Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

Gut, 1989, 30, A704-A752

British Society of Gastroenterology

The 1989 Spring Meeting of the British Society of Gastroenterology was held from 12-14 April, at the University of Bradford under the Presidency of Dr J H Baron. Below are printed the abstracts of the 209 communications selected by the Programme Committee for presentation at the meeting.

Cardiorespiratory changes during upper GI under conditions relevant to endoscopy. I-N [)OSCOPY endoscopy The following inocula were prepared in triplicate: (1) Cell free HIV in 10% serum at Comparison of GP and clinic referrals for A W MURRAY, J R ANDERSON, ANt) G N C KENNY 1(0 TCID (TCID=reciprocal of highest upper GI endoscopy (University Departments ofAnaesthlesia and virus dilution infecting tissue cultures in Surgery, Glasgow Royal Infirmary, 8-16 seven days); (2) 1(0 HIV-infected T- S R BROWN, D D KERRIGAN, AND G H HUICHIN- Alexandra Parade, Glasgow) A study was lymphocytes in 1(0% serum; (3) Cell free SON (Royal Hallamshire Hospital Sheffield performed to assess cardiorespiratory HIV (l10 TCID) in neat serum. Inocula and Halton District General Hospital, changes induced by sedation and endoscopy were dried onto sterile coverslips at 20(C Runcorn) Open-access endoscopy offers to identify periods of high risk and evaluate then immersed in 1% or 2% alkaline patients the opportunity of rapid diagnosis suitable monitoring for endoscopy. Twenty glutaraldehyde (AG; Cidex, Surgikos Ltd). and treatment. Many endoscopists are, patients undergoing prolonged endoscopic At intervals from 30 seconds to 15 minutes however, reticent about providing an open- procedures requiring heavy sedation were disinfectant was rinsed off with buffered access service, fearing an unacceptable studied. Continuous recordings of ECG, saline. Cell free inocula, but not cell associ- increase in the number of unnecessary, pulse and arterial oxygen saturation were ated, were then ultrasonicated in culture normal examinations. We report a retro- performed and arterial blood pressures medium to loosen remaining virus. spective study of 1545 patients referred to were recorded at one minute intervals. The Lymphocytes were added and cultures one DGH consultant for their first endo- study commenced immediately before examined to cytopathic effect and antigen scopy. Open-access (OA) referrals (1091) administration of sedatives, continued for expression for 21 days. Disinfectant free were accepted solely on the GP's clinical the duration of the examination and for one and toxicity controls were performed. In http://gut.bmj.com/ diagnosis. Endoscopic findings in these hour after the examination. Oxygen satura- 10% serum, cell free and cell associated patients were compared with those found in tion fell in all patients during the examina- HIV were inactivated in one and two 454 patients referred via hospital colleagues tion (min 82%, SEM 2.72). remained so for minutes respectively by both dilutions of and the outpatient clinic. the duration of the examination and per- AG. 2% AG inactivated virus in neat serum Normal examinations were found in 34% sisted into the recovery period. At the end at a similar rate. One per cent AG, how- of OA referrals and in 31% of patients of the study, 11 patients had not returned to ever, failed to inactivate virus in neat serum referred *ia the clinic. Endoscopic evidence baseline saturation. Of 20 patients, 16 within the 15 minutes tested. Protein is a

of gastro-oesophageal reflux (oesophagitis, developed tachycardia during the examina- physical and chemical barrier to AG. Use on September 24, 2021 by guest. Protected copyright. benign ulceration and strictures) was tion. Ten patients developed ectopic foci for 14 days in endoscopy units can reduce equally prevalent in OA and clinic patients which were both supra-ventricular and 2% AG to almost 1% which protein then (23% and 24%, X'2=018, p=NS), as was ventricular in origin. ECG changes resolved renders much less effective against HIV. peptic ulcer disease (19% and 16.5%, X= during the recovery period. Significant Protein must be removed by cleaning before 1-58, p=NS). Open-access referrals had a increases and decreases in systolic blood disinfection. preponderance of patients with duodenitis pressure and rate pressure product were as the sole diagnosis (8% v 2%, X'= 194, seen during the examination when com- p<0.001), although the reverse was true for pared with baseline levels. Significant Prediction of rebleeding in peptic ulcers by gastritis (7% v 12o5%, X'= 10-82, p=0-.001). correlation was found between S-T seg- visual stigmata and endoscopic Doppler Upper G6 malignancy was more common in ment depression and hypoxia (r=0 941, ultrasound those patients referred through the clinic p

The British So(iety ofGastroenterology A705S

Rebleeding was decided independently. Of entered metaphase), killed two hours later generated in the gastric corpus and antral 711 patients endoscoped for upper G6 and the gastrointestinal tract removed, glands, duodenal, ileal and colonic crypts at haemorrhage over an 18 month period 180 weighed and fixed. Samples of small a rate of 22() (0.8), 3.2 (0.9), 25 (4). 18 (5). (25%) were found to have a peptic ulcer. intestine and colon were later micro- and 12 (4) per hour (means (SD)). Our data One hundred and twenty four had either dissected to determine the mean number of cast doubt on the reliability and repro- minor or no SRH at time of endoscopy and metaphases per crypt. No significant effect ducibility of the in lvitro 3H-TdR method for none of these patients rebled. Fifty six on intestinal tissue mass or the two hour assessing DNA synthesis, particularly in the patients had a single peptic ulcer with either collection of metaphases was observed. It is case of the ileum, where the variability was active haemorrhage, a visible vessel or consequently concluded that PYY is not particularly marked. In viv'o 3H-TdR adherent clot and 22 were entered into the trophic to the gastrointestinal tract. studies, however, give a reproducible trial. Overall nine patients (41%0) in this pattern of DNA synthetic rates. Thus, for a group rebled. Rebleeding occurred in 300 g rat given 40 fiCi of 3H-TdR (sp activity seven of eight (87%o) patients who were Oestradiol has a trophic effect on gastro- 27 Ci/mmol) intravenously, DNA labelling Doppler positive compared with two of 14 intestinal cell lines which is not blocked by in the gastric corpus. antrum. duodenum, (14%0) Doppler negative cases (p<0-05). tamoxifen ileum and colon was, respectively, 7-4 (2.5). Eight of nine (89o%) patients with visible 10() (1.8), 30(2 (5.0). 34-2 (5.5). and 13 vessels rebled compared with one of 13 J D HARRISON, S WATSON, AN!D 1) 1 MORRIS (2.5) dpm/4g DNA (means (SD)). The (8%0) with other SRH (p<0.0)2). These (Department of Surgery, Queen's Medical stathmokinctic technique is the method of results suggest that the TVD can predict Centre, Nottinghiam) Tamoxifen has a choice in the study of gut proliferation. but rebleeding in peptic ulcers with a similar negative effect on survival in patients with it is time consuming. requiring tissue micro- accuracy to the endoscopic identification of oestrogen receptor (ER) positive gastric dissection, staining and metaphase count- a visible vessel. carcinoma. In an in ivitro study we have ing. In viv'o 3H-TdR labelling of DNA is a measured the effect of serial dilutions of useful alternative, offering reliable and oestradiol alone and oestradiol+tamoxifen reproducible results where the experiment on 75Se Selenomethionine incorporation in does not alter mucosal lymphocyte density. the growth of two human gastric and five BASIC SCIEINCE- colorectal cell lines. A consistent significant (>2 SD's) stimulation of the two gastric Peptide YY in rats after urogastrone-EGF (both 24% greater than control) and two Developmental changes in enterocyte iron administration. A proliferative role for PYY colorectal cell lines (200% and 34% greater binding proteins in the guinea pig in the intestinal epithelium? than control) occurred at physiological con- centrations of oestradiol (nanomolar). The S K S SRAI, G CHOWRIMOOT00, I. DBENAM, ANI) http://gut.bmj.com/ R A GOODLAD. M A GHATEI. J DOMIN, S R addition of 4-hydroxytamoxifen (I fig/ml) O EPSTIEIN (Academic Department of Bl-OOM, H GR-EGORY, AND N A WRIGHI to the same dilutions of oestradiol resulted Medicine, Royal Free Hospital, London and (Imperial Cancer Researcht Fund, Histo- in greater stimulation (of up to 60)% greater Depalrtment of Plyysiology, Royal Free pathology Unit, 35-43 Lincoln's Inn Fields, than control) of the gastric cell lines, and no Hospital, London) Like the human London, Department of Medicine, Royal diminution in the stimulation caused by newborn, neonatal guinea pigs absorb con- Postgraduate Medical School, Ducane oestradiol in the colorectal lines. We con- siderably more iron than adults. Factors Road, London, and ICI, Alderley Park, clude that oestradiol stimulates gastric and controlling the switch from the positive iron Macclesfield) Urogastrone-epidermal colorectal cell lines, and this effect is syner- balance of the neonate to the normal on September 24, 2021 by guest. Protected copyright. growth factor (URO-EGF), completely gised rather than inhibited by tamoxifen. balance of the adult are unknown. Prelimi- reverses the marked hypoplasia seen in the These findings help to explain the negative nary studies indicate a fundamental differ- intestine of intravenously fed (TPN) rats. effect on survival found in tamoxifen ence in the iron binding proteins of neonatal Although plasma enteroglucagon and treated ER positive patients. and suggest an and adult enterocytes. We have followed gastrin concentrations increased slightly alternative hormonal approach to the the developmental pattern of enterocytc after URO-EGF, the response was far less therapy of gastric carcinoma. iron binding proteins from the day of birth than the change in tissue mass, thus it is to adulthood. Duodenal loops were per- unlikely that they were involved in modulat- fused in situ with `Fe-ascorbate followed by ing the proliferative response of the Comparison of three methods for assessing isolation of enterocytes. The soluble super- intestine to URO-EGF. Peptide tyrosine gastrointestinal epithelial proliferation natant from enterocytes was subjected to tyrosine (PYY) concentrations were, how- gel-filtration on Sepharose-61B. Radioactive ever, very highly significantly increased S LEVI AND H J F HODGSON (Department of iron resolved into four distinct peaks (1, 11, by 60 p.glrat/day of URO-EGF, suggesting Medicine, Royal Postgraduate Medical Ill, and IV). In the first 21 days after birth that PYY may have a role in modulating School, Hammersmitil Hospital, Ducane peak IV (MW 12O)(K) was the major peak intestinal cell proliferation. This was investi- Road, London) We have studied and com- (7(-80o% of cluted counts), whereas peak I gated in a further study in which groups of pared the merits and drawbacks of three (MW 450()(X)) accounted for 5-15%, the six intravenously maintained rats were in- methods for the rapid assessment of rat remainder cluting with peaks 11 and 111. By fused with 0, 5, 20), or 80 fIg/rat/day of PYY gastrointestinal epithelial cell turnover: the day 28, however, the profile was similar to for three days, giving mean plasma levels assessment of S-phase DNA synthesis by in the adult with 45-55S% of radioactivity of 39.3+7.4, 349-0+34-6, 715.5+ 108-2, vitro and in i'i'o 3H-thymidine (3H-TdR) cluting with peak 1. Immunoprecipitation and 3803-8±321. 1 pmol/l per group respect- incorporation, and the vincristine induced with antiferritin revealed that the radio- ively. The rats were then injected with 1 mg/ mitotic arrest (stathmokinctic) method. activity in peak I was associated with kg of vincristinc (to arrest cells as they Using the latter method, new cells are ferritin. This study suggests that ferritin is Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A706 The British Society ofGastroenterology present in low amounts in neonatal entero- examine the effects of enkephalins on glucagon,3x10 'M,for2,5,orl10min.The cytes, but that it becomes the major iron colonic tissue obtained from patients suffer- tissue cAMP was extracted, dried, acety- binding protein between three and four ing from idiopathic chronic constipation lated and assayed by radioimmunoassay, weeks after birth. It is possible that this (ICC), ulcerative colitis (UC), or cancer expressing results as pmol cAMP in l1W cells change is important in establishing control (control). In the circular muscle of the (mean (SEM), n=4) at 2, 5, and 10 min of iron absorption in the adult. sigmoid colon, non-adrenergic, non- respectively. Basal levels were 11 81 (1.69), cholinergic inhibitory junction potentials 8-125 (1.98), and 9-25 (1-05) pmol cAMP/ (lIPs) were evoked by single pulses of I 0h cells. Glucagon stimulated hepatocytes Antigliadin antibodies in the induction of electrical field stimulation of the intramural had markedly raised levels (31 44 (2.59), experimental enteropathy nerves. 35.26 (4-(X)), and 42(X) (1-24) pmol cAMP/ Methione-enkephalin (MENK) and 10h cells); in contrast, hepatotropin caused C J SMART, L K [TREJDOSIEWICZ, AND P D leucine-enkephalin (LENK) reduced the no increase in hepatocyte cAMP levels at HOWDLE (Department of Medicine, St IJP amplitude in a concentration dependent any time point (12.19 (1.29), 9.28 (1.62), James's University Hospital, Leeds) Coeliac manner. Both MENK and LENK, how- and 11-13 (2.15) pmol cAMP/10 cells). patients have raised circulating antigliadin ever, were significantly (p<0(05, Mann- These results suggest that the second mess- antibodies, and there is evidence that anti- Whitney U-tests) less potent in tissues from engers triggered by hepatotropin do not gen antibody complexes may mediate diet ICC-patients than from control or UC- involve cAMP dependent pathways to exert induced enteropathies. We have used a patients. The median pD2 values (negative their effects on the hepatocyte cell cycle. murine model to test the hypothesis that log of half-maximal concentration) for high titres of antigliadin antibodies can MENK, given with the range in paren- mediate enteropathy. We raised a murine theses, were 6-9 (7.1-6.6), 6-8 (7.1-6-5), IgGl monoclonal antibody, which recog- and 6-6 (6.7-5-5) for six control, six UC-, Further characterisation of Na- HCO3 nises all major fractions of wheat gliadin and six ICC-patients, respectively. LENK cotransport in rat hepatocytes: electro- and other prolamins by Western blotting. was inactive up to 1 FM on tissues from two genicity and contribution to baseline intra- The antibody was administered intra- ICC patients and its median pD2 values cellular pH (pH;) venously into gluten free syngeneic mice, were 7-6 (8.5-6 7), 7 6 (7.9-7.4), and 5.3 and mediated an inflammatory (type 111) (7.2->5) for the control, UC- and ICC- D GLEESON (INTRODUCED BY R HOILMES), N I) hypersensitivity response after footpad chal- patients, respectively. For neither LENK SMIIH, AND J L BOYER (Liv,er Centre, Yale lenge with gliadin, but not with ovalbumen nor MENK was there a significant differ- University School of Medicine, New Haven, or saline controls. Peak responses were ence between tissues from control and UC- CT, USA) pH. recovery from an intracellu- observed between four and eight hours, with patients. lar acid load (NH4 pulse) in rat hepatocytes a mean increment of 265 im (±52) for There is a marked decrease in sensitivity is partly mediated by Na'-HCO3 cotran- http://gut.bmj.com/ gliadin, versus control values of 71 sim of colonic opioid receptors in patients with sport. In renal cells this system is electro- (+61) and 40 sim (+52), respectively. This chronic constipation but not ulcerative genic (Na':HCO3 stochiometry 1:3). To antibody did not, however, mediate a colitis. Abnormalities in opioid receptors determine if rat hepatocyte Na'-HCO3 significant enteropathy in animals fed daily may contribute to the motility disturbances cotransport is electrogenic and to assess its with 25 mg unfractionated gliadin. There in chronic constipation. contribution to baseline pH., we used the were no increases in intraepithelial lympho- pH, sensitive dye BCECF and a con- cyte counts, nor were there any significant tinuously perfused subconfluent monolayer

morphological changes. Nevertheless, the cell culture system. on September 24, 2021 by guest. Protected copyright. antigliadin antibody was being removed Hepatotropin exerts its effects on the hepato- Baseline pH, was (mean (SD)) 7 28 (0.09) from the circulation: footpad responses cyte cell cycle via a cAMP independent and 7-16 (0(14) respectively in the presence became negative after four days of gliadin mechanism (+) and absence (-) of HCO3 (p<0)01). feeding in experimental animals, but Blocking Na'/H exchange with amiloride remained positive in controls. These data C SELDFN AND H J F HODGSON (Department of (1 mM) did not affect pH, in +HCO3 but suggest that circulating antibodies capable Medicine, Royal Postgraduate Medical caused reversible 0(1-0.2 unit acidification of mediating inflammatory responses are School, Hammersmith Hospital, Ducane in -HCO3 or in +HCO3 after preincuba- insufficient alone to induce enteropathy in Road, London) Partial hepatectomy tion of cells with the anion transport presence of homologous dietary antigen. induces hepatotropin, a circulating growth inhibitor DIDS (1 mM). Acute Na' removal factor which stimulates hepatocyte DNA in + HCO3 also caused reversible acidifica- synthesis in vitro and enhances the phos- tion which was amiloride independent but Reduced activity of enkephalins in the colon phorylation of a 17kD liver membrane DIDS inhibitable. Acute Cl removal, how- of patients with idiopathic constipation protein. This may be directly by protein ever, had no consistent effect on pH,. kinase C activation or via a cAMP depend- Deplorisation of hepatocytes (raising C H V HOYLE, M KAMM, G BURNSTOCK, J F ent process. This study determined the external K' from 5 mM to 25 mM) caused ILENNARD-JONES (Department of Anatomy effect of hepatotropin on hepatocyte intra- reversible alkalinisation (0.05-0.1 unit), and Developmental Biology, University cellular cAMP, in comparison with which, however, was neither Na' nor HCO3 College London and Department of Gastro- glucagon, a known stimulator of hepatocyte dependent, nor DIDS inhibitable, findings enterology St Marks Hospital, London) cAMP. Cultured rat hepatocytes (10' cells) consistent with electroneutral Na -NCO3 Opioids have been implicated in the dis- were incubated in medium containing iso- cotransport. turbed motility of the gastrointestinal tract butylmethylxanthine, a phosphodiesterase Rat hepatocyte Na'- HCO3 cotransport in patients with severe constipation. A inhibitor. Cells were stimulated with (a) contributes to baseline pH, regulation modified sucrose-gap technique was used to medium, hepatotropin 340 ig/ml or (b) appears to be electroneutral. Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A7()7

