Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

Gut, 1978, 19, A432-A458

The British Society of

The Spring Meeting of the BSG, together with the BSDE, took place at Warwick University, Coventry, from 31 March to 1 April. The meeting was largely given up to parallel sessions of scientific communications, abstracts of which appear below. During the proceedings, the President of the BSG, Dr. W. Sircus, presented Dr. D. B. Silk with the Research Medal for 1977-8: Dr. Silk later addressed the Society on 'Peptide transport in the human '. A varied social programme included a medieval banquet in Warwick Castle.

R. FERGUSON AND MICHAEL ATKINSON recently managed three patients who bled ENDOSCOPY (General Hospital, Nottingham) In 43 from an angiomatous lesion of the patients (mean age 67 years) with benign gastric antrum. Each patient presented Disinfection of upper gastrointestinal fibre- oesophageal stricture caused by gastro- with a profound iron deficiency anaemia optic equipment oesophageal reflux, after initial dilatation due to persistent gastrointestinal blood by the Eder Puestow method, active loss. Barium studies of the upper and D. L. CARR-LOCKE AND P. CLAYTON medical measures were instituted. lower failed to (Area Endoscopy Unit and Department of Ten subjects have not required further demonstrate the cause for the bleeding. Microbiology, Leicester General Hospital, dilatation after periods ranging from Gastroscopy in each patient demonstrated Leicester) As there is little information three months to three years, and 27 a striking antral abnormality consisting of available on the bacteriological con- have needed further dilatation. After the linear angioid streaks running longi- tamination of upper gastrointestinal fibre- initial dilatation three patients underwent tudinally towards the pylorus. Endoscopic optic endoscopes and ancillary equip- surgery, two died of unrelated , biopsies were essentially normal and http://gut.bmj.com/ ment during routine use and the effect of and one of a perforation of the stricture, angiography in two cases failed to display disinfecting solutions, a detailed evalua- the only death in the 132 dilatations. any abnormality. One patient was unfit tion was made of different cleaning Of the 37 patients followed up, 27 for surgery and subsequently died but the methods using (a) water, (b) an aqueous underwent dilatation over one year ago, remaining two patients were subjected to solution of 1 % cetrimide with 0-1% and of these nine have not required Billroth I antrectomy. At operation chlorhexidine, and (c) activated aqueous dilatation since. Eight patients required there were multiple, linear areas of 2 % glutaraldehyde (Cidex). All over five dilatations, and continuing punctate haemorrhage on the crests of

equip- on September 24, 2021 by guest. Protected copyright. ment was found to be heavily contaminat- medical treatment did not diminish the the longitudinal antral mucosal folds. ed after use with a wide variety of organ- frequency of dilatation. Four of the 37 Following surgery, these patients have isms of which 53 % were Gram positive. patients have died ofother conditions, and remained well and free of anaemia. Cleaning of the endoscope and other in two of these adenocarcinoma was Microscopically, there were groups of equipment with water and cetrimide/ found at the site of the fibrous stricture. arteries and veins, larger and more chlorhexidine alone or in combination The use of the Eder Puestow dilators numerous than usual, situated in the was inadequate to produce disinfection, at fibreoptic endoscopy, combined with submucosa of the antral specimens. These but immersion in glutaraldehyde for medical measures to control reflux, offers vessels ran mostly in a longitudinal two minutes consistently produced sterile relatively safe management of benign direction. In places there were thrombosed cultures with our sampling method. As a oesophageal stricture in the elderly. and dilated superficial vessels. result of this study a rapid and simple Remission from dysphagia of over a year The appearances were characteristic method for disinfection has been adopted occurs in one-third of patients. of an angiomatous hamartoma. and will be described in detail. It is especially suitable for busy endoscopy units. A new cause of upper gastrointestinal Bleeding gastric arteriovenous malforma- bleeding tion diagnosed by endoscopy

M. H. WHEELER, P. M. SMITH, P. B. COTrON, M. VAN BLANKENSTEIN, J. DEES, AND D. M. D. EVANS, AND B. W. LAWRIE (Welsh F. J. W. TEN KATE Introduced by Dr J. R. National School of Medicine, Cardiff Bennett, Gastro-Intestinal Unit, Hull Outlook with conservative treatment of and Department of Gastroenterology, The Royal Infirmary, Hull (Department of benign oesophageal strictures Middlesex Hospital, London) We have Internal Medicine II and Department of A432 Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from The British Society of Gastroenterology A433 PathologyI, Rotterdam University Hospital, diverticula had (12/25 of the Department of Diagnostic Radiology, Rotterdam, Holland) Over a five-year 98/42, p < 0-01), and/or previous chol- Leeds General Infirmary) Although period 21 cases of a recognisable vascular ecystectomy (10/38 of 62/755, p < 0-001). chronic pancreatitis is often associated abnormality in the stomach and In conclusion, the incidence of peri- with biliary disease, little data are avail- have been seen at endoscopy, one in 285 ampullary diverticula was 5%. Where able to indicate how often patients with examinations. These abnormalities present present, they were associated with an biliary disease develop structural changes as red spots with a diameter between 1/4 increased rate of failure of cannulation. in the pancreas. Our experience with and 3/4 cm. On close inspection the spots There was a significant correlation of ERCP over two years has led us to suspect are seen to consist of clusters of blood- duodenal diverticula with gallstones and/ that this is very common. vessels. The average age of the patients or previous cholecystectomy. We found We have therefore reviewed all success- was 75 years (range 50-87 years); in 19 of no evidence that these diverticula were the ful pancreatograms performed during the the 21 cases the patient was being in- cause of biliary or pancreatic obstruction. investigation of patients with biliary vestigated for acute or chronic gastro- disease or jaundice. The pancreatograms intestinal bleeding. Five cases were were assessed independently by two operated on, three had a local excision Endoscopic pancreatography in the experienced observers, without clinical under endoscopic guidance. Histology of diagnosis of pancreatic cancer information, using criteria previously two ofthese resected areas revealed arterio- described by Ashton et al. (1977). Sixty- venous , the endoscopically I. T. GILMORE, J. PEMBERTON, AND R. P. H. five pancreatograms were assessed and visible vessels being found to consist of THOMPSON (Gastrointestinal Laboratory, then grouped on clinical grounds as centripetal dilated veins in the submucosa. Rayne Institute, and Department of follows: group I: patients with biliary No recurrent bleeding has been seen in Radiology, St. Thomas' Hospital, London) disease in whom was suspect- the operated cases. This type of arterio- Thirty-two of the 400 patients who under- ed (25); group II: patients with biliary venous malformation, which is easily went endoscopic retrograde cholangio- disease and jaundice in whom pancreatitis recognised by endoscopy, is probably a pancreatography (ERCP) during the last was not suspected (28); group III: controls significant cause of acute and chronic three years were shown to have a pan- known not to have biliary disease and in upper gastrointestinal bleeding in the creatic carcinoma at laparotomy or whom pancreatitis was not suspected (12). elderly. necropsy. Pancreatic carcinoma was diag- Abnormal pancreatograms were found nosed by endoscopy and ERCP in 20. in 12 patients (48%) in group I, in 13 In three the diagnosis was established by patients (47%) in group II but in only one Significance of periampullary duodenal endoscopy and biopsy alone, and in two patient in the control group III (8%). diverticula at ERCP a stricture of the common duct was The results confirm a high incidence demonstrated on the endoscopic chol- (48 %) of associated http://gut.bmj.com/ A. P. KIRK AND J. A. SUMMERFIELD angiogram, while in 15 the pancreato- with biliary disease and show that in half Introduced by Professor Sheila Sherlock gram was abnormal. Pancreatogram these cases (group II) this was an unex- (Medical Unit, Royal Free Hospital, abnormalities included a complete block pected finding. pancreatitis Pond Street, London) A retrospective (nine) or a localised area of irregular is common in patients with biliary disease. study of periampullary duodenal diverti- narrowing or dilatation (four) in the main cula was performed on 755 ERCP pancreatic duct. A simple method for removal of gallstones examinations carried out at R.F.H. from In four patients the pancreatogram was after endoscopic sphincterotomy

1973-77. Duodenal diverticula were noted normal. In the remaining eight patients on September 24, 2021 by guest. Protected copyright. in 38 (5 %)-22 males and 16 females the pancreatic duct was not filled; in four L. WITZEL, W. HACKI, U. SCHEURER, AND (ages 42-84 years). The main presenting the ampulla was cannulated but no dye F. HALTER (Gastrointestinal Unit, Uni- symptoms were jaundice (16), right could be introduced, and in four the versity Hospital Inselspital, 3010 Berne, hypochondrial pain (seven), and chol- ampulla or duodenal wall appeared ab- Switzerland) To facilitate endoscopic angitis (three). Ten patients had jaundice normal but biopsy specimens contained removal of concrements from the bile- or cholangitis following cholecystectomy. no tumour. There have also been six false- duct after sphincterotomy we have modi- Investigation revealed biliary calculi in positive investigations where an ERCP fied Zeiss's method, which is a routine 12 patients, biliary strictures in two, diagnosis of pancreatic cancer was not procedure in urology. A Teflon catheter (four), the others hav- substantiated. of 1.5 mm in diameter is fitted with a small ing primarybiliary , carcinomas of Although we have confirmed that ERCP nylon thread fixed to the tip. This thread liver, pancreas, or duodenum, or un- and endoscopy are useful in the diagnosis passes through the wall of the tubing at a diagnosed abdominal pain. of pancreatic carcinoma, a significant point 10 cm from the tip. After endoscopic It proved impossible to cannulate any number of patients (4/32) have a normal sphincterotomy the catheter is introduced duct in 15 (40%Y) patients compared with pancreatogram. through the channel of the duodenoscope a 20 % overall failure rate. In the presence and guided into the bile-duct until the of duodenal diverticula cholangiography tip is above the stone. By retraction of the revealed abnormalities in 18 of 25 patients Pancreatogram abnormalities in biliary thread a loop is formed on the catheter (72%.), an incidence which was not disease tip which is easily placed around the stone. significantly different from that of bile These manipulations can be controlled by duct lesions in the rest of the group- M. G. ASHTON, A. T. R. AXON, AND D. J. a radiography with image intensifier and 52% (212/402). However, a significantly LINTOIT (University Department of instillation of contrast medium through greater number of those with duodenal Medicine, the Gastroenterology Unit and the catheter. The stone is removed by Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A434 The British Society of Gastroenterology continuous pulling on the catheter. This J. D. REED, AND J. G. STEPHEN (Depart- thick layer of mucus suspended between procedure is repeated when several stones ment of Physiology, Medical School, mesh supports separated 10 ml stirred have to be extracted. We have used this University, Newcastle upon Tyne) solutions of equimolar HCI and NaCl. method in 11 patients and have removed Histamine H2-receptor antagonists are [H+] rose to 15 mEq/l in the saline after stones of up to 2-5 cm diameter. reported primarily to inhibit gastric 120 minutes, whereas it took only three hydrogen ion concentration [H+] rather minutes with the mesh alone. Even after than flow, whereas anticholinergics and 180 minutes (H+) only reached 36% of somatostatin are reported to have a equilibration values. Similar restrictions OESOPHAGUS/STOMACH/DUODENUM I primary effect on flow and thus thought to Na+ movement occurred. Isotopic to have poor potential in peptic ulcer fluxes approximated to those for diffusion therapy. However, it is well known that of Na+ in unstirred water. Similar rates of Lower oesophageal high pressure zone [H+] is dependent on flow. We have H+ transfer occurred through a 1 mm (HPZ) and reflux during abdominal established this relationship as a rectangu- layer of inert, freely permeable, filter compression lar hyperbola in six conscious cats with paper. chronic gastric fistulae secreting from We conclude that (a) mucus has limited J. CLARK AND A. CUSCHIERI (Department 0-16 ml 15 min-" in response to penta- buffering power, and (b) it effectively ofSurgery, Ninewells Hospital andMedical gastrin 0-5-64 &g kg-' h-1. The maximum limits H+ transfer across it, probably by School, Dundee, Scotland) Controversy [H+] observed was 168 mM at flow rates maintaining an 'unstirred layer' of water surrounds the mechanism for the control of 6 ml 15 min-1 and above. in its mesh. of gastro-oesophageal reflux during Somatostatin 1-20 pg kg-'h-I produced abdominal compression. We studied dose dependent inhibition of acid output reflux and HPZ characteristics simul- (26-82%) stimulated by pentagastrin An explanation of the paradoxical effect taneously during abdominal compression. 8 Ag kg-" h-1. Cimetidine and metiamide of pentagastrin on gastric motility Standard slow pull through perfused cath- 2 mg kg-1 h-1 produced significant eter manometry was performed on 58 inhibition of acid output stimulated by C. M. WHITE, M. R. B. KEIGHLEY, AND subjects (a) at rest with the stomach both pentagastrin 1 and 8 lAg kg-1 h-1 J. ALEXANDER-WILLIAMS (The General empty, (b) with a gastric load of 300 ml (38 % and 40%; 57 % and 47 % respective- Hospital, Birmingham) Although penta- 0-1N.HCl, (c) with 50 mmHg ab- ly). Atropine lg100 kg-1 h- produced gastrin stimulates antral contractions it dominal compression (C) in addition to 63 % inhibition of pentagastrin 1 ,ug delays gastric emptying. The delayed the gastric load. Oesophageal pH was kg-1 h-1 and 14% inhibition of penta- emptying may result from loss of co- cm monitored at 5 above the HPZ. gastrin 8 ,ug kg-' h-1 stimulated acid ordination between antral and duodenal http://gut.bmj.com/ Twenty-six subjects did not reflux output. In no case did the relationship contractions or from a 'physiological (lowest pH 5 9 ± 0-7). HPZ pressures between [H+] and flow differ from the stricture ofthe antrum'. We have examined (mmHg ± SD) were (a) 17'3 ± 7-1, (b) control data. the effects of pentagastrin on gastroduo- 15-6 ± 6-5, (c) 12-6 + 57, and intra- These data are consistent with all these denal motility in man. abdominal lengths HPZ as percentage of forms of inhibition of acid output being A six channel tube, centred on the total length (± SD) were (a) 62-3 + 15-3, due to a simple reduction of gastric pylorus by potential difference monitoring, (b) 54-1 ± 12-5, (c) 60*3 ± 17-4. secretion. continuously and simultaneously measures

Thirty-two subjiects refluxed (lowest intraluminal pressure in the antrum (A), on September 24, 2021 by guest. Protected copyright. pH 2-1 ± 0-8). HPZ pressures (mmHg + pylorus (P), and duodenal bulb (D). SD) (a) 13-6 ± 7 0 (p > 0-05), (b) 10.2 ± Fifteen normal subjects were studied 4-2 (p < 0.001), (c) 8-9 ± 4-5 (p < 0-01). Gastric mucus: studies of its 'protective' during intragastric infusion of saline; the Intra-abdominal lengths (% total length properties effects of subcutaneous pentagastrin + SD) (a) 47*9 ± 18-1 (p < 0.005), (b) (6 sg/kg) during saline infusion were 40 4 ± 17-1 (p < 0 001), (c) 42-5 ± 18-4 S. E. WILLIAMS AND L. A. TURNBERG measured in five. (p < 0-001). (Department of Medicine, Hope Hospital Two types of activity were observed: We consider that (1) augmentation of (University of Manchester School of 'discontinuous' contractions arising in HPZ pressure is not required for reflux Medicine), Salford) Mucus is commonly only one or two sites, usually A or D prevention; (2) resting HPZ pressure is held to protect gastric mucosa but whether and 'concerted' contractions of the whole not lower in subjects who reflux under or how this occurs is uncertain. We gastroduodenal region. The mean pres- abdominal compression; (3) a high intra- examined two of its possible protective sures ± SD (Cm H2O) during discon- abdominal proportion of HPZ length properties using fresh porcine mucus. tinuous contractions were: A 22 5 + 11 7, may be more significantly related to (1) Buffering capacity, measured by P 18-0 + 7-8, D 14-9 ± 5 3 and during reflux prevention than is a high HPZ titration against 01M HCI, was 1 46 concerted contractions were: A 31-8 + pressure. mEq H+/g dried weight mucus (1 g = 11-3, P 26-7 + 8-6, D 22-6 ± 8-9. The 40 ml mucus approximately) at pH 3 and injection of pentagastrin stimulated rhyth- 0 99 mEq/g at pH 315. After repeated mic discontinuous contractions, with washing these fell by approximately two- pressures significantly higher in the Effect of inhibitors on the relationship thirds, a loss which could be only partially pylorus and lower in the antrum than between hydrogen ion concentration and replaced by adding bicarbonate. (2) Its before. Means ±SD: A 12-2 + 9-5, flow of gastric juice in the cat capacity to prevent H+ transfer across it P 33-2 + 9 0, D 16-9 ± 4-4. B. H. HIRST, E. L. BLAIR, L. A. LABIB, was studied in a 'flux' chamber. A 1 mm Pentagastrin produces a type of activity Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

