6 N unwarranted invalidism as cardiac after cholecystectomy; increasingly pa- TCA and the activity of the precipitated cripples. tients are referred who still have gall- protein counted in a gamma-counter. bladders in place. We have attempted After the infusion, tin colloid was given sphincterotomy in 56 patients (mean age by bolus intravenous injection and a (F7) 73 years) presenting with jaundice and pancreatic subtraction scan performed. Effect of vagotomy on gastric nitrosamine cholangitis. Sphincterotomy was possible The rate of incorporation of Se75-methio- production in 55 patients, and duct clearance was nine into pancreatic proteins was signifi- achieved in 48 (87 %). Stones were cantly greater in all the patients with P I REED, P L R SMITH, F R HOUSE, AND greater than 15 mm in diameter in five of chronic pancreatitis, suggesting that in C L WALTERS (Gastrointestinal Unit, the seven patients whose stones could not chronic pancreatitis the surviving acinar Wexham Park Hospital, Slough, Berk- be extracted. There were no fatal com- cells undergo compensatory increase in shire; British Food Manufacturing Indus- plications. One patient required a blood their capacity to synthesise and secrete tries Research Association, Leatherhead, transfusion, and two needed urgent proteins. Synthetic rate studies can detect Surrey, and Department ofPharmacology, cholecystectomy for acute cholecystitis chronic pancreatitis before secretory Guy's Hospital Medical School, London) within seven days of sphincterotomy. insufficiency occurs. Gastric cancer develops more frequently Clinical follow-up (mean 14 months, in achlorhydric conditions, including range six to 48 months) has been possible partial gastrectomy and vagotomy with in 44 of the 46 remaining patients with drainage, a recent report noting a much gallbladders and successful bile duct (F6) shorter induction period after the latter clearance. None has suffered cholangitis Ergometrine provocation in the diagnosis procedure. There is strong evidence or jaundice; nine have undergone elective of oesophageal spasm indicating that N-nitroso compounds, cholecystectomy because of relative youth formed by gastric flora converting dietary and fitness, and four others because of H ALBAN DAVIES, M KAYE, A M DART, nitrate (via nitrite) and dietary or endo- biliary pain. from six weeks to one year A H HENDERSON, AND J RHODES (Depart- genous nitrosatable amines, may be http://gut.bmj.com/ after sphincterotomy. The remaining 31 ment of Gastroenterology and Cardiology, important in gastric carcinogenesis in patients are well. Duodenoscopic sphinc- University Hospital of Wales, Cardiff) achlorhydria. Animal studies using N- terotomy is recommended for acutely ill Oesophageal disease frequently mimics Methyl-Nl-nitro-N-nitrosoguanidine have patients with duct stones even in the cardiac pain; we have investigated 42 demonstrated accelerated gastric cancer presence of a gallbladder; longer follow- patients with apparent angina but no formation after vagotomy. Recently we up is required to judge the indications for cardiovascular abnormality (all had exer- demonstrated a highly significant rela- subsequent cholecystectomy, but it seems cise tests and 35 had coronary angio- tionship between a rise in gastric pH, reasonable to postpone this graphy), by giving them ergometrine to increase in total concentra-

indefinitely N-nitrosamine on September 27, 2021 by guest. Protected copyright. in many elderly and frail patients. provoke oesophageal spasm. tion and growth of nitrate reducing gut Oesophageal motility was studied with flora in upper gastrointestinal disease, a triple lumen assembly perfused with including cancer, and also during cime- (F5) water (05 ml/min) by syringe pump. tidine treatment. Pancreatic synthetic rates: a new test of Ergometrine (500-1000,ug intravenously) Forty-eight fasting gastric juice speci- pancreatic function was given to the patients as well as to 10 mens from 29 vagotomised patients, 26 volunteers after an injection of saline, and when not treated and 22 during cimeti- E J S BOYD AND KG WORMSLEY (Depart- full resuscitation facilities were available. dine treatment, were analysed bacterio- ment of Therapeutics, University of Dun- The tracings were masked and read logically, for pH, nitrite, and total N- dee, Dundee) Ten patients with no 'blind' by an experienced observer. nitroso compounds. Vagotomy resulted evidence of pancreatic disease and seven Barium swallow examinations were also in significantly higher bacterial growth patients with unequivocal chronic pan- performed. (P 0-014) and mean N-nitrosamine con- creatitis (two of whom had normal Asymptomatic oesophageal spasm was centration (P< 002) compared with nor- enzyme outputs in response to secretin/ present in nine patients at rest and there mal controls, especially when performed CCK) had synthetic rate estimations were minor abnormalities in another 13. more than six years previously. Levels using the incorporation of Se75-methio- After ergometrine 22 of the 42 patients also rose during cimetidine treatment, nine into pancreatic proteins. After the had oesophageal spasm and 19 of them significantly so in six patients studied patient had been fasted overnight a tube experienced their typical pain. Another serially, N-nitrosamines (P < 0-002) and with vented gastric and duodenal aspira- eight patients developed pain without pH (P < 0-05). These data confirm the tion channels was positioned under radio- definite spasm; seven of these showed an significant relationship between pH and logical control. Pancreatic secretion was increase in abnormal oesophageal mo- N-nitrosamine production especially in stimulated for two hours by constant tility, but no coronary vasospasm, after achlorhydria. More detailed studies are Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A429 required to establish which vagotomy is used increasingly for rectal carcinoma gastric juice before ultrastructural operation enhances this risk. because it obviates the need for a per- examination. manent colostomy and is statistically as There was no macroscopic evidence of curative as total excision. However, alginate at endoscopy in these patients, (F8) where an anastomosis is technically diffi- but on electron microscopy dark-staining Late mortality after curative surgery for cult. alternatives to total excision are globules could be identified in the inter- peptic ulcer described but have not gained widespread cellular spaces of the deeper functional acceptance. and prickle cell layers. Globules were A H MCLEAN ROSS, J R ANDERSON, M A Since 1973, 75 patients with rectal seen in seven of 18 patients examined up SMITH, AND W P SMALL (Gastric Follow- carcinoma in a situation unsuitable for to one hour after alginate treatment, but up Clinic, Department ofSurgery, Western anterior resection have had sphincter in only two patients examined thereafter. General Hospital, Edinburgh) For many function preserved by an overlapping These appearances could be reproduced years it has been suggested that surgical sutured anastomosis performed within by incubation in alginate of oesophageal treatment of benign peptic ulceration the anal canal from the perineal aspect. biopsies from untreated patients. No such results in a shortened lifespan. This study The results have been analysed. globules were found in more than 100 examines this suggestion and its possible The pathological characteristics of other oesophageal biopsies from patients causes. these tumours were comparable with not receiving alginate treatment. The prospectively gathered records of those of all rectal carcinomas treated at Alginate pretreatment partially pre- 856 men aged 30-59 years who underwent St. Mark's Hospital between 1948 and vented the severe damage expected after curative surgery (gastrectomy 86 %, drain- 1972. Two patients developed pelvic incubation in autologous gastric juice age±vagotomy 13 %; other 1 %) for sepsis after colonic necrosis and anasto- pH 1 in each of three patients. In two benign gastric or duodenal ulceration motic breakdown. Eight developed pelvic other patients with gastric juice pH 7 or during the period 1947-65 were examined. sepsis without major anastomotic break- 8 no protection was observed. Patients with subsequent recurrent peptic down. Four patients have developed The protective action of alginate may ulceration were excluded from this group, recurrent pelvic tumour. Twenty-one of resaLlt from plugging of the oesophageal as were patients dying less than one year 32 patients are alive without sign of intercellular spaces and prevention of the after surgery. Nine per cent of the group recurrence at three years and 12 of 19 are cytotoxic effects of retrograde reflux. were lost to follow-up. By 1980 46.2 % alive five years after a curative operation. had died. Sixty-nine of the 70 patients whose Actuarial life table analysis demon- colostomies had been closed at the time (Fl1) strated highly significant increases in of assessment had normal or near normal Elemental diet composition: effect on bile

death rate between each age group bowel function. acid metabolism and hepatic lipids http://gut.bmj.com/ studied (30-39, 40-49, and 50-59 years) The operation is straightforward, has a and predicted death rates for a compar- morbidity and mortality comparable with LESLEY M NELSON, I WILLIAMSON, AND able population (P < 0 001, < 0.001, alternative procedures, and produces R I RUSSELL (Gastroenterology Unit, < 0-001, respectively). The operated good functional results. Royal Infirmary, Glasgow) We have group died on average 9.1 years prema- previously demonstrated that treatment turely. with the low fat elemental diet Vivonex Eighty-four per cent of the study group reduces faecal bile acid excretion and were smokers and of all the deaths improves cholerheic diarrhoea in man. recorded 675 % were from diseases In this study the mechanism of these on September 27, 2021 by guest. Protected copyright. related to smoking. Death from causes THERAPY effects and the influence of elemental diet traditionally related to peptic ulcer F10-F24 composition have been investigated by surgery (gastric carcinoma, pancreatic feeding rats Vivonex (n = 6), Flexical carcinoma, TB, suicide, alcoholism) (n=6), or control diet (n=6) for three amounted to 11.9%. of the deaths (2.2%, months. 4.7 %, 0-6 %, 2-5 %, 1.9 % respectively). (FIO) Median (range) faecal bile acid excre- This study confirms that patients who Alginate: microanatomy of drug action? tion was reduced from 1094 (855-1115) undergo surgery for peptic ulcers are [Lmol/kg body weight/wk for control diet likely to die prematurely. The contribu- M C BATESON, D HOPWOOD, W S HISLOP, to 541 (407-695) for Flexical and 207 tion to mortality of diseases related to AND I A D BOUCHIER (Departments of (126-280) for Vivonex (P <0002 in all smoking or peptic ulcer surgery is dis- Medicine and Pathology, Ninewells Hos- cases). Cholic acid half-life increased cussed and compared with figures for the pital and Medical School, Dundee, Scot- from 2-8 (2.5-3.7) days to 4-2 (3.3-7.5) general population. land) Forty-seven patients with a nor- for Flexical and 10(5 (8-8-11-6) for mal oesophagus were given 20 ml alginate- Vivonex (P<0003). Liver cholesterol was sodium bicarbonate mixture (Gaviscon) 198 (135-220),umol/kg body weight for (F9) up to five hours before upper digestive control diet, 241 (211-358) for Flexical, Results of resection and colo-anal anasto- endoscopy. Biopsies were taken on entry and 725 (397-1054) for Vivonex (P< mosis for carcinoma of the rectum 30 cm from the incisors. Sections were 0.005). cut, stained, and examined with the Thus, reduced faceal bile acid excretion J P PERCY AND A G PARKS (St. Mark's electron microscope. In five patients during elemental diet feeding does not Hospital, London) Restorative resection biopsies were incubated in autologous result from a reduced bile acid pool but Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A430 The British Society of Gastroenterology reduced turnover of a normal sized pool acid mixtures at the low concentration (F14) and a rise in liver cholesterol reflects (40 mmol ocNH2/l), were absorbed to a Old ladies, drugs, and gastric ulceration reduction of necessary bile acid synthesis. greater extent (P < 005) from the peptide Liver histology showed marked fatty mixture at the high concentration (100 P COOKE AND M R THOMPSON (Depart- change in 5/6 Vivonex and slight changes mmol aNH2/l). ment of Surgery, Bristol Royal Infirmary, in 516 Flexical. Total liver lipid was We conclude that the greater absorp- Bristol) The controversy over the extent increased from 5 9 (3.6-7.3) mmol/kg tion of amino acids from protein hydroly- to which non-steroidal anti-inflammatory body weight to 8.3 (7-2-12.6) for Flexical sates compared with their equivalent drugs (NAD) cause peptic ulceration and 25.7 (14'1-29.8) for Vivonex (P< amino acid mixtures is a concentration continues. In view of this, the medication 0 005). dependent phenomenon and that intes- taken by 202 patients with gastric ulcer This study indicates that, although the tinal perfusion studies do not allow any admitted to the Bristol Royal Infirmary composition of Vivonex has a more statement regarding the relative nutri- between 1974-78 was reviewed. Thirty- marked effect on bile acid turnover than tional merits of different nitrogen sources. seven patients (10/108 men=9 %; 27/94 Flexical, the latter may be preferable if women =29%) were on a non-aspirin the development of fatty liver during long- NAD (NANAD). Thirty-four (91 %) term elemental diet therapy is to be (F13) were aged over 60 years and 25 (68%) avoided. Dietary nitrogen formulation: does it were women over 60 years. Thus, 25 out really matter? of 70 women (36%) aged over 60 years were on NANADS (indomethacin, 14; (F12) K J MORIARTY, J E HEGARTY, P D FAIR- phenylbutazone, seven; other NANAD, Effect of concentration on amino acid CLOUGH, M L CLARK, AND A M DAWSON four). This was significantly greater absorption from a protein hydrolysate and (Department of Gastroenterology, St. (P<0.01, x2 test) than an age-matched an equivalent amino acid mixture Bartholomew's Hospital, London) A group of 220 women admitted to the variety of enteral diets containing either same hospitals over the same time period J E HEIGARTY, K J MORIARTY, P D FAIR- whole protein, protein hydrolysates, or with either a colonic carcinoma or gall- CLOUGH, M L CLARK, AND A M DAWSON free amino acids as the nitrogen source stones (5/220 indomethacin; 3/220 phenyl- (Department of Gastroenterology, St. are available for the treatment of protein- butazone; 2/220 other NANAD). Bartholomew's Hospital, London) Jeju- calorie malnutrition. However, the opti- Seven gastric ulcer patients were taking nal perfusion studies in man demonstrat- mal composition of the nitrogen source NANADS for rheumatoid arthritis, six ing greater absorption of amino acids used in these diets has not been estab- for osteoarthritis and three for non- from complex mixtures of peptides lished, although intestinal perfusion specific arthritis. In nine the reason was