sis: 16 steatosis+fibrosis) completed a reaching a peak at eight weeks and becom- LIVER course of three deltoid intramuscular injec- ing normal by eight weeks after therapy. tions of 20 p.g Engerix B given at 0, one. and The HBV-DNA fell to undetectable levels Criteria for HBV screening of women attent- six months. Antibody titres were measured by four weeks after therapy, the HBeAg by ing antenatal clinics by radio-immunoassay (AUSAB) 4-6 one to two months and HBsAg two to three weeks after the 3rd injection. Patients were months later. Treatment was well tolerated. RUIH KING, HEATHER SMITH, YVETTE WHITE, classified as non-responders (50 units). Controlled trial of haem arginate in acute Hill, London) Antenatal clinics have widely hepatic porphyria differing policies on screening for HBV Results Non- Poor (Cood Total infection. At our institution, which serves respx)nders resrx)nders rcsrx)n(trs K E 1 MCCOLL, A HERRICK, A COOK, M R MOORE, an inner city area, women routinely AND A GOLDBERG (Univers-ity D)epartmnent of screened include those from defined areas ( irrhotics 17 7 122 3 Medic.ine, Western Infirmary, Glasgow) We of Asia, Europe and Africa, or with specific Non-cirrhotics 3 4 16 report a double blind study comparing features in their medical or social histories placebo and haem arginate in nine patients suggesting risk of exposure to HBV. To Although non-cirrhotics responded better experiencing recurring attacks of acute

assess the efficacy of this approach during than cirrhotics (median antibody titre 81u v intermittent porphyria. Two days after antenatal care we compared the HBsAg 13u p=-0.05) their response was much admission in attack they were randomised seropositivity rate among 500 women poorer than would be expected in a normal to receive haem arginate 3 mglkg/24 h iv for defined by our current criteria as being 'at population. Women responded better than four days or placebo. On readmission in risk' and a further 500 tested regardless of men irrespective of liver damage and active their next attack they received the alterna- exposure to any risk factors. drinkers responded less well than abstain- tive therapy. Before randomisation the Among the 'at risk' group 18 (3-6%) were ers. Five of 16 non-responders showed a paired attacks were of similar severity with HBsAg seropositive, the highest rate (18%) response to a fourth injection of Engerix B. respect to both urinary porphobilinogen being among women of SE Asian or Far We conclude that in addition to cirrhosis (PBG) excretion and clinical manifesta- Eastern origin who comprised 6% of the alcohol abuse alone is associated with tions. With haem arginate the median PBG group. African women made up over 50% impaired antibody response to HB immuni- excretion (normal range (t-16 Rmol/l) fell of the at risk group and 4% were HBsAg sation. This should be taken into considera- from 332 (range 137-722) on admission to seropositive. Of the four women (0.8%0) in tion when assessing defective response to 40 (range 22-105) on the final day of therapy the second group who were HBsAg positive hepatitis B vaccination. (p<0.0l). With placebo, PBG excretion three were African and the fourth had a was 382 (range 196-542) on admission and http://gut.bmj.com/ history of jaundice. not significantly altered on final day of Our local criteria applied to this popula- Treatment of HBV with alpha interferon therapy. Median duration of admission tion, in which nearly 1% of all women after commencement of therapy was 1 1 days attending antenatal clinics are HBsAg M BROOK, G CHAN, I YAP, P KARAYIANNIS, (range 2-28) for placebo and eight days positive, are clearly effective though it is A M L LEVER, M JACYNA, J MAIN, AND H C (range 3-26) for haem arginate (p=0.4). apparent that the major factor is ethnic HOMAS (Department of Medicine, lOt/ Median total analgesic requirement origin and more selective screening criteria Floor, QEQM Building, St Mary's between commencing therapy and dis- could be defined. Although no Caribbean Hospital, South Wharf Road, London) charge was 8150 mg pethidine equivalents on September 24, 2021 by guest. Protected copyright. women were HBsAg positive in this study we Thirty seven adult caucasian male patients (range (-13225) with placebo versus 6425 have found, on local population screening, with chronic hepatitis B virus infection were (range 50-20650) with haem arginate (p= a positivity rate of around 3%, suggesting treated with 5-10 mega units/m' lympho- (.1). Phlebitis occurred following four that this group should also be screened. blastoid alpha interferon daily for five days courses of haem arginate versus one course then thrice weekly for 11 weeks. Twelve of of placebo. In conclusion, haem arginate these patients cleared HBeAg and HBV- effectively reduces porphyrin precursor Effect of alcohol abuse and alcoholic liver DNA whereas only one of 28 untreated overproduction in the acute porphyric attack damage on the immune response to recom- controls seroconverted over the same time but this is not accompanied by dramatic binant DNA hepatitis B vaccine period (p<0-02). The response rate was resolution of the clinical manifestations of highest in the anti-HIV negative patients the attack. H 1. SMARI, R I VAN-HEGAN, AND D R TRIGER (12/31, 39%, p<0'05), in those showing (Departments of Medicine, Royal Hallam- chronic active hepatitis before treatment s/lire Hospital, Sheffield and PHLS, (12/26, 46%, p<()0(X)5) and in those with a Survey of drug induced liver disease in the Northzern General Hospital, Sheffield) Pre- pretreatment AST >70 IU/I (12/21, 57%. community vious studies have suggested that patients p<0.05). These three pretreatment with alcoholic liver disease respond sub- variables were the only ones to predict I K DANESHMENI), 0 WAIKIER, P J I()lHII I normally to hepatitis B immunisation, but it response, and when combined they pre- AND M J S LANGMAN (Depts of Therapeutics, is unclear whether this poor response is dicted response with a 1())% sensitivity and Medicine and Clinical Chemistry, University caused by alcohol abuse or to liver damage. an 80% specificity. Four (33%0) of the Hospital, Nottinghiam) There are few We offered 60 patients with biopsy proven responders, who had all been infected for community surveys of drug induced liver alcoholic liver damage a standard course of less than two years, also lost HBsAg. disease. We monitored requests for recombinant DNA hepatitis B vaccine Response was characterised by a rise in standard LFTs from general practitioners (Engerix B). Fifty two patients (36 cirrho- AST starting after four weeks of therapy, (GPs) in the Nottingham area. After an Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A708 The British Society ofGastroenterology

interval of about two months, a further copy Four of the patients improved rapidly measurements of superior mesenteric of LFTs with abnormal results was sent to on stopping diclofenac, and were fully artery blood flow (SMABF, pulsed the GP, together with a questionnaire about recovered within three months. One went Doppler, Ultramark 8 ATL), blood the patients' prescribed drug usage and on to develop features suggestive of chronic pressure (BP), and heart rate (HR) diagnosis. In 1987 there were 428 sets of active hepatitis which is steroid responsive. (Sentron). cardiac index (Cl) (continuous results from 392 patients with one or more wave Doppler, Exerdop), and digital skin values outside our normal range. One blood flow (DSBF, laser Doppler, Periflux hundred and eighty eight patients (48%) Beta carotene and vitamin E deficiency in Pf2b), were made before and at 10 min were on no prescribed drug, while 96 (24%) alcoholics: a potential defence against free intervals after the meal. were on one and the rest (28%) took more radicals Basal SMABF was higher and vascular than one drug. The abnormal LFTs were resistance (SMAVR) lower in cirrhotics ascribed to alcohol (131 patients), viral G P BUICHER, JONATHAN M RHODES, N compared to normal subjects (p<0-05). hepatitis (55), malignant disease (48), and KRASNER, R WAIKER, AN[) M J JACKSON After the meal, SMABF rose and SMAVR previously known liver and biliary disease (University Department of Medicine and fell in both groups (p<0-05), the latter to (42). In 116 patients the diagnosis was Walton Hospital, Liverpool University, PO much lower levels in cirrhotics (p<0.05). unclear or a drug was suspected. Of these, Box 147, Liverpool) Free radicals have Resting Cl was higher in cirrhotics 15 had heart failure, 11 possibly had a high been postulated as mediators of alcohol (p<0(05), and rose after the meal in both alcohol intake, two each had Gilbert's induced liver damage, and antioxidants are groups (p<0.05). There were no significant disease, connective tissue disease and thought to represent an important defence differences in mean BP before or after the malaria, and one had haemolytic anaemia. against free radical attack. Evidence for this meal in both groups. Basal HR was higher In 11 patients the abnormal LFTs were includes increased circulating concentra- in cirrhotics (p<0-(5) but rose significantly ascribed to specific drugs. Five other tions of the diene conjugate of linoleic acid after the meal in normals alone (p<0-05). patients were on phenytoin. In 72 (18%) the (DCLA), which we have previously con- Basal DSBF was higher and vascular resist- cause of the abnormality had not been firmed. We have assayed serum concentra- ance (DSVR) lower in cirrhotics compared clarified. Overall, abnormal LFTs from the tions of two efficient antioxidants vitamin E with normal subjects (p<0-05) and were community could be ascribed to drugs in and beta carotene and compared them with unchanged after the meal in both groups. only 16 (4%) patients, half these being due DCLA. Sera were collected from normal Higher basal CI and HR with lower to dose dependent enzyme induction. individuals (n=12) and alcoholics (n=17) SMAVR and DSVR in cirrhotics compared within 24 hours of their last drink and with normal subjects, accompanied by a assayed for DCLA, vitamin E, and beta further rise in Cl and fall in SMAVR after Diclofenac associated hepatitis carotene by HPLC, with measurement of the meal in cirrhotics, may be caused by OD at 234 nm for DCLA, 292 nm for increased levels of vasodilator substances http://gut.bmj.com/ N G RYLEY, T J IVESON, P M A KELLY, J M vitamin E, and 450 nm for beta carotene. resulting from their reduced hepatic TROWELL, J O'D MCGEE, AND R W G CHAPMAN Beta carotene in alcoholics was markedly inactivation. (Dept of Gastroenterology, Nuffield Dept of reduced 7-6 mg/I (9-4) (mean (SD)) com- Pathology and Bacteriology, Nuffield Dept pared with normals 41-8 mg/l (18.0). of Medicine, John Radcliffe Hospital, Vitamin E was also reduced in alcoholics 9-3 Endogenous heparinoid concentrations in Headington, Oxford) Diclofenac is the most mg/I (6-2) compared with normal subjects portal hypertensive patients commonly prescribed non-steroidal anti- 11-8 mg/I (3.9). The molar ratio per cent of inflammatory drug in the United Kingdom. DCLA to linoleic acid was increased in RUFH F MCKEE, O J GARDEN, JOAN DAWES, AND on September 24, 2021 by guest. Protected copyright. Single cases of diclofenac associated alcoholics 3-1 (2.0) compared with normals D C CAR[ER (University Department of hepatitis have been described previously, 1-3 (0-5). There was, however, no correla- Surgery, Royal Infirmary, Glasgow and including three which proved fatal. This tion between concentrations of either MRC/SNBTS Blood Components Assay report describes five cases of hepatitis antioxidant and DCLA in alcoholics. Group, Edinburgh) Bleeding as a complica- associated with diclofenac in one unit over a This study shows that alcoholics have tion of liver disease can occur in the absence 12 month period, suggesting that hepatitis markedly reduced serum concentrations of of recognised haemostatic defects. It has may be commoner than hitherto supposed. important antioxidants, particularly beta recently become possible to measure the The average age of the patients was 63 carotene, which might contribute to free concentrations of endogenous heparinoid (four women, one man). The presentation radical mediated damage. substances in the blood, using a competitive was that of an acute hepatitis, three with binding assay. We have assayed one such jaundice, the others with more non-specific Postprandial changes in superior mesen- substance, heparin sulphate (normal range symptoms. All were on diclofenac at teric artery blood flow in normal subjects <600 ng/ml), in the plasma of 49 patients presentation, four of the five having started and in patients with alcoholic liver cirrhosis with portal hypertension admitted because the drug within the previous three months. of oesophageal varices. In 27 patients who Liver function tests were grossly abnormal J S KOONER, M R JACYNA, C I MATHIAS, AND H C had had an upper gastrointestinal bleed in all cases. There was no history of foreign THOMAS (Department of Medicine, 10/th within the previous 28 days the median travel or blood transfusion, there were no Floor QEQM Wing, St Mary's Hospital and plasma heparin sulphate was 17()( ng/ml (IQ stigmata of chronic liver disease, viral Medical School, Norfolk Place, London) range 900-3900) compared with 390 ng/ml markers were absent, and liver ultrasound We investigated the haemodynamic (IQ range 256-800) in 22 patients who had was normal. A liver biopsy was performed rcsponses to a liquid meal (66 g carbohy- had no recent bleed (p<0-01). in four cases. The pathology was that of an drate, 22 g fat, 18 g protein) after a 12 h fast As heparin sulphate is metabolised by acute hepatitis, in which cell damage and in 11 normal subjects and in six patients with the same route as exogenous heparin we inflammation dominated. alcoholic liver cirrhosis. Non-invasive tried to establish a cause of the raised Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A709' heparin sulphate concentrations by efficacy in controlling acute variceal bleed- reperfusion) where minor changes in ICP measuring the clearance of exogenous ing. profoundly affect cerebral perfusion. In heparin in 10 portal hypertensive patients in addition, the time taken for reversal of the comparison with 10 controls. The median cerebral defect after implantation of a half-life of heparin in plasma in the portal Cholangiography and interventional biliary functioning graft is now known. hypertensive patients (25-5 min; IQ range procedures after orthotopic liver trans- We have studied six patients transplanted 22-34) was significantly longer (p<0.007) plantation for FHF (aetiology non-A, non-B 5, than the median half-life in the controls hepatitis A 1) who had extradural monitors (18.7 min; IQ range 17-21-5). R A EVANS, N D RABY, J B KARANI, J G O GRADY, inserted pre-operatively and had experi- Thus there is evidence of raised levels of R Y CALNE, AND R WILLIAMS (Department of enced episodes of raised ICP. The ICP endogenous heparin-like substances in Radiology and The Liver Unit, King'.s tended to be lowest in the anhepatic phase portal hypertensive patients after gastro- College Hospital, Denmark Hill, London) and highest after reperfusion. The cerebral intestinal bleeding. These high concentra- Biliary tract reconstruction is responsible perfusion pressure was low throughout but tions may be because of reduced hepatic for most technical complications after liver improved at the time of graft reperfusion. In clearance. transplantation. The gall bladder conduit the first 12 hours postoperatively, three anastomosis has been the most frequently patients had severe episodes of raised ICP used technique in the Cambridge/King's that required further treatment with hyper- College Hospital programme since 1976. osmolar mannitol. We conclude that ICP Effects of vasoactive drugs on the collateral Experience outside the United Kingdom is monitoring in patients transplanted for FHF circulation of rats with portal hypertension largely with the end to end bile duct anasto- is essential and should continue for at least mosis. Cholangiographic procedures per- 12 hours postoperatively.