The British Society of Gastroenterology A435 of the gastroduodenal region that is not control remains largely unexplored. those patients with symptoms had a seen during saline infusion alone. The Using a Gamma camera, we studied the significantly shorter T* and greater fall segment of rhythmic contractions of high effect of adrenergic and adrenergic in plasma volume than the postoperative, pressure at the pylorus corresponds to the blocking drugs on gastric emptying of a symptom-free patients (Wilcoxon 'physiological stricture' observed by solid meal labelled with Indium'13 in p < 0-05). Hamilton and his colleagues. healthy volunteers and patients with These studies show that, despite preser- hypertension. vation of the vagal supply to the antrum Mean control gastric emptying time and pylorus, the gastric emptying rate for Hormonal influence of pyloric diameter and (T*) in 10 subjects (32 25 ± 22-2 M ± SE) liquids is increased in some patients after antral motility in man was prolonged after 20 mg isoprenaline PGV, at least in the early postoperative sublingually 30 minutes before the meal period. This tendency to more rapid J. F. MUNK, MARY HOARE, AND A. G. (55*6 + 12-8, p < 0 05). No effect was emptying is not as marked as after vag- JOHNSON (Professorial Department of observed when isoprenaline was given otomy with a drainage procedure, but Surgery, Charing Cross Hospital Medical immediately before the meal. Salbutamol explains the occasional occurrence of School, London) This paper describes a 4 mg q.d.s. for one week significantly dumping after PGV. method of direct endoscopic measure- prolonged gastric emptying in four sub- ment of pyloric diameter and tone and the jects (p < 0-05). response to exogenous hormones in man. The effect of isoprenaline on gastric Physiological actions of luminal gastrin A deflated Fogarty balloon catheter, emptying was blocked by propranolol in human gastric juice previously calibrated with concentric 40 mg q.d.s. for one week. In 10 subjects rings drawn on the inflated balloon, is the mean T* after propranolol 40 mg R. G. FIDDIAN-GREEN AND T. S. QUINN (De- passed into the duodenum through an q.d.s. alone for one week (28-6 ± 2 5) partment of Surgery, University of Mich- endoscope (G1F-D). was less than their mean control T+ igan, Ann Arbor, Michigan, USA) The The balloon is inflated and withdrawn (38-8 ± 3-1, p < 0-005), suggesting that physiological potential of luminal gastrin against the pyloric sphincter, allowing normal gastric emptying is subject to some was explored in 21 healthy subjects. The pyloric diameter to be assessed by two degree of adrenergic inhibition. intragastric titration technique was used to observers, between normal rhythmic antral Paracetamol 1 g was given with each maintain the luminal pH at 7, to prevent contractions. Pyloric pressures are re- meal and the plasma levels measured. degradation of gastrin in acidic gastric corded by withdrawing the balloon, Isoprenaline appeared to decrease and juice, and to monitor acid secretion. Timed connected to a Statham transducer, into propranolol to increase the rate of drug aspirations and George's technique were the stomach. Basal measurements of absorption. Persistently higher plasma used to measure gastric emptying. Six- diameter and pressure are recorded levels after propranolol alone may teen subjects were examined with the http://gut.bmj.com/ before hormone administration. indicate an additional effect on hepatic intragastric titration technique. Each In 36 patents with duodenal ulcer metabolism or blood flow. subject was exposed to 12 successive 10 (eight), gastric ulcer (10), (11), minute periods: The first three periods to and no gastroduodenal disease (seven) water; the second three to saline (60 mM); the gastric ulcer patients had the largest Proximal gastric vagotomy (PGV) and the third to water; and the fourth to resting pyloric diameter. Cholecystokinin early dumping saline. Five subjects were exposed to the (G.I.H., Karolinska), 1 IDU/kg produced same stimuli in the reverse order. Six pyloric contraction and antral in- D. N. L. RALPHS, F. EBIED, AND M. HOBSLEY subjects were exposed to three periods of on September 24, 2021 by guest. Protected copyright. hibition in all subjects, this change in (Department of Surgical Studies, The water and nine periods of water containing diameter being significantly greatest in Middlesex Hospital Medical School, different physiological concentrations of the gastric ulcer patients. Pentagastrin, London) The dumping provocation test exogenous G17. Each of five subjects had 0-6 ug/kg, also produced pyloric con- has been used to determine the effect of five emptying tests: two with water and traction, but increased antral motility and PGV on gastric emptying, plasma volume, three with water containing physiological also the linkage between antral and duo- and consequent symptomatology. Thirty- concentrations of G17. Water did not re- denal contractions. six patients were studied within three lease immunoreactive gastrin (IRG) into Although reflux is more common in months of a PGV, 10 were also tested gastricjuice or serum. Saline released IRG gastric ulcer patients, this study shows that preoperatively. They were challenged with into juice (p < 0.01), decreased secretion this is not due to failure of the pylorus 150 or 200 ml 50% glucose solution labell- (p < 0-01), and increased emptying to respond to these hormones. ed with Indiumll3m to enable measure- (p < 0-001) relative to water. Exogenous ment of gastric emptying with a gamma G17 increased secretion (p < 0 02) and camera. emptying (p < 0-005) without increasing Effect of ,B adrenergic drugs and a , Symptoms experienced postoperatively the serum IRG concentration. Exogenous blocking agent on gastric emptying in man after normal meals were as follows gastrin could be recovered from neutral (figures on testing in parentheses): gastricjuice in vitro but not in vivo unless M. R. REES, R. A. CLARKE, C. D. none, 24 (21); equivocal 7 (4); dumping administered in very high concentrations. HOLDSWORTH, AND P. HOWLETT (Depart- 5(11). It is concluded that luminal gastrin ments Of Medicine and Medical Physics, There was no significant difference in participates in the physiological control of The Royal Infirmary, Sheffield) Choliner- the T+ or maximum plasma volume fall acid secretion and gastric emptying by gic control of gastric emptying has been between the preoperative and symptom- binding to receptor sites in the lumen of extensively studied, but its adrenergic free postoperative patients. However, the stomach. Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A436 The British Society of Gastroenterology Urogastrone in man, light and electron (10 or 20 tg) in five healthy conscious 15 minutes. microscopical localisation female dogs. The dogs were catheterised These results demonstrate a consistent and received 0 9 M saline at 90 ml h-1 response of motilin to food stimuli. PH. U. HEITZ, S. VAN NOORDEN, J. M. to ensure good urine flow. After injection The influence of intravenous nutriments POLAK, M. KASPER, H. GREGORY, AND of hUg serial rapid sampling of both on motilin release suggest the possibility A. G. E. PEARSE (Institute of Pathology, blood and urine was undertaken and hUg that this motor-stimulating hormone may University of Basel, Switzerland, Depart- concentration measured by specific radio- unexpectedly have a role in co-ordinating ment of Histochemistry, RPMS Hammer- immunoassay. The dogs showed no un- gastrointestinal function with metabolism. smith Hospital, London, Pharmaceutical toward side-effects and remained quiescent Division, ICILtd., Macclesfield, Cheshire) in the slings. Analysis of the exponential Urogastrone (UG), isolated from human part of the curve gave a range of i-life Release of gastrointestinal hormones after urine, is a powerful inhibitor of gastric for hUg of one to four minutes, virtually an oral water load and atropine in man acid secretion with a marked structural none being detectable in blood 10 minutes and biological resemblance to the epi- after injection. Immunoreactive hUg D. L. SARSON, N. D. CHRISTOFIDES, R. H. dermal growth factor (EGF) found in appeared in the urine within two to five ALBUQUERQUE, T. E. ADRIAN, M. A. GHATEI, mouse submandibular gland. minutes of intravenous injection but the I. M. MODLIN, AND S. R. BLOOM (Depart- Immunocytochemical methods which total amount excreted in the urine was ment of Medicine, Royal Postgraduate were successfully used to identify EGF only 3-6% of the dose injected. Prelimin- Medical School, London) The post- at light and electron microscopical levels ary experiments using a radio-labelled prandial hormone rise is a vital part of have now been used to localise UG in hUg in the rat followed by whole body normal digestive control, yet very little human tissue, with a rabbit antibody to sections submitted to autoradiography is known of its mechanisms. To investi- UG. The indirect unlabelled antibody suggests that a substantial proportion of gate this, six healthy, fasted volunteers enzyme method of Sternberger was used a small molecular weight form appears in were given an oral water load of 15 ml/kg at both levels with the appropriate the lumen of the stomach after being body weight. Five of these subjects controls. cleared equally rapidly from the blood. repeated the experiment on another day Among a wide variety of tissues scanned These findings raise the possibility of after an intravenous injection of 600 ,ug the only positively reacting cells were luminal secretion of urogastrone. atropine. Regular blood samples were found in some acini of the submandibular taken and nine gut hormones with a wide gland and a larger amount in the duodenal anatomical distribution were measured Brunner's glands. Electron immunocyto- Release of motilin in man by oral and by radioimmunoassay. chemistry showed that the UG was present intravenous nutriments Both gastrin and PP demonstrated a http://gut.bmj.com/ in the granules of the cells. Both Brunner's very rapid rise (gastrin peak five minutes, and submandibular glands secrete in an N. CHRISTOFIDES, S. R. BLOOM, H. S. mean increment 12 ± 4 pmol/l, P < 0 05, exocrine manner. UG must therefore BESTERMAN, T. E. ADRIAN, AND M. A. PP peak two minutes, mean increment reach the urine either by secretion into the GHATEI (Department of Medicine, Royal 37 + 7.5 pmol/l, P < 0-001). After atro- blood from sources as yet undiscovered or Postgraduate Medical School, London) pine, gastrin rose identically, but levels by absorption across the intestinal mucosa. Motilin is a hormone affecting gastric remained raised longer, while the PP UG can stimulate cell proliferation and emptying and intestinal motility which is rise was completely suppressed and levels has a healing effect on experimentally- likely to play an important role in gut remained below basal throughout the on September 24, 2021 by guest. Protected copyright. induced ulcers. Its possible roles thus motility disorders. We, therefore, in- test. The rise of VIP and motilin was include topical protection in the vestigated the normal response of plasma slower (VIP peak 30 minutes, motilin intestine as well as gastric acid supression. motilin to oral and intravenous nutri- peak 40 minutes) and neither was affected Further study in both normal and patho- ments in a group of healthy colleagues. by atropine. GIP, EG, PG, insulin, and logical conditions is now indicated. After ingestion of 120 g fat, plasma secretin were not significantly stimulated motilin levels rose by 74 ± 29% at 30 by the water load. minutes (p < 0 05). An identical rise was Thus much of the postprandial rise of Half-life of urogastrone in conscious dogs also observed after a 30 minute intra- gastrin, PP, motilin, and VIP is not venous infusion of fat (8 g as 40 ml of mediated by meal nutriments. Only the J. B. ELDER, E. S. KIFF, AND H. GREGORY 20% intralipid). PP response depends on vagal stimuli, and (University Department of Surgery, Royal After ingestion of 50 g glucose levels the mechanisms of release of the other Infirmary, Manchester and Research De- fell by 51 ± 4% (p < 0-001) at 90 bormones remain to be discovered. partment, I.C.I., Alderley Park, Maccles- minutes. A fall of the same magnitude was field, Cheshire) The polypeptide uro- also seen after intravenous infusion of gastrone recently localised to the sub- glucose (20 g as 50 % solution). Oral Effect of motilin on gastric emptying of mandibular salivary glands and to protein did not cause any significant solid meals in man Brunner's glands is a potent inhibitor of change in plasma motilin. However, gastric acid secretion. In a preliminary after infusion of amino acids (25 g as N. D. CHRISTOFIDES, I. MODLIN, M. L. study in two dogs Gregory and his 250 ml of 10% Aminosol) motilin levels FITZPATRICK, AND S. R. BLOOM (Depart- colleagues estimated the I-life in blood of dropped by 50 ± 5 % (p < 0 005). ment of Medicine and Department of human urogastrone (hUg M.W. 6000) After ingestion of a standard meal by a Medical Physics, Royal Postgraduate to be 1 5 minutes. We have extended the group of 28 healthy subjects, motilin Medical School, London) Motilin has study using bolus injections of hUg levels rose by 34 ± 7°% (p < 0-001) at been shown to inhibit gastric emptying Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from The British Society of Gastroenterology A437 in man. To investigate its effect on the (IR-GIP5000), (2) eluting in the void Hypergastrinaemia due to cimetidine emptyingof solid meals, weinfused natural volume, reduced by pre-treatment with porcine motilin into five healthy subjects. 6 M urea and probably representing K. D. BUCHANAN, A. SPENCER, J. ARDILL, Cowley et al.'s previously described complexing between GIP and a plasma AND T. L. KENNEDY (Department of method for determining the gastric evacua- protein (GIPvo), and (3) eluting ahead of Gastroenterology, Royal Victoria Hospital, tion of solid meals, employing 129Cs, was the porcine standard, with a postulated and Department of Medicine, Queen's used. The rate of gastric emptying of each molecular weight of 7500-8000 (proGIP). University of Belfast) The release of subject was measured on four separate The ratio of the IR-GIP components was gastrin is inhibited by gastric acid days. On two of these, normal saline was GIPvo > < GIP5000> ProGIP. The later secretion and under conditions of achlor- infused; in the other two days motilin at IR-GIP response was characterised by a hydria massive hypergastrinaemia ensues a dose of 0-6 pmol/kg/min was given. reversal of the ratios of GIP5000 and -fasting plasma gastrin ng/l in normal All infusions were given blind. ProGIP. controls 46 ± 4 (M ± SEM) (N = 50), The mean half-emptying time during the ProGIP may be a precursor of G'P5000, in achlorhydrics without pemicious placebo runs was 121 ± 21 minutes. released during prolonged stimulation of anaemia 324 ± 46 (N = 10). It might be After the infusion of motilin there was a the same cell, or it may be the product of a predicted therefore that treatment with considerable acceleration of the gastric different population of APUD cells, the potent H2 receptor antagonist drug, emptying, with mean half-emptying times distal to cells producing GIP5*00. GIPvo cimetidine, would result in hypergastrin- of 70 ± 10 minutes, a percentage decre- may be biologically inactive and therefore aemia. Fasting plasma gastrin levels were ment of 41 ± 6% (p < 0O001, n = 5). excluded from direct correlation between estimated in a group of patients with Infusion of motilin at the above dose measurable IR-GIP and biological re- recurrent ulcer (RU) after surgery, and produced a plasma motilin increment of sponse. medically treated peptic ulcer (PU) 97 ± 11 pmol/l. As the motilin rise after subjects before treatment, during treat- water or fat ingestion is of a similar order ment with cimetidine (1 g), during of magnitude, and fasting motilin con- Distribution of gastrin within the antrum maintenance treatment (0 4 g) and six centrations often exceed 100 pmol/l, weeks after discontinuing the therapy. this increment appears to be within the T. P. CORBISHLEY AND R. C. G. RUSSELL Gastrin levels before treatment in 14 physiological range. (Department of Surgical Studies, The RUs (55 ± 8) did not differ significantly Thus, motilin appears to be an import- Middlesex Hospital, London) The entity from those in the control group subjects ant physiological mechanism controlling of antral G cell hyperplasia is a possible (46 ± 4) but became significantly raised the gastric emptying of a solid meal in cause of recurrent duodenal ulcer. To during treatment 83 ± 13 (p < 0-025) and man. exclude this condition an accurate and remained raised during maintenance

reproducible measure of antral gastrin 110 + 25 (p < 0-025) and after cimetidine http://gut.bmj.com/ content is required. A study was under- withdrawal 89 ± 32 (p < 0-05). In the Nature of endogenous gastric inhibitory taken to determine if gastric biopsy could group of 24 PUs the plasma gastrin rose polypeptide give an accurate assessment of gastrin significantly during treatment from 60 ± content. 12 pretreatment, to 82 + 16 on cimetidine JILL R. DRYBURGH, R. A. PEDERSON, AND Three stomachs, removed during pan- (p < 0-05) but retumed to within the J. C. BROWN Introduced by Julia M. creaticoduodenectomy, were subdivided normal range on the maintenance dose of Polak (Department of Physiology, Uni- into 1 cm squares after stripping the the drug. cimetidine versity of British Columbia, Vancouver, mucosa from the serosa. The antral In conclusion, treatment with on September 24, 2021 by guest. Protected copyright. B.C., Canada) The acronym, GIP, stands gastrin content of each square was raises fasting plasma gastrin levels and for either Gastric Inhibitory Polypeptide determined, after extraction, by radio- even after six weeks' withdrawal of or Glucose-dependent Insulinotropic Poly- immunoassay. therapy the trend remains. The potential peptide. The original studies, performed The mean gastrin content for each of of cimetidine to increase gastrin cell mass with pure porcine polypeptide, given the three stomachs was 1489 ± 1779, must be considered when long-term intravenously in doses producing levels n = 72, 2665 ± 3461, 1 n= 97 and therapy is planned. of IR-GIP comparable with those pro- 1476 + 3384, n = 43 ng/g with a co- duced by the physiological secretagogues, efficient of variation between squares at oral glucose or fat, indicated a clear-cut 120%, 130%, and 229% respectively. dose-response relationship, whether the In each stomach the gastrin content on SPRUE/ABSORPTION/ response measured was acid inhibition the greater curve was less than on the or insulin release. When either activity lesser curve and the gastrin content nearer was compared with the levels of endogen- the pylorus was significantly greater A non-invasive approach to intestinal ous polypeptide the relationship was much (P < 0 01) than that near the body of the permeability in less marked. The nature of the endogen- stomach. ous peptide was examined after gel It is concluded that even multiple I. COBDEN, R. J. DICKINSON, J. ROTHWELL, filtration on Sephadex G50. Serum biopsies will not accurately assess the AND A. T. R. AXON (Gastroenterology samples, taken at the initial peak IR-GIP gastrin content of the antrum, and that Unit, The General Infirmary, Leeds) Most response to either stimulus, chromato- studies of antral gastrin content must take oral intestinal absorption tests are graphed to show three regions of immuno- into account the wide variation of gastrin inaccurate because they are influenced reactivity: (l) corresponding to the content even within the adjacent areas of by extraneous factors such as gastro- elution pattern of pure porcine GIP the antrum. intestinal transit and renal and bladder Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A438 The British Society of Gastroenterology function. Coeliac patients absorb less of groups. All but five patients responded to coeliacs with hyposplenism compared with an oral dose of xylose than normal but a gluten free diet; these five, who required six (24%) of 25 coeliacs without hypo- paradoxically their absorption of di- steroids, were B-8 positive. splenism (p < 0 02). saccharides is increased. This observation Associated illnesses with possible The results suggest that CD is the has led to the use of a new oral test of allergic and 'immunological' aetiologies most frequent cause of hyposplenism intestinal permeability which simultan- -for example, asthma, pemicious found on blood film screening, and there eously measures the urinary excretion of anaemia, thyroid disease-were present is a high incidence of associated auto- the ingested molecules. The results are in 18% of patients with B-8 and 11 % immunity. There may be a link between expressed as a ratio, thus cancelling out the without this antigen. Detailed family the autoimmune manifestations of CD inaccuracies usually present in oral tests histories in 76 patients showed that and the defect in splenic function. of intestinal function. 36 % of first-degree relatives of B-8 Two passively absorbed molecules, positive patients had allergic or other cellobiose (Mol. radius 5 0 A) and man- immunological disorders as compared to Jejunal surface pH in gastrointestinal nitol (Mol. radius 4 0 A), were taken by 8 % of B-8 negative patients. disorders and its impact on serum folate mouth in hyperosmolar solution and It is concluded that, although B8 urinary excretion over five hours was positivity will affect the expression of G. KITIS, M. L. LUCAS, B. T. COOPER, W. T. measured in three groups of patients: autoimmune , it does not affect DUNNE, W. T. COOKE, R. N. ALLAN, AND 10 untreated patients with villous atrophy; the presentation of the disease. None of J. A. BLAIR (Nutritional and Intestinal 11 patients with treated coeliac disease, the patients showing complications of Unit, The General Hospital, Birming- and 16 patients with normal jejunal coeliac disease was B8 negative. ham, and Chemistry Department, Uni- biopsies. Patients with villous atrophy versity of Aston in Birmingham, Birming- absorbed more cellobiose and less man- ham) An acidic layer on the proximal nitol than patients with normal jejunal Relationship of hyposplenism, adult coeliac jejunal luminal surface has been demon- biopsies. Ratios of cellobiose and man- disease (CD) and autoimmunity strated in healthy subjects. Jejunal biop- nitol in the urine separated the two groups sies were obtained from a wide variety completely. Treated coeliacs occupied an A. W. BULLEN, R. HALL, G. GOWLAND, AND of subjects and surface pH measurements intermediate position. M. S. LOSOWSKY (University Department made during incubatiom in Krebs phos- In four coeliac patients, serial changes of Medicine, St. James's Hospital, Leeds, phate buffer. Mean surface pH in healthy in permeability have been studied after and University Department ofImmunology, subjects 5 98 ± 0-03 (50 subjects), un- the institution of a gluten-free diet. The The General Infirmary, Leeds) The blood treated coeliac disease 6 56 ± 0-14 (nine), recurrent aphthous stomatitis 6-19 ± 0 16