compared with their equivalent amino studies have suggested that diets contain- indefinite. http://gut.bmj.com/ acid mixtures have suggested that pep- ing small peptides as the nitrogen source In comparison with the 35 women aged tides might confer nutritional advantages. may confer nutritional advantages. The over 60 years not on NANADS the 25 However, the relative rates of absorption purpose of the present study was to on NANADS were more likely to have a of amino acids from single peptides and evaluate the relative merits of different giant ulcer (11/25 vs 4/35; p< 0.05), need equivalent amino acid mixtures is critic- nitrogen sources in the maintenance of a blood transfusion (19/25 vs 15/35; ally dependent on concentration. The nitrogen balance in normal man. (p< 0-05), be on a diuretic (12/25 vs 4/35; present studies were designed to examine, Nitrogen conservation was induced by p< 0.01), less likely to have an operation using a jejunal perfusion technique in feeding four healthy volunteers for 38 vs 18/35; p<0.05), and had a

(5125 on September 27, 2021 by guest. Protected copyright. man, the effect of concentration on the days a low nitrogen intake (47 mgN/kg/ significantly shorter history of dyspepsia relative rates of absorption of amino 24 h), which produced a state of negative (p < 0'001). acids from a protein hydrolysate contain- nitrogen balance. All diets were isonitro- Thus the majority of NANAD gastric ing a complex mixture of peptides and genous and isocaloric, energy (151 kJ/kg) ulcers occur in elderly women in whom from an equivalent mixture of free amino being provided by a glucose polymer and it is a significant problem. These ulcers acids. a fat emulsion. After an 18 day adapta- have several features which distinguish Studies were performed using solutions tion period, there was equal conservation them from idiopathic ulcers. Diuretics of a hydrolysate of lactalbumin and an of nitrogen by the three forms of dietary may be important cofactors. equivalent amino acid mixture containing nitrogen used, as shown by comparable 40 and 100 mmol aNH2/l. The results urinary excretion of nitrogen over 10 day show that the five amino acids (isoleucine, study periods in the subjects fed lactal- (FI 5) leucine, methionine, proline, arginine), bumin whole protein, its hydrolysate, Pirenzepine in the treatment of duodenal which were absorbed to a greater extent and an equivalent amino acid mixture. ulcer: a multicentre controlled trial versus (p< 0-05) from the amino acid mixture We conclude that whole protein is as cimetidine than for the hydrolysate at the low con- effective as amino acids and protein centration (40 mmol aNH2/l), were ab- hydrolysates in maintaining nitrogen M GUSLANDI, A TITTOBELLO, M GALEONE, sorbed to a similar extent from the high balance and that there is therefore no G MOISE, E BIANCHINI, P BODINI, A VOLTA, concentration (100 mmol aNH2/l). Simi- nutritional logic in the current practice of G VERCELLINO, E BAFFELLI, AND M GIORGI- larly, those amino acids (phenylalanine, prescribing liquid feeds containing expen- CONCIATO (introduced by P I Reed) tyrosine, serine, histidine, threonine, sive hydrolysates and amino acids to (Third Medical Clinic, University of glutamine), which were absorbed to a subjects with normal gastrointestinal Milan; Surgery Department, Hospital of similar extent from the peptide and amino function. Castel Goffredo, 2nd Medical Department, Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A431

Hospital of Cremona, 2nd Medical De- pancreatin alone; (2) cimetidine alone; During 72 hours after a single dose of partment, Hospital of Sesto S. Giovanni; (3) pancreatin plus cimetidine. We have di-5-ASA, less than 5% of the amount Medical Department, Hospital of Breno; compared these results with those on no ingested appeared intact in the urine. Clinical Department, Istituto De Angeli, treatment. On pancreatin alone, there Nineteen to 41 % (median 26.7 %) of the Milano, Italy) Pirenzepine, a selective was an increase in mean lipase (15-1 vs dose was recovered in the urine, and anti-muscarinic agent, was found to be 37 U/i, P<0.01) and lipolysis (12.5 vs 7-36% (median 17.3%) in the faeces, as effective in promoting healing of peptic 8.8%, P <0 05), but no increase in 5-ASA and acetyl-5-ASA. Serum 5-ASA ulcer. In a controlled clinical trial involv- aqueous-phase lipid (6.4 vs 79 mM/I, levels were negligible. ing five hospitals we have compared NS) because bile acid precipitation re- During long-term oral ingestion (0.25 g pirenzepine and cimetidine in the treat- mained unchanged (313 vs 27.5% NS). daily) the serum half-time of di-5-ASA ment of duodenal ulcer. Fifty-nine per cent of the meal entered was 74-10 days. After 1.0 g di-5-ASA One hundred and two outpatients with the jejunum below the critical pH of 5; had been taken daily for eight days, the endoscopically proved duodenal ulcers on the cimetidine regimens all the meal 24 hour faecal recovery of total 5-ASA were randomly allocated to a six week was at pH>6. On cimetidine alone, bile was 19-70% (median 35.8 %) of the daily treatment with either pirenzepine (100 mg acid precipitation was reduced compared dose. daily) or cimetidine (1 g daily). The two with pancreatin alone (178±3.8 % vs The quantity of 5-ASA reaching the groups were comparable as regards sex, 31*3±10*1 %, NS) and aqueous lipid was colon after ingestion of di-5-ASA is age, disease history, smoking, and alcohol increased (9.0 vs 6-4 mM/i, P < 0.05) similar to that found after ingestion of and coffee consumption. Ninety-six despite minimal lipase and lipolysis. The sulphasalazine. patients completed the study, but only 84 combined regimen was significantly better agreed to undergo endoscopical control than either pancreatin or cimetidine alone at six weeks. Endoscopy was performed for lipase (40.5 U/l P < 0.01), lipolysis by endoscopists unaware of the adminis- (19-7%, p< 0-05), and bile acid precipita- (F18) tered treatment and healing was defined tion (4.3 %, P < 0.05). This led to a marked Sulphasalazine retention enemas in ulcera- as complete re-epithelisation of ulcer improvement in aqueous phase lipid tive colitis: a double-blind trial area. Statistical analyses were carried out (18.8 mM/I, P<0.05). We conclude that by an independent statistician. for optimum therapy of pancreatic stea- K R PALMER, J R GOEPEL, AND C D HOLDS- The healing rate was 71.5 % with piren- torrhoea, bile acid precipitation, as well WORTH (Department of Gastroentero- zepine and 59.5 % with cimetidine. The as pancreatin inactivation, must be logy, Royal Hallamshire Hospital, Shef- difference is not statistically significant, prevented. field) Oral sulphasalazine is of proven showing that both drugs are equally value in the treatment of ulcerative effective. No differences in the two groups colitis, but in up to 20% of cases side- http://gut.bmj.com/ as regards pain relief and antacid con- effects preclude its use. Sulphasalazine sumption were observed. (F17) retention enemas represent an alternative Side-effects were mild and infrequent Disposition in normal volunteers of sodium approach in these subjects, though their with both drugs. Only one patient in the azodisalicylate, a potential therapeutic efficacy has not been adequately demon- pirenzepine group and one in the cimeti- agent in inflammatory bowel disease strated. dine group discontinued treatment be- Thirty-four patients with active ulcera- cause of severe side-effects (dry mouth C P WILLOUGHBY, J K ARONSON, H AGBACK, tive colitis therefore completed a double- and diarrhoea respectively). N 0 BODIN, E ANDERSSON, AND S C TRUELOVE blind assessment of the efficacy of two (Gastroenterology Unit and the Depart- weeks of treatment by nightly retention on September 27, 2021 by guest. Protected copyright. ment of Clinical Pharmacology, John enemas containing 3 g sulphasalazine, (F16) Radcliffe Hospital, Oxford, and the compared with placebo. Clinical, sig- Effect of cimetidine on intraduodenal bile Analytical Research Department, Phar- moidoscopic and rectal biopsy grading acid precipitation, pancreatin inactivation, macia AB, Uppsala, Sweden) Colonic and diary records were used to assess and lipid solubilisation in pancreatic bacteria split sulphasalazine to liberate change in disease activity and side-effects. steatorrhoea sulphapyridine and 5-aminosalicylic acid Significant advantage of active drug was (5-ASA). 5-ASA is the active constituent; shown by change in clinical and sig- P L ZENTLER-MUNRO, D R FINE, M GANNON, many adverse effects of the compound moidoscopic scores (p < 0.05), stool AND T C NORTHFIELD (Department of are attributable to its sulphapyridine consistency, and percentage bloody stool Medicine, St. George's Hospital Medical content. An oral agent which released (p < 0.05) and by histological improvement School, London) In pancreatic steator- only 5-ASA in the colon would, in theory, in seven subjects, contrasting with rhoea cimetidine enhances the effect of be a preferable drug. deterioration in four of the controls. pancreatin on fat absorption. Our hypo- Sodium azodisalicylate (di-5-ASA) is Improvement occurred only in those thesis is that this enhancement is due, not two 5-ASA molecules linked by a diazo subjects not already taking oral sulpha- only to prevention of pancreatin inactiva- bond. We have studied its disposition in salazine. tion by gastric acid, but also to prevention eight normal volunteers. Serum, urinary, Overall assessment showed improve- of pH-dependent bile acid precipitation. and faecal concentrations of di-5-ASA ment in 70% of patients on active treat- To test this, we have aspirated jejunal and total 5-ASA were measured after a ment, but only 11 % on placebo (p < 0.01). contents after a Lundh meal in seven single oral dose (0.5 g di-5-ASA) and No significant side-effects were observed patients with pancreatic steatorrhoea on during long-term treatment (0-25 g or even in patients (two) previously in- three regimens in random order: (1) 1.0 g daily). tolerant of oral sulphasalazine. Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A432 The British Society of Gastroenterology