J YATES, D M NOII, S ELLlENBOGEN, I COOKE, formed over a three year period were

R SHIELDS, AND S A JENKINS (Univ'ersNity reviewed retrospectively. These involved 76 Department of Surgery, Royal Liverpool liver transplant recipients (79 transplants). Hospital, Liverpool) It is generally assumed Cholangiograms were abnormal in 63 GASTIROI)UOI)ENAI that control of variceal bleeding by vasoac- (80%) of transplants with biliary strictures, tive drugs results from a reduction in inspissated bile formation, bile leak and T- Clinical diagnosis in dyspepsia: a valueless collateral blood flow secondary to tube malposition occurring in 50, 23, 14, exercise splanchnic vasoconstriction and a reduction and three transplants respectively. Most in portal pressure, a hypothesis which has anastomotic strictures occurred at the M I HAI.LISSEY, A J JEWKES, W H Al.lIUM, D J never been validated directly. The aim of proximal anastomosis (24/32) and inspis- ELLIS, AND J W L FIEI,DING (Department http://gut.bmj.com/ this study was to investigate the effects of sated bile and the T-tube in relation to these of Surgery, Queen Elizabeth Hospital, vasoactive drugs on collateral blood flow contributed towards subsequent biliary Birmingham) Classical symptom patterns and portal pressure simultaneously in rats obstruction. Non-anastomotic strictures have long been used to select dyspeptic with portal hypertension. were associated with a high position of the patients for treatment and further investiga- Rats with portal hypertension (partial T-tube tip near the liver hilum. The aetio- tion. Rational therapy is only possible, portal vein ligation) received bolus iv doses logy of strictures is probably ischaemia. Bile however, with an accurate diagnosis and, of 2 Ftg somatostatin (SRIF), 2 [ig SMS leaks were observed less frequently than in therefore, the value of clinical diagnosis was 201-995, 0-4 IU vasopressin or the same published series using the end to end tested in a group of unselected patients with volume of isotonic saline over 30 sec. anastomosis. Saline irrigation of the bile upper abdominal symptoms. on September 24, 2021 by guest. Protected copyright. Arterial blood pressure, portal pressure ducts for inspissated bile or its removal via Six hundred and thirty four consecutive (PP) were recorded continuously whilst the endoscopy were effective measures but dyspeptic patients, over 40, underwent collateral blood flow was measured before percutaneous balloon dilatation and endo- endoscopy regardless of clinical diagnosis. (consecutive intrasplenic injection of a non- scopic stent insertion for biliary strictures Both GP and the hospital practitioner (HP) diffusable marker, 'Tc methylene diphos- were found to have a limited role. recorded their clinical diagnoses, before phonate and 'Tc albumin microspheres) investigation and these were compared with and after the administration of drugs or the final diagnosis. Overall diagnostic saline. Vasopressin elicited the greatest Intracranial pressure (ICP) changes accuracy was only 23.8% for GPs and reduction in portal pressure (13.00 (0(71) to before, during and after liver transplanta- 36.9o% for HPs. Peptic ulcers were correctly 6-88 (0.75) mmHg; p<0O001 Student's tion for fulminant hepatic failure predicted in 57.0o% of cases by HPs; the site paired t test) but had no significant effect on of ulcer being correct in only 128X% of GUs collateral blood flow. Both SRIF and SMS R KEAYS, D POlTER, 'I' PEACHHEY, G Al EXANDER, and 44.9% of DUs. GPs correctly diag- 201-995 also significantly reduced portal J G O'GRADY, AND ROGER WILLIAMS (Liver nosed only 44 8% of ulcers. Hiatus hernia pressure but to a lesser degree than vaso- Unit and Dept of Anaesthetics, King's was correctly predicted in 39.8% of cases by pressin. Both SRIF and SMS 201-995, how- College Hospital, Denmark Hill, London) HPs and 35.9o% by GPs. For gastric cancer, ever, significantly reduced collateral blood Signs of raised intracranial pressure (ICP) only advanced lesions were diagnosed flow (SRIF 26-83 (4.42) to 11-33 (1.79)%; occur in 81% of patients with fulminant clinically, the accuracy being 26.7% for HPs SMS 201-995 36-25 (6.93) to 20-88 (6.4)%, hepatic failure (FHF) progressing to grade 4 and 13.3% for GPs. p<0-OOl). These results indicate that SRIF coma and it is usual at that stage that liver Clinical impression is unreliable and and SMS 201-995 although having a less transplantation is performed, if indicated. cannot distinguish curable gastric cancer marked effect on portal pressure, produce a The problem of cerebral oedema is compli- from benign disease. If patients are to much greater effect on collateral blood cated by hypotension in each phase of the receive appropriate treatment and poten- which may partly explain their greater operation (dissection, anhepatic, and graft tially curable disease is not to be missed, all Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A710 The British Societv ofGasstroenterology patients over 40, presenting with dyspepsia biopsied? To assess this we studied the relapse, if blood bismuth rose above 1(X) require endoscopy. sensitivity and specificity of endoscopic tg/l, or if side effects developed. examination compared with histology, CBS was superior to placebo in the pre- microscopic evidence of C pylori, CP- vention of ulcer relapse (p<0-05, log-rank Twenty four hour ambulatory study com- TEST, culture and serum IgG and IgA test). The cumulative relapse rates at six paring gastric antral and body pH antibody titres to C pylori in order to and 12 months were 57% and 62% respect- determine if endoscopy and antral biopsies ively for placebo patients, and 29% on both K E L MCCOLL, G MCLAUCHLAN, G M FULLAR- really are useful. One hundred and seven occasions for those receiving CBS. No CBS TON, AND G P CREAN (University Depts of consecutive dyspeptic patients (mean age 43 treated patient had to be withdrawn Medicine, Western Infirmary and Gastro- years) were entered. Four antral biopsies because of rising blood bismuth levels or the intestinal Centre, Southern General were taken routinely for evaluation by development of side effects. Hospital, Glasgow) In spite of the increas- histology, microscopy, CP-TEST, and CBS is a safe and effective maintenance ing use of intragastric pH monitoring, the culture. Serum IgG and IgA antibody treatment for patients with duodenal ulcer importance of the intragastric positioning of concentrations were measured in all disease. the electrode is unclear. To investigate this, patients. Of symptoms, postprandial bloat- simultaneous ambulatory records of gastric ing was statistically more common in C antral and body pH were made over 24 pylori positive than in negative patients. Comparison of the yield of early gastric hours in nine healthy volunteers by means Endoscopy had the poorest sensitivity cancer from a population based screening of endoscopically positioned and anchored (37.1%) and specificity (53.3%) followed programme for gastric cancer with open glass electrodes. Intragastric pH was by the serum IgA titre (sensitivity 56% and access gastroscopy temporarily raised after the endoscopy with specificity 78%0), by culture (sensitivity the median pH value 30 minutes after the 82% and specificity 100%), by the serum J D HARRISON AND D L MORRIS (Department of procedure being 3-9 (range 1-5-7.0) for the IgG titre (sensitivity 90% and specificity Surgery, Queen's Medical Centre, Notting- antrum and 4-1 (range 1-5-7.0) for the 96%), and by the CP-TEST (sensitivity ham) The aim of this study was to evaluate body. Daytime pH (median pH value 94% and specificity 100%). Patients with the yield of gastric carcinoma using a postal between 12 00 h and 23 00 h) was lower in normal endoscopic appearances but histo- dyspepsia questionnaire compared with the antrum (median=1.9, range 1.6-2.6) logically confirmed gastritis had signific- that from a group of open access endoscopy than in the body (median=2-7, range 1-8- antly higher IgG and IgA titres than the patients. The questionnaire was sent to 3186 4.5) (p<0-05) and this was due to the rise in patients normal by both endoscopy and subjects aged 50-75, of whom 2694 (85%) pH on eating being less marked in the histology and without evidence of C pylori. replied. Of those who replied 27% were antrum than in the body. The median peak This study has shown that endoscopy is positive for symptoms of dyspepsia. To date pH recorded during the evening meal was unhelpful in dyspeptic patients if endo- we have gastroscoped 320 patients from this http://gut.bmj.com/ 4-1 (range 2-4-6.2) in the antrum compared scopic biopsies are not routinely taken. group. Three hundred and thirty patients with 6-3 (range 4-4-6.7) in the body from an open access gastroscopy service (p<0-01). Preprandial pH (median value serving three group practices were gastro- over the hour before the evening meal) was scoped over the same period. Three similar in the antrum (median=1.9, range Safety and efficacy of colloidal bismuth sub- carcinomas were diagnosed in the question- 1-2-2.5) and body (median= 1.9, range 1-3- citrate maintenance therapy in patients with naire screened group. two of which were 2-8). Night-time pH (median value between duodenal ulceration early cancers with disease limited to the 23 00 h and 05 00 h) in six subjects remained submucosa. By comparison six carcinomas on September 24, 2021 by guest. Protected copyright. low and was similar in the antrum (median= A A DUNK, U H PRAHBU, AND N A G MOWAI were diagnosed in the open access gastro- 1-4, range 1.2-1.7) and body (median= 1-3, (Department of Medicine, Royal Infirmary, scopy group, all of which were advanced range 11-1.7). In two subjects, however, Aberdeen) Patients whose duodenal ulcers lesions. In addition, four patients (1%) had there were episodes of raised night-time pH heal with H2-receptor antagonists (H2- dyspepsia, five (1.6%) had intestinal meta- which were more marked in the antrum RAs) or De-Nol (colloidal bismuth sub- plasia (IM) in the questionnaire group. In than in the body. In conclusion the position- citrate, CBS) often relapse when therapy is the open access group 10 (3%) had dys- ing of in situ electrodes is important in stopped. This problem, which may be less plasia and 24 (7.3%) had IM. These data studies of intragastric pH. common with CBS than with H2-RAs, has suggest that questionnaire screening may be led to the development of longterm main- a viable method for the early detection of tenance treatment regimes. Fear of bismuth gastric carcinoma, and that this method Is endoscopy without biopsies worthless toxicity, however, has so far precluded the probably has a higher rate of detection of when gastritis is considered? investigation of CBS as a maintenance EGC than open access gastroscopy. agent. In this study 60 patients with duo- D VAIRA, J HOILTON, J OSBORN, J DOWSETr, N I denal ulcers were given De-Nol 2 tabs bd MCNEIL, S WILLIAMS, A R W HATFIELD, AND P R (CBS 480 mg) for four weeks. Healing Gastroduodenal adenomas in polyposis - is SALMON (Departments of Gastroenterology occurred in 42 (70%). These patients were bile the missing link? and Microbiology, School of Hygiene, then randomly allocated to receive either Mortimer Street, London) Dyspepsia may De-Nol 1 tab nocte (CBS 120 mg) or an A D SPIGELMAN, C B WILLIAMS, M CRANOWSKA, be an early symptom of diseases, such as identical placebo. Patients were seen AND R K S PHILLIPS (St Mark's Hospital, City peptic ulceration, cholelithiasis, or gastric monthly and blood bismuth measured. Road, London and St Bartholomew's carcinoma, but often no organic lesion is Endoscopy was performed at three, six, and Hospital, West Smithfield, London) found. Should dyspeptic patients coming to 12 months and if symptoms recurred. Familial adenomatous polyposis (FAP) endoscopy with 'normal' findings also be Patients were withdrawn from study upon patients have a 10()-fold increased risk of Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A71 1 duodenal cancer without an increased risk well as duodenum (26% in DNA synthesis, were studied. All PUD patients had endo- of gastric cancer. p<0-0S, and 20% in crypt cell production scopy every six to 12 months if asympto- Eighty FAP patients (48 men) underwent rate); there was no macroscopic damage. matic or whenever symptoms recurred. gastroduodenoscopy (side viewing video- We conclude that the blunted gastric The first 2()( (of 224) patients had a total endoscope 73, forward viewer seven). Duo- regenerative response accounts in part for of 338 silent and 371 symptomatic relapses denal adenomas were proven histologically the acute gastric damage induced by high during follow up. The commonest lesions in (including five microadenomas) in 73 (91%) dose indomethacin, but that mucosal the silent and symptomatic phases were, and gastric adenomas in four (5%). Polyps adaptation with stimulation of epithelial cell respectively: duodenal erosions 49% l13% were seen in the duodenal bulb in eight turnover occurs with chronic low dose (p<0.0 1); duodenal ulcer (DU) 20(% v 44% patients (10%) and in the second part in administration. (p<0.01); prepyloric erosions 7% vl 1%; 70 (88%; two of these were non- prepyloric ulcer 4% vn 3%; gastric (body) adenomatous). Gastric and duodenal bulb ulcer 2% v 4%. During MT, relapses were adenomas were always accompanied by Pepsinogen I and gastrin: a screening test for more often silent than symptomatic, 84% t' denser distal duodenal involvement. The gastric cancer? 30(% (p<0(01) whereas the converse was ampullary area (within 5 mm of the papilla) observed off treatment, 16% v 70% was adenomatous in 52/72 (72%). Gastric M I HALL ISSEY AND J W 1. IELIDING (INIRO- (p<0.OI). On follow up off MT (n=55), adenoma patients were tested for duodeno- DUCED BY MR J G FEMPLE) (Department of silent PUD healed in 27 (49%) patients in gastric biliary reflux. 80 mBq "Tc DIDA Surgery, Queen Elizabeth Hospital, 7 4 months (mean); remained active but was given intravenously, followed by 5 ig Birmingham) The Japanese have shown silent in two (4%) patients for 15.5 months; ceruletide, serial gamma camera images that diagnosis of gastric cancer at an early and became symptomatic in 26 (47%) at 6-2 obtained, and a 30 mBq 'mTc labelled milk stage is achievable and reduces mortality months. The corresponding figures for drink given to outline the stomach. Bile from the disease. Their use of radiographic patients on MT (n= 169) were: 117 (69%) at reflux was seen in three patients (grades la, screening is clearly impractical in low risk 9-1 months; 17 (10%) for 13-2 months; and 3b, 3b) but not in the fourth, where scan- areas such as the UK and another method of 35 (21%) at 8-4 months, respectively; the ning was interrupted when the patient selection for investigation is required. The latter included two DU patients who complained of nausea (reflux not seen on serum concentrations of pepsinogen I and developed (one each) haemorrhage and resumption). gastrin, both markers of gastric function perforation. These observations parallel mucosal and pathology, have been evaluated as a The principal conclusion is that silent exposure to bile and may be explained by method of identifying both established PUD which develops during MT has a good abnormalities in FAP bile, mucosa or both. cancer and high risk changes. prognosis: healing occurs frequently if Serum was obtained from 422 sympto- therapy is continued. matic patients before endoscopy and 25 http://gut.bmj.com/ Indomethacin toxicity may be explained by normal controls. All samples were stored at its effects on gastric and duodenal prolifera- -40°C before assay which was by radio- Patients and surgeons assessment of the tion immunoassay for both peptides. The results of peptic ulcer surgery normal range for the laboratory was calcu- S LEVI, D VESEY, AND H J F HODGSON (Depart- lated from the control samples. A low P SIANTON AND J R ANDERSON (University ment of Medicine, Royal Postgraduate pepsinogen I (<30 ng/ml) or a raised gastrin Department of Surgery, Royal Infirmary, Medical School, Hammersmith Hospital, (>70 pg/mb) were considered abnormal. Glasgow) Two hundred and forty five Ducane Road, London) Indomethacin The test correctly identified 60% of the patients attending a gastric follow up clinic on September 24, 2021 by guest. Protected copyright. causes gastric and duodenal damage usually cancers and 60-9% of the high risk groups more than one year postoperatively were attributed to a direct toxic effect and a rising to 75% when these changes were asked to complete a self-assessment reduction in prostanoid synthesis. We have present in the fundus. Curable and questionnaire. The results obtained were investigated the effects of indomethacin on advanced cancers were identified equally. correlated with contemporary Visick epithelial cell proliferation in rat stomach Pepsinogen I and gastrin have potential grading. We considered patients in three and duodenum, using in vivo 3H-thymidine as a screening test for both gastric cancer groups: (a) good (Visick 1, n=69); (b) incorporation and stathmokinetic indices of and the high risk changes. Evaluation in an satisfactory (Visick 1I and Ills, n= 104); (c) cell renewal. A single high subcutaneous asymptomatic population is required to poor (Visick Illu+IV, n=72). Question- dose of indomethacin (30 mg/kg) univers- assess their role further. naire scores were divided into an equal ally induced an erosive gastritis within three number of groups (good score >53, n =83; to six hours, with concomitant reduction of satisfactory=score 36-52, n=99; poor- DNA synthesis in the gastric corpus and Silent peptic ulcer disease (PUD) score <35, n=63). Seventy two per cent of antrum (by 60%, p<0-05, and 31%, p<()-05 patients grade themselves the same as their respectively). There was no duodenal K D BARDHAN AND MARY IHOMPSON (District surgeon. No patient coming to revisional damage at this time, nor effect on duodenal General Hospital, Rotherham) The relation surgery scored themself above 41, and only proliferation. Single low doses of indo- between the recurrence of PUD and type of three such patients (of 23) graded them- methacin (<5 mg/kg) produced no macro- lesions, the presence or absence of symp- selves out of the poor group. Contrary to scopic gastric damage, and had no effect on toms, the influence of maintenance therapy other reports patients in Visick grades I and proliferation. In contrast, chronic low dose (MT) (mainly cimetidine 400 mg nightly), 11 did segregate in terms of questionnaire indomethacin (2 mglkg/d for eight weeks), and the outcome of silent PUD was scores. markedly increased proliferative activity assessed. Two hundred and twenty four One major cause of disagreement was in the gastric corpus and antrum (56%, patients (drawn randomly from 778 seen - recurrent ulceration (if asympto- p<0-05, and 27%, p<0.05 respectively) as patients) with -1 episode of silent PUD matic or controlled by medication) is often Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A712 The British Society ofGastroenterology viewed more 'leniently' by patients. We previously. Vagotomy was incomplete in Comparison of barium enema and colono- suggest that in the H2 blockade era this 18% of 455 patients after HSV, 16% of 515 scopy with an independent marker of distinction is worth making in grading after TV and 14% of 161 after SV (NS). colorectal disease surgical results; that is, patients be graded Wide inter-surgeon variation (0 to 50% on symptomatic grounds only, subclassified incomplete) was found, irrespective of the J J IATE, G 1 ROYLE, AND I IAYLOR by the presence or absence of recurrent type of vagotomy used. Consultants per- (University Surgical Unit, F Level, Southl- ulceration. formed HSV, but not TV, better than ampton General Hospital, Southampton) Our experience suggests that a patient registrars (p<0.02). Comparison of the diagnostic sensitivity of selfassessment questionnaire is an accept- Incomplete vagotomy is no more double contrast barium enema (DCBE) and able means of follow up after ulcer surgery. common after HSV than after truncal colonoscopy is controversial. We report a vagotomy, differences being between study using an independent marker of surgeons rather than between types of colorectal disease to assess results. Recurrent ulceration after highly selective vagotomy. When vagotomy was complete, Six hundred and twenty consecutive vagotomy and ulcer excision (HSV(E)) for the incidence of RU 10-20 years after HSV patients referred for investigation of type I gastric ulcer was 8%; when incomplete, 26% (p<0-001). the large bowel were sent a three day Haemoccult test to complete beforehand. I G MARTIN, K S NAIK, R C MACDONALD, A G The test was read by a single observer. MORGAN, W A F MCADAM, AND D JOHNSION COLOREC AL Patients had DCBE or colonoscopy per- (University Department of Surgery, The formed in a routine fashion by radiologists General Infirmary, Leeds and Airedale Haemoccult screening for colorectal cancer and endoscopists of comparable seniority District General Hospital) Since 1969, we - The role of dietary restriction and selective who were blind to the Haemoccult result. have treated 108 patients with GU by three month rescreening Three hundred and fifteen patients (age HSV(E) and 990 patients with DU by HSV. 19-89, median 62 yr) had DCBE of whom Our hypothesis was that because maximal W M THOMAS, G PYE, R M CHARNLEY, J 49 (15-6%o) had a positive Haemoccult result acid output is normal in both GU and DU, CHAMBERLAIN, ANDJ D HARDCASILE (Depart- and 24 (49%) of these had mucosal disease. H2 blockers are equally effective for both ment of Surgery, University Hospital, Two hundred and fifty seven patients (age conditions, and HSV reduces bile reflux, Nottinglham and Royal Marsden Hospital, 18-89, median 62 yr) had colonoscopy of HSV(E) would prove as effective in the Sutton, Surrey) Haemoccult can detect whom 42 (16.3%) were Haemoccult posi- treatment of GU as DU. Patients were asymptomatic colorectal cancers at a less tive and 31 (73.8%) of these had mucosal followed up annually in a special clinic. advanced pathological stage than those disease. There was no statistically signifi- Median time to recurrence was 11-5 occurring in a matched control population. cant difference in the number ot months in GU and 44 months in DU Foods rich in peroxidase and ingested Haemoccult positive patients in the two http://gut.bmj.com/ (p<0.001). Incidences of recurrent ulcera- animal haemoglobin may result in a false groups but a significantly greater number of tion by life table analysis, at 10 years follow positive reaction. This study examines the such patients were found to have mucosal up, were 12.9% in GU and 14-0% in DU. role of selective three month retesting after disease among those investigated by Recurrence was not more common after dietary restriction in a mass population colonoscopy (p= <0.05). emergency surgery. No patient died of RU, screening programme. Given that the performance of but four GU and 22 DU patients required Eighteen thousand, nine hundred and Haemoccult was a constant, we conclude reoperation. twenty five participants 50-74 yrs com- that colonoscopy is significantly more