findings will be presented. film features of hyposplenism without http://gut.bmj.com/ previous splenectomy are found par- (six), iron deficiency anaemia 5 89 ± 0 17 ticularly in CD and also in a spectrum (three), non-specific diarrhoea 6-13 ± 0-25 Relationship of HLA status to the clinical of other conditions often associated with (11), and subjects with folate deficiency findings and autoimmunity in coeliac autoimmunity. However, the relation- without coeliac disease 6-03 ± 0-06 (nine). disease ship of hyposplenism to the well- Surface pH correlated inversely documented increased incidence of auto- (p < 0 005, n = 17) with intestinal lactase PARVEEN J. KUMAR, R. T. D. OLIVER, D. P. immunity in CD has not been assessed. levels and with villous height (p < 0 001, n = 98), two independent indices of gut O'DONOGHUE, L. NGAHFOONG, AND A. We have investigated all patients found on September 24, 2021 by guest. Protected copyright. PILLAI (Departments of Gastroenterology to have hyposplenic blood films without function underlining that the surface pH and Oncologgy, St. Bartholomew's Hospital, previous splenectomy during one year, in vitro is not an artefact. London) The histocompatibility antigen to assess the need for an intestinal biopsy In patients with untreated coeliac B-8 is associated with an increased pre- and the incidence of autoimmunity. disease (mean serum folate 2-3 ng/ml), valence of immunological disorders. Of 27 patients, 10 were known, and six surface pH was significantly less acid than Patients with coeliac disease have an discovered, on intestinal biopsy, to have in control subjects. This observation and increased incidence ofthis antigen. Ninety- CD. Two patients (one with dermatitis the normal surface pH in treated coeliac five patients with coeliac disease (24 M, herpetiformis, one with IgA deficiency) subjects supported the hypothesis 61 F) were studied to see if the presence had raised interepithelial lymphocytes, that the rate of folic acid transfer is or absence of HLA B-8 influenced their and one (with hereditary thrombocyto- controlled by surface pH. In subjects with age of diagnosis, duration of symptoms, pathia) had markedly raised eosinophils nutritional folate deficiency but no circulating autoantibodies, family history, in otherwise normal biopsies. Two evidence of coeliac disease, surface pH or associated illnesses. patients (one with myxoedema, one was indistinguishable from that of Seventy-two percent of patients were with pyelonephritis) had no mucosal controls. There was a highly significant HLA B-8 positive; the incidence was abnormality. Six patients (five over 75 correlation between the mean surface similar in the 22% of patients diagnosed years old) were not biopsied, although pH and the mean serum folate levels in childhood. Life-long symptoms were one had dermatitis herpetiformis, and (p < 0-001, r = 0-995) providing further present in a similar proportion of patients malabsorption was suspected in three evidence for the pH microclimate theory whether theywere B-8 positive or negative. others. for folate absorption. The presence ofcirculating autoantibodies Auto-antibodies were significantly more measured in the routine laboratory (ANF, frequent in the 27 patients with hypo- Gut hormone profile in post-infective reticulin, gastric thyroid, smooth muscle) splenism than in age-matched controls, tropical malabsorption (acute tropical did not differ significantly in the two and were present in 11 (69%) of the 16 sprue) Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from The British Society of Gastroenterology A439 H. S. BESTERMAN, G. C. COOK, D. L. SARSON, disease were returned to a normal diet. for gluten antibodies. All patients under- N. D. CHRISTOFIDES, AND S. R. BLOOM Jejunal biopsies were obtained before and went jejunal biopsy, which was examined (Department of Medicine, Royal Post- at varying intervals after starting the diet grossly and histologically, and disac- graduate Medical School, London and or when symptoms appeared. Ten patients charidase levels measured. Department of Clinical Tropical Medicine, had been diagnosed in childhood (CCD) Twenty-eight per cent of the 50 patients School of Hygiene and Tropical Medicine, and 16 in adult life (ACD). Patients had had haematological deficiency. Screening London) We have previously reported been on a gluten free diet for a mean of for IGA-reticulin and gluten antibodies that there is a characteristic pattern of eight and three years respectively. was negative in all patients. Two patients gut hormone release in coeliac disease, In the CCD group, four patients had (4%) were found to have subtotal villous which appeared to be related to the area of symptoms within four weeks and all atrophy: both were deficient in folate gut involved. showed jejunal deterioration. Six patients and one in iron. Post-infective tropical malabsorption remained asymptomatic, two showing It is suggested that only those recurrent (acute ) is characterised by jejunal abnormalities within two weeks aphthae patients with a deficiency of persisting malabsorption after an acute but in three patients an abnormal mucosa folate should have a jejunal biopsy onset of diarrhoea in a tropical country. was not found until five, eight and 10 performed routinely. Typically, there is partial villous atrophy months. The remaining patient has a which probably involves a greater length normal mucosa at two years. In the ACD of the small intestine than in coeliac group, 15 of 16 had jejunal abnormalities In vitro assessment of clobetasone butyrate disease. Gut hormones were measured within six weeks, 12 of whom also had on coeliac mucosa in eight patients with severe tropical symptoms, one patient remains well at malabsorption and in 12 healthy subjects 18 months. M. G. BRAMBLE, A. J. WATSON, AND C. 0. after a standard breakfast. The release of Of 22 patients who were HLA typed, RECORD (Departments of Gastroenter- gastrin and pancreatic polypeptide was 17 were B8 positive. Both patients who ology and Histopathology, Royal Victoria identical in the two groups. In those with have not relapsed are B8 negative. There Infirmary, Newcastle upon Tyne) The tropical malabsorption, basal concentra- was little correlation between the time of deleterious effect of gluten on coeliac tions of motilin (144 ± 28 pmol/l) and relapse and the length of time on a gluten mucosa in organ culture is reduced by the enteroglucagon (261 ± 73 pmol/l) were free diet. Symptoms were variable and addition of prednisolone. Clobetasone both significantly raised compared to often mild; only eight had diarrhoea. butyrate (Molivate, Glaxo) is a steroid controls (36 ± 10, 27 + 7 pmol/l res- The results from this study show that, with systemic activity similar to prednis- pectively, P < 0 01). There was a small in contrast with children, adult patients olone, but which possesses topical activity equivalent rise in motilin in both groups, retain a greater sensitivity to gluten. 250 times greater. This drug is poorly but no significant change in entero- absorbed and may be useful in patients http://gut.bmj.com/ glucagon after the breakfast. Basal con- requiring corticosteroid therapy for failure centrations of gastric inhibitory poly- Coeliac disease in patients with recurrent to respond to a gluten-free diet. peptide were similar in all groups, but aphthae Five patients with active coeliac disease those with tropical malabsorption had a and nine controls had multiple biopsies much reduced postprandial rise D. WRAY, H. A. CARMICHAEL, M. M. from the D/J region using a Quinton (10 + 1 pmol/l), compared to normal FERGUSON, F. D. LEE, AND R. I. RUSSELL hydraulic biopsy tube. These were then subjects (21 ± 2 pmol/l, P < 0 001). (Gastroenterology Unit and Department cultured for 24 hours in medium alone

The gut hormone profile in tropical of Pathology, Royal Infirmary, Glasgow, and medium pius 0 75 mg ml-' Frazers on September 24, 2021 by guest. Protected copyright. malabsorption is thus diagnostically differ- and Department of Oral Medicine and fraction III with and without clobetasone ent from healthy subjects and from coeliac Pathology, Dental Hospital, Glasgow) butyrate. Alkaline phosphatase, lactase, disease. In a previous series of 130 aphthae and morphological appearances were patients an incidence of 5% of gluten examined. was found when those Alkaline phosphatase activity rose Clinical and morphological assessment of patients with folic acid deficiency were significantly from 203-3 + 31 2 uM gluten challenge in children and adults screened for malabsorption. Subsequently min-" mg-1 (mean + SEM) to 421 + with coeliac disease an incidence of 25% of coeliac disease in 85-2 in medium alone (p < 0-025). The recurrent aphthae patients was reported, corresponding rise with 0 75 mg ml-" PARVEEN J. KUMAR, D. P. O'DONOGHUE, further suggesting a strong association Frazers fraction III added was 324-7 + M. L. CLARK, AND A. M. DAWSON (Depart- between the two diseases. 81-2 (p > 0-1). The addition of 8 uM, ment of Gastroenterology, St. Bartholo- A study was therefore undertaken to 2 uM, and 0 5 uM clobetasone resulted in mew's Hospitai) Coeliac disease is con- screen 50 unselected patients presenting rises similar to medium alone. Gluten firmed by jejunal deterioration after with recurrent aphthae for gluten entero- had no effect on control cultures. reintroduction of gluten following a pathy. Haematological screening In conclusion, clobetasone butyrate period of gluten withdrawal. No estab- included haemoglobin, absolute values, exerts a protective effect against gluten lished guidelines exist for reintroducing blood film, serum vitamin B12, corrected on the mucosa in organ culture of active gluten and in this paper the time course of whole blood folate, iron and total iron coeliacs. symptomatic and morphological relapse binding capacity. The patients were in children and adults with coeliac disease examined for the presence of circulating is delineated. IgA-reticulin antibodies, as this has been Kinetic studies of fructose absorption in Twenty-six patients with treated coeliac found to be a useful screening test, and the rat in vivo Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from A440 The British Society of Gastroenterology

P. J. MILLA, U. B. RASSAM, D. P. R. MULLER, Na-K ATPase activity and sodium or Research Unit and Department ofSurgical AND J. T. HARRIES (Institute of Child chloride transport after ouabain. The only Pathology, St. Thomas' Hospital, London, Health and The Hospitalfor Sick Children, statistically significant effect of ouabain and St. George's Hospital, London) Nine Great Ormond Street, London) In a infusion was a reduction in the rate of females, aged 32 to 51 years (mean 43 previous communication we presented bicarbonate secretion. Thus, the results of years), who underwent jejunoileal bypass data suggesting that fructose is transported our experiments suggest that mucosal for obesity in 1971-72 were investigated by a phlorhizin-sensitive system, and that Na-K ATPase activity is not a rate- for metabolic bone disease. Histological low (2 mM) but not high (56 mM) limiting step in the absorption of sodium measurement of transiliac biopsies re- concentrations of glucose stimulated and chloride in the dog . vealed osteomalacia in five (55 6°/), with fructose (20 mM) absorption. evidence of secondary hyperparathy- Using the same in vivo perfusion tech- roidism in four. Three of these patients nique we have studied the kinetics of Defective small intestinal absorption of complained of bone pains. The presence fructose absorption, and the effects of neutral non-polar amino acids in pancreatic of osteomalacia was unrelated to post- adding 2 mM glucose. A saturable mech- insufficiency (PI) operative weight loss. anism is present at concentrations of Total serum alkaline phosphatase, and less than 40 mM (Km = 22-1 mM; P. J. MILLA, U. B. RASSAM, R. ERSSER, AND the bone isoenzyme were raised in only Vmax = 0 52 ,umol/min/g wet wt). Above J. T. HARRIES (Institute of Child Health two patients with osteomalacia, and this concentration kinetics appear to and The Hospital for Sick Children, serum calcium was low in two osteomala- become linear. Addition of glucose Great Ormond Street, London) In vitro cic and two non-osteomalacic patients. stimulated fructose absorption at or studies have demonstrated impaired small Serum calcium, phosphate, and alkaline below the apparent Km, but not at higher intestinal uptake of neutral non-polar phosphatase were all normal in one concentrations. amino acids (phenylalanine) but not of patient with osteomalacia. Plasma 25- These results suggest that, at low basic amino acids (lysine) in patients with hydroxyvitamin D concentrations were concentrations, a carrier-mediated trans- cystic fibrosis (CF); these amino acids are low in six patients, but did not correlate port system is involved in fructose absorbed by separate transport systems. closely with bone histology, and plasma transport, and that this system is stimula- We have applied a steady-state per- immunoreactive parathyroid hormone ted by glucose. We suggest that these fusion technique to study in vivo absorp- levels were raised in one osteomalacic observations are compatible with the tion and transmucosal potential difference patient. Radiological assessment by meta- concept of multiple membrane carriers (PD) in the proximal jejunum of patients bolic bone survey identified only one for monosaccharides, and that such with CF and congenital pancreatic in- patient with osteomalacia and hyper- carriers may behave in a manner sufficiency (CPI). The perfusates contained parathyroidism. http://gut.bmj.com/ analogous to allosteric enzyme proteins. phenylalanine (56 or 20 mM) or lysine It is concluded that osteomalacia is (56 or 5 mM) and were perfused in common afterjejunoileal bypass, and that random order. bone biopsy is the only reliable method of Effect of ouabain on Na-K ATPase Net absorption of phenylalanine was diagnosis. The effect of therapy with activity and electrolyte transport in the significantly reduced (P = <0-002) from oral la-hydroxyvitamin D, is currently dog ileum both concentrations in CF patients, but being assessed. this was not the case for lysine. Similar N. W. READ, G. J. KREJS, V. E. JONES, AND J. S. CPI. abnormalities were demonstrated in on September 24, 2021 by guest. Protected copyright. FORDTRAN (Department ofInternal Med- In one patient with coeliac disease absorp- OESOPHAGUS/STOMACH/DUODENUM II icine, The University of Texas Health Sci- tion of both amino acids was reduced. ence Center at Dallas Southwestern Med- PD was also reduced (P = 0-01) during ical School, Dallas, Texas 75235, USA) It perfusion of 56 and 20 mM phenylala- Effects of long-term cimetidine on gastric is currently believed that the rate and nine, but not with either concentration of acid secretion, gastric emptying, and direction of sodium transport in the small lysine; PD was reduced during perfusion serum gastrin intestine may be regulated by the activity of both amino acids in coeliac disease. of Na-K ATPase in the basolateral celt These results confirm and extend pre- J. A. H. FORREST, M. R. FETTES, G. LIDGARD, membrane. We tested this hypothesis by vious in vitro studies on phenylalanine G. P. MCLOUGHLIN, AND R. C. HEADING selectively infusing ouabain, a known and lysine transport in CF, and demon- (University Departments of Therapeutics inhibitor of Na-K ATPase, into the strate a defect in active absorption of and Medical Physics and Regional Hor- mesenteric artery supplying a perfused neutral non-polar amino acids in PI. mone Laboratory, Royal Infirmary, loop of ileum in 18 dogs. Before ouabain We speculate that a pancreatic 'factor' Edinburgh) Gastric acid secretion, gastric infusion there were significant correla- may participate in the absorption of this emptying, and the serum gastrin response tions between the activity of Na-K group of amino acids. to food were studied in duodenal ulcer ATPase and net and lumen to plasma patients before and seven to 10 days fluxes of sodium and chloride. After after completion of six months' treatment ouabain, there was no significant change Osteomalacia after jejunoileal bypass with cimetidine (600 mg b.d). The empty- in sodium and chloride transport, uni- ing and gastrin studies were also per- directional fluxes or transmucosal poten- J. E. COMPSTON, L. W. L. HORTON, H. J. formed midway through the period of tial difference, despite a 50% reduction in BULL, M. F. LAKER, A. B. AYERS, J. S. treatment. Conventional pentagastrin mucosal Na-K ATPase activity. Further- WOODHEAD, J.-C. GAZET AND T. R. E. tests were used to measure acid secretion; more, there was no correlation between PILKINGTON (From the Gastrointestinal gastric emptying of a standard meal Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from The British Society of Gastroenterology A441 containing 11am In was measured scinti- significant increase in pepsin secretion, wounds were made at the antrofundic graphically and blood samples with- most marked at 0-32 ug/kg/h of penta- junction in the stomachs of 80 male drawn at intervals after the meal for gastrin (p < 0 05). The changes in pepsin Sprague-Dawley rats, which were then estimation of serum gastrin. secretion may in part reflect changes in randomly allocated into four treatment Both basal and maximal acid outputs secreted volume. groups as follows: (1) daily oral saline were increased after six months' therapy as control; (2) daily oral cimetidine, by an average of 1-5 and 6-0 mmol/h 100 mg/kg/day; (3) daily subcutaneous respectively (n = 18, p < 005 and Effect of cimetidine on renal function in saline as control; and (4) daily sub- p < 0-02). Compared with pretreatment man cutaneous EGF, 80,g/kg/day. values, the three-hour integrated gastrin Five rats from each group were killed response after three months' therapy M. DUTT, P. SANDERSON, AND T. C. NORTH- at weekly intervals for four weeks and the increased by 106% (n = 9, p < 0-01) FIELD (Norman Tanner Gastroenterology ulcers photographed, measured, and sub- and was still raised by 41 % (p < 0-05) Unit and Department of Clinical Path- mitted to histological examination. One after treatment ceased. Basal gastrin ology, St. James' Hospital; and Depart- death occurred in the cimetidine control concentrations were unaltered. Gastric ment of Medicine, St. George's Hospital group, and all treatment groups gained emptying rates at three and six months Medical School, London) Cimetidine is weight. There was progressive reduction were faster than those observed before being widely used in the treatment of in mean ulcer size in each treatment treatment but the differences were not peptic ulcer, but it causes an increase in group but this was greatest in the EGF statistically significant. plasma creatinine. We have therefore group (p < 0-01). Long-term cimetidine therapy ap- determined glomerular filtration rate All ulcers in the EGF group were parently enhances both the serum gastrin (GFR) from creatinine and 51Cr EDTA completely healed at one month, whereas response to food and the gastric acid clearances, and effective renal plasma 40% of ulcers in the cimetidine group and secretory capacity. These changes may flow (ERPF) from 125I hippuran clearance 20% in the control groups were healed. contribute to recurrence of ulceration in nine patients receiving cimetidine These results were confirmed by histo- after the drug is stopped. (1-6 g daily) for peptic ulcer. Plasma logical examination. creatinine (hmol/l) rose from 97 5 ± 18-4 (mean ± SD to 110-3 + 10-7 at one day Dose response of acid and pepsin secretion (P < 0-01), 122-0 ± 19-7 at three weeks Cimetidine relieves symptoms of gastro- to pentagastrin infusion during treatment (P < 0-001) and 108-3 + 19-5 at 12 weeks oesophageal reflux with cimetidine (NS). Creatinine clearance (ml/min) fell from 87-5 ± 35-4 to 59 5 ± 31-3 at one P. R. POWELL-JACKSON, H. BARKLEY, AND

R. J. HOLDEN, M. WEETCH, N. ARACH- day (P < 0-02), but rose again to T. C. NORTHFIELD (Norman Tanner http://gut.bmj.com/ MANDRMS, J. HEARNS, AND G. P. CREAN 80 6 ± 41 0 and 93-0 + 49 7 at three and Gastroenterology Unit and Department of (Gastro-Intestinal Centre, Southern General 12 weeks. 51Cr EDTA clearance (ml/min) Histopathology, St. James' Hospital; and Hospital, Glasgow) The response of fell from 1213 ± 18-7 to 104-5 + 18-4 Department of Medicine St. George's acid and pepsin secretion to doubling at one day (P < 0-01) but rose again to Hospital Medical School, London) doses of intravenous pentagastrin (0-16 to 120-3 + 17-3 and 123-3 + 16-9 at three Twenty-seven patients were investigated 1 28 ug/kg/h) has been studied in 10 and 12 weeks. 1251 hippuran clearance fell in a double-blind trial of cimetidine in patients before, during 16 weeks' treat- from 591-5 ± 100-2 to 520-6 + 89-9 symptomatic gastro-oesophageal reflux. ment up to at one < rose to All with cimetidine, and eight day (P 0-01), but again 27 complained of retrosternal chest on September 24, 2021 by guest. Protected copyright. weeks after therapy was discontinued. 592-7 + 77*3 and 599-0 ± 92-0 at three pain, related to posture, and eased by During treatment with cimetidine acid and 12 weeks. We conclude that cimetidine antacids. They received cimetidine (1 6 g secretion was depressed in response to causes an early, and short-lived, fall in daily) for six weeks, and matching placebo each dose of pentagastrin (P < 0-005) ERPF and GFR, but that the later in- for six weeks (crossover design, random and the dose response slopes at two, crease in plasma creatinine is due to order). As subjective assessment, symp- eight, and 16 weeks were indistinguishable increased production and not impaired toms and antacid consumption were from each other. The maximal response renal function. recorded daily. As objective assessment, in control tests occurred with 0 64 ug/kg/h oesophagoscopy, oesophageal biopsy, and pentagastrin; this dose also produced the a quantitative oesophageal acid perfusion maximal response seen during treatment Comparison of cimetidine and epidermal test were carried out at 0, six, and 12 with cimetidine. After four months' growth factor in the healing of experi- weeks. During the first week of placebo, treatment the dose response curve one mental gastric ulcers the number of episodes of pain was week after withdrawal of therapy was 7.9 ± 1 2 (mean + SEM) compared with indistinguishable from the pretreatment C. G. KOFFMAN, JACQUELINE BERRY, AND 4-3 + 0-8 on cimetidine (P < 0 0025). curve and remained so at two, four, and J. B. ELDER (University Department of The number of antacid tablets consumed eight weeks after treatment. Surgery, Royal Infirmary, Manchester) during the first week on placebo was The dose response of pepsin secretion Epidermal growth factor (EGF) is a 14-3 ± 2-8, compared with 7-2 + 2-0 was flatter with maximal output occurring naturally occurring polypeptide of similar on cimetidine (P < 0-0005). These differ- at Iowerdosesofpentagastrin(0*32ug/kg/h structure and bioactivity to urogastrone, ences were maintained during the six- and there was much less depression of which is itself a potent inhibitor of week period. At six weeks, the amount pepsin secretion during therapy. When gastric acid secretion. of N1o HCI necessary to cause chest pain therapy was withdrawn there was a Standardised 5 mm diameter mucosal (at 10 ml/min) was 94 ± 12 ml on Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from A442 The British Society of Gastroenterology placebo, and 90 + 14 ml on cimetidine Cambridge) As the high incidence of weeks, with 90 patients followed beyond (NS). There was no significant difference recurrence remains a major problem in six months. No significant laboratory in endoscopic and histological appear- the medical management of gastric abnormalities were found. One patient ances. We conclude that cimetidine re- ulceration, we are studying the efficacy receiving cimetidine was withdrawn after lieves the symptoms ofgastro-oesophageal of cimetidine in the prevention of re- 14 weeks because of myalgia. Two patients reflux, but that it is acting like an ant- lapse. on cimetidine who were withdrawn after acid without altering the underlying Patients with gastric ulcer who have six months were in clinical and endo- mucosal sensitivity to acid. received treatment with either cimetidine scopic remission. Of the remaining 93 or placebo in a four-week trial, and whose patients clinical relapse confirmed endo- ulcers have been shown to be healed at scopically, occurred in 32/48 receiving Apparent healing of malignant gastric endoscopy, are admitted to the study placebo and 4/45 receiving cimetidine ulcers with cimetidine and are randomly allocated into groups, (p > 0.001). Three of those patients one receiving cimetidine 200 mg three relapsing on cimetidine were hyper- RODNEY H. TAYLOR, N. MENZIES-GOW, times daily with 400 mg at night and the secretors or hypergastrinaemic. Of 34 D. LOVELL, S. J. LA BROOY, AND J. J. other identical placebo tablets. Both asymptomatic patients endoscoped rou- MISIEWICZ (Departments of Gastroenter- groups are supplied with antacid tablets. tinely after six months' treatment, six ology and Histopathology, Central Middle- Follow-up is at monthly intervals, had chronic ulcers (placebo five and sex Hospital, London) Malignant gastric when symptoms and antacid consumption cimetidine one). ulcers (GU) may present in a similar way are recorded together with haematological Cimetidine 400 mg b.d. appears to be to benign GU. The endoscopic appear- and biochemical parameters. Endoscopy effective in preventing relapse of duodenal ances may seem benign and careful is repeated at five months and 11 months, ulcer. multiple biopsies and cytological brush- or at any stage if symptoms recur. ings fail to show malignant tissue. Thirty-one patients have entered the We report four cases of GU which trial to date and 17 have either com- INFLAMMATORY BOWEL appeared benign at endoscopy, biopsy, pleted the 11 months' treatment or re- and cytology and were treated with lapsed. In 10 patients, gastric ulceration cimetidine. All had symptomatic improve- has recurred, nine on placebo and one on Eosinophils in the rectal mucosa: a prog- ment, which was complete in two patients. cimetidine. In seven patients the ulcers nostic indicator for ulcerative ? At repeat endoscopy two ulcers had healed remained healed at 11 months, five on and the other two were greatly improved, cimetidine and two on placebo (p < 0035). P. D. JAMES AND R. V. HEATLEY (General