(F19) fore widely believed that the underlying an increase in biliary UDCA from 0-3.8 % 5 aminosalicylic acid, a weak inhibitor of mechanism of action is a reduction in to 323-858% of the biliary bile acids human colonic prostaglandin synthetase hepatic cholesterol synthesis. Our hypo- after treatment. UDCA was 90-99 % thesis is that this is secondary to an glycine conjugated after therapy. After C J HAWKEY (Nuffield Department of effect on bile canalicular membrane correction for the increased biliary UDCA Clinical Medicine, John Radcliffe Hospital, because bile acids are known to content the lithogenic index did not Oxford) 5 aminosalicylic acid (5ASA) is have marked membrane effects. We have change. probably the active therapeutic moiety of therefore isolated bile canalicular mem- Gallstone calcification was an un- sulphasalazine. Although it is assumed to brane from hamster by the method of common event on UDCA therapy (five act through inhibition of prostaglandin Evans. The hamster was chosen because of 54 cases) but was not seen in 122 synthetase there is no direct evidence that it provides a good model for formation patients we have viewed after chenodeoxy- it does so in human colonic muocsa. A of cholesterol gallstones, which can be cholic acid therapy. This difference is method allowing construction of dose- prevented by chenodeoxycholic acid but unlikely to have arisen by chance (p< response curves using single rectal biop- not by cholic acid. Purity of bile canali- 0.006, Fisher's exact test), and must be sies was therefore developed, and used to cular membrane vesicles was checked considered when comparing the relative investigate the effects of 5ASA, sulpha- enzymically and by electron microscopy. therapeutic influences of these bile acids. pyridine, prednisolone, indomethacin, and They were incubated (37°C, pH 7.4) for flurbiprofen. five minutes with conjugated bile acids Rectal biopsies taken from untreated 1-4 mM. Chenodeoxycholic acid solu- (F22) colitics in remission were homogenised in bilised less cholesterol than cholic acid Is recurrence inevitable on withdrawing ice cold Tris HC1 pH 7.4. Aliquots in (mean±SD: 18-0±1.3% vs 24.2±3-5% treatment after complete gallstone dissolu- duplicate or triplicate were preincubated at 1mM, 38.5_--4-1% vs 504±4.9% at tion with chenodeoxycholic (CDCA) and on ice with serial dilutions of inhibitor 2mM, 48-8±5.9% vs 85.4±5.5% at ursodeoxycholic (UDCA) acids? before incubation for 30 minutes at 4 mM) but more phospholipid (14.3 ± 37°C with arachidonic acid 6.1 x 10-5 M, 1.2 % vs 7.2±0.9% at 1 mM, 62.0±5.8% D C RUPPIN AND R H DOWLING (Gastro- adrenalin 3.0x 10-3 M, and reduced glu- vs 11.9±1.9% at 2mM, 77.5±1.2% vs enterology Unit, Department of Medicine, tathione 1.3 x 10-3 M (final concentra- 31.0±2.0% at 4 mM). Guy's Hospital and Medical School, tions). The reaction was stopped by Dehydrocholate, a non-micelle-forming London) Recurrence rates of 10-30 % addition of indomethacin (final concen- bile acid, solubilised no lipid. We con- have been reported after discontinuing tration 10-3 M) in ice-cold ethanol. After clude that these findings are consistent treatment but surprisingly little is known extraction, the prostaglandin E2 synthe- with the micellar theory of biliary lipid about the frequency, timing, and risk

sised was measured by radioimmunoassay secretion; and that they provide a novel factors of gallstone recurrence. Since 1972 http://gut.bmj.com/ Mean IC50s -50% inhibitory concen- explanation for the finding that chenode- we have seen complete gallstone dissolu- trations (with 95 % confidence limits) oxycholic acid, but not cholic acid, tion on 61 occasions in 56 patients were: for 5ASA, 2.68 (194-3A42) x 10 -2 M reduces biliary cholesterol saturation. followed with annual radiographs for up (n=4); for indomethacin, 3.55 (0.59- to five years after discontinuing CDCA 6.51)x10-7M (n=4); for flurbiprofen, (n=47) or UDCA (n=14). 5-17 (2-89-7.45)x 10-7 M (n=3). Neither (F21) Excluding 11 patients lost to follow-up sulphapyridine nor prednisolone was Gallstone calcification caused by ursode- and seven who have not yet had post- effective. oxycholic acid (UDCA) dissolution cholecystograms, to date These results provide the first direct there have been 23 recurrences in 22 on September 27, 2021 by guest. Protected copyright. demonstration that 5ASA can inhibit M C BATESON, D P MAUDGAL, D B TRASH, patients (21 of 30 (70%) after CDCA and human colonic prostaglandin synthetase. T C NORTHFIELD, AND I A D BOUCHIER two of eight (25%) after UDCA), while However, its low potency makes it ques- (Department of Medicine, Ninewells Hos- 16 patients have remained gallstone free. tionable whether this is its therapeutic pital, Dundee; Norman Tanner Institute of In five, recurrent stones were dissolved by mode of action in ulcerative colitis. Gastroenterology, St. George's Hospital, further therapy only to recur again in one. London; Manor Hospital, Walsall) Gall- Mean time from discontinuing treat- stone calcification has been observed in ment until detection of recurrence was (F20) five patients after therapy with UDCA 20±SD 14-9 months (range 3-63 months), Novel mechanism of action for chenodeoxy- 500-1000 mg daily for initially radio- 20 of the 23 recurrences (87 %) appearing cholic acid in gallstone dissolution lucent gallbladder stones. This occurred within two years. Time-related recurrence after six to 12 months' therapy. rates were nine of 46 (20%) at one year, J GRAHAM, R BIRD, AND T C NORTHFIELD In three patients there was a con- 11 of 31 (37%) at two, one of 12 (8%) at (Departments of Biochemistry and Medi- current reduction in stone size of at least three, and two of seven (29 %) at four to cine, St. George's Hospital Medical 50%, but after calcification no further five years. School, London) Chenodeoxycholic acid, response in gallstone sizes has occurred. There were no significant differences but not cholic acid, makes fasting Biliary lipid analysis in four of the between 22 patients with gallstone recur- gallbladder bile unsaturated in cholesterol patients showed consistent falls in choles- rence and the 16 who remained gallstone and causes dissolution of cholesterol terol content (14.3 to 6-7, 9.3 to 5.3, 6-8 free, in age (57±6 vs 53±13 years), body gallstones. It also reduces biliary to 3.1, and 6.1 to 3.2mol%), and litho- weight (64±10 vs 67±12kg), pretreat- cholesterol secretion and hepatic genic index (1-82 to 1.00, 1.90 to 1.06, ment stone size (6.8±4 vs 78±t5 mm HMGCOA reductase levels. It is there- 0-76 to 0.68, and 0.78 to 0.53). There was diam) or number (9410 vs 19 ±6), dose Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A433

(14.5±1-8 vs 15-3-LI-9mg CDCA/kg/ Hospital, London) In primary biliary There has been a significant reduction day) and (10.0 vs 89- -2-00 mg UDCA/ cirrhosis, immunological damage to intra- in the number of elective operations for kg/day) or duration of treatment to dis- hepatic bile ducts causes chronic chole- both gastric and duodenal ulcers since solution (16±8 vs 13 --5 months), nor stasis, liver fibrosis on liver copper reten- 1977 (61-38 duodenal ulcers, 13-10 between pretreatment and on-treatment tion. The immunological, cupriuretic, and gastric ulcers; per six month period; SIs (1-45-_03 vs 1-46 -0 3 and 0.74±0-2 antifibrotic effects of d-penicillamine P<0-01 Mann-Whitney U test). As there vs 0-76 -0 2 respectively). However, the make it potentially suitable for the treat- was no similar reduction in the number female:male ratio was significantly higher ment of primary biliary cirrhosis. We of cholecystectomies or admissions for (p<0-05) in the recurrence group (22:1) have evaluated d-penicillamine (Hom- perforated duodenal ulcer, it would seem than in the non-recurrence patients (11:5). burg) in a radomised trial. Fifty-five that this decrease is not due either to a With up to 70%0 gallstone recurrence, patients received penicillamine (600 mg/ reduction in hospital facilities or to a post-dissolution treatment seems essential. day), and 32 were given an identical reduction in the incidence of the disease. placebo. The groups were matched for Further, there was a reduction in the age, duration of follow-up, liver tests, number of emergency duodenal ulcer (F23) immunoglobulins and liver copper con- operations, excluding perforation (41-37 Diarrhoea and bile acid malabsorption in centrations. There were similar propor- per six month period; P>0-05) and an mild radiation enteropathy tions of symptomatic and asymptomatic overall reduction (16-12; P<0-05) in the patients. Stage 4 histology was more number of emergency gastric ulcer M VAN BLANKENSTEIN (Department of common in the penicillamine group, and operations. Internal Medicine II, Rotterdam Univer- stage 3 in the controls. Eighteen patients These data suggest that cimetidine has sity Hospital, Dijkzigt) From a group on penicillamine developed major side- reduced the referral rate for elective of women being investigated for diarrhoea effects. Over a mean follow-up of 33 operations and is also possibly affecting after pelvic radiotherapy 15 were selected months (range six to 71 months), four the natural history of the disease. who had painless, urgent diarrhoea with (7 %) penicillamine treated patients, and incontinence. All had regained their 10 (31 %) controls died (p<0-02). All original weight, they had no anaemia, deaths occurred in patients with stage 3 (F26) vitamin deficiency, steatorrhoea, or signi- or 4 histology on entry to the study. The Does insulin-stimulated gastric secretion ficant ileal stricture on radiographic improved survival is only apparent in change with time after vagotomy? examination of the small intestine. patients surviving 24 months in the study. Bile acid metabolism was studied by Changes in liver tests, immunoglobulins D J BUTTERFIELD, J V PARKIN, P F WHIT- the cholyl-14C-glycine breath test, 24 hour and liver copper concentrations in sur- FIELD, AND M HOBSLEY (Department of Studies, The Middlesex Hospital faecal bile acid excretion, and the per- viving patients are similar to those pre- Surgical http://gut.bmj.com/ centage faecal excretion of a tracer dose viously reported. There was evidence of and Medical School, London) Insulin- of tauro-14C-cholic acid (TCA) in four histological improvement in treated stimulated gastric secretion in the post- days. patients, but not controls. vagotomy patient has been reported to The breath test was abnormal in 14 of be stable with time, and to be an accurate 15 patients, the 24 hour faecal bile acid predictor of the liability to clear recur- excretion in 12 of 15 (mean 2-05 mmol/ rence when corrected for pyloric loss and 24 h, range 0.6-5.9, normal < 1-25), the duodenogastric reflux and standardised TCA in all 15 (mean 78-3 % range 62-91, CLINICAL DIAGNOSTIC/SURGICAL for height. normal < 56 %). Mean 24 hour faecal F25-F39 We measured the half to two hour VG on September 27, 2021 by guest. Protected copyright. production was 200 g (range 92-297 g). in 47 patients who had had various forms All patients reported alleviation of of vagotomy, twice (40 patients) or three symptoms on cholestyramine 1-8 g daily. (F25) times (seven patients) at various times Diarrhoea in mild radiation entero- Effect of cimetidine on the surgical man- after the operation. pathy is associated with impaired ileal agement of peptic ulcer disease The mean VG did not differ between bile acid absorption. This may be respon- the recurrent and non-recurrent ulcer sible for urgency. However, the low stool M R THOMPSON (Department of Surgery, group at the time of the first test, and did volumes suggest abnormal continence Bristol Royal Infirmary, Bristol) When not alter in the non-recurrent group at mechanism as an additive factor. Patients cimetidine was introduced many clini- the time of the second test. However, the responded well to low dose cholestyra- cians, with varying degrees of delight and mean VG of the recurrent group at the mine therapy. dismay, felt that it heralded the rapid time of the second test had risen signi- disappearance of surgery for peptic ulcer ficantly over the VG of the same group disease. It is now possible to measure in when first tested (P <00025) and was (F24) real terms what effect cimetidine has significantly higher than the VG of the D-penicillamine treatment improves sur- actually had on the number of operations non-recurrent group when tested for the vival in primary biliary cirrhosis performed for this disorder. This was second time (p < 00005). done in the Bristol area for the three year It would seem that within the first year 0 EPSTEIN, S JAIN, R G LEE, D G COOK, period before and after the introduction after operation, the VG cannot differen- A M BOSS, P J SCHEUER, AND S SHERLOCK of cimetidine, using data from the South tiate between the recurrent ulcer and non- (Academic Department of Medicine and Western Health Authority Statistics recurrence groups. After this, patients Department of Pathology, Royal Free Bureau. who develop recurrent ulcer have a Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from