Highly selective vagotomy is as effective pleted Haemoccult tests on a normal diet. sensitive than DCBE for the diagnosis of on September 24, 2021 by guest. Protected copyright. in the treatment of type I gastric ulcer as in 647 (3.4%) were positive. All repeated the colorectal mucosal abnormalities. the treatment of duodenal ulcer. test with dietary restrictions. Two hundred and fifty one people remained positive and were referred for further investigation. The Serum gastrin concentrations are higher in Is incomplete vagotomy commoner after remaining 396 patients were sent a further colorectal cancer patients highly selective vagotomy than after truncal test at three months. Three hundred and or selective vagotomy seventeen (80%) completed the test; 31 R M CHARNLEY, W M IHOMAS, J STANLEY, AND (9.8% ) were positive. Further investigation D 1. MORRIS (Department of Surgery, I G MARlIN, D JOHNSTON, AND) G SALFER revealed four carcinomas (1 Dukes' stage University Hospital, Nottingham) Many (University Department of Surgery, Thze A, 1 stage B, and 2 stage C), and 20 human colorectal cancers are stimulated in General Infirmary, Leeds) A partial adenomatous polyps. vitro by gastrin but gastrin is also synthesised gastrectomy is a partial gastrectomy, but a Three hundred and sixty five (56%0) fewer by in vitro cultures of colorectal cancers. We vagotomy is not necessarily a complete or colonoscopies were performed as a result of have measured fasting serum gastrin con- adequate vagotomy. If vagotomy is incom- dietary restriction retesting. centrations by radioimmunoassay in 47 plete, recurrent ulceration (RU) is more With median follow up of 24 months (18- patients with colorectal cancer and in 12 age likely. Thus some reports of high incidences 33 months), one patient has presented with matched patients who had normal colono- of RU after HSV led us to analyse the a rectal cancer after a negative three month scopy and clinical evidence of malignancy. completeness of our vagotomies. retest. In colorectal cancer patients the median Incidences of incomplete vagotomy after Dietary restriction retesting is important serum gastrin level was 50-66 pg/ml (range elective TV+D, SV+D and HSV for DU in reducing the rate of false-positive reac- 19.0-953 0) and in patients with normal were determined five to 10 days after opera- tions. In those who become negative after colonoscopy 40-65 pg/ml (range 31-5-53-3), tion, by the insulin test and Hollander's dietary restrictions, however, we advocate a p=-(09. Forty three per cent of cancer criteria. Results after V+D were reported further test at three months. patients had raised (greater than mean +2 Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterologgy A713

SD of normal subjects) serum gastrin con- Intra-operative localisation of colorectal ated for survival prediction. We have found centrations. To determine the origin of the cancers and their metastases with a radia- no evidence of c-myc DNA amplification in raised serum gastrin 37 patients with tion detecting probe 10 fresh tumours by Southern blotting. We colorectal cancer had tumour draining have shown, however, varying levels of the mesenteric blood samples taken at surgery B R DAVII)SON, W A WADDINGilON, M D SHORI, p62 c-myc protein product of the oncogene before their colonic resection and simul- ANI) P B BOUI.OS (Department of Surgery, c-myc in archival paraffin embedded taneously a peripheral venous blood sample UCMSM and Department of Plysics and tumours. A double labelling technique was was taken. Median serum gastrin concen- Bioengineer-ing, University College used to quantify the protein of extracted trations were 47.1 pg/mi (range 60-(X10018) Hospital, London) Radiolabelled mono- nuclei with a monoclonal antibody (MYCI- for mesenteric vein blood and 50-8 pg/ml clonal antibodies (MAB's) to tumour 6E10) and a second fluorescein labelled (range 20-0-953-0) for peripheral blood. associated antigens may be used to localise immunoglobulin. The levels of p62 c-myc Peripheral vein and mesenteric vein values colorectal cancers by external gamma were quantified using a flow cytometer and were very similar in individual patients camera imaging but cancers less than 2 cm expressed as fluorescence units (FU). Vary- (correlation coefficient r=0.986). diameter are rarely detected. We have ing expression of p62 c-myc was confirmed Colorectal cancer patients exhibit hyper- therefore investigated the intra-operative in fresh tumours by Western blotting, p62 gastrinaemia compared with age matched (10) use of a radiation detecting probe in 16 c-myc levels were significantly lower in controls. Because peripheral venous and patients with colorectal tumours (14 Dukc's A (Wilcoxon's rank-sum test mesenteric venous gastrin levels do not cancers, one lipoma, one adenoma) three to p=0.01). but did not significantly vary in the differ, hypergastrinaemia appears to be six days after administration of '"'n labelled other Duke's stages: stage A (n=7). related to tumour aetiology. MAB to epithelial membrane antigen median=7 FU (range )-45), stage B (n= (EMA) (1 mg MAB/2 mCi `"In). 45), median=45 ((1-150), stage C (n= 17), At operation 3x2() second counts were median=38 (4-1(X)), stage D (n=14), Immunohistochemical study of a tumour taken over the primary tumour, normal median=51.5 (3-120)). Patients with values associated antigen recognised by monoclonal colon, liver and suspected nodal meta- less than 20 FU (n=21) had a significantly antibody C466 stases. Resected specimens were also better survival than those with higher probed and biopsies of tumour and normal expression (n=62) (logrank analysis X' N D ROTHNIE, S U HUICI, N ROONEY, C B WOOD, colon gamma counted. Tumour antigen 4.69, dfl, p=0.03). In conclusion p62 c-myc R C N WILLIAMSON, [) C C BARIOIO, AND N A expression was assessed by immunohisto- expression is a significant prognostic HABIB (Department of Surgery and Histo- chemistry. variable in CRC. pathology, Bristol Royal Infirmary and The tumour to normal colon (T/N) ratio Department ofSurgery, Royal Postgraduate of counts in viio was > 1-5:1 in nine of the 14 Medical School, Hammersmith Hospital, patients with cancer (1-83 (0-21)) and 0(96:1 http://gut.bmj.com/ London) C466 is a murine monoclonal and 1-06:1 in the two patients with benign Specific 5-hydroxytryptamine receptor antibody (MoAb) raised against the human tumours. T/NC ratio for excised specimen (TYPE 3) antagonist GR38032F slows colorectal carcinoma cell line SW 620. This probing was significantly higher than in vivo colonic transit study assessed the difference in staining in (4.44 (1.37:1 ) t' 1-51 (0-44: 1), p= 00(X)00) and colonic tissues. Immunohistochemistry correlated with gamma counting ratios S GOREI, i Gil MOREi, C G HAIGH, AND A I using the avidin-biotin peroxidase method (2.26 (0.78:1), R=0-73, p<(-(X)I). EMA MORRIS (Gastroenterology Unit, Royal were performed on paraffin sections of expression by cancers was associated with Liverpool Hospital, Prescot Street, Liver- tissue from patients with colonic adenocar- higher T/NC ratios (2 45 (0(65:1) v 1.30 pool and Department of Gastroenterology, on September 24, 2021 by guest. Protected copyright. cinomas (n=59), lymph nodes (n=32), liver (0.25:1), p=-0.(X)5). Lymph nodes (<1 cm Glaxo Group Research Ltd, Greenford, metastases (n=7), ulcerative colitis (n=20), diam) containing tumour could be differen- Middlesex) GR38032F is a selective antago- and histologically normal colon (n=62). tiated from those without tumour in viv,o by nist of 5-hydroxytryptamine (5-HT) type The antigen recognised by C466 was their uptake of activity relative to that of three receptors, which is being investigated detected in 1000% of colonic carcinomas normal colon (1.71 (0((X)6:1) v 0 84 in the treatment of disorders of the central (88% of cases with >50(% of cells staining). (0.33:1), p=0.017). The uptake ratio of nervous system and the gastrointestinal All cases of tumour metastases in lymph normal liver to primary cancers was 2 48 tract. Irritable bowel syndrome and other nodes and liver stained positively, while 17 (1.1): 1). The data suggest a value to the 10 gastrointestinal complaints have been nodes without tumour showed no staining. probing of "'In MAB in detecting colorectal associated with the disordered gastro One case of colitis showed staining of 1b% cancer metastases but not liver deposits. intestinal motility, and drugs that modify cells. Normal colon showed no staining on (Mean (SD).) gut motility may therefore be of benefit. the left but 69% of cases were positive on A randomised, double blind, crossover the right, but with a different pattern of study was undertaken to evaluate and com- cellular localisation to that seen in the pare the effect of GR38032F with placebo cancer cells. c-myc Oncogene in the progression of on gastrointestinal transit in 10 healthy male Absorption studies indicate that C466 colorectal cancer (CRC) volunteers. Gastric emptying rate was binds to H type 2 oligosaccharide chains assessed by a radioisotope labelling with the structure: PL Fuc (1-2) P D Gal S ROWLEY, J P NEiOIYIOLEMOS, A DONOVAN, method; small bowel transit time by the (1-4) ,3 D GIcNAc. This study suggests that AND) M R B KEIGHiLEiY (BirminghIam University assessment of breath hydrogen; and whole this tumour associated antigen is expressed and Dudley Road Hospital, Birmingham) gut transit time by the use of radio-opaque in colonic cancers and the antibody C466 Improved methods of predicting survival markers. The dose and duration of treat- may be useful in the histopathological are required in CRC. Oncogenes are ment was 16 mg tds GR38032F for seven detection of metastases. expressed in CRC but have not been evalu- days. Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A714 The British Society ofGastroenterology

There were no significant differences Plasma somatostatin (SMS) concentrations graphically derived anismus index com- between placebo and GR38032F on either in the irritable bowel syndrome (IBS) pares objectively the EMG activity during gastric emptying rates (mean times were 54 defecation straining with the EMG activity minutes for placebo and 58 minutes for L J D O'DONNELL, A J M WATSON, D CAMERON, during voluntary squeezing. Biofeedback GR38032F) or small bowel transit time K DAVIDSON, J A H WASS, AND M J G FARTHING using visual display of the EMG signal has (mean times 169 minutes for placebo and (Departments of Gastroenterology and been used as a retraining exercise in 15 184 minutes for GR38032F). Significant Endocrinology, St Bartholomew's Hospital, subjects (12 women and three men with a differences in mean whole gut transit time London) Relief of irritable bowel symp- mean age of 45 (17) years) who presented were observed, however - that is, 54-8 toms by SMS have been described. As with constipation caused by anismus. The hours with GR38032F and 32 1 hours with circulating somatostatin derives predomi- anismus index pretreatment was 69.5 (28.7) placebo (p value 0-(X)1). Therefore, 5HT3 nantly from the gastrointestinal tract we (range 43-160). All subjects were taught receptors may be involved in the regulation determined whether patients with IBS have biofeedback suppression of the non- of colonic transit. decreased plasma concentrations of SMS, relaxing pelvic floor signal in hospital and fasting and postprandially. Seven healthy continued with twice daily sessions using controls (median age 29; range 24-37 yr) portable domiciliary biofeedback equip- and seven 'diarrhoea' predominant IBS ment for two to four weeks. The duration of patients (46; 18-65 yr) after an overnight treatment depended on their subjective Longterm treatment of irritable bowel syn- fast, received a standard breakfast and 40) responses (defecation time, defecation drome with cimetropium bromide, a double ml lactulose. Plasma SMS concentrations difficulty) measured on an analogue scale. blind placebo-controlled clinical trial were determined fasting and at 15, 30, 45, The anismus index after biofeedback was 60, 90, and 180 min postprandially. Com- 13-7 (16) (range -25-35.7); p<0-01. All G DOBRILLA, l. PIAZZI, B P IMBIMBO, AND G bined gastric and small intestine transit subjects had corresponding subjective BENSI (Divisione di Gastroenterologia, time was measured by monitoring end- improvement in defecation times and in Ospedale Generale di Bolzano Stradella S expiratory concentrations of breath H2. IBS analogue scores for difficulty. Maurizio, 39100 Bolzano, Italy) Cimetro- patients had lower mean (SEM) plasma pium bromide is a new antimuscarinic com- concentrations of fasting SMS (19 (2) v 33 pound with strong antispasmodic activity. (6) pg/ml; p=0-06, two-tailed Mann- The aim of this study was to evaluate its Whitney U test) and peak postprandial SMS Is anismus the result of reduced anorectal efficacy in improving symptoms of patients (49 (8) v 76 (8) pg/ml; p=0-06) compared sensation in slow transit constipation with irritable bowel syndrome over a three with controls but postprandial area under month period. Seventy consecutive out- the SMS concentration curve was similar in G S DUIHIE, D CC BARTOLO, R MILLER, M J MCC patients were given cimetropium (50 mg tid) both groups (2715 (613) v 3178 (1163) pg/I MORIENSEN, AND J VIRJEE (Univ,ersity http://gut.bmj.com/ or placebo according to a double blind, min; NS). Combined gastric and small Department of Surgery, Bristol Royal randomised, parallel groups design. intestine transit times were also similar in Infirmary, Bristol) To determine the role of Symptoms were evaluated at baseline and both groups (69 (12) v 71 (12) min; NS). The anismus in slow transit constipation (STC) monthly up to the end of therapy. One older age of IBS patients compared with we carried out manometric, radiological patient receiving placebo withdrew because controls in this study does not explain the and neurophysiological measurements on of treatment failure. Pain score decreased observed differences as fasting plasma SMS 94 patients with STC who were divided into by 40, 66, 85% in the cimetropium group, at concentration normally increases with age. 53% with anismus (STCa) and 47% with the end of the first, second, and third As SMS has known effects on opiate normal defecograms (STCn). Both groups on September 24, 2021 by guest. Protected copyright. months respectively, compared with 26, 32, receptors and gut motility, these observa- exhibited significantly increased anal sensi- and 52% reductions among controls (p= tions of lowered concentrations of plasma tivity thresholds (STCa; 6-97, 7-06, 8.46 in ()0005). At the end of treatment there was SMS in IBS may have important implica- mAmps at 1, 2, and 3 cm respectively: an 86% reduction in the number of daily tions for its pathogenesis, diagnosis and STCn; 8-77, 9-12, 10-96: v controls; 4.65. abdominal pain episodes in the cimetro- management. 4.35, 5.40; p<04))l). STCa had a higher pium group compared with 50% in the volume of first rectal sensation (STCa placebo group (p=-0.001). Bowel disturb- 162-07; il STCn 77-25; p=-0(X)8). The ances score decreased by 56% in the EMG biofeedback as a domiciliary treat- anorectal angle was more acute at rest cimetropium treated patients, compared ment of anismus (STCa 92.3; v STCn 105-3; p<0-001), on with 42% in controls, the difference squeeze (STCa 88.4; v STCn 93-9; p=().05), between being not significant. At the end of N R BINNIE, B M KAWIMBE, M PAPACRYSOS- and during straining (STCa 102-6; i STCn the study 89% of the patients treated with TOMOU, AND A N SMITIH (Department of 119-2; p<0.001). Both groups showed cimetropium considered themselves as Surgery, University of Edinburgh, Western increased perineal descent with STCn globally improved as opposed to 69% in the General Hospital, Edinburgh) Anismus descending further than STCa on straining placebo group (p=0.039). The correspond- (spastic pelvic floor syndrome) is the func- (STCa - 2 17 cm; i STCn - 3.81; p<0.001). ing 95% confidence intervals for the differ- tional abnormality of inappropriate con- The distribution of markers on transit ences between the proportion of improved traction of the pelvic floor while straining studies and duration of symptoms were patients in the two groups were from 11% to at stool. This causes various anorectal similar. In conclusion, both groups have 29%. Six patients taking cimetropium com- disorders including a form of constipation sensory impairment but reduced rectal plained of slightly dry mouth. The results of as a result of the outlet obstruction. The awareness in anismus may be responsible this study showed that cimetropium non-relaxation abnormality of the pelvic for the failure to relax. There is no evidence bromide is effective in relieving pain in floor is detected using an anal plug from this study that anismus contributes to patients with irritable bowel syndrome. surface EMG electrode. An electromyo- the genesis of slow transit constipation. Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterologyA1 A715

