Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

Gut, 1986, 27, A592- A634

The British Society of Gastroenterology

The 1986 Spring Meeting of the British Society of Gastroenterology was held on 9-11 April 1986 at the University of Lancaster under the presidency of Dr G P Crean. The following are the abstracts of the 70 oral and 112 poster communications selected for presentation at the meeting.

the presence of an autoregulatory reflux T3 GASTRODUODENAL involving acid the control of gastric HCO- Tl-4 Which upper GI bleeders require secretion in man. endoscopy? TI Effect of acid on bicarbonate secretion T2 S A RAIMES AND C W VENABLES .(Depart- ment Surgery, Freeman Hospital, New- in man: evidence for an Mechanism of the gastroduodenal of by the stomach castle upon Tyne) Less than one-third of autoregulatory reflex brake patients with upper GI bleeds will have their immediate management affected by J R CRAMPTON, L C GIBBONS AND, W D W N PARR, S GRIME, J BAXTF[R, M CRITCHIFY, urgent endoscopy, in the remainder endo- REES (Department of Medicine, Hope AND C MACKIE (University Departments scopy will only provide a diagnosis. The Hospital (University of Manchester School of Surgery and Nuclear Medicine, Royal aim of this study was to determine whether of Medicine), Salford, Manchester) A pH Liverpool Hospital, Liverpool) Duo- it was possible. at the time of admission, to gradient exists across the gastric adherent denojejunal receptors may slow gastric identify patients in whom endoscopy was mucus gel layer maintained by bicarbonate emptying by inhibiting fundal tone and most likely to change their management. (HCO 3) secretion from the epithelial cells. increasing outflow resistances. This study Multiple factors in the history, examination Evidence in animals suggests that acid itself investigated the contribution of post- and initial blood count were analysed in may stimulate alkali secretion via a local pyloric resistances. Six dogs had gastric 198 consecutive patients, of whom 38 re- http://gut.bmj.com/ reflex. We have studied this possibility in emptying of 250 ml 15% dextrose, labelled quired surgery. No factor in the history was man. with 'Tc"-DTPA, measured by gamma helpful except for the nature of the pre- Seven healthy volunteers swallowed a camera imaging (preoperative studies: senting bleed. Significant factors included a polyvinyl multilumen gastroduodenal tube n=18). A proximal duodenal cannula was pulse rate > 100/min (p<0.05) and after an overnight fast. After aspiration inserted and studies repeated in four systolic BP <100 mmHg (p<0001). of gastric contents and administration of modes: with the cannula closed (n.= 12); Haemoglobin duodenum with '4C-PEG. Samples con- at a constant rate (n= 12) equivalent to were more useful when combined to form a tinuously aspirated from antrum and distal emptying measured in studies without simple scoring system with a 'weighting' for duodenum allowed measurement of HCO 3 diversion; with diversion and total re- patients over 60) or with concomitant concentration from the pH and pCO2, instillation of effluent (n= 12). Mean disease. One hundred and forty patients volume from marker dilution, and duo- emptying for individuals at 90 min was scored less than 3 points of whom only 5% denogastric reflux from marker distribu- compared by Wilcoxon's paired test: required surgery. Of the 58 patients scoring tion. Saliva was aspirated and not cannula closed 51% (mean:range 41-60)%Yo); 3 or more 53% required surgery (p<0001). swallowed. After equilibration HCO 3 preoperative 50% (3(t-70%, NS); total This study shows how a scoring system can secretion was measured during a 60 minute diversion 97% (90-99%, p<0(025); equiv- help in the selection of patients in whom baseline period. The gastric perfusate was alent rate reinstillation 59% (31-85%, NS); urgent endoscopy may influence sub- then changed to 3H-PEG with acid total reinstillation 36% (25-46%, p<0-05). sequent management. (100 mM HCI 2 ml/min) for 30 minutes With total reinstillation emptying, was in producing a fall in gastric pH to 2. In the 30 steps, while curves were smooth in the minute return to neutral period following other studies. These results indicate that T4 pH HCO 3 secretion was 531±86 tmol/ the gastroduodenal brake is mediated pre- 30 min (mean±SE) compared with dominantly via intragastric mechanisms, Natural history and prognostic factors 258±38 ,umol/3() min before acid per- post-pyloric resistances contributing little. in gastric cancer fusion (p<0(05). The change was due to Furthermore, total reinstillation scans an increase in both gastric volume and suggest that increments of rapid duodeno- D CUNNINGHAM, D tiOLE, D J TAGGART, M bicarbonate concentration. Duodenogastric jejunal filling provoke an exagerated SOUKOP, D C CARTER, AND C S MCARDLE reflux was unaltered. This result indicates braking response. (Department of Medical Oncology and A592 Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from The British Society of Gastroenterology A593 University Department of Surgery, Royal adding n-acetyl cysteine (NAC) or prosta- T7 Infirmary, Glasgow and Cancer Surveil- glandin E2 (PE2) to the cleansing solution. Mechanism of acute stimulation of lance Unit, Ruchill Hospital, Glasgow) The electrode system was found to be colonic Na and K transport by gluco- We have reviewed the records of 328 robust, reliable, and reproducible. After corticoid hormone patients with gastric cancer treated in saline cleansing juxta-mucosal pH was 6-48±0-11 (M±SEM, n=6) and micro- Glasgow Royal Infirmary between January G I SANDLE AND F MCGLONE (Department 1974 and December 1984. One hundred climate depth 975±80 pm. After NAC the of Medicine, Hope Hospital (University of and twenty eight (39%) had curative re- values were 6-81±0-07 and 450±75 rim. Manchester School of Medicine), Salford, section (CR), 32 (9-8%) palliative resec- PE2 produced a lower pH 6-09±0-15 and Manchester) Single pharmacological tion (PR), 33 (10%) gastroenterostomy thicker microclimate 1475±160 ,um. In doses of glucocorticoids stimulate rectal Na (G), 26 (7-9%) had a Celestin tube inserted conclusion rat distal colon has a micro- and water absorption, K secretion, and (CT), 58 (17-7%) had a laparotomy alone climate 975 p.m thick with a pH 6-48 electrical potential difference in normal (LA) and 51 (15-5%) had no surgical adjacent to the colonocytes. This is in subjects and patients with active ulcerative procedure (NS). Operative mortality for agreement with absorption studies and colitis after five hours. To determine the the CR group dropped from 17-6% between 3 mm glass electrode studies of human cellular bases for these effects, Na and K 1974-79 to 8-4% between 1980-84. Overall mucosa. The importance of mucus is shown transport properties of cell membranes of five year survival was 11%, but all long by changes in the microclimate produced rat distal colon were studied in vitro five term survivors (except one) came from the by NAC, a mucolytic, and PE2, which hours after in vivo treatment with dexa- CR group which had a five year survival stimulates mucus secretion. methasone (600 ug/100 g bw). Compared rate of 24%. The best predictor of long with control tissues (n=14), dexamethasone term survival for the CR group was serosal (n=8) increased transepithelial voltage involvement (p<0.001). Patients with a T6 from -6±1 mV to -20±5 mV (p<0-005) long duration of symptoms (>six months) Common antigens on lymphocytes and and electrical conductance from 5-4± had better five year survival rates (51%) Yersinia enterocolitica: a link between 0-2 mS/cm2 to 8-4+1-1 mS/cm2 (p<0-005). than those with a short history (14%; Apical addition of 0-1 mM amiloride (a Na p<0-01). Median survival for the PR group an enteric pathogen, ankylosing spondylitis and inflammatory bowel channel blocker) and then 30 mM tetra- was six months, significantly better than ethylammonium chloride (a K channel survival of the other groups (G=4 months, disease blocker) had no effects in control tissues, CT=2 months, LA=2 months and NS=1 but produced changes in transepithelial month; p<0-05). Serosal spread is the main P E PEASE, M R LANE, H CHAHAL, R L electrical parameters in dexamethasone- prognostic indicator following curative re- BARTLETT, J E TALLACK, J R IBBOTSON, AND treated tissues which were consistent with section of gastric cancer. Patients with a R N ALLAN (Department of Medical inhibition of apical Na and K channels. http://gut.bmj.com/ long duration of presenting symptoms also Microbiology, University of Birmingham Studies of the kinetics of the basolateral had a relatively good prognosis. and General Hospital, Birmingham) One hypothesis for the aetiology of inflamma- Na-K pump showed that dexamethasone tory bowel disease (IBD) and ankylosing had no effects on Vmax or Km. Thus, the spondylitis (AS) is that the initiating agent acute stimulatory effects of glucocorticoids carries an antigen in common with host on distal colonic Na absorption and K tissue which perpetuates the immune secretion reflect increased apical mem- response. To explore whether such a brane conductance to Na and K, without BASIC SCIENCE common antigen exists an antiserum was change in the capacity or the affinity of the on September 29, 2021 by guest. Protected copyright. T5-8 made by vaccinating a rabbit with formal- basolateral pump for Na and K. ised Yersinia enterocolitica type 0:9 (Ye T5 0:9). This antiserum was then absorbed T8 Importance of mucus in the colonic with lymphocytes obtained from controls microclimate (n=30), AS (n=28) and IBD patients Fibrin-mucus interactions at the (n=20). IgG anti-Ye 0:9 was then meas- gastric mucosal surface and their role N I MCNEIL AND J WAGER (Department of ured in pre and postabsorption antisera in mucosal protection Medicine, University College London and using an ELISA technique with results Middlesex Hospital Medical School, The expressed as a percentage fall in optical L A SELLERS, A ALLEN, M BENNE1r, AND C Rayne Institute, London) The small density. Lymphocytes from patients with HUDSON (Department of Physiological intestinal microclimate is important in AS and IBD absorbed antiserum with Sciences, Medical School, University of health and disease. A large intestinal significant falls in optical density both in Newcastle upon Tyne and Department of microclimate with pH 6-5 was proposed AS (11.9%±9-6, p<0.001) and IBD Histology, Freeman Road Hospital, New- after drug absorption studies and we have 21 78%+11, p<0.001). There was no castle upon Tyne) The protective mucus examined this hypothesis with pH micro- absorption with 96% of control lympho- barrier is a continuous, translucent layer of electrodes. After being killed, rat distal cytes. In the AS group alone B27+ gel, median thickness 70 pm and 180 p.m in colon was cleansed with 50 ml saline, lymphocytes absorbed more than B27- rat and man respectively. After acute excised, and mounted in oxygenated buffer. cells. In conclusion AS and IBD lympho- mucosal damage by ethanol extensive re- Five micrometres pH microelectrodes were cytes absorb an antisera raised against Ye epithelialisation of gastric mucosa can lowered onto the mucosa recording pH and 0:9 implying the presence of a crossreacting occur under a gelatinous layer. depth. The place of mucus was assessed by antigen. A ligated stomach of an anaesthetised Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A594 The British Society of Gastroenterology rat was infused for 45 sec with ethanol supports the hypothesis that oesophageal a better understanding of oesophageal (70% v/v) followed by recovery with iso- blood supply is abnormal in these dis- physiology the effects of operations to tonic saline for 60 minutes. After damage orders. The technique opens up new possi- control gastro-oesophageal reflux are still and recovery, a thick (median 680 iim) bilities in oesophageal investigation. controversial. At present the pressure and sloppy, opaque, gelatinous coat was ob- length of the lower oesophageal sphincter served on unfixed mucosal sections, in (LOS) are thought to be particularly contrast with the normal thin (median 70 sim) T10 important. We have measured the pressure translucent adherent mucus layer of un- Pill or probe? An assessment of and intra-abdominal length of the LOS in damaged control mucosa. Histological ambulatory oesophageal pH monitor- 76 patients before and six to 12 months examination showed thick bands of ing systems. after floppy Nissen fundoplication. Sixty fibrinogen (peroxidase-anti-peroxidase) in seven (88-2%) had control of reflux this coat, fibrin demonstrated by 24 h pH gelatinous indicating W G CASE, G A DAVIES, J H M HOLMFIELD, D G recording. deposition. Exfoliated cells were found There was no significant change in LOS above and below this fibrin band admixed HICK, D A WATSON, N S WILLIAMS, AND D length. In 21 cases LOS pressure did not JOHNSTON (Department of Surgery, The with mucus. In undamaged mucosa fibrino- General Infirmary, Leeds and Department change or was reduced (median change gen was observed only in blood vessels. of Cardiothoracic Research, Killingbeck -2 5 mmHg range 0-14-2). Despite this, Measurement of prothombin times in vitro, Hospital, Leeds) The radiotelemetry reflux was controlled in 17 (80-1%). Con- halved by addition of mucus gel, suggests versely, LOS pressure was increased capsule (RT) led the way for ambulatory 24 that mucus may act as a template in hour oesophageal pH monitoring. Even (range 3-1-11-4) in five of nine cases in formation of fibrin in vivo. which reflux was not controlled. These after a nine month learning period with We conclude that after acute ethanol RT, however, (when 24 hour reflux quanti- results suggest that the increased LOS damage the gastric mucosa is protected pressure which occurred in most cases fication was only possible in 30% of against further damage by a most effective (median 6-2 range 0.3-30-7) may be a investigations), we suffered problems with gelatinous coat of fibrin with mucus and traces because of signal loss, interference surgical artefact as reflux control is inde- necrotic cells. and calibration drift. If 24 hour pH moni- pendent of the change. toring aims to quantify reflux, such varia- tions are unacceptable and so a system based on an antimony/glass microelectrode T12 (ME) was constructed for ambulatory use. Dietary guidelines for ambulatory OESOPHAGUS All tests conducted in the second nine oeosphageal pH monitoring months traces T9-12 experience with RT (51 pH http://gut.bmj.com/ in 51 patients (29 men: 22 women, aged 52 LR JENKINSON, T L NORRIS, AND A WATSON T9 years, range 19-73) were compared with 69 (Department of Oesophageal Investigation, Oesophageal ischaemia - its potential traces in 64 patients (35 men: 29 women, Royal Lancaster Infirmary, Ashton Road, role in oesophageal disease aged 53 years, range 10-84) from the first Lancaster) Twenty four hour ambulatory nine months experience with ME 78% of pH monitoring is becoming widely used for tests with RT were successful in the J F MACKENZIE, JJ F BELCH, D V LAND, AND the diagnosis and quantification of gastro- J C WYATT (Gastroenterology Unit, Uni- quantification of reflux over 24 hours oesophageal reflux. At present, there are compared with 93% for RT (p<0O05 X2 versity Department of Medicine, Royal few guidelines as to the most appropriate on September 29, 2021 by guest. Protected copyright. Infirmary Glasgow and Faculty of Natural test). This difference was due to less partial diet to be followed during the investiga- Philosophy, University of Glasgow) technical failure and patient intolerance tion. Most publications describe the diet as Oesophageal chest pain may be related to with ME. In successful traces there was excluding foods with a pH<5 only and give oesophageal ischaemia rather than to significantly less trace loss with ME (0, no further details. We have analysed the oesophageal smooth muscle spasm. Oeso- 0-25%) than with RT (5, 0-46%) p<0-0001. pH of 50 breakfasts, lunches, and suppers phageal blood supply has been assessed in Calibration drift was also less with ME in an NHS hospital to identify foods which patients with disorders of oesophageal (0-1, 0-0*5 pH units) cf (0.5, 0-2 pH units) should be avoided during the study and to motility. Oesophageal rewarming rate after p

The British Society of Gastroenterology A595 In conclusion, specific foods have been would appear to be no less common than T16 identified which should be excluded during expected. Olsalazine and mesalazine: therapeutic monitoring and a diet developed which The distribution of the bowel lesions in options for patients intolerant of contributes towards standardisation. older patients did differ with 107 (60%) of them having disease confined to the large sulphasalazine bowel compared with 153 of 694 (22%) of the S S C RAO, P A CANN, AND C D HOLDSWORTH under 60s. More distal involvement of the (Gastrointestinal Unit, Floor H, Clinical colon also tended to be a feature of the Research Unit, Royal Hallamshire Hospital, older patient and only one third of these We required a major resection. Overall in 122 Sheffield) assessed the tolerance and INFLAMMATORY BOWEL safety of two new preparations designed to T13-16 patients with large bowel disease requiring release 5-aminosalicylic acid (5-ASA) in surgery 19 of 49 (38%) over 60 died in the the colon in patients with ulcerative colitis T13 perioperative period compared with five of who the younger patients (7%). Significant re- were intolerant of sulphasalazine (SP). Colonic cytomegalovirus infection in current disease occurred in a quarter of Twenty eight of 37 patients (76%) pre- inflammatory bowel disease scribed mesalazine and 18 of 21 patients these survivors regardless of age. (86%) prescribed olsalazine tolerated The disease is, therefore, not uncommon the S A C DUNDAS AND I A EYRE-BROOK (Uni- in the older patient where large bowel new preparations with no adverse versity of Sheffield Medical School, Shef- effects. No haematological or biochemical involvement is frequent. Although many of abnormalities field) Evidence of colonic cytomegalovirus these improve on medical therapy, surgery were detected. Each of the (CMV) infection has been found in three of carried a formidable mortality. two preparations appears likely to prove a 26 consecutive patients requiring colonic satisfactory alternative for SP intolerant resection for inflammatory bowel disease patients, but 24% of patients prescribed (IBD) confined to the colon. Colonic tissue mesalazine and 14% of patients prescribed from all cases was examined by light olsalazine were also intolerant of the new microscopy for CMV inclusions and for preparations. Adverse reactions to the new CMV antigen using an immunoperoxidase T15 preparations were usually but not always technique. The primary CMV antiserum Employment prospects and problems similar; a few patients experienced rash was obtained from one of the patients with in patients with inflammatory bowel and diarrhoea, which they had not en- CMV infection and its specificity for CMV disease countered with SP. In some patients found antigen confirmed using CMV infected to be intolerant of one of the new prepara- tions, their tolerance to the other was fetal lung fibroblasts. In the three cases R J WYKE, F C EDWARDS, AND R N ALLAN http://gut.bmj.com/ CMV antigen and inclusion bodies were (Gastroenterology Unit, General Hospital, assessed. Three patients with an adverse confined to endothelial cells and cells Birmingham) The employment prospects reaction to mesalazine were prescribed between blood vessels in the lamina of inflammatory bowel disease patients is olsalazine with no adverse effects. propria. One patient demonstrated a rising vital but has received little attention. This Similarly three other patients intolerant of titre of IgG to CMV. Treatment with study assessed 170 patients (UC 75, olsalazine tolerated mesalazine. Not all acyclovir eradicated CMV from the colon Crohn's 95) selected at random in 1978, adverse effects of SP are due to the without altering the course of her colitis. interviewed with a detailed proforma and sulphapyridine part of the molecule. Some All three cases required urgent surgery but are probably due to the released 5-ASA reviewed in 1985 by postal questionnaires on September 29, 2021 by guest. Protected copyright. none had toxic megacolon. In contrast with (93% response rate). One hundred and and some to the parent compound. previous reports we found no evidence of twenty one patients had undergone resec- CMV infection in three other cases with tion of whom 65 had an ileostomy. Seventy toxic megacolon. Our study suggests that two per cent were working in 1978 and CMV infection does not alter the course of 67% in 1985, other categories included POSTERS colonic IBD. housewives (17%), retired (8%). Un- employment rose from 2 to 5% (regional average 15%). Discrimination in obtaining T14 work or promotion was not uncommon LIVER Crohn's disease in the older patients particularly in stoma patients. Stoma T17-26 patients experienced less sickness absence C J SIMPSON, I S SMITH, AND S YOUNG (Vic- (p<005) and fewer problems at work than T17 toria Infirmary and Stobhill General the others. More changes in work,(p<005) Prednisolone pharmacokinetics after Hospital, Glasgow) A recent report from were necessary after panproctocolectomy orthotopic liver transplantation Birmingham suggested that Crohn's disease than after colectomy and ileorectal was rare in the over 60s accounting for just anastomosis. Convalescence was more P R POWELL-JACKSON, JUDIE ENGLISH, J M 8% of their 600 patients. often prolonged after panproctocolectomy TREDGER, AND ROGER WILLIAMS (Liver In the present study of 879 patients (30% off work two years later). Gastro- Unit, King's College Hospital and School of resident around Glasgow between 1961 enterologists may be too optimistic about Medicine and Dentistry, London) and 1980, 187 (21%) were over 60 at first time-off work after surgery and employers Pharmacokinetic studies have shown that diagnosis. In the area 20% of the popula- and occupational physicians clearly need the metabolic clearance of paracetamol, tion were aged over 60 and thus the disease informed and consistent advice. morphine and aminopyrine may be im- Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A596 The British Society of Gastroenterology paired after orthotopic liver transplanta- correlation of response with reduction bacteriuria. Women with recurrent bac- tion. Side effects of prednisolone are in free DHT suggests that hormonal man- teriuria may have a decreased survival. frequent in such patients, possibly because ipulation may be effective in HCC if free Natural history and potential benefit of of impaired metabolic clearance. In this DHT is reliably reduced; this can be antimicrobials in PBC bacteriuria are not study, we compared the pharmacokinetics achieved by CPA in combination with lose known. One hundred and twenty eight of the 'free' drug after its intravenous dose oestrogen or with LHRH agonists. PBC consecutive outpatients were administration (0.25 mg/kg) in 12 liver screened: 25 had asymptomatic bacteriuria, transplant recipients and in six pred- 14 randomised to repeated courses of nisolone treated patients without liver T19 antimicrobials (AB) and 11 to no treatment disease. Plasma albumin concentrations Hospital costs of upper gastrointestinal (NAB) 13 had symptomatic bacteriuria (SB) were lower in the transplanted patients bleeding in cirrhotics all treated. Weekly dip-slide specimens and than controls (29-4±1-9 and 36-6±1-9 g/l a standard questionnaire were used in respectively, p> 0-05) and, one hour A K BURROUGHS, M QADIRI, F D'HEYGERE, follow up. E coli were sero and biotyped to after the administration of prednisolone, S H THORNE, M T ELSE, K E F HOBBS, AND separate reinfection from relapse. The AB the percentage of 'free' drug was 36 and N MCINTYRE (Academic Department of and SB groups had 31 and 30 bacteriuric 16% respectively. Total body clearance Medicine, Surgery and Finance Depart- episodes and 18/7 and 14/6 reinfections/ was lower (26.2±3-9 and 76-8±5-2 ml/min ment, Royal Free Hospital and School of relapses respectively compared to 12 re- respectively, p<0-001) with the lowest Medicine, London) American studies of infections (similar organisms) in the NAB values occuring in three patients during variceal bleeding have recently included group in which bacteriuria was present for episodes of rejection. Thus 'free' plasma comparative treatment costs; there are 179 of 234 weeks (76%) of follow up. Over prednisolone concentrations are much none from UK. One hundred and thirty five years 193 PBC women were screened: higher after transplantation than expected seven consecutive admissions using a at first urine specimen 35 (18%) were and conventional doses of prednisolone standardised treatment protocol were infected (21 now dead) compared with 172 may be inappropriately high. documented. Medical/nursing man hours, non-infected (32 now dead) x2= 11-6 laboratory/other tests, medical/paramedical p<0-001. Bacteriuria may be a risk factor therapy were directly costed or hospital for survival in PBC. T18 and speciality cost statements were used at Possible role for antiandrogens in 1984/5 prices. Cirrhotics with variceal treatment of hepatocellular carcinoma bleeding (n=101): mean cost £3530/admis- T21 sion (mean stay 17 days) - only conserva- Are azygos blood flow measurements

tive measures needed (n=55), £195/day; http://gut.bmj.com/ A FORBES, M L WILKINSON, M JAWED IQBAL, acute sclerosis (n= 18), £205/day; staple accurate? P J JOHNSON, AND ROGER WILLIAMS (Liver transection (n= 18), £215/day. Cirrhotics Unit, King's College Hospital and School of non variceal bleeds (n=29), £215/day J G FREEMAN, M WILLIAMSON, AND C 0 Medicine and Dentistry, Denmark Hill, RECORD (Gastroenterology Unit, Royal The male (mean stay 10 days). Non-cirrhotic variceal London) preponderance in bleeds (n=7), £199/day (mean stay 17 Victoria Infirmary and University of New- cirrhotic patients with hepatocellular castle upon Tyne) Azygos blood flow and days). Admissions general medicine carcinoma (HCC) presence of andro- (n=2741), surgery (n=3537), all specialities (ABF) has recently been advocated as a gen receptors in tumour tissue suggest measure of portal blood flow diversion.

(n=24,413) cost £1142, £986 and £1100/ on September 29, 2021 by guest. Protected copyright. possible benefit from anti-androgenic When measured by a dual thermister therapy. Seventeen cirrhotic admission, respectively. Upper GIT bleed- patients (15 ing admission in cirrhotics costs 3 x thermodilution technique, values of up to men) with HCC were treated with the anti- average hospital admission. There is little 1400 ml/min have been claimed. The androgen cyproterone acetate (CPA), accuracy of this technique for measuring 100 to 300 difference in cost between various treat- mg increasing mg daily. Hepatic ments, a situation different from the USA, blood flow in large vessels is, however, not ultrasound, alphafetoprotein (AFP) and and thus these may not influence treatment known. Using a dummy loop system of sex steroid concentrations were monitored. choice in the UK. silastic tubing with an internal diameter of In one man there was a 50% reduction in 1 cm, and containing 50% glycerol at 37°C, tumour volume with stabilisation of pre- flow rates measured by thermodilution viously rising AFP for seven weeks (sur- using water as injectate were compared with vival 14 weeks). In another, AFP level fell T20 values generated by a paediatric cardiac by 63% and remained so for eight weeks Natural history of bacteriuria in bypass pump. Mixing of water and glycerol without increase in tumour volume (sur- primary biliary cirrhosis at the catheter tip was assessed by photo- vival 53 weeks). A possible delayed re- graphy. There was no significant correla- sponse was seen in one woman. Six other A K BURROUGHS, I R ROSENSTEIN, 0 EPSTEIN, tion between calculated and known flow patients had documented stable disease. J M T HAMILTON-MILLER, W BRUMFITr, AND N rates from 250-1500 ml/min (r=0-54; Median survival for all evaluable patients MCINTYRE (Academic Departments of p> 0-05) although a linear relationship was 19 weeks. Apart from transient Medicine and Microbiology, Royal Free between 250 and 750 ml/min was demon- paranoia in two cases side effects were Hospital School of Medicine, London) strable (r=0-83; p<0-05). Altering the minimal. Total testosterone and dihydro- Female patients with primary biliary injectate rate did not improve the results testosterone (DHT) fell during therapy but cirrhosis (PBC) have a high prevalence while still photography revealed poor an increase in free DHT was found except (19%) and incidence (35%) of pre- mixing at the catheter tip. We would in the two responding men. The apparent dominantly asymptomatic significant conclude that ABF measured by the Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from The British Society of Gastroenterology A597 thermodilution technique is unlikely to tion of hepatic arterial and portal necrosis was assessed and histological sec- accurately measure high flow rates when venous components of liver blood flow tions prepared. The coefficient of variation errors of up to 500 ml/min may be en- for the diameter of the well-defined nec- countered. P MACMATHUNA, M O'CONNOR, P FREYNE, rotic lesions produced was 8% with maxi- AND P W N KEELING (Departments ofClini- mum diameter 16 mm. Extent of necrosis cal Medicine and Nuclear Medicine, Trinity depended on both power (optimum 1 watt) T22 College and St James' Hospital, Dublin, and total energy used (optimum 600 Joules). Propranolol versus endoscopic sciero- Ireland) It has been established that Histology showed coagulative necrosis therapy for prevention of recurrence of portal venous blood flow (PVBF) decreases which healed by granulation with small variceal bleeding in patients with cirrhosis and associated fibrous nodule at 60 days. We conclude portal hypertension, however, it has been that this technique produces coagulative difficult to measure the portal venous (PV) necrosis which is clearly demarcated from P ALEXANDRINO, M MARTINS ALVES, AND surrounding undamaged tissue; its extent is J PINTO CORREIA (Department of Medicine component of total liver blood flow (LBF). In this study we describe a method of non- highly controllable, depending on power 2, University Hospital of Santa Maria and energy; and it heals by fibrosis. Lisbon, Portugal) There is increasing evi- invasively assessing PVBF using dynamic dence that it is possible to prevent the hepatic scintigraphy (DHS) and using recurrence of oesophageal variceal bleed- Deconvolutional Analysis (DCA) modified ing. We report here a prospective from the technique described by Juni et al randomised trial, between endoscopic (1985). Intravenous "mTc 04 was given to T25 sclerotherapy (ES) and continuous pro- 41 fasting patients (15 controls (CS), 23 cirrhotics (six child A, 17 child B+C) and Management of giant cavernous pranolol in patients with previous endo- haemangiomas of the liver scopically proven oesophageal variceal three with portal venous thrombosis bleeding. Patients were randomised by (PVT)). Using splenic arterial isotopic flow curves to represent the hepatic arterial H A BRADPIECE, M KRAACHT, J N THOMPSON, separate sealed envelopes for Child's A R A HEMINGWAY, AND L H and B groups, either to oral propranolol (HA) curve, by DCA, HA/PV ratios were N GIBSON, calculated. Patients with Child grade B+C BLUMGART (Department of Surgery, (34) or to ES (31) in order to evaluate the Royal Postgraduate Medical School, effect on rebleeding and mortality. Oral have significantly greater % HA flow com- pared with that found in CS (x=56±5-6, Hammersmith Hospital, London) From propranolol was given to reduce the resting July 1979 to December 1985, nine patients pulse rate by 25%. ES was done using n=17 vs x=21±2-1, n=15, p<0-001). Furthermore the % HA flow in patients with symptomatic giant (> 4 cm) ethanolamine oleate intravascularly in a cavernous haemangiomata have been three weeks' schedule. The two groups with PVT had increased to 98±2-1. In conclusion, it is possible to determine assessed and treated. were similar in age, sex, cause of portal The maximum dimension of the lesions http://gut.bmj.com/ hypertension or Child's grade. During a the per cent change in hepatic arterial and indirectly portal venous flow in patients ranged from 5-54 cm (mean 17-0 cm) and follow up period from six months up to seven of nine were situated in the right three years, 16 of 34 patients in the with cirrhosis and in those with PVT by this non-invasive technique. lobe. Computed tomography scanning was propranolol group and 18 of 31 patients in accurate in determining the dimensions of the sclerosis group have had rebleeding the lesion in all the patients. Angiography from oesophageal varices. The cumulative showed portal vein compression (four percentages of patients free of oesophageal T24 patients) and venacaval compression (five variceal rebleeding after inclusion were Biological effects of intrahepatic Nd patients). on September 29, 2021 by guest. Protected copyright. 46% in the propranolol group and 60% in YAG laser photocoagulation Surgery or embolisation was undertaken the sclerosis group. The difference between in patients with pain or discomfort at the two groups after six (log-rank test) K MATrHEWSON, P COLERIDGE-SMITH, J P presentation. The six patients who had months of follow up was statistically O SULLIVAN, T C NORTHFIELD, AND S G hepatic resections at the outset had the significant (p=0-02). The cumulative per- BOWN (Gastroenterology Unit, University largest tumours and were unsuitable for centage of patients free of bleeding from College Hospital and Gastroenterology Unit embolisation. There were no perioperative any source, however, (oesophageal and and Department of Pathology, St James' deaths but two were re-explored for post- gastric varices, acute oesophageal and Hospital, London) Attempts to target operative bleeding. Subsequently they gastric ulcers or erosions) was 20% in the therapy at hepatic tumours via the hepatic remain symptom free. Embolisation was propranolol group and 37% in the sclerosis artery have met with limited success. A used in three patients with improvement of group (NS). Up to now, there was no theoretical alternative would be to target symptoms seen in two. No significant difference in survival in the two groups. the deeply penetrating beam of the Nd tumour shrinkage was observed after We conclude that endoscopic sclerotherapy YAG laser via thin fibres inserted into the embolisation, and the patient who re- seems to be more successful than oral tumour under ultrasound or laparoscopic mained symptomatic came to resection. propranolol in the prevention of recurrent control. To assess the biological effects on Two patients underwent laparotomy for oesophageal variceal bleeding, but not in normal liver tissue, 0-4 mm optical fibres diagnostic purposes but were not resected. the prevention of all bleedings. were inserted into livers of anaesthetised The follow up is one to 58 months all Wistar rats at laparotomy. These were then patients remaining asymptomatic. Surgical irradiated with pulsed Nd YAG laser light resection is the treatment of choice for T23 using 0-5 to 2 watts for 50 to 2400 seconds. symptomatic giant haemangiomas of the Dynamic hepatic scintigraphy: evalua- One hour to 60 days later the extent of liver. Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A598 A59ieBeitiush SocietY of Gastroenterology