again with negative biopsies and cytol- These results suggest that cimetidine Hospital, Nottingham) There is at present http://gut.bmj.com/ ogy. Three patients relapsed sympto- 1 g daily is effective in reducing the inci- no satisfactory means of predicting the matically soon after the completion of dence of gastric ulcer relapse. clinical outcomeof patients with ulcerative treatment and at repeat endoscopy the proctocolitis. We have examined 50 GU had recurred at the original site. In patients with proctocolitis who have been the fourth case biopsies after treatment Maintenance of remission of duodenal followed for periods of up to 220 months showed malignancy. All patients had ulcer by cimetidine: a double-blind con- (mean 70). Sequential rectal biopsies were partial gastrectomies and all the resected trolled trial examined and divided into four patho-

stomachs contained intramucosal gastric logical grades according to the chronic on September 24, 2021 by guest. Protected copyright. carcinoma. Subsequently (three months- D. J. HETZEL, D. J. C. SHEARMAN, J. HANSKY, inflammatory infiltrate in the lamina pro- two years) there has been no evidence of M. G. KORMAN, R. HECKER, R. JACKSON, pria and the presence of acute mucosal recurrence. B. W. GABB, AND R. SHEERS (Departments inflammation. The pathological grades Cimetidine gave symptomatic relief of Medicine and Gastroenterology Units, werecompared with theclinical outcome of and promoted healing ofthe inflammatory Royal Adelaide Hospital and Prince the patients but no consistent difference lesion in these gastric carcinomas. In GU Henry's Hospital, Melbourne, Australia) was found to separate the clinical groups. (treated with cimetidine) where there is Cimetidine 1 2 g daily for six weeks The tissue eosinophilia was assessed using incomplete symptomatic relief, early relieves symptoms and promotes healing a micrometer grid and an average count relapse, inadequate healing, or recurrence in Australians with duodenal ulcer. This per grid was taken for each biopsy. at the same site, the suspicion of malig- study assesses whether relapse can be pre- Patients with high eosinophil counts in nancy must be high. Repeat endoscopy vented by long-term therapy. biopsies with acute inflammatory changes with multiple biopsies and cytological Ninety-six patients with duodenal ulcer had a good prognosis and the disease in brushings is'mandatory and early surgery were treated with cimetidine and healing these patients either followed a self- must be considered. of the ulcer confirmed endoscopically. limiting course or was well controlled They were randomly allocated to a with therapy. Patients who failed to maintenance dose of cimetidine 400 mg respond to treatment and had persistent Maintenance cimetidine in the prevention b.d. or placebo. Clinical and laboratory symptoms or who came to surgery had of gastric ulcer relapse assessment was made monthly. When significantly lower eosinophil counts. symptomatic relapse occurred, further It would appear that the assessment of R. J. MACHELL, P. J. CICLITIRA, M. J. G. endoscopy was performed. Endoscopy tissue eosinophilia in rectal biopsies from FARTHING, J. D. R. ROSE, A. P. DICK, AND was repeated on 34 asymptomatic patients patients with active proctocolitis provides J. 0. HUNTER (Department of Medical who completed six months' treatment. an easy and reliable predictive test for the Gastroenterology, Addenbrooke's Hospital, Mean duration of follow-up was 38 outcome of this disease. Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from The British Society of Gastroenterology A443

Chronic immune complex -an ex- five patients with UC, five patients with These results suggest that a loss of Con perimental model CD and five control subjects. After the A induced suppressor cells is not merely a injection of "1'I-Clq, serial plasma samples concomitant of acute inflammation; it A. S. MEE, J. E. MCLAUGHLIN, H. J. F. and 24 hour collections of urine and faeces may be that an inability to suppress HODGSON, AND D. P. JEWELL (Departments were obtained during a six day period. The damaging immune responses directed ofMedicine andHistopathology, RoyalFree datawere analysed by standard techniques. against the gut contributes to the patho- Hospital, London) A previous study has The fractional catabolic rate (FCR) of genesis of and Crohn's shown that immune complexes injected Clq was markedly raised in all patients disease. intravenously in non-immunised rabbits except for one with UC in remission induce an acute, but not chronic, colitis (mean FCR: UC 4-66 ± 0 91; CD 5-99 + under appropriate conditions. An attempt 1-14; controls 2-34 ± 0-23%IV pool/h). Mechanisms for zinc deficiency in Crohn's to produce a chronic colitis has therefore Synthesis rates were also increased (UC disease been made by injecting immune complexes 019 ± 0-036, CD 0-368 ± 0043, controls into rabbits previously immunised with a 0*118 ± 0 017mg/kg/h). For the patients, G. STURNIOLO, M. MOLOKHIA, L. SANDLE, colonic bacterial antigen. there was an increase in the extravascular R. SHIELDS, AND L. A. TURNBERG (Depart- Rabbits were immunised with Kunin distribution of Clq, suggesting active ment of Medicine, Hope Hospital (Univer- antigen, antibody titres greater than 1/512 sequestration in inflamed tissue. sity of Manchester School of Medicine), being obtained. 1 ml of 1 % formalin was These data show that activation of the Salford) Patients with Crohn's disease instilled into the re tum of immunised classical pathway of complement occurs may develop clinical features of zinc rabbits. Two hours later the rabbits were in UC and CD and therefore supports the deficiency. We have looked for evidence given an intravenous injection of HSA/ concept that immune complexes are in- of such deficiency and studied possible anti HSA complexes made in antigen volved in the pathogenesis of mucosal mechanisms for it by measuring zinc excess. inflammation. absorption and elimination rates. Rectal biopsies were obtained before Twenty-three patients with small bowel each procedure and then serially during Crohn's disease had reduced serum zinc the subsequent six months. Control Suppressor cells and control of immune concentrations (65 + 14-1 ,tg 100 ml-' rabbits were immunised with Kunin response in ulcerative colitis and Crohn's (± SD)) compared with normal subjects antigen, given formalin and injected with disease (89 ± 11.3 ,tg 100 ml-'). saline, HSA or anti HSA. After oral administration of 69mZn Control rabbits showed an inflam- H. J. F. HODGSON, J. R. WANDS, AND K. J. (half-life 13-9 h) with 2 mg cold zinc, to matory infiltrate present at 24 hours and ISSELBACHER (Harvard Medical School eight fasting Crohn's patients, plasma up to one week after injection but the and Gastrointestinal Laboratory, Massa- appearance curve peaks were significantly http://gut.bmj.com/ rectal mucosa had returned to normal by chusetts General Hospital, Boston 02114, reduced compared with five control six weeks. For rabbits receiving complexes USA) Deficient suppressor T cell activity subjects. (Range 0-2 to 1 5 % of dose -1- a brisk inflammatory infiltrate persisted occurs in some 'autoimmune' diseases; plasma compared with 1-4 to 2-8% d1-1 throughout the six months and there was this may permit unchecked expression of in controls). The peak appearance was evidence of gland atrophy, with distortion damaging immune responses. In Crohn's delayed in three Crohn's patients. of the surface epithelium. disease and ulcerative colitis, cellular After intravenous injection of 69mZn These results suggest that when an hypersensitivity to gutantigens is reported. there was an abnormally rapid elimina-

acute colitis develops in an animal sensi- We therefore investigated suppressor cell tion rate in three of the eight Crohn's on September 24, 2021 by guest. Protected copyright. tised to bacterial antigens a chronic control of lymphocyte reactivity in these patients compared with controls. mucosal lesion may develop. diseases. Net zinc absorption, calculated from We generated suppressor cell activity appearance and disappearance curves, from peripheral blood mononuclear cells using a deconvolution computer pro- Clq metabolism in patients with inflam- of 21 normal subjects by pre-incubation in gramme, was significantly reduced in the matory bowel disease vitro with concanavalin A. Such cells then Crohn's patients. (Range 8 to 45% after suppressed the blast transformation re- eight hours compared with 38 to 74% in B. J. POTTER, A. S. MEE, H. J. F. HODGSON, sponses induced in fresh lymphocytes by normal subjects). AND D. P. JEWELL (Department of lectins or mixed lymphocyte culture (mean We conclude that zinc absorption is im- Medicine, Royal Free Hospital, London) suppression 27-4 ± 4 2%). However, in paired in most patients with Crohn's Immune complexes have been implicated studies on 11 patients with inflammatory disease and that some may also eliminate in the pathogenesis of ulcerative colitis bowel disease, pre-incubated lymphocytes zinc from the plasma abnormally rapidly. (UC) and Crohn's disease (CD). To test did not suppress but enhanced fresh lym- whether the increased metabolism of C3, phocytes' responses (mean suppression observed in these patients, could be a -9-2 ± 11-8%, P <0 005 compared with Further evidence for a mycobacterial result of classical pathway activation by controls). This enhancing, or helper cell, aetiology of Crohn's disease complexes, the metabolism of Clq has response was seen only in patients with been studied. active disease, and not in remission. Five S. A. WHITE, E. NASSAU, W. R. BURNHAM, Highly purified Clq was isolated from other subjects with active inflammatory J. L. STANFORD, AND J. E. LENNARD-JONES fresh human serum, labelled with 126J, conditions such as lobar pneumonia (School ofPathology, Middlesex Hospital, and shown to be functionally active. showed normal suppressor responses London, and St. Mark's Hospital, London) Metabolic studies were then performed in (21-8 + 5 5%). We have recently reported that a variety of Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A444 The British Society of Gastroenterology Mycobacterium kansasii, possibly in cell was given for the second month. The tion of the aetiology and pathogenesis of wall deficient form, may be involved in order of the treatments was randomised. this condition-in particular, the theory the aetiology of Crohn's disease. This Assessments were repeated at the end of that pseudomembranous colitis might be work has been extended to look for anti- each treatment period by a clinician who a clostridial disease. body to this organism in the sera of was unaware of which treatment had been patients with inflammatory bowel disease, given. The patients recorded their symp- using an indirect fluorescent antibody toms and treatment on a diary card. Prolyl hydroxylase activity in serum and technique which has been employed with Two patients were withdrawn from the rectal mucosa in inflammatory bowel success in tuberculosis. All samples were study. No difference was observed in any disease coded and the tests read 'blind'. of the parameters between the active and Nine of 11 patients with Crohn's placebo treatments. Assessments of the M. J. G. FARTHING, A. P. DICK, G. HESLOP, disease, eight of 10 with ulcerative colitis, two treatment periods by clinician and AND C. I. LEVENE (Department ofMedical but none of 22 controls were positive at a patient agreed on 16 occasions. Seven Gastroenterology, Addenbrooke's Hospital 1/20 dilution of serum; six of the Crohn's favoured the placebo treatment, four the and Department ofPathology, University of patients and five of those with colitis were active treatment and in five no difference Cambridge) The enzyme prolyl hydroxy- recorded as being strongly positive at this between the two was noted. lase, which has been used as an indicator dilution. At a 1/40 dilution of serum, five We conclude that oral disodium cromo- of collagen synthesis in many tissues, was of 11 patients with Crohn's disease and glycate 200 mg qds given for one month is measured in serum and homogenates of seven of 10 with ulcerative colitis were of no value in the treatment of chronic rectal mucosa from patients with inflam- positive; four of the Crohn's patients and persistent colitis. matory bowel disease by a method based two of those with colitis were strongly on the stoichiometric formation of (3H) positive at this dilution. water from an underhydroxylated protein These results confirm our previous Antibiotic-associated colitis, an animal substrate labelled with 3,4-(3H) proline. work. The negative results in some of our model Prolyl hydroxylase activity was found patients may indicate an analogy with to be significantly greater in 11 patients leprosy, in which antibodies are easily A. B. PRICE AND H. E. LARSEN (Northwick with Crohn's disease (mean 620-0 ± SE demonstrated in the lepromatous form Park Hospital and C.R.C., Harrow, 129-0 cpm/mg protein) than 11 control but not in the tuberculoid form. Middlesex) Clindamycin and Linco- subjects with the mycin produce a fatal colitis in Syrian (mean 190-4 + SE 71-9 cpm/mg protein, hamsters. Twenty-seven animals were P < 0 005). Seven of the patients with Crohn's disease had a histologically

Controlled trial of disodium cromoglycate given single intraperitoneal injections of http://gut.bmj.com/ in chronic persistent colitis Clindamycin (50 mg/kg) and eight animals normal . This abnormality in were injected with Lincomycin (50 mg/kg), apparently normal mucosa supports the S. R. GOULD, N. A. BUCKELL, D. W. DAY, Upjohn Co. Eight hamsters received single concept that Crohn's disease is a 'con- A. M. EDWARDS, AND J. E. LENNARD-JONES intraperitoneal injections of saline and tinuous' disease of the gastrointestinal (St. Mark's Hospital, London and The four received ampicillin (50 mg/kg). These tract. Although there was no significant Medical Department, Fisons, Lough- animals acted as controls. Seventy per difference in prolyl hydroxylase activity borough) Some patients with ulcerative cent (25) of the animals given Clinda- between control subjects and 16 patients colitis are resistant to treatment with mycin or Lincomycin died or were mori- with ulcerative colitis, those patients with sulphasalazine and/or corticosteroids and bund within three weeks. None of the quiescent disease tended to have lower on September 24, 2021 by guest. Protected copyright. appear to need additional treatment. The control animals died. Pathological ex- values than those with active mucosal beneficial effects ofdisodium cromoglycate amination of the affected animals showed inflammation. Prolyl hydroxylase activity in chronic and maintenance a haemorrhagic caecitis. In all cases of could not, however, be detected in the treatment of ulcerative colitis have been caecitis suspensions of the caecal con- sera of either healthy control subjects or reported. In this trial the effect of adding tents produced a cytopathic effect in patients with inflammatory bowel disease. disodium cromoglycate to an apparently human embryonic lung fibroblast cultures Estimation of prolyl hydroxylase activity ineffective conventional regime has been which was identical to that described in in the rectal mucosa may be useful in studied. human pseudomembranous colitis. This distinguishing Crohn's disease from other Twenty-six patients with symptoms of effect was also neutralised by Clostridium bowel disorders when the rectum appears active colitis of at least two months sordellii anti-toxin. We failed to grow C. normal and may help clarify the diagnosis duration which had been resistant to sordellii from any of the animals, but from when the rectum is involved in inflam- conventional therapy and who showed the two toxogenic C. difficile has been isolated. matory bowel disease. changes of active mucosal inflammation Culture filtrates from these two isolates on sigmoidoscopy have been studied. An behaved identically to the caecal suspen- initial assessment of the symptoms, sig- sions including cross neutralisation of the moidoscopic appearance, rectal biopsy, tissue culture cytopathic effect with C. PANCREAS haematological and biochemical (in- sordellii anti-toxin. cluding seromucoids) parameters was Morphologically the caecitis differs Gut hormone profile in pancreatic disease made. Patients were treated with oral from human antibiotic-associated pseudo- disodium cromoglycate 200 mg qds or membranous colitis, but in the other H. S. BESTERMAN, T. E. ADRIAN, N. D. placebo in addition to their usual therapy aspects described here the hamster has CHRISTOFIDES, D. L. SARSON, S. R. BLOOM, for one month. The alternative treatment proved a suitable model for the investiga- C. N. MALLINSON, A. PERA, M. SOUTH, R. Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from The British Society of Gastroenterology A445

MODIGLIANI, AND S. GUERIN (Department with chronic pancreatitis, eight patients PP were demonstrated in all patients of Medicine, Royal Postgraduate Medical with pancreatic cancer, and nine control studied except one, the major form cor- School, London, Department of Gastro- subjects who were being investigated for responding to the elution position of PP enterology, Greenwich District Hospital, suspected pancreatic disease and found standard (M wt 4300), whereas the minor London, Division of Gastroenterology, to be normal. Trypsin levels were (mean + form eluted in similar position to cyto- Ospedale Mauriziano, Turin, Italy, Depart- SEM): controls 31-16 ± 6-5; pancreatic chrome C (M wt 12000). All immuno- ment of Surgery, St. George's Hospital, cancer 4-8 ± 1-2; chronic pancreatitis 22-6 reactive peaks demonstrated were London, and Hopital St Lazare, Paris Xe, 5 8 g/ml. suppressed in patients studied with France) Different abnormalities of gut Trypsin levels in pure pancreatic juice of somatostatin infusion. hormone release are found in diseases patients with pancreatic cancer were sig- Delineation of multiple forms of cir- affecting different parts of the gastro- nificantly lower than those in controls (p = culating tumour-secreted hormones and enteropancreatic tract. Pancreatic function 0.003). The levels in chronic pancreatitis their detection in plasma provides a is modulated by gut hormones probably by were not significantly different from those further aid for the diagnosis of endocrine complicated feedback mechanisms. of controls. They also showed no correla- neoplasms. Wehavethereforeinvestigated 17 patients tion with the mean tryptic activity with proven pancreatic insufficiency, 28 measured in duodenal juice after a Lundh patients with chronic pancreatitis (without test meal. insufficiency) and 15 healthy subjects. Our results suggest that the measure- Origin of serum trypsin: evidence for Gut hormones were measured after a ment of trypsin in pure pancreatic juice is intestinal reabsorption standard breakfast. a helpful test in the diagnosis of pan- The release of gastric inhibitory poly- creatic cancer but is less helpful in the G. LAKE-BAKAAR, G. SMITH-LAING, AND peptide and gastrin was similar in all assessment of chronic pancreatitis. How- J. A. SUMMERFIELD. Introduced by Sheila groups. In all patients with pancreatic ever, when lactoferrin levels were Sherlock (Department of Medicine, The disease, there were significantly raised measured in addition to trypsin, all Royal Free Hospital, Hampstead, London) concentrations of motilin (basal 78 ± 8, patients with chronic pancreatitis could be The origin of serum trypsin in man is peak 112 ± 12 pmol/l) and of entero- distinguished from controls and from unknown. Animal studies have suggested glucagon (basal 55 ± 7, peak 86 ± 10 those with pancreatic cancer. an enteropancreatic circulation and we pmol/l), compared with normal subjects have investigated this by estimating the (motilin basal 43 ± 6, peak 58 6, P < trypsin concentration in the portal venous 0-001; enteroglucagon basal 35 8, peak Chromatographic analysis of tumour- system using a sensitive radioimmuno- 49 9, P < 0.01). produced hormones assay.