Serotonin is increased and VIP decreased in ing. Twenty four enuretic children served as gen rise coincided with test meal arrival in the sigmoid colon in idiopathic constipation controls. Portable anorectal manometry the pouch. In the other six patients, two had equipment was used comprising a BBC an early hydrogen rise coinciding with the P MuLNE:R, J LINCOLN, R CROWE-, M KAMM, J E master computer linked via pressure trans- meal in an area of jejunum bacterial over- ILENNARD-JONES, G BURNSTOCK (Department ducers to an anal probe with three water growth and four did not exhibit any hydro- of Anatomy and Developmental Biology, filled anal sensor balloons and a terminal gen increase either because of low areobic University College London, and St Mark's 200 ml air filled balloon. or acid microclimate. Radiographic transit Hospital, City Road, London) Changes in Eighteen patients had high and 21 had time was 28 (17-74 minutes)*. This did not the levels and distribution of neurotrans- low spinal lesions. Mean anal resting correlate with frequency of defecation (t= mitters in the intestine may be important in pressure was lower than that of controls 0(076 NS). In view of these findings we do chronic idiopathic constipation. Sigmoid (37.6 (21.5) v 44 mmHg). Resting pressure not advocate this method for measuring colon from patients with idiopathic consti- of the first balloon was significantly lower intestinal transit after ileal reservoir forma- pation and carcinoma controls were than that of controls (41-5 (21-5) v 52.3 tion. prepared for immunohistochemical exami- (18.4) mmHg) but similar in the second *Median range. nation of serotonin-, dopamine ,- balloon (33.7 (24.3) v 35-7 (15.3)). Maximal hydroxylase-, vasoactive intestinal poly- rectal distension induced an anal tone peptide (VIP)-, substance P (SP)- and reduction in the first two balloons compar- Improving the diagnosis of pouchitis: an neuropeptide Y (NPY)-staining. Dissected able with controls (- 19-0 (17.8) v -17-0 appraisal of "'Indium labelled granulocytes mucosal, whole wall minus the mucosa, and (11 1) mmHg and -11.5 (19.7) v -11-1 circular muscle preparations were assayed (18.9) mmHg), but a tone increase occurred W A KMIOI, L K HARDING, S R HE.SSEI.WOOD, N for total indoles (to allow for breakdown of in the third and innermost balloon (2.6 SMIIH, AND M R B K-IGHIEY (Tlue General serotonin) and noradrenaline by HPLC (15.4) v 9-2 (15.3) mmHg). The anal rhyth- Hospital, Birmingham) After restorative with electrochemical detection and VIP, mical activity frequency was slower than proctocolectomy 5-20% of patients develop SP, and NPY by an inhibition ELISA tech- that of controls (7.5 (3-3) v 12-14 waves/ pouch inflammation (pouchitis) 80(% of nique. min). Twenty six patients of 31 asked could which improve after treatment with metro- There was a significant increase in the defecate the balloon on demand. nidazole. The neutrophil infiltrate is patchy levels of total indoles in the circular muscle The internal sphincter tone and and clinical features non-specific, thus to and mucosa in constipation (median 5-55, behaviour is normal although slow define an objective diagnostic method, we interquartile range 4-27-10-73, n=7 and rhythmical activity suggests altered have performed `'Indium labelled granulo- 13-29, 11 71-18-(X), n=8 nmol/g tissue, dynamics of this muscle. There is no clear cyte scans in 25 patients: 22 (7-46 months)* respectively) compared with controls (2.93, evidence of megarectum on anorectal after pouch formation. Gamma camera 1-87-4-15, n= 12 and 8-31, 8-04-9-13, n= 13 manometry. Easy defecation and low anal scans were performed at four and 24 hours http://gut.bmj.com/ nmol/g tissue, p<0-02, respectively). Vaso- tone suggests that the cause of faecal incon- and a four day stool collection was counted active intestinal polypeptide levels were tinence is neurogenic rather than overflow for granulocytes. Results correlated with also significantly different in this disease incontinence. histology, clinical findings and blood para- and showed a decrease in the whole wall meters of inflammation (WCC, ESR, CRP, minus mucosa (54-8, 29-5-843, n=7 com- and cal AGP). After one month's therapy pared with 144-1, 112-2-194-8, n=10 Intestinal transit after restorative proctoco- with metronidazole, all five patients with pmol/g tissue, p<005 Mann Whitney U lectomy by breath hydrogen sampling: a positive scans initially had decreased pouch test). There were no differences in the levels pilot study activity on rescanning (p<0.01)***. This on September 24, 2021 by guest. Protected copyright. of noradrenaline, SP and NPY in any of the correlated with reduced faecal granulocyte layers of intestine analysed and this was W A KMIOI, J 0 BRIEN, A COPPELL, AND M RB excretion (initially >2%) (t=0-71, consistent with the immunohistochemical KEIGHLEY (The General Hospital, Birming- p<0-01). Also, 24 h defaecation frequency studies. ham) The lactulose breath hydrogen tech- had significantly improved, pre-treatment: These studies indicate that there is nique enables non-invasive determination 8 (7-1 )* v post treatment: 6 (4-18)*, a disturbance in the serotonergic and of orocaecal transit. Reports have docu- p<0.05**; with the latter group having VIPergic innervation of the colon in consti- mented both an increased anaerobic: similar values to the negative scan group*: 6 pation which may initiate or contribute to aerobic ratio and fold anaerobes after ileal (3-8) (NS). There was no difference in the functional changes in this condition. pouch formation. The fermentation proper- inflammatory indices between patients with ties of these bacteria may allow study of positive and negative scans. Serial biopsy small bowel transit in such patients. We neutrophil counts and bore no relationship Anorectal function in children and adoles- have compared oropouch transit in 12 to clinical results. These data show that cents with spina bifida patients at 20 (9-46 months)* after surgery indium scanning is a valuable additional with 10 control subjects. After 18 hours of tool in the management of pouchitis. U AGNARSSON, C GORDON, G MCCARIHY, N fasting, all subjects drank 30 ml lactulose *Median (range), **Wilcoxon's rank-sum EVANS, AND G CLAYDEN (Royal Alexandra (20 g) in 4(X) ml chicken soup and 100 ml test. Hospital for Sick Children, Brighton, 30% barium solution. Breath hydrogen Sussex) In order to assess bowel function in collection occurred at five minute intervals children and adolescents with spina bifida, together with radiographic screening. In Videoproctographic assessment after restor- 39 patients, 21 men and 18 women aged 3- controls, the head of the meal had arrived in ative proctocolectomy 22 years (mean 12-3 (5-3) years) had anorec- the caecum at the time of breath hydrogen tal manometry performed. Level of spinal rise and transit time was 70 (33-86 min)*. In W A KMIOI, M PINHO, K YOSHIOKA, AND M RB lesion was assessed by motor-sensory test- six of 12 pouch patients, the breath hydro- KEIGHITY (Thie General Hospital, Birming- Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A716 The British Society ofGastroenterology ham) lleal reservoir emptying was analysed than 8W() ml (n= 13) pathogens were present Foscarnet is effective treatment of CMV and quantified in 28 patients after restora- In nlne. infection of the gut and no major toxicity is tive proctocoleetomy (FU: 22 months (four Barium studies were normal except for encountered. to 45 months)) and results compared with 26 flocculation in two patients with crypto- age/sex matched control subjects. A 1:1 sporidium. Twenty five patients had mal- ratio by weight baritop/Readybrek mixture absorption - 22 on xylose test (severe in Safety and efficacy of acetarsol suppositories diluted with 20 ml water to the consistency five), 20 on Schilling test. Where the in unresponsive proctitis of soft faeces and weighing 120 g was Schilling test was severely impaired (n= 14) introduced per annum. Dynamic video- a pathogen was present in 10 (including all A FORBES, T C BRITION, M HOUSE, AND B G proctography and freeze frame analysis was five with cryptosporidium and two patients GAZZARD (Department of Gastroenterology, performed at rest, during pelvic floor con- with only moderate diarrhoea/weight loss). Westminster Hospital, London and Poisons traction and attempted defecation. There Malabsorption is frequently associated Unit, New Cross Hospital, Avonley Road, was no difference in median emptying with diarrhoea in HIV- infected patients London) Acetarsol suppositories have been between pouch patients and control sub- and is most profound in patients with identi- successfully used in ulcerative proctitis. jects (NS) (Pouch 40 g at one minute: fiable gut pathogens. A simple five point Although concern about arsenic toxicity has controls 60 g at one minute). Of the 14 score based on degree of weight loss and limited recent use, arsenic absorption has patients who passed less than 40 g, eight had Schilling test result helps to identify these not been examined previously. a stenosis at the ileoanal anastomosis com- patients. In a prospective open study, 10 patients pared with none of the remainder (p<-(05), (four men) (median age 50; range 26-67) and seven had had an episode of pelvic with intractable proctitis (more than four sepsis compared with none of the remainder Foscarnet in the treatment of cytomegalo- weeks sulphasalazine/mesalazine plus rectal (p<0-02). Patients with impaired pouch virus infection of the gut in patients with steroids) treated with acetarsol supposi- emptying did not have increased stool fre- AIDS tories, 250 mg bd for four weeks, were quency (8/24 h ' 7/24 h). Pouch design had monitored clinically, biochemically and no influence on emptying. There was no G M CONNOLLY, AlASTAIR FORBES, MIKE toxicologically. significant difference in anorectal angle, YOUILE, AND BRIAN GAZZARD (Departments of Proctitis resolved symptomatically and anal canal length or pelvic floor descent Medicine, St Stephen's and Westminster sigmoidoscopically within two weeks in nine between patients and controls at rest, Hospitals, London) While treatment of cases. There was no effect in one patient. during pelvic floor contraction and attemp- cytomegalovirus (CMV) infection of the gut The only side effect was of transient ted defecation. with Ganciclovir is established only thrombocytosis in a single patient. Maximal We conclude that pelvic floor sepsis and anecdotal reports are available of the use of blood and urinary arsenic concentrations pouch anal stenosis adversely affects pouch an alternative agent Foscarnet. During a occurred after one week's treatment with a http://gut.bmj.com/ emptying, but is not the cause of frequency prospective study of gastrointestinal symp- total inorganic arsenic in the hazardous of defecation. toms in AIDS 26 patients with cytomegalo- range in six patients; subsequent concentra- virus infection (two in multiple sites) were tions fell despite continuing therapy and at identified. four weeks potentially hazardous values Eight of nine patients with oesophageal persisted in only one patient. Continued Investigation of apparently pathogen ulceration responded to two weeks intra- renal excretion and diminishing absorption negative diarrhoea in patients infected with venous treatment with Foscarnet with loss across an improving rectal mucosa is human immunodeficiency virus (HIV) of symptoms and endoscopic and histo- thought responsible for this paradox. on September 24, 2021 by guest. Protected copyright. logical abnormalities. Remission was main- Arsenic levels fell rapidly when acetarsol G M CONNOLLY, A FORBES, AND B G GAZZARD tained for two to eight months. was withdrawn and were indistinguishable (Department of Gastroenterology, St Four of eight patients with CMV colitis from pretreatment values within four Stephen's and Westminster Hospitals, responded to intravenous Foscarnet with weeks. London) Thirty three consecutive male reduction in stool volumes and sigmoido- Short term acetarsol therapy offers a patients with HIV infection (aged 18-54, scopic and histological resolution. useful and safe additional measure when median 28) and undiagnosed diarrhoea Remission was maintained for three months local steroids have failed to control ulcera- (greater than three loose stools per day for or more. Two of the non-responders had tive proctitis; formal controlled compari- more than one month with six negative stool additional pathology (cryptosporidiosis) sons with other therapeutic options are cultures) were investigated for malabsorp- and two patients died of perforation at one therefore legitimate. tion. All had xylose and Schilling tests, and 1) days from starting treatment. In distal duodenal biopsy, comprehensive contrast, although three of six other barium studies and further stool micro- patients responded to intravenous scopy. Ganciclovir, all relapsed within a week. In A microbiological or histological diag- two further patients CMV infection compli- INFILAMMATORY BOWEL DISEASE nosis of infection was made in 12 (multiple cated established inflammatory bowel organisms in three): five cryptosporidium, disease and produced marked symptomatic Mesalazine or olsalazine in ulcerative four cytomegalovirus, two of giardia, H deterioration. colitis? Intraluminal colonic concentra- simplex, C jejuni, salmonella, E histolytica. One case each of duodenal ulcer, tions and systemic bioavailability of 5- When weight loss was less than 5 kg or stool hepatitis and scierosing cholangitis caused aminosalicylic acid volume less than 400 ml/day (n=9) no by CMV all responded symptomatically. organism was found; where weight loss was biochemically or histologically to Foscarnet 1. S LAURSEN, M STOKHOLM, K BUKHAVE, J greater than 10 kg and stool volume greater therapy. RASK-MADSEN, AND K lAURITSEN (Odense Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A717

University Hospital, Bispebjerg Hospital, ELISA and Cu/Zn-thionein (MT) was assessed sigmoidoscopically (24.1 (5.8), University of Copenhagen and Technical determined by a RIA in homogenates of n= 1 1 inactive; 69.4 (18.0), n=6 active, University, Denmark) To compare the dis- representative intestinal tissues divided p<0.0l). Addition of AA increased PGE2 position of 5-aminosalicylic acid (5-ASA) according to grade of inflammation. The release by colitic (144 (32) ng/G wet weight and its acetylated metabolite (Ac-5-ASA) results were evaluated by the Wilcoxon's to 426 (122). n=7. p<0.0l) but not by during treatment with mesalazine and rank-sum test. normal mucosa (127 (60), 161 (46), n=5). olsalazine (OLZ) 14 patients with inactive The SOD content of IBD tissue samples The finding that exogenous AA greatly ulcerative colitis were randomly assigned to was found to decrease with increasing increased eicosanoid synthesis in colitic Asacol (A; 800+400+800 mg), Pentasa (P; severity of inflammation and was signific- mucosa indicates enhancement of 5- 750+500+750 mg), Salofalk (S; 750+500+ antly decreased in inflamed tissue compared lipoxygenase and cyclo-oxygenase activity 750 mg), or OLZ (1 g bd) in a crossover with control tissue and to non-inflamed IBD and supports the proposal that dietary design so that all patients received each tissue. The MT content was decreased in all reduction of mucosal AA may be beneficial. drug for seven days. Intraluminal colonic IBD tissue samples compared with control concentrations of 5-ASA were estimated tissue samples irrespective of the grade after five days by equilibrium in vivo dialysis inflammation (see below). No differences of faeces. A predose serum sample and 24 h were found between Crohn's disease and Effect of essential fatty acid supplemetation urine collection were obtained on day 7. ulcerative colitis. on red cell lipids in ulcerative proctocolitis 5-ASA and Ac-5-ASA were determined by Cu/Zn containing SOD and MT are HPLC. decreased in intestinal tissue of patients A GIREEN, S HOWELL, NA PUNCHAR13, AND Concentrations (mean (SEM)) of 5-ASA with IBD and for SOD this decrease is R P H THOMPSON (Gastrointestinal Labora- (mM) in faecal dialysates were 23.7 (1.9) related to the severity of inflammation. tory, The Rayne Institute, St Thlomas' (OLZ); 23-3 (3.1) (A); 12-6 (2-2) (P; These findings might give rationale to anti- Hospital, London) Increased colonic p<0O05 v OLZ); and 15-0 (2.0) (S; p<0-05 v oxidants as anti-inflammatory therapy in synthesis of the proinflammatory arachi- OLZ). By contrast, serum concentrations IBD. donic acid (AA) products prostaglandin E2 of 5-ASA (tM) and Ac-5-ASA ([tM) as (PGE2) and leucotriene B4 (LTB4) occurs well as urine excretion of 5-ASA+Ac-5- n g SOD/mg protein n ig MT/mg protein in ulcerative proctocolitis (UC(). We ASA (% of daily dose) decreased (p<005) attempted to alter their production by during OLZ treatment: 2-4 (0.6), 5-4 (1.0), Contiols 1 2 13(0(10) 16 036((00(4) dietary supplementation with Efamol (1O)% IBD 22 (4)% (OLZ); 6-4 (1.5), 11-5 (2.2), 31 Non-inflamed 3. 2 24(0(1) 35 (.23(00.3) gammalinolenic acid, GLA) or MaxEPA (7)% (A); 2-6 (0-8), 8.1 (1.6), 36 (10)% (P); Moderately inflamed 39 89(0 10()' 36 () 16(06(1 (20% cicosapentanocic acid, EPA) in and 13-7 (6.5), 18-3 (4.7), 54 (12)% (S). Severely inflamed 12 82(0.(09) 1(2(()4)(0 patients with UC. http://gut.bmj.com/