T26 GOR. 13 of whom were investigated on were sustained for the duration of the Aberrant expression of HLA-DR in two occasions. The investigations com- distention period, and showed phasic pressure salivary tissue of patients with primary prised RNT (transit image and 90(% transit variation independent of swallowing. time), endoscopy (oesophagitis graded With distention, secondary peristalsis was biliary cirrhosis (-4), biopsy (histological oesophagitis stimulated above the balloon (threshold graded (-11) and 24 hour ocsophageal pH 1-5 cm) and showed stepwise increases M G lOMBARD. S FORSTER. P D)F RVAN. AND monitoring (DDe Meester score). Reflux of with inflation (maxim response 6(9±2-48 J P CROWi (Departments of Ga.stroeniter- Technetium labelled water was readily contraction/min). Distal propagation of olog anid Pathology, Mater Misericordiae identifiable on the transit image and was peristalsis, however, became progressively Hospital anid UniversitY College, Dulblini, inhibited. Irelanid) Primary hiliairy cirrhosis (PBC) almost exclusively the causc of prolonged 90%/ transit. The mean 90)X transit time of The definition of these interrelated is commonly associated with autoimmune 3x 10 ml water swallows correlated with dynamic responses to distension now pro- phenomena and 750,, patients haive sicca vides a rational approach to investigation syndome. Previous studies have suggested the grade of oesophagitis at endoscopy (rS= 04, p=0 ()2) but not with the histo- of patients with suspected UOS malfunc- that aberrant expression of class 11 MHC logical grade nor the Dc Meester score. tion or impaired oesophageal clearaince but antigens on bile duct epitheliulll in PBC is The De Meester score correlated with the with normal standard manometry. relevant to its pathogenesis. grade of oesophagitis at both endoscopy Liver and gingival biopsy specimens (rS=0-7, p<(.)(XX)l) and histological examin- from 15 patients with PBC were examined ation (rS=0-4, p=0-02). (Spearman's Rank for the expression ot HLA-DR aintigen and T29 inflarmmatory infiltrate using monoclonal Order test). If pathological reflux is defined as a raised De Meester score (> 18). the What is the significance of the aperi- antibody techniques. Results were com- diagnostic accuracy of endoscopic and histo- staltic oesophagus? pared with 44 liver biopsy and five gingival logical oesophagitis together was 87-5% biopsy spccimens from non-PBC piatients. whereas that of radionuclide reflux was only W J OWEN. J l INSEL I., AND A ANGGiANSAH Seventy per cent PBC patients expressed 65% (pepithelium. Of the non-PBC patients, with the degree of macroscopic oesophagitis. defined by failure of oesophageal peri- 10% expressed HLA-DR on bile duct radionuclide reflux on RNT is inadequate for stalsis and of relaxation of lower oeso- and 20%( on saliviary gland epithelium the diagnosis of pathological reflux. phageal sphincter. Radiology may fail to epithelium. There was no statistical corre- identify achalasia and this work investi- lation between HLA-DR expression and gates the usefulness of manometry. The inflammatory infiltrate in either tissue. A with

manometric data ot patients aperi- http://gut.bmj.com/ common aintigen on bile duct epithelium T28 stalsis were compared with the radiological and salivary gland may be responsible for Responses of the oesophageal upper findings on barium swatllow and with the the association between PBC and sicca sphincter and body to graded disten- final diagnosis. In a series of 196 consecu- syndromc. sion tive patients presenting with chest pain and dysphagia who underwent oesophageal NA ANDREOL1O, D G I'iIOMPSON, G P N manometry using a Galetec microtrans- KENDALL, AND R EARLAM (Departments ducer system 18 patients (90/O) were found Gastroenterologs anid Surgery, The to have aperistalsis and impaired relaxation of on September 29, 2021 by guest. Protected copyright. upper of the lower sphincter. The OESOPI iACiUS London Hospital, London) The oesophageal T27-31 oesophageal sphincter (UOS) serves the diagnosis of achalasia was confirmed in important function of protecting the airway 14 patients after successful treatment T27 from reflux. We tested UOS responses to (myotomy=5 dilatation=9). All 14 intraluminal distension of the oeso- patients with achalasia were successfully Is of the transit of radio- graded the study phageal body to determine its response identified using manometry by the criteria nuclide labelled water through the threshold and to define the functional of aperistalsis and impaired relaxation of oesophagus of value in the diagnosis relationships between it and the oeso- the LOS whereas the diagnosis was only of pathological gastro-oesophageal phageal body. Nine normal subjects under- made in eight of 14 patients by barium reflux? went oesophageal manometry using an 8 swallow. This difference is statistically lumen tube with three ports in the UOS significant (x=25 42 p<()(2). In the

W G CASL, I P BEI TON, M C J BARKIR., AND N S and five sited at intervals on either side remaining four patients with aperistalsis Wll liAMS (Department ovf Surgery anid of an inflatable balloon sited 1() cm termed 'pseudo achailasia' the following Department of Nuclear MediCinle, The below the UOS. Motor responses to six diagnosis were made gastric carcinoma General Infirmnary, L.eels) Although the graded balloon inflations between 1-10 ml (two) gastric lymphoma (one) mediastinal place of radionuclide labelled wiater (RNT) (0(8-2.2 cm diameter) were recorded three fibrosis (one). Radiology in this group in screening for oesophageal dysmotility is minutes at each inflation and compared with suggested the correct diagnosis in half. established, the significance of reflux of interposed non-distension control periods. Oesophageal manometry has a greater isotope in patients with gastro-oesophageal The mean basal sphincter pressures sensitivity in the detection of aperistalsis reflux (GOR) is unknown. We have pro- were 32 7±3-34 mmHg (mean+SEM). than barium swallow but radiology is help- spectively studied 27 patients (17 men: 1t) Tonic pressures rose progessively to ful in selecting out patients with pseudo women, 54 years, r=21-71) referred with 118-7±2-97 mmHg at highest distension, achalasia. Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

The British Society of Gastroenterology A599 T30 new endoscopic means to stop variceal T33 Vagal function in achalasia bleeding. Double rows of staples were Erythrocyte stearic acid desaturation delivered endoscopically to COJ in human in patients with colorectal carcinomas H L SMART, A L OGILVIE, AND M ATKINSON cadaveric and canine survival studies. (Department of Surgery, University of Poultices impregnated with steroid, cyto- N A HABIB, M J HFRSHMAN, P CARTER, K Nottingham, University Hospital, Notting- protective or cytotoxic drug were stapled APOSTOLOV, R C N WILLIAMSON, AND C B ham) Morphological vagal truncal endoscopically to gastric targets in survival WOOD (Departments of Surgery, Bristol abnormalities have been described in studies in dogs. Staples designed with Royal Infirmary, Bristol and Royal Post- achalasia but doubt remains about their threaded eyes were secured to the stomach graduate Medical School, London and significance and their relationship to wall at endoscopy. Thread was tied to Department of Virology, Royal Post- ganglion cell loss in the myenteric plexus. Ryle's tubes which were pulled into the graduate Medical School, Lonidon) To assess the functional significance of stomach using the eyed-staple as pulley and Patients with cancer often suffer systemic these vagal changes, vagally mediated re- secured. This study shows that endoscopic effects of the disease suggesting that the flexes were studied in 24 patients with stapling devices can terminate ulcer bleed- tumour produces a factor(s) which act on achalasia. The lower oesophageal sphincter ing, ring the oesophagus with staples and the normal cells and are responsible for the response (LOS) to abdominal compression secure drug impregnated poultices or systemic changes. To assess this phenome- was subnormal in only one of nine patients feeding tubes in the stomach. non we have studied the desaturation of with untreated achalasia, but in 11 of 15 erythrocyte cell membranes in patients patients who had undergone forceful dila- with large bowel cancer. Total lipid ex- tation or cardiomyotomy in the past. These tracts of erythrocyte cell membranes from findings presumably result from thera- 50 normal subjects, 20 patients with in- peutic disruption of the circular muscle of flammatory bowel disease and 44 patients the LOS rather than vagal dysfunction. with colorectal carcinoma were analysed by Efferent vagal function, as assessed using COLORECTAL gas liquid chromatography (GLC). The the insulin/pentagastrin secretory ratio, T32-40 ratio of stearic to oleic acid was obtained was normal in each of nine patients, as was from the GLC tracing and was expressed as the pulse rate variability with deep respira- T32 the saturation index (SI). The mean SI in tion used to assess cardiac vagal function. cancer patients (0.71+0.22) was about half These findings suggest that the preganglion Prognostic significance of DNA aneu- the value in normal subjects (1.54±0.32; vagal fibres in achalasia are functionally ploidy in rectal adenocarcinomas p<0-001), and in those with inflammatory intact. bowel disease (1.30±0 4; p<0)(01). After P QUIRKE, P DURDEY, M F DIXON, A D radical resection the SI increased above http://gut.bmj.com/ CLAYDEN, J E D DYSON, N S WILLIAMS, AND unity, only to fall again with the onset of CC BIRD (University Departments of Path- tumour recurrence. Thus, it would appear T31 ology, Surgery, Radiotherapy and Com- Endoscopic stapling in the oesophagus that a desaturation producing factor is munity Medicine, University of Leeds, being released by the malignant cells. The and stomach Leeds) DNA aneuploidy in colorectal erythrocyte SI is therefore of potential tumours is a poor prognostic indicator. We value in the diagnosis and postoperative C P SWAIN, G BROWN, S MARGARET ROE, M R have investigated its importance in a series monitoring of patients with carcinoma of LEWIN, AND T N MILLS (Departments of of 125 rectal adenocarcinomas and com- the large bowel. on September 29, 2021 by guest. Protected copyright. Medical Physics and Gastroenterology, pared DNA content, and the presence of University College and St George's tumour heterogeneity of DNA content, to Hospitals, London) We designed an histopathological factors and patient sur- endoscopic stapling device which can vival. Flow cytometric DNA analysis was T34 deliver a double-row of staggered staples to done on all available paraffin embedded Faecal carcinoembryonic antigen stop bleeding in the stomach or encircle the blocks of the primary tumour using the (CEA) in patients with large bowel oesophagus with staples without lapar- method of Hedley et al. cancer otomy. Another stapler was designed to Significant prognostic factors using Man- secure objects within the GI tract with tel Cox log rank statistics were ploidy R S STUBBS, D M NADKARNI, AND II A single staples. Both exploit suction of an (p<002) Dukes's stage (p<0.001), grade MONSEY (Department of Surgery, Hilling- artifical 'polyp' of tissue which is then (p<0 02) and lymphoid infiltration don Hospital, Middlesex) The possibility transfixed with staples. Choice of metals (p<0.03). The survival curve of tumours that faecal CEA may be more useful than and pattern of tissue-compression allowed containing both diploid and DNA aneu- serum CEA for the detection of large design of staples to remain in GI tissue for ploid areas was identical to the DNA bowel cancer has received very little atten- (1) hours, (2) days, (3) indefinitely. Bleed- aneuploid curve. DNA tetraploid tumours tion. For this reason faecal CEA was ing was terminated in 15/15 standard (Diploid index 1.8-2.2), however, showed measured before and after tumour resec- canine ulcers by driving a double-row of a similar prognosis to the Diploid tumours. tion in colorectal cancer patients and in a staples across the ulcer; 0/10 controls Thus the finding of DNA aneuploidy in a variety of control subjects. CEA was ex- stopped bleeding (p<0.01). Stapling rectal carcinoma is an adverse prognostic tracted with 3M KCI and assayed by an stopped bleeding quicker than heater- feature but a subgroup of DNA tetraploid EIA technique utilising two monoclonal probe (p<005). Stapling at the cardio- tumours must be identified as they appear antibodies. Mean±SE faecal CEA in 32 oesophageal-junction (COJ) might offer to have a better prognosis. cancer patients was 4-15+1-17 [tg/g pre- Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A600 The British Society of Gastroenterology operatively. Values were not related T36 (25O0%). All recurrences occurred within to either stage of disease or serum CEA Low powered Nd YAG laser treatment two years and were significantly associated and they fell to 0(83±0+34 Ftg/g (n=20) of colonic tumours with Duke's C stage (p<0 (5) but not to after tumour resection (p<0'05). tumour height from the anal verge or sex of Mean±SE faecal CEA in 34 control K MATHEWSON, T BARTON, M R LEWIN, J P the patient. Log Rank Testing showed no patients with no known colorectal disease O SULLIVAN, T C NORTHFIELD, AND S G significant difference in survival between was 0 94±0 49 sg/g which was significantly BROWN (Gastroenterology and Surgical the two groups. lower than in the cancer patients (p<0'05). Units, University College Hospital and We conclude that the circular stapler has Furthermore faecal CEA in 25 patients Gastroenterology Unit and Department of a mortality, morbidity, and risk of local with non-malignant colorectal disease was Pathology, St James' Hospital, London) recurrence comparable with radical exci- 1-44±0 63 [tg/g which again was signifi- Current treatment of colorectal tumours by sion with a permanent colostomy. cantly lower than that in the cancer patients. Nd YAG laser uses high power settings and We conclude that CEA is present in the a non-contact technique. We have evalu- faeces of the majority of colorectal cancer ated a low power, contact Nd YAG laser patients even at early stages of the disease T38 technique in the treatment of dimethyl- Cytocidal washout and and its measurement here may be more hydrazine induced rat colonic carcinomas. pelvic/local useful for the detection of large bowel Thirty tumour bearing Wistar rats were recurrence of colorectal cancer cancer than that in serum. colonoscoped using a paediatric broncho- scope. A 400 sim laser fibre passed through M R B KEIGHLEY AND CHRISTINE HALL the biopsy channel was inserted into the (Department of Surgery, General Hospital, tumour which was then exposed to pulsed Birmingham) Exfoliated malignant cells can be identified from the bowel at some T35 Nd YAG laser light with an average power of 1 watt for 100 to 600 seconds. Treated distance from the original tumour and Detection of metastatic and recurrent certain agents are able to inhibit the growth cancer colon was removed for histological assess- colorectal by immunoscinti- ment one hour to 21 days later. Random of these cells. Despite this, there are no graphy animals were followed up colonoscopically. clinical trials which show that cytocidal A 300 second exposure was sufficient to washout reduces the incidence of local K C BALLANTYNE, A C PERKINS, N C ARMIT- cause a 1 cm tumour to undergo complete recurrence. We have conducted a random- AGE, M V PIMM, M L WASTIE, R W BALDWIN, coagulative necrosis, which was followed ised study in all patients having a restora- AND J D HARDCASTLE Departments of by sloughing and the development of a tive resection for solitary carcinoma of the Surgery, Medical Physics and Cancer Re- clean based ulcer which healed within 28 sigmoid and rectum without distant disease search, University Hospital, Nottingham) days. Shorter exposures caused incomplete since 1982 (excluded: patients with fixed http://gut.bmj.com/ The monoclonal antibody 791T/36 localises necrosis whilst longer ones increased the tumours having pelvic radiotherapy). Rec- in colorectal cancer enabling its detection risk of complications, including perforation tal and proximal colonic irrigation was by external gamma camera imaging. The and enterocolic fistula formation. We con- done with hypochlorite solution or had no aim of this study was to evaluate prospect- clude that this technique may be of value in irrigation. So far 47 patients fulfilled these ively the use of this antibody in the man in the treatment of sessile polyps or criteria. There were two hospital deaths. detection of suspected recurrent and meta- inoperable carcinomas. The number of local recurrences in static colorectal cancer. Forty six patients December 1985 was eight (16%) and they

(25 men, 21 women) underwent 52 im- were equally distributed, four of 25 having on September 29, 2021 by guest. Protected copyright. munoscans. Of these 42 had 'NmTc liver washout compared with four of 22 having scintigraphy, 28 abdominal ultrasono- T37 no washout. graphy, 28 computerised axial tomography Rectal cancer: abdominoperineal or These early results suggest either that and 17 laparotomy. The indications for stapled anterior resection? hypochlorite is a poor cytocidal agent or investigation were pain (46%0), a mass that the theory of local implantation as a (27%), hepatomegaly (13%) and raised P GILLEN AND A L G PEEL (Department of major cause for recurrence is incorrect. serum carcinoembryonic antigen (CEA) Surgery, North Tees General Hospital, (65%). In 19% patients raised CEA was Stockton-on-Tees, Cleveland) Fifty five the only detectable abnormality. Fifty seven patients with rectal cancer were treated by sites of recurrent disease were detected in stapled anterior resection (SAR) and 45 by T39 37 patients; 37 of these sites were positively abdominoperineal resection (APR) by one Increased risk of colorectal cancer identified by immunoscintigraphy, giving a surgeon over seven years. Duke's classi- after gastric surgery sensitivity of 64%. Nine patients remain fication, degree of differentiation and local disease free with a median follow up of 12 spread were similar in both groups. Opera- C P J CAYGILL, M J HILL, J S KIRKHAM, AND T C months (9-27 months). Thirteen had false tive mortality was 7.2% for SAR and 2.2% NORTHFIELD (PHLS-CDSC, Colindale positive immunoscans giving a specificty of for APR. Anastomotic leakage after SAR Avenue, London, Bacterial Metabolism 70(%. Immunoscintigraphy is a clinically occurred clinically in two patients (3-6%), Research Laboratory, PHLS-CAMR, useful imaging modality in the detection of one of which proved fatal, and radiologic- Porton Down and Norman Tanner Gastro- recurrent and metastatic colorectal cancer, ally in five patients. Morbidity after SAR enterology Unit, St James Hospital, and is likely to prove of particular value and APR was otherwise similar. There was London) We reported previously to the where computerised tomography is not no significant difference in local recurrence Society that after gastric surgery there is an available. rates after SAR (14-7%o) and APR groups increased risk of a wide range of cancers, Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from The British Society of Gastroenterology A601 including colorectal cancer (CRC). The and one of the vesicociolic had developed a Middlesex Hospital, London) Between present study analyses factors influencing tumour. All the rats in the vesicocolic May 1983 and December 1985 endoscopic this risk. Analysis ('years at risk' calcula- group had tumours at four months which insertion of a large diameter prosthesis was tion in five year bands) of 4466 ulcer were adenocarcinoma s with some transi- attempted in 64 patients with hilar stric- patients in Balham showed a non-statistical tional elements. tures due to cholangiocarcinoma (42), car- drop in mortality from CRC (relative rate This study also shiows that colon in cinoma of the gall bladder (10) and meta- (RR)=0-7) in the first 20 post-operative contact with urine un[dergoes hyperplasia stases (12). The stricture involved both left years followed by a 1 6-fold (p<0-05) rise. and premalignant chainge; the addition of and right hepatic ducts plus intrahepatic This decrease in the first 20 years was faeces promoting a m,alignant transforma- ducts (Type 3) in 41, involved left and right entirely because of a large decrease in the tion. hepatic ducts (Type 2) in nine and the 659 men who had a Bilroth I for gastric common hepatic duct within 2 cm of the ulcer (GU) (RR=-02; p<0 01). The excess bifurcation (Type 1) in 14. This was a high risk after 20 years was almost entirely risk group of patients unsuitable for because of the large increase in risk (9.5- PANCREATICOBILIARY operation - median age 68 years (34-91) fold; p<0-001) in the 381 women who had T41-52 mean bilirubin 405 umol/l; 16 patients a Bilroth I for GU. All other patient (25%) had renal impairment. Biliary pros- groups (including 2286 who had a Bilroth T41 theses were straight with proximal and II) had the expected risk of mortality from Safer endoscopic retrograde pan- distal flaps. The external diameter was CRC except for the small group (123) of It) Fr or 11 5 Fr except for two patients with female vagotomy patients who had an creatography? very tight strictures where 8 Fr prostheses increased (8-0 fold: p<0-05) risk with a 20 were inserted. A prosthesis was success- year latency. We conclude that the risk of A K BANERJEE, S L GRAINGER. RACtEL fully inserted in 52 patients (81%); with developing CRC after gastric surgery is MANNERS, AND R P H - higher success in Type 1 and 2 strictures strongly influenced by sex and type of intestinal Unit, The Rayne Institute, St (96%) than Type 3 (73%/o). The serum surgery. Thomas' Hospital, Losidon) A small per- bilirubin fell in 44 patients overall (73% of centage of patients un(dergoing endoscopic attempted procedures): - 91% of Type 1 retrograde pancrea.tography .ERP and 2 strictures and 56% of Type 3 develop acute pancre atitis causing mor- (p<001X2). The 30 day mortality for T40 bidity and occasional (deaths. To minimise successfully inserted prostheses was 7 Tumour formation after colonic pancreatic damage lowv osmolality contrast patients (13%) and was similar for each urinary diversion media have been use:d, but with incon- type of stricture. Early complications sistent benefit. We hiave compared in a occurred in nine patients (15%), mainly http://gut.bmj.com/ J R STRACHAN, JOYCE MAnHEWS, H REES, double-blind parallel sttudy the incidence of cholangitis. At the time of analysis 17 AND T COOKE (Department of Surgery, pancreatitis after ERIP using either Uro- patients remained alive. The mean survival Charing Cross & Westminster Medical grafin 290 (osmolality 5mHol/k)g HT) otr of patients with successfully inserted pros- School, London) Urinary diversion into Omnipaque (t).69 mo I/kgH0. Twenty theses was four months. Endoscopic inser- the colon produces adenocarcinoma at the five patients receiv,ed Urografin, 24 tion of a biliary prosthesis can provide site of anastomosis in both man and Wistar Omnipaque. The indications, quality of palliation for this difficult group of rats. pancreatograms and ffinal diagnosis were patients. The presence of intrahepatic stric- Four groups of rats had either a vesico- similar in both group!Ns. tures makes palliation more difficult. colic anastomosis, urothelium implant into iviumaiiMedsian inirrementMtIWIUIIIC;11L 10c))f N~UIlJ31,ernlm dlilY1dNV,imvli,ce, NIA-oy on September 29, 2021 by guest. Protected copyright. the colon, a colonic conduit or acted as an hours after ERP was similar (after Uro- operative control Crypt cell production grafin +277 lU/l; after Omnipaque +238 rate (CCPR) was measured at one and IU/I). Five patients, however, developed T43 three months in the rectal mucosa at the biochemical pancreatitis (increment of Bacteria, biofllms and biliary sludge anastomosis site. The rats were killed at 20 amylase > 1000 IU/I) after Urografin, minute intervals after vincristine injection. whilst no patient did after Omnipaque A G SPEER, H FARRINGTON, J W COSTERTON, Colonic crypts were microdissected and (p=0.027, Fisher's exact test). Four of AND P B COrrON (Department of Gastro- arrested metaphases were plotted against these developed fever and three prolonged enterology, The Middlesex Hospital, time to derive the CCPR. abdominal pain delaying their discharge Mortimer Street, London) Clogging of There was no significant difference in from hospital. The absence of pancreatic biliary prostheses limits long term function- CCPR between the control and urothelial damage after Omnipaque 300 makes this ing. Previous investigation has shown the implants, but there was a five times in- an ideal contrast medium for ERP, but lumen occluded by biliary sludge consisting crease in the CCPR in both the vesicocolic may be unrelated to its low osmolality. of calcium bilirubinate embedded in a and colonic conduits at one month fibrous matrix. We have examined five (p<-OOI). The increase in CCPR was blocked prostheses by electron microscopy maintained at three months. T42 (EM). The specimens were prepared in a Histology of the control and urothelial Endoscopic palliation of malignant manner designed to preserve the structure groups was normal throughout. Both hilar strictures of organic material. Scanning EM showed vesicocolic and colon conduits had dys- that the internal and external surfaces of plastic changes at one month. At three A G SPEER, P B COTION, ANI) L P DINEEN the prostheses were covered in bacteria months the colon conduits had dysplasia (Department of Gastroenterology, The embedded in a condensed fibrous matrix. Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from A602 The British Society of Gastroenterology On transmission EM a mixed population of T45 was confirmed by biochemical and radio- gram negative and gram positive bacteria Mechanism of biliary prosthesis block- nucleotide studies. were seen to be surrounded by anionic age: scanning electron microscopy evi- Eighteen patients had pancreatic adeno- fibrous material that stained with ruthen- dence carcinoma; six had cholangiocarcinoma; ium red. The material was identified as an two had adenocarcinoma of the gall exopolysaccharide glycocalyx produced by bladder and five had biliary obstruction of the bacteria. This J W C LEUNG (Combined Endoscopy Unit, glycocalyx anchors the Departments of Medicine and Surgery, benign aetiology. Seven patients (26.9%) bacteria to the stents and to each other to Prince of Wales Hospital, Hong died whilst in hospital and their mean form a biofilm. We that Kong) survival was 18-1 propose stent Scanning electron microscopy of (2-62) days. The remain- is initiated bacterial (SEM) 24 were clogging by adhesion sectioned blocked prostheses revealed bac- ing (73 1%) discharged with com- and growth of a biofilm. The bacteria then plete relief of jaundice. The mean survival deconjugate bilirubin in bile and the terial attachment to the internal surface of lumen the prosthesis and presence of of those with malignant biliary obstruction is progressively occluded amorphous was 7-79 by deposition of material in the luminal content. This study (1-24) months. The five patients calcium bilirubinate and further biofilm who had obstruction are tested the hypothesis that live bacteria are benign biliary still formation. Conventional doses of anti- associated alive five years following surgery. biotics have been unsuccessful in with sludge formation. Seg- Dacron killing ments of 10 FG polyethylene, Teflon, and bypass effectively relieves bacteria protected by biofilms on other obstructive jaundice in patients considered biomedical devices. Further research polyurethane prostheses were perfused is continuously at 37°C for one week with (1) technically inoperable for conventional needed to identify effective antibiotics. infected bile procedures. The proximal anastomosis can The deposition of on containing 106 E colilml (2) be sludge biliary pros- centrifuged bile to remove the bacteria (3) completed quickly, where access is theses may be a useful model for pigment limited by railroading the prosthesis on a stone formation. formalin treated and (4) autoclaved bile to kill the bacteria, and (5) sterile bile. A continuous prolene suture. The efficacy of second study was carried out using bac- Dacron bypass needs to be compared with terial broth containing E coli and sterile percutaneous or endoscopic biliary drain- T44 broth. SEM examination was done on age procedures. Towards a selective policy of operative inner surface of these tubes and luminal cholangiography? A prospective content. Results showed that, for tubes clinical study perfused with infected bile and broth con- T47 taining live E coli, deposition of Hepatotomy for high bile duct stricture C J SIMPSON, A D amorphous material was heavy with forma- SMITH, C SMITH, AND G tion of concretion. By contrast, tubes

GILLESPIE (Department of M J COOPER AND R C N http://gut.bmj.com/ Surgery, Vic- perfused with WILLIAMSON (Uni- toria Infirmary, Glasgow) A prospective sterile bile or broth showed versity Department of Surgery, Bristol study in 108 patients undergoing elective scanty deposits. These in vitro studies show Royal Infirmary, Bristol) Resection (or cholecystectomy assessed the effect of a that live bacteria are necessary for the of inititation of sludge formation in biliary bypass) intrahepatic bile ducts for hilar selective policy, based on surgical judge- carcinoma or stricture is facilitated by ment, on the rate and results of operative prosthesis, and this is independent of the liver material used for making the splitting parenchyma - that is, hepat- cholangiography. The operating surgeon prosthesis. otomy. Between 1981-1985 we have under- was asked to decide, given the knowledge taken 12 such operations on 11 patients (six of the patients history, physical men: examina- five women; median age 55 years; on September 29, 2021 by guest. Protected copyright. tion, liver function tests, the size of gall range 40-79). There were three benign and bladder stones at operation, and having T46 eight malignant strictures of the bile duct assessed but not measured the cystic duct Dacron biliary bypass: an appraisal of within the liver hilus. In seven patients the and common duct calibre, and having the efficacy in 31 patients lesion was approached by a 10-15 cm palpated the bile duct, whether an opera- hepatotomy; excision of the quadrate lobe tive cholangiogram was indicated. Of H J SCOT-, I F LANE, I M MURRAY-LYON, AND improved access in four patients. For re- 25 patients thought to require a cholangio- K W REYNOLDS (Gastrointestinal Unit, construction a Roux loop was anastomosed gram, 13 cholangiograms were normal, and Charing Cross Hospital, Fulham Palace either to dilated ducts (five) or to the 11 abnormal and these included one false Road, London) A Dacron graft has been adjacent liver capsule (five). In two positive and one false negative examina- inserted in 31 patients to bypass an obstruc- patients (one with a previous median tion. Eighty three patients were thought tion of the biliary tree. This procedure, as hepatotomy) decompression was achieved not to require cholangiography and of opposed to conventional surgical measures, by splitting the umbilical fissure and these two cholangiograms were abnormal, was used as the patients were considered anastomosis to the left hepatic duct. including one false positive examination. unsuitable for biliary-enteric anastomosis Transhepatic stents were routinely used Three cholangiograms were abnormal, but or hepatico-jejunostomy due to tumour and were removed at a median of four only one patient had unsuspected stones. A extending to the porta hepatis; direct duo- weeks. There were no postoperative selective policy would have avoided 77% of denal invasion of tumour; previous biliary deaths. One patient each developed examinations and avoided a fatal negative tract surgery and previous gastrectomy. In cholangitis and delayed biliary fistula. duct exploration. The incidence of unsus- all cases a 6 mm Dacron prosthesis was Three patients have died of carcinoma at pected stones (0.9%) is too small to support successfully anastomosed to the proximal four, eight, and 16 months, but without the routine use of a technique incorrect in biliary tree and duodenum using non- further jaundice. The other eight are alive 2-7% of cases. absorbable sutures. Patency of the graft and anicteric at four to 28 months Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