A434 The British Society of Gastroenterology significant rise in VG which does not values of lactic dehydrogenase and B- the entero-PP axis is still uncertain. A occur in patients without recurrence. glucuronidase. rise in the neurotensin response may be The diagnostic subgroups studied com- responsible for the reduction of upper prise 28 patients with normal findings; gastrointestinal motility and enteroglu- (F27) 42 with gastric adenocarcinomas; 14 with cagon for the mucosal hypertrophy which Cimetidine and duodenal ulcer: can surgery gastritis and intestinal metaplasia; 11 ensues; both effects may be viewed as cure the failures? with gastric ulcers; nine with duodenal &normalising strategies'. If anything, these ulcers; and nine post-gastrectomy patients. differences become more marked with R L BLACKETT AND D JOHNSTON (Univer- The distribution of lactic dehydrogen- time. sity Department of Surgery, The General ase and B-glucuronidase were both Biliopancreatic bypass results in pro- Infirmary, Leeds) If cimetidine is con- positively skewed; accordingly, subse- found weight reduction and the hormonal sidered to be a 'medical' form of vago- quent analysis was based on their cube changes observed after surgery relate tomy, then cimetidine failures might fare roots. In all patients there was good largely to their cellular distribution. These badly after vagotomy also. correlation between lactic dehydrogenase changes provide unique clues to the Since 1977, 53 patients with duodenal and B-glucu ronidase values, 0-412 physiology of gastrointestinal weight and ulcer (M 38, F 15, mean age 40 years) who (p < 0-001). appetite control. had failed to respond to cimetidine in Both variables discriminated substan- full dosage, have undergone highly selec- tially between the diagnostic subgroups tive vagotomy (HSV). Fifty-three consecu- and, in particular, the presence or absence (F30) tive patients (M 39, F 14, mean age 41 of malignancy could be predicted with a Non-invasive measurement of duodeno- years) who were treated by HSV between high degree of accuracy (p < 0O001). gastric reflux and its association with 1969 and 1971 served as controls. Mean In this study both cases of early gastric flatulent dyspepsia in patients with gall- length of history was 10 years for both cancer were correctly diagnosed by gastric stones groups. juice analysis. Preoperative BAO, 6.2±1 mM/h and The test is easy to perform and readily I A EYRE-BROOK, A M HOLROYD, AND A G PAOP G, 47±2 mM/h, in the cimetidine reproducible. In addition to being useful JOHNSON (University Departments of Sur- treated patients were similar to controls, in the investigation of symptomatic gery and Medical Physics, Royal Hallam- 7±1 mM/h and 44±1 mM/h respec- patients it may be of value in the identi- shire Hospital, Sheffield) A relationship tively. After operation, mean BAO was fication and screening of patients at between flatulent dyspepsia and duodeno- 1 mM/h in both groups and PAOP G, increased risk of gastric malignancy. gastric reflux has been demonstrated in 20 mM/h in both groups. Mean PAO patients with cholelithiasis. In those

(minus BAO) was 0.7±0-2 mM/h in studies, however, nasogastric intubation http://gut.bmj.com/ cimetidine failures and 0-04±0-02 mM/h (F29) was used, which may well affect pyloric in the controls (p< 0.01). Effect of biliopancreatic bypass surgery function. We have studied post-prandial After a follow-up of one to three years, for morbid obesity on the hormonal duodenogastric bile reflux in gallstone 84% of the cimetidine failures and 86% response to food patients using a non-invasive technique. of the control patients had obtained good Severity of each of nine symptoms and results (Visick grades I and II). In the D L SARSON, N SCOPINARO, D CIVALLERI, their frequency were scored separately on cimetidine-treated patients there were E GIANETTA, AND S R BLOOM (Depart- a three point scale (0-1-2). The scores

three proven recurrences and in the ment of Medicine, Royal Postgraduate were summated to provide a numerical on September 27, 2021 by guest. Protected copyright. controls two suspected recurrences. Medical School, London, and II Patologia value for flatulent dyspepsia (range 0-36). Thus so far the results of surgery in Chirurgica Universita, Ospedale S Mar- Duodenogastric bile reflux was moni- cimetidine failures have been as good as tino, Genoa, Italy) Biliopancreatic by- tored scintigraphically; the position of the results obtained in the pre-cimetidine pass entails a roux-en-y reconstruction the stomach being first established with era. with the small bowel transected at its intravenous technetium 99 sodium per- mid-point and an enteroenterostomy technecate (100 ,uCi). Biliary secretion fashioned 50 cm proximal to the ileo- after a Lundh meal was then studied (F28) caecal valve. We have therefore investi- dynamically (one minute frames) using Gastric juice enzymes-an aid in the gated the gut hormone responses to a technetium p butyl iminodiacetic acid diagnosis of gastric cancer normal meal in 13 lean controls, 16 obese (3 mCi). Reflux was recorded as the per- subjects, 21 patients within six months centage of bile secreted by the liver which K ROGERS AND G T WILLLAMS (Depart- and 17 patients six to 12 months after appeared in the stomach area. Five per ments of Surgery and Pathology, Welsh surgery. After biliopancreatic bypass cent reflux was considered significant. National School of Medicine) Raised glucose-dependent insulinotropic poly- Fifteen patients were studied before levels of lactic dehydrogenase and B- peptide (GIP), pancreatic polypeptide cholecystectomy and eight were reinvesti- glucuronidase are found in gastric juice (PP), and insulin release were much gated one month after operation. Three in disease states. reduced, while the distally produced patients with high preoperative symptom We have studied fasting gastric juice in enteroglucagon and neurotensin were scores (>10), but none of four patients 113 patients in whom double contrast considerably raised. Gastrin responses with low scores (< 5) had significant barium examination and endoscopic were little changed. The poor insulin reflux ( >5 %). Two of eight patients with biopsy have been carried out and corre- response may be the result of the reduc- intermediate scores (5-10) had significant lated the pathological diagnosis with the tion of GIP, although the mechanism of reflux. Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A435

Postoperatively, two asymptomatic Research Unit, Royal Infirmary, Aberdeen) six had severe diverticulosis, and 25 had patients (score=O) had no significant A prospective study of the familial inci- perianal conditions which can bleed. reflux (<5 %), while six symptomatic dence of cancer has been performed on Twenty-one had no clinical or radio- patients (scores 2-11) had significant 50 consecutive patients treated for adeno- logical abnormality and are still under reflux (> 5 %). carcinoma of the colon and rectum. All review. Six had colorectal neoplasms, This study confirms the association diagnoses were confirmed histologically four benign and two malignant. Three between postprandial duodenogastric re- and the presence or absence of adjacent more patients in Frome presented with flux of bile and flatulent dyspepsia and polyps was noted. Each patient was colonic tumours during the study. Two establishes that reflux is not a feature of questioned about all first-degree relatives, had refused to comply with the protocol asymptomatic patients. particularly in regard to intestinal cancer. because of cancerphobia; the third had Confirmation was obtained from patho- been negative in the trial. logy reports or close relatives. The con- Mass occult blood screening does (F31) trol group consisted of 50 patients, detect asymptomatic colonic neoplasms, Diagnosis of acute pancreatitis-have we matched for age and sex, and who did not but a sympathetic national publicity improved on the plasma amylase? have cancer. campaign is required to increase the Nine out of the 50 patients had a compliance if this method is to achieve M J MCMAHON AND JAHAN HODGSON parent, sibling, or child with colorectal its optimum potential. (Department of Surgery, The General cancer (18 %). In five out of the nine Infirmary, Leeds) The occasional un- families the mother was the other affected reliability of plasma (or serum) amylase member. In the control group only two (F34) estimation has led to enthusiasm for patients had an affected relative (4 %). Ultrasound monitoring of liver metastases numerous alternative methods of measur- The difference is highly significant from colorectal cancers ing amylase in order to detect acute (x2=8.13; 0-01 > p>0.001). pancreatitis. Measurement of urinary The familial incidence was comparable R H TAYLOR, J M GILBERT, MAGGIE G EVANS, amylase was developed into the amylase- with the 16 % incidence noted in HEATHER G LANE, AND P G CASSELL (De- creatinine clearance ratio, and advant- Nebraska, but the 'cancer families' with partment of Gastroenterology, Central ages have been claimed for selective more than two affected members were Middlesex Hospital, London; Ultrasound measurement of pancreatic isoamylase and not encountered in the present series. Department, University College Hospital, the heat-labile fraction of the plasma There was no difference in the frequency London; Imperial Cancer Research Fund amylase. There has been no comparative of polyps in the group of patients who Laboratories, London, and Wexham Park study of these alternatives. had affected relatives (22%) compared Hospital, Slough) Patients with liver Twenty patients with acute pancreatitis with the group whose close relatives to metastases from colorectal cancer often http://gut.bmj.com/ were studied on the first, fifth, and 10th date are free from colorectal cancer receive chemotherapy. It is valuable in days after admission. Plasma was taken (24%). The implications for screening selecting patients and supervising their for total amylase (Phadebas) pancreatic programmes are discussed. clinical condition to monitor the develop- isoamylase (separated using polyacryla- ment and size of metastases. We report mide gel electrophoresis) and heat-labile a prospective study using static grey- fraction (60°C for 15 minutes). Simul- scale ultrasound scanning to detect and taneous urine samples were collected for (F33) measure liver metastases. amylase measurement and calculation of A practical solution to the diagnosis and Fifty patients with resected colorectal amylase-creatinine clearance. Results were treatment of colorectal cancer? cancers had ultrasound scans as part of on September 27, 2021 by guest. Protected copyright. considered abnormal if they were >2 SD their routine follow-up at three monthly above the mean for normal subjects. P A FARRANDS, R L GRIFFITHS, AND D C intervals for between three months and Amylase-creatinine clearance and the BRITTON (Royal United Hospital, Bath) four years (median 15 months). Scans heat-labile fractions were of little value, If early colonic tumours bleed, faecal were performed by one operator using a being 35 % and 36 % respectively of occult blood estimation of the asympto- standard method on the same machine results being abnormal on day 1. Total matic populace may prevent 20 000 (Diasonograph NE4102, 3.5 MHz trans- amylase, pancreatic isoamylase, and deaths annually, and eliminate the mor- ducer). Half were receiving chemo- urinary amylase were all grossly abnormal bidity of colonic cancer surgery. therapy. on day 1, 40-50% abnormal on day 5, A well-publicised prospective trial was Scans on nine patients were abnormal. and 30-47 % abnormal on day 10. undertaken in the single-practice market Four had metastases shown on their first Neither pancreatic isoamylase nor urinary town of Frome, Somerset. Each of the scan and five developed metastases during amylase appeared to have any advantage 9050 townspeople aged over 40 years follow-up. Ultrasound detected these over total plasma amylase, and the clinical received an envelope containing a per- three to six months before they were relevance of these alternatives must be sonal letter of explanation, three Haemoc- detectable clinically. Serial ultrasonic open to doubt. cult test slides, and an instruction sheet. measurements of tumour size increased Completed slides were returned by 1817 during follow-up. The remaining scans on people, 59 with positive tests were ex- 41 patients were normal and these patients (F32) amined and endoscoped in a special continue to be well clinically. Tumours Familial incidence of colorectal cancer clinic. Barium enema was arranged when were graded at surgery and pathologically indicated and haemorrhoids treated with on a modified Dukes's classification. J L DUNCAN AND J KYLE (Gastrointestinal sclerotherapy. One patient had colitis, None of the four Dukes's A patients, 1/1S Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A436 The British Society of Gastroenterology Dukes's B, 4/22 Dukes's C, and 4/'6 the Royal Naval Hospital, Haslar, Gos- which three were associated with extra- Dukes's D have developed hepatic port, Hants) Many methods have been luminal abscess. Only the early uncom- metastases. described for the outpatient treatment of plicated postoperative fistulas closed Ultrasound appears to be a simple, haemorrhoids to reduce the number of spontaneously. All others required sur- non-invasive method of early detection patients requiring admission. These may gical resection before permanent closure. and monitoring of hepatic metastases be painful and complications such as Of the 12 enterovaginal fistulas none from colorectal tumours. necrosis and incontinence have been healed with conservative management, reported. A new technique using infrared although some have minimal symptoms. coagulation was described in 1977. Five have undergone proctectomy and (F35) A prospective trial comparing infrared one a successful operative closure. One Portal vein liver scanning for early detec- coagulation with conventional treatment patient developed an adenocarcinoma in tion of liver metastases in colorectal cancer (injection or rubber band ligation) has the fistula tract. been conducted. One hundred patients One early postoperative enterovesical B MOONEY, M CRITCHLEY, S GRIME, AND I with non-prolapsing and 100 with pro- fistula closed spontaneously; three others TAYLOR' (Departments of Slurgery and Nui- lapsing haemorrhoids were allocated required bowel resection. clear Medicine, Royal Liverpool Hospital, randomly to infrared coagulation or The 23 enteroenteric fistulas did not Liverpool) The methods currently avail- conventional treatment groups. cause specific symptoms related to the able for the preoperative detection of Age, sex, length of history and previous fistula but 21 of them have needed sur- colorectal liver metastases are limited in treatment were similar in each group. At gical treatment for indications such as their ability to detect small lesions. This six weeks, sympatomatic improvement stenosis. Two remain symptom free. has both prognostic and therapeutic was achieved in 90% of all patients with Except for uncomplicated early post- implications. no difference between the groups. At operative fistulas, conservative treatment Access to the portal circulation via the three months 80% of patients with non- has no place in the management of obliterated umbilical vein is available prolapsing haemorrhoids were asympto- Crohn's fistulas. A chronic symptomatic and is used for the cytotoxic treatment of matic after infrared therapy, compared fistula requires excision of the diseased established liver metastases as well as with 50 % after injection (x2 =4-84, DF = 1, bowel from which it originates. Short- delivery of adjuvant therapy. P= <005). There was no significant term total parenteral nutrition, if needed, In this study the cannulated umbilical difference between infrared coagulation is only to make the patient fit for vein has been used to perform (1) portal and conventional treatment in the pro- operation. venography; (2) liver blood flow measure- lapsing haemorrhoids. Seventy per cent of ments using Xenon133 clearance; and (3) patients complained of pain after conven- liver perfusion studies using TC99m tional treatment compared with 85 0% (F38) microspheres (average 10 ,u diameter). A after infrared coagulation (x2 = 35-03, Long-term effects of proctocolectomy on http://gut.bmj.com/ portal venogram and hepatogram phase DE=1, P= <0 001). No complication genitourinary function in patients with are obtained. Liver blood flow and occurred in either group. inflammatory bowel disease perfusion studies were performed using a Infrared appears to be superior to gamma camera with online computer and injection in non-prolapsing haemorrhoids D E NEAL, A J PARKER, N S WILLIAMS, AND data storage facilities. This allowed and as effective as rubber band ligation D JOHNSTON (University Department Of qualitative and quantitative measure- in most patients with prolapsing haemor- Surgery, The General Infirmary, Leeds) ments of blood flow to different areas of rhoids. It is a simple technique and is less Bladder dysfunction and sexual problems after the the normal and metastatic liver. painful than conventional methods. abdominoperineal excision of on September 27, 2021 by guest. Protected copyright. The results of these studies have been rectum for carcinoma are not uncommon. compared with preoperative Tc99m sul- Sexual dysfunction and bladder dysfunc- phur colloid and ultrasound scans of the (F37) tion after proctocolectomy for inflamma- liver as well as liver function tests. Management of fistulas in Crohn's disease tory bowel disease are also not uncom- The initial results of these studies mon, despite the opinion of many sur- suggest that as many as 30%0 of patients J C GIVEL, P C HAWKER, M R B KEIGHLEY, geons. This study was carried out to with macroscopically normal liver at R N ALLAN, AND J ALEXANDER-WILLIAMS determine the frequency and type of initial surgery for colorectal cancer have (Gastroenterology Unit, The General bladder dysfunction in the long-term after evidence of metastatic disease. Hospital, Birmingham) Our manage- proctocolectomy for inflammatory bowel These techniques may allow prognosis ment of 68 patients with Crohn's disease disease. Thirty-five patients (18 F, 17 M: to be refined and treatment to be planned complicated by fistula, excluding perianal age=47±14 years) were studied a mean on a more rational basis. fistula, treated between 1970 and 1980 is of eight years after proctocolectomy. reviewed. With the use of voiding pressure cysto- Although many were complex, the metry, they were compared with a series (F36) principal fistula connection was cutaneous of controls (18 M, 16 F: age=48±17 Infrared coagulation in the treatment of in 29. Four developed soon after opera- years) who had undergone bowel resec- haemorrhoids tion as the result of an anastomotic leak. tion for carcinoma of inflammatory Twelve occurred later from the site of an bowel disease with no pelvic dissection, R J LEICESTER, R J NICHOLLS, AND C V operation, six after appendicectomy, six a mean of five years previously. MANN (St. Mark's Hospital, London, after resection. Thirteen arose spon- Abnormal symptoms (impotence, ejacu- The London Hospital, Whitechapel, and taneously from recrudescent disease, of latory failure, or dyspareunia, nocturia Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from