Thus OLZ almost doubles the colonic Mean (SE). *p<0.02 v non-inflamed; tp<(0(0; +p<(0( 10 controls. Thirty six patients with stable UC concentrations of its therapeutically active (unchanged treatment >six weeks) ingredient (5-ASA) compared with equi- received capsules of Efamol, MaxEPA, or molar doses of P and S. At the same time, placebo (olive oil) for six months in addition the low systemic bioavailability of 5-ASA, Exogenous arachidonic acid potentiates to usual treatment in a randomised double provided by OLZ, reduces the risk of LTB4 and PGE2 synthesis by colitic mucosa blind study. Each group received 6 g daily nephrotoxicity. in vitro for one month then 3 g. Red cell fatty acids were measured at 0, 3, 6, and 9 - that is, D J GERINER, G DE NUCCI, D S RAMPTON, E three months after supplements - months on September 24, 2021 by guest. Protected copyright. Copper (Cu)/Zinc (Zn) containing proteins CYNK, AND J E LENNARD-JONES (St Mark's by gas liquid chromatography. with anti-oxidant function are decreased in Hospital, City Road, London and William The treatment groups were initially com- the intestinal mucosa of patients with inflam- Harvey Research Institute, Charterhouse parable. EPA levels (expressed as % of matory bowel disease (IBD) Square, London) Arachidonic acid (AA) total fatty acid content. Mean (SD) were metabolites appear to play an important significantly raised on MaxEPA (0.5 (0.35), I P J MULDER, A R JANSSENS, H W VERSPAGET, role in ulcerative colitis and, a reduction, 1 23(0-95), 1.48(1.1),0.55(0.45)at0,3,6, P A F DE BRUIN, A S PENA, T WEIERMAN, AND for example by dietary means, of the AA and 9 months) but unchanged in the other C B H W LAMERS (Department of Gastro- component of membrane phospholipid groups. Arachidonic acid levels were enterology and Hepatology, University could be therapeutically useful. We have reduced on placebo and MaxEPA and Hospital, Leiden, The Netherlands) Oxida- studied release of immunoreactive leuco- increased on Efamol non-significantly. tive damage of the intestinal tissue might triene B4 (LTB4) and prostaglandin E2 Dihomogammalinolenic acid (DGLA) play a role in the pathogenesis of IBD. It has (PGE2) by normal and colitic mucosa levels were significantly increased on been shown recently that 5-ASA containing incubated in Tyrode's solution for 40 Efamol (0 8 (0.5), 1.1 (0.37) at 0 and 6 drugs possess anti-oxidant potentials which minutes with or without the addition of AA months) but fell on MaxEPA (0.95 (0.17), could contribute to their therapeutic (10 [og/ml) at 20 minutes. Basal release of 0)59 (0.23)) and placebo (0.94 (0.35), 0(64 effects. In the present study we determined LTB4 in colitic mucosa was 6-0 (3-8) (mean (0.34)). two endogenous intestinal anti-oxidant (SEM)) ng/G wet weight (n=7) but was GLA and EPA compete with AA for metalloproteins in resection specimens of undetectable in normal mucosa (n=5, cyclooxygenase and lipoxygenase enzymes 28 Crohn's disease and 12 ulcerative colitis p<0.01). Exogenous AA increased the and may reduce production of proinflam- patients and compared the results with release of LTB4 in colitic (39-8 (9.4), n= 17, matory compounds. Thus the increase in those of normal mucosa from 18 colorectal p<0.01) and to a lesser extent in normal DGLA (derived from GLA) and EPA may cancer patients. Cu/Zn-superoxide mucosa (6.0 (1-4), n=5). AA-stimulated competitively reduce the production of dismutase (SOD) was determined by an LTB4 release increased with disease activity PGE2 and LTB4 derived from AA. Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A718 The British Society ofGastroenterology

Pregnancy in inflammatory bowel disease nant and benigh disease. We describe the drink. In contrast, their response to (IBD) patients on azathioprine serum measurement of CP and its hetero- C albicans is indistinguishable from that geneity by crossed immunoelectrophoresis seen in normal controls. Hypersensitivity to E M ALSTEAD, J RITCHIE, J LENNARD-JONES, (CIE). Sera was collected from 25 patients S cerevisiae may play a role in the patho- M J G FARTHING, AND M L CLARK (Departments with well documented Crohn's disease in genesis of Crohn's disease, and may result of Gastroenterology, St Bartholomew's and both an active and inactive phase for each from dietary exposure or antigenic cross St Mark's Hospitals, London) We report a patient and the clinical activity expressed as reaction with an infective agent - for preliminary survey of the outcome of 14 the Harvy Bradshaw index. Crossed example, yeast mannans may cross react pregnancies in 12 patients with IBD who immunoelectrophoresis was performed on with mannans present in mycobacteria. have received azathioprine during preg- Agarose gel with CP antisera. The results nancy. Although azathioprine has been were expressed as a ratio of the height of the reported to be safe in pregnancy in renal two peaks. The serum CP was measured by Comparison of ultrasound with 111 Indium transplant recipients and patients with radial immunodiffusion (normal range scintigraphy for assessing disease extent in systemic lupus erythematosus, there has 0-15-06 g/l). The median HB index in the inflammatory bowel disease been no study in IBD. Most clinicians active group was 8 (range 4-15) and in the

report that the drug should be discontinued inactive group 1 (range (-3). The median S H SAVERYMUHl'U, K I KHAW, AND A F A or even the pregnancy terminated. peak height ratio was 3.5 (range 0.56-6-50) JOSEPH (St Georges Hospital Medical The median age at delivery was 27-5 yr in the active group and 185 (range 1-14- Schtool, London) A non-invasive assess- (range 25-32) and mean duration of IBD 6.00) in the inactive group (p<0.02). The ment of inflamed bowel in Crohn's disease was 4-4 yr (range (1-8 yr). Duration of median CP in the active group was 0-62 g/l and ulcerative colitis would be valuable in treatment with azathioprine before (range 0-37-1-59) and in the inactive group management. 1 1 1 Indium granulocyte pregnancy was 6-60 months. In addition 0-42 g/l (range 0-25-0-89) p<(.-()l. There is scintigraphy provides such an assessment to azathioprine, 10 patients received a significant correlation between the HB but its use is limited by restricted avail- prednisolone, five sulphasalazine, and one index and the peak height ratio p<(-01 and ability, cost and radiation dosage. We have mesalazine. Eight patients had previously the CP level p<0l01. Serum ceruloplasmin investigated whether abdominal ultrasound undergone surgery, usually right hemicolec- is useful as a marker of activity in Crohn's can determine disease extent in IBD in tomy. Six patients continued azathioprine disease and its heterogeneity changes from comparison with 1 1 1 Indium scintigraphy. throughout pregnancy, four stopped it inactive to active disease. Eighty scans were performed in 53 patients before 16 weeks gestation and two pregnan- (12 with ulcerative colitis and 41 with cies were terminated. Pregnancy was com- Crohn's disease). The ultrasound was per- plicated in one woman by acute hepatitis B Antibody responses to selected strains of formed by an operator unaware of the 111 infection. There was one premature birth at Saccharomyces cerevisiae and Candida Indium scan result and inflamed bowel http://gut.bmj.com/ 32 weeks after elective delivery for placenta albicans in Crohn's disease recognised by thickening of the bowel wall. praevia. Five were delivered by Caesarian For analysis the bowel was divided into section. There were no congenital abnor- H MCKENZIE, J MAIN, C R PENNINGTION, AND D seven regions. Ultrasound identified 150/ malities and no perinatal problems. The 12 PARRA-lI (Departments of Medical Micro- 178 inflamed bowel regions shown by 111 children (age 3 mo-16 yr) are alive and well. biology and Medicine, Ninewells Hospital Indium scan giving an overall sensitivity of Growth and intellectual development have and Medical School, Dundee) We have 85%. There was a marked regional differ- been normal. previously found raised levels of antibody to ence in sensitivity - 97% for terminal ileum,

The study suggests azathioprine may be Saccharomyces cerevisiae (baker's yeast) in 90% sigmoid colon, 86-88% for proximal on September 24, 2021 by guest. Protected copyright. continued in pregnancy in patients with Crohn's disease but not ulcerative colitis. small bowel, descending, transverse and severe extensive IBD in whom it is neces- Although S cerevisiae is the species of yeast ascending colon, but only 43% for rectum. sary for maintenance of remission. used in both brewing and baking, individual There were nine false positives on ultra- strains are specific for each application and sound - specificity 95%. These studies show may differ antigenically. Using ELISA, we that ultrasound is a promising non-invasive Ceruloplasmin as a marker of activity in have measured IgG antibody to a repre- assessment of disease extent in lBD. Crohn's disease sentative selection of ale (three), lager (three), baking (two), distilling (two), and L D JUBY, A J LOBO, A T R AXON, E COOPER, AND wine (two) strains of S cerevisiae in patients C J SAMPSON (Gastroenterology Unit and with Crohn's disease (15), ulcerative colitis University Department of Cancer Research, (15), and normal controls (15). Antibodies SMALL BOWEL The General Infirmary, Great George Street, to the commensal yeast Candida albicans Leeds) Assessment of activity of Crohn's were also measured. Omeprazole reduces secretory diarrhoea in disease can be difficult. Reliable laboratory The results confirmed a significant some patients with the short bowel syndrome tests are needed to accompany a clinical increase in antibody in Crohn's disease (SBS) index as this may be high without active patients compared with ulcerative colitis disease. In the acute phase response patients and normal controls for 11 of 12 J M D NIGHIINGALE, E R WALKKER, W R orosomucoid (AGP), C reactive protein strains of S cerevisiae (p<0-01 for all I l ). No BURNHAM, M J G FARi'HING, AND J E LENNARD- (CRP), and ceruloplasmin (CP) are raised. such increase was detectable for antibody to JONES (St Mark's Hospital, City Road, AGP and CRP are known to correlate with C albicans. London and Oldchurch Hospital, Romford) disease activity and in certain disease states Crohn's disease patients therefore have Inhibition of gastric acid secretion may the heterogeneity of AGP and CP reflect raised levels of antibody to S cerevisiae reduce intestinal output in patients with the activity and differentiate between malig- antigen(s) commonly present in food and SBS thereby reducing the amount of fluid Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofCastroenterology A719 supplementation. We therefore studied the the study period. Median fluxes for water (Department of Gastroenterology, St effect of omeprazole in 10 patients all need- were 89 (8-188) mI/h fasting (n=6), 171 Bartholomew's Hospital, London) ing additional fluid replacement due to a (142-326) during passage of meal (n=6) and Polymeric glucose may increase efficacy high intestinal output (1.5-6.5 kg/day). 106 (105-110) after the meal (n=3). of oral rehydration solutions (ORS) by Six patients had a net secretory output Corresponding figures for sodium were 6 providing glucose at a low osmolality. The (intestinal output>oral intake) and (1-27), 14 (2-28), and 9 (7-21) mmol/h. critical size and concentration of polymer required between 1 and 5 of intravenous These results suggest that the post- required to optimise water absorption has fluid daily. Four patients were net absorbers prandial fluid loss in short bowel patients is yet to be determined. We have studied the (intestinal output

A720 The British Society ofGastroenterology

(1-10 ig; n=6) into an 'open' 30 cm test prevents mucosal atrophy that occurs on a disease rests on the demonstration of a segment and (3) intrajejunal CT (25 Fg; diet of Vivonex HN+glucose. This implies histological abnormality in jejunal biopsy n=6) into a 'closed' test segment isolated by that Efamol maintains a mucosal trophic which responds to gluten withdrawal and proximal and distal occluding balloons. stimulus that is reduced by the elemental deteriorates on rechallenging with gluten. Oral administration of CT (6-15 [tg) failed diet. Three jejunal biopsies are needed and this is to produce a secretory state. In the 'open' unpopular with patients. This paper des- segment only administration of CT 10 Fg cribes a gluten challenge using the La/Ma produced a secretory state for water which test. Twelve patients with known coeliac was maximal at three hours (-3-5 ml/cm/h). Effect of poorly absorbed solute on human disease (CD) on a gluten free diet per- The response was too variable to use as a small intestinal absorption formed a La/Ma test before, one, and five bioassay. Administration of CT (25 ig) in weeks after the ingestion of 30 g gluten daily the 'closed' system produced water secre- A P JENKINS, S MENZIES, W S NUKAJAM, C for seven days. The test solution comprised tion at 0-5 h (-0.8 (1.8)), with constant MYERS, AND B CREAMER (Depts of Gastro- 5 g lactulose and 2 g mannitol in 1()( ml secretion between two hours (-2-7 (1.0)) enterology and Chemical Patlhology, St water with 22-42 g glucose as an osmotic and 3 hours (-3-1 (0-8)). This was paral- Thomas' Hospital, London) The influence filler. This was ingested after a six hour fast leled by secretion of Na and Cl. Perfusion of of poorly absorbed solute on absorption was and urine collected for five hours. Lactulose PES in non-CT controls (n=5) produced investigated by measuring the effect of was measured by an enzymatic method and mean net water absorption (+2.6 (0.7)). lactulose on ileostomy output of ingested mannitol by spectrophotometry, the result Low dose intrajejunal administration of CT test sugars with differing absorption being expressed as a ratio of the percentage into a 'closed' system produced a reproduc- characteristics. recoveries. The median La/Ma test before ible and biologically relevant secretory Ten fasted patients (age 25-78 years) with gluten was 0-024 (range 0.0 12)-0032), after state. This may be a useful model system ileostomies ingested L-rhamnose 1 g, one week this had risen to )-052 (range with which to evaluate new antisecretory D-xylose 5 g, 3-O-methyl-D-glucose 2.5 g, 0.032-0116) p<0.0l and after five weeks therapies. and 5lCr-EDTA 50 [tCi in isoosmolar had fallen to 0.028 (range 0)008A)-068) solution. The '50% 51Cr-EDTA transit p<0-01. In all cases the La/Ma test was time' and the five hour effluent volume, normal before gluten and became abnormal osmolality, sugar, and electrolyte content after gluten. Eight returned to normal at Efamol prevents atrophy of the small were measured. Patients were retested a five weeks, the remaining four became intestinal mucosa in rats fed an elemental week later receiving the same solution+5 g normal three months later. In patients with diet lactulose. CD in remission, the La/Ma test becomes Lactulose reduced '50(% 51Cr-EDTA reproducibly abnormal on gluten challenge A P JENKINS AND R P H THOMPSON (Gastro- transit time' from 5-00 (t)81) to 2-88 and returns to normal on withdrawal of http://gut.bmj.com/ intestinal Laboratory, Rayne Institute, St (0.38) h, mean (SEM), p<0())5, and gluten. The La/Ma test is an acceptable Thomas' Hospital, London) The essential increased both five hours ileostomy effluent alternative to multiple jejunal biopsies. fatty acid rich oil Efamol is trophic to the rat volume (158-4 (28-9) to 270(6 (26-6) ml, small intestinal mucosa when substituted p<0-01) and osmolar output (51-85 (10-54) for glucose in an elemental diet given for 21 to 115-() (34.97) mmol, p<0-01), 80% days. The speed and mechanisms of this being the result of increased electrolyte. Persistent adenovirus in coeliac disease action are, however, unknown. To clarify Lactulose also increased recovery of D- these points, the time course of the effect xylose (6.7 (1.9) to 15-1 (2.4)% oral dose. M J CARTER, M M WILCOCKS, H C MITCHISON, C 0 on September 24, 2021 by guest. Protected copyright. was studied. p<0-01) and L-rhamnose (35.9 (8-2) to 57.8 RECORD, AND C R MADELEY (Departmenit of Two groups of 21 female Wistar rats (6-9)%, p<0-005) but not of 3-O-methyl-D- Virology and Gastroenterology Unit, Royal (180-200 g) were isocalorically fed liquid glucose (2.6 (1-3) to 2.6 (1.2)%O, NS). Victoria Infirmary and University of New- diets of Vivonex HN with 50% calorie Small amounts of ingested lactulose can castle upon Tyne) Because of an aminoacid substitution either by glucose (G) or Efamol impair absorption of sugars. This relates homology with gliadin and possible (EFA), giving 82 kcal/rat daily. Seven inversely to their natural efficiency of immunological cross reactivity, adenovirus animals from each group were killed at 7, absorption, being greater for L-rhamnose 12 infection has been implicated in the 14, and 21 days, the small intestines divided than D-xylose, and absent for 3-0-methyl- aetiology of coeliac disease. Adenoviruses into three equal segments and mucosa D-glucose, and is probably because of the are known to establish persistent infections, scraped off and weighed. dilution and accelerated transit that accom- and in tissue culture cell transformation Total mucosal weights/cm of the two pany osmotic retention of fluid and electro- may occur. The association of coeliac groups were similar at seven days (G 17-13 lyte in the intestine. Poorly absorbed disease with small bowel malignancy has led (1.06) v EFA 19-41 (1.48) mg/cm, means dietary solute could modify drug and us to suggest that one step in a role for (SEM) NS) and at 14 days (G 16-73 (1.25) v nutrient absorption similarly. adenovirus in coeliac disease might be the EFA 19-67 (2.12) mg/cm, NS). At 21 days, establishment of persistent infection. however, they were different (G 13-71 Endoscopic small bowel biopsies were (0.91) v EFA 17-45 (0.79) mg/cm, p<0-01), obtained from 13 coeliac patients and 13 resulting from changes in all three intestinal Gluten challenge using lactulose mannitol non-coeliac patients. DNA was extracted segments. The fall in mucosal weight for G, (LA/MA) test and probed using Southern Blot techniques though not for EFA, between 7 and 21 days with two probes: one from adenovirus 12 was statistically significant (p<0(05). L D JUBY, J ROIHWEII., ANT) A U R AXON grown in KB cells and the other from a The trophic effect of Efamol relative to (Gastroenterology Unit, The General cloned preparation of adenovirus 41 (the glucose becomes marked at 21 days and Infirmary, Leeds) The diagnosis of coeliac commonest enteric adenovirus in the New- Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A721