The British Society of Gastroenterology A603 (cholangiocarcinoma) or six to 24 months phase of gall bladder contraction. We have at 100 000 g. We measured bile acids and (postcholecystectomy stricture). Hepat- studied in six healthy volunteers (four men, total amphiphilic lipids (TAL, comprising otomy and Roux-Y hepatojejunostomy two women; 20-24 yr) the effect of atro- fatty acid, monoglyceride and phospholipid). provide effective management for intra- pine on plasma CCK and gall bladder The concentration of bile acid correlated hepatic bile duct strictures. contraction in response to fat and to a dose with that of TAL (r=0.99, p<0Ol1 in of exogenous CCK inducing similar plasma health). The slope of the regression line CCK concentrations. Plasma CCK con- was 0-74 in health, identical to that pre- centrations (RIA using antibody T204 dicted for the micellar phase limits in vitro T48 specific for the sulphated tyrosine region of by Carey's group, using model solutions. In Potent induction of cytochromes P448 CCK) and gall bladder volumes (real time CF, the slope was -0 13 (r= -0-89, p<0(05), by corn oil in Syrian golden hamsters ultrasonography) were measured at 10 min indicating an unsaturated micellar phase. intervals for 40 min before and 100 min We conclude that a true micellar phase G PARKER, S BRANIGAN, J B HOUSTON, AND after the stimulus. A 10 min intraduodenal can be identified in normal chyme; and that J M BRAGANZA (Depdrtment of Pharmacy, infusion of 250 ml 20% Intralipid induced a this phase is unsaturated in pancreatic University of Manchester and Department peak plasma CCK increment of 10-2±1-6 steatorrhoea. of Gastroenterology, Manchester Royal pM compared with 10-7±0-7 pM during Infirmary) Corn oil promotes develop- infusion of 1 IDU/kg/h CCK. These in- ment of pancreatic cancer in Syrian golden creases in plasma CCK were accompanied hamsters treated with nitrosamines which by similar decreases in gall bladder volume. require metabolic activation by cyto- Integrated gall bladder contraction after fat chromes P450. Therefore we examined the was 3939±288 compared with 3301 + 359 % min during CCK infusion (ns). T51 effect of six month feeding with 2% or 14% Ileal absorption efficiency for corn oil diets on cytochromes P450 induc- Atropine (0-015 mg/kg as bolus followed tion by phenobarbitone, 200 ppm. Groups by 0-005 mg/kg/h) did not change plasma 75SeHCAT in ileal dysfunction of 4 hamsters were killed at 2, 6, 12 and 24 CCK concentrations (peak plasma CCK weeks and microsomes prepared from liver increment 11-7±1-9 pM after fat and R JAZRAWI, R FERRARIS, C BRIDGES, A E and pancreas. Total cytochromes P450, the 10-0±0-9 pM during CCK infusion), but JOSEPH, AND TC NORTHFIELD (Depart- activity of ethoxycoumarin o-deethylase induced similar inhibition of gall bladder ments of Medicine and Nuclear Medicine, (ECOD) which provides a global index of contraction to 2296±511 % min (p<005) St George's Hospital Medical School, P450 isozymes, and of ethoxyresorufin-o- after fat and to 1756±456 % min (p<005) London) We have validated a quantita- deethylase (EROD) which is a specific during CCK infusion. tive, physiologically meaningful measure- We therefore conclude that atropine ment of bile acid absorption using marker for polycyclic aromatic hydro- http://gut.bmj.com/ carbon-inducible forms, cytochromes inhibits the gall bladder response to intra- 75SeHCAT. This was derived from either P448, were measured. In the low oil group duodenal fat and that this inhibition is not total abdominal counting of 75SeHCAT by these activities in liver microsomes re- due to a reduction of CCK secretion but to y camera or from stool counting by y mained stable over 24 weeks. In the other an inhibition of the sensitivity of the gall counter, 'CrCl3 being used for both groups each value increased over 2-12 bladder for CCK. methods as a non-absorbable correction weeks and then plateaud (p<0-01, multiple marker for colonic retention of 75SeHCAT t and for incomplete stool collection. The tests). aim of this was to Corn oil induces EROD to an extent study compare this T50 measurement with the conventional best on September 29, 2021 by guest. Protected copyright. that is not improved by phenobarbitone, Does chyme contain a true whilst augmenting the ECOD response to micellar test of ileal function - '4C faecal radio- the drug. These data may help to explain phase? activity following '4C-glycocholate using a the tumour promoting effect of corn oil in combustion chamber. We studied four animals. D FINE, P ZENTLER-MUNRO, C BROWN, AND groups of subjects: healthy controls (n=8), T C NORTHFIELD (Department of Medicine, ulcerative colitis (n=16), Crohns' disease St George's Hospital Medical School, Lon- with minimal ileal involvement (n= 16), T49 don) We have recently reported to the and small ileal resections (n=8). Correc- Society that ultracentrifuged chyme con- tion for colonic retention increased the Role of cholecystokinin and the tains two previously unidentified phases, sensitivity of both 75SeHCAT measure- cholinergic system in the intestinal containing liquid crystals and liposomes. ments from 33% and 38% to 90% and 92% phase of gall bladder contraction in The aims of the current study were to respectively (p<0-001). Specificity was man check whether it also contain, a true 85-90% for both methods, even for un- micellar phase; and to check the prediction corrected values. For '4C-faecal radio- W P M HOPMAN, J B M J JANSEN, G ROSEN- that pancreatic steatorrhoea is because of activity, sensitivity was 95% and specificity BUSCH, AND C B H W 1.AMERS (Depart- unsaturation of this phase. We studied six 94%. We conclude that ileal absorption ments of Gastroenterology and Hepatology, healthy controls and six patients with pan- efficiency using 75SeHCAT is of similar and Department of Radiology, Universities creatic steatorrhea caused by adult CF. sensitivity and specificity to "4C-faecal of Leiden and Nijmegen, The Netherlands) Jejunal samples were aspirated following a radioactivity. It has the advantage of being There is substantial controversy about the Lundh meal and immediately inactivated. more physiologically meaningful, and of contributions of cholecystokinin (CCK) The optically clear aqueous phase was requiring apparatus that is much more and the cholinergic system to the intestinal separated by ultracentrifugation overnight widely available. Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A604 The British Society of Gastroenterology T52 effects of DeNol, PGE2, sucralfate and stat titration. PGE, (10 ,tM, topically) Endoscopic management of hydatid cimetidine on ethanol induced gastric ero- increased alkalinisation from 1-63±0 34 to disease of the liver. Analysis of 128 sions, and further the ability of DeNol to 3 07±0 54 Req/h/cm (mean+SEM, n=5). stimulate mucosal PGE, Fasted Luminal acid exposure (10 mM HCI for cases synthesis. Wistar rats (130-150 g) received intra- 10 min) increased the rate of alkalinisation gastric treatment and at various times from 1-54±0 43 to 2 69±0 76; subsequent N GRIMA, A GINESTAL-CRUZ, AND J PINTO thereafter either 1 ml ethanol (lesions) or addition of PGE2 further increased this rate CORREIA (Department of Medicine 2, Uni- versity Hospital of Santa Maria, Lisbon, were killed (PGE2 determinations). One to 3 27±0 54. Recovery of inulin in the hour after ethanol the rats were decapitated luminal perfusate after intravenous injec- Portugal) Hydatid disease is a common condition in southern Europe and South and mucosal injury scored on prepared tion was less than 10% of that of urea. stomachs. To stimulate PGE, generation Topical PGE, had no significant effect on America, and represents an important mm were the recovery of either marker. Luminal diagnostic problem in countries where this 3 biopsies from the washed fundus vortexed for 60 sec in Tris/HCI buffer (pH acidification increased the rate of appear- disease is endemic, particularly in cases 8 4). Indomethacin (200 was added ance of urea by 130±30% (p<0O01, n=6); with biliary involvement. We report our [tm) experience of endoscopic retrograde and PGE2 determined by RIA. DeNol recovery of inulin was not significantly (30-120 mg/kg) was less potent than PGE2 different from control. Thus stimulation of cholangiography (ERC) with 148 proce- dures in 128 patients with hepatic hydatid (60-240 p.g/kg), though four times more mucosal alkaline secretion by luminal potent than sucralfate (120-480 mg/kg) at PGE. or acid have different effects on disease (HHD): 62 men and 66 women inhibiting gastric lesions. Cimetidine mucosal permeability. The time course of (ages 7-89 years; average 51 years). Ultra- (480 mg/kg) inhibited weakly the increase in permeability in response to sound or surgical diagnosis of HHD had (30%/). been achieved before ERC in 107 patients Complete, partial and no protection was acid was similar to the transient rise in afforded by DeNol at 0-25, 8 and 16 hours alkaline secretion occurring in indo- (84% ). Indications for examination were: cholestasis/cholangitis 70%; abdominal respectively. Basal levels of PGE, synthesis methacin-treated animals. PGE2 produced pain 13% and postoperative evaluation were 95±7 pg/mg tissue (SEM; n=9). no changes in permeability and therefore 17%. 143 successful ERC (97%) showed: DeNol increased generation (p<005) presumably acts via cellular mechanisms. (1) Hydatic biliary lesions alone in 99, with ranging from 70% (30 mg/kg) to 300% internal fistulae in 52 (30 showed hydatids (480 mg/kg). Maximum generation occurred at 0-25 hour and basal levels returned at six in the common bile duct), and bile duct T55 hour after DeNol (120 mg/kg). We con- compression or amputation in 47 (2) Mixed clude that DeNol produces potent gastric Luminal epidermal growth factor in hydatic and non-hydatic (mostly stones) in upper gastrointestinal disease 19 mucosal protection and increases the ability

patients (3) Non-hydatic biliary lesions http://gut.bmj.com/ alone in 20 (stones in 18, malignant of mucosa to generate PGE,. The latter may represent an underlying biochemical G D CORCORAN, J WARE, C RICHARDS, C obstruction in two;) (4) Normal bile ducts mechanism for its protective properties. PORTER (R SHIELDS) (Departments of in five. Therapeutic approach included Surgery and Microbiology, Liverpool Uni- endoscopic sphincterotomy in 15 patients, versity, Liverpool) Human epidermal with clearance of hydatids in 10 and of growth factor (hEGF) has been localised to stones in five, followed by cystectomy in six T54 the submandibular and Brunners glands, patients. Our data support the need of bile Duodenal epithelial permeability in and is a normal component of gastric juice. duct imaging as an important part of the relation to stimulation of alkaline Luminal hEGF levels in upper GI disease on September 29, 2021 by guest. Protected copyright. workup of these patients, particularly in secretion were examined by obtaining gastric juice at those with cholestasis. Cholangiographic endoscopy from subjects with no abnormal findings may have a great impact on clinical J M WILKES, A GARNER, AND T J PETERS findings (N), active DU, GU and gastric decision, namely surgery versus endoscopic (Bioscience Department, ICI Pharma- adenocarcinoma (GC). The hEGF levels and/or medical treatment alone. ceuticals Division, Alderley Park, Maccles- were measured by specific radioimmuno- field, Cheshire and Div Clinical Cell assay and the Mann-Whitney U test was Biology, Clinical Research Centre, North- used for statistical analysis. Forty six sub- wick Park, Harrow, Middlesex) Para- jects were studied and the hEGF levels BASIC SCIENCE cellular permeation accounts for about (+±1 SE) were: - N (n=18) 3-5±0-29 T53-60 75% of ion fluxes in the duodenum and (range 1-2-5.8) ng/ml, DU (n= 10) 3-2±0-36 passive diffusion of base via shunt path- (16-5-8), GU (n=10) 2-2±0 28 (1.1-3 7), T53 ways may be an important mechanism of GC (n=8) 9-5±1+83 (1.9±19.4). No Gastric mucosa barrier protection and luminal alkalinisation. The effect on significant difference was found between PGE2 generation in rats after De Nol epithelial permeability of two treatments normal and DU subjects. Gastric ulcer had which stimulate mucosal alkaline secretion significantly less hEGF (p<0-01), how- D W R HAI-L AND W E VAN DEN HOVEN (PGE2 and low luminal pH) was studied in ever, and GC subjects had significantly (INTRODUCED BY P SALMON) (Gist- vivo by measuring transmucosal fluxes of more hEGF (p<0.01) than normal subjects. brocades NV, PO Box 1, MA Delft, The the radiolabelled markers 14C urea (M Wt Gastric ulcer was associated with low Netherlands) Prostaglandins at non- 76) and 3H inulin (M Wt 5000). In hEGF levels supporting a cytoprotective antisecretory doses stimulate numerous anaesthetised rats, segments of distal role, while the elevated levels in GC processes that increase gastric mucosal duodenum were perfused with saline and suggest an altered intraluminal kinetics in barrier defence. We have examined the rates of alkalinisation monitored by pH gastric malignancy. Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

The British Society of Gastroenterology A605

T56 stomach and duodenum. Alkaline secre- 70 3% increase respectively p=0.01). The Inherent trypsin resistance of small tion was measured by automatic back time to maximal activity was also signifi- intestinal mucosa titration in the stomach, duodenum, ileum cantly faster after lunch (10-0±2-9 min) and colon of the rat in vivo and the frog in compared with breakfast (29-57±7.57) and dinner (24-67±4-99) (p<0-02). The dura- H J BALLARD AND B H HIRST (Department vitro. Basal rates of alkalinisation in of Physiological Sciences, University of ,ueq/h/cm (stomach in 1xeq/h/cm2) are given tion of the response lasted for up to 135 min. A significant increase in interfood Newcastle upon Tyne, Medical School, as mean±SEM (n). In anaesthetised rat colonic activity was observed in the after- Newcastle upon Tyne) The small intest- values were; stomach 12±010 (6), noon and evening (11-88±2-15 and inal mucosa is exposed regularly to condi- proximal duodenum 6-2±1+07 (12), distal tions of digestive attack, yet it becomes duodenum 3-2±0 54 (12), terminal ileum 12 59±1-08) compared with the prebreak- fast and mid-morning interfood periods damaged in only a few individuals. We 10-4+1-71 (12), colon 3-8±1-12 (12). In have investigated the resistance of rabbit amphibian mucosa mounted in chambers (8 60±2-55 and 7-99±4-26 p<0.02). This small intestinal brush border membrane corresponding values were; 0-23+±001 previously undescribed finding has import- vesicles to trypsin, using the sodium driven (221), 1 51±0-21 (16), 1-67±0-19 (16), ant implications in studies of colonic motility. Recordings from the colon should uptake of D-['4C]glucose as an indication 2 51±0-37 (5), 1-13±0-16 (5). With the of their functional integrity. Vesicles exception of frog ileum, tissues responded be done at the same times of the day if retained their ability to accumulate D- to an E-type prostaglandin and/or direct meaningful comparisons are to be made. ['4C]glucose after incubation with trypsin activation of adenylate cyclase by forskolin (protease: membrane protein ratio 1:10) at although the magnitude of the increase in 30°C for up to 30 min. Exposure to trypsin, secretion varied considerably between T59 however, for 60 min significantly reduced individual regions. For example in the rat Effects of aldosterone on Na and K the equilibrium volume of the vesicles from intestine, forskolin (10 sg/ml topically) increased alkalinisation by 368±60% over transport properties of colonic epi- 0 39±0-03 il/mg protein (mean±SEM; thelium n=4) to 0-17±0-03 RI/mg (n=4; p<0-002). basal in distal duodenum compared with The decrease in equilibrium volume was only 65±17% in the colon. These data demonstrate the ability to alkalinise G I SANDLE AND F MCGLONE (Department time dependent for up to 80 min, after of Medicine, Hope Hospital (University of which no further decrease was seen; thus luminal bathing solutions is a general property of gastrointestinal mucosa. There Manchester School of Medicine), Salford, 48-7+5-1% (n=4) of the original internal Hyperaldosteronism second- volume remained after 80-120 min of appears to be no relationship, however, Manchester) between rates of alkaline secretion and ary to chronic dietary Na depletion stimu- trypsin treatment. There were no observ- Na K secretory able differences between the trypsin resist- intrinsic resistance to gastric juice or pre- lates active absorptive and

processes in colonic epithelium. The cell- http://gut.bmj.com/ ant vesicles and the control population as vailing luminal acidity in different regions of the gastrointestinal tract. ular bases for these effects were studied judged by electron microscopy, whilst with intracellular microelectrodes in distal SDS-polyacrylamide gel electrophoresis colon from control and Na depleted rats. indicated no discernable change in the Transepithelial voltage and conductance in major membrane proteins after trypsin Na depleted animals (-35±5 mV and treatment. We conclude that the brush 11-3±0+9 mS/cm2 respectively) were border membranes of the small intestine T58 greater than in controls (-6±1 mV, have an inherent resistance to proteolytic Normal daily variation of colonic 2 attack. p

A606 The British Society of Gastroenterology T60 Patients whose DU remained unhealed tions in response to insulin after vagotomy: Pharmacokinetics of galanin in man after two months' treatment with cimeti- 94%, 89-100 non-healers, 93%, 77-100, and its effect on glucose homeostasis dine (0-8-1 g) or ranitidine (0-3 g) daily healers. were randomly allocated to receive a In healers and non-healers vagal and F E BAUER, L GINSBERG, M VENETIKOU, T E further six weeks' treatment with either C gastrin drives on the parietal cell are ADRIAN AND S R BLOOM (Department of 0-8 g daily (n=64) or with C+P 100 mg daily similar. Non-healing may select those Medicine, Royal Postgraduate Medical (n=67). The two groups of patients had patients who have a higher parietal cell School, Hammersmith Hospital, London) comparable demographic features includ- mass or sensitivity to gastrin but reduction The novel gut peptide galanin shows potent ing duration of H2 treatment before entry in gastric secretion after vagotomy is com- biological actions on smooth muscle con- to the study. parable in the two groups. tractility and inhibits insulin secretion in Six patients (C n=4, C+P n=2) were animals and it is suggested it has a role as excluded from analysis because of protocol neurotransmitter or neuromodulator. Syn- violations. Of the remaining 125 patients, thetic porcine galanin and saline was in- healing occurred in 39 of 60 (65%) on C, T64 fused into volunteers at 10 (n=4) and compared with 39 of 65 (60%) on C+P Sucralfate produces a dose dependent 40 pmol/kg/min (n=6) over 60 minutes (70% and 72% respectively of patients who increase in PGE2 synthesis by and plasma galanin and glucose (after completed the study). The reduction in daytime and night time pain was similar in mammalian gastric and duodenal 20 min glucose bolus 25 g iv) were meas- mucosa ured over 90 minutes. The galanin plateau both groups. Four patients on C and 11 on concentration was 182±34 (10 pmol group) C+P were withdrawn, two and 10 respect- and 748±89 pmol/l (40 pmol group) ively for side effects, the commonest prob- J R CRAMPTON, L C GIBBONS, AND W D W (x±SEM). The half-time was 2-3+0-4 min, lem being blurred vision. REES (Department of Medicine, Hope the clearance 49-2±4-6 ml/kg/min and the In conclusion, in RDU, combined treat- Hospital (University of Manchester School distribution space 148-4±23-8 ml/kg. In the ment with C+P does not hasten healing of Medicine), Salford, Manchester) 40 pmol group the glucose elimation con- any quicker than that achieved by C alone Prostaglandins (PG) synthesised by cells stant was significantly lower compared with in standard dose. within gastric and duodenal mucosa may controls (0-0232±0.0032 vs 0-0148±0-0008, play an important role in protecting the p<0-05, t test). In the 10 pmol group there mucosa from damage. The effect of thera- peutic and damaging agents on PG meta- was no difference (p> 0-05). Galanin is T63 eliminated by first order kinetics and it may bolism is therefore worthy of study. We be involved in the regulation of glucose Cimetidine non-healing duodenal have examined the effect of the cytoprotec- homeostasis. This study provides for the ulcer - is vagotomy enough? tive drug sucralfate on synthesis and http://gut.bmj.com/ first time pharmacokinetic data and a bio- degradation rates of PGE2 by rabbit gastric logical effect of galanin in man. M DEAKIN, C CAHILL, D N TULLOCH, E P and -duodenal mucosa. Fresh mucosa was DEWAR, AND J G WILLIAMS (Department of homogenised in ice cold buffer. Aliquots Gastroenterology, RNH Haslar, Gosport, were incubated at 37°C with cofactors and Hants) Nocturnal intragastric acidity arachidonic acid (synthesis assay) and 3H (0030-0730) was higher after placebo in a PGE2 (degradation assay). Inclusion of group of 13 patients with duodenal ulcers blanks enabled measurement of PGE2

which failed to heal on cimetidine 400 mg formed during the procedure rather than on September 29, 2021 by guest. Protected copyright. bd for six weeks (non-healers) when com- generated by prior processing. Prostanoids GASTRODUODENAL pared with a group of 13 that healed were separated by thin layer chromato- T62-74 (healers). H+ activity (median, 25-75%ile) graphy and measured by radioimmuno- was 33-0 27-7-35-2 mmol/l vs 22-59, assay. Inclusion of sucralfate 0 5 g/l in the T62 21-7-25-53, p<005. assay mix caused an increase in PGE2 Combined histamine H2 and anti- The gastrin response to a standard meal synthesis to 157±23% control (n=6, muscarinic receptor blockade in the in 10 non-healers was no different from p<005) rising to 330±48% (n=6, p<0.05) treatment of refractory duodenal ulcer that in 10 matched healers but significantly at 1 g/l using antral mucosa. Similar greater in the duodenal ulcer group as a changes were observed when fundic or K D BARDHAN*, MARY THOMPSON, K BOSE, whole when compared with 10 normal duodenal mucosa was used (Fundus: R F C HINCHLIFFE, J CROWE, D WEIR, subjects (p<0-01). 0.5 g/l=229±26%; 1 g/l=269±80%, n=6; C MCCARTHY, J WALTERS, T J THOMSON, Standard pentagastrin and insulin tests duodenum: 0-5 g/l=138±12%, 1 g/l=285+ M THOMPSON, J E GAMT, AND C KING *(Roth- were done before and after highly selective 16%, n=6; p<005). Smaller increases in erham District General Hospital, Rother- vagotomy in a group of 15 non-healers and PGE2 degradation were not significant. ham.) The optimal medical management of 11 patients who underwent surgery for These results contrast with the effect of refractory duodenal ulcer (RDU) is un- healing but frequently relapsing ulcers. indomethacin which significantly inhibited known. As the acid secretion in many such Basal and postinsulin acid outputs were PGE2 synthesis in parallel experiments patients is under high vagal drive, we not different between the two groups. Peak (105 M=80±8% control, 10-3 M=6+2% examined whether the results of treatment acid output after pentagastrin was signifi- with fundic mucosa). Sucralfate appears to with cimetidine (C) alone could be improved cantly greater in the non-healing group (57, enhance the activity of mucosal cyclo- upon by adding the antimuscarinic, piren- 48-65 mmol/h) vs healers (48-6, 27-4-53*5, oxygenase and this may in part explain its epine (P). p<0-05). Both groups had similar reduc- therapeutic activity. Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

The British Society of Gastroenterology A607 T65 nists on C pyloridis colonisation, 54 non- and 40±19 respectively. Using the bacteria Effect of enprostil on gastric secretion ulcer dyspepsia patients (mean age 42 -ve group mean plus two standard devia- and gastrin release in man years) were biopsied before and after six tions as cut off value the sensitivity, spec- weeks cimetidine (800 mg daily) or ificity and predictive value of a +ve test K E L MCCOLL, N BUCHANAN, G LAFERLA, J placebo. The presence and severity of was 93%, 97% and 98%. These results HEARNS, K BUCHANAN, AND G P CREAN chronic gastritis and of C pyloridis colon- demonstrate that the serum assay fulfills (Gastrointestinal Centre, Southern General isation (using the Warthin-Starry stain) the necessary criteria for a diagnostic test Hospital, Glasgow) The effect of single were recorded in antral and body biopsies. of C pyloridis infection. oral doses of enprostil, a synthetic Chronic gastritis was present in one or both dehydroprostaglandin E2, on gastric secre- biopsies on each occasion in 33 patients, tion and gastrin release has been studied in consistently associated with C pyloridis in T68 normal volunteers and patients with 28. Three gastritic patients had C pyloridis In vitro production of Campylobacter achlorhydria secondary to pernicious on one occasion only. In individual pyloridis specific antibodies by gastric anaemia (PA). In normal subjects 35 [tg biopsies C pyloridis were significantly mucosal biopsies enprostil inhibited basal acid output by a associated with activity of gastritis, but not severity. Cimetidine treatment in 20 mean of 71% (p<0.001 vs placebo), penta- B J RATHBONE, JUDITH WYATI, D TOMPKINS, gastrin (6 sg/kg im) stimulated output by gastritic patients did not affect colonisation or the gastritis. All 24 histologically normal R V HEATLEY, AND M S LOSOWSKY (Depart- 46% (p<002), sham meal stimulated out- ments of Medicine and Pathology, St put by 48% (ns) and histamine (40 ug/kg patients (13 on cimetidine) remained normal and C pyloridis negative six weeks James's University Hospital, Leeds and im) stimulated output by 16% (ns). Basal Department of Microbiology, University of secretion was examined from 60-105 min later. Campylobacter associated gastritis is a Leeds, Leeds) We have previously de- after dosing and stimulated secretion from scribed an ELISA assay for antibodies to 105-165 min postdosing. In each case there chronic condition which is uninfluenced by cimetidine. C pyloridis colonisation of Campylobacter pyloridis. Raised serum was a reduction in both the volume and IgG and IgA titres to the organism were acidity of the gastric juice. Pepsin output histologically normal subjects did not occur during a six week course of cimetidine. demonstrated in colonised patients. To was unchanged. Enprostil did not affect investigate the gastric mucosal production basal gastrin concentrations or the inte- of antibody, gastric biopsy cultures were grated gastrin response to sham meal. The undertaken. effect of various doses of enprostil on T67 Antral endoscopic biopsies were taken serum gastrin was examined in three PA Diagnostic IgG ELISA for gastric from 15 dyspeptic patients. Two biopsies patients with hypergastrinaemia secondary were cultured for six days with daily change Campylobacter pyloridis infection using http://gut.bmj.com/ to achlorhydria. At two hours after dosing serum samples of culture medium. One biopsy was im- the gastrin concentration was reduced by a mediately frozen for subsequent sonica- mean of 38% after 35 ,ug, by 46% following B J RATHBONE, JUDITH WYATI, D TOMPKINS, tion, protein and antibody assay. Another 70 [ig and by 60% following 105 [tg of was formalin fixed for histology and C enprostil. The gastric pH was unaffected R V HEATLEY, AND M S LOSOWSKY (Departments of Medicine and Pathology, pyloridis identification by the Warthin- by enprostil, remaining between 6 5 and Starry technique. The ELISA was carried 7 5 throughout the study. St James's University Hospital and Depart- ment of Microbiology, University of Leeds, out using a C pyloridis sonicate as antigen. In conclusion enprostil reduces basal and Seven of eight patients with chronic stimulated gastric acid secretion without Leeds) Using whole Campylobacter on September 29, 2021 by guest. Protected copyright. pyloridis organisms as antigen in an ELISA gastritis were colonised with C pyloridis, inducing secondary hypergastrinaemia as it the one exception having pernicious also inhibits gastrin release. we have previously showed significantly raised serum IgG and IgA antibodies in C anaemia. The colonised patients had high pyloridis +ve patients with chronic gastritis. titres of C pyloridis specific IgA in both the The differentiation, however, between the biopsy sonicate and culture media. Titres T66 titres of the bacteria +ve and -ve patients of specific IgG were also raised in six of Campylobacter pyloridis and cimeti- was insufficient for the assay to be of use in seven of the colonised patients. No specific dine diagnosis. IgG or IgA antibodies were seen with the We have found that a sonicate of organ- pernicious anaemia or seven normal biop- JUDITH WYATT, B J RATHBONE, AND R V isms acts as a superior antigen in the IgG sies. HEATLEY (Departments of Pathology and ELISA giving a better separation of bacteria These results show local gastric tissue Medicine, St James's University Hospital, +ve and -ve patients. To determine the production of C pyloridis specific anti- Leeds) Mucosa associated Campylo- diagnostic value of this assay 73 dyspeptic bodies in colonised patients. No antibodies bacter pyloridis are present in 90% of patients attending for endoscopy had were found in patients with normal his- patients with chronic gastritis. Cimetidine serum and gastric biopsies taken. In addi- tology or the one patient with pernicious has been reported to be bactericidal to the tion to H and E staining for histology, anaemia. organism, and may reduce colonisation in Warthin-Starry stains were carried out to treated patients. Theoretically, however, the identify C pyloridis colonisation. cimetidine induced hypochlorhydria might Forty two patients (all with chronic T69 predispose previously normal subjects to C gastritis) were colonised with C pyloridis. Relationship between the presence of pyloridis colonisation. The mean optical density values from the duodenal campylobacter like organ- To investigate the effect of H2 antago- bacteria +ve and -ve patients was 194±72 isms and duodenal ulcer healing Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A608 The British Society of Gastroenterology