The British Society of Gastroenterology A437

> 2, incontinence and a poor stream) who develop sepsis after surgery for this (F41) were more common after proctocolec- disorder usually have pre-existing infec- Effect of catechin (cyanidanol-3) on tomy (x2 18, on 4 DOF; P< 0-001). tion; and (3) that prolonged antimicrobial alcoholic fatty liver There was no difference in mean peak cover is required to prevent postoperative flow, maximum detrusor pressure, or complications. P R RYLE, J CHAKRABORTY, G K SHAW, compliance between the two groups. AND A D THOMSON (Department of Seven proctocolectomy and two control Gastroenterology/Liver Unit, Greenwich patients had abnormal cystometry; in the District Hospital, Vanbrugh Hill, London, proctocolectomy group (1 F, 6 M) three and Department of Biochemistry, Univer- had bladder neck obstruction and four sity of Surrey, Guildford, Surrey) The had denervated bladder; two control bioflavanoid, catechin, acting as a free patients had bladder neck problems. PHYSIOLOGY II radical scavenger, protects the liver Thus both symptoms and objective F40-F54 against carbon tetrachloride toxicity. It is signs of genitourinary dysfunction were also reported to inhibit collagen synthesis found to be common in the long-term and to reverse the raised NADH1:NAD after proctocolectomy for inflammatory ratio that arises from ethanol oxidation. bowel disease. (F40) We have studied the effect of catechin on Prostacyclin-like activity in experimental the development of fatty liver. portal hypertension in dogs Two groups of 10 Sprague-Dawley rats (males, 200-260 g) were fed a nutrition- (F39) ally complete liquid diet containing 28%0 Prolonged antibiotic cover is required to J J CORZO, J M ZOZAYA, F GUARNER, AND of the total calories as ethanol, replacing prevent sepsis after operations for inflam- J PRIETO (introduced by R E Pounder) an isocaloric amount of carbohydrate, matory bowel disease (Department of Medicine, Universitary and compared with control groups. Clinic, University of Navarra, Pamplona, Concomitant administration of catechin Spain) A possible relationship between (intragastrically, 200 mg/kg, once daily) M M HARES, F GRECA, E NEVAH, R N ALLAN portal hypertension and platelet aggrega- significantly reduced the raised hepatic AND M R B KEIGHLEY (Department tion was investigated in dogs. Animals levels of total lipid (by 29% compared of Surgery, The General Hospital, Birm- were anaesthetised with pentobarbitone. with controls), triglycerides (by 32 %), ingham) Operations for inflammatory A catheter was placed in the mesenteric free fatty acids (by 53 %), and microsomal bowel disease are frequently complicated vein for pressure determinations and protein (by 51 %) observed after ingestion

by sepsis, probably because many patients blood collections. In five (group A), of ethanol for three weeks. No toxic http://gut.bmj.com/ are receiving steroids, and there is a high pressure was increased to twice the basal effects attributable to the drug were incidence of pre-existing sepsis particu- level during 30 minutes by partial ligation observed. larly in Crohn's disease. of the portal vein. In four (group B), These results suggest that catechin We have undertaken a trial of anti- 300 mg/kg of aspirin were administered increases utilisation and lowers synthesis biotic cover in 74 patients undergoing intravenously 30 minutes before the of fatty acids, rather than facilitating lipid elective operation for inflammatory increase of pressure. Platelet aggregation removal from the liver. The detailed bio- bowel disease. Excluded were patients by thrombin was measured in platelet- chemistry will be presented, but catechin emergency those rich plasma obtained from basal and is clearly effective at preventing fatty requiring operations, on September 27, 2021 by guest. Protected copyright. with obvious intra-abdominal sepsis or 30 minute post-portal hypertension liver. These studies confirm the drug's enterocutaneous fistulae. Patients were samples in group A and from basal, importance as a powerful hepatoprotec- allocated to one of three groups: three 30 minute post-aspirin and 30 minute tive agent which may be valuable in the doses of metronidazole and gentamicin post-portal hypertension in group B. treatment of all stages of alcoholic liver (group A: n=21), identical placebo In group A, a significant decrease of disease. solutions (group B: n=27), or five day the platelet aggregation was observed cover with metronidazole and gentamicin when basal and 30 minute post-portal (group C: n=26). The overall incidence hypertension were compared (P < 0 0005). (F42) of sepsis was 42% in group A, 44% in In group B there were no significant Motilin-induced gallbladder contraction: a group B, and 120% in group C. Hence differences in platelet aggregation among new mechanism only the group receiving five day anti- basal, 30 minute post-aspirin and post- biotic cover received clinical benefit. portal hypertension samples. It is con- T E ADRIAN, P MITCHENERE, G R SAGOR, Failure of antimicrobial prophylaxis did cluded that (1) portal hypertension in- N D CHRISTOFIDES, AND S R BLOOM (De- not relate to steroid therapy but was duces a decrease in mesenteric venous partment of Medicine, Royal Postgraduate associated with established infection at blood platelet aggregation; (2) this Medical School, London) Gallbladder the time of operation. With five day anti- action is prevented by a large dose of function has not been fully investigated biotic cover the incidence of abdominal aspirin; (3) as this dose of aspirin blocks for the influence of the newer gut hor- wound sepsis was 8 %, abscess 8 %, and both the platelets and vessels cyclo- mones-for example, motilin, which con- septicaemia did not occur. oxygenase, it is reasonable to think that tracts smooth muscle and is released by a These results indicate that (1) steroids the hypoaggregation observed after por- fatty meal. do not increase the risk of sepsis in in- tal hypertension is mediated by PGI2 In the conscious healthy pig we have flammatory bowel disease; (2) patients liberation by portal vascular bed. continuously monitored intraluminal gall- Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from