There was a gross failure of release of In seven patients following transhepatic http://gut.bmj.com/ pancreatic polypeptide in patients with M. G. BRYANT, S. R. BLOOM, T. E. ADRIAN, sclerosis of oesophageal varices, blood was pancreatic insufficiency (basal 15 ± 5, AND C. N. MALLINSON (Department of sampled along the course of the splenic, peak 36 ± 8 pmol/l), compared with Medicine, Royal Postgraduate Medical portal, and superior mesenteric veins. The normal subjects (basal 27 ± 6, peak 147 School, London and Gastrointestinal Unit, mean concentration of trypsin at the distal + 24 pmol/l, P < 0.001). Thus the Greenwich District Hospital, London) end of the splenic vein (186 ng/ml SEM + hormonal changes found in pancreatic in- Considerable delay still occurs in the 34) differed significantly from that deep in sufficiency all tend to minimise the gastro- diagnosis of patients with pancreatic the superior mesenteric vein (245 ng/ml

intestinal dysfunction. Pancreatic poly- endocrine tumours, thus there is a need for SEM + 37; t = 2*412 P 0-05) and in the on September 24, 2021 by guest. Protected copyright. peptide, a hormone known to inhibit reliable plasma measurement of the portal vein (217 ng/ml SEM + 35-45; t = pancreatic enzyme production, is very hormones produced. However, little work 2*068 P 0-05). low, while motilin, which modulates gut has been done to characterise the different In six patients, following stimulation transit, and enteroglucagon, which plasma forms of these tumour hormones. with CCK-PZ and secretin, samples were appears trophic to the mucosa, are both Using Sephadex G50, we carried out collected at one minute intervals from raised. chromatographic studies on plasma from either the superior mesenteric, portal, or seven patients with the glucagonoma and splenic veins. Samples from the superior six with the VIPoma syndromes, all of mesenteric and portal veins showed an Radioimmunoassay of trypsin in pure pan- whom had raised plasma pancreatic poly- increase three to four times above fasting creatic juice peptide (PP) concentrations. Two major level, four to eight minutes after stimula- peaks of pancreatic glucagon (PG) im- tion; simultaneous peripheral blood S. S. FEDAIL, P. R. SALMON, R. F. HARVEY, munoreactivity were observed, one eluting samples showed much smaller changes. P. B. BROWN, AND A. E. READ (University identically with PG standard (M wt 3500) Samples from the mid-portion of splenic Department of Medicine, Bristol Royal and the other between cytochrome C and vein showed only a one- to two-fold rise Infirmary) We have measured trypsin insulin-1251 (approximate M wt 9000). and these changes were paralleled in and trypsinogen in pure pancreatic juice The immunoreactive content of each peak peripheral blood. Amylase (Phadebas) obtained endoscopically from a series of varied from patient to patient (range 100 % estimations showed similar but less pro- patients with suspected pancreatic diseases 9000 M wt to 100% 3500 M wt). nounced changes. using radioimmunoassay (Hoechst Phar- For VIPoma patients, a broad peak of We conclude that circulating trypsin is maceutical/Behring Institute Kit). We also immunoreactive VIP was observed sug- derived principally from the superior compared these with pure pancreatic juice gesting the presence of several related mesenteric vein and suggests the presence lactoferrin levels. There were 17 patients molecular forms. Two distinct peaks of of an enteropancreatic circulation. Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from A446 The British Society of Gastroenterology Plasma trypsin in the diagnosis of steator- pancreatitis. individual figures did not suggest that any rhoea due to chronic pancreatitis In 18 healthy volunteers, the mean particular predisposing factor accounted fasting level was 268 ± SD 71 nd/ml; the for this variation. T. E. ADRIAN, H. S. BESTERMAN, C. N. mean trypsin concentration at 30 minutes Analysis of the distribution of the 214 MALLINSON, C. GALAROTIS, AND S. R. BLOOM (279 ± 70), one hour (281 ± 70) and two patients within the defined population (Department of Medicine, The Royal hours (290 ± 79) after stimulation showed area has shown that there are considerable Postgraduate Medical School, London, and no significant difference from fasting local variations in the incidence of acute Gastrointestinal Unit, Greenwich Hospital, levels. pancreatitis. In three wards, the number London) Measurement of tryptic activity Of the 35 patients, 11 with no pan- of cases was significantly greater than in plasma is not possible because of the creatic disease, one with recurrent pan- might be expected by chance. These areas presence of specific circulating inhibitors. creatitis and one with cancer, a normal receive their tap water supply exclusively We have estimated plasma trypsin by use response was found. from Burton Joyce pumping station. Its of a simple radioimmunoassay (Hoechst In six patients, two with chronic renal chemical composition differs markedly UK Ltd) specific for this human endo- failure, one , one car- from other local supplies, and has a high peptidase. cinomatosis, and two alcoholic , calcium content. Fasting plasma trypsin was measured in trypsin levels remained raised before and 17 healthy subjects and 30 patients with after stimulation (range 460 to 1100 chronic pancreatitis, 13 having marked ng/ml). New specific long-acting somatostatin steatorrhoea and 17 having x-ray evidence In 11 patients, two with carcinoma of analogues in the treatment of pancreatic ofcalcification or ERCP abnormalities but the pancreas and nine chronic pancrea- endocrine tumours no overt exocrine deficiency. Fasting titis (steatorrhoea in five), constantly low plasma trypsin in the controls was 11 9 ± levels were found (range 0 to 105 ng/ml). S. R. BLOOM, T. E. ADRIAN, A. J. BARNES, 1 1 nmol/l (mean + SEM), with pancreatic In five patients stimulation caused a R. G. LONG, J. HANLEY, C. N. MALLINSON, disease without steatorrhoea 13-8 + 3-5 rise in serum trypsin of greater than 75% J. E. RIVER, AND M. R. BROWN (Depart- and with exocrine deficiency 0 7 + 0 3. above fasting level; four had duct obstruc- ment of Medicine, Hammersmith Hospital The mean fasting trypsin level in 12 tion (two cancer, one pseudocyst, one and Greenwich Hospital, London, and Salk patients with active coeliac disease was pancreatic duct stones) and one steator- Institute, San Diego, USA) Somatostatin 14-2 ± 1 8 and in 12 patients with tropical rhoea following gastroenterostomy. is a powerful inhibitor of pancreatic sprue 12-5 ± 1-2. On ingestion of a The fasting trypsins in 20 out of 21 hormones. Its therapeutic use for endo- standard breakfast there was a small but patients with pancreatic disease were crine tumours has been impeded by its significant rise in plasma trypsin concen- abnormal. lack of specificity and very short action of http://gut.bmj.com/ tration of 15 ± 4% (p < 0-005) in the We conclude that in the diagnosis of only a few minutes. We have used three normal subjects. However, trypsin levels pancreatic disease, the pattern of serum recently developed selective analogues in were unaffected by an infusion ofcaerulein trypsin levels after Lundh meal is not patients with functioning metastatic gastri- (a cholecystokinin analogue) in five superior to fasting trypsin estimations nomas, PPomas, glucagonomas, and normal subjects, at a dose known to except in cases of pancreatic duct obstruc- VIPomas. cause maximal pancreatic enzyme secre- tion. D Try8 D Cys14 somatostatin infused tion. Thus it appears that secretion of intravenously at 8 tg/min caused marked pancreatic enzymes into the gut is not hormone suppression. In a PP/VIPoma on September 24, 2021 by guest. Protected copyright. accompanied by much rise in circulating Variations in the incidence and the spatial case, for example, mean basal VIP fell trypsin. distribution of patients with primary acute from 198 + 6 to 43 + 3 pmol/l, while PP The simple measurement of trypsin in a pancreatitis in Nottingham, 1969-1976 fell from 403 ± 14 to 52 + 3 pmol/l. In a single blood sample, fasting or post- glucagonoma, also producing PP, gluca- prandial, is thus of great assistance in the J. B. BOURKE, J. A. GIGGS, AND D. S. EBDON gon fell from 1800 + 26 to 282 + 13 differential diagnosis of steatorrhoea. (Departments of Surgery and Geography, pmol/l, whilePPfell from21 ± 0 3to 6-4 + The University ofNottingham) Data have 0'2 nmol/l. D Try8 and D Try8 D Cys14, been studied on the 332 patients admitted Des1'2,4,5,12,13 somatostatin analogues Assessment of the value of changes in in their first attack of acute pancreatitis to had a dramatic prolongation of effect. A serum concentration of immunoreactive the Nottingham Hospitals during the eight single 2 mg subcutaneous dose suppressed trypsin after a Lundh meal year period 1969-76. The City of Notting- glucagon 65% for three hours, with a ham and the four adjacent former urban resulting reduction in hyperglycaemia. A G. LAKE-BAKAAR, S. MCKAVANAGH, T. districts had a population of 469 720 in larger dose (5 or 10 mg) resulted in greater WOOD, M. REDSHAW, AND J. A. SUMMERFIELD 1971, and an attempt was made to obtain hormone suppression ( < 80%), which was Introduced by Sheila Sherlock (Royal details of all patients from within this well maintained for over 12 hours. No Free Hospital, London, and Hoechst Phar- defined population area; 214 patients came side-effects were noted. maceutical Research Laboratories, Milton from this area. The annual incidence Thus all three analogues appear effective Keynes, Buckinghamshire) We have varied five-fold during this eight year in suppressing tumour hormone produc- studied the changes in serum trypsin period from a peak incidence of 100 per tion. The new long-acting analogues were following pancreatic stimulation with a million population in 1975 to a lower active for at least 12 hours and, being Lundh meal in 18 healthy volunteers and incidence of 21 2 per million in 1970. effective by twice daily subcutaneous 35 hospitalised patients including five with There was no detectable pattern behind injections, offer a new therapeutic carcinoma of the pancreas and 12 with the variation and consideration of the approach for the treatment of endocrine Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from The British Society of Gastroenterology A447 tumours and perhaps other hormone J. CROKER AND P. COTrON (Middlesex with the . excess states. Hospital, London) Cimetidine appears to The fasting neurotensin level in duo- be useful in the prevention and control of denal ulcer patients was 24 ± 3 pmol/l bleeding from acute erosive lesions in the and was not different in either post- PLENARY SESSION upper gastrointestinal tract in severely operative group. The rise in neurotensin stressed patients, but its efficacy in was minimal in both the preoperative and haemorrhage in non-stressed patients has postoperative asymptomatic groups, but Instant outpatient endoscopy for patients not been fully evaluated. The effectiveness was very large in the patients with dump- with upper abdominal pain of cimetidine was therefore examined in a ing symptoms (20 minutes increment 4 + multicentre prospective double-blind con- 4 pmol/l, 8 ± 5 pmol/l, 43 ± 6 pmol/l A. K. BEAVIS, S. LA BROOY, AND J. J. trolled study. One-hundred-and-one respectively, P < 0-001). MISIEWICZ (Department of Gastroenter- patients with acute upper gastrointestinal The pathophysiology of the dumping ology, Central Middlesex Hospital, London) haemorrhage within 24 hours ofadmission syndrome is incompletely understood. We Many patients are referred for the investi- were divided into groups according to age have shown that neurotensin is released in gation of upper abdominal pain. Several and severity ofhaemorrhage and allocated excess in this syndrome. Neurotensin, a attendances are needed for clinical and randomly to treatment either with oral hormone with powerful hypotensive diagnostic procedures. We have investi- cimetidine 400 mg initially and 200 mg six actions, may thus be responsible for some gated the feasibility and patients' accept- hourly for seven days or placebo. Diag- of the previously unexplained aspects of ance of endoscopy at the first hospital nosis was established endoscopically with- this condition. visit. in 12 hours of admission. Haemorrhage Patients referred with upper abdominal recurred or continued in 22 patients: pain attended fasting at a special clinic. 27 3 % (6/22) patients under the age of 60 Grey-scale ultrasonography in cholestatic After history, clinical examination, and years rebled on cimetidine and 13*6 % jaundice blood sampling, upper GI endoscopy was (3/22) on placebo. In those over 60, performed with a P2 Olympus panendo- 17-8% (5/28) on cimetidine and 27-6% A. G. VALLON, W. R. LEES, AND P. B. COTTON scope, using only topical pharyngeal (8/29) on placebo had recurrent haemor- (Gastrointestinal Unit and Department of anaesthesia. The patients were informed of rhage. Twelve of these required surgery. Clinical Measurement, The Middlesex the findings and were able to leave im- Treatment with cimetidine had no signifi- Hospital, London) Grey-scale ultrasono- mediately after the procedure, the whole cant effect on the outcome of the haemor- graphy was performed without clinical session lasting on average 50 minutes. A rhage and the recurrence rate showed no information in a prospective study of 55 letter with the findings and suggested improvement on comparison with studies jaundiced patients; 41 were eventually management was sent to the GP the same on untreated patients. The results suggest proved to have an extrahepatic 'surgical' http://gut.bmj.com/ day. that cimetidine has no role in the pre- cause, and 15 had intrahepatic disease. One-hundred-and-twenty-one patients vention of rebleeding in acute upper Satisfactory images were obtained in 54 (71 male, 50 female, aged 17-81 years) were gastrointestinal haemorrhage in unstressed patients, and the calibre was studied during six months. Endoscopy was patients. The management of these correctly reported in 53. Correct medical/ attempted in 120 and was successful in 110, patients should continue according to surgical classification was made in 52 only eight patients not tolerating the endo- established clinical principles. (95 %). All 14 medical cases were correctly scope, with two technical failures. Thirty- identified. Two patients with gallstones six examinations were normal, while the (one with a normal sized duct) were in- on September 24, 2021 by guest. Protected copyright. lesions found included two gastric cancers, Neurotensin and the dumping syndrome correctly classified as medical. A specific four gastric and four duodenal ulcers, and and correct disease diagnosis was given in 11 hiatus . A. M. BLACKBURN, S. R. BLOOM, F. H. EBEID, five of the 14 medical cases (one meta- The acceptability of the procedure was AND D. N. L. RALPHS (Department of stases, four cirrhosis) and in 23 of the 41 high as measured by verbal and analogue Medicine, Hammersmith Hospital, London, surgical cases (12/14 pancreatic cancer, scales. The findings were compared with and Department of Surgical Studies, The 5/14 bile duct stones, 5/5 bile duct com- barium rDeal examination. This study Middlesex Hospital, London) Neuroten- pression, 1/3 bile duct cancer). shows that instant outpatient endoscopy sin is a recently discovered hypotensive Ultrasonography is safe and reasonably is practicable and acceptable to the hormone found in large concentrations in cheap. It should be the first imaging in- patient. It saves repeated visits to hospital. the endocrine cells of the mammalian vestigation in jaundiced patients, pro- ileum. No human plasma neurotensin viding remarkable diagnostic accuracy assay has yet been reported. and important guidance for further Is there a role for cimetidine in the manage- We have developed a radioimmunoassay management. ment of acute upper gastrointestinal using antibodies raised to pure synthetic haemorrhage? neurotensin, sensitive to 5 pmol/l plasma. No cross-reaction was seen with any other Mechanisms of diarrhoea production in S. LA BROOY AND J. J. MISIEWICZ known gut hormone. patients with inflammatory disease of the (Central Middlesex Hospital, London), Three groups of patients were studied colon J. EDWARDS AND P. M. SMITH (Llandough after 75 g oral glucose: 20 preoperative Hospital, Cardiff), s. J. HAGGIE, L. duodenal ulcer patients, 20 patients after P. C. HAWKER, K. MASHITER, J. MCKAY, AND LIBMAN, M. SARNER, AND J. H. WYLLIE surgery for duodenal ulceration without L. A. TURNBERG (Department ofMedicine, (University College Hospital, London), dumping, and 19 postoperative patients Hope Hospital (University of Manchester Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A448 The British Society of Gastroenterology School of Medicine), Salford) Possible ments of Radiology and Endocrinology, present in 63% of IBS but only 15% of mechanisms of diarrhoea in patients with Hammersmith Hospital, London) The OGID patients. All four symptoms were colonic inflamrmatory disease include; cause of the rash in the glucagonoma absent rarely in IBS (6%) but commonly impaired electrolyte absorption, altered syndrome is unknown but resembles that in OGID (52%). Two other symptoms intestinal permeability, and active electro- in zinc deficiency syndromes. In spite of commoner in IBS (but P just > 0-05) were lyte secretion. These possibilities were inconclusive changes in zinc levels in passage of mucus and feelings of incom- investigated using the in vitro 'short- plasma, skin, and hair, in a patient with a plete evacuation. All six symptoms were circuit' preparation of Ussing and Zerahn. severe rash associated with a malignant present in six IBS but only one OGID Mucosal segments obtained at resection glucagonoma, oral zinc sulphate was given patient. from six patients with ulcerative colitis, in three separate courses. During each We conclude that the use of specific three with Crohn's colitis, were stripped, course the plasma glucagon and amino questions can increase diagnostic con- clamped between Perspex half chambers acid levels were grossly abnormal but the fidence and reduce the need for investiga- and bathed with oxygenated isotonic rash cleared, to recur between each course. tion in patients with abdominal symptoms. buffer. Results were compared with The patient then underwent selective previously obtained normal values. hepatic artery catheterisation on two Electrical potential difference and short occasions when Sterispon fragments of Indomethacin-responsive diarrhoea in irrit- circuitcurrent (Isc) were significantly lower successively larger diameter were injected able bowel syndrome than in normal tissues (PD = 8-5 ± 1-4, into theartery, bringing about occlusion of cf 19-4 ± 1-06 mv, Isc = 104 ± 15-6, cf arterial blood supply to all demonstrable J. RASK-MADSEN AND K. BUKHAVE (Gastro- 207 + 10 6 ,uA. Cm-2). Tissue resistance, liver metastases. This was followed by a enterology Department C, Herlev Hospital, reflecting tissue permeability, was un- dramatic fall in plasma glucagon and University of Copenhagen, Denmark) changed. pancreatic polypeptide levels. The patient Irritable bowel syndrome (IBS) is at best Isotopic flux studies delineated two has gained weight steadily since and now a negative diagnosis, made by the groups: those receiving steroids, without requires less insulin than before and no systematic exclusion of all other differ- diarrhoea, showing normal sodium and oral zinc. Thus the rash can be cleared ential diagnoses. In some cases of IBS, independently of plasma glucagon and diarrhoea is a prominent feature, but even chloride absorption (J Neat = 5-89 + 0*79, amino acid levels, and zinc appears to then the syndrome probably encom- have some role in its production. Embo- passes a range of pathophysiological cf 6-93 0 43 lisation of and mechanisms. Recent perfusion studies ± ,uEq.Cm-2.h-1J CNt = 2*24 secreting slowly growing metastases has been shown to be a useful suggest that the small intestinal epithe- + 1*4, cf 2*35 ± 0-78 jsEq.Cm-2.h1- n = palliative procedure. lium may be prestimulated by some un- http://gut.bmj.com/ 6); those not receiving steroids, with identified biological agent causing marked diarrhoea, showing reduced secretion of Na+ and Cl-, primarily due to Na Towards more positive diagnosis of the abnormally high plasma-lumen fluxes. sodium = 1 absorption (J Net 96 + 0 79 irritable bowel Since infusion of prostaglandin E (PGE) PEq.Cm-2.h-1 n = 6) due entirely to can simulate all the symptoms of the W. G. THOMPSON, A. P. MANNING, AND K. W. syndrome and appears to mediate reduction in mucosal to serosal flux (J Nas HEATON (University Department ofMedi- diarrhoea by increasing the named fluxes,

cine, Royal Infirmary, Bristol) The classic we have measured PGE2 in fasting jejunal on September 24, 2021 by guest. Protected copyright. = 5.0 + 0-88, cf 9-81 ± 0-6 ,uEq.Cm-2. symptoms of irritable bowel syndrome secretions of 12 patients with chronic h-1). Passive sodium permeability was (IBS)-abdominal pain, , diarrhoea classified as IBS associated with unaltered. Net chloride absorption re- and/or diarrhoea-are also found in diarrhoea. mained unchanged. There was no active patients with organic gastrointestinal Immunoreactive PGE2 levels of 10 secretory process. disease (OGID). Symptoms specific to patients were within the narrow range of We pro- conclude that the major defect IBS have been suggested but not estab- 13 controls (130 + 16 pg/ml, mean ± SD), ducing diarrhoea is diminished active lished and, unsatisfactorily, diagnosis is sodium and were consistently raised in two absorption (probably reversible usually based on negative investigations. patients (340 and 330 pg/ml). As PGE- by prednisolone), and not permeability Symptoms reputed to be IBS-specific biosynthesis is inhibited by indomethacin, changes or active secretion. were sought by questionnaire in 109 un- a 14 days' trial of oral indomethacin was selected outpatients referred with carried out. Solidification of the stools abdominal pain and/or change in bowel and a marked reduction of stool volume CLINICAL habit. Final diagnosis, confirmed 17-26 and frequency was noted within 72 hours months later at 'blind' review of case of medication, while relapse with 15-20 records by two gastroenterologists, was watery diarrhoeas occurred after with- Treatment of malignant pancreatic gluca- definiteIBSin 32 and definite OGID in 33. drawal. Subsequently, an intensive design gonoma: effect of zinc on the rash and Symptoms commoner in IBS were for evaluation of drug effect was applied hepatic arterial embolisation on liver abdominal distension (P < 0-01), pain in a double-blind study of one case. Indo- metastases relief after defaecation (P < 0.01), more methacin proved to be effective in pre- frequent defaecation coinciding with on- venting diarrhoea compared to placebo. C. N. MALLINSON, J. HANLEY, D. J. ALLISON, set of pain (P < 0.01), and looser stools at Thus, indomethacin blockade seems to T. E. ADRIAN, AND S. R. BLOOM (Greenwich onset of pain (P < 0-001). Three or all of have important therapeutic implications, District Hospital G.L Unit and Depart- these four discriminating symptoms were not only in certain neoplastic and inflam- Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