BELINDA J JOHNSTON, P I REED, AND M H for the above histological features and the K LAURITSEN, L S LAURSEN, T HAVELUND, P ALI (Departments of Gastroenterology sum of the grades used to assign each BYTZER, LB SVENDSEN, AND J RASK- and Histopathology, Wexham Park Hos- patient a 'reflux score' ((-15). 46 peptic MADSEN (Department of Medical Gas- pital, Slough, Berks) The significance of ulcer patients were CLO-positive com- troenterology, Odense University Hospital, campylobacter like organisms (CLO) in pared with only six postoperative patients Odense, Odense C, and Department of duodenal biopsies from patients with (X-. p<0(0001 ). The absence of CLO also Surgical Gastroenterology, Bispebjerg Hos- duodenal ulceration (DU) remains uncer- correlated significantly (p<0O001) with pital, University of Copenhagen, tain. Duodenal and antral biopsies from 42 high reflux scores (> 10), hypochlorhy- Copenhagen NV, Denmark) The synthe- patients were examined for CLO before dria (pH>4) and increased BAC's tic dehydro-prostaglandin E2, enprostil and after six weeks treatment of DU using (> 1 mmol/l). These results further (E), has antisecretory effects comparable standard regimes. Duodenal biopsies were suggest that RG is a distinct histological with those of the H, receptor antagonists, assessed as normal, non-specific duodeni- entity and imply that peptic ulcer patients in addition to mucosal protective effects tis, active duodenitis or duodenal ulcer, may undergo a transition from CLO-re- (against - for example, aspirin induced according to the criteria defined by White- lated chronic gastritis before to RG after damage) in doses below those required for head. All results are based on histology. operation. acid inhibition. To determine whether this Thirty nine patients had duodenal CLO dual action might be of clinical benefit 180 pretreatment, two CLO negative were patients with endoscopically proven receiving NSAIDs at the time of study. Of T71 duodenal ulcers were randomly allocated the 24 treated with ranitidine, CLO dis- of histamine H2-receptor anta- to double blind treatment with E 35 mcg Effect bid for to six weeks. appearance was only seen in the 10 patients therapy on mutagenic bid or R 150 mg up with histologically healed inflammation, gonist (H2RA) The study was completed if ulcer healing the remainder having both CLO and active activity in gastric juice and pain relief had occurred at two or four duodenal inflammation. Eight patients weeks. One hundred and sixty three H J O'CONNOR, S E RILEY, A T R AXON, AND R C were treated with di-sodium di-citrato bis- patients completed the trial. The duration GARNER (Gastroenterology Unit, General muthate of whom five became CLO nega- of medication was longer in the E group Infirmary at Leeds, Leeds Microtest Re- (p<0005) and the cumulative healing rates tive with no active inflammation, but three Research active CLO search Ltd., York and Cancer at two, four, and six weeks were 51%, with inflammation remained The positive. All six patients treated with suc- Unit, University of York, York) 74%, and 85%, respectively. In the R ralfate remained CLO positive with active properties of carcinogenicity and group the corresponding figures were 65% are closely related. If H2RA was no mutagenicity (p<004), 89% (p<002), and 99% inflammation. There change in the levels CLO status of four carbenoxolone treated therapy causes increased intragastric (p<0)002). More patients treated with R

of N-nitroso compounds, an issue not yet http://gut.bmj.com/ patients. There was poor correlation experienced pain relief (p<0004 at weeks resolved by analytical studies, correspond- 5 and 6). The observed superiority of R 150 between endoscopic and complete histo- of healing. The only factor found to ing changes in the mutagenicity gastric mg bid to E 35 mcg bid questions the logical might be anticipated. In this study influence CLO presence after ulcer therapy juice clinical relevance of using so called 'cyto- mutagenic activity and pH were measured was the complete histological healing of the protection' as treatment for duodenal ulcer ulcer. in fasting gastric aspirate from 18 peptic disease in the short term. ulcer patients before and during the final week of therapy with ranitidine (n=10, x mean 81 or cime- T70 150 mg bd 4-20 wk, ) on September 29, 2021 by guest. Protected copyright. Campylobacter like organisms and re- tidine (n=8, 400 mg bd x 6-2() wk, mean flux gastritis 8X9). Mutagenic activity was assessed using S typhimurium TA98 and TA 100. No T73 significant change in mutagenic activity was H J O'CONNOR, J I WYAIT. M F DIXON, AND Double blind clinical trial comparing A T R AXON (Gastroenterology Unit and detected after therapy. Mutation frequen- night time enprostil with ranitidine in University Department of Pathology, Gen- cies (mutants per 108 bacteria, mean±SD) duodenal ulcer eral Infirmary at Leeds, Leeds) We have for TA98 and TA100 were respectively, com- previously shown that reflux gastritis (RG) 53X8±113 7 and 171 9±227-1 before R P WALT, R G lONG, R F A LOGAN, K W and 142-2±246-4 has a characteristic histology comprising pared with 21 6+49-4 SOMERVILLE, M J S LANGMAN, AND C J marked foveolar hyperplasia, oedema, and during therapy (p> 0.05). Changes in HAWKEY (Department of Therapeutics, smooth muscle infiltration, and vasodilata- mutagenic activity were similar in both University and City Hospitals, Notting- tion of the lamina propria, and a paucity of treatment groups and unrelated to duration ham) Enprostil, a prostaglandin ana- acute and chronic inflammatory cells. In of therapy, ulcer healing or pH changes. logue, accelerates ulcer healing when used this study, 98 patients (normal endoscopic These results provide no evidence that twice daily and has been shown to inhibit findings, 19; peptic ulcer, 56; postpartial increased intragastric levels of genotoxic gastric acidity. Single night time dosing gastrectomy or vagotomy and drainage, 23) chemicals, such as N-nitroso compounds, with ranitidine is effective treatment for underwent gastric biopsy and measurement occur during H2RA therapy. duodenal ulcer. We have therefore con- of pH and total bile acid concentration ducted a double blind, endoscopically con- (BAC) in their fasting gastric aspirate. trolled comparison of enprostil and raniti- Biopsies were stained by HE and the T72 dine given as single night time doses for Warthin-Starry method for campylobacter Effect of enprostil and ranitidine on duodenal ulcer. One hundred and two like organisms, (CLO), graded blind (0-3) duodenal ulcer healing patients were enrolled over 11 months and Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from The British Society of Castroenterology A609 randomly assigned treatment with either macroscopic oesophageal erosions or enprostil 70 [tg or ranitidine 300 mg each PLENARY SESSION more extensive ocsophageal ulceration night. The groups were well matched for T75-80 were raindomised to reccive omeprazole age, sex, smoking habits, and previous (20 mg or 40 mg daily) or placebo treat- treatment. At four weeks, ulcers had T75 ment. Symptoms were recorded daily and healed in 39 of 51 patients taking ranitidine Peptic ulcer complications and non- endoscopy was repeated after four weeks. (76%) and in 26 of 51 receiving enprostil steroidal anti-inflammatory drugs Endoscopic healing was defined as resolu- (51%) (p<0.02). At eight weeks nine of 12 tion of all visible erosion or ulceration. remaining ulcers had healed on ranitidine C P ARMSTRONG, A L BLOWER (INTRODUCED Data were analysed according to intention compared with eight or 25 in patients BY T V TAYILOR) (Leighton Hospital. Crewe, to treat and five withdratwals were included taking enprostil (p<005). Nocturnal pain Cheshire) Peptic ulcer complications are in the analysis as unhealed. Healing of recorded during the first week occurred a major cause of morbidity and mortality oesophagitis in all omeprazole treated more frequently than had been recalled and these have recently been linked to the patients (25/31, 8X1°) was markedly superior before treatment with enprostil but less use of non-steroidal anti-inflammatory to placebo (2/32, 6WY%, p<0.00l). Before frequently with ranitidine. Three patients drugs (NSAIDs). We have studied 235 treatment severity of oesophagitis and cli- on ranitidine complained of headaches (vs consecutive patients from South Cheshire nical characteristics were similar in both none on enprostil). Seven patients on who either died from or required surgery groups. Of patients with heartburn 16/25 enprostil experienced loose stools or for bleeding or perforated peptic ulcers. (64°/O) treated with omeprazole, and 4/29 diarrhoea (vs one on ranitidine). Night Seventy eight patients died; 25 at home. 19 (14%) of placebo treated paticnts became time dosing with 70 tg enprostil is less in hospital before surgery and 34 postoper- symptom free (p<00())1). Minor adverse effective treatment for duodenal ulcer than atively. Ninety eight had bleeding ulcers, events occurred in both groups but none night dosing with ranitidine. 132 perforations and five had both. Fifty were specifically attributed to omeprazole. three had gastric ulcers, 179 duodenal These data suggest that omeprazole is a ulcers and three had both. One hundred highly effective short term therapy for and forty one of 235 (60%) were taking a ulcerative oesophagitis. NSAID. The first sign of a peptic ulcer was the complication in 58% of patients taking T77 T74 NSAIDs in contrast with only 24% of patients not using these drugs. Repeat Natural history of bleeding in cirrhotics The alginate raft: a scintigraphic eva- prescriptions had been given to 20 patients with varices and no previous bleeding luation for more than one year despite a history of A K dyspepsia and the use of H,-antagonists did BURROUGHS, F 1) IIIAGERE, N MCIN- http://gut.bmj.com/ A P MCKAY, E P WRAIGHT, AND J 0 HUNTER not prevent the complication. Six patients rYRi (Academic Department of Medicine, (Departments of Gastroenterology and using a NSAID had 'silent' perforations for Royal Free Hospital and School of Medi- Nuclear Medicine, Addenbrooke's Hos- more than three days. Sixty one of the 78 cine, Lonidon) Beta-blockers and scler- pital, Cambridge) There is little objective patients (78.2%) who died were taking a otherapy have a very low directly related evidence to support the widely held belief NSAID. The mortality for patients taking mortality. This again hais raised the issue that an alginate suspension will form a NSAIDs was more than twice that for of preventing the first variceal bleed in neutralising raft floating on the gastric those with no such drug history. This study cirrhotics. To re-evaluate the occurrence contents. We have of bleeding, 106 cirrhotics with endo- critically evaluated a shows a clear relationship between peptic on September 29, 2021 by guest. Protected copyright. new alginate preparation (W H Rorer). 12 ulcer complications and the ingestion of scopically verified varices and no previous subjects with proven gastro-oesophageal NSAIDs. Much of the associated morbidity bleeding were followed up [median (mfu) reflux (five men, seven women, age range and mortality may be potentially avoid- 47 weeks (range 5-306)1. Nineteen patients 20-76 years, mean 56 years) were studied able. (18%) bled trom varices, six died within 42 after a 12 hour fast. Three hundred milli- days of first haemorrhage and four from later litres of 99Tc-labelled milk was given, haemorrhage; 11 died of non-bleeding followed 10 minutes later by 10 ml of T76 causes. Patients bleeding by Pugh's grading "3In-labelled alginate. Radionuclide scan- Omeprazole heals reflux oesophagitis: at initial endoscopy: nine of 48 grade A (mfu ning over oesophagus and stomach was a placebo controlled trial 63 w), 6/38 grade B (mfu 48 w), 4/20 grade C continued for one hour. Gastric emptying (mfu 27 w). Only two remained as grade A, curves for the two isotopes were plotted D J HETELi, J DENT, B H LAURENCE, W D whilst eight were B and nine C. Median time after correction for radioactive decay. In 11 REED, F NARIFiVAiA, AND D J C SHEARMAN to bleed was: A (51 w), B (37 w), C (11 w); of 12 subjects studied the ''3In raft was (Royal Adelaide Hospital, Flinders large (20 w), small varices (30 w). Thus the demonstrated by inspection of the images Medical Centre, Repatriation Hospital, first variceal bleed is fatal in only a very small to form a layer above the "9Tc-labelled Adelaide, South Australia and Sir Charles minority, and is strongly associated with milk. Comparison between curves showed Gairdner Hospital, Perth, Western Austra- hepatic deterioration and large size varices. the emptying rate of the raft to be signifi- lia) Omeprazole is a potent inhibitor of To improve survival in non-selected cirrho- cantly slower than that of the milk gastric secretion with prolonged duration tics solely by preventing bleeding is unlikely (p=<001). This preparation of alginate of action. Its effects on peptic oesophagitis to succeed, or to be proven by controlled does indeed form a raft, and its emptying were investigated in a double blind placebo trials. Reliable selection of high risk patients rate from the stomach is slower than liquid controlled trial. should be a prerequisitc for prophylactic gastric contents. Sixty three patients aged 18-8() years with treatment of varices. Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A610 The British Society of Gastroenterology T78 and tissues showing active inflammation had already aggressive disease for years, Adaptation of the shortened gut: role of from 15 acute colitics. Nuclear suspensions surgery did not seem to interrupt the were prepared from immediately adjacent course of the disease: extensive ileal lesions the distal small bowel paraffin sections and analysed by flow and stenosis developed within a few cytometry. Eight out of 12 cases with months to two years after surgery. The G V N APPLETON, J B BRISTOL, AND R C N dysplasia (66-7%) and none of the 15 cases development of abscesses and fistula was WILLIAMSON (University Department of Surgery, Bristol Royal Infirmary, Bristol) without dysplasia (0%) showed aneuploidy always preceded by stenosis. It is con- The postresectional hyperplasia previously (Fisher's exact test: pjejunum proximal to the TVF (JR; n=12), K GEBOES, P RUTGEERTS, J BEYLS, G VANTRAP- cantly after highly selective vagotomy to another had resection of the ileum distal PEN, G COREMANS, AND R KERREMANS the TVF n= while controls (IR; 13), (n= 15) (Department of Medicine, Pathology and D C WARD, D JOHNSTON, I P BELTON, AND had no further procedure. When killed 10 Surgery, University Hospital, Gasthuisberg, M C J BARKER (University Department of days postoperatively rats with IR weighed Leuven, Belgium) In a previous study we Surgery and The Department of Nuclear (178-4±12 3 g), less than controls showed that mucosal lesions reappear in Medicine, The General Infirmary, Leeds) (2214±+14.6 g; p=(-(XX)l) or those with JR the neoterminal ileum within one year of Excessive duodenogastric reflux (DGR) (209 2±13 9; p= 0008). Crypt cell produc- ileal resection. These apthous lesions is harmful to the gastric mucosa, causing http://gut.bmj.com/ tion rate (CCPR) was determined by a probably are the first macroscopic signs of changes in the mucosal structure and metaphase arrest technique in mucosal recrudescent Crohn's disease. The aim of symptoms after both partial gastrectomy samples taken from the centre of the TVF. the present study was to carry out a pro- (PG) and truncal vagotomy and drainage JR produced an 81% increase in CCPR over spective follow up of these postoperative (TV+D). Whether DGR is excessive in DU control values (28.5±4.2 vs 15 8±2-3 cells/ lesions. Fifty patients, who had undergone and GU patients before operation is crypt/h: p=0 025), whereas IR had no an ileocolonscopy within the first year of disputed. Highly selective vagotomy has demonstrable effect (17.5+2.3 cells/crypt/h). surgery and consented in prospective been reported previously to diminish DGR, Adaptive hyperplasia in isolated small bowel

follow up, were included in the study. At but the methods were criticised because of on September 29, 2021 by guest. Protected copyright. is modulated by factors localised to the distal the time of the first postoperative examina- nasogastric intubation. small intestine, enteroglucagon being a tion 10 patients had no lesions, 32 pre- We used a tubeless, scintigraphic techni- plausible candidate. sented with apthous ulcers and 10 had que with 99Tcm-EHIDA, to measure fast- larger ulcers. Of the 10 patients having a ing and postprandial DGR in 14 normal macroscopically normal neoterminal controls and 108 patients with DU and GU T79 ileum, four developed apthous ulcers over before operation, and after PG, TV+D DNA aneuploidy and dysplasia in 8 to 10 cm of neoterminal ileum without and HSV. Paired tests were conducted in ulcerative colitis symptoms within one year after the first 10 DU patients, before and four to 12 endoscopy, two developed acute symptoms months after HSV. H S GOH, J R JASS, AND J M A NORTHOVER and acute ulcerations extending over 20 Duodenogastric reflux was found to be (ICRF Colorectal Cancer Unit, St Mark's and 25 cm resp of the ileum; in the four greater than normal both in DU (p<002) Hospital, City Road, London) Dysplasia other patients the ileum remained macro- and in GU (p<001) patients. After PG in ulcerative colitis is a premalignant lesion scopically normal. Of the 42 patients who and TV+D, DGR was greater than in DU and its detection underlies follow up sur- presented with lesions at the first endo- (p<005), or GU (p<005), patients. After veillance. Histological interpretation of scopy, 12 remained unchanged for a mean HSV, DGR was less than after PG dysplasia is subjective and the change may follow up period of three years; in 16 (p

The British Society of Gastroenterology A611

changes in the gastric mucosa - gastritis, to receive either cimetidine or tri-potas- (65-1558) pmol/l in the patients with perni-

metaplasia, dysplasia and carcinoma - will sium dicitrato bismuthate for six weeks. cious anaemia. These results demonstrate prove to be less common after HSV than Gastroscopy was then repeated to docu- 24 hour hypoacidity in patients with perni- after PG or TV+D. ment treatment efficacy. Antral biopsies cious anaemia, and an unremitting eleva- were taken at both gastroscopies and tion of 24 hour plasma gastrin which may assessed histologically and microbiologi- be the cause of enterochromaffin like cell F2 cally for the presence of C pyloridis. hyperplasia in some pernicious anaemia Problem of postvagotomy diarrhoea One hundred and eleven consecutive patients. patients were included in the study. put into perspective Seventy four per cent were C pyloridis positive at initial gastroscopy, (duodenal F5 S A RAIMES, V SMIRNIOTIS, E J WHELDON, C W ulcer having the highest incidence at 83%, Late outcome of bleeding gastric ulcers VENABLES, AND I D A JOHNSTON (University oesophagitis the lowest at 54%). C pyloridis Department of Surgery, Newcastle upon of status was unaffected by cimetidine, 7290 H 1. SMART AND M J S L1ANGMAN (Depart- Tyne) The incidence and significance being positive at 0 and six weeks. Bismuth- postvagotomy diarrhoea remains con- ment of Therapeutics, Universitv Hospital, because of the varying ate significantly (p<0-05) decreased Nottingham) No substantial data exist to troversial, largely C pyloridis incidence (76 to 47%0). definitions and a lack of a true 'control show the late outcome of bleeding gastric group'. Using carefully chosen definitions C pyloridis status did not affect outcome ulcers. We have therefore followed the with cimetidine. When treated with we have compared the bowel habit of 102 subsequent progress of 152 patients treated bismuthate, healing was significantly corre- men, 10 or more years after truncal vago- medically in the Nottingham hospitals for tomy and pyloroplasty (TVP) (Mean fol- lated with the presence of C pyloridis on bleeding gastric ulceration. Data obtained initial gastroscopy (700o vs 30%). Clear- low up=13 3 years) with 62 men taking four to eight years after initial admission by long term maintenance cimetidine (Mean ance of C pyloridis with bismuthate was reference to hospital records and question- associated healing of the lesion in all follow-up=5-4 years). All were duodenal with naires completed by patients' GPs was ulcer patients randomly selected from cases. analysed by the life table method. Eight We conclude that bismuthate eradicates prospective gastric clinics. Subjects com- patients were lost to follow up (50o) and 39 C pyloridis from the antrum in peptic pleted a standardised questionnaire and (26%0) had died from non-ulcer related disease in a significant number of cases. were interviewed about their bowel habit causes. The overall cumulative risk of ulcer since ulcer treatment. Cimetidine treat- The effect is associated with lesion healing. haemorrhage or perforation was 19%, ment was not associated with any consis- being greater for women (21°/) than men tent change in bowel function and bowel (14%). The risk of developing a late habit was similar to that expected in the F4 complication fell with time in both groups. http://gut.bmj.com/ general population. Attacks of diarrhoea Twenty four hour intragastric pH and Women were older than men at the time of were significantly more common in the 24 hour plasma gastrin concentration their initial admission and women who TVP group (54/102 vs 4/62; p<0001). in healthy volunteers and patients with suffered a late complication were older Eleven per cent of TVP patients still had pernicious anaemia than those remaining well at the end of the diarrhoea nearly every day and a further follow up period. No similar difference 22% had attacks at least once a week; only existed for men. The risk of having a late S LANZON-MILLER, R E POUNDER, S J BALL, complication from a bleeding gastric ulcer one cimetidine patient had attacks as fre- N A F CHRONOS, M I R HAMILTON, R NEAME, with that on September 29, 2021 by guest. Protected copyright. quently as this. Twenty four per cent of AND J MERCEICA (Academic Department of compares favourably reported TVP patients were displeased with the under similar circumstances for duodenal Medicine, Royal Free Hospital School of ulceration. to reduce the late change in bowel function and 8% com- Medicine, London) Twenty four hour in- Attempts plained that diarrhoea seriously interfered complication rate should concentrate on tragastric acidity and plasma gastrin were those at risk - women. with their lifestyle and had been resistant measured in 10 healthy volunteers and greatest elderly to treatment. We feel that this is unaccept- eight pernicious anaemia patients. Their able and sufficient reason to avoid the use median (range) ages were 22 (21-23) and of truncal vagotomy and pyloroplasty 60 (53-69) years respectively. The perni- F6 whenever possible. cious anaemia patients had been diagnosed Acid suppression in healing duodenal as having pernicious anaemia a median of ulcer: how much is enough? 60 (11-128) months earlier. The median F3 peak acid output to pentagastrin in the two C W HOWDEN, D B JONFS, D W BURGET, G D Effect of therapy on Campylobacter groups were 45 (43-69) and 0 (0-0) mmol/h KERR, AND R H HUNT (Division of Gas- pyloridis - a randomised trial respectively. Six standard meals were troenterology, McMaster University, served with homogenised pH values of 5- 1, Hamilton, Ontario, Canada, and Royal H HUMPHRIES, C DOOLEY, D O'LEARY, S 6-2, 5-4, 6-4, 5-4 and 5-5. The 24 hour Shrewsbury Hospital, Shrewsbury) The BOURKE, D MCKENNA, B POWER, C KEANE, E median intragastric pH for the healthy degree and duration of acid suppression, SWEENEY, AND C A O'MORAIN (Depart- volunteers was 1-7 (20( mmol1l) but it was and the relative importance of suppression ments of Gastroenterology, Microbiology 5.5 (0-003 mmol/l) for the patients with by day and night, in the treatment of DU and Histology, Meath and Adelaide Hos- pernicious anaemia. The median 24 hour have yet to be precisely defined. We have pitals, Dublin) Patients with endoscopically plasma gastrin concentration was 14 (5-50) analysed 141 controlled trials comprising diagnosed peptic disease were randomised pmolUl in the healthy subjects and 497 over 11 500 patients, and correlated healing Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from A612 The British Society of Gastroenterology rates with acid suppression data from 22 in 24 patients receiving maintenance treat- first hour but significantly increased published studies in DU patients. Eleven ment. Patients were endoscopically ex- (p<0.05) them during the second from 1-71 dose regimens of H,-receptor antagonists amined at monthly intervals for up to eight to 9 57 and 9-63 to 17-29 mmol/l respec- (H.RA) show a correlation between four months after ulcer healing. In patients with tively. Bile salt precipitation was signifi- week healing and suppression of intragas- asymptomatic recurrences treatment and cantly reduced (p<0.05) in the second hour tric acidity over 24 hours (r=0 62; follow up continued unchanged. Eight from 62-4%-305%o. p=0-04), and at night (r=0 93; p=0.0001), patients developed recurrent ulcers, of Adjuvant ranitidine therapy improves but not by day (r=002; p=0.96). By which seven occurred within two months of conditions for digestion within the duo- stepwise linear regression, the contribu- ulcer healing. Only one ulcer was sympto- denum in CF. particularly in the second tions to healing of suppression at night or matic at the time of detection. No asympto- hour after a meal. Longer term studies are daytime can be defined. Suppression of matic recurrence underwent spontaneous indicated. nocturnal acidity accounts for 86 1% of healing during follow up, although one observed healing rates. later gave rise to pain. Single nocturnal dosing with H.RA We conclude that although ulcers often targets the pharmacological effect to the recur early during maintenance treatment F9 night when the basal acid secretion is more and are usually asymptomatic. rehealing Can antacids prevent duodenal ulcer easily controlled. Suppression of acidity by does not occur at rates which make the Chi relapse? day does not appear to be important in this model valid. A model of maintenance analysis. Any eight hour period of suppres- therapy based on our findings indicates A MUILTICENTRE STUDY (PRESENTFD BY K D sion, however, may be as effective, and that current trial design and interpretation BARDHAN) (Rotherham District General longer periods of adequate suppression gives a satisfactory indication of true re- Hospital, Rotherham) Antacids can heal might accelerate healing. currence rates. duodenal ulcers (DU) but their effectiveness in preventing recurrence is unknown. We therefore investigated the value of F7 F8 Maalox Concentrate (neutralising capacity 27 mmol/tablet) in a double blind double Does maintenance treatment keep Combined ranitidine and enteric dummy study. Patients with endoscopically duodenal ulcers healed? An evaluation coated microspheres (Pancrease) im- confirmed DU healed within the previous of the Chi model proves maldigestion in cystic fibrosis year were eligible provided they were currently ulcer free at endoscopy. They E J S BOYD, D A JOHINSTON, J G PENSTON, AND M G MILLFR, D M CHALMERS, J M LH1- EWOOD, were stratified for smoking and randomised K G WORMSLFY (Ninewells Hospital, Dun- J KELILEHER, AND M S l.OSOWSKY (Depart- to receive one of four treatments for one http://gut.bmj.com/ dee, Scotland) In maintenance trials ments of Medicine, St James's Hospital anid year: Maalox 3 tablets bd; Maalox 3 tablets apparent recurrence rates (ARR) are de- Chapel Allerton Hospital, anid Department at bedtime; cimetidine 400 mg at bedtime; rived from the incidence of symptomatic of Paediatrics, St James's Hospital, Leeds) or placebo. Endoscopy was repeated at six recurrences and the point prevalence of Enteric coated microspheres (Pancrease, and 12 months when asymptomatic or asymptomatic recurrences at pre-arranged Creon) improve but do not completely whenever symptoms recurred. endoscopic examination - for example, at correct maldigestion in cystic fibrosis (CF). Patients in the four groups were demo- four, eight, and 12 months. Calculation of Previous studies of adjuvant cimetidine graphically similar. In 173 evaluable true recurrence rates (TRR) requires that and conventional enzymes have shown patients, the cumulative relapse rate at one on September 29, 2021 by guest. Protected copyright. the incidence of asymptomatic recurrences reduction in steatorrhea but no nutritional year was: placebo 53%, bedtime Maalox be determined. A lower ARR in patients benefit. As correct pH of duodenal con- 43%, Maalox bd 25% and cimetidine 27%. on maintenance than on placebo, however, tents is critical for enzyme release and Cimetidine and Maalox bd were equally has usually been interpreted as indicating subsequent digestion, we have studied the effective and superior to placebo (p<0-01) fewer recurrences in the maintenance effect of combining a more potent H, and bedtime Maalox (p<004). Bedtime group. antagonist, ranitidine, and Pancrease on Maalox was numerically but not statistically Chi has produced a mathematical model the composition of duodenal contents. significantly superior to placebo. The to interpret placebo controlled mainte- Seven patients (aged 15 to 29 years) with benefit of treatment was greater amongst nance studies. Assuming that prop- CF were studied using a double blind smokers than non-smokers. ortionately more recurrences are asymp- crossover design. Ranitidine 300 mg or Four patients on Maalox were with- tomatic on active than placebo treatment, placebo was given 30 minutes before a drawn because of adverse events. Serum and that asymptomatic recurrences on standard meal with Pancrease. Samples aluminium and magnesium levels did not maintenance treatment reheal at rates simi- were aspirated for two hours. Ranitidine change significantly. lar to those documented in patients on significantly increased duodenal pH and We conclude that Maalox Concentrate 3 active treatment in healing studies, then the mean aspirate volume fell from 624 to tablets bd provides an effective method of marked differences in ARRs may occur 494 mIs. At all values of pH<5, intact reducing DU recurrence. although TRRs are identical. That is, enzyme granules were observed. Mean maintenance therapy may not lower ulcer lipase concentration increased from It) 430 recurrence - some recurrences iu/I to 19 321 in the first hour (NS) and it is just that FIO are not detected because they are painless from 296(1 to 123 000 in the second hour and reheal quickly. (p<0)(01). Ranitidine did not alter micellar Tripotassium dicitrato bismuthate ver- We have tested the Chi model clinically bile salt or lipid concentration during the sus two different dosages of cimetidine Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from The British Society of Gastroenterology A613 in the treatment of resistant duodenal and plasma concentrations of SMS 201-995 and the integrated gastrin response to an ulcers were measured. Faecal chymotrypsin was OXO meal. In a patient with Zollinger- estimated at days 6 and 7. Ellison syndrome nifedipine did not affect G BIANCHI PORRO, F PARENTE, M LAZZARONI, SMS 201-995 prolonged the duration of the two-fold rise in gastrin during stimula- AND S ARDIZZONE (Gastrointestinal Unit, postprandial increases of intragastric pH, tion with calcium gluconate (4 mg/kg/h). In L Sacco Hospital, Milan, Italy) The use but did not raise median nocturnal intra- conclusion nifedipine reduces basal acid of tripotassium dicitrato bismuthate (TDB) gastric acidity above pH 3. Peptone- secretion and that stimulated by low dose has been recently suggested for cimetidine stimulated gastric acid secretion (placebo: but not high dose infusions of pentagastrin resistant duodenal ulcers. The purpose of 46-7+5 4 mmol H+/3 h; mean±SEM) was suggesting a competitive inhibitory this study has been to compare the efficacy reduced to 2-3+0 3 by 25 tg and to mechanisms. The increased gastrin concen- of TDB with that of two different cimeti- 2-2±0-4 mmol H'/3 h by 100 [tg. Stimu- trations can be explained by the reduced dine dosages in the treatment of duodenal lated gastrin release was abolished by both gastric acidity. ulcer patients who failed to respond to an doses. At the end of one week's treatment eight-week therapy with H,-blockers. the effects on intragastric pH and acid Forty three patients (34 men, nine women) output were significantly lower. SMS 201- were randomly allocated to one of the 995 neither influenced urinary volume and LIVER following three oral regimens: (1) TDB osmolality nor faecal chymotrypsin concen- F13-24 120 mg qid, (2) cimetidine 400 mg tid (3) trations. As side effects intragastric reten- cimetidine 400 mg with meals plus 800 mg tion of food, flatulence, abdominal spasms, F13 at bedtime. and steatorrhoea occured. Halothane hepatitis - a clinical update Endoscopic control was carried out after SMS 201-995 proved to be a powerful four weeks of therapy; if the ulcer was not inhibitor of parietal cell function during J G KENNA, J NEUBERGER, AND R WILLIAMS healed patients continued with the same day-time. Its lower effect on nocturnal (The Liver Unit, King's College Hospital treatment for a further four weeks and intragastric pH might be due to delayed and School of Medicine and Dentistry, were subsequently reassessed by endo- gastric emptying and its diminishing effi- London) Halothane hepatitis may be scopy. After four weeks similar percent- cacy due to a down regulation. diagnosed by the finding in serum of speci- ages of ulcer healing were registered in the fic IgG antibodies to halothane induced two cimetidine schedules (46.7% with liver cell antigens. Serum from 40 patients C 1 2 and 42-9% with C 2.0), whereas TDB F12 with presumed halothane induced -liver resulted in a significantly higher healing damage was tested using an enzyme-linked on acid rate (85.7%) (p<0.05). After eight weeks Effect of nifedipine gastric immunosorbent assay (ELISA) to detect release in man the healing rates were 69 2% on C 1.2, secretion and gastrin these halothane antibodies. All patients http://gut.bmj.com/ 71,4% on C 2() and 92.9% on TDB (p ns). developed hepatitis between January 1983 These results confirm previous opinions K E 1 MCCOLL, N BUCHANAN, G LAFERLA, J and December 1985 and 21 of the patients that resistant duodenal ulcers are more HEARNS, K BUCHANAN, AND G P CREAN being seen in 1985. The median was 50 responsive to an agent which strengthens (Gastrointestinal Centre, Southern years, and three were aged less than four the mucosal defences than to antisecretive General Hospital, Glasgow) As calcium is years. Seventeen patients developed compounds. important in the regulation of gastric acid fulminant hepatic failure and 13 died. All secretion and gastrin release we have stu- patients had undergone at least one pre- died the effects of the calcium antagonist vious anaesthetic (range 1-8) but in only 20 on September 29, 2021 by guest. Protected copyright. nifedipine on these processes. In healthy Fl1 was a previous halothane exposure docu- volunteers basal acid output (mean±SEM) Diminishing sensitivity of human mented. A previous reaction to halothane studied from 60-105 min after nifedipine (unexplained post-operative pyrexia or parietal cell function to SMS 201-995 30 mg orally was reduced to 18±+0-51 meq/h jaundice) was noted in 12. Halothane anti- treatment compared with 2-84+±054 meq/h after bodies were detected in 28 of 38 serum placebo (p<0.025). Nifedipine also inhi- samples tested, and the proportion was W LONDONG, M ANGERER, K KUIL, AND VERA bited acid secretion stimulated by low dose similar in those who developed fulminant LONDONG (Gastrointestinal Unit, Chirur- but not high dose iv infusions of pentagas- hepatic failure compared with those 21 who gische Klinik Innenstadt, University of trin. Compared with placebo nifedipine did not. These results indicate that the Munich, Munich, W. Germany. Depart- 30 mg reduced acid output stimulated problem of halothane hepatitis continues ment of Medical and Biological Research, with pentagastrin 0-031 ug/kg/h by a mean to occur and, contrary to published reports, Sandoz AG, Basle, Switzerland) In this of 44% (p=0.05), with pentagastrin can affect children. In some cases the con- double blind, and randomised study we 0(062 ig/kg/h by 39% (p<0.025), and with dition may have been avoidable if a full investigated the efficacy, tolerability, and pentagastrin 0(248 tg/kg/h by 17% (ns). anaesthetic history had been available pharmacokinetics of SMS 201-995, an With maximal pentagastrin stimulation before surgery. octapeptide analogue of somatostatin. (0-992 [tg/kg/h) acid output was unaffected Twenty five and 100 itg SMS 201-995 or by nifedipine. The stimulated outputs placebo were given tid subcutaneously to were examined from 105-150 min post- F14 12 healthy male subjects for one week. At nifedipine and corrections were applied for days 1 and 6 intragastric pH per 24 hours, gastroduodenal loss and duodenogastric Comparison of two methods of estimat- at days 2 and 7 peptone-stimulated acid reflux. Nifedipine 30 mg caused a slight rise ing liver blood flow in patients with output and gastrin release, renal function. in the basal serum gastrin concentration liver disease using indocyanine green Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from A614 The British Society of Gastroenterology