castle area) grown in bacteria and uncon- Non-steroidal anti-inflammatory drug on visual endoscopic criteria in 43 cases taminated with human DNA. This probe induced small intestinal strictures: radio- (95.5%) but in only 14 cases (31 1%) from also recognised adenovirus 12 DNA. This logical features barium studies alone. Radiology was technique is capable of detecting one copy normal in 22 cases where pathological of viral genome per cell. No evidence of S LEVI, I BJARNASON, G DE LACEY, A PRICE, M changes were documented (oesophageal either adenovirus 12 or 41 DNA was BURKE, M GUMPEL, AND A J LEVI (Depart- candidiasis in 21 cases) and diagnosed single detected. ments of Gastroenterology, Surgery, lesions in five cases of dual pathology. Absence of adenovirus DNA in the Radiology, Rhleumatology, and Histopath- Amongst the 40 cases with a pathological coeliac biopsies argues against persistant ology, North wick Park Hospital, Watford diagnosis endoscopy (without pathological adenovirus infection in the aetiology of Road, Harrow) Radiological features support) had a sensitivity of 97.5% and a coeliac disease. Persistent infection might in four patients are described where specificity of 100%, compared with 25% be relevant, however, in the aetiology of non-steroidal anti-inflammatory drugs and 1000% for barium studies. The differ- small bowel tumours in coeliac disease, and (NSAIDs) appear to have caused small ence between the sensitivities of the two Southern Blot analysis of such tissue for intestinal strictures. The patients had methods was highly significant (p<0(X).5). viral DNA would be the next appropriate received NSAIDs for arthritis for 1-5-15 The coexistence of oral candidiasis and investigation. years. Clinical presentation was with upper gastrointestinal symptoms in the features of malabsorption or subacute small absence of dysphagia or weight loss was bowel obstruction. Barium studies showed strongly associated with uncomplicated Serum, salivary, and intestinal IgA anti- multiple discrete jejunal and ileal strictures, oesophageal candidiasis (negative predic- gliadin in coeliac disease some representing narrow diaphragm like tive value 93%; p<0)025); these features septae encroaching on and markedly are proposed as a basis for therapy without C P KELLY, C F FEIGHERY, AND D G WEIR narrowing the lumen to as little as 1 mm in the need for further investigation, but when (Departments of Clinical Medicine and diameter. There are several important required, endoscopy is the method of Immunology, Trinity College Dublin, Eire) aspects of the radiology of these NSAID- choice. In screening for coeliac disease serum IgA induced strictures. They are often not antigliadin assay is claimed to be superior detected, and always underestimated, by to IgG assay although neither is entirely barium studies. They may be particularly Absence of gastrin inhibitory activity in the sensitive nor specific. Because coeliac difficult to appreciate because of their IgG fraction of serum from patients with disease is primarily a mucosal disorder it resemblance to the plica circularis. When pernicious anaemia seems likely that secreted, mucosal, IgA they occur in the terminal ileum, they may antigliadin may provide a more relevant easily be confused with Crohn's disease. J TI1 SMIIH, A GARNER, S E HAMPSON, AND R E measurement of gluten sensitivity than that The NSAID induced strictures, however, POUNDER (Acad Dept of Med, Royal Free http://gut.bmj.com/ obtained from serum tests. tend to be more discrete and narrow than in Hospital School of Medicine, London and Using a biotin-streptavidin based ampli- Crohn's disease, and pathologically they Bioscience Department, (1 Plharmaceuti- fication system we have developed sensitive show submucosal fibrosis but no granulo- cals, Macclesfield) Serum from patients with ELISA assays to measure IgA antigliadin in mas. Although rare, this entity should be Addisonian pernicious anaemia (PA) has serum and in secretions. Serum IgA (and considered in the differential diagnosis in been reported to contain an antibody IgG) antigliadin was markedly increased in patients on NSAIDs presenting with diarr- directed against the parietal cell gastrin untreated coeliacs (n=31) as compared with hoea or colicky abdominal pain, when a receptor. We purified IgG from 15 PA normal or disease controls (n=20 and 39, small intestinal stricture has been shown. patients and 15 healthy controls in an effort on September 24, 2021 by guest. Protected copyright. p<0.000l). Concentrations were lower in to show attenuation of gastrin specific bind- treated (n=30) than untreated coeliacs ing in vitro and inhibition of gastrin- (p<0.0001). Salivary IgA antigliadin levels, stimulated acid secretion in vii'o. by contrast, were not significantly raised in Binding of the IgG fraction was deter- untreated coeliac disease. In intestinal GASJ RODUODENAI, POSTERS mined in a radioreceptor assay utilising the aspirates both treated and untreated coeliac rat pancreatic carcinoma cell line AR42J patients had similar levels of IgA antigliadin Investigation of upper gastrointestinal which displays high affinity gastrin binding but both were significantly higher than in symptoms in patients with AIDS sites (K,=5 x "' M). In comparison with controls (n=16, 17, and 19; p<0.001). control serum, there was no significant IgA antigliadin concentrations are G M CONNOLLY, A FORBES, AND) B G GAZZARD displacement (p<0-1) of human gastrin-17 increased in both serum and intestinal (Department of Gastroenterology, St binding by the PA samples at either 0(3 mg aspirates in untreated coeliac disease. Stephen's and Westminster Hospitals, protein/mI (control mean= 1489 (131) cpm; Measurement of serum antibody levels, London) Double contrast barium radiology PA mean= 1858 (174) cpm) or 3 mg protein/ however, provides the best marker of gluten and upper gastrointestinal endoscopy were ml (control mean= 1930 (1 10) cpm; PA sensitive enteropathy (sensitivity 84%, compared prospectively on 45 occasions in mean= 2195 (1t)7) cpm). specificity 88% in this study). Serum anti- 43 patients (42 men, median age 36 years) In a perfused stomach anaesthesised rat gliadin assay is also more useful in monitor- infected with the human immunodeficiency preparation (n=83), the effect of iv injec- ing dietary adherance as antibody levels in virus who presented with upper gastro- tion of the IgG (6(-20() mg/kg) was deter- aspirates remain raised even on gluten free intestinal symptoms. mined over a 60 min period after stimula- diet. The enhanced mucosal IgA antigliadin In 40 (of whom nine had dual pathology) tion of acid secretion by iv (1 sg/kg) human antibody response of coeliac disease shows a definite pathological diagnosis was gastrin-17. There was no significant differ- site specificity as salivary antigliadin levels reached and in four no cause was found. A ence in gastrin-stimulated acid output are normal. correct and complete diagnosis was madc between control (28 (2.4) ftmolH'/h; Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A722 The British Society ofGastroenterology n= 15) and patient (29 (1.02) [molH'/h; Western General Hospital, Unit of Repro- mediastinum which produces duodenal n= 15) samples. ductive Biology, Cardiovascular Research ulceration in 45% of animals at seven days. We cannot confirm in two assay systems a Unit, Edinburgh) It has been suggested that Three days after irradiation all mice previous report (Clin Exp Immunol, 1985; the falling incidence and virulence of DU is received vincristine (1 mg/kg ip) and were 61: 315) of antigastrin receptor antibodies in directly related to increased dietary essen- killed at intervals from 3(-180 minutes the serum of PA patients. tial fatty acid consumption. We have pre- thereafter. The stomach, duodenum, small viously shown that in normal subjects bowel, and caecum were immediately gastric prostaglandin (PG) output can be removed and fixed for subsequent prepara- Deficiency of parotid salivary epidermal enhanced by dietary LA supplementation tion of histological sections. The number of growth factor in oesophagitis and gastric and this is associated with a fall in gastric cells arrested in metaphase were estimated ulceration, but not in duodenal ulceration acid secretion. in 20 well orientated crypts per section and To determine whether the diet of DU plotted against time to give CCPR in cells AN KINGSNORTH, P SMITH, AND R C RICHARDS patients is relatively deficient in LA, we per crypt per hour. Within the proximal (INIRODUCED BY 1 GILMORE) (Departments measured the adipose tissue fatty acid pro- duodenum CCPR was trebled in the ulcer of Surgery and Cell Biology, University of file of control and DU patients. Mean % group, from 7-5 (control) to 21 cells/crypt/h Liverpool, PO Box 147, Liverpool) In man, adipose LA concentration in 35 men aged (p<005 Mann Whitney U test); A lesser, the major salivary source of epidermal 21-79 (mean 45) years with proven DU non significant, rise was seen at other intest- growth factor (EGF) synthesis is the parotid was 9-4 (0.59) (SEM). That of 35 control inal sites in the ulcer group. Thus cell gland. In physiological concentrations in men aged 18-75 (mean 46.1) years with production is markedly stimulated during animals EGF leads to rapid healing of no dyspeptic history was 12*1 (0(89)% the induction phase of duodenal ulceration erosive and ulcerative lesions in the (p