The British Society of Gastroenterology A4491 matory diseases, but also in irritable . Its value in diagnosing as abnormal (cancer two, pancreatitis colon-type diarrhoea associated with is already reported. The aim two). Among the total of 42 patients with raised levels of PGE2 in the jejunal of this continuing study is to assess its pancreatitis, ultrasound correctly idenu- secretions. potential in diagnosing obstructive fied or excluded a local mass lesion in 40. jaundice. Seventy-eight per cent of the reports in the Sequential image frames of one minute whole study were ranked as certain, and Simple technique for measuring liver blood duration are taken by gamma camera over all were correct. Ultrasound provided flow: intrasplenic injection of 133Xenon the first hour following intravenous in- more valuable information than the jection of 4m Ci 99m Tc pyridoxylidene- clinical assessment in 60% of patients. P. H. M. LAM, R. T. MATHIE, A. M. HARPER, glutamate. Playback of these images in Grey-scale ultrasonography is an excellent AND L. H. BLUMGART (University Depart- 'cine mode' enables anatomical definition. screening method in patients with known ment of Surgery, Glasgow Royal Infirmary This will be demonstrated briefly on film. or suspected pancreatic disease. and Wellcome Surgical Research Institute, Functional curves generated by monitor- University of Glasgow) The inert gas ing over liver, , bile ducts, and clearance technique has been used to duodenum add quantitative dimension. measure liver blood flow (LBF) in animals Each cholescintogram was interpreted and recently in man. This involves direct 'blindly' by the same two observers. Use of scintiscanning for the diagnosis of intraportal injection of the isotopes. Intra- Of 24 patients studied to date 10 had : a comparative trial splenic injection of 133-Xenon was in- proven biliary tract obstruction. All 10 with contrast radiology vestigated in dogs, as this would allow were correctly diagnosed by this technique. LBF measurements to be made at the In the remaining 14 patients cholescinti- A. W. HALL, M. L. WISBEY, F. HUTCHINSON, time of splenoportovenography. graphy was incorrectly interpreted as R. A. B. WOOD, AND A. CUSCHIERT (Depart- Hepatic clearance was recorded with a showing duct obstruction in only three. ment of Surgery and Medical Physics, scintillation crystal after intraportal in- Two patients with severe hepatitis failed Ninewells Hospital, Dundee) Accurate jection of 133-Xenon. This was then to excrete the isotope over 24 hours, diagnosis of gallbladder disease allows repeated with direct injection of the giving the false impression of total duct early surgical intervention, reducing mor- isotope into the splenic pulp. A multi- obstruction, and in the third with post- bidity, with no increase in mortality. exponential clearance curve was obtained hepatic hyperbilirubinaemia there was a Clinical criteria are incorrect in 15 %. by either route of injection and the fast simple anatomical error. Thirty-eight patients with acute right component was used for flow calculations. Cholescintigraphy is useful in diag- upper abdominal pain were studied by

The total LBF in the portal vein and nosing extrahepatic obstruction, par- contrast radiology (intravenous cholangio- http://gut.bmj.com/ hepatic artery at the time of the clearance ticularly if combined with liver biopsy. graphy 30 cases, oral cholecystography recordings was also monitored with Interpretation may be difficult in patients eight) and hepatobiliary scanning after electromagnetic flowmeters. with severe liver dysfunction. injection of Tc 99m pyridoxylidene gluta- Twenty-eight pairs of observations mate. Absence of gallbladder opacifica- were made in 10 dogs. Both routes of tion on scan by three hours was deemed injection gave almost identical flow values Prospective study of pancreatic ultrasono- positive. Conventional radiological over a wide range of flow rates. The ratio graphy criteria were used and diagnosis confirmed

of the flow value from splenic injection to by laparoscopy or laparotomy. Thirteen on September 24, 2021 by guest. Protected copyright. that from intraportal injection was 0-98 + W. R. LEES, A. G. VALLON, M. E. DENYER, had acute cholecystitis, 12 chronic chole- 0-12 (SD). The electromagnetic flow- S. P. VAHL, AND P. B. COTTON (Depart- cystitis, and 13 no gallbladder pathology. meters finctioned satisfactorily in eight ment of Clinical Measurement and Gastro- Results were expressed as predictive dogs and correlated well with the Xenon intestinal Unit, The Middlesex Hospital, values, both when the tests were positive, technique. London) We have studied 124 patients indicating gallbladder disease, and when Intrasplenic injection is a simple way to prospectively with a Nuclear Enterprises negative, excluding cholecystic pathology. measure LBF and initial results have diasonograph with grey scale facility, Results were as follows: (1) predictive shown it to be applicable in man. using diagnostic criteria established in a value of a positive test for gallbladder previous study of 94 patients. Ultrasound disease was 91 % for contrast radiology reports were given with knowledge of the but 100% for scans; (2) predictive value of Clinical value of 99m technetium pyri- clinical context, and conclusions were a positive test for acute cholecystitis was doxylideneglutamate imaging in hepato- classified as certain or probable. Five 75 % and 77 % for contrast radiology and biliary disease studies failed because of excessive bowel scans respectively; (3) in excluding acute gas, and four patients were excluded from cholecystitis the predictive value of a D. N. CLARKE, P. W. BRUNT, G. DASCOMBE, analysis through lack of a satisfactory normal gallbladder scan was 100% as A. F. MACDONALD, N. A. G. MOWAT, AND independent diagnosis. Twenty-two opposed to 61 % for x-ray examination. P. F. SHARP (Department of Medicine, patients were already known to have We conclude that hepatobiliary scinti- Department of Biomedical Physics and relapsing pancreatitis, and 98 were scan- scanning and contrast radiology give Bioengineering, Department of Radiology, ned as problems in diagnosis. Of these 98, similar results for the diagnosis of cystic University of Aberdeen, Scotland) 99m ultrasound correctlv identified all 33 with duct patency. Scanning has fewer tech- Tc pyridoxylideneglutamate imaging pancreatic disease, and correctly classified nical failures. A negative test excludes (cholescintigraphy) is a simple non- them as cancer (13) or pancreatitis (20). acute cholecystitis. A positive scan con- traumatic method of visualising the Four normal patients were falsely reported firms gallbladder disease. Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A450 The British Society of Gastroenterology Palliative transhepatic catheter manage- Postoperative small bowel : con- patients who were asymptomatic before ment of obstruction by servative management with intravenous the perforation, 12 are at follow-up still tumour hyperalimentation asymptomatic with a symptom-free interval of 25 months. H. HERLINGER AND E. RING (St. James's R. L. BLACKETIT AND G. L. HILL (University If routine definitive surgery had taken University Hospital, Leeds, and Hospital Department of Surgery, The General place at the time of the perforation, 48 % University of Pennsylvania, Philadelphia, Infirmary at Leeds, Leeds) A consecutive of the patients would have undergone un- USA) Fine needle transhepatic cholan- series of 24 patients who developed entero- necessary operative treatment. It would giography is an established and safe cutaneous small bowel fistulas within two appear that a policy of simple suture of a method of diagnosing the existence and weeks of surgery was studied. duodenal perforation with careful clinical causation of obstructive jaundice. In Of the 24 patients, average age 39 + 18 follow-up is justified, even though patients patients in whom carcinoma is shown to years, six had duodenal fistulas and 18 with previous dyspepsia are more likely to be the cause of obstruction and in whom jejunoileal fistulas. In all, the pathology require a definitive operation in the future. resective surgery is not considered feasible was benign and 12 had inflammatory (tumour size, patient's age or state) pallia- bowel disease. In 17 patients the daily What alterations in the management of tive catheter management is now available. output was greater than 500 ml. patients with acute upper gastrointestinal A catheter and guide wire are introduced Management involved an initial period (UGI) bleeding are likely to influence transhepatically into the opacified biliary of resuscitation with blood, albumin, and outcome? system, the tumorous portion of the crystalloid, followed by intravenous hyper- common bile duct is dilated, and a larger alimentation and total bowel rest. Stoma M. W. DRONFIELD AND M. J. S. LANGMAN catheter is taken as far as the duodenum management was by a closed collection (Department of Therapeutics, City and left in situ. The size of the lumen and system using skin barriers and drainable Hospital, Nottingham) The overall mor- the presence of numerous side holes in the collection bags. tality rate in patients admitted to hospital catheter wall ensure adequate hepatofugal Spontaneous closure occurred in 15 with acute UGI bleeding has not changed bile drainage. Twelve patients have now patients (63%) in an average time of 28 over the past 30 years, and improved been treated in this way, two of them for days. Six patients underwent elective diagnostic techniques do not seem to eight months. surgical treatment after 56 days because of influence outcome. failure to close. Overall closure was 17 We have analysed the causes of death in (71 %) and the mortality five (21 %). a prospective study of 484 consecutive Adverse prognostic factors were faecal patients admitted to hospital with acute Primary closure of common bile duct after output > 500 ml/day (mortality 29%); UGI bleeding over 28 months. Fifty-five http://gut.bmj.com/ exploration with a choledoscope inflammatory bowel disease (mortality (11.4%) of these patients died, but 33 of 33%) and weight loss > 20% (mortality these deaths were unavoidable, being due M. A. CHAUDARY AND B. S. ASHBY (South- 50%). The results agree with other recent mainly to inoperable malignant disease or end General Hospital, Southend) The series which show reduced mortality and to coincident medical disorders. technique of operative choledochoscopy morbidity with conservative management. All but four of the remaining 22 deaths has been described by Ashby. Twenty-six occurred in patients over 70 years old. patients with biliary calculi underwent ex- Two deaths were due to sudden uncon- ploration of the common bile duct with Natural history of perforated duodenal trollable bleeding shortly after admission, on September 24, 2021 by guest. Protected copyright. choledochoscopy and primary closure of ulcers treated by simple closure six were due to continued bleeding in the duct. A comparative group of 26 patients thought too old for operation, and patients underwent conventional supra- J. K. DRURY, A. J. MCKAY, AND S. N. JOFFE 14 occurred postoperatively. The mortality duodenal choledocotomy followed by T- (University Department of Surgery, Royal rate in patients over 70 years old subjected tube drainage of the duct. Infirmary, Glasgow) The initial manage- to emergency surgery for benign condi- The mean hospital stay of patients ment of acute perforation of duodenal tions was 11 out of 38 (29%) compared undergoing choledochoscopy was 8-6 ulcers at the Glasgow Royal Infirmary has with one out of 36 (3 %) in patients under days (range five to 13 days) compared with been a simple operative closure of the 60. 12-6 days (range eight to 24 days) for the perforation and then a 'wait-and-see' The treatment of patients under 60 with conventional group. After choledocho- attitude. A total of 50 patients have been acute UGI bleeding is satisfactory with a scopy 11 patients (42.3 %) went home interviewed three to 80 months after very low hospital mortality. The large within one week. There were two cases of operative closure of the acute perforation majority of potentially avoidable deaths retained stones in the conventional group of a duodenal ulcer. There were 36 occur in the elderly and outcome could and one case of biliary . One case symptomatic patients, with dyspepsia perhaps be improved by: (1) a more con- with primary closure of the common bile suggestive of a peptic ulcer for 9 9 years servative surgical approach in the elderly, duct required drainage of a bile collection before their duodenal ulcers perforated. and (2) the development of non-surgical in the subhepatic space. Postoperative At follow-up, 24 of these patients were methods of controlling acute UGI bleed- sepsis was equal with one case of chest still symptomatic, and the symptom-free ing-for example, laser photocoagulation. and would cause in each group. interval postoperatively was 9 9 months. Operative choledochoscopy apparently Only 12 who were symptomatic before the shortens the patient's convalescence and perforation are asymptomatic at present, Cancer presenting to hospital as 'un- hospital stay after exploration of the with a symptom-free interval post- explained' acute abdominal pain-a study common bile duct. operatively of 19-7 months. Of the 14 of 98 cases Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

The British Society of Gastroenterology A451

F. T. DE DOMBAL, JANE C. HORROCKS, SUSAN height of tumour above the anus (mean- often of secondary carcinoma and 10 % of E. CLAMP, AND S. MATHARU (University M 8 5 cm, B 8*4 cm) and length of history 50 such patients had AFP levels above 10 DepartmentofSurgery, St. JamesHospital, (mean-M 10-8 months, B 11 6 months). IU/mI. Leeds) The 'standard' insidious presenta- Symptoms of anorectal bleeding and Documentation of an AFP level above tion of various forms of gastrointestinal increased bowel frequency occurred more 10 IU/ml is thus of great value in both cancer is well documented. It is also well- commonly in group M and tumour pro- detecting and excluding the development recognised that gastrointestinal cancer lapse in group B. ofHCC in cirrhosis (1 % false positive, 3% may present occasionally as an emergency In palpable tumours induration was false negative), but is less useful (10% withacute obstructionorperforation of the never noted in group B (0/74 but was com- false positive, 42% false negative) in bowel. During studies of acute abdominal monly felt in group M (41/82). Malignant distinguishing between primary and pain, however, we became impressed with tumours were more frequently circum- secondary tumours arising in patients the frequency with which cancer pre- ferential (39) than benign tumours (eight) without cirrhosis. sented to hospital in an 'intermediate' (X2 = 21X59, p < 0 001): they were also way-'de novo'-(as mild unexplained, larger (mean of maximum diameter M = acute abdominal pain). We therefore re- 5'9 cm SD 2-4, B = 3-8 cm SD 2 5, p viewed 4892 cases of acute abdominal < 0.001). Liver regeneration and dialysis pain to explore the extent of this clinical Incision biopsy was unreliable in con- problem. firming malignancy. The first such biopsy W. R. ELLIS, S. CALANGU, P. K. CHU, M. E. Of 4892 cases presenting to hospital in gave a positive yield of 45 % of group M, PHILLIPS, AND I. M. MURRAY-LYON Leeds, Edinburgh, Airedale, Bolton, and the second increased the yield to 68%, (Department of Gastroenterology and Copenhagen with hitherto undiagnosed and the third to 73% and the fourth to Medicine, Charing Cross Hospital, Lon- 'acute abdominal pain', 98 (2.0%) were 74%. don) Liver regeneration is essential for subsequently shown to have cancer. The We conclude that the detection of in- recovery from fulminant hepatic failure sites of cancer were mostly gastro- duration is an important clinical sign of (FHF). As haemodialysis is being in- intestinal, the commonest site being large malignant invasion within an adenoma. creasingly used for treatment of FHF we bowel. Only 28 of the 98 cases (28 6%) However, an accurate diagnosis is made decided to investigate the effects of presented as acute or only by histopathological examination of dialysis on liver regeneration in the rat. perforation. In the overall group, there the whole tumour. Male Wistar rats underwent standard were some 32 patients aged over 50 years, 70% partial hepatectomy and regenera- of whom 89 (6-7 %) had cancer. The tion was assessed at 24 hours by uptake of incidence of cancer in patients aged over 3H thymidine into liver DNA. Peritoneal LIVER-BILIARY http://gut.bmj.com/ 60 years at presentation was 77/972 dialysis was performed for four hours in (7-9%). Moreover, as continuing follow- test animals, between seven and 11 hours up is currently revealing further cancer Detection and exclusion of hepatocellular postoperatively using the commercial cases, these figures are-if anything- carcinoma in British patients using alpha dialysis solution Dialaflex 61, either plain underestimated. fetoprotein or enriched with 21 aminoacids in the Cancer is thus an unexpectedly common concentrations found in normal rat underlying cause in patients aged over 50 P. J. JOHNSON AND ROGER WILLIAMS (Liver plasma. years who present to hospital with acute Unit, King's College Hospital and Medical Mean DNA specific activity in animals on September 24, 2021 by guest. Protected copyright. abdominal pain. The data raise the School, London) Now that remission can dialysed against plain Dialaflex was question as to whether all such patients be induced in 30-40% of cases of hepato- 1261-9 cpm/,ug and differed significantly warrant urgent screening for cancer if no cellular carcinoma (HCC) with adria- (P < 0 001) from that in both undialysed other 'obvious' cause is found for their mycin, early and accurate diagnosis has controls (414*3 cpm/ug) and animals symptoms. become of more importance. In Great dialysed against the aminoacid-enriched Britain one of the major problems is in solution (354 9 cpm/,ug). Plasma ammonia determining when HCC has supervened and glucose levels were similar in all three Diagnosis ofmalignancy in rectal adenomas in patients with cirrhosis. In the present groups. Plasma levels of most amino- study serum alpha fetoprotein (AFP) acids were increased by dialysis with the P. ROBERTS AND J. P. S. THOMSON (St. levels were estimated using a sensitive plain solution but were unaltered or Mark's Hospital for Diseases of the radioimmunoassay in 35 patients with reduced by dialysis with the aminoacid Rectum, London) Rectal adenomas may cirrhosis complicated by HCC and 100 enriched solution. contain areas of malignant change. This with cirrhosis in whom malignancy was We conclude that liver regeneration is study compares the clinical and mor- excluded at necropsy. Thirty-four of 35 enhanced by peritoneal dialysis, an effect phological features of 128 sessile rectal (97%) of patients with HCC had levels abolished by adding aminoacids to the adenomas associated with malignancy above 10 IU/ml (median, 1000 IU/ml), dialysis solution. This finding may in part (group M) and 121 without malignancy whereas in those with cirrhosis alone only explain the encouraging clinical results of (group B) seen consecutively during a 10 1/100 (1 %.) patients had a level above 10 haemodialysis in FHF. year period. IU/mI. There was no difference between the In contrast, only 11/19 (58%) of groups in age (mean-group M 61-0 patients developing HCC in an apparently Oral and intravenous cholic acid clearance years, group B 63-7 years); sex (M-male normal liver had levels above 10 IU/mI. and serum bile acids compared in the 76, female 52; B-male 71, female 50); In this group the differential diagnosis is detection of chronic Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A452 The British Society of Gastroenterology