D CLEMENTS, R WEST, AND E ELIAS (Queen vent a second cycle, and infusing distally F17 Elizabeth Hospital, Edgbaston, Birming- 7"SeHCAT plus 5'CrC13 as a recovery Endoscopy versus surgery for common ham) Conventionally, measurement of marker. Plateauing of absorbed 75SeHCAT bile duct stones: a randomised trial liver blood flow (LBF) involved hepatic on y camera indicated completion of one vein catheterisation and a continuous infu- cycle. Recovery of unabsorbed 75Se and A GINESTAL CRUZ, P FIDALGO, A MENDES DE sion. A method of estimating LBF without 5'Cr was then achieved by total gut wash- ALMEIDA, N GRIMA, AND J PINTO COR- hepatic vein catheterisation using a two out distally, using y counter. Ileal clearance was 95, 95, 96, 98 and 96%. FTR was REIA (Departments of Medicine 2 and compartmental analysis of the plasma Santa clearance of indocyanine green (ICG) after measured from decay of 75SeHCAT over Surgery 3, University Hospital of Management of a peripheral intravenous bolus has recently the gall bladder, on 4 successive days and Maria, Lisbon, Portugal) stones is still been described. This new method has only used to derive daily ileal absorption effici- common bile duct (CBD) been assessed in normals. ency (49, 72, 81, 72 and 86%). From these open to controversy and the need of a The two methods were compared in 25 data, recycling frequency was calculated direct comparison between endoscopic and patients with liver disease (13 with cir- (13, 6, 6, 15 and 5 cycles/day). We con- surgical approaches has been often stres- rhosis) undergoing therapeutic hepatic vein clude that first pass ileal clearance of a bile sed. In order to clarify the relative merits catheterisation. acid can be measured in man; this is highly of both treatment modalities we set up a and There was an excellent agreement be- efficient in health, whereas daily absorp- randomised trial, between April 83 tween the values for ICG clearance from tion efficiency varies considerably because February 85. Sixty patients (20 men, 40 the two techniques (r=0.97), with the infu- of differences in recycling frequency. women) were included and stratified in two sion method tending to produce the higher groups: group A: 30 patients with previous cholecystectomy - 16 randomised for endo- result. The estimated and measured extrac- F16 tion ratio and LBF compared less well, scopic sphincterotomy (ES) and 14 for B: 30 however, there was only a significant corre- Abnormal T cell activation process in surgical anastomosis (SA); group lation in patients without cirrhosis, and the chronic hepatitis B patients with gall bladder in situ, 16 for ES agreement between the actual values was (eventually followed by cholecystectomy) poor. K T NOURI-ARIA, G J M ALEXANDER, S MAGRIN, and 14 for SA plus cholecystectomy. Therefore, although the two methods of M G ANDERSON, A L W F EDDLESTON, AND Treatment groups showed no significant measuring ICG clearance correlated and R WILLIAMS (Liver Unit, King's College differences concerning age, sex, length compared well, unfortunately, in patients Hospital and School of Medicine and and s'everity of clinical disease, previous with liver disease, the peripheral bolus and Dentistry, London) To investigate acute biliopancreatic episodes and two compartmental analysis cannot replace whether low Interleukin-2 (IL-2) activity in maximal CBD/stone diameters. Comobidity more severe in hepatic vein catheterisation in the chronic hepatitis B (CHB) is due to abnor- alone was significantly http://gut.bmj.com/ measurement of liver blood flow. The peri- mal T cell or monocyte function, periph- ES patients with gall bladder in situ pheral iv bolus technique therefore re- eral blood mononuclear cells from 43 (p=O0O5). quires further study and validation before patients and 20 controls were cultured with Success rate (defined as complete CBD its widespread adoption in patients with a monocyte dependent (PHA) or a mono- clearance) has been 100% for both treat- liver disease and normals for assessing cyte independent T cell mitogen (PMA). ments in group A and 88% (ES) versus haemodynamic responses. Early and late T cell activation markers 86% (SA) in group B. As a whole, ES were then sought by an immunofluorescent rated 94% success versus 93% for SA. to IL-2 Failures in group B were due to unsuccess- assay using monoclonal antibodies on September 29, 2021 by guest. Protected copyright. receptor, T9 and HLA-DR, while DNA ful ES (1/16) or SA (1/14) and incomplete F15 synthesis was measured by H3-Thymidine stone removal in one patient for each treat- First pass ileal clearance of a bile acid uptake. HLA-DR expression was signifi- ment. Major complications occurred in in man cantly higher in unstimulated T cells (med- 12% of ES and in 18% of SA patients, ian 27.7%) from patients than in controls with no mortality. Length of hospital stay G GALATOLA, R JAZRAWI, C BRIDGES, A E (1-2%, p<0*01). In contrast, after PHA after ES was significantly shorter than JOSEPH, AND T C NORTHFIELD (Depart- stimulation, both early and late T cell after SA in group A (2-6±3-1 vs 8-6±5-2 ments of Medicine and Nuclear Medicine, activation markers were significantly lower days, p=005) and in group A plus B St George's Hospital Medical School, Lon- in patients than in controls (IL-2 receptor, (5-1±7-4 vs 10-5±4-5 days, p=002). don) Although first pass hepatic clear- 14-0 vs 20 5%, T9 5.5 vs 15 3%. HILA-DR Difference in group- B though favouring ance of bile acids is known to be very effi- 7 0 vs 206-6%, p<0.01) and DNA synth- ES, did not reach statistical significance. cient, it has not been previously possible to esis was significantly reduced (25 413 vs We conclude that, in the short term, no measure first pass ileal clearance. Our aim 58 634 cpm respectively, p<0d05). Using treatment modality proved superior. was to measure this, using the new y PMA (50 ng/ml), IL-2 receptor expression except for a definitely shorter hospital stay labelled bile acid 75SSeHCAT, and to relate (11.5 vs 10%) and DNA synthesis (34 060 in ES patients with previous chole- it to fractional turnover rate (FTR). We vs 20 834) were not significantly different in cystectomy. Long term follow up under have previously validated that FTR for patients and controls respectively. These strict clinical, endoscopic and chole- 75SeHCAT measured by y camera is the results indicate that the reduced IL-2 cintigraphic criteria in our patients, and same as for 14C taurocholate by the clas- activity in patients with CHB is unlikely to other (multicentre?) randomised trials may sical Lindstedt technique. We have studied be because of a primary T cell defect, but detect further differences and help to sub- five subjects without ileal disease, occlud- rather a defect of monocyte function or stantiate treatment choice in the individual ing the duodenum with a balloon to pre- the interaction between these cells. patient. Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from The British Society of Gastroenterology A615 F18 membranes). Identical membrane prepara- F21 HLA phenotypes in primary sclerosing tions, not exposed to acetaldehyde, were Role of major hepatic resection for cholangitis and ulcerative colitis controls. The effect of the adduct on the colorectal liver metastases neutrophil was assessed by measuring (a) P T DONALDSON, M L WILKINSON, A L W F superoxide production using cytochrome c H A BRADPIECE, I S BENJAMIN, AND L H EDDLESTON, AND R WILLIAMS (Liver Unit, reduction before and after the addition of BLUMGART (Department of Surgery, Royal King's College Hospital and School of superoxide dismutase. (b) Degranulation Postgraduate Medical School, Hammer- Medicine and Dentistry, London) Pre- using release of 1-glucuronidase. Acetal- smith Hospital, Ducane Road, London) vious studies have shown a positive associa- dehyde preincubation significantly in- From July 1979 to September 1985, 44 tion between HLA B8/DR3 and primary creased superoxide production from patients with colorectal liver metastases sclerosing cholangitis (PSC), and a nega- 15 6±1 8 (mean±SEM, n=7) to 59 1+16 1 were referred for consideration of hepatic tive association with HLA B12. There are nanomoles 0-2/10 cells/min (n=4), p<001, resection. Twenty one patients (47.7%) conflicting reports on HLA associations and significantly increased degranulation underwent major hepatic resection. Eight- and ulcerative colitis (UC). To investigate from 16.9±1.85%, v, to 24-6±2-34% een patients had solitary tumours, and the influence of HLA status and inflam- (r=4) p<005. Acetaldehyde alone did not three had more than one deposit, of which matory bowel disease on the aetiology of cause degranulation or superoxide produc- one was in the contralateral lobe. Twelve PSC, HLA A and B antigens were deter- tion. We suggest that the activation of right hepatic lobectomies, six extended mined in 54 British patients with PSC (35 neutrophils by the acetaldehyde/membrane right hepatic lobectomies, one left hepatic with UC) and DR antigens in 45 of these adduct may be a further mechanism which lobectomy and two segmental excisions (30 with UC) and compared with British initiates inflammation in alcoholic hepatitis. were undertaken. laboratory controls (n=50 and 38 respec- Survival data of the 21 patients show an tively). Frequencies of HLA B8 (25/54) actuarial median survival of 47 months with and DR3 (27/45) were both significantly in- a 64 7% two year survival (11/17). Four- creased compared with the control popula- F20 teen patients are alive (two with recurr- tion, p<0-05 in each case. No negative Free HBV-DNA in leucocytes of chro- ence). There was no death within 30 days association with B12 was demonstrated but nic HBV carriers of operation but one patient died of liver a negative association with DR4 (3/45), failure at two months. The follow up is p<0005, was shown. There was no differ- from two to 47 months. ence in antigen distribution between pati- F DAVISON, G J M ALEXANDER, C ANASTASSA- This represents the largest British series ents with or In KOS, E A FAGAN, AND ROGER WILLIAMS without UC. addition there (Liver Unit, King's College Hospital and of major hepatic resections for colorectal was no increase in the frequency of the School liver metastases. While there are no of Medicine and Dentistry, London) http://gut.bmj.com/ combination HLA Al, B8, DR3 (14/45) prospective randomised studies of resec- with controls Preliminary reports indicate that HBV- compared (10/38) despite an DNA is present in extrahepatic tissues tion versus non-resection in this disease, increased frequency of the individual anti- two comparative studies suggest that resec- gens. These are in including peripheral blood leucocytes. The findings keeping with a relationship between infection of leuco- tion offers hope of cure. Our early results recent British study which demonstrated show that resection can be undertaken with no HLA association with and cytes and clinical expression of disease, the UC, point to phenotype(s) of the infected cell and a low mortality in a specialised unit, these the interaction of immunogenetic factors data suggest that resection is the treatment with bowel disease in the pathogenesis of whether the HBV-DNA is free or inte- grated are not known. To investigate these of choice in appropriately selected cases. PSC. on September 29, 2021 by guest. Protected copyright. questions, 34 patients with chronic hepati- tis B (16 with cirrhosis) have been studied using molecular hybridisation. Mononuc- F22 lear cells from 23 contained HBV-DNA Oral contraceptive use and hepa- F19 but no relationship to histology or HBeAg tocellular carcinoma Acetaldehyde altered liver membranes status was observed as eight of 13 with stimulate neutrophils in the rat CAH, 9/13 with CPH and two of three with J NEUBERGER, D FORMAN, R DOLL, AND ROGER minimal liver damage were positive, and WILLIAMS (Liver Unit, King's College A J K WILLIAMS, AND R E BARRY (Depart- these included 15/23 with HBeAg and eight Hospital and School of Medicine and De- ments of Medicine and Biochemistry, Uni- of 11 with anti-HBe. In each HBV-DNA ntistry, London and ICRF Radcliffe Infir- versity of Bristol, Bristol) Acetaldehyde was present in the 3-2 Kb free monomeric mary, Oxford) Although the association binds to liver plasma membranes and the form and in two (both cirrhotic with anti- between oral contraceptive use and the membrane/acetaldehyde product is capable HBe) higher molecular wei-ht HBV- development of benign hepatic adenoma is of initiating inflammation. Acetaldehyde is DNA, indicative of integration, was well recognised, the association with hepa- the metabolic product of ethanol and the observed. In six patients with infected tocellular carcinoma remains controversial. neutrophil is a characteristic feature of mononuclear cells, polymorphonuclear Between January 1976 and March 1985, 26 alcoholic hepatitis. We have therefore, cells were also positive while in five women aged below 50 years were seen with studied the effect of the plasma membrane/ patients T cell enriched fractions, but not B a histologically confirmed hepatocellular acetaldehyde product (adduct) on neu- cells, were infected. HBV-DNA is present carcinoma arising in a non-cirrhotic liver. trophils in the rat. Rat liver plasma mem- frequently, but is unrelated to histology or Eighteen had been taking the pill for branes were preincubated in 1 mM acetal- HBeAg and is present in the free form, periods of up to 12 years (median eight dehyde, pH 7-4 for two hours at 37°C (test while integration is rare. years). One of the pill users and three of Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from A616 The British Society of Gastroenterology the non-users had serum markers of pre- F24 epithelium were studied by the peroxidase- vious HBV infection (p=0.07). To assess Human lymphoblastoid interferon: in antiperoxidase technique. We examined 20 the role of the pill in hepatoma develop- vitro and in vivo studies in hepatocellu- normal specimens, 21 metaplastic polyps ment the women with hepatoma were lar carcinoma and 103 adenomas. Twenty eight adeno- divided into five age and four calendar mas showed mild dysplasia, 27 moderate periods and the use of the contraceptive dysplasia, 32 severe dysplasia and 16 inva- A A DUNK, T IKEDA. M PIGNATELLI, AND H C was compared with that of 1330 women sive carcinoma. The three oncogene pro- THOMAS (Department of Medicine, Royal interviewed in part of another study. With- ducts were present in superficial colonic Free Hospital, Lonidon) We have ex- in each age/period group the expected mucosa in both normal and neoplastic amined the effects of interferon (IFN) on cases tissue. were absent in the number of for each duration of pill the in vitro and in vil'o growth of the HCC They depths of use category was calculated using the pro- the crypts in normal and metaplasic mu- cell line PLC/PRF/5, and we have studied portion found amongst the controls, and cosa but present in varying degrees in some of the mechanisms whereby IFN the relative risk calculated by multivariate neoplastic tissue. The distribution and in- might be cytotoxic in HCC tumour xeno- of in the analysis and summation over all the grafts. In vitro, IFN produced dose depen- tensity staining deeper part of the groups. increased as Use of the pill for less than four dent inhibition of 3H-thymidine uptake by epithelium the tissue progres- years is not associated with an increased sed from mild through moderate and PLC/PRF/5 cells and this was noted at IFN risk, use for eight or more years is associ- severe dysplasia to carcinoma. All three concentrations as low as 125 iu/ml. ated with a 4-4 fold increase (p<0()1) and Hepatocellular carcinoma xenografts of the oncogene products were present in the if those with markers of HBV are ex- cytoplasm, myc and sis in the nucleus and PLC/PRF/5 cell line were grown in athymic cluded, the relative risk is 7 2 (p<001) only sis at the colonic cell brush border. mice, allocated in groups of eight to receive although the absolute risk remains low. Therefore, the degree of expression of this daily injections of or 2x iu/day 10' 105 of oncogene product appears to correlate with IFN or a saline control. Tumour growth malignant transformation of colonic adeno- was assessed weekly by measuring tumour mas. F23 base area and serum alphafoetoprotein Indocyanine green clearance falls in concentrations. Interferon produced sig- acute rejection after liver transplanta- nificant reductions in tumour growth rate F26 tion and prolongation of mouse survival. HLA Cell proliferation in patients at high class I glycoprotein display and the activity risk of developing colorectal neoplasia of the enzyme 2-5 oligoadenylic acid syn- D CLEMENTS, S HUBSCHER, S C [I SMIThI, E thetase were measured in tumours of ELIAS, AND P MCMASTER (Queen Elizabeth JOYCE MATfHEWS, M GLYNN, A control and IFN treated animals. Both PARKINS, Hospital, Edgbaston, Birmingham) After AND 1 COOKE (Departments of Surgery and http://gut.bmj.com/ were significantly increased by IFN treat- liver transplantation acute allograft rejec- Gastroenterology, Charing Cross and West- ment, suggesting that IFN may affect HCC tion remains a considerable problem. It is minster Medical In- growth in vivo by direct antiproliferative School, London) defined as graft dysfunction because of an creased is seen in the and immunomodulatory mechanisms. proliferative activity immune response and regarded as distinct early stages of experimental colonic carci- from other causes (such as ischaemia, nogenesis so we have measured this in obstruction and infection) which are con- patients at high risk. ventionally excluded. Cells from the upper region of the COLORECT[AL

To study the nature of acute rejection colonic crypts were obtained by cytological on September 29, 2021 by guest. Protected copyright. F25-36 indocyanine green (ICG) clearance (with a brushings at colonoscopy in four groups of two compartmental analysis which permits patients. In 20 control subjects cells were the estimation of extraction ratio (ER) and F25 obtained from different regions of the blood flow (LBF)) was measured serially Oncogene expression in the human colon and these were compared with nor- (n=45) in seven patients during the first colonic adenoma - carcinoma sequence mal looking mucosa of 14 patients with a month after orthotopic liver transplanta- solitary adenoma, 22 with a single carci- tion. All had biochemical, clinical, and N A HABIB, G IGBOAKA, J B W BRADFIELD, K noma and 18 with multiple neoplasms. Cyto- histological evidence of allograft rejection; SIKORA, G EVAN, R C N WILLIAMSON, AND C B preparations were stained with Feulgen and other causes of graft dysfunction were WOOD (Department of Surgery, Royal and the DNA of 100 cells was measured by carefully excluded. Postgraduate Medical School, London; microdensitometry. The proliferative index There was a consistent fall in ICG Departments of Surgery and Pathology, (PI) was derived from the percentage of clearance, and estimated ER and LBF Bristol Royal Infirmary, Bristol and cells containing more than a diploid DNA after grafting which was most marked at Department of Molecular Biology, Ludwig content. about one week, and which responded to Institute for Cancer Research, Cam- There were no significant regional differ- additional immunosuppression. The bridge) Oncogenes are thought to be ences in the PI of the control patients. The volume of distribution of ICG also fell involved in the control of proliferation and mean PI of patients with isolated adenomas during the first weeks after transplantation. differentiation of normal cells. Using (3.3±0.5) or carcinomas (3.6±0.6) was These results suggest that in rejection there monoclonal antibodies to p20, p2 1. and similar to the controls (2.5±0+4) although is not only a fall in ICG clearance but also p62 we studied the expression and distribu- there was hyperplasia in some patients. In LBF. Ischaemia and rejection may there- tion of c-sis, c-ras and c-myc oncogene patients with multiple neoplasms that PI fore be interrelated, with each important in products (respectively). Histological sec- was significantly higher (6-9±0.9) than the the others pathogenesis. tions from normal and neoplastic colonic controls (p<0*001). Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

The British Society of Gastroenterology A617 The abnormal PI in the colonic epithe- Thirty polyps discovered at colonoscopy the routine use of double contrast barium lium is associated with increased risk of were measured and single cell suspensions enemas and an increasingly aggressive en- further neoplasia and this technique is were produced by cytological brushing. doscopic policy has resulted in an increased being used to screen these subjects. The excised specimens were formalin fixed detection rate of symptomatic Dukes A for routine histology and cytopreparations cancers. of the cells were stained by Feulgen and the F27 DNA content of 100 epithelial cells was Why increased dietary fibre or laxatives measured by microdensitometry to pro- F30 may fail in the treatment of severe duce ploidy profiles. The histological sec- Assessment of local invasion in rectal constipation tions were assessed for dysplasia. carcinoma - a comparative study of Nine of the polyps contained hypertetra- endoluminal ultrasound and computed G K TURNBULL, J E LENNARD-JONES, AND C I ploid cells so were classified as aneuploid. tomography BARTRAM (St Mark's Hospital, City Road, Of these, five were found to be malignant, London) In a group of 13 women with two had severe dysplasia and two had moderate dysplasia. Of the 21 diploid J BENYON, D M A FOY, I N TEMPLE, N J MCC intractable constipation three experimental MORTENSEN, J VIRJEE AND P GODDARD models of rectal evacuation have shown polyps, three had severe dysplasia, seven (Departments of Surgery, Pathology, that a disorder of defecation was present had moderate dysplasia and 11 had mild Medical Physics and Radiology, Bristol in every one. A water filled balloon (50 ml) dysplasia. There was a positive correlation of the and the Royal Infirmary, Bristol) The assessment was used to simulate a soft faecal bolus; between the size polyps of local invasion in low rectal cancer is a barium paste (120 ml) and physiological number of cells containing a hyperdiploid necessary preliminary to surgical treat- saline (500 ml) respectively simulated semi- DNA content (r=0.63, p<0.0)01). with size of ment. The inaccuracy of digital assessment solid or liquid stool. Only three of the 13 The increase in DNA polyps has highlighted the need for a more accu- could expel the balloon in the sitting may reflect an increase in proliferation or number of rate method. position whereas all of six normal subjects the presence of a small Twenty three patients with primary rec- could do so easily. Using the technique of hypotetraploid aneuploid cells. This tech- of tal carcinomas and three with benign rectal defaecating proctography with continuous nique provides an objective assessment lesions have been studied pre-operatively video recording, none of the 13 could expel malignant potential and is not subject to of with both endoluminal ultrasound and barium paste as fast (mean 46±17 vs 10±5 observer error as is the interpretation computer aided tomography (CT). SD secs p<0-001) or as completely (mean dysplasia. With CT prediction of invasion beyond % decrease in area 11±31 vs 88±16 the muscularis propria has a sensitivity of p<0-001) as 10 normal women; six patients 88%, a specificity of 67% and a predictive could evacuate hardly any barium. Four of value of 83%; while ultrasound was more http://gut.bmj.com/ the most severely affected patients with F29 Rising detection rate of early colorectal successful with a sensitivity of 94%, a repeated straining efforts could expel no specificity of 89% and predictive value of more than 10% of the infused saline cancer 94%. whereas six normal subjects rapidly evacu- Using endoluminal ultrasound tumours ated 40-80%. Electromyography showed K D VELLACOIT AND N J MCC MORTENSEN can be graded according to the UICC- that these patients contracted rather than (Department of Surgery, Bristol Royal Infirmary, Bristol) From 1970 to 1980, TNM classification. Sonographically two relaxed the striated muscle of the pelvic cases were TI, four cases T2, 15 cases T3 floor on attempted defaecation. Dietary 197 patients were diagnosed as having on September 29, 2021 by guest. Protected copyright. Dukes A colorectal cancers in one Bristol and two cases T4 this showing a high and drug treatment designed to soften and degree of accuracy when compared with increase the bulk of the stools fails to help Hospital. Between 1970 and 1979, 9 4 cases were treated per annum with only 14% postoperative histopathological examina- some patients because they find it difficult tion (r=0-91, p<00l0). to evacuate even semi-solid or liquid stool. diagnosed by barium enema and 9 5% by colonoscopy, and in 19% single contrast Transrectal ultrasound is more effective enemas failed to detect the cancers. By than CT in grading rectal tumours and F28 1985 those treated had risen to 20 per predicting invasion beyond the musclaris Aneuploidy and cell proliferation in annum, and in the last six years 39% were propria; and will have an expanding role colonic polyps diagnosed by double contrast enemas and in the pre-operative assessment of these 14 5% by flexible endoscopy with increas- patients. JOYCE MATTHEWS, A PARKINS, M GLYNN, S ing detection of right sided colonic lesions SHOUSHA, AND T COOKE (Departments of and less than 5% missed by barium ene- Surgery, Gastroenterology and Pathology, mas. Overall 52% of the cancers were F31 Charing Cross and Westminster Medical detected by rectal examination or rigid Occult hepatic metastases in colorectal School, London) The malignant poten- sigmoidoscopy and though 24 (12%) were carcinoma tial of adenomatous colonic polyps is re- asymptomatic only one was detected by lated to their size, histological type and planned screening. In 75 cases (38X4%) the I G FINLAY AND C S MCARD[E (INIRODUCED degree of epithelial dysplasia. Because cancers were confined to the mucosa or BY D C CARrER) (University Department of epithelial dysplasia is subjective, we have submucosa with a recurrence rate of 5% Surgery, Royal Infirmary, Glasgow) We studied the DNA content of cells from compared with the overall rate of 8%. previously reported that 29% of patients polyps in order to assess their biological There has been no equivalent increase in considered to have a disease free liver at activity. the total incidence of colorectal cancer but the time of laparotomy for colorectal carci- Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from A618 The British Society of Gastroenterology noma had 'occult' hepatic metastases but 11 died at one to 39 (mean 13) weeks. undertaken to assess the value of flexible (OHM). The influence of these OHM on Laser therapy achieved safe and effective fibreoptic sigmoidoscopy or colonoscopy five year survival is presented. palliation in 15 (88%) and should be while patients were still bleeding or within Consecutive patients undergoing considered in patients unfit for surgery. 24 hours of the event. Thirty two patients apparently curative resection were studied. were studied (16 men and women, mean On the basis of liver CT in the immediate aged 67 years). All had subsequent barium postoperative period, patients were consi- F33 enemas and follow up ranged from three dered to have a disease free liver or to Role of impaired puborectalis recruit- months to four years. A correct diagnosis possess OHM. Of the 71 patients studied, ment in the descending perineum syn- was made in 20 (62-5%), consisting of 31 (45%) have died; 19 with hepatic drome diverticular disease (10), inflammatory metastases, two with disseminated disease bowel disease (five), intussusception without hepatic metastases, and 10 with N R WOMACK, J F B MORRISON, AND N S (two) - one due to a carcinoma of the local recurrence alone. WILLIAMS (University Department of caecum, carcinoma (one) and haemor- Seven, 30, and 33 patients were allocated Surgery, The General Infirmary, Leeds and rhoids (two). In a further two the bleeding to the conventional Dukes stages A, B, and Department of Physiology, University of was noted to be coming from the right C with corresponding five years survival of Leeds, Leeds) The cause of the descend- colon and in three the examination was 100%, 66%, and 39%. Occult hepatic ing perineum syndrome is uncertain. terminated due to excessive blood or metastases were detected at the time of Perineal position is influenced by the ac- faeces. In four patients the cause of bleed- surgery in 17 patients; only one, (6%) tion of the puborectalis muscle, which itself ing could not be identified either on endos- survived five years. Of the remaining 54 is regulated by a myogenic stretch reflex. copy or subsequent investigations and patients with a 'disease free liver', three Therefore, the lower perineal position at three patients had an incorrect diagnosis have died with hepatic metastases and a rest, in DPS, may result from a defective made, one of whom bled from a small further two with disseminated disease. stretch reflex. To test this hypothesis bowel leiomyoma. There was only one These data suggest that after curative perineal position at rest was measured in 25 serious complication, septicaemia associ- resection, the presence or absence of OHM patients (21 women: four men, age 62±10 ated with an arterio-enteric fistula. determines death from disseminated dis- years (mean ±SD)) with DPS and 24 age ease. and sex matched controls (20 women: four men, age 60±17, p=NS). The threshold F35 for the recruitment of activity in the Does cigarette smoking protect against F32 puborectalis by intra-abdominal pressure ulcerative colitis by affecting colonic Endoscopic treatment of inoperable (IAP) was determined by monitoring mucus production? http://gut.bmj.com/ colorectal cancers with the Nd YAG puborectalis EMG activity during increases of IAP produced by graded Valsalva man- laser G F COPE, R V HEATLEY, AND J KELLEHER oeuvres. The perineal position was (Department of Medicine, St James's confirmed to be lower at rest in DPS S G BOWN, H BARR, K MATHEWSON, R University Hospital, Leeds) The (0-4±0-6 cm above ischial tuberosities) HAWES, C P SWAIN, C G CLARK, AND P B proposed protective effect of cigarette BOULOS (Department of Surgery, Uni- than in the controls (1-9±0-4 cm p<0-01, smoking on ulcerative colitis prompted versity College, London) Seventeen t test). A greater rise in IAP was required investigation of the effects of smoking on for puborectalis recruitment in DPS

patients (11 men, six women; mean age 71) colonic mucus production. Colonic biop- on September 29, 2021 by guest. Protected copyright. with colorectal cancers deemed inoperable (7-9±5-2 cm water) than in the controls sies were obtained from patients attending because of metastatic disease in nine and (0-5±1-8 cm water, p<0-01, t test). There for routine colonoscopy, cultured for 24 concomittant disability in eight were was a highly significant inverse correlation hours in the presence of [3H] glucosamine treated by laser therapy. The tumours were between the recruitment threshold and the and the quantity incorporated into newly 4-27 cm from the anus, circumferential in perineal position (Rs=0-68, p<0-0001). synthesised mucous glycoproteins deter- 13 and localised in four. Via a flexible Thus DPS may result from an abnormal mined (DPM/mg proteinx 1000). The endoscope under minimal sedation 50- stretch reflex and the neurogenic damage patients studied were a 'control' group 80 W laser power was delivered to vaporise present in the muscles in DPS may occur as (colonic carcinoma, polyps and those with- or coagulate exophytic tumour. Each a secondary phenomenon as a result of out colonic disease) and patients with patient required one to six treatments traction on the pelvic nerves. ulcerative colitis. Current smoking history (mean 2-3) with 2-5 days mean hospital was documented, as were other relevant stay per treatment and no complications. clinical details. Among current smokers, Rectal bleeding was controlled in 11 of 12, F34 colitic patients (n=11, 153-4±35-6) had diarrhoea in 10 of 10. Incontinence was Early endoscopy for lower gastrointes- similar mucus production to controls relieved in four of five, tenesmus in seven tinal haemorrhage (n=51, 146.4±16-3) but the non-smoking of eight and obstructive symptoms in eight colitics (n=71, 112 1±10.2) had significantly of nine. One failure required a defunction- K D VELLACO1-r (Department of Surgery, lower levels (p<0-05) than non-smoking ing colostomy. Recurrent symptoms were Bristol Royal Infirmary, Bristol) Lower controls (n=70, 151-7±27-3). The addition relieved by further laser therapy in two but gastrointestinal haemorrhage is a relatively of nicotine, nicotine-i-oxide, and cotinine one required a colostomy. After treatment uncommon cause of emergency admission to the culture medium had no significant six are living at home without troublesome to hospital and often the precise cause is effect on mucus production. symptoms at four to 36 (mean 23.5) weeks, not established. A prospective study was This study indicates that ulcerative colitis Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