A438 The British Society of Gastroenterology bladder pressure using a fundally attached Three contractile patterns have been of inducing controlled stress may prove microradio pressure capsule. Pressure identified: useful in further studies of gastrointes- responses to motilin, pancreatic polypep- A contractions have a low amplitude tinal function, but the results emphasise tide (PP), vasoactive intestinal peptide and a frequency of 10-17 cycles per that individual variation in the response (VIP), and somatostatin were compared minute (cpm) and are not associated with to stress is an important variable. From with changes induced by feeding and pressure wave changes. our data, we conclude that stress may cholecystokinin octapeptide. B contractions are A contractions on delay motor complexes, but that adapta- After a meal pressure rose by 108 + a raised baseline and occur in conjunction tion occurs as stress is sustained. 1.6 mmHg at 30 minutes with a peak at with type III pressure waves which they 65 minutes (increment 14.8±2.3 mHg, resemble closely in shape and character. meaniSEM, P<0 005, n=5). CCK-OP C contractions have a high amplitude (F45) (doses 0.4, 1-5, 6, and 24 pmol/kg/h) and low frequency (2.2-42 cpm), and Effect of porcine gastric fundic factor caused a dose-related increase in pressure have been associated with pressure wave (GFF), bombesin, neurotensin, glucagon of 2.5±05, 6.2±1'4, 11.9±3.0, and changes with similar shape and character. and VIP on jejunal glucose absorption 16-5±2-3 mmHg respectively. Motilin C contractions represent segmentation. (doses 1.8, 7, 24, and 96 pmol/kg/h) also Three patients with the irritable bowel N J ANDREWS, S RINNO-BARMADA, K significantly increased gallbladder pres- syndrome who were symptomatic at the BURDETT, AND J B ELDER (University sure by 2.7±1.3, 4-0+P14, 7.5±1O0, and time of the recording, all had C con- Departments of Surgery and Medical 12.0±2.0 mmHg respectively. Somato- tractions. Biochemistry, Manchester) Recently a statin, VIP and PP all caused a dose- The strain gauges respond to changes peptide fraction isolated from gastric related fall in gallbladder pressure-for in radius of lumen and measure smooth fundic mucosa was shown to decrease example, PP (doses 6, 25, 100, and 400 muscle contraction directly, unlike pres- jejunal glucose absorption. Comparison pmol/kg/h) reduced pressure by 2.2+0-9, sure recordings which respond to smooth of gastric fundic factor (GFF) with 8.2±0.4, 11.6±7, and 14.8±0.8 mmHg muscle contractions indirectly. candidate fundic hormones has been respectively. Changes in smooth muscle tone may be made. 10 mM glucose in 0 15 M NaCI Thus CCK caused the expected rise and differentiated from distension or deflation containing 0-1 % PEG was continuously PP the expected fall in gallbladder by combining intraluminal pressure mea- perfused for up to one hour through a pressure. Low doses of motilin produced surement with the strain gauge probe at 10 cm jejunal segment in a rat bioassay a rise in gallbladder pressure as large as the same level. (n=80). Bolus caval injections of albumin CCK. This is of great interest, as motilin in NaCl as control (n=17), GFF (n=8), circulates in concentrations than bombesin, neurotensin, and VIP (1, 0-1, higher 0.01 ±g/rat, n=12 for each peptide), and CCK and rises greatly after fat ingestion. (F44) http://gut.bmj.com/ glucagon (10, 1, 0-1 gg/rat, n=12) were Stress and jejunal motor activity given. Samples of perfusate were taken at 15 minute intervals for measurement of (F43) D L WINGATE, SHEENA MCRAE, KIRSTEN glucose and PEG concentrations. Absorp- New method for the direct recording of YOUNGER, AND D G THOMPSON (London intestinal contractions tion of glucose was calculated. Hospital Medical College, London) While At 15 minutes bombesin (1 pg/rat) and it is often assumed that stress influences neurotensin (0-1 ,ug/rat) gave increases of JOHN CUMMING, J M KELLY, AND C L intestinal motility, previous studies of 28 % and 46% respectively in glucose

SMITH (Department of Surgery, Queen this effect have usually been brief and on September 27, 2021 by guest. Protected copyright. Alexandra Hospital, Portsmouth, Hamp- have not allowed for the normal periodi- absorption, whereas GFF decreased ab- shire) Previous methods for recording city of fasting motor activity. In this sorption by 25 %. No significant effect on motor activity of the colon, have relied study, 11 healthy fasted volunteers were glucose absorption was demonstrated on intraluminal pressure recordings using subjected to controlled mental stress for with any of the doses of VIP or glucagon balloons of various sizes and perfused four hours using a modified dichotomous or with the other doses of bombesin or open-ended tubes. However, intraluminal listening test; jejunal motor activity was neurotensin throughout the experiment. pressure is the result of a number of monitored using a radiotelemetry capsule Of the known peptides present in the factors, among them being the contrac- tethered at the duodenojejunal flexure. gastric fundic mucosa, the gastric fundic tion of the intestinal smooth muscle. It is Each subject was also studied for a four extract used contained negligible amounts these contractions in which we are hour unstressed control period on the of somatostatin and substance P. This primarily interested. same day. Pulse rate and blood pressure observation, together with the present We describe a new method for record- were measured at regular intervals, and a data using other candidate fundic hor- ing intestinal contractions directly, by stressful response was arbitrarily defined mones, strengthens the evidence that a their action on the strain gauge pairs of as an increase greater than 5 % in mean novel fundic peptide may be involved in an intraluminal strain gauge probe. aggregate pulse and blood pressure the control of jejunal glucose absorption. A comparison of pressure (open-ended between control and stress periods. tube) and contraction (strain gauge Thus defined, 7/11 subjects showed a (F46) probe) recordings shows there is a high stressful response, and they also showed Simultaneous recording of myoelectrical correlation between the two methods a significant (p=0-016) reduction in the activity and motility from the human colon (r=0-8; P < 0-01) when comparing motility number of activity fronts in the first two indices before and after stimulation with hours of stress compared with the control I MORRIS, C DARBY, P HAMMOND, AND neostigmine (0-6 mg subcutaneously). period, but not thereafter. This method I TAYLOR (Departments of Surgery and Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from

The British Society of Gastroenterology A439

Bioengineering, University of Liverpool, Thiry-Vella fistula. Half of this group mical in terms of animals and time Liverpool) A new method of studying were allowed food ad libitum, while the expenditure, and, because the experi- human colonic motility has been assessed. rest were fed intravenously. mental period is short, is suitable for Variations in electrical resistance at an In the colectomy group, ileal CCPR/h monitoring ephemeral proliferative events. intramuscular electrode correspond to increased from 18 ±09 after ileal transec- The method has been compared with local movement of the muscle. Thus, tion to 31 2±1.1 after subtotal colectomy the more elaborate and time-consuming simultaneous recordings of myoelectrical (P< 0001). Similarly, enteroglucagon in- autoradiographic methods; in both con- activity and motility can be obtained from creased from 108.8±32 pmol/l in ileal trol and experimental situations there was a single intraluminal suction electrode. transection, to 234 5±20 8 pmol/l after excellent agreement. These were compared with motility colectomy (P<0-005). In the Thiry-Vella We therefore propose that the crypt measured by intraluminal pressure group, in the ileum in continuity, CCPR/h cell production rate is the most appropri- changes. was greater in orally fed rats (52±8), ate proliferative estimator in work on In 15 normal subjects at rest, motility compared with intravenously fed animals intestinal adaptation. was detected by resistance changes for a (18±5) (p<0-01). In the excluded fistula, greater proportion of the time (mean CCPR/h was reduced to 23.8±2 in orally 748 ±6.7 %) compared with percentage fed animals but this was greater than in motility measured by intraluminal pres- the intravenously fed group (16±1.5) (F49) sure (mean 32.9±7.4%). This increased (P < 0.01). Plasma enteroglucagon was Faecal excretion of intravenous 3H-25- observation of motility was also seen in greater with oral (566±59 pmol/l) than hydroxyvitamin D3 in normal subjects and 15 patients with diverticular disease with intravenous feeding (250±41.9 in patients with intestinal malabsorption (resistance motility-mean 88-5±4.6 %, pml/l) (P < 0-01). pressure motility 170O±4.2%) and in five These studies indicate that luminal patients with the irritable colon syndrome nutrition and intestinal secretions cannot J E COMPSTON, A L MERRETT, J E LEDGER, (resistance motility 92-6±3.8%, pressure explain all the changes in crypt cell AND B CREAMER (Gastrointestinal Re- motility 28.2±16.5 %). production site and suggest that a humoral search Unit, Rayne Institute, St. Thomas' In five normal subjects and in five agent plays a part. Enteroglucagon is still Hospital, London) Interruption of an patients with the irritable colon syndrome, the most favoured candidate. enterohepatic circulation of 25-hydroxy- intravenous glucagon (0025 mg/min in- vitamin D (250HD) has been postulated travenously) resulted in complete inhibi- as a mechanism for the development of tion of motility. This is additional evi- vitamin D deficiency in intestinal malab- dence that the resistance method accur- (F48) sorption. We have determined faecal ately detects colonic muscle motility and Search for an appropriate measurement of excretion of intravenously administered http://gut.bmj.com/ not other movement. proliferative status in experimental work 3H-250HD3 in three normal subjects and The method appears to be a sensitive in intestinal adaptation six patients with malabsorption (three technique for studying motility and, by jejunoileal bypass, three small intestinal simultaneously recording myoelectrical resection). activity, should prove a valuable tech- N A WRIGHT, M AL-MUKHTAR, G SAGOR, 10 ,uCi of 3H-250HD3 in 20 ml of 10% nique for examining the relationship AND S BLOOM (Departments of Histo- ethanol was injected intravenously and between the two. pathology and Medicine, Royal Post- stools were collected for five to six days.

graduate Medical School, Hammersmith Faecal radioactivity was determined in on September 27, 2021 by guest. Protected copyright. Hospital, London) Workers in the field homogenates by liquid scintillation count- of intestinal adaptation need a precise ing after oxidative combustion and silicic (F47) measurement of proliferative status, which acid chromatography was performed on Enteroglucagon and intestinal adaptation is economical in terms of time and effort; faecal extracts. serious doubt has been cast on the use of The mean daily excretion of radio- tritiated thymidine incorporation into activity in the normal subjects was 0-8- G R SAGOR, M Y T AL-MUKHTUR, M A DNA as an estimator of proliferative 1.6 % of the injected dose. In four patients GHATEI, N A WRIGHT, AND S R BLOOM rate and consequently we have sought for with malabsorption faecal radioactivity (Royal Postgraduate Medical School, more appropriate measurements. The was increased; in two of these, the mean London) Luminal nutrition and intes- three factors which control crypt cell daily excretion was over 6% of the tinal secretions are known to be important proliferation are the cell cycle time, crypt administered dose. There was a significant in intestinal adaptation; however, growth fraction, and crypt population correlation between faecal fat excretion humoral agents may also play a part. To size; an ideal measurement would be and faecal radioactivity excretion (r= investigate the relationship further, we sensitive to all three parameters. +0-89; P<0 005). Faecal chromato- measured plasma enteroglucagon in two Such a measurement is the crypt cell graphy revealed unchanged 3H-250HD3 experimental rat models, and related production rate; we have combined a in patients with malabsorption and in these findings to the most reliable indica- crypt microdissection method with vin- normal subjects. tor of proliferative status, the crypt cell cristine metaphase arrest to provide an These results provide support for the production rate (CCPR). One group had estimate of the crypt cell production rate existence of an enterohepatic circulation either subtotal colectomy or ileal transec- which gives acceptable interval estimates of 250HD in man and demonstrate that tion. A second group had 75 % proximal and excellent statistical discrimination in faecal loss of circulating 250HD may be small bowel fashioned into an isolated experimental work; the method is econo- increased in intestinal disease. Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from

A440 The British Society of Gastroenterology

(F50) elements containing vasoactive intestinal as follows: proximal colon 16-5 %, colonic Prolonged organ culture of human colonic polypeptide (VIP), as determined by anastomosis 23-5 %, distal colon 40 %, mucosa using a supplemented medium: immunocytochemistry, and in VIP con- rectum 200%. Consistent with this left- observations on the degeneration and tent, as estimated by radioimmunoassay, sided predominance, left hemicolectomy regeneration of epithelial crypts in patients with Crohn's disease. reduced the number of tumours by 52- In the present study, endoscopic recial 58 % compared with transection or P V SENIOR, C J PRITCHETT, J P SUNTER, biopsies from control subjects (n 13), controls (P=005-0.005). Caecal resection D R APPLETON, AND A J WATSON (Depart- patients with ulcerative colitis (n= 13), had no effect. A twofold increase in distal ments of Pathology, Surgery, and Medical and Crohn's disease, affecting (n=9) or tumours after transection and right hemi- Statistics, University of Newcastle upon not involving (n =5) the rectum, have colectomy (p < 0.02) reflected the many Tyne) Using a system which proved been examined for possible changes in anastomotic tumours found after each successful in preserving adult mouse the levels of VIP nerves. The assessment operation. Moreover, one rat receiving colonic mucosa we have cultured adult was carried out in a double-blind fashion. vehicle (not carcinogen) developed an human colonic mucosa and report the In patients with Crohn's disease affect- invasive mucinous adenocarcinoma at the sequential morphological changes ob- ing the rectum all biopsies had increased colorectal anastomosis after left hemi- served. levels of VIP innervation, with six showing colectomy. During the initial 48 hours of culture very marked changes including distortion Ileocolic and colorectal anastomoses the normal microarchitecture of the of individual fibres. In patients without are favoured sites for tumour develop- tissue is well preserved although there is rectal involvement some minor increases ment after partial colectomy. The lack of some progressive depletion of cytoplas- were found. In 10 of the patients with adaptive hyperplasia may explain un- mic mucus from crypt epithelial cells. ulcerative colitis VIP nerves were the altered carcinogenesis in the remaining Subsequently accelerated degenerative same as in the normal controls. However, colon. changes are seen and cells are lost from in the three cases with the most severe the upper third of the crypt. By between inflammatory reactions VIP nerves were 72 and 96 hours the upper part of the found to be increased, although the crypts are denuded, leaving small acini or morphology of individual fibres was solid clusters of epithelial cells in the essentially normal. (F53) lamina propria discontinuous with the This study confirms the finding of Increased colonic carcinogenesis after intact surface epithelium. hyperplasia of VIP nerves in Crohn's jejunoileal bypass in rats is prevented by These remnants then display intense disease and suggests that this is related extreme reduction in body weight proliferative activity until by 186 hours to the level of transmural inflammation.