L T. GILMORE AND R. P. H. THOMPSON by measuring the change in gallbladder rings were sought and were absent in 10 (Gastrointestinal Laboratory, Rayne Insti- area during a carefully standardised oral children. tute, St. Thomas' Hospital, London) Para- cholecystogram. We studied 27 This evidence of copper overload sug- doxically, the rate of disappearance of patients and 27 controls with a normal gests that penicillamine might be useful in intravenously injected bile acid is not as cholecystogram, matched for age, sex, IHCC. sensitive an indicator of liver disease as weight, height, and race. In 14 of these the serum total bile acid concentration matched pairs, we also measured the rise (SBA). One explanation for this lies in the in serum cholecystokinin (CCK) by bio- Does obesity complicate chenodeoxycholic efficient first-pass extraction of bile acids assay. Maximum gallbladder emptying acid (CDCA) treatment of gallstones? by the liver. In the absence of portal- during the first postprandial hour was systemic shunting, recirculating endo- 32-7 ± 2-7% (mean ± SEM) in controls. A. REUBEN AND R. HERMON DOWLING genous bile acids absorbed from the In gallstone patients, it was 43-2 3-5 % (Gastroenterology Unit, Guy's Hospital intestine must all pass through the liver (p < 0-025), rising to 48-6 4-3% and Medical School, London) Obesity before reaching systemic blood, and their (p < 0-005) if the area occupied by the and cholelithiasis are both associated with clearance, unlike when given intra- gallstones was subtracted. The maximum bile supersaturated (SS) in cholesterol but venously, is therefore influenced more by postprandial rise in serum CCK (milli whether their effects are additive is un- liver cell function than blood flow. The Ivy dog units/ml) was 23-6 ± 6-3 in con- known. Furthermore, during weight re- clearance of an oral dose should behave trols, and 31-3 ± 9-8 in gallstone patients duction, bile of obese subjects allegedly similarly. (NS). We conclude that gallstone patients becomes more SS and in obese gallstone To test this, the clearance of cholic acid have increased gallbladder emptying in (GS) patients, bile remains SS despite given both orally and intravenously has response to food. 13-15 mg CDCA KgBW-1 day-'-doses been measured in 14 control subjects and which desaturate bile in the non-obese. 20 patients with anicteric chronic liver To extend these observations, we com- disease (ACLD). Although both clear- Liver copper levels in intrahepatic chole- pared biliary cholesterol saturation index ances were impaired in ACLD (P < 0-05), stasis of childhood (IHCC) (SI) in eight obese patients with choleli- intravenous clearance (controls 271 ± 15 thiasis (151 ± SD 13-5% ideal BW) and ml min-' m-2, ACLD 219 ± 19, mean + J. EVANS, S. P. NEWMAN, AND S. SHERLOCK 17 obese without (151 ± 24-5% IBW), SEM, 20% decrease) was maintained (Departments of Medicine and Medical measured SI in 12 obese patients without better than oral clearance (controls 1248 Physics, Royal Free Hospital, Pond Street, GS before and during 8-1 ± 4-4% weight + 104, ACLD 655 ± 65, 48 % decrease). London) Hepatic copper concentration loss (18 studies) and in seven obese GS

Furthermore, when results for SBA and was studied in four groups of age matched patients before and during two to nine http://gut.bmj.com/ clearances were divided into normal and children N = 38 (normals, non-cirrhotic months treatment with 15-1-21-9 mg abnormal, SBA and oral clearance agreed liver disease, cirrhosis and IHCC) and CDCA KgBW-1 day-1. in 13 of 16 patients with ACLD but SBA nine patients with Wilson's disease (pre- Results showed that mean SI in obese and intravenous clearance agreed in only treatment) of comparable age. Neutron patients with GS (1 -69 + 0-56) was sig- eight. activation analysis of liver copper con- nificantly (p < 0-05) greater than in those Thus for detecting ACLD oral clearance centration revealed raised hepatic copper without GS (1 -16 ± 0-40). During weight of cholic acid is more sensitive than levels in two groups: (1) Wilson's disease loss, although mean SI fell from 1-33 +

intravenous clearance and is of similar 9-8 (1-9-22-5) ,umol/g (median and range) 0-36 to 1-19 ± 0-34, individual response on September 24, 2021 by guest. Protected copyright. sensitivity to the established investigation P < 0-001, and (2) IHCC 4-9 (-8-17) was variable (p > 0-1) and unrelated to of fasting SBA. ,umol/g (median) P < 0-001. There was no magnitude or rate of weight loss. Unlike significant difference between liver copper previous results, obese GS patients in these two groups. Hepatic copper con- achieved unsaturated bile during CDCA Increased gallbladder emptying in gallstone centration in children with liver disease treatment, the mean SI falling from patients was not significantly different from normal 1-86 + 0-65 to 0-67 ± 0-20 (p < 0-05) and was < 1-6 ,umol/g. Necropsy of one except in one patient resistant to D. P. MAUDGAL, C. E. MARSHALL, A. G. patient with IHCC confirmed high liver 21-9 mg CDCA/kg. JOHNSON, AND T. C. NORTHFIELD (Norman copper values (17 ,umol/g), while other We conclude that (1) bile is more SS in Tanner Gastroenterology Unit, St. James' tissues, including brain and kidney, gave obesity + cholelithiasis than in obesity Hospital; Department of Medicine, St. normal results. alone; (2) weight reduction is recom- George's Hospital Medical School; and Plasma copper, caeruloplasmin, and 24 mended in obesity since SI usually falls Department of Surgery, Charing Cross hour urinary copper were measured in 14 during weight loss; (3) larger CDCA doses Hospital, London) Gallstone patients children with IHCC. Plasma copper was (15-1-19-3 mg/kg) desaturate bile in most have a reduced bile acid pool size. This is increased in 11 of 13 cases (P < 0-001), obese GS patients. associated with an increased recycling caeruloplasmin was increased in three of frequency of the pool. Our hypothesis is 14 cases (P < 0-04) and 24 hour urinary that gallbladder emptying is increased in copper was slightly increased in five of 12 Mechanism of the hyperinsulinaemia of gallstone patients, so this could account (P < 0-001). No test accurately pre- cirrhosis for the increased recycling frequency and dicted hepatic copper concentration, but thus the reduced pool size. In order to test increased 24 hour urinary copper was G. SMITH-LAING, SHEILA SHERLOCK this hypothesis, we derived gallbladder associated with hepatic copper concentra- (Academic Department ofMedicine, Royal emptying in response to a standard meal tion > 3-9 /imol/g. Kayser-Fleischner Free Hospital, London), D. G. JOHNSTON, Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

The British Society of GastroenterologyA A453 G. M. M. ALBERTI (Department of Human petitive protein binding assay. SHEILA SHERLOCK (The Royal Free Metabolism, Southampton General The histological and biochemical res- Hospital, London) Hepatic siderosis is Hospital, Southampton), and o. FABER, C. ponse to treatment of osteomalacia was said to be common in alcoholics, though BINDER (Hvidore Hospital, Emiliekildevej studied in 4 patients with symptomatic accurate figures for its incidence are not 1, DK-2930 Klampenborg, Denmark) primary biliary cirrhosis (PBC). Two were available. We therefore set out to assess Hyperinsulinaemia is a common finding treatedwith oral 25-hydroxyvitamin D325- this in a population of British alcoholics. in cirrhosis. It has been demonstrated that OHD3), 50 ug daily, while two received One hundred and fifty-seven alcoholics this is due to reduced hepatic insulin intramuscular vitamin D2, 150,000 units (120 males; 37 females) were evaluated. degradation attributable to hepatocellular once weekly. Trans-iliac biopsies were Personaldetailsweredocumentedincluding damage or portal-systemic shunting. histologically quantitated before and after in the females a menstrual history. The We studied insulin degradation follow- treatment, and plasma 25-hydroxyvitamin drinking histories were detailed and the ing oral glucose in 12 controls and nine D (25-OHD) concentrations were alcohol (g) and iron (mg) taken from the patients with portal vein thrombosis measured by a competitive protein- alcoholic beverages per day calculated. (PVT) with extensive portal-systemic binding assay. The degree of histological damage and of shunts but normal liver function and siderosis was assessed on a needle biopsy histology. specimen of liver. The degree of siderosis Blood was obtained fasting and for three was graded 0 -* IV. hours after glucose ingestion and assayed Bromocriptine in the treatment of chronic Siderosis was present in 57% of the for glucose, insulin, and C-peptide. portal systemic encephalopathy patients irrespective of the degree of liver Glucose levels were higher in the PVT damage. There was no sex difference. group and this was significant at 150 M. Y. MORGAN, A. W. JAKOBOVITS, I. M. Significant siderosis (grades Ill and IV) minutes (6-34 SEM ± 0-60 mmol/l in JAMES, R. LENNOX, AND S. SHERLOCK (The occurred in 7 % ofthe patients there being, patients, 4-83 ± 0 43 mmol/l in controls, Royal Free Hospital, London) Bromo- in the females, a correlation between age p < 0-05). Insulin response did not differ criptine is a specific dopamine receptor and degree of siderosis (p< 0-05)-four of in the two groups. Reduced C-peptide agonist with a prolonged action. It should, the five females with significant siderosis levels were observed in the PVT group theoretically, be useful in the treatment of being premenopausal. and this was significant at 60 and 90 chronic portal-systemic encephalopathy There was no correlation between the minutes (1P31 ± 0-14 nmol/l in patients, (PSE), a condition in which defective excess iron contained in the alcohol or the 2-10 ± 0-23 nmol/l in controls, P < 0-02 dopaminergic neurotransmission has been grams of alcohol consumed per day and at 60 minutes; 1 90 ± 0-20 nmol/l in postulated. Six male patients with cirrhosis the degree of hepatic siderosis. However, patients, 2'99 ± 0-38 nmol/l in controls, and portal systemic shunting were studied. the percentage saturation of iron binding p < 0-05 at 90 minutes). The C-peptide/ Three had natural portal systemic shunts protein and the degree of siderosis cor- http://gut.bmj.com/ insulin ratio was reduced in the PVT and in three the shunts had been surgi- related significantly. group at 150 and 180 minutes suggesting cally induced. All had suffered from PSE In this population of alcoholics the minor impairment of insulin degradation for one to eight years and had shown poor incidence of significant hepatic siderosis is only at high secretion rates. response to conventional treatment. Bro- only 7 %. We conclude that the hyperinsulinaemia mocriptine was given in a double-blind of cirrhosis is caused primarily by hepato- randomised crossover trial versus placebo. cellular dysfunction and not portal- While receiving bromocriptine (15 mg systemic shunting. daily), all showed improvement clinically Hepatitis B in a hospital for the mentally on September 24, 2021 by guest. Protected copyright. and by psychometric testing. In three subnormal patients the electroencephalogram became Treatment of hepatic osteomalacia with normal. Cerebral blood flow increased J. G. C. KINGHAM, M. J. MCGUIRE, D. H. D. parenteral vitamin D2 or oral 25-hydroxy- from 32-6 + 5-8 (ISD) to 40 5 ± 3.7 PAINE, AND R. WRIGHT (Southampton vitamin D3 ml/100 g brain/min (p < 0-05); cerebral University Hospitals, Southampton) We glucose metabolic rate from 2-02 ± here report the incidence of hepatitis R J. E. COMPSTON, L. W. L. HORTON, AND 1P6 to 6*6 ± 3.9 ml/100 g brain/min (p < virus (HBV) infection in 340 patients and R. P. H. THOMPSON (Gastrointestinal Re- 0.02), and cerebral oxygen metabolic rate 268 staff of a hospital for the mentally search Unit, Rayne Institute, and Depart- from 2-2 + 1P0 to 3-3 + 1-0 ml/100 g subnormal in Wessex, using as markers ment of Surgical Pathology, St. 7homas' brain/min (p < 0.02). On crossover from HBsAg, anti-HBs, anti-HBc, eAg, and Hospital, London) The histological and placebo to drug, the patients showed im- anti-e. Twelve per cent of patients and biochemical response to treatment of provement in the measured parameters. 3.7% of staff had HBsAg or anti-HBc, osteomalacia was studied in four patients No serious side-effects were seen. The indicating current infection; 43% of with symptomatic primary biliary cir- bromocriptine was well tolerated and is a patients and 16% of staff had anti-HBs rhosis (PBC). Two were treated with oral useful treatment for chronic portal alone. Of patients with HBsAg, 46 % had 25-hydroxyvitamin Ds (25-OHD,), 50 ,ug systemic encephalopathy when the eAg and none had anti-e, whereas none of daily, while two received intramuscular response to conventional therapy is poor. 26 HBsAg-positive blood donors from the vitamin D2, 150 000 units weekly. Trans- general population had eAg and 12 had iliac biopsies were histologically quantita- anti-e. Although the numbers of HBsAg- ted before and after treatment, and in the livers of alcoholics positive staff were few, they resembled plasma 25-hydroxyvitamin D (25-OHD) blood donors in that none had eAg. HBV concentrations were measured by a com- A. W. JAKOBOVITS, MARSHA Y. MORGAN, markers were more frequent among males. Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A454 The British Society of Gastroenterology and among mongols (83 %) and epileptics Experimental study of a 133Xenon clear- were noted in six cases. HBsAg was (67%) than other patients (39 %). They ance method for measurement of liver blood detected in five patients but persisted in declined with age after 30 years. Abnormal flow only one. HBsAb was found in a further LFTs were found in 88 % of patients with four cases. Our concem for patients in HBsAg, but only 31 % without HBV R. T. MATHIE, R. L. HUGHES, A. M. HARPER, whom abnormal liver enzymes persisted markers. Among staff, HBV markers AND L. H. BLUMGART (University Depart- for more than six months prompted us to correlated with duration of employment ments ofSurgery and Anaesthesia, Glasgow undertake percutaneous liver biopsies and, and patient contact. Royal Infirmary and Wellcome Surgical to date, four such biopsies have been per- We suggest that the carrier state in the Research Institute, University of Glasgow) formed. All patients were symptom-free mentally subnormal, particularly mongols Liver blood flow measurement using at the time of biopsy. The biopsies were and epileptics, is less benign and more 133Xenon clearance is made complicated performed under Factor VIII cover with- infectious than in the general population by the multiexponential form of the out incident and examined under light and or staff, as shown by the high incidence of clearance curve obtained. It has recently electron microscopy and by immuno- eAg and abnormal LFTs. been shown, however, that the slow ex- logical techniques. A spectrum of histo- ponential components of the curves are logical changes varying from chronic Comparison of small intestinal bypass and generated by extrahepatic sources of lobular hepatitis to established cirrhosis equivalent small bowel resection on body radioactivity and that the true intrahepatic was observed. weight and liver function in the Wistar rat clearance is monoexponential. We conclude that (1) liver biopsy may The present study in eight dogs was be safely performed in haemophiliacs K. R. P. RUTrER, H. CLEEVE, AND J. D. carried out to compare measurements of under Factor VIII cover; (2) chronic liver MAXWELL (Departments of Surgery, liver blood flow calculated from the fast disease appears to be a significant problem Chemical Pathology, and Medicine, St. component of the hepatic 133Xenon in severe haemophiliacs; (3) in our ex- George's Hospital Medical School, London) clearance curve to simultaneous electro- perience persistent HBsAg infection is The effect on body weight and liver magnetic flowmeter measurements of infrequent. function of a 90% jejunoileal bypass total blood flow in the portal vein and operation in male Wistar rats was com- hepatic artery. Injections of isotope were an pared with equivalent small bowel made into the portal vein, and the SMALL AND LARGE BOWEL resection. Sham-operated animals served clearance curves treated simply as bi- as controls. Surgery was performed under exponentials. A total of 50 pairs of flow thiopentone anaesthesia. Postoperatively data was obtained over a range of values Effect of pectin on small bowel structure rats were allowed free access to food and from 80 to 1400 ml/min and a close and function http://gut.bmj.com/ water. correlation found (r = 0-91) between the Substantial weight loss occurred in both two measurement techniques. R. C. BROWN, J. KELLEHER, AND M. S. resected and bypassed groups in the first It is therefore concluded that liver blood LOSOWSKY (Department of Medicine, two weeks (18 % and 24% of initial weight flow can be accurately measured with the St. James's Hospital, Leeds) Pectin is respectively). Thereafter the resected 13"Xenon clearance method, using the the form of dietary fibre with the most group steadily increased to 94 % of clearance rate of the fast component for consistent hypocholesterolaemic effect in initial weight by 10 weeks, with no deaths. flow calculation. The technique offers an man. This may be due to malabsorption The bypassed group however, pro- opportunity for clinical liver blood flow of cholesterol, but pectin also increases on September 24, 2021 by guest. Protected copyright. gressively lost weight to 66% of initial measurements after single portal vein the rate of absorption of paracetamol, weight by 10 weeks (P < 0 01 > 0-001 injection, and has the advantage that it suggesting more complex changes in and eight of 23 died. gives a measure of the actual hepatic absorptive function. This study examines There were no differences in standard tissue perfusion. the effect of high dose pectin feeding on liver function tests betweer. resected and intestinal structure and function in the control animals, but compared with the rat. resected group, bypassed rats showed Liver biopsy in haemophilia Three groups of rats were fed either a significant rises in alanine aminotrans- standard pelleted diet, or a basal fibre- ferase (118 ± SD 82 lU/l v 42 ± SD 39 D. R. TRIGER, F. E. PRESTON, V. E. MITCHELL, free diet, or the basal diet with 18% IU/1, P < 0.02 > 001) and aspartate J. C. E. UNDERWOOD, R. M. STEWART, C. pectin added. After 12 to 16 weeks on aminotransferase (265 + SD 190 IU/l v BARDHAN, AND E. K. BLACKBURN (Uni- diet rats fed added pectin had significantly 93 + SD46IU/1,P < 0-05 > 002) anda versity Departments of Haematology, longer small bowels than those on basal lower plasma albumin (27-8 ± SD 4-3 Medicine, and Pathology, University of diet alone (p = <0-001) or standard g/l v 30'8 ± SD 3.8 g/l, P < 0-1 > 0-05). Sheffield) Abnormalities in liver function pellets (p = >0 05). Histological Jejunoileal bypass causes significantly tests are commonly found in haemo- measurements showed that the pectin- greater disturbance of homeostasis in rats philiacs receiving frequent infusions of fed rats had a thicker muscle layer, than comparable resection. These studies Factor VIII preparations but data con- particularly in mid-jejunum and ileum, also suggest that the presence of a long cerning liver histological changes is scanty. and the mucosa was also thicker in the isoperistaltically emptying bypassed loop Sixteen out of20 of our regularlytreated pectin-fed rats, mainly due to increased of small bowel adversely affects liver haemophiliacs had abnormalities in crypt depth, with less variation in villus function, and may be relevant to the routine liver function tests which tended to height. There were no significant differ- pathogenesis of post-bypass hepatic persist on serial testing. Symptoms sug- ences between the pellet-fed and basal disease in man. gesting a history of hepatitis-like illness diet rats. Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from The British Scciety of Gastroenterology A455