The British Society of Gastroenterology A619 patients have a reduced colonic mucus Royal Hallamshire H.spital, Sheffield) (RI%), and ileocaecal clearance in % production compared with controls, and We have previously shown that ileal counts/h (ICC). IT/2 was 21±8 min in that smoking in colitis increases mucus infusion of a 50% corn oil emulsion re- normal subjects (mean±SD) but only one production to control levels. Mucus pro- duced food intake and induced early satiety with IBS was less than I h (p<001). duction does not appear to be influenced in human volunteers, this result is probably Peak% in caecum was greater in normal by tobacco products in vitro. Because explained by enhanced gastric distension subjects (44.7±9-2 vs 14 2±10; p<001) colonic mucus production is reduced in caused by delayed gastric emptying. In this and RI% less (10-3.6-5 vs 61 3±18-6; colitis, increased colonic mucus production study the effect of jejunal infusion of the p<001). Ileocaecal clearance was signifi- may be a mechanism by which smoking same 50% lipid emulsion on food intake cantly faster in normal subjects (65.8±10 could protect against colitis. and satiety was measured in six healthy vs 18-6±8-4; pbloating and F36 pared with infusion of isosmotic saline the technique could prove an exciting Angiodysplasia: a new concept in the (25±2 vs 18±2 min; p<001), and con- diagnostic tool. localisation and aetiology of colonic sumed less food (1143+ 103 vs 577 ±76 g or 2157±196 vs 1076±202 Kcal; p<0)01), angiodysplasia while the quantity of liquid drunk and the F39 rate of drinking were not affected by the ANNE P HEMINGWAY AND D J ALLISON (De- Effect of diet on nitrogen losses from partment of Diagnostic Radiology, Royal lipid infusion. In contrast with the previous the small bowel Postgraduate Medical School, Hammer- ileal studies, the rate of eating was signifi- cantly slower (33±3 vs 51±6 g/min; A CHACKO AND J H CUMMINGS (MRC smith Hospital, London) Angiodysplasia less is the term used to describe microvascular p<001) and subjects felt hungry Dunn Clinical Nutrition Centre, Cam- before starting the meal during infusion of bridge) There is now evidence to show abnormalities usually located in the In two further mucosa and submucosa of the right hemi- lipid compared with saline. that substantial proteolytic fermentation experiments, jejunal infusion of lipid occurs in the human hind gut. The prin- colon. A number of theories have been with postulated as to its aetiology although none delayed gastric emptying compared cipal substrate for this is material entering of them is entirely satisfactory. infusion of isosmotic saline. Jejunal lipid from the ileum. To investigate what deter- We have demonstrated angiodysplasia may thus induce early satiety because of mines the amount of nitrogen lost from the angiographically in 76 patients and over enhanced gastric distension during eating small bowel we fed three diets for two days half of these have undergone laparotomy and by release of a neural or humoral each to six ileostomists all of whom had and right hemicolectomy. The resected mechanism which reduces feelings of colectomy for ulcerative colitis. The diets specimens have been examined using injec- hunger before the meal is commenced. were protein free (PF), N content http://gut.bmj.com/ tion techniques followed by microradio- 0-16 g/day; PF+ 100 g soya beans either graphy and histological examination. whole or pureed, N=6 16 g/day; and a high The site of the lesions has been recorded F38 fibre diet (HF), N= 106 g/day. Daily N and mapped; the majority have been found de- losses (g/day) were: PF 0 91±0 04; soya - Bloated irritable bowel syndrome whole 2-26±0-15; soya- pureed 142±0 12 to be located on the antemesenteric border fined by dynamic 'All Bran' Scan immediately opposite the ileocaecal valve. (soya whole vs pureed (t=8-042, p<0001) and HF 2-2±0-11. Exocrine pancreatic In one patient in whom a recurrence I F TROTMAN AND C C PRICE (Department of occurred after surgery the lesion was lo- function was normal on PF diet (effluent on September 29, 2021 by guest. Protected copyright. Medicine, Mount Vernon Hospital, North- amylase 223±48 units/ml; total proteolytic cated on the antemesenteric border of the wood, Middlesex) A new scanning tech- transverse colon opposite the ileocolic activity 4 6x 104±07 sg azocasein nique has been used to examine the hydrolysed/h/ml). Ten free living ileosto- anastomosis. We wish to postulate, there- ileocaecal region of 10 women with irrit- fore, that the small bowel contents exert mists on a dietary fibre intake of 18 g/day able bowel syndrome (IBS) (median age also collected 24 h effluent which contained some chemical effect on the mucosa of the 43; range 20-70 years) whose presenting colon at this site which makes it more 2-1±0 12 g/day N. Fractionation of ileo- symptoms were bloating and abdominal stomy effluent showed that insoluble frac- susceptible to vascular damage and forma- pain, and the results compared with eight tion on angiodysplastic lesions. tion accounted for 80-85% of nitrogen normal women (median age 36; range losses except low N diet (66%). We con- 22-63 years). Bran (5 g) labelled with 37 clude that endogenous N losses from the MBq 99m-Tc was given orally.to fasted small intestine are about 1 g/day. Physical subjects and three hours later scintiscans SMALL BOWEL BILIARY form of food influences N loss but not the were acquired in 30 sequential two minute dietary fibre content. F37-48 intervals by gamma camera with an on-line after a standard F37 computer immediately 400 Cal liquid meal. The caecum and ileum F40 Effect of jejunal infusion of lipid on were defined as regions of interest and feeding and satiety in human volun- activity time curves plotted after correction HLA: Intestinal permeability, struc- teers for decay and geometric variation. Vari- ture and lymphocytes in coeliac disease ables analysed were ileal half-emptying relatives C P SEPPLE, I MCL WELCH, AND N W time (IT/2), peak% in caecum (PC% ), READ (Clinical Research Unit, H Floor, counts% in ileum one hour after meal M N MARSH, I BJARNASON, A ELLIS, AND T J Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from A620 The British Society of Gastroenterology PETERS (Hope Hospital, Salford, CRC, tory bowel disease we took 10 endoscopic studies show that in heterotopic small Harrow, Broadgreen Hospital, Liver- biopsies from the macroscopically normal bowel allografts mucosal architecture is pool) Small intestinal mucosa in CD/DH distal ileum during routine coloscopy. preserved but glucose, water and sodium is abnormally permeable to the probe 51Cr- Brush border vesicles (BBMV) were iso- absorption is impaired. EDTA. To extend these observations, we lated from pooled biopsies by a Mg"t/ investigated and related intestinal per- EGTA precipitation method. Structural meability in coeliac disease (CD) family integrity of BBMV was examined with F43 relatives to HLA/DR status, mucosal mor- electron microscopy. Alkaline phosphatase phology and epithelial lymphocyte (EL) and maltase were enriched 20-fold in Effect of essential fatty acids on small populations. Twenty seven first degree BBMV. In BBMV of the three groups we intestinal structure relatives were studied: (i) intestinal per- studied NA+/D-glucose, Na+/L-alanine, meability was measured as % of an oral Na+/taurocholic acid and Na+/phosphate D G MAXTON, E U CYNK, AND R P H 10 ml dose (100 ,uCi 51Cr-EDTA) excreted transport at 15 sec and 60 min time points. THOMPSON (Gastrointestinal Laboratory, in a 24 h urine sample; (ii) HLA and DR Uptake rates of the four substrates tested St Thomas Hospital, London) Long chain status was determined by standard im- in the ulcerative colitis group did not differ essential fatty acids (EFAs) are potent munologic methods; (iii) peroral jejunal from controls. In BBMV from seven trophic dietary constituents, and as the mucosal specimens were quantitated by patients with Crohn's disease we found a precursors of prostaglandins may promote image analysis in terms of (a) surface significantly depressed Na+/D-glucose and small intestinal growth. Rats (n=7) were epithelial volume (V) relative to 104.m2 Na+/taurocholic acid transport capacity fed isocalorically for one month normal muscularis mucosae, (b) 'absolute' number after 15 sec (-35% 5%, p<0005), chow (N), an amino acid elemental feed of EL (N,) (c) mean corrected EL nuclear whereas enzyme activity did not differ Vivonex HN (V), or Vivonex HN with diameter (D) and (d) mitotic index (MI) of significantly. Our results demonstrate that 50% calorie substitution by EFA EL (% mitotic figures per 3000 EL per Crohn's disease is a systemic disease of the (V+EFA). The small intestine was divided specimen). gut with distinct transport defects in the into three equal segments and their weights Based on EL populations (N,), subjects histologically normal distal ileum. with mucosal weight, DNA and protein were divided into 'abnormal' (n=12) with measured. Weight gain was significantly increased EL (513±52: M±SE) and 'nor- less than N in both V and V+EFA mal' (234±28: p<0-01). Despite this differ- (N37±2-7, V 2-3±3-1, V+EFA 1-8±3-1 g, ence, permeabilities were identical (2-1% F42 mean±SEM, p<0.001). Whole gut total vs 2-3%) and hence unrelated to EL Glucose transport by rat heterotopic and mucosal weights were greater in population size. Surface epithelial volumes small bowel transplants V+EFA than V animals (V+EFA 57±1-8 (V) (2-3 vs 2-0x106,um3); mean EL dia- and 19±1-1 vs V 47±1-1 and 13±0-7 http://gut.bmj.com/ meters (4-4 vs 4-4 Rtm); and MIs were A J M WATSON, P A LEAR, A J D'ARDENNE, mg/cm, mean±SEM, both p<0005); identical. Apart from one non-B8/DR3/7 R F M WOOD, AND M J G FARTHING (Depart- EFAs also increased mucosal DNA and with a raised Nv, all other individuals in the ments of Gastroenterology, Surgery and protein. Despite lower body weights, abnormal group were either B8 and/or DR Pathology, St Bartholomew's Hospital, EFAs increased mucosal weight above N in 3/7, whereas less than half of the normal London) Jejunal allografts were carried the proximal (N 20±1-7 vs V+EFA group carried these genes. We conclude out between inbred strains of rats treated 23±1-2 mg/cm, mean±SEM, p=NS) and that (1) intestinal permeability in CD with intramuscular cyclosporin A (CyA) middle (N 17±0-8 vs V+EFA 22±1-5, relatives is normal, and independent of EL for seven days. Graft ends were exterio- p<0-01), but not distal, segments. V feed- count. (2) in -35% subjects, EL were rised. Controls had a Thiry-Vella loop ing reduced all gut indices, especially in the on September 29, 2021 by guest. Protected copyright. markedly raised, appeared related to DR constructed from their own jejunum and distal segments. Essential fatty acids are status, but did not cause abnormal villous received CyA. Glucose transport was stu- therefore a potent dietary stimulus to morphology. died in 'successful' jejunal allografts at nine intestinal growth, possibly through en- and 21 days after transplantation using in hanced prostaglandin synthesis. situ perfusion of isotonic glucose-saline (Na 145, Cl 145, glucose 30 mmol/l, F41 osmolality 305mOsm/kg). Both groups had Detection of transport defects in nor- similar body weights at the time of per-- F44 mal ileal mucosa of patients with fusion. Nine days after transplantation net Frequency of gastrointestinal endo- Crohn's disease water and sodium absorption was reduced crine tumours in Northern Ireland three-fold compared with controls R STOLL, W MATEK, H SCHMIDT, H RUPPIN, (p<0-01). Net glucose absorption was un- R G P WATSON, C F JOHNSTON, M M T O'HARE, AND W DOMSCHKE (Department of Medi- changed however (11-5±1-9 vs 13-2±1-8 J M SLOAN, AND K D BUCHANAN (Depart- cine, University of Erlangen, West Ger- smol/l/min/g dry wt; n=6). At 21 days ments of Medicine and Pathology, The many) If there are functional defects in water and sodium absorption was reduced Queen's University of Belfast, N Ireland) the histologically normal small intestinal still further but glucose transport was The assessment of the incidence of any mucosa of patients with Crohn's disease is reduced (5.5±1-6 vs 25-6±3-5; p<0-01). rare condition requires the reliable collec- still controversial. From three groups of Surprisingly, routine light microscopic tion of data from a sizeable well defined patients: (1) 10 patients with active colitis examination of the transplanted jejunum population. In Northern Ireland a central Crohn, (2) seven patients with ulcerative (n=6) showed normal villous height with register for gut endocrine tumours has colitis, (3) 10 patients without inflamma- minimal lymphocytic infiltrate. These been established since 1970. The popula- Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

The British Society of Gastroenterology A621 tion of over 15 million is numerically Plasma CCK concentrations were mea- F47 stable and the centralisation of clinical, sured in 10 Group II and eight Group III Migration of gall stones laboratory and pathology services facili- subjects. There was no significant rise in tates data collection. In 15 years there have plasma CCK after sham feeding in either T V TAYI.OR AND C P ARMSTRONG (Depart- been 109 cases. The annual incidence group. The overall mean basal level was ment of Surgical Gastroenterology, Man- steadily increased at first but has tended to 12 2±0 9 pmolUl, and following sham feed- chester Royal Infirmary, Oxford Road, stabilise in the last five years. This pattern ing was 18-4±2 3 pmol/l. These results Manchester) Factors influencing the suggests that all new cases may now be suggest that there is a cephalic phase to migration of gall stones are ill understood. reported. Overall the frequency of tumours GBE which is atropine sensitive, indepen- Three hundred and thirty one patients was 54% for carcinoids; insulinomas 17%; dent of an intact vagus nerve, and indepen- undergoing cholecystectomy were prospec- islet cell tumours of unknown type 14%; dent of CCK. tively studied. Cystic and common bile gastrinomas 9%; multiple endocrine ade- duct diameters and stone size in the gall nomatosis (MEA) 5%; VIPomas two bladder and bile ducts were measured. cases; glucagonomas one case. The annual F46 Increasing pressure was applied to the incidence per 100 000 of the population Loperamide abolishes gall bladder freshly excised gall bladder in an attempt to since 1980 is 0-32 for carcinoids; insulino- evacuate stones through the cystic duct. mas 0*09; islet cell tumours of unknown contraction in response to cholecysto- Migration of stones through the cystic duct type 0-05; gastrinomas 0-04 and MEA 0 05. kinin occurred in 22%. In patients with Typically only the insulinomas, gas- choledocholithiasis (45), stones passed in trinomas and VIPomas presented with en- W P M HOPMAN, H J A MULDERS, (i ROSEN- 56%'o; in those with gall stone pancreatitis docrine syndromes. Only two of the 59 BUSCH, AND C B H W l.AMERS (Departments (67) stones passed in 67%. In those with patients with carcinoid tumours developed of Gastroenterology and Hepatology, and neither common duct stones nor pancre- the syndrome. Department of Radiology, Universities of atitis (227) stones migrated in only 3% Leiden and Nijmegen, The Netherlands) (p<0c00001). Stones migrated in 3% with a Loperamide is a synthetic peripherally normal cystic duct diameter (<4 mm), acting opiate agonist with a strong anti- compared with 32-5% in those over 4 mm diarrhoeal action. It is generally accepted F45 that loperamide exerts its constipating (X2=26-7, p<0()OOOl). Patients at risk of Mechanisms responsible for the cepha- stone migration and thereby pancreatitis effect by inhibition of ileal and colonic and jaundice have large ducts. These can lic phase of gall bladder emptying motor funetion. Because it is not known be detected by ultrasound and early admis- whether loperamide also affects gall sion should then be arranged to obviate the S ELLENBOGEN, S GRIME, C MACKIE, J CALAM, bladder motility, we investigated the effect risk of life threatening complications of http://gut.bmj.com/ C SPRINGER, S A JENKINS, AND J N BAXTER of oral loperamide on gall bladder contrac- their gall stones. (University Department of Surgery, Uni- tion as determined by real time ultrasono- versity of Liverpool, Department of Nuc- graphy. After an overnight fast eight lear Medicine, Royal Liverpool Hospital, healthy volunteers (four men, four women, Liverpool; Department of Gastroenter- 22-27 years) were studied in random order F48 ology, Royal Postgraduate Medical School, at two mornings with and without prior Effect of Proglumide on canine gall London) Little is known about the loperamide administration (16 mg at 12 bladder contraction

mechanisms responsible for gall bladder and 2 5 hours before infusion of cholecys- on September 29, 2021 by guest. Protected copyright. emptying (GBE), in particular, whether or tokinin (CCK)). Gall bladder volume was R S STUBBS, R 0 PLAIL, P CARTER, AND 1 H not a cephalic phase to GBE exists. Using monitored before and every 10 minutes for BLUMGART (Department of Surgery, Royal 9Tcm-EHIDA cholescintigraphy and sham 90 minutes during infusion of 1 IDU/kg/h Postgraduate Medical School, Hammer- feeding, the cephalic phase of GBE was CCK for 60 minutes. This dose of CCK smith Hospital, Ducane Road, London) studied in 29 healthy volunteers who were results in plasma CCK concentrations in Proglumide is a specific CCK/gastrin sham fed either a sandwich (n= 15; Group the physiological range. Cholecystokinin receptor antagonist which might be capable I), or a cooked meal (n=14; Group II). A infusion without loperamide induced a of inhibiting endogenously stimulated gall further 11 healthy volunteers were given highly significant gall bladder contraction bladder contraction. Such an action would atropine before sham feeding a cooked from a basal volume of 17-2±1-3 cm3 to a be important both in terms of elucidating meal (Group III). Eleven patients with a residual volume of 2.9+±07 cm3 at 50 mechanisms of gall bladder contraction and truncal vagotomy and pyloroplasty were minutes (p<0-001). After loperamide gall predicting therapeutic usefulness of CCK also sham fed a cooked meal (Group IV). bladder volume was 16-6±1-8 cm3 and did receptor antagonists for conditions such as The gall bladder emptied 24±3% of its not change during CCK infusion. From 10 biliary colic. Studies were undertaken in contents in response to sham feeding in to 90 minutes gall bladder volumes in four conscious dogs with chronic biliary eight Group I subjects (53%), eight Group response to CCK with loperamide were and gastric fistulas to examine the ability of II subjects (57%), only one Group III significantly greater than those without proglumide to inhibit endogenously and subject (9%; p=0.03, Group III v Group loperamide (p<0005-p<0(0005). exogenously stimulated gall bladder con- II) and three Group IV subjects (27%; In conclusion, loperamide abolishes gall traction. The latter was monitored by p=0-28, Group IV v Group II). Plasma bladder contraction in response to CCK. measuring bilirubin output (mol/lO min) cholecystokinin (CCK) was measured us- This finding supports the hypothesis that from the biliary fistula. Dose response ing a specific radioimmunoassay with Anti- CCK induces gall bladder contraction by curves were constructed for both an intra- body R15 donated by Professor Dowling. an opiate sensitive mechanism. duodenal (ID) perfusion of mixed amino Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A622 The British Society of Gastroenterology acids and an IV infusion of octapeptide of F50 obtained. For patients with acute hepatic CCK each with and without an IV bolus of Factors affecting the prognosis of failure, there was a significant positive proglumide-Na 300 mg/kg. Proglumide vir- primary biliary cirrhosis correlation between plasma GLA and the tually abolished the gall bladder response latencies of VEP waves P1, (p<0-05); N2, to all doses of ID amino acids and IV CCK. B M GOUDIE, A D BURT, G MACFARLANE, P (p<0-001); P2, (p<0-001); and N3, We conclude that these studies support BOYLE, R N M MACSWEEN, AND G WATKINSON (p<0-OOl). There was no correlation be- the hypothesis that CCK is the principal (University Departments of Medicine and tween plasma GLA and VEP wave laten- physiological mediator of gall bladder con- Pathology, Western Infirmary, Glasgow; cies in patients with chronic liver disease. traction and suggest a possible therapeutic Cancer Surveillance Unit, Ruchill Hospital) From these observatons, we propose use for CCK receptor antagonists in dis- We have studied the relationship between that if GABA is implicated in the orders of gall bladder motility. a wide range of clinical and histological pathogenesis of hepatic encephalopathy, parameters and survival in 195 patients then the mechanism by which it acts in (171 women, 24 men) who satisfy stringent acute hepatic failure may be different from biochemical, serological, and histological that seen in chronic liver disease. criteria for the diagnosis of primary biliary POSTERS cirrhosis. The mean age at presentation was 54 (range 25-78) years and mean F52 duration of follow up (range 0-17) years. Reticuloendothelial system activity and LIVER The mortality from liver failure was 40% hepatic haemodynamics in an ex- F49-56 after five years and 60% after 10 years. perimental model of cirrhosis and por- One hundred and sixteen patients died tal hypertension F49 during the follow up period: 84% as the result of liver disease and 16% from non- D-penicillamine-induced toxicity in S A JENKINS, J N BAXTER, D W DAY, AND R primary biliary cirrhosis (PBC): the hepatic causes. Univariate analysis was SHIELDS (Departments of Surgery and conducted with survival curves drawn using role of sulphoxidation status Pathology, University of Liverpool, Liver- the Kaplan-Meier estimate and differences pool) The phagocytic activity of the re- investigated using the log-rank test. There- H C MITCHISON, R H WARING, E ELIAS, 0 F W ticuloendothelial system (RES) is reduced after separate multivariate analysis of in cirrhosis. The aim of this study was to JAMES, AND M F BASSENDINE (Department (a) clinical, biochemical and immunol- of Medicine, Freeman Newcastle examine RES activity during the develop- Hospital, ogical and (b) histological factors, was upon Tyne, and Queen Elizabeth Hospital, ment and following the establishment of

carried out using Cox's Proportional http://gut.bmj.com/ Edgbaston, Birmingham) The use of D- cirrhosis and to relate any changes to Hazards Model and (a) age, serum bili- in penicillamine (D-P) as a treatment for rubin level, ascites, variceal haemorrhage alterations hepatic haemodynamics. primary billiary cirrhosis (PBC) has been RES activity (uptake of 'Technetium sul- and (b) degree of hepatic fibrosis, presence hampered by its toxicity. D-penicillamine phur colloid by the liver and spleen), of cholestasis and presence of Mallory's is structurally similar to carbocysteine (C- hepatic and systemic haemodynamics (dual hyaline were found to be independent risk were measured in c) and in rheumatoid arthritis a significant factors correlating with shortened survival. microsphere technique) association between impaired sulphoxida- rats before and at four weekly intervals tion of C-c and D-P toxicity has been during the development and after the

establishment of on September 29, 2021 by guest. Protected copyright. reported. We have measured C-c sulph- F51 dimethynitrosamine- oxidation in 20 PBC patients who had induced cirrhosis. Hepatic RES activity either received D-P for > three years Gamma aminobutyric acid (GABA)- decreased progessively until 16 weeks after without side effects (13) or had developed like activity and visual evoked poten- the cessation of DMNA administration adverse reactions (seven) whilst taking the tials (VEPs) in acute and chronic liver (11.1±0-8 to 2-6±0-4, p<0-001 Student's t- drug (lupus erythematosis (one), protein- disease) test). In contrast, splenic RES activity urea (one), thrombocytopaenia (one), skin increased from 4-8±0-5 to 12-9±0-8 over rash with positive ANF (two), taste distur- L J LEVY, R P BOLTON, AND M S LOSOWSKY the same period. Significant increases in bance (one) and severe malaise (one)). (Department of Medicine, St James's Uni- portal pressure, portal venous inflow, The sulphoxidation status was determined versity Hospital, Leeds) Visual evoked splanchnic blood flow and cardiac output by a standard method after a single 750 mg potentials (VEPs) are said to differentiate were observable as early as 4 weeks after oral dose of C-c and expressed as the between the grades of hepatic encephalo- the start of DMNA administration and sulphoxidation index (SI). Eight of the 13 pathy, and gamma aminobutyric acid increased progressively throughout the ex- patients (62%) with no D-P toxicity and (GABA) has been implicated in the patho- perimental period. The extent of portal- five of the seven patients (71%) with genesis of this syndrome. systemic shunting was 11±5% at the end of adverse reactions to D-P had impaired We have measured plasma GABA-like DMNA administration and increased pro- sulphoxidation (SI> 80), the remainder activity (GLA) on 29 occasions in seven gressively to 74±11% by the end of the were extensive sulphoxidisers. patients with acute hepatic failure and on study. The results of this study clearly We conclude that this study confirms a 41 occasions in 14 patients with chronic indicate that hepatic RES activity is pro- high prevalence of impaired sulphoxidation liver disease with and without hepatic gressively reduced during the induction of carbocysteine in PBC patients, but fails encephalopathy using a radio-receptor and development of cirrhosis and that to show a strong association between poor assay. Visual evoked potentials were mea- these changes are associated with altera- sulphoxidisers and D-P toxicity. sured whenever a sample of blood was tions in hepatic haemodynamics, in parti- Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