the crypts are repopulated with a mono- J B BRISTOL AND R C N WILLIAMSON (Univer- http://gut.bmj.com/ layer of columnar epithelial cells, again sity Department of Surgery, Bristol Royal continuous with the surface, possibly Infirmary, Bristol) Small bowel resection utilising the fibrocellular sheath of the (F52) consistently promotes experimental intes- crypt to guide their migration. From 264 Partial colectomy promotes experimental tinal carcinogenesis, whereas subtotal hours goblet cells are again seen among carcinogenesis only at the site of intestinal bypass may have a protective effect. As the crypt epithelial cells. anastomosis changes in body weight might be critical, These findings suggest that the primary colorectal carcinogenesis was studied after

control of crypt cell production, migra- R C N WILLIAMSON, P W DAVIES, J B various types of enteric bypass. Male on September 27, 2021 by guest. Protected copyright. tion, and differentiation is inherent in the BRISTOL, AND M WELLS (University De- Sprague-Dawley rats weighing 117±0-8 g tissue. This will be a useful in vitro partment of Surgery, Royal Infirmary, (SEM) were given six subcutaneous system for studying the response of Bristol) The possibility that metachro- injections of azoxymethane (15 mg/kg) at mucosa to various insults. nous colorectal cancers arise in mucosa weekly intervals. One week later, each rat rendered hyperplastic by partial intestinal was subjected to 85-90%. jejunoileal by- resection was tested in male Sprague- pass (three groups) or sham bypass, Dawley rats (N=200) weighing 159±14 g which comprised jejunal transaction, (F51) (SD). Rats received mid-colonic transec- ileotomy, and resuture. Bypass was (1) VIP nerves in endoscopic rectal biopsies tion, right or left hemicolectomy, caecal end-to-side; (2) end-to-side with a Thiry- from patients with inflammatory bowel resection, or no operation (controls). Vella fistula; or (3) end-to-end with disease: a double-blind study Each operation was performed either drainage of the bypassed loop into the before or one week after a course of five descending colon. C O'MORAIN, ANNE E BISHOP, JULIA M weekly subcutaneous injections of azoxy- At 30 weeks the 46 surviving rats were POLAK, S R BLOOM, A J LEVI, AND T J methane (10 mg/kg/wk) or water. The killed. Sham bypass rats weighed 586± PETERS (Divisions ofClinical Cell Biology timing of operation did not affect ultimate 23 g and had 3.9±1-0 colorectal tumours and Clinical Sciences, Clinical Research tumour yields. per rat. End-to-side bypass more than Centre, Harrow, Middlesex, and Depart- Although caecal resection and right doubled the number of colorectal tumours ments of Histochemistry and Medicine, hemicolectomy both increased ileal wet to 10-3±1i4 (P<0.01), despite reducing Hammersmith Hospital, London) Pre- weight by 22-40% (P<0005), there was body weight to 73 % of that of sham vious reports, using surgically resected no evidence of adaptive growth in the bypass rats (p < 0-001). Bypass with specimens, have suggested that there is a colon after partial colectomy. A total of Thiry-Vella fistula or loop into descending selective increase in the mural nervous 217 large-bowel tumours were distributed colon caused even greater weight loss to Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A441

55 % of sham bypass. Colorectal tumour Gastroenterology and the Department yields of 5.3 ±08 (Thiry-Vella fistula) and POSTERS of Medical Physics, Manchester Royal 5.8 - 1.2 (loop into descending colon) FP1-FP12 Infirmary, Manchester) In a six month were not significantly different from sham period 140 consecutive patients referred bypass rats (p>005), but were less than because pancreatic disease was considered after end-to-side bypass (e < 0-02; p < 0.05 a serious possibility, or after recrudes- respectively. (FP1) cence of symptoms from chronic pan- Enhanced neoplasia after jejunoileal Faecal microbial flora in the irritable creatitis, were investigated by a modified bypass may reflect compensatory colonic bowel syndrome PABA test. Drugs were withdrawn and hyperplasia, as after enterectomy, but after an overnight fast each subject drank this effect is abolished by profound M GUSLANDI, A TITTOBELLO, A BALSARI 500 ml of a flavoured cocktail containing reduction of body weight. AND E FESCE (introduced by S Gottfried) 25 g casein, 0.5 g N-Benzoyl-L-Tyrosyl- (Institutes of 3rd Medical Clinic and of p-aminobenzoic acid and 5 pCi 14C- Veterinary Microbiology and Immunology, labelled PABA. Urine was collected for University of Milan, Milan, Italy) The six hours, PABA and 14C content mea- irritable bowel syndrome is a functional sured (expressed as percentage of ingested (F54) gut disorder associated with an abnormal Bile acid binding to dietary protein doses) and their ratio calculated to give intestinal motility. In clinical situations a PABA excretion index which in health with altered peristalsis changes in intes- is 0.76-112 (-3SD to +3SD). A LANZINI, R BIRD, W FITZPATRICK, P tinal microflora can be detected. We have The diagnosis arrived at after full ZENTLER-MUNRO, AND T C NORTHFIELD investigated the behaviour of intestinal investigation of each patient was com- (Department of Medicine, St. George's flora in patients with the irritable bowel pared with the PABA excretion index. Hospital Medical School, London) Bile syndrome. 1. Drug or isotopic interference invali- acid precipitation occurs in jejunal Stool samples were collected from 20 dated 16 tests. samples after Lundh meal in patients with outpatients with the irritable bowel 2. PABA excretion index was repro- pancreatic or ileal resection steatorrhoea syndrome and 20 healthy controls. None ducible (r=0-97 in 10 studies). and healthy controls-50% at pH < 5 and of them had received antibiotics during 3. PABA excretion index was normal in 20 % at pH > 6. In pure solutions, bile the previous month. Stool specimens 67 of 70 patients with non-pancreatic acids do not precipitate unless pH < 5 for were immediately placed in sterile plastic abdominal disorders-that is, specificity, glycine and <2 for taurine conjugates. containers with Aranki diluting fluid to 95.7 %. When gastrointestinal anatomy We have therefore investigated in vitro prevent damage to anerobic bacteria, was intact and renal function normal (64 transferred in a 'glove box', homogenised, whether precipitation at pH>5 is due to patients) 76.6±1.9% of the administered http://gut.bmj.com/ bile acid binding to Lundh meal consti- and diluted up to 10-9. Bacteriological 14C was recovered in urine in six hours. tuents. We incubated these with tauro- examinations were performed within two 4. PABA excretion index was reduced cholate (3706, pH 6.5) for one hour. hours and bacterial populations of each in 32 of 43 patients with chronic pan- Adsorption was calculated from difference species were compared by the method of creatitis or pancreatic cancer-that is, between total and aqueous phase bile Kruskal and Wallis. sensitivity, 74.40%. acid concentration after ultracentrifuga- Compared with control subjects, the The predictive value and efficiency of tion at 100 000 g for eight hours, and irritable bowel syndrome patients showed the test has been analysed. expressed as mM/g protein. At 5 mM/1, a significant decrease of coliforms 4.7±0t9x 10-smM/g (mean±SEM) was (P < 0001), lactobacilli (P <002), and on September 27, 2021 by guest. Protected copyright. adsorbed using Lundh meal, 5.3±04x bifidobacteria (P < 0 05). No significant (FP3) 10-5mM/g using milk protein (Casilan), changes in the other bacterial populations Premature bone ageing in primary biliary and none using corn oil, sucrose, saline, were observed. Disturbances of peristaltic cirrhosis or calcium. Very little binding occurred movements may account for removal of using hydrolysate of Casilan. Adsorption some of the autochthonous microflora O EPSTEIN, Y KATO, R DICK, AND S SHERLOCK isotherms for Casilan showed that binding from the intestinal tract. (Academic Department of Medicine, and reached a maximum of 101.2±12 x 10-5 The significance of this altered micro- Department of Radiology, Royal Free mM/g at bile acid concentration of 24 bial pattern in the maintenance and in Hospital, London) The study of bone mM, suggesting a saturable process. At the severity of the irritable bowel syn- disease in primary biliary cirrhosis has pH 4.5, adsorption was markedly in- drome remains unknown. However, ad- been restricted to patients with an indica- creased at all concentrations. Binding was ministration of autochtonous lactobacilli tion for bone biopsy, and, therefore, the greater for dihydroxy than tridroxy bile and bifidobacteria can sometimes induce prevalence and pattern of bone disease acid, but was uninfluenced by type of symptomatic improvement in these has not been fully established. An alterna- amino conjugation at pH 6.5. We con- patients. tive radiological approach is to measure clude that marked bile acid binding the shaft (S) and medullary cavity width occurs to dietary protein-for example, (FP2) (M) of the second right metacarpal, at its milk; that this may contribute to steator- Diagnostic accuracy of the PABA excre- mid-point. From these values, cortical rhoea in patients with low total bile acid tion index (using 14C-PABA) thickness can be measured (S-M), as well concentrations-for example, ileal resec- as the percentage cortical area (100 tion; and that it can be prevented in vitro V A TETLOW, G KAY, H HERMAN, AND J M S2-M2/S2), which reflects the proportion by using the constituent amino acids. BRAGANZA (University Department of of bone in the bone envelope. Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from A442 The British Society of Gastroenterology

We have measured these parameters in EMI brain scan (CAT scan) showed (358 g; 88-440) and propranolol (274 g; 83 patients with primary biliary cirrhosis normal examination but both temporal 87-450). (age range 37-78 years), and compared lobes were faintly visualised. Straight We conclude that doses of propranolol them with normal age-matched controls. radiograph of the abdomen showed liver which produced significant cardiovascular Cortical thickness was significantly de- enlarged up to the iliac crest. Liver biopsy beta-blockade were ineffective in the creased in all age groups, especially in the disclosed a histologically normal liver, treatment of bile acid-induced diarrhoea. 5th to 7th decades (p < 0001). The bone while liver scintigram showed an enlarged thinning was due to marked endosteal liver with normal spleen. There was resorption, reflected by a significant increased activity in the spleen relative to (FP6) increase in medullary width (p < 0001) the liver but the features were those 14C-triolein breath test as an outpatient and a significant reduction in percent suggestive of hepatitis rather than early screening test for detecting steatorrhoca cortical area (p < 0-025). There was no cirrhosis. Liver ultrasound disclosed no correlation between the reduction in specific diagnostic lesion. The biliary A AVGERINOS, A K BEAVIS, JJ MISIEWICZ, cortical thickness and serum bilirubin, system was not dilated. AND D B A SILK (Department of Gastro- nor was there a correlation with the Known causes of hepatomegaly-for enterology, Central Middlesex Hospital, histological stage of the disease. example, malignant deposits, leukaemia, London) The poor acceptability of the In primary biliary cirrhosis, there is Hodgkin's disease, amyloidosis, conges- faecal fat excretion test by patients, metacarpal cortical thinning, predomin- tive cardiac failure, gross steatosis-were physicians, and chemical pathologists has antly due to endosteal resorption, rather excluded clinically, radiologically, bio- led to the development of tests in which than failure of accretion. This resembles chemically, and histologically. This rare breath 14CO2 is measured after the inges- the normal pattern of ageing, occurring case is unique and interesting because of tion of triglycerides labelled with 14C. In prematurely. the unusual hepatomegaly at such a the present study we have compared the young age with such a short history of specificity of a triolein breath test with heavy drinking. measurement of faecal fat excretion in 35 (FP4) patients, 16 of whom had normal faecal Unusually enlarged liver due to heavy fat excretion and 19 steatorrhoea (>18 drinking for one year in a girl of 20: a (FP5) mmol fat/24 h). Hourly collections of case report Propranolol in the treatment of bile acid breath 14C02 were performed for eight induced diarrhoea hours after ingestion of 5 IuCi '4C- S K MAJUMDAR, A D THOMSON, G K SHAW, P triolein dissolved in a test meal containing O GORMAN, E J APS, AND J BUGLER (Gastro- M J HALL, L M NELSON, R G MURRAY, AND 25 g fat.