The DNA content (per cm length of tal, University of Copenhagen, Denmark) ectomy. The relative contributions of bowel) in mucosal scrapings showed The mechanism by which a subgroup of bile and pancreatic juice to ileal hyper- no significant differences, but the mucosal patients with irritable bowel syndrome plasia were studied in rats (N = 141) protein content was greater in pectin- (IBS) produced painless (nervous) after diversion of bile alone (BD) or of fed rats, particularly in the upper jejunum. diarrhoea is not known. Therefore, the combined pancreatobiliary effluent Specific activities of alkaline phosphatase experiments were performed in which the (PBD) to mid small bowel. BD was and leucyl-fi-naphthylamidase were sig- effect of increasing prostaglandin E, performed by ligation and cannulation nificantly lower in the pectin-fed rats. (PGE2) concentrations on net transfer of the choledochus above the pancreas These findings suggest that diet- rates (Jnet) and bidirectional fluxes of and PBD by transposition of a duodenal induced variations in intestinal structure Na+ and Cl- was evaluated in the in segment containing the papilla. Control and function are of importance in nutri- vitro short-circuited human jejunum. animals had jejunal transection (T). tion and drug absorption. PGE2 caused a prompt dose-related In ileal mucosa, BD and PBD caused increase in short-circuit current ([sc) and similar increments in RNA (16-50%) electrical potential difference (PD), de- and DNA contents (33-41%) over con- Roles of prostaglandins (PG) and calci- creased net Na+-transfer and elicited trol values both 48 h and postoperatively. tonin (CT) in the diarrhoea of medullary Cl--secretion primarily due to a rise in 3HTdR-labelled specific activity of DNA, carcinoma of thyroid (MCT) the serosa to mucosa fluxes, although a indicating the proportion of proliferating significant reduction of the mucosa to cells, was higher after PBD than BD T. M. COX, E. FAGAN, D. ALLISON, AND V. S. serosa fluxes was observed as well. These (p < 0 05). At one month nucleic acid CHADWICK (Department of Medicine, effects were potentiated by preincubation contents in rats with PBD were 27-59% Royal Postgraduate Medical School, of the tissue with indomethacin higher than T (p < 0 001) or BD (p < London) Diarrhoea in MCT could be (3 x 10-5M), indicating blockade of 0-005). Likewise, villous height and crypt caused by tumour secretion of PG or CT, endogenous PGE biosynthesis, as found depth were increased one week after BD as both inhibit small intestinal fluid for the rabbit gall-bladder. Furthermore and PBD, but one month after PBD absorption: PG by stimulating cAMP this increased sensitivity, obtained by alone. The colonic response was similar production in gut mucosa and CT by an indomethacin blockade of the tissue but smaller. In the jejunum, though unknown mechanism. We studied the revealed a dose-dependent relation be- pancreatobiliary deprivation caused trans- roles of PG and CT in a patient with tween PGE2 concentration and Ise, PD, ient hypoplasia, the mere absence of bile diarrhoea due to MCT. Distal ileal flow, had no effect. measured by marker perfusion techniques JNeat and J while no change was An increased luminal concentration of was increased to 3'5 1/24 h (N 2-3 + SD cnt bile is sufficient for prompt ileal hyper- 0-5) confirming decreased small intestinal observed in tissue resistance (G) and plasia, but the additional presence of http://gut.bmj.com/ fluid absorption. Arterial, venous, and residual flux (JR). The threshold con- pancreatic juice prolongs this adaptive tumour effluent PG levels and small centration (10-1lM) for effect of exo- response. intestinal mucosal cAMP concentrations genous PGE2 and the concentration for were not increased; furthermore inhibitors half maximal response (10-9M) during of PG (indomethacin and nutmeg) and indomethacin blockade was 100-1000 Effect of prednisolone on the adapted cAMP (nicotinic acid and colchicine) times less than for exogenous PGE2 ileum following jejunal resection failed to reduce the diarrhoea. Plasma CT alone. The observed value for half levels were markedly raised (283 tg/l N < maximal response corresponds well to J. SCOTT, R. M. BATT, AND T. J. PETERS on September 24, 2021 by guest. Protected copyright. 0'08) but plasma VIP gastrin and urinary the dissociation constants for interaction (Royal Postgraduate Medical School, 5-HIAA were normal. Plasma from the between PGE and high affinity binding London) Jejunal resection results in an patient was infused into the superior sites (receptors). adaptive hyperplasia of the distal small mesenteric artery of dogs and mean net These results indicate not only an intestine without markedly affecting the fluid absorption fell from 32-8 to important physiological role of PGE2 function of the individual enterocytes. 8-2 ml/30 cm loop/h in the jejunum and for the lubrication of the intestinal Prednisolone, in contrast, has been shown 21-7 to 5'7 ml/30 cm loop/h in the ileum. contents, but also that even a small to enhance both the absorptive and Pooled normal plasma was used as con- increment in endogenous intestinal PGE2 digestive capacities of jejunal and ileal trol. Diminished absorption was not production may result in diarrhoea. enterocytes without altering the size of associated with raised cAMP levels in the the cell population or cell kinetics. In mucosa. We conclude that CT and not the present study, the effects of predniso- PG was responsible for the diarrhoea in Adaptation of the shortened gut: the role lone on the adapted ileum have been this patient and that it acts through a of endogenous secretions investigated. non-cAMP mediated mechanism. Adult male Wistar rats (weight 230- R. C. N. WILLIAMSON, F. L. R. BAUER, 270 g, N = 15) were randomised into the J. S. ROSS, AND R. A. MALT (Department following groups: (1) 50 % proximal Effect of prostaglandin E2 and indo- of Surgery, Bristol Royal Infirmary and small intestinal resection, (2) 50% proxi- methacin-blockade on electrolyte transport Surgical Services, Massachlusetts General mal small intestinal resection and oral in human jejunum Hospital, Boston, USA) Besides food prednisolone (0 75 mg/kg/day for seven and humoral agents, pancreatobiliary days) beginning three weeks after surgery, V.. BUKHAVE AND J. RASK-MADSEN (Gastro- secretions may contribute to distal in- (3) transection, reanastomosis controls. enterological Department C, Herlev Hospi- testinal adaptation after proximal enter- Animals were pair fed and killed four Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A456 The British Society of Gastroenterology

weeks after surgery. plication of diarrhoea, is not directly R. F. G. J. KING, S. MILLWARD, AND G. L. Although both the resected groups had related either to stool weight or to HILL (University Department of Surgery, enhanced activities of the brush border sphincter pressures or strength. The General Infirmary, Leeds) Although marker enzymes-for example-a-gluco- Treatment with lomotil dramatically there are a number of very good accounts sidase per centimetre of intestine com- increased the maximum amount of fluid available which describe different aspects pared with the control group, prednisolone which could be retained in the rectum in of ileostomy excretion there has been no induced a further increase in the enzyme five out of six incontinent subjects. comprehensive description of ileostomy activity. chemistry in a single group of patients a-glucosidase activity with well-functioning ileostomies. For this Group mUnits/cm out mUnits/mg DNA Neurotensin and enteroglucagon in obesity reason 16 patients with well-established Resection 296±67 161 ± 10 ileostomies, all of whom had had proven Resection 67-7 + 82 37-0 ± 84 S. E. HOBBS, J. M. POLAK, A. G. E. PEARSE, ulcerative colitis but with no ileal resection + steroid p < 0-05 p < 0 05 H. S. BESTERMAN, S. R. BLOOM, G. R. andreceiving no medication,entered a trial In contrast, the activities of lysosomal GREENBERG, J. CLEARY, J. C. GAZET, J. in which complete ileostomy collections (N-acetyl-,-glucosaminidase) and mito- MONSON, AND T. L. PILKINGTON (Depart- were made for five consecutive days. chondrial (cytochrome oxidase) marker ments of Histochemistry and Medicine, We have found that in this group there enzymes per enterocyte were unaltered by RPMS, Hammersmith Hospital, London, was a correlation between the body weight prednisolone. Department of Medicine, St. James' of a patient and the weight of ileostomy This study indicates that the adaptive Hospital, London, and Department of discharge (r = 0-83, p < 0'01). The aver- response of the remaining small intestine Surgery, St. George's Hospital, London) age daily weight of ileostomy fluid was after jejunal resection can be enhanced Excessive food intake gives rise to a con- 467 ± 154 g/day. by prednisolone. This may be due to a siderable morbidity. Much of the patho- The concentration of each respective direct increase in the brush border physiology remains unknown and it is electrolyte measured was generally similar enzyme activity of the individual entero- likely that the gut itself plays an import- in all patients and the mean losses in cyte. ant role. In particular, enteroglucagon and ileostomy fluid of these electrolytes were neurotensin, two ileal hormones, with as follows; sodium 53-5 ± 18-1 mmol/ distinct cellular origins, are thought to day; potassium 3-2 + 1'1 mmol/day; Anal sphincter competence in patients with influence metabolism. Operative speci- calcium 8-19 ± 3-48 mmol/day; mag- chronic diarrhoea mens were obtained, during jejunoileal nesium 3-67 + 1'86 mmol/day; zinc by-pass, from 16 patients with morbid 15'6 ± 6'8 umol/day; copper 3'31 + MARIA READ, N. W. READ, CAROL SANTA- obesity (aged 28-33 years) averaging 1i11 umol/day; bicarbonate 6'62 + 2.96 http://gut.bmj.com/ ANNA, AND J. S. FORDTRAN (Department 237 ± 8% of ideal body weight. For mmol/day; chloride 28 + 12'2 mmol/ of Internal Medicine, University of comparison, ileum was obtained from four day; and phosphate 5 68 + 2'01 mmol/ Texas Health Science Center at Dallas, patients undergoing surgery for colonic day. The loss of water was found to be Southwestern Medical School, Dallas, carcinoma, who had lost more than 10% 419 + 141 ml/day, protein 10-4 + 3.8 Texas, USA) The competence of the ideal body weight. Immunocytochemistry g/day, and fat 3-6 + 2'2 g/day. anal sphincter was assessed in 15 healthy was carried out on appropriately pre- We conclude that, in patients with well- control subjects and 23 patients with pared tissue using antibodies specific to functioning ileostomies, faecal volume is chronic diarrhoea, 15 of whom were and neurotensin. enteroglucagon related to body size and the losses of on September 24, 2021 by guest. Protected copyright. habitually incontinent of faeces. The Light microscopy revealed a substantial sodium, water, and protein are greater following measurements were recorded: increase in both cell populations in the than those in normal faeces but the fluid (1) a profile of the resting and squeezing obese group. Quantitative studies were losses of the other ions measured would sphincter pressures using fluid filled undertaken using the Quantimet 720D appear to be of little consequence. catheters; (2) the suspended weight image-analysing computer. required to pull a I in cork ball out of the Neurotensin cells were significantly anus, during voluntary contraction and greater in number (p < 0-001) in the obese Phagocytosis and intracellular killing in relaxation; (3) the maximum volume of group (8'0 ± 1-0 cells/mm2) when com- inflammatory bowel disease (IBD) fluid (pumped in at 60 ml per min) which pared with underweight patients could be retained in the rectum. (0 4 ± 0 3 cells/mm2). Similarly, signifi- A. S. MEE, M. SZAWATKOWSKI, AND D. P. While all the continent subjects (con- cantly (p < 0-01) more enteroglucagon JEWELL (Departments of Medicine and trols and patients) retained at least 1300 ml cells were observed in the obese group Microbiology, Royal Free Hospital, of fluid, none of the incontinent subjects (5 4 ± 0 9 cells/mm2) as compared with London) Macrophages present in granul- was able to retain this volume (mean = underweight patients (0 7 ± 0'5 cells/ omata are derived from circulating blood 442 ± 77 ml). The results of the other mm2) monocytes. Phagocytosis and intracellular tests, although lower in the incontinent Alterations in gastrointestinal hormones killing by monocytes have therefore been group, showed some overlap. Twenty- may provide further understanding of the investigated in 15 patients with Crohn's four hour stool weights were not signifi- pathophysiology of abnormal nutritional disease (CD) and 13 with ulcerative colitis cantly higher in incontinent (442 + states such as obesity. (UC) and compared with normal (23) 111 ml) compared to continent patients and disease (13) control groups. (331 ± 46 ml). Mononuclear cells were isolated from Our findings suggest that anal inconti- Chemistry of ileal fluid in well-functioning peripheral blood over a Ficoll-Triosil mence, a common and distressing com- ileostomies gradient. The cell suspension was adjusted Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

The British Society of Gastroenterology A457

to 1 x 107 monocytes/ml (identified) by numbers of bacteria were associated with bacterial activity. peroxidase staining) and incubated with colonic tissue (106-107 per g) than with 1 x 107 Staph. aureus (Oxford strain) tissue from the jejunum (103-10' per g). for two hours at 37°C. This difference was statistically sig- Comparison of rectosigmoid myoelectrical Colony counts were carried out before nificant (p < 0-03). Samples from the activity in the irritable colon syndrome and after incubation. Lysostaphin was terminal ileum were quantitatively inter- during relapses and remissions then added to kill extra cellular organisms mediate between jejunum and colon. and the number of viable intracellular There was no statistical difference in the I. TAYLOR, C. DARBY, AND P. HAMMOND bacteria were determined by further numbers of bacteria associated with (Departments of Surgery and Bioengin- colony counts. Phagocytosis and intra- Crohn's tissue compared with histologic- eering, Liverpool) Recent studies have cellular killing were calculated from the ally normal tissue from the control group suggested that an abnormally high inci- three colony counts. of patients. dence of 3 c/m electrical activity exists For the normal and disease control within the colon of patients with the groups the mean phagocytosis (± SEM) irritable colon syndrome. However, this was 42'5% ± 2-6 and 43'4% ± 4-1. Measurement of glycosidase activities in condition is known to be a chronic Phagocytosis was significantly increased faeces relapsing disorder and in this study we in patients with IBD. For patients with have compared myoelectrical recordings, CD 53X2% ± 3-4 of organisms were G. NEALE, J. R. HOPKINS, S. PEACH, AND using an on-line frequency analyser, phagocytosed (p < 0-05) and for patients S. TABAQCHAU (Trinity College Dublin, during periods of severe symptoms and with UC 57 9% ± 4-8 of organisms were Royal Postgraduate Medical School, and asymptomatic phases. phagocytosed (p < 0'01). St. Bartholomew's Hospital, London) Treatment with either bran or an anti- For all groups intracellular killing was It is difficult to isolate and measure spasmodic resulted in 12 of the 20 patients greater than 95 % of the organisms faecal bacterial activity accurately. The becoming symptom-free after one to three phagocytosed and there was no difference measurement of bacterial enzymes might months. In those patients who were between groups. provide an alternative method of study. initially constipated a statistically sig- These results suggest that monocytes Using methyl-umbelliferyl substrates nificant increase in mean stool weight are activated in IBD but no difference we have devised sensitive reproducible (84-8 ± 9.3 g/day to 107 ± 11-3 g/day) was detected between UC and CD. assay systems for five faecal glycosidases. and a decrease in mean transit time Optimal conditions have been established (82 ± 12 h to 53-4 + 6 5 h) occurred for each enzyme with reproducible results but this was not associated with any Intestinal mucosal flora in Crohn's disease down to 0d1-0-2 mU per g wet weight alteration in either percentage motility faeces. Faeces from 15 normal subjects or electrical activity. The percentage http://gut.bmj.com/ SUSAN PEACH, R. LOCK, D. KATZ, AND SOAD gave the following values: a-glucosidase incidence of 3 c/m electrical activity TABAQCHALI Department of Medical 608-2685 mU/g, ,B-glucosidase 380-3832 before treatment was 67-8 ± 6-7% and Microbiology, St. Bartholomew's Hospital, mU/g, a-galactosidase 340-3418 mU/g, after treatment 65 0 ± 6 3 %. London) Previous bacteriological studies f-galactosidase 1025-10 178 mU/g and In patients with predominant diarrhoea of Crohn's disease have concentrated on ,B-glucuronidase 277-3485 mU/g. (Co- no statistically significant difference oc- the intestinal lumen and little is known of efficient of variability: 5 5-7 5 %.) curred in either transit time or stool weight the bacterial flora associated with the Forty-one hospitalised patients with after treatment nor did the abnormal mucosa of the intestine. We therefore were studied in- myoelectrical activity return towards on September 24, 2021 by guest. Protected copyright. examined the bacterial flora of the cluding the effects of a 'bowel sterilisation' normal with symptomatic improvement. mucosa of patients with Crohn's disease antibiotic regime. Comparative studies These results suggest that a fixed basic and compared it with the mucosal flora were made on conventional and gnoto- myoelectrical abnormality exists which is of a control group. biotic mice. unrelated to symptoms. This may help to Specimens were obtained at operation Results were as follows: (1) apart from explain the chronic relapsing nature of the from patients undergoing intestinal surg- a-glucosidase, the glycosidase activities irritable colon syndrome. ery. Whole thickness intestinal sections in normal faeces are primarily bacterial were taken from the diseased segment in origin; (2) enzyme activity is reduced and from a portion of uninvolved in- up to 10-fold in patients with diarrhoea Anal pressure studies in and testine. Each specimen was examined without a specific pattern for individual incontinence histologically. diseases; (3) diet influences faecal bacterial Twenty-two specimens of Crohn's enzymes-for example, a four-fold in- M. R. B. KEIGHLEY, Y. ARABI, N. SHINAGAWA, tissue (12 ileum, 10 colon) and 16 control crease in ,-galactosidase activity on feed- AND J. ALEXANDER-WILLIAMS (The samples from small and large bowel were ing lactose to a subject with hypolactasia; General Hospital, Birmingham) Some examined using strict anaerobic techniques (4) faecal bacterial enzyme activity was patients with rectal prolapse and all in an anaerobic chamber. reduced to the lower limit of assay patients with idiopathic anorectal in- A mucosal flora was found to exist sensitivity by the administration of effect- continence have an abnormal anorectal in all the large bowel samples and in ive 'bowel sterilising' antibiotics but not angle and a weak external anal sphincter. three-quarters of the small bowel samples. affected by metronidazole. Manometric studies have been per- It was qualitatively similar in all the It is suggested that enzyme estimations formed before and after treatment in 36 samples, consisting mainly of Gram may provide a relatively simple and patients presenting with rectal prolapse or positive facultative bacteria. Greater sensitive method of monitoring faecal incontinence. Anal pressures were re- Gut: first published as 10.1136/gut.19.5.A432 on 1 May 1978. Downloaded from

A458 The British Society of Gastroenterology corded with a closed water-filled balloon after rectopexy. Dramatic clinical and One - hundred - and - fifty-three probe under resting conditions and after manometric improvement was demon- patients were studied; 57 (37 5 %) patients voluntary external sphincter contraction. strated after sphincter repair for trauma. had had at least one previous anorectal Analysis included maximum basal pres- These results confirm a correctable ab- abscess; 118 (77-1 %) abscesses were sure (MBP) and the maximum increase normality of the puborectalis in two- perianal, 35 (22 9%) ischiorectal. Sixty- after external sphincter contraction, thirds of patients with rectal prolapse and three (41-2%) patients had a fistula laid defined as the voluntary component (VC). anorectal incontinence. open at the first operation or at an EUA In rectal prolapse without incontinence within 10 days. In 104 (68 0%) patients (n = 6) the MBP and VC did not differ the infecting organism was intestinal in from age matched controls. In rectal Anorectal infection: the relationship origin; all 63 patients with a fistula prolapse with incontinence (n = 15) between the infecting organism, the finding belonged to this group. In 33 (21 6%) the MBP was normal, but the VC was of fistulae, and the recurrence rate patients the organism was cutaneous and significantly lower than controls. in not one of these patients was a fistula Compared with controls the MBP and R. H. GRACE, I. A. HARPER, AND R. G. found. Nineteen (12-4%) patients have VC were both significantly lower in THOMPSON (The Royal Hospital, Wolver- developed a recurrent abscess; 11 were patients with idiopathic (n = 11) and hampton) Between a quarter and a third at the same site; four further fistulae were traumatic (n = 4) anorectal incontinence. of all patients presenting with an ano- found. Eight were at a different site; two Pelvic floor faradism did not increase rectal abscess will develop a recurrence. further fistulae were found. Only one of VC and there was little clinical benefit. In this study all patients were admitted the 63 patients with a fistula had a re- Rectopexy cured the prolapse, but had under the care of one of us (RHG) currence and this was thought to be due to no influence on VC or continence. Levator between January 1974 and August 1977; initial inadequate surgery. ani repair increased the VC by 66% with all patients have been followed in the The significance of these results in good clinical results in anorectal in- clinic. The surgical management will be relationship to the surgical management continence and in patients still incontinent described. will be discussed. http://gut.bmj.com/ on September 24, 2021 by guest. Protected copyright.