The British Society of Gastroenterology A623 cular an increase in the extent of porta- abuse on PBM eicosanoid metabolism. F56 systemic shunting. PGE2 and LTB4 production by zymosan- Cholestatic liver disease in neonates stimulated PBMs, in the presence and with Niemann - Pick Type C. F53 absence of exogenous arachidonic acid (AA), was measured. Without exogenous Hypogonadism in alcoholic liver dis- D A KELLY, B D LAKE, A MOWAT, R STEPHENS, AA, PGE2 production by PBMs in ALD is AND S SHERLOCK (Royal Free Hospital, ease; abnormal release of luteinizing less than normal (n= 12, 16-9±4-6 vs n=24, King's College Hospital, Hospital for Sick hormone is a contributory factor 38-3±5-1 ng/106 monocytes, x±SEM, Children, Great Ormond Street, ALD vs controls, p<0-01), and LTB4 London) Niemann - Pick Type C is a P BANNISTER, T HANDLEY, C CHAPMAN AND production was not greater than normal rare cause of neonatal hepatitis. Forty five M s LosowsKY (Department of Medicine, St (n=11, 6-3±2-4 vs n=7, 2-9±1-4 ng/106 patients with this disease were reviewed in James's University Hospital and the Depart- monocytes). With exogenous AA, PBMs order to establish how many presented ment of Nuclear Medicine, The General from ALD patients secreted an insignifi- with liver disease and whether the disease Infirmary, Leeds) Men with alcoholic cantly greater than normal amount of process and outcome differed from those liver disease (ALD) are hypogonadal. This PGE2 (n=12, 973-7±217-8 vs n=24, presenting later with neurological disease. may be secondary to a defect at any level of 585±55 6 ng/106 monocytes), and signifi- Twenty eight patients (62%) presented in the hypothalamic-pituitary-testicular axis. cantly more LTB4 (n=12, 21-8±4-1 vs infancy with hepatosplenomegaly and all It has recently been shown that the release n=7, 12-6±1-8 ng/106 monocytes, had cholestatic liver disease. Detailed in- of luteinizing hormone (LH) must be pul- p<0-01). These findings show an altered vestigation was done in 17/28 only, and satile to be biologically functional. ratio of PGE2 to LTB4 synthesis by PBMs liver biopsies were done in 10 in whom a The present study investigated the re- in ALD suggesting an imbalance which correct diagnosis was made in eight. Two lease of LH in men with proven alcoholic promotes inflammation rather than cyto- children died in the neonatal period and liver disease. Venous blood was sampled protection. cholestasis improved in the other 26 every 15 minutes for eight hours and although hepatosplenomegaly remained. analysed for LH by specific radioimmu- F55 Neurological complications have de- noassay. Luteinizing hormone pulses were Neonatal and adult 64 copper kinetics veloped in 16/28 so far while 9/28 have died identified visually and by computerised (mean age of death 8 years). In contrast the analysis. Spectral analysis was used to in the pig and its relationship to copper 17 patients who presented with neurological identify a secretion of LH with a long half- kinetics in Wilson's disease complications (peak age of presentation 5 life. In control subjects (n=8) 4-5 pulses years) have progressed slower with a mean C D BINGLE, S K S M AND 0 and a slower release of LH, half-life 240 SRAI, LEE, age of death of 12 years. min, were seen. In three men with ALD EPSTEIN (Departments of Medicine and http://gut.bmj.com/ It is important to consider Niemann - but clinically no hypogonadism both LH Surgery, Royal Free Hospital School of Pick Type C in babies with undiagnosed pulsatility and the slower release of LH was Medicine, Hampstead, London) Neo- neonatal hepatitis so that genetic counsell- natal mammals a copper maintained. In four men with advanced have profile ing may be arranged. The presence of a similar to In ALD and clinical hypogonadism no pulses Wilson's disease (WD). WD, larger spleen than liver is a guide to the copper is the liver or slower release of LH was seen. Mean avidly taken up by but diagnosis which can be established by levels of LH was similar in all three groups. little reappears in the serum due to reduced identifying storage in macrophages in liver To test In conclusion, men with advanced ALD incorporation into caeruloplasmin. and bone marrow, and neuronal storage on have an abnormal release of LH which may the hypothesis that WD is caused by rectal biopsy. on September 29, 2021 by guest. Protected copyright. be a major contributory factor in the perpetuation of the fetal mode of copper pathogenesis of the hypogonadism seen in metabolism into childhood, we have stu- these men. died copper profiles and 64 Cu kinetics in neonatal and adult pigs. At birth caerulo- F54 plasmin was <10% of adult level but by 48 hours had increased to > 30%. Serum Abnormal prostaglandin E2(PGE2) copper also increased in a similar manner. and leukotriene B4 (LTB4) synthesis by After iv injection (20 ug/kg) into adults, COLORECTAL peripheral blood monocytes (PBM) in 64 Cu in serum reached a nadir at 10 hour alcoholic liver disease (ALD). and then increased to > 14-7% of the F57-68 administered dose at 24 hour. In neonates F57 W J MAXWELL, N P KENNEDY, J P WALSH, FP a secondary rise did not occur, and at 24 HOGAN, F J BLOOMFIELD, AND P W N KEELING hour <3% was detected. Ft;xthermore Should colonoscopy be the first inves- (Department of Clinical Medicine, TCD each gram of neonatal liver contained tigation for colonic disease? Medical School, St James' Hospital, Dub- > 1.2% of the administered dose whilst lin) Prostaglandins in the liver are cyto- adult livers contained <0-04%. This study D C LINDSAY, I COBDEN, AND C 0 RECORD protective and stimulate hepatocyte regen- shows that 64 Cu kinetics in neonatal pigs (Gastroenterology Unit, Royal Victoria eration. Alcohol abuse causes extensive are similar to WD. In addition, the switch Infirmary and University ofNewcastle upon abnormalities in lipid metabolism and from fetal to adult copper metabolism Tyne) Many patients with suspected col- membrane composition. Peripheral occurs rapidly after birth and failure of this onic disease undergo sigmoidoscopy, monocytosis is a feature of ALD. Our process in man might underlie the meta- double contrast barium enema (DCBe) objective was to assess the effect of alcohol bolic defect in WD. and then colonoscopy. The need for radi- Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A624 The British Society of Gastroenterology ology to precede the latter has not been neither affected the end point nor influ- F60 formally assessed. One hundred and sixty enced the magnitude of variation. An investigation of the cause of solitary eight consecutive patients, (mean age 55-6 Such marked variation both within and rectal ulcers (SRU) years) were therefore randomly allocated between individuals requires consideration to have either a DCBe or total colonscopy whenever rectal compliance is measured N R WOMACK, J H M HOLMFIELD, J F B (TC). The indications were altered bowel and raises doubts about the suitability of MORRISON, AND N S WILLIAMS (Department habit (71%), abdominal pain (52%), the technique either for diagnosis or for the of Surgery, The General Infirmary, Leeds macroscopic rectal bleeding (39%/) and assessment of therapy. For example, for a and Department of Physiology, University anaemia/iron deficiency (19%). Significant crossover trial of a drug to show a 25% of Leeds, Leeds) The cause of SRUs is pathology was found in 54 (32%) patients change (with 90% confidence), at least 100 uncertain but rectal prolapse and abnormal (and included carcinoma (8%), polyps patients would need to be studied. anal sphincter function may be involved. (6%), proctitis (9%) and diverticular dis- The roles of these factors were investigated case (12%). Of the 89 patients allocated to in nine patients (five women: four men, DCBe, 23 subjects (26%) required a subse- aged 27±8 years (mean±SD)) with SRUs quent TC, the indications being suspected F59 by radiological visualisation of the rectum tumour/polyps/stricture (42%), incomplete during voiding of a semi-solid medium, radiological examination (17%) and Rectal intussusception: the commonest in the descending whilst simultaneously measuring intra- barium negative rectal bleeding (39%). In abnormality rectal pressure, by radiotelemetry, and the 15, this yielded further information or perineum syndrome EMG activity of the external anal sphinc- therapy (65%). Of those undergoing ter. Nine normal volunteers (five women: TC(79), only six subjects (7-5%) required D CC BARTOLO, A M ROE, J LOCKE-EDMUNDS, De- four men, 47±8 years) were studied for subsequent DCBe (p<0-01). Since a quar- AND N J MCC MORTENSEN (University comparison. ter of patients initially undergoing DCBe partment of Surgery, Bristol Royal Infir- Sphincter relaxation, to 30% ±27 of rest- are likely to require TC, this may be the mary, Bristol) Obstructed defecation ing activity, accompanied voiding in eight preferred initial procedure. (OD) in the descending perineum syn- of the nine controls. Sphincter activity drome has been attributed to anterior increased to 60% ±45 of maximum volun- mucosal prolapse (AMP). Manometric and tary activity during voiding in seven SRU radiological measurements together with patients with obstructed defecation (OD). evacuation proctograms in 42 patients with Sphincter activity decreased to 55% ±50 of obstructed defecation and normal whole resting activity in two SRU patients with- F58 gut transit times were carried out and out A rectal prolapse (two anterior http://gut.bmj.com/ Can the proctometrogram provide use- compared in a total of 27 controls. Proc- OD. ful data for the clinician? wall prolapses, three rectorectal intus- tography delineated four groups: (a) susceptions, and three full thickness rectal puborectalis accentuation, n=9; (b) rectal prolapses) was demonstrated in the eight G P N KENDALL, D G THOMPSON, S J DAY, AND intussusception, n=23; (c) anterior rectal SRU patients who voided. SRU patients J E LENNARD-JONES (The London and St wall prolapse, n=6; (d) miscellaneous, (112±38 cm water) required higher intra- Mark's Hospital, London) Pressure n=4. The anorectal angle at rest, maxi- rectal pressures to void than controls volume responses to rectal distension by mum basal and maximum squeeze sphinc- (74±27 cm water, p<0.05, t test). balloon are used both diagnostically and to ter pressures and the rectoanal inhibitory

Thus abnormal sphincter function, on September 29, 2021 by guest. Protected copyright. assess therapy despite a paucity of data on reflex did not differ between the groups although correlating with obstructive the response in normal individuals and lack and controls. Groups b and c achieved a symptoms, was not essential for rectal of a normal range. greater increase in anorectal angle on ulceration. This resulted from the com- We studied rectal responses to 469 dis- straining than group a (b-rest, 88-5 (70- bination of rectal prolapse and a high tensions in 10 normal subjects (six studies/ 112)' degress vs strain, 118 (85-140); c- voiding pressure and should, therefore, be day/subject on at least six days) to provide rest, 99 (73-110) vs strain, 134-5 (120-140) amenable to surgical treatment. data on inter- and intra-individual variation (p<0-001); a-rest, 93 (73-106) vs strain, under controlled conditions, and with 95-5 (83-118) (p<0-05); controls-rest, differing inflation speeds (70, 150, 92-5 (78-102) vs strain, 111 (80-130) 240 ml/min). (p<0OOl).' Groups b and c exhibited signi- As expected maximum rectal volume ficant perineal descent below the pubococ- F61 showed wide intersubject variation (me- cygeal line whereas group a did not (b, Sensory impairment and muscle weak- dian 393 ml, range 58-908 ml). Intra- -5-2 (-1-2 to -11) cm; c, -6-0 (-4-0 to ness combine to cause an inadequate individual variation was also large, both -8-0); controls, -1-7 (-0-9 to -4-3) within days (median 10% range±30% of (p<0-001)*; a, -2-7 (-0-8 to -6-0) anal sphincter in idiopathic faecal in- initial distension), and between days (me- (p<0-05)). In perineal descent rectal intus- continence (IFI) dian +13%, range -10% to +30% of first susception was the commonest morpholo- day p<0-05) though the sensory endpoint gical abnormality associated with OD. Iso- N R WOMACK, J F B MORRISON, AND N S did not change. Variation lessened with lated AMP was not observed making local WILLIAMS (University Department of order of study days as subjects became treatment aimed at reducing its bulk ques- Surgery, The General Infirmary, Leeds, accustomed to the technique. Pressure and tionable. and Department of Physiology, University volume changes correlated closely in all .median (range); 'Wilcoxon's signed rank of Leeds, Leeds) Idiopathic faecal incon- subjects (r=0.7). Altering the inflation rate for pairs; *Mann Whitney U test. tinence may result from neurogenic Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

The British Society of Gastroenterology A625 weakness of the voluntary anal sphincter and appeared to be independent of age or F64 yet continent patients with the descending sex. Three patients with incontinence had A double blind study of ispaghula in perineum syndrome (DPS) have a similar absent reflexes; the remainder showed irritable bowel syndome degree of neurogenic weakness as patients prolongation (56±12.2 ms, p<0-01; Wilco- with IFI. Because the sphincters are nor- xon's rank sum test), and diminution of A PRIOR, F A AKBAR, N E SHROFF, AND P J mally controlled subconsciously this para- amplitude (4-5±3.4 cf 1-95±1-9 RV, WHORWELL (Department of Medicine, dox may be explained by defective sphinc- p<0-01). Motor unit potential duration University Hospital of South Manchester, ter recruitment in IFI. Assessment of was prolonged in incontinence (12-23±1 83 Manchester) Although bulking agents, sphincter function by manometry and cf 8-66±1-39 ms, p<0.01) and showed particularly ispaghula, are commonly used radiography was performed in 21 patients significant correlation with PAR latency in irritable bowel syndrome (IBS), clinical with IFI (four men: 17 women, age 64±12 (T=0.56, p<0-001, Kendall's Rank correla- trial assessing their efficacy have, in the years, mean±SD), 19 patients with DPS tion; r=0-69, p<0-001, linear correlation). past, proved largely disappointing. (two men: 17 women, age 55±11), and in This study confirms that the latency of Eighty patients with IBS were randomly 19 controls (three men: 16 women, age this polysynaptic spinal reflex is a reliable assigned to receive either ispaghula (Reg- 60±18, p=NS, t test). Thresholds for index of neuropathy of the EAS in the ulan) or matching placebo for 12 weeks. recruitment of puborectalis by raised intra- investigation of incontinence. Diary cards were used to record abdominal abdominal pressure (IAP) were deter- pain, bloating, and bowel habit. At the mined by monitoring puborectalis EMG beginning and end of the trial dietary fibre activity during increases in IAP produced intake, transit time and pre and postpran- by graded Valsalva manoeuvres. The dial colonic motility were measured. voluntary component of anal canal pres- F63 Bowel habit was unchanged in the sure (VP) (IFI 94±52 cm water, DPS Treatment of functional abdominal placebo group whereas constipation signifi- 84±58, p=NS) and anorectal angle pain by transcutaneous nerve stimula- cantly improved in patients taking ispag- achieved by contraction of the pelvic floor tion hula (p=0 026). Transit time was signifi- (CA) (IFI 940±11, DPS 930±7, p=NS) cantly reduced in those taking ispaghula were impaired by similar degrees in IFI and compared with placebo (p=0.001) especially DPS compared with controls (VP 140±42, G P N KENDALL, K SYLVESTER, AND J E in patients with initially high transit times. No p<0-01, CA 810±5, p<0.01). Higher IAP LENNARD-JONES (Departments of Medical significant changes in colonic motility were was required for sphincter recruitment in Research and Physiotherapy, St Mark's observed. Abdominal pain and bloating IFI (7-8±5 cm water), than in DPS (3-4±3, Hospital, City Road, London) Trans- improved in both groups with no significant p<0.01) and controls (0-5±2, p<0-01). cutaneous nerve stimulation (TNS) is an differences between ispaghula and Deferred recruitment was not motor in effective method of relieving chronic soma- placebo. Global assessment judged treat- http://gut.bmj.com/ origin as the puborectalis was always toni- tic pain which is free from side effects. It ment to be satisfactory in 82% of patients cally active at rest. These findings imply a has not, however, been used for treating receiving ispaghula and 50% of the placebo deficient sensory component of the reflex functional abdominal pain (irritable bowel group (p=0-002). Four of the eight with- combines with muscle weakness to cause syndrome). drawals on ispaghula and 10 of the 15 an inadequate anal sphincter in IFI. In an open trial 29 patients with func- withdrawals on placebo were due to treat- tional abdominal pain, unresponsive to ment failure. drug therapy, were treated at home with In im- The elec- conclusion, ispaghula significantly TNS (minimum one month). proved overall wellbeing in patients with on September 29, 2021 by guest. Protected copyright. trodes were placed either over the site of IBS, and in those with constipation favour- F62 pain or paraspinally over the dorsal nerve ably affected bowel habit and transit time. Correlation of latency of the pudendo- root. Using established criteria, pain relief at one, two, four, and six months was anal reflex (PAR) and mean motor measured as a percentage alteration of a motor unit potential duration (MUPD) visual analogue scale done before treat- of the external anal sphincter (EAS) in ment. At one month 16 patients (55%) F65 neurogenic faecal incontinence obtained good relief (>60% reduction), Effect of diet on the metabolic activity five (17%) moderate (33-59% reduction) of human faecal microflora J S VARMA AND A N SMITH (University and eight (28%) none (<33% reduction). Department of SurgerylUrology and Wolf- This improvement has been maintained B J FEHILLY, A K MALLE-rr, I R ROWLAND, AND son Gastrointestinal Laboratories, Western during follow up (three to nine months). M J G FARTHING (Department of Gastroen- General Hospital, Edinburgh) The latency Transcutaneous nerve stimulation seems terology, St Bartholomew's Hospital, Lon- of the PAR was studied in 38 asymptomatic a good long term method for relieving don and BIBRA, Carshalton, Sur- control subjects and 20 women with neuro- functional abdominal pain. Organisation of rey) Diet and colonic microflora have genic faecal incontinence, supplemented a double blind controlled study however is been implicated in colorectal cancer by determination of the mean motor unit not possible as a cutaneous sensation is pathogenesis. We have investigated the potential duration (MUPD) of the EAS required to induce pain relief and effective effects of daily pectin (18 g), wheat bran using conventional electrophysiological electrode position cannot be predeter- (30 g) and fat (total intake > 150 g) techniques. mined. The persistence of the pain relief supplements on relevant microbial enzyme Pudenodo-anal reflex latency in the con- for the duration of follow up suggests these functions in six volunteers on normal diet. trol group was 38-5±5 8 (mean±SD) ms findings are not a placebo effect. Dietary regimens lasted 20-22 days with Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from

A626 The British Society of Gastroenterology alternate control and supplement periods abundant faecal sterol and the degradation in particular, information on bowel run concurrently over five months. Three was very low (10-4+17-6% of total sterols, function after intestinal reconstruction. In fresh faecal specimens were collected dur- versus 86-1+10-5% of adults, p<0.001). In a review of 33 patients (21 women and 12 ing the last five days of control and test children of group b, c and d the percent of men) undergoing the Hartmann procedure periods. Pectin supplementation signifi- degradation was progressively higher than for complicated diverticular disease, four cantly decreased 3-glucosidase and P- that of group a reaching, in group d, the died. After a median interval of 17 weeks, glucuronidase activities per g faeces by values of adults. 22 of the 29 survivors underwent restora- 50% (p>0.001) relative to control periods We conclude that the intestinal degrada- tion of bowel continuity. There were no (-60 and 30 RM/h/g, respectively). Faecal tion of cholesterol is a process which begins deaths but one anastomosis leaked and ammonia formation was two to three fold from the first years of age in some subject wound infections occurred in 35%. A greater during pectin supplementation and progressively reaches during the questionnaire of postoperative bowel (p> 0-001). Wheat bran and fat supple- adolescence the pattern typical of adults. function revealed that eight of the 22 mentation had no effect on these microbial suffered from faecal incontinence albeit enzyme activities. None of the dietary minor, and wore pads at all times to regimens changed nitrate or nitro reduc- prevent soiling. A prospective study of tase activities. F67 anorectal physiology and function in six patients before and after reanastomosis has Thus, bacterial ,3-glucosidase and f- Mucosal proctectomy with J-shaped glucuronidase activities are reduced by ileal pouch formation in the treatment confirmed the questionnaire findings, two patients wearing pads. There was no cor- relatively short term pectin supplementa- of ulcerative colitis tion of a free choice diet. Reduction in relation, however, with anal pressure glucoside and glucuronide hydrolysis may changes pre- and post- reconnection. T V TAYLOR (Department of Surgical Gas- Although the Hartmann procedure is decrease the formation of toxic bacterial troenterology, Manchester Royal Infirmary, products in the colon. regarded as the safest operation for compli- Oxford Road, Manchester) Total col- cated diverticular disease, restoration of ectomy, mucosal proctectomy and ileal bowel continuity is associated with con- pouch formation has been carried out in 17 siderable morbidity to the patient. F66 patients over a four year period. Mucosal Excretion and degradation of faecal proctectomy was carried out with the rec- neutral sterols in children tum lying in situ. A 'J'-shaped ileal pouch was formed with a 15 cm limb. The ileoanal a C SACCHETrI, L RONCUCCI, P DI DONATO, F anastomosis was performed as mucosal BALLI, D GALLI, N CARULLI, AND M PONZ DE graft technique with a large tube left in situ http://gut.bmj.com/ LEON (Istituto di Patologia Medica ed across the anastomosis for seven days. Two patients had an initial colectomy for toxic SMALL BOWEL Istituto di Clinica Pediatrica Universita di F69-81 Modena, Italy) It has been shown that in dilatation of the colon and mucosal proc- tectomy with pouch formation was carried adults a large fraction of the unabsorbed F69 cholesterol is converted to two metabo- out at a later date. All patients had a loop lites, coprostanol and coprostanone, by the ileostomy for four months. The only Do patients on home parenteral nutri- bacterial intestinal flora. We proposed to serious postoperative complication prior to tion (HPN) become vitamin and min- define the pattern of excretion and intesti- ileostomy closure was a case of intestinal eral depleted? on September 29, 2021 by guest. Protected copyright. nal degradation of neutral sterols in children obstruction which required a further lapar- of different age in order to determine at otomy. Two patients over the age of 45 J L SHAFFER, A SHENKIN, K SHIPLEY, I which age the pattern typical of adults is years developed incontinence, two, over HOLBROOK, M MUGHAL, S PElTIT, AND M H established. Twenty nine children hospital- the age of 40 years have had recurring IRVING (Departments of Medicine, ised for minor diseases were studied; they electroyte problems. One patient who had Surgery and Chemical Pathology, Hope were divided in the following groups: (a) toxic dilatation developed a fistula between Hospital (University of Manchester), Sal- from 1 to 12 months old (n=9); (b) from 1 the pouch and the vagina. Twelve patients ford and Department of Biochemistry, to 3 years (n=7); (c) from 4 to 7 years have a satisfactory life style being continent Royal Infirmary, Glasgow) Protein, fat (n=6) (d) from 8 to 13 years (n=7). The with an average of four bowel actions in the and carbohydrate requirements are well results were compared with those observed daytime. established for patients on HPN. This is in 38 adults. Faecal samples were collected not so for most minerals, vitamins and for three to six days, and sterols analysed trace elements. In our HPN programme by GLC. The mean daily excretion of F68 the feeding regimen routinely only pro- neutral sterols, in children, was 260±209 Outcome after the Hartmann proce- vides zinc, magnesium, manganese and mg/day S D M versus 412±31 mg/day in the dure for complicated diverticular vitamins. For the past two years we have adult group (p<0-005). Sterol excretion monitored plasma levels of iron, magne- increased from group a (80-150 mg/day) to R G TUDOR, G D OATES, AND M R B KEIGHLEY sium, zinc, copper, chromium, mangane- group d (360-400 mg/day), becoming simi- (Department of Surgery, General Hospital, sium, selenium, and vitamins A, E and B lar to that of adults. All the adults con- Birmingham) The Hartmann procedure complex in 21 patients on HPN for longer verted the large majority of cholesterol to is an operation commonly undertaken for than five months. Sixteen patients require its metabolites. In contrast, in children less complicated diverticular disease. There either total (n= 11) or partial (n=5) than 1 year old cholesterol was the most are, however, few reports of outcome and, parenteral nutrition. Six patients, able to Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from The British Society of Gastroenterology A627 maintain oral nutrition require regular F71 jejunum of seven patients without inflam- intravenous fluids and electrolytes. In the Calmodulin antagonists regulate cal- matory bowel disease and from normal intravenously fed group three patients be- cium transport in vesicles of human jejunum of five patients with Crohn's came anaemic: one because of copper disease elsewhere in the small intestine or depletion and two iron deficiency: three duodenum colon using a Mg++/EGTA precipitation others were found to be iron deficient. Six method. Zinc uptake by BBMV was satur- patients have been started on selenium R STOLL, H RUPPIN, H STERN, AND W DOMS- able, dependent on temperature, luminal replacement because of low plasma sele- CHKE (Department of Medicine, Univer- pH and medium osmolarity. Zinc uptake nium and red cell glutathione levels. In the sity of Erlangen, West Germany) was three-fold enhanced after 1 min in the Calmodulin (CAM) was introduced as a electrolyte group, one patient has become regulator of intestinal presence of an outside K+-gradient as iron deficient and three developed tetany Ca++-transport. We compared with the uptake in the presence due to hypomagnesaemia. We have found investigated the effect of the calmodulin- of a Na+-gradient. K+-dependent zinc no vitamin deficiency, aluminium toxicity antagonists loperamide (LOP) and uptake could be stimulated by adding 0*5 calmidazolium (CaLM) on Ca++-transport or metabolic bone disease. The underlying in mM D-glucose, 0-5 mM L-alanine, 0-5 mM disease process appears unrelated to the brush border (BBMV) and basolateral L-glycine or 0-5 mM L-glycylleucine to the likelihood of developing deficiency states. (BLMV) vesicles. Brush border vesicles transport medium. Conversely 0-1 mM zinc In 52% of patients on long term PHN a and BLMV were isolated from surgically in the transport medium did not stimulate depletion of one or more micronutrients resected pieces of human duodenum by a uptake of these organic substrates. K+- has developed. We recommend monitoring Percoll-gradient procedure. Alkaline dependent zinc uptake by BBMV of five and selective supplementation in these phosphatase was enriched 20-fold in patients with Crohn's disease was signifi- patients. BBMV, whereas Na+/K+ATPase was cantly depressed (-20%±5%, p<0.05) as enriched 15-fold in BLMV. Brush border compared with zinc uptake after 15 sec by vesicles or BLMV were incubated with BBMV of controls. We conclude, that zinc 5 ,M LOP or 5 [iM CaLM for 1 h at 5°C. In transport is inhibited in the histologically LOP or CaLM-pretreated BBMV the normal jejunum of patients with Crohn's F70 CAM-activity was significantly (-50% +5%, disease, it can be stimulated by K+-gradient Rat model for the ileal brake p

F73 http://gut.bmj.com/ into the human ileum delays small bowel itory effect of LOP and CaLM. In BLMV transit time. To investigate the response we found a Na+/Ca+ + exchange and a Hyperglycaemia: evidence for sequen- further it was necessary to develop a good ATP-dependent Ca"+-transport. Loper- tial changes in glucose transport at animal model to measure small bowel amide had no effect. CaLM inhibited ATP- the microvillus membrane (MVM) transit time (SBTT). The technique of dependent Ca"+-transport significantly and basolateral membrane (BLM) of monitoring excreted hydrogen was used to (-40%+5%, p<0005). This effect could jejunal enterocytes measure SBTT of the head of a not be reversed by CAM. We conclude radiolabelled test meal in 120 rats fed by that CAM-anatagonists block CAM- E S DEBNAM, W H KARASOV, AND C S gavage, after 18 hours starvation. Results sensitive Ca++ entry, CaLM inhibits ATP- THOMPSON (Department of Physiology, on September 29, 2021 by guest. Protected copyright. were compared with the distribution of a dependent Ca"+-transport through an Royal Free Hospital School of Medicine, test meal in the gastrointestinal tract in rats CAM-independent mechanism. London and University of Wisconsin, killed at different time intervals after Madison USA) It is known that both gavage. Values for SBTT were compatible acute (iv, glucose, four to six hours) and with the distribution of labelled meals in chronic (>48 h diabetic) hyperglycaemia 90-8% of animals. Repetitive values (x4) F72 enhance glucose transport by the rat je- obtained for SBTT using hydrogen analysis junum. The cellular mechanisms involved showed consistent reproducibility in six Transport of zinc in brush border remain uncertain. In this present work rats, the coefficients of variation ranging vesicles from human jejunum. A using hyperglycaemic rats we have mea- between 4.4% and 13-9%. In a further six role for luminal factors and Crohn's sured in vivo glucose absorption across the animals with chronic indwelling ileal can- disease jejunum and used an in vitro method to nulae, this technique of monitoring SBTT study unidirectional movement of glucose was used to investigate the effect of ileal R STOLL, H STERN, H RUPPIN, AND W across the MVM. Animals were either infusion of 20% intralipid versus infusion DOMSCHKE (Department of Medicine, Uni- infused iv with 1-44 M glucose in 154 mM of isosmotic saline (0-3 ml/h), on the versity of Erlangen, West Germany) In NaCl for five hours or injected seven days passage of a meal down the small intestine. order to elucidate the different transport before use with streptozotocin. Uptakes Ileal infusion of intralipid delayed the steps involved in the epithelial transloca- were corrected for passive movement and stomach to caecum transit time from tion of zinc we studied zinc uptake of brush calculated as nmol/cm/min. Acute hyper- 106±3-3 min to 218±21 min (p<0-001). border vesicles (BBMV). Brush border glycaemia induced a 66-2% increase in Therefore there is a good model to further vesicles were isolated from surgically absorption in vivo (p<0.001) but only a investigate the ileal brake. resected pieces of histologically normal modest increase of 21-1% in vitro (p>0.2). Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from A628 The British Society of Gastroenterology

Intestine from diabetic rats, however, RR MOSS, J C WYA1r, D A FARAH, AND R I measles mean ratio 14 (p<0.001) and showed an enhanced absorption both in RUSSELL (Gastroenterology Unit, Royal correlated with lactosuria in those drinking vivo (77-2% increase p<0-001) and in vitro Infirmary, Glasgow) We have previously milk. Those with chronic diarrhoea mal- (80-3% increase p<0.025). These data shown that wheat bran significantly impairs nutrition had jejunal subtotal villous suggest that the initial response to hyper- zinc absorption in normal subjects. We atrophy resolving with effective treatment. glycaemia is a rapid adaptation of glucose have now examined the effect of fibre and Enteropathy with gastrointestinal and transport at the BLM. During more pro- phytate, the two major components of systemic infection is associated with mal- longed hyperglycaemia, changes in uptake wheat bran, on zinc absorption. Zinc nutrition in The Gambia where food sup- at the MVM are involved in the cellular absorption was studied in 18 normal sub- plies are adequate. response. jects by seven day whole body 65 Zn retention. The subjects were randomised into three groups: a, b and c; all received F77 the isotope in combination with a loading Cryptosporidium: an understated F74 dose of zinc sulphate and 20 g of Rice cause of gastroenteritis Study of the role of truncal vagotomy Krispies - a low fibre, low phytate food. in glucose malabsorption after gastric Group a received zinc and Rice Krispies M P O CONNOR, M E DILLON, E O CONNOR, alone, group b had pure phytate added to surgery P W N KEELING, AND D G WEIR (Depart- their test meal in an amount equal to that ment of Clinical Medicine, Trinity College, present in 20 g untreated bran, and group c S A RAIMES, V SMIRNIOTIS, E J WHELDON, C W St James' Hospital, Public Health Labora- took 20 g of bran from which most of the AND I D A JOHNSTON (University tory and Cherry Orchard Hospital, Dublin, VENABLES, phytate had been removed. Zinc absorp- Department of Surgery, Newcastle upon Ireland) Cryptosporidium was recognised Tyne) We have shown that after TV&P tion was 15-65±5-5% (mean±SD) in group initially as a cause of severe diarrhoea in a, 3-4+1-4% in group b and 7 0+4 1% in few patients fully absorb a hyperosmolar the immunocompromised but is now being group C. The absorption in groups b and c detected more frequently in the immuno- glucose load - this is abnormal when com- than in pared with non-operated controls and was significantly lower (p<005) competent host with gastroenteritis. This Group a, and that in group b nearly operations without truncal vagotomy. The study reports the incidence and clinical matched that seen with pure bran aim of the present study was to separate manifestations in a large population of in our previous study. We of in gastric drainage (2-4±1-3%) immunocompetent gastroenteritis patients. the effects changes conclude that the phytate component of from those of vagotomy by comparing the Faecal smears from 948 inpatients pre- wheat bran is the most important factor senting with symptoms of gastroenteritis handling of a 150 ml 50% glucose drink in affecting zinc absorption. 12 patients after Billroth I gastrectomy (a) were examined for cryptosporidium using http://gut.bmj.com/ and 12 patients with the same operation the safranin-methylene blue method. Thirty plus truncal vagotomy (b). Glucose malab- eight cases (4%) were identified, mean age sorption (detected by a breath hydrogen F76 24-4±4-0 months (range 2 months-9 method) was significantly more common in years). Family screening detected two Diarrhoea and malnutrition in Gam- further cases. Clinical manifestations were group b (B:11/12 vs 4/11; p<0-01). Plasma bian infants glucose rose and fell significantly faster in compared with an age- and sex-matched control group of gastroenteritis patients. the vagotomy group although the peak R BEHRENS, P LUNN, C NORTHROP, P HANLON, levels were similar. The maximum fall in The mean duration of diarrhoea was 15