enterology and Liver Unit, Greenwich R I RUSSELL (Gastroenterology Unit, Breath 14CO2 increased slowly, peaking http://gut.bmj.com/ District Hospital, London, Elmdene Alco- Royal Infirmary, Glasgow) Propranolol at six to eight hours. Mean hourly 14C02 holic Treatment Unit, Bexley Hospital, has been shown to inhibit bile acid- was higher at five, six, seven, and eight Bexley, Kent, Queen Mary's Hospital, induced adenylate cyclase activity in hours (p >0 01 or less) in the steatorrhoea Sidcup, Kent, and Brook General Hospital, human colon in vitro, and deoxycholic compared with the control group. The London) (introduced by A D Thomson) acid induced sodium and water secretion maximum specific activity of 14C02 in the Hepatomegaly due to chronic ethanol in rat colon in vivo. breath at five to eight hours provided the ingestion is well known. We report below To determine if propranolol is effective best discrimination between the two a rare case of ethanol-induced hepato- in man we studied seven patients with and at groups, eight hours only four on September 27, 2021 by guest. Protected copyright. megaly in a young unmarried English girl bile acid-induced diarrhoea. Propranolol (21 %) of the 19 steatorrhoeic patients (accounts clerk) aged 20 years (date of or placebo was given for four weeks and had normal '4C02-breath excretion values birth 19 January 1960). She was admitted the alternative preparation after a two (within normal mean+t2 SD). for conventional detoxification treatment week washout period. The design allowed These findings confirm that the 14C- for ethanol withdrawal syndrome. She for an increase in propranolol dosage triolein breath test is a sensitive non- started social drinking at the age of 14 depending on the degree of beta-blockade invasive, and simple outpatient screening years but admitted drinking heavily for as assessed by exercise testing up to a test for the detection of steatorrhoea, the last one year (about three-quarters of maximum of 360 mg daily. The patients although in our hands its specificity is a bottle of vodka daily). Her parents are kept diary cards, were interviewed blindly, not as precise as previously reported. both social drinkers. She was depressed and a five day stool was collected before clinically. There was no history of drug and after each treatment period. addiction. Six patients were beta-blocked on the (FP7) The results of investigations (routine dosage used. Three patients reported a Bacterial colonisation of the jejunum: an haematological profile, prothrombin time, subjective improvement in diarrhoea on evaluation of five diagnostic tests serum folate, alpha fetoprotein, blood propranolol, but, of these, two reported group (A-RhD positive), autoantibodies, a similar improvement on placebo. There R H TAYLOR, A AVGERINOS, A J TAYLOR, plasma urea, creatinine, electrolytes, and was no significant difference (Wilcoxon's M J HILL, AND J J MISIEWICZ (Department radiograph of the chest (P-A view)) were signed ranks test) between the daily of Gastroenterology, Central Middlesex all within normal limits. Serum B2= 1250 number of bowel motions on placebo Hospital, London, and Bacterial Meta- (N=160-900ng/l); Red cell folate=158 (median 3-6; range 2 0-8.0) and pro- bolism Research Laboratory, Central Pub- (N= 160-640 tg/l); Australia antigen- pranolol (3-2; 0.9-6.6) and none in daily lic Health Laboratory, London) When negative. faecal wet weights between placebo bacterial colonisation of the jejunum is Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from The British Society of Gastroenterology A443 suspected clinically, investigations to 12 admitted to self-digitation of the plications showed a sustained rise in confirm the diagnosis can be difficult, rectum. At presentation solitary or C-reactive protein but, in other patients, time-consuming, and unreliable, requiring multiple ulcers were found within 13 cm levels fell from a peak at about 48 hours. the use of expensive equipment. In this of the anal margin in 25 patients and were C-reactive protein may have potential study we have compared the results of often sited anteriorly. In 14 patients for the early detection and investigation five tests with quantitative analysis of macroscopic ulceration was absent. Rec- of complications of acute pancreatitis. aerobic and anaerobic bacteria, including tal prolapse was found in 20 patients. identification of all isolates, in samples of The diagnosis was confirmed histologic- jejunal fluid from 95 symptomatic ally in all patients; delay in diagnosis (FP10) patients. after onset of symptoms was common, on Antral gastrin (G) cells in man after one Gas/liquid chromatography of volatile average being five years. year's treatment with cimetidine fatty acids on 95 samples of jejunal juice Thirty patients were followed-up for a gave positive results in 6/23 patients with mean of 4-6 years. Patients without J F MORRIS, N J MCC MORTENSEN, R W significant colonisation (>104 faecal macroscopic ulceration at presentation SPENCE, L R CELESTIN (Department of organisms/ml) and 11/72 without did not develop an ulcer during follow-up; Human Anatomy, Oxford; Department of colonisation. thus two types of solitary ulcer were Surgery, Bristol University; and Depart- Analysis of urine for phenols as apparent. Covert rectal prolapse was ment of Surgery, Frenchay Hospital, evidence of bacterial overgrowth in 23 frequently associated with both but in some Bristol) G cell hyperplasia occurs in patients gave positive results in 0/6 with patients prolapse was not demonstrable. achlorhydria and might complicate cime- colonisation and 3/17 without. The clinical course was unpredictable and tidine treatment. Integrated gastrin res- Glucose/hydrogen, lactulose/hydrogen neither medical nor local surgical treat- ponses (IGR) were raised three-fold over and 14C-glycocholate breath tests were ment consistently achieved symptom pretreatment levels in 24 patients with done on 11 patients with confirmed relief or ulcer healing. duodenal ulcer treated with cimetidine colonisation and 18 patients without. (16 g daily) for one year. Antral biopsies One or more breath tests were positive were taken from these patients both pre- in 8/11 colonised and 9/18 without (FP9) treatment (nine suitable) and after one colonisation. Positives in colonised pa- Prediction of the course of acute pancrea- year of treatment. The one year treated tients occurred in 6/11 on 14C-glycocho- titis using acute phase reactant proteins group were divided into low integrated late, 4/11 on glucose/hydrogen, and 1/11 gastrin responses (< 14 000 ng/min/l; on lactulose/hydrogen. In those without P BRADLEY, MARGARET BOWDEN, E H seven patients) and high integrated gas- colonisation, positives occurred in 7/18 COOPER, AND M J MCMAHON (Unit for trin responses (> 14 000 ng/min/l; nine on on and were 14C-glycocholate, 3/18 glucose/ Cancer Research, University ofLeeds, patients) subgroups. Gastrin cells http://gut.bmj.com/ hydrogen and 2/18 on lactulose/hydrogen. University Department of Surgery, The analysed immunocytochemically and ul- After treatment of the colonised patients General Infirmary, Leeds) It is important trastructurally. The numerical density of all breath tests became negative except to identify patients who develop severe G cells identified either immunocyto- for lactulose/hydrogen in one patient. complications of acute pancreatitis such chemically or ultrastructurally was not None of these tests individually, or in as abscess or pseudocyst, but often significantly different among the three combination, appears to give a reliable difficult to do so, especially in the early groups and did not correlate well with measure of the degree and nature of stages of an attack. We have investigated integrated gastrin responses. This does jejunal bacterial colonisation. acute phase proteins for this purpose as not preclude hyperplasia due to increased rapid nephelometric methods of assay antral mass. The size of individual G on September 27, 2021 by guest. Protected copyright. (FP8) may soon be available. cells was not significantly changed but, in Clinical course of solitary ulcer of the Daily blood samples were collected the high-integrated gastrin response rectum from 17 patients with acute pancreatitis group, cells contained significantly more for measurement of C-reactive protein, immature granules (26±2/100lm2 Cyto- M J FORD, J ANDERSON, S HOLT, H M al-antitrypsin, acid glycoprotein, anti- plasm; pretreatment 17 ± 3; low-inte- GILMOUR, R C HEADING, AND W SIRCUS chymotrypsin, white cell count, and ESR. grated gastrin response 18±2 (mean ± (Departments of Therapeutics and Patho- Three patients had a severe attack of SEM), and increased rough endoplasmic logy, Royal Infirmary, and the Gastro' pancreatitis complicated by a pseudocyst reticulum. This suggests that the raised intestinal Unit, Western General Hospital, (two) or abscess (one), 11 were classified integrated gastrin response associated Edinburgh) A review of 39 patients (18 as moderate, and were without complica- with one year of cimetidine treatment males, mean age 35 years, 21 females, tions, and three were mild. results from hyperactivity of individual mean age 42 years) with solitary ulcer of A rise in the level of each parameter G cells rather than G cell hyperplasia. the rectum has provided additional was seen in all patients, but with the information about the natural history of exception of C-reactive protein was not this usunusal condition. Symptoms usu- of value in differentiation of the groups. (FP1 1) ally comprised the passage of blood and The level of C-reactive protein (g/l-3; Biological diagnosis of the hepatocellular mucus from the rectum, alteration in mean ± SD) two days after admission carcinoma associated with liver cirrhosis: bowel habit, and anorectal or lower was 189±47 for severe, 117±55 for clinical and experimental study abdominal pain; two patients were moderate, and 22±15 for mild pancrea- asymptomatic. Difficulty with defaeca- titis (P < 0-05 for all differences; M MUNOZ, J A AMIGUET, F CONCHILLO, tion was reported by 25 patients, of whom Wilcoxon). Patients who developed com- J PRIETO, AND P LISO (introduced by R E Gut: first published as 10.1136/gut.22.5.A414 on 1 May 1981. Downloaded from

A444 The British Society of Gastroenterology

Pounder) (Department of Medicine, liver cirrhosis showed us that, in four colon cancer. The possible interest of University Clinic, University of Navarra, cases, a rise in the haptoglobin level this protein indicator for purposes of Pamplona, Spain) Hepatocellular car- correlated with malignity. early diagnosis motivated this experi- cinoma develops frequently from liver Furthermore, an experimental study of ment. cirrhosis and it is often very difficult to haptoglobin in rats with liver cirrhosis The weekly administration of 40 mg/kg diagnose clinically. With this in mind we and with liver cirrhosis plus hepato- weight of 1,2 dimethylhydrazine to Wistar studied two oncofetal antigens (carcino- cellular carcinoma confirmed these results. rats produced early neoplastic lesions embryonic antigen and alpha-fetoprotein) In conclusion, acute-phase reactants from the 15th week. Haptoglobin was and five acute-phase reactants (alpha-i- and alpha-fetoprotein are good biological quantified by simple radial immuno- acid glycoprotein, alpha-1-antitrypsin, indicators for the diagnosis of hepato- diffusion against a specific immunoserum haptoglobin, ceruloplasmin and alpha-2- cellular carcinoma which has developed anti-human haptoglobin 1-1, obtained by macroglobulin) in 10 patients with from liver cirrhosis. us through an original technique. This hepatocellular carcinoma associated with antiserum had been previously used in liver cirrhosis. measuring haptoglobin in experimental As controls we used 56 healthy subjects (FP12) hepatoma of the rat. This subtype hapto- and 58 patients who had liver cirrhosis Experimental carcinoma of the colon: globin 1-1 possesses crossed antigenicity without hepatocellular carcinoma. serum haptoglobin in early diagnosis with the rat variety. We found that the hepatocellular carci- Early histological lesions coincided noma associated with liver cirrhosis can J A AMIGUET, M MUNOZ-NAVAS, F CON- with a statistically significant rise of be biologically differentiated from liver CHILLO, E ORTIZ DE LANDAZURI, AND haptoglobin in serum. cirrhosis by the positivity of the alpha- P LISO (introduced by R E Pounder) The cause of haptoglobin serum in- fetoprotein and by a significant increase (Department of Medicine, University crease in neoplasms is still unknown. of haptoglobin and the other four acute Clinic, University of Navarra, Pamplona, In conclusion, we have found that phase reactants. Moreover, regular deter- Spain) Haptoglobin has shown its use- haptoglobin is a useful biological marker minations of haptoglobin in patients with fulness in the biological diagnosis of in early carcinoma of the colon. http://gut.bmj.com/ on September 27, 2021 by guest. Protected copyright.