AND G NEALE (MRC Dunn Nutrition Unit, on September 29, 2021 by guest. Protected copyright. plasma volume was significantly greater in days (range 2-56 days), being severe (¢5 Cambridge and Tropical Research Unit, BM/day) in 16 (42%). Vomiting occurred group b (median fall - b:11% vs a:6%; Fajara, The Gambia) Sixty eight Gam- in 95%. These symptoms were similar to p<0.001). Symptoms experienced were re- bian infants (aged 0-24 months) were corded in all patients. There was no signifi- the control group. A leucocytosis (62% vs followed for eight months. Each month 29%, p<0-01) and a pyrexia > 37-5°C cant difference in systemic symptoms intestinal integrity was measured by the scores despite the difference in plasma (45% vs 21%, p<0.05) occurred more differential urinary excretion of lactulose frequently in the cryptosporidial group. volume fall. Gastrointestinal symptoms (L) and mannitol (M) and correlated with were significantly more common in the Intravenous rehydration was required in clinical progress. More detailed studies significantly more patients with cryptospor- vagotomy patients (median score - b: 10-5 were undertaken in 15 hospitalised infants. vs a:0; p<0-001). idium (26% vs 5%, p<0-05). For well infants of normal weight the mean This study shows that cryptosporidium is We conclude that whilst destruction of Log L:M ratio was 0-41 (range 0-11-1-42) the pyloric sphincter mechanism increases an important and common cause of child- (255 tests); for those underweight (60-80% hood gastroenteritis. The diarrhoea is the rate of gastric emptying of liquids, norm) mean ratio 0-52 (45 tests) (p<0.01). truncal vagotomy had an additional and often severe requiring hospitalisation and Infants suffered much ill health (clinic iv rehydration. These results indicate that a profound effect on the handling of an visits: diarrhoea 20%, respiratory infection absorbable hyperosmolar load. leucocytosis and a pyrexia are more com- 19%, skin infection 9%). Irrespective of mon than has previously been reported. bowel function pathogens were found in 20% of 583 stool specimens. Permeability ratios were raised in sick children- for F75 example, short lived diarrhoea (76 tests) F78 Reduction of zinc absorption by com- mean ratio 1-03 (p<0.001); chronic diar- Detection of Giardia antigen in duo- ponents of wheat bran rhoea (17 tests) mean ratio 2-85 (p<0()(1); denal fluid by ELISA Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from The British Society of Gastroenterology A629

A SA'ADU, A K J GOKA, S G WRIGHT, AND M J G effects of beta blockade on gastric emptying ulceration induced by the anti- FARTHING (Department of Gastroenter- and intestinal motility. Colonic arrival of inflammatory drugs indomethacin and ology, St Bartholomew's Hospital, London; the carbohydrate was detected by a rise in flurbiprofen Department of Clinical Tropical Medicine, exhaled breath hydrogen. London School of Hygiene and Tropical Polysaccharide transit was accelerated J A TURTON, R M HICKS, J RODE, AND J Medicine, London) To detect Giardia by Atenolol, 182 6±26 min (m±SEM) vs GWYNNE (INTRODUCED BY P B COTTON) antigen in duodenal fluid when microscopy P, 272±27 min p<001. Repeat studies (Bland-Sutton Institute and School of Path- for trophozoites is negative, we have de- with propranolol showed similar responses, ology, Middlesex Hospital Medical School, veloped an ELISA for use on material 192 3±16-1 vs 271±27 min (p<001). In London) Non-steroidal anti-inflamma- obtained from 'string' tests (n=29) and contrast, lactulose transit was unaffected tory drugs (NSAIDS) cause ulceration of duodenal aspirates (n=7). Eleven of these by beta blockade 56 0±3-7 min vs the gastrointestinal (GI) tract both in man patients had Giardia in stool or duodenal 585±36 min (p>01). and, as shown here, in rats. The effect of fluid on microscopy, nine were Giardia- Beta-blockers thus accelerate polysac- indomethacin (INDO) and flurbiprofen free but had other enteric parasites and 16 charide but not lactulose transit through (FRO) on the rat intestine can be reduced were parasite free. Duodenal juice was the upper gut indicating a mechanism or prevented by co-administration of eluted from strings into buffer and then which is independent of gastric emptying or specific retinolds. like aspirates, used as antigen source in the jejunal motor activity. Reduction of pan- In the rat, FRO (c 55 mg/kg body wt/day ELISA. Phenylmethylsulphonyl fluoride (a creatic secretion causing carbohydrate mal- in drinking water) induced GI ulceration, protease inhibitor) was required to pre- digestion seems a likely explanation for sparing only the stomach, proximal fifth of serve assay sensitivity. ELISA was positive these results. the small intestine and distal large intes- in seven of eight string test patients with tine. INDO (c 10 mg/kg body wt/day in giardiasis, in three of whom duodenal fluid F80 water) primarily ulcerated the mid- and microscopy was negative. Three Giardia- and manometric assess- distal small intestine. The lesions involved positive aspirates were also ELISA- Scintigraphic transmural necrosis and led to peritonitis positive. ELISA was negative in eight of ment of human ileocaecal transit and death in four to six days. Other nine patients with other parasites, but was NSAID-treated rats were fed concurrently also falsely positive in four other patients R C SPILLER, M L BROWN AND S F PHILLIPS with diets containing either one of six returning from the tropics with diarrhoea. (Gastroenterology Unit and Department of retinamides, 13-cis retinoic acid, vitamin A The ,sensitivity and specificity of the Nuclear Medicine, Mayo Clinic, Rochester, acetate or 5-carotene. No ulceration de- ELIS4A are 91% and 80%, respectively. USA) The patterns of motility controlling veloped in the GI tract of INDO-treated This study shows that Giardia antigen can terminal ileal emptying in intact man are rats also fed N-(4-hydroxyphenyl)retinamide be detected in duodenal fluid by ELISA largely unknown. We have therefore and none died over a period of five weeks. http://gut.bmj.com/ (with protease inhibitor), a method which studied ileocaecal (IC) transit in 15 Other retinoids also gave dose-related pro- may compliment other diagnostic healthy volunteers using an 11-lumen oro- tection but etretinate and 5-carotene had techniques. caecal tube. 9"Tc DTPA (0-5 mCi in 1 ml of no protective effect. The degree of protec- saline) was injected via a port 50 cm from tion afforded varied both with the indivi- the IC junction and IC transit assessed by dual retinoid and with the particular NSAID serial 1 min y-scans. Ileal motility was used. recorded via side-opening manometry F79 ports spanning the last 70 cm of the tube. Beta blocking drugs accelerate the Isotope was injected either fasting (n=5) on September 29, 2021 by guest. Protected copyright. passage of carbohydrate to the colon or 2 1/2 h after a 400 Kcal mixed meal (n= 10). J O BRIEN, D G THOMPSON, W R BURNHAM, Postprandially the time for 50% of the INFLAMMATORY BOWEL DISEASE AND E WALKER (Department of Gastro- isotope to enter the colon (T50) was 66±8 enterology, The London Hospital, London) min, significantly faster than during fast- F82-90 Although diarrhoea is the commonest ing, T50= 183±37 min, p<001. The slower gastrointestinal side effect of beta-blocking fasting transit was associated, in four out of F82 drugs the precise mechanism is unknown. five subjects with prolonged (> 20 min) Reproducibility of endoscopic findings In animals pancreatic secretion is inhibited periods of 'ileal stasis' which were not seen in colonic Crohn's disease (CCD): a by beta-blockers suggesting that in man, after the meal (significant difference from mutlicentre prospective interobserver nutrient maldigestion with colonic over- fasting, p<001). Phase III of the MMC variation study load could be a contributory factor. was rarely (0.8±0.2/24 h) seen in the ter- We therefore compared in eight sub- minal ileum nor was there any relation A WORK BY THE GEIAIDT PRESENTED BY R jects, the effect of beta blockade using between T50 and ileal motility indices. MODIGLIANI AND J Y MARY (INSERM Atenolol (A) 100 mg or placebo (P) on We conclude that fasting IC transit in U290, Hopital Saint-Lazare, 75010 Paris, nutrient transport through the upper gut man is slow and erratic compared with France) A colonoscopy was done in 130 following ingestion of a standard meal transit 21/2 h after a meal. colonic Crohn's disease (CCD) patients: containing carbohydrate, either as polysac- each examination (colo) was simulatenously charide (homogenised beans) or as lactulose. done by a pair of endoscopists (endoP) Lactulose being neither digested nor F81 who did not communicate with each other. absorbed, served as a control for any Retinoid prevention of intestinal One hundred and twelve colos were carried Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from A630 The British Society of Gastroenterology out by 18 intracentre (INTRAC) endoPs radiology or colonoscopy. The Harvey and activity in inflammatory bowel disease (endoscopists from the same centre) and 22 Bradshaw index was used to assess Crohn's (IBD) colos by 14 intercentre (INTERC) endoPs disease activity. In 14 patients scan results (endoscopists from different centres). The corresponded with the extent of disease H W VERSPAGET, P A F DE BRUIN, I T WETER- endoscopic form included (1) For the five shown by other investigation. Two patients MAN, J H VERHEIJEN, M NAP, AND C B H W segments defined (a) a list of nine lesions to had falsely negative scans. In Crohn's LAMERS (Department of Gastroenterology be ticked: pseudopolyp, healed ulceration, disease there was a good correlation (rS and Hepatology, Department of Pathology, erythema, swollen mucosa, aphtoid, super- 0-80, p<0-01) between the severity of University Hospital and Gaubius Institute ficial, deep ulceration, ulcerated and non- disease assessed by the activity index and TNO, Leiden, The Netherlands) Plasmi- ulcerated stenosis; (b) two linear analogue the percentage of faecal isotope excreted. nogen activators have been shown to play a scales for estimation of the total surface of This test is non-invasive, may be used in role not only in fibrinolysis but also in the lesions (SL) and of ulcerations (SU). debilitated patients, and provides an objec- tissue remodelling, carcinogenesis and in- (2) For a global assessment of lesion tive assessment of disease activity in flammation. We investigated the activity of severity, a five gradation- and a linear patients with IBD. tissue type plasminogen activator (t-PA) analogue scale. The reproducibility of and urokinase-type plasminogen activator lesion detection - appa statistics (K) and (u-PA) in homogenates of intestinal mu- predictive values - was fair good or very cosa from Crohn's disease (CD, n=40), good (p<0-05, 0-01, and 0-001) except, in F84 ulcerative colitis (UC, n=16), diverticular the INTERC study, for erythema and Postheparin plasma diamine oxidase disease (n=5) and controls (normal mu- swollen mucosa. Intraclass correlation (DAO): a non-invasive marker of ac- cosa from adenocarcinoma resections, coefficients r were > 0-85 (p<0-001) for tive ileal Crohn's disease? n=78). Inflammatory bowel disease tissues SL and SU in both studies. Assessment of were divided into three groups: non-, a overall severity by qualitative (INTRAC M AND R H moderately and severly inflamed. With and T ROKKAS, S VAJA, G MURPHY, K=0*64; INTERC K=0-57, p<0001) DOWLING (Gastroenterology Unit, Divi- a sensitive spectrophotometric enzyme quantitative scale (INTRAC r=0-86, sion of Medicine, United Medical and assay we could determine u-PA and t-PA p

M V TOBIN, S HUGHES, A I MORRIS, AND I T mmol/24 h (NS) and 11-1±+42 compared to be accompanied by major perturbations of GILMORE (Gastroenterology Unit, Royal 0-07±0-03 Fmol/I (p<002). The concen- immunoregulatory T cell subpopulations. Liverpool Hospital, Liverpool) The con- tration of the acetylated metabolite in centration of platelets in peripheral blood faecal water was similar in the two groups. may be raised in Crohn's Disease, as in Polymer coating is a very effective method other inflammatory conditions, and in one of promoting delivery of 5ASA to the F89 previous study in a small number of colon, stool dialysate concentrations being Transit time in ulcerative proctitis patients the platelet count correlated with 20 fold more than those in controls. Increased trough plasma levels probably serum orosomucoid concentration. We C C AINLEY, D A BLACK, A SENAPATI, AND have compared the platelet count with the reflect delayed absorption but no evidence R P H THOMPSON (The Gastrointestinal objective Van Hees Index (VHI) and the of plasma accumulation after 21 days of Laboratory, The Rayne Institute, St largely subjective Bristol Index (BI) in 93 therapy was found. Thomas' Hospital, London) Constipation patients with active Crohn's Disease, 32 of is a feature of ulcerative proctitis but has whom were also studied after treatment. been studied little. We have measured There was a positive correlation between whole gut transit time in 20 patients with platelet count and disease activity, particu- F88 ulcerative proctitis and in age and sex larly as assessed by the VHI (r=0-48, Mucosal T lymphocytes and HLA-DR matched controls. p400x109/l), 13 (72%) fell to immunoregulatory T lymphocytes are from the stools of the controls after within the normal range. This reduction thought to play a major role in ulcerative colitis although their subset distribu- 50-2±14-6 h and this was delayed in the did not depend on the type of treatment, (UC), patients to 76-1±31-1 h (p<0.01); both steroids or surgery. tion and relationship to MHC antigens has with active disease 70 5±29*9 h (p<0-05) Thus there is a strong correlation be- not been extensively studied. We have and with inactive disease 81-8±35-5 h tween platelet count and Crohn's disease used simultaneous double labelling of cryostat sections of colonsoscopy (p<005). In the patients the nature of the http://gut.bmj.com/ activity, and this simple test may be as biopsies stools was related to the dye disappearance useful as more complex indices in following with monoclonal antibodies in 21 UC time (T=0-46, p<0-05). the progress of individual patients. patients (10 total colitis) and 30 controls T lymphocyte subsets: large individual varia- We conclude that the whole gut transit tions in both groups were observed. In the time is prolonged in ulcerative proctitis and intraepithelial compartment, the T4:T8 this appears to be a primary abnormality as F87 helper/suppressor ratio was 1:1 in UC and it is unrelated to disease activity. This is Effect of polymer coating on faecal controls; in the lamina propria, the ratios due principally to a prolonged colonic

be on September 29, 2021 by guest. Protected copyright. recovery of ingested 5 amino salycyclic were 2-9:1 (UC) and 2-4:1 (controls). A transit time which may important in acid in patients with ulcerative colitis higher percentage of T8+ cells expressed both the pathogenesis and treatment. the T2 ('T-blast') antigen in UC patients. H AL MARDINI, D LINDSAY, C DEIGHTON, AND These differences, however, were not sta- C 0 RECORD (Gastroenterology Unit, Royal tistically significant, and there were no Victoria Infirmary and University of New- changes in the percentage of T8+ cells of F90 castle upon Tyne) It has been suggested either compartment which coexpressed Hypolactasia and Crohn's disease - a that polymer coating might retard jejunal the Ti antigen. Neither treatment, dura- myth absorption of 5 amino salicylic acid (5ASA; tion nor extent of inflammation produced the active moeity of salazopyrin) and thus affected the results. MHC antigens: the R H R PARK, A DUNCAN, AND R I RUSSELL promote delivery to its colonic site of epithelium of control patients was invari- (Gastroenterology Unit, Royal Infirmary, action. Fifteen patients and 8 controls were ably negative for HLA-DR and HLA-DQ. Glasgow) There is growing evidence that given Asacol (Tillots, UK) 400 mg four By contrast, in the majority (60%) of UC Crohn's disease (CD) is a diffuse disease of times/day for one week after which they patients, the epithelium was strongly HLA- the GI tract and in particular the preva- ingested six 1 ml dialysis membrane sachets DR+ and HLA-DQ+, especially in lence of hypolactasia in Crohn's patients which were recovered from the stool in the patients with total colitis (80%), irrespec- with unaffected proximal small bowel has next 48 h. Asacol was continued through- tive of treatment. Class I antigens (HLA- been estimated as being as high as 30%. out the study period. The concentrations of A, B, C) were expressed by enterocytes in We have undertaken jejunal biopsies for 5ASA in the faecal dialysate, urine and UC and control groups. Whereas expression histology and disaccharidase levels in 62 fasting plasma were respectively: 25-4±5-1 of class II antigens by epithelial cells is re- patients with CD, three (5%) oral disease compared to 1-2±0-4 mmol/I (p<0-001); garded as indicative of active cell mediated alone, eight (14%) diffuse small bowel, 16 0-338±0-212 compared to 0-695±0-288 immunity, our data suggest this need not (25%) terminal ileum (TI) alone, 19 (31%) Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from A632 The British Society of Gastroenterology TI and colonic and 16 (25%) colonic alone. dence of PPU in the latter period after gastrointestinal haemorrhage is Only two patients, an Asian female with TI (p<0-001) which was due to a decreased presumed to result from hepatic catabolism and colonic disease and a caucasian woman number of perforations in men. This de- of the absorbed amino acid load. Haemor- with diffuse small bowel disease, had hypo- crease concurs with the findings of other rhage arising distal to the absorptive sur- lactasia. In two other patients the sucrase regions and may reflect a reduction in the face would therefore not be expected to level was slightly below the lower limit of incidence of peptic ulcer in this country. produce uraemia, a distinction of possible normal. Histological abnormalities were significance. Cases of acute GI haemor- present in four patients all of whom had no rhage were reviewed in whom the source of radiological evidence of proximal small F92 bleeding (upper versus lower bowel) was bowel disease and only one had hypolac- not clinically evident but was discovered by tasia. All had increased chronic inflam- Does ulcer position influence presenta- subsequent investigation. The admission matory cellular infiltrate, one had mild tion or prognosis of acute gastrointes- serum urea to creatinine concentration blunting of villi with normal crypts, and tinal bleeding? ratio was calculated in each case. Ninety only one had evidence of granuloma forma- two per cent of upper GI bleeders (35 of tion. C P SWAIN, P R SALMON, AND T C NORTHFIELD 38) had a ratio of over 100, while 95% of The prevalence of hypolactasia in CD is (Norman Tanner Gastroenterology Unit, lower GI bleeders (20 of 21) had a ratio of not increased and routine trials of lactose St James' Hospital and Department of under 100, an overall segregational accu- free diets in Crohn's patients are unnecess- Gastroenterology, University College Hos- racy of 93%. In cases of GI haemorrhage ary and only produce further interference pital, London) We tested the hypothesis where early gastroscopy is non-diagnostic, with patients' diets which may already be that ulcer position influences presentation the admission urea to creatinine ratio will considerably restricted. Jejunal biopsies or risk of recurrent bleeding in patients provide a guide to selecting the most may be useful in detecting microscopic admitted with acute gastrointestinal (GI) appropriate second line investigation and proximal small bowel disease. haemorrhage. Proximity of large vessel to assist in deciding whether a lesion dis- ulcer (left gastric to high lesser curve, covered is relevant or incidental. gastroduodenal artery to postero-inferior duodenum) might influence occurrence or outcome of GI bleeding. Duodenal ulcers were categorised as antero-superior (AS) F94 or postero-inferior (PI), gastric ulcers as GASTRODUODENAL prepyloric (P) (<5 cm from pylorus), mid- Should all patients with gastrointes- F91-102 gastric (M), or high (H) (<10 cm from the tinal haemorrhage be transfused? cardio-oesophageal junction). Ulcer

F91 position and presence of visible vessel as a S D BLAIR, S B JANVRIN, AND R M http://gut.bmj.com/ Trends in perforated ulcer in Belfast predictor of rebleeding were categorised in GREENHALGH (INTRODUCED BY R A PARKIN) 1967-1983 320 patients found to have an ulcer after GI (Departments of Surgery and Gastro- bleeding and compared with ulcer position enterology, Charing Cross and Westminster J S A COLLINS, J A MCKNIGHT, P C PYPER, AND in 320 dyspeptic controls without GI bleed- Medical School, London) It has been A H G LOVE (Departments of Medicine and ing. There were no significant differences suggested that mortality due to upper Surgery, The Queen's University of Belfjast, in ulcer position at presentation with GI gastrointestinal haemorrhage may be re- Belfast, N Ireland) Recent epidemi- bleeding compared with dyspepsia. Inci- duced by restricting blood transfusion. We ological studies of defined populations in dence of rebleeding, however, was related have assessed whether this is due to an on September 29, 2021 by guest. Protected copyright. England and Scotland have shown a de- to ulcer position in 98 patients found to anticoagulant effect in a prospective rando- cline in the incidence of perforated peptic have visible vessels (8/23 AS, 21/27 PI, 2/13 mised trial. ulcer (PPU) but no comparable study has P, 9/13 M, 17/22 H): postero-inferior Thirty four patients with severe, acute been reported in Ireland. A review of the duodenal ulcers rebled more commonly gastrointestinal haemorrhage were rando- case records of all PPU cases presenting to than anterosuperior ulcers (21/27 vs 8/23, mised to receive either at least 2 units of five main Belfast hospitals, between the p<001) and high gastric ulcers rebled blood during the first 24 hours of admis- years 1976-83, was undertaken and the more than prepyloric ulcers (17/22 vs 2/13, sion, or no blood unless their haemaglobin results were compared with a previous p<0-01). We conclude that ulcer position was less than 8 g/dl or they were shocked. study carried out in the city between does not influence initial presentation but Minor bleeds and varices were excluded. 1967-74. A total of 389 cases with a male to does influence the risk of further bleeding. As hypercoagulation cannot be measured female ratio of 2-2:1 was recorded from using conventional coagulation tests, fresh 1976-83. Perforation site was duodenal in whole blood coagulation was measured by the Biobridge Impedance Clotting Time 350 (90%0), gastric in 36 (8XO) and not F93 recorded in the remainder. In 352 (90%O) a (ICT). Coagulation was assessed at 24 hour detailed clinical history was available and Value of simple biochemical indices in intervals and compared with age matched recorded dyspepsia of longer than three distinguishing upper and lower sites of controls with the results expressed as months duration in 192 (54°O) before gastrointestinal haemorrhage mean ±sem. perforation. Only 36 (10%) had previously The ICT on admission for the transfu- received H2 antagonist therapy. Compari- J A SNOOK, G E HOLDSTOCK, AND J BAMFORTH sion group (n=16) was 3-2 minutes+0 2 son between the 1976-83 and 1967-74 (Southampton General Hospital, Tremona compared to 10 minutes±0-2 in controls. studies showed a significantly reduced inci- Road, Shirley, Southampton) Uraemia This hypercoagulable state was partially Gut: first published as 10.1136/gut.27.5.A592 on 1 May 1986. Downloaded from The British Society of Gastroenterology A633 reversed to 6-4 minutes±03 at 24 hours F96 large field of view gamma camera. The (p<0001). Four rebled and one died. The Angelchik prosthesis - a national small bowel region was defined and counts 18 allocated to receive no blood had a survey within this region computed, correcting for similar ICT on admission of 4-4 scattered gastric activity. Mean emptying of radiolabel into the small bowel during minutes±0-4 and the hypercoagulable state D L MORRIS, AND J D HARDCASTLE (Depart- was maintained with ICT at 24 hours of 4-3 ment ofSurgery, University ofNottingham, feeding was: controls 4-2% (mean:range minutes±0-4. Three of these patients went Nottingham) The Angelchik prosthesis is 03-6 8%). DU 15.8%:(5-6-37-0%), onto transfusion, and one patient not very effective in preventing gastro- TV+D 39-7% (9.2-74.3%). Differences transfused rebled. oesophageal reflux. Several serious com- between groups were significant, (p<0O001 These findings show there is a hyper- plications have been described. Published analysis of variance). Small bowel filling coagulable response to haemorrhage which long term follow up studies are few and curves over 30 minutes were linear for is partially reversed by blood transfusion relate to small numbers of patients. It is controls but showed an early rapid phase and may lead to rebleeding. therefore difficult to assess the incidence of for the DU group. Conventional assess- complications. We circulated all UK ment of postprandial gastric emptying surgeons via a commercial mailing house failed to show this difference. For patients with a simple questionnaire. Five hundred with TV+D, failure to account for gastric surgeons replied, 120 had used the pros- emptying occuring during test meal inges- thesis and implanted a total of 810 devices, tion will result in gross errors of assess- F95 84 of the surgeons had used five or less and ment. Variations in tissue enzyme levels in only 12 had used 20 or more. Forty one of relation to gastric cancer the surgeons had seen significant compli- cations including severe dysphagia in 56 patients (6-9%) and erosion into the gut in P FINCH, K ROGERS, AND G T WILLIAMS six patients. Forty eight prostheses have (Northern General Hospital, Sheffield. been removed to date (6%), mainly for F98 Welsh National School of Medicine, Cardifj) dysphagia migration (five), disruption Raised levels of LDH and beta- (25), Factors influencing the risk of develop- (three) and sepsis (two). The removal rate ing gastric cancer after gastric surgery glucuronidase (bGLU) have been found in in patients treated by the 12 surgeons who gastric juice of patients with gastric cancer, had done 20 or more procedures (6-2%) but also of some without neoplasia. The was no different from the remaining group C P J CAYGILL, M J HILL, J S KIRKHAM, AND T C latter may be at increased risk of develop- NORTHFIELD (PHLS-CDSC, Colindale ing gastric cancer. We have correlated (5.6%). Avenue, London, Bacterial Metabolism Re- This national survey has recorded the search http://gut.bmj.com/ enzyme levels in resected stomach speci- results of 120 surgeons who have implanted Laboratory, PHLS-CAMR, Porton mens with histology. Down and Norman Tanner Gastroenter- Ten mucosal samples from each of 13 810 Angelchik prostheses, a significant ology Unit, St James Hospital, London) incidence of serious complications have For many years there has been controversy gastric resections were divided. One half been seen, requiring removal of the pros- was fixed, sectioned and stained with thesis in 6%. concerning the increased risk of gastric H&E, and HID/Alcian blue for histologi- cancer (GC) after surgery for ulcers. cal diagnosis and ranking of inflammatory Analysis ('years at risk' calculation in five infiltrate and intestinal metaplasia (IM). year bands) of 4466 ulcer patients 20+ The other half was homogenised and analy- years after surgery showed no increase in on September 29, 2021 by guest. Protected copyright. sed for bGLU, LDH and mLDH subunit. F97 GC mortality within the first 20 years Levels of bGLU and LDH were signifi- Early small bowel flling in patients followed by a 4 5 fold (p<0-001) increase cantly raised in the carcinoma group with duodenal ulcer and after vago- thereafter. When analysed separately, duo- (psecretions either group. The mean hourly pepsin (PDR) or both together (CR). These were F101 compared with control animals with no concentration was higher in both groups at http://gut.bmj.com/ night than during the day in each study. Intragastric concentrations of ascorbic reflux. After nine months the animals were The changes in pepsin concentration were acid: relationship to plasma levels and killed and the stomachs examined histologi- not wholly volume dependent. These gastric pH cally. The incidence of adenocarcinoma in observations suggest the importance of the CR and PDR was significantly higher further study on central control of secre- H J O'CONNOR, C J SCHORAH, A T R AXON, AND than controls (X2=4-84 p<0 05 and tion and the appropriate target period for R COCKEL (Department of Gastroenter- x2=7 79 p<0-01 respectively). In addition ulcer therapy in night workers. ology, Selly Oak Hospital, Birmingham, significantly more adenocarcinomas were Gastroenterology Unit and Department of found in the PDR group when compared Chemical Pathology, General Infirmary at with BR (X2=5 95 p<0.02). Although the on September 29, 2021 by guest. Protected copyright. Leeds, Leeds) Ascorbic acid (AA) in- premalignant changes only occurred in the F100 hibits the formation of N-nitroso com- two groups in which adenocarcinomas de- Correlation between endoscopic and pounds by scavenging nitrite and thus may veloped (PDR and CR), three was no histological diagnosis of duodenitis and be of value in the possible chemopreven- significant difference when compared with antral gastritis tion of gastric cancer. In this study, fasting the two groups without adenocarcinomas AA in gastric aspirate and plasma and pH (controls and BR), with the exception of BELINDA J JOHNSTON, P I REED, AND M H were measured in 69 patients undergoing adenocystic proliferation which occurred ALI (Departments of Gastroenterology endoscopy. There was significant correla- more frequently in the CR group than BR and Histopathology, Wexham Park Hos- tion between aspirate and plasma levels and controls (X2=6-3 p<002 and X2=8 1 pital, Slough, Berks) Duodenal inflam- (p<0-01). Intragastric and plasma AA p<0-01 respectively). These findings sug- mation is easily recognised at endoscopy, levels (mean±SD, mg/dl) were signifi- gest that duodenogastric reflux plays an but this is not necessarily true for the cantly lower in hypochlorhydric patients important role in rat gastric carcinogenesis stomach. The correlation between endo- (pH >4; n= 19) compared with those and that pancreaticoduodenal secretions scopic and histological diagnosis of gastro- pH<4 (n=50); gastric aspirate, 0-38±0-21 not bile are responsible. This may help duodenitis was therefore studied in 143 vs 0-87±0-83 (p<0.01):plasma, 0-43±0-28 explain the phenomenon of operation patients, 212 paired antral and duodenal vs 0-79±0-54 (p<0-02). Intragastric levels sequeal gastric carcinoma in man.