The British Society ofGastroenterology A723

Compromised EGF production may be as With indomethacin, all subjects had (p<0() l) when compared with PUD important in predisposing RA patients to mucosal damage at day 1 (scores: 15 (0(2), (16.74 (1.72)), normals (17.46 (0(98)), and peptic ulceration as the currently empha- n= 10). By seven days, damage had during NSAID's therapy (23 11 (2.30)). sised drug consumption. improved (score: 0-8-402) and by 28 days After six weeks treatment with Rioprostil adaptation was complete with virtual total (n=5) or a placebo (n=5), there was a resolution of damage. PGE, levels in significant increase in mean GS activity in Endoscopic findings in the stomach and fundus (36 (11) pmollmg) and antrum (83 gastritis patients taking Rioprostil (15.94- duodenum after treatment with enteric (21)) were significantly reduced at day 1 46.33 [+290%], p<0(l) not seen in the coated and plain naproxen tablets in healthy (fundus: 21 (7), p<0e05; antrum: 30; (9), placebo group (21.39-1892, NS). subjects p<0(05) but remained reduced in both This study suggests that the aetiology of fundus and antrum at days 7 and 28 when gastritis in PUD and after NSAID adminis- E ODDSSON, H GUDJ6NSSON. AND B mucosal damage had resolved. With tration differs from NSG where mucus bio- TIHJODLEWI'SSON (National University fenbufen, there was mild damage at day I synthesis may be retarded. Rioprostil Hospital, Reykjavik, Iceland) Non-steroidal (score: 0.33 (0.21), n=6) more severe increases mucin glycoprotein biosynthesis anti-inflammatory drugs (NSAID) can damage at day 7 (score: 0(67 (0.33)) but in gastritis and although associated with injure the gastric and duodenal mucosa again, by 28 days, damage had resolved. symptomatic remission, there is no associ- through local and systemic mechanisms. Fenbufen produced similar reduction in ated histological improvement. To compare with endoscopy the effect on mucosal PGE2 levels in both fundus and Reference: the stomach and duodenum of plain and antrum (fundus: baseline=41 (13), day 1 Hawkey C. Rampton DS. Prostaglandins and enteric coated Naproxen tablets. 1=24 (9); antrum: baseline=89 (19), day the gastrointestinal mucosa. Gastroenzterologs The trial was randomised, double blind, 1=42 (14), n=6, p<0.05) but less severe 1985: 89: 1162-88. double dummy with crossover design. mucosal damage (p<0001 for damage at Twelve healthy subjects were endoscoped day 1). Again, the reduction of PGE, per- before and after two seven days treatment sisted throughout the study period. PGE, Iron deficiency anaemia (IDA) in patients periods with plain and enteric coated degradation was not influenced by either with rheumatic diseases receiving non- Naproxen tablets (500 mg). The endo- agent. steroidal anti-inflammatory drugs (NSAID). scopies were done with a Welch-Allyn In conclusion, there is no correlation Role of upper gastrointestinal (UGI) lesions videoscope and recorded on a videotape. between the severity of mucosal damage The recordings were evaluated collectively and the magnitude of PGE2 suppression by R UPADHYAY, H iORLEY, A W MCKINIAY, R D and mucosal lesions graded on a scale from these agents. Gastric mucosal adaptation to STURROCK, AND R RUSSLI (Gastro- 0-4. damage by these drugs occurs indepen- enterology Unit and Centre for Rheumatic In the stomach the mean injury score for dently of changes in PGE2 metabolism. Diseases, Royal Infirmary, Glasgow) The http://gut.bmj.com/ enteric tablets were 1 08 which is signific- presence of UGI lesions associated with antly lower than for plain tablets 2 25 NSAID therapy is frequently implicated (p<0.05). In the duodenum the mean score Effect of non-steroidal anti-inflammatory in the IDA in patients with rheumatic for enteric coated tablets was 0 33 which is drugs (NSAID's) and a synthetic prosta- diseases. An aetiological role can only be also significantly lower than for plain tablets glandin analogue (Rioprostil) on gastric established where the anaemia improves 0(58 (p<0.05). The morning concentration mucus biosynthesis after treatment of UGI lesions. We of Naproxen in plasma was significantly examined 81 patients (mean age 58 1 yr; higher after enteric-coated tablets 75 1 VAtLERIE. A POXON, K WHEATILEY, M C WINSiLETi, M= 14, F=67, smokers= 1 ) with rheumatic on September 24, 2021 by guest. Protected copyright. (75.1 [ig/ml) than after plain tablets 47.4 P W DYKES, AND M RB KEIGHLEY (Gastro- diseases (rheumatoid arthritis 73, others 8) [tg/ml (p<0)-(2). enterology Dept, The General Hosspital, and bone marrow evidence of IDA (mean Both plain and enteric coated Naproxen Birmingham) The aetiology of gastritis is Hb 8 4 mg/dl). Endoscopically 34 of 81 tablets caused considerable damage to the unknown but may be associated with peptic (41.9o%) had either ulcers (gastric 19, duo- gastric and duodenal mucosa but enteric ulcer disease (PUD) or NSAID's. In many denal three, oesophageal one) or erosions coating provides partial protection. cases there are no predisposing factors (all gastric) of the UGI tract. After treat- (non-specific gastritis - NSG). Gastritis may ment of the UGI lesions a sustained rise in occur secondary to a breadkdown in the haemoglobin (> 1.5 g/dl) was achieved in 20) Adaptation to NSAID-induced gastric mucus barrier by luminal acid, pepsin and of 34 (58 8% ) patients ( 17 of 23 ulcers; three mucosal damage: role of local PGE2 meta- ulcerogenic agents, with subsequent reduc- of 11 erosions) suggesting a definite aetio- bolism tion in mucus production. Increased mucus logical relationship. Faecal occult blood secretion after oral synthetic prostaglandin (FOB) test was available in 35 cases, UGI C J SHORROCK AND W D W REES (Department therapy' suggest it may be cytoprotective; lesion was present in six of 10 (60%) FOB of gastroenterology, Hope Hospital, Eccles the mechanism remains unclear. positive cases and 1 1 of 25 (44%) FOB Old Road, Salford) Sixteen healthy volun- Glucosamine synthetase (GS) is a rate negative cases (NS). Upper gastrointestinal teers were gastroscoped before, 1, 7, and 28 limiting enzyme in mucin glycoproteins lesions were present in eight of 19 (42%) days during treatment with indomethacin 50 biosynthesis, precursors of mucus. dyspeptic patients and 26 of 62 (41.9%) mg tds or the NSAI prodrug fenbufen 450 Glucosamine synthetase activity was asymptomatic patients (NS). mg bd. Mucosal integrity was scored (OS measured in gastric biopsies from patients Thus, a definite aetiological relationship (normal) to 4 (severe damage)) and 3 biop- with PUD n-15, NSG n= 10, patients of UGI lesions with IDA was established in sies taken from both fundus and antrum for taking NSAID's n=12 and controls n=9. only 20 of 81 (24.6%) patients. The aetio- measurement of PGE2 and PGE2 degrada- Mean GS activity (mM/g/h) in NSG (1t).37 logical role of UGI lesions has previously tion capacity. (1.08) (SEM)) was significantly lower therefore, been overestimated. There was Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A724 The British Society ofGastroenterology no association of dyspepsia with UGI patients with endoscopy-proven chronic dine had a gastric juice pH of >5.0 com- lesions. No significant difference in UGI DU were randomly allocated to a first pared with seven of eight of those taking lesions was found between FOB positive or healing course with either CBS 2 tablets omeprazole. In patients with a pH of >5.0 negative cases. (240 mg) bd (n=88) or RAN 150 mg bd the median AA concentration was 0-09 mg/ (n=92) for up to 12 weeks. After healing, dl compared with 0.55 mg/dl if the pH was patients were followed off treatment for up <5.0. Similarly, levels of total vit C werc Effect of cisapride on gastric emptying in to 18 months if asymptomatic or until 0- 18 and 1 15 mg/dl respectively. patients with previous surgery symptomatic ulcer recurrence (endoscopy Thus, if treatment increases gastric juice proven), whereupon half the patients from pH to >5 0 then AA and vit C concentra- J KREUNING, J W ARNDT, E K J PAUWELS, AND each group received the opposite treatment tions are reduced to negligible levels. This C B H W LAMERS (Departments Gastro- (second healing course) and the procedure effect depends on pH rather than agent, enterology-Hepatology and Nuclear repeated. The rapid urease test to detect although omeprazole is more effective at Medicine, University Hospital, Leiden, The antral Campylobacter pylori (CP) was done raising pH to >5 0. These findings suggest Netherlands) This placebo controlled, only in the later stages of the study. caution in the longterm use of potent anti- double blind study was undertaken to deter- Cumulative healing at one and three secretory agents. mine whether the new gastrokinetic drug months was: first course CBS 80%, 96%; cisapride enhances gastric emptying in RAN 75%, 93%; second course CBS patients with previous upper gastro- (n=48) 56%,89%; RAN (n=48) 58%, 83% Differentiation of cephalic and gastric intestinal surgery complaining of post- respectively. Cumulative symptomatic secretion phases during H2-antagonist treat- prandial epigastric fullness. On separate relapse at 6, 12, and 18 months in the first ment days 10 mg cisapride or placebo were given follow up period was similar: CBS 39%, by slow iv injection to five patients with 52%, 58%; RAN 34%, 56%, 57% respect- IH ERNST, B ZEYEN, C WILDER-SMITH, M previous distal oesophageal surgery, seven ively; but was significantly less after CBS in GENNONI, J ROHMEL, R WALI, F HALTER, AND with vagotomy and eight with partial the second follow up period: CBS 21%, H MERKI (Gastrointestinal Unit, Inselspital, gastrectomy, while nine non-operated 40%,44%; RAN 58%,63%, 63% (p<0401) Berne, Switzerland and University Hospital, patients with postprandial epigastric fullness respectively. The median time to second Birmingham) Antisecretory effectcs of H2- served as controls. Gastric emptying was relapse in patients who were CP positive receptor antagonists are limited by food. measured after ingestion of a 'Tc-labelled (n=37) and negative (n=26) after the The stimulatory role of the cephalic and pancake and the results (mean and range) second healing course was 3.8 and 4.5 gastric phase of secretion were investigated were analysed by the paired Wilcoxon's months respectively. in a placebo (P) controlled, randomised, test. In conclusion, IT as a therapeutic strategy double blind study in 12 healthy volunteers In the patients with previous oesophageal proved effective, healing being quick and (HV) using intravenous ranitidine (R) and http://gut.bmj.com/ surgery cisapride did not influence the lag about half the patients continuing in either sham-feeding or standardised food as phase but significantly enhanced the empty- symptomatic remission for > 1 year; and for secretory stimulus. Intragastric acidity was ing rate form 33 (5-39) to 44 (25-99)%/hr such treatment, CBS proved at least as measured with combined glass electrodes (p<005). In the vagotomised patients effective as RAN. and a new pH-feedback controlled micro- cisapride shortened the lag phase from 27 infusion pump (GastroJet). The effect of R (20-120) min to 10 (2-18) min (p<005) and or P on basal acidity was monitored for the increased the emptying rate from 10 (0-37) Low gastric juice ascorbic acid during treat- initial six hour period and for a further six to 47 (30-58)%/h (p<0.05). In the gastrec- ment with cimetidine and omeprazole; a risk hours with either feeding, sham feeding or on September 24, 2021 by guest. Protected copyright. tomised patients neither the lag phase nor factor for gastric cancer? continued fasting. R or P doses were con- the emptying rate was significantly affected tinuously adapted by the GastroJet pro- by cisapride. In contrast, in the non- C J SCHORAH, J N PRIMROSE, G M SOBALA, M J grammed at a target pH of 7. During the operated patients both the lag phase, SANDERSON, M ROGERS (INTRODUCED BY R I initial basal time period median pH's were from 25 (5-120) to 10 (2-120) min, and HALL) (Departments of Chemical Pathology consistently >6 in all R groups (cf placebo: the emptying rate, from 50 (0-79) to 23 and Surgery, University of Leeds, Leeds) 1-4, 1.5, or 1.55) and at least 89% (median) (0-58)%/h, were significantly (p<005) Ascorbic acid (AA), the reduced form of of pH values were >4. Under continued improved by cisapride. vitamin C (vit C) is an important scavenger fasting pH was 6.55 (6.35-6.6 interquart Cisapride accelerates gastric emptying in of nitrite in the stomach thus preventing the range) on R and 1-5 (1 2-1.5) on P. Sham unoperated patients and in those with pre- formation of potentially carcinogenic N- feeding resulted in a drop to pH 3-5 (2 75- vious vagotomy or oesophageal surgery, but nitroso compounds. The aim of this study 49) on Rand to 1 15 (1.1-1.4) on Pin the not gastrectomy. was to determine the effects of the anti- first three hour post-stimulus. In the next secretory agents cimetidine and omeprazole three hours pH resumed the level of the on gastric juice AA and total vit C. continued fasting group. Food, however, Intermittent treatment (IT) for chronic duo- Subjects were 10 patients taking part in attenuated the initial antisecretory activity denal ulcer (DU): colloidal bismuth sub- an observer blind crossover study of four of R to a lesser degree (pH 4 5 (3 95-4.8) citrate (CBS) versus ranitidine (RAN) weeks cimetidine, 400 mg bd or omeprazole and this sustained effect was even more 40 mg om in the treatment of refractory pronounced during the final three hours K D BARDHAN, S SINGH, P MORRIS, M THOMP- DU. Gastric secretory studies were per- (pH 3.0 (1.9-4.2). SON, R F C HINCHLIFFE, M GAMMIE, C BLAKE- formed before and after four weeks of The two phases of gastric secretion were MORE, AND R WALL (District General treatment. Vit C and AA were measured in clearly distinguished by the stimuli under R Hospital, Rotherham and Gist-Brocades, the gastric juice by HPLC. blockade. Food stimulation was not UK) To assess the suitability of CBS for IT, Three of six patients treated with cimeti- counteracted by R for over six hours, sham Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A725 feeding resulted in a more profound, two either placebo or sufotidine 600 mg bd. more OME patients were free of day hour secretion stimulus. All 24 h studies included simultaneous (p0.05). The used for treatment of DU, and this study tidine were 51 and 89%. On an intention-to- median time (hours) during which pH was compared omeprazole 20 mg om (OME) treat analysis, the difference between 7.5 above 3 was 9.5 for R2, 9.0 for R4, and 0 for with ranitidine 300 mg nocte (RAN) and and 30 mg was significant (p=0.001, Fisher's P1. paid particular attention to symptom relief. exact test, two-tail). AG-1749 was well on September 24, 2021 by guest. Protected copyright. More frequent administration of 150 mg Patients with endoscopically verified tolerated. Clinically significant alterations doses of ranitidine did not increase its symptomatic DU (97%-5 mm diameter) of laboratory screen were not detected. antisecretory effect. This dosage schedule were randomised to receive, double-blind, This large study documents for the first would not therefore be expected to increase OME (125) or RAN (122). These groups time a dose related duodenal ulcer healing ulcer healing rates. were comparable. After two weeks, with AG-1749 in Caucasians. For further patients were assessed symptomatically and trials in peptic ulcer disease a daily dose endoscopically. Those who were symptom of 30 mg AG-1749 om is recommended. Can a long acting H2-antagonist eliminate free and had healed ulcers left the study AG-1749 provides - similar to omeprazole 25 h intragastric acidity in man? while those remaining continued treatment - faster healing of duodenal ulcer than for a total of four weeks. ranitidine. J T L SMITH AND RE POUNDER (Academic Overall, 79% (99/125) of OME patients Department of Medicine, Royal Free and 62% (75/122) of RAN patients had Hospital, London) Sufotidine is a long healed ulcers at two weeks (p<001); at four Rebound intragastric hyperacidity after acting competitive H2-antagonist, and the weeks the corresponding figures were 91% acute withdrawal of cimetidine, famotidine, object of these studies was to determine (OME) and 80% (RAN) (p<005)). After or nizatidine is not mediated by persisting whether oral sufotidine can control intra- two weeks 77% (91/118) of OME patients hypergastrinaemia gastric acidity throughout the 24 hours. were symptom free compared with 59% Fifty nine 24 h studies were performed in (68/115) of RAN patients (p<001). C U NWOKOLO, J T L SMITH, AND R E POUNDER healthy subjects, who were dosed for one Patients both symptom free and with (Academic Department of Medicine, Royal day with either placebo or different doses of healed ulcers comprised 67% of the OME Free Hospital, London) Three groups of sufotidine. Seven duodenal ulcer patients group and 40% of the RAN group eight healthy male subjects were dosed for were studied twice, two weeks apart, on the (p<0-01). Diary cards were completed for 35 days with either cimetidine 8()0 mg, fifth day of double blind oral dosing with days 2-14 by 90% of patients. These showed famotidine 40 mg or nizatidine 300 mg at Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A726 The British Society ofGastroenterologv bedtime. They were studied on three occa- files suggest that the higher dose of R is as methodology is, however, invasive, semi- sions; before dosing (day 0), on the first day well tolerated as the standard dose. quantitative, and has hindered progress. of dosing (day 1), and on day 36 (starting 24 These results suggest that Rbid affords an We have devised a new computerised hours after the last dose of the H2-blocker). overall gain in terms of DU healing which is non-invasive quantitative test called 24 h plasma gastrin concentration and 24 h statistically significant only at four weeks. Surface Vibration Analysis (SAV), which in intragastric acidity were measured using a This schedule may be particularly advanta- this study was evaluated against radio- standard protocol. geous in special subgroups of patients. telemetry for detection of the gastric MMC Compared with day 0, every subject in 10 volunteers. Studies were carried out showed a decrease of integrated 24 hour over four hours both in the fasting phase acidity on day 1. On day 36, 20 of 24 showed New computerised method for display and and again and liquid in all subjects. Signals a rise of nocturnal acidity (median +21%, analysis ofelectronic signals from the gastro- from the SVA system and gastric radiopill range -18 to +152%; p<000(1) and 17 of intestinal (G1) tract were synchronously digitised and addrcssed 24 showed a rise of 24 h acidity (+9%; -30 to a central computer for data storage, to +62%; p<0.01). display and analysis. B E STOREY, P T CUILLEN, AND F C CAMPBEI.F. Compared with day 0, every subject (Departments of Surgery and Physics, Surface Vibration Analysis detected showed a rise of integrated 24 hour plasma University of Dundee, Dundee, Scotland) phases 11 and III of the gastric MMC in 7/10 gastrin concentration on day 1, but on day Conventional analogue tests of G6 motor fasting volunteers, with a synchronous 36 there was no significant difference in function provide very long paper chart response which was proportional in ampli- either night-time (- 1%; -44% to + 141%) records which are suitable only for semi- tude to the intragastric pressure change. or 24 h plasma gastrin concentration (+5%; quantitative manual analysis. The administration of liquid abolished fast- -35 to +67%). We have developed a microcomputer ing patterns in only two volunteers, but The modest, but significant, rise of intra- based technique for acquisition and display enhanced the SVA response to the MMC in gastric acidity observed after abrupt with- of 3-16 electronic signals emanating from the remainder. After liquid, gastric MMCs drawal of H2-blockade is not mediated by pressure transducers in the G6 tract, each were detected by SVA in all eight subjects hypergastrinaemia. digitised at variable sampling frequency with persistent fasting patterns. (typically 4 Hz), by an AID converter inter- Surface Vibration Analysis is a non- faced to an IBM-AT compatible (OPUS V) invasive test which accurately detects the microcomputer. The system allows gastric MMC after a small volume oral Ranitidine 300 mg/nocte (Rhs) v ranitidine synchronous data display during collection liquid marker. 300 mg mane and nocte (Rbid) in the treat- and after each four hour run all (864 Kb) ment of duodenal ulcer (DU): a double blind data are 'compressed' and displayed on one of http://gut.bmj.com/ multicentre endoscopic trial screen then conveniently archived onto a Electrogastrographic (EGG) study the single 1-2 Mb floppy disc. This method effects of the vagus and of cholecystokinin G DOBRILLA AND COLLEAGUES FROM 21 facilitates statistical tests of signal correla- (CCK) on gastric myoelectrical activity in ITALIAN GI UNITS (Department of Gastro- tion and allows detailed examination of any healthy adults enterology, General Regional Hospital, data segment lasting from seconds to hours. Bolzano, Italy) It has recently been shown This system has been addressed to four S ZWEEGMAN, H KLOMP. H GELI)OF, M VAN that the inhibition of both daytime and night hour radiotelemetry signals in 1 1 volunteers BLANKENSTEIN, E J VAN DER SCHEE, AND J H P time intragastric acidity induced by Rbid is in the fasting phase and then after standard WILSON (Depts of Internal Medicine and very marked (98% and 92%, respectively). liquid and solid meals. Fasting gastric and Medical Technology, Erasmus University, on September 24, 2021 by guest. Protected copyright. The aim of this double blind study carried jejunal migrating motor complexes (MMC) Rotterdam, The Netherlands) To determine out in 21 Italian GI Units was to determine were recorded (x (SD)= 18 (0.6); and 2-7 the role of CCK and the vagus on the gastric whether the Rbid schedule also produces a (1.3)) over a four hour interval. All MMCs myclectrical activity changes in response to Du healing rate superior to that induced by were recognisable in compressed form. Fed a meal, we studied the effects of CCK, Rhs. Three hundred and forty five patients atropine, and bethanechol on the EGG, with endoscopically proven DU, all patterns were similarly detected in all recorded by skin electrodes and the record- informed and consenting, were randomly subjects. ing analysed by running spectrum analysis, to or This method facilitates easy evaluation of allocated Rhs Rbid. Patients unhealed a in six healthy volunteers. The standard meal 2 an two week complex GI contraction patterns and adds induced the usual by week received additional convenient new extension to the method- postprandial frequency course of treatment. Endoscopy showed the of dip and increased power ratio. Atropine did following healing rates: (a) two weeks: Rhs ology G6 motility. not influence this response. After CCK 55 8% (86/157) v Rbid 64-2% (107/159); (b) instead of a meal no postprandial frequency second two week course: Rhs 65-6% (40/61) dip was observed, but there was a slight v Rbid 88-6% (39/44); (c) cumulative rates Non-invasive detection of the gastric migrat- power ratio increase which was inhibited by by week 4: Rhs 85.7% (126/147) v Rbid ing motor complex (MMC) atropine. Bethanechol given alone or in 96-6% (141/146). Differences between combination with CCK only increased the treatment proved to be statistically signifi- P I CULLEN, F C CAMPBELL, AND B E SIOREY power ratio in most, but not all individuals. cant (p<0.01) in (b) and (c). Healing rates (Departments ofSurgery and Physics, Nine- The power increase after CCK could with Rbid prove to be statistically greater wells Hospital and Medical School, Dundee) represent an excitatory effect on pyloric (p<0-05) than those with Rhs by both 2 and The MMC is the key to elucidation of the activity possibly inducing delayed gastric 4 in the subgroup of patients with larger complex relationship between gastro- emptying. The power decrease after ulcer diameter (:-1 cm) and/or smokers. intestinal (G1) motor activity and common atropine suggests that this CCK effect Laboratory analysis and adverse events pro- dyspeptic symptoms. Conventional may be vagally mediated. The power Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A727 ratio increase after vagal stimulation were regular smokers. After an initial half Sensation and reflex activity in oesophageal (bethanechol) suggests increased motor hour basal period, a 50% submaximal disorders activity. As none of the drugs modified or plateau was induced with a histamine mimicked the frequency dip, this is prob- infusion (16-25 nmol/kg/h, '/8 maximal), this T O'HANRAHAN, J BANCEWIC/., D G IHOMPSON, ably not mediated by either the vagus or by was continued for three hours. Half way M MARPLES, D WILI.IAMS (University Depart- CCK. through the subject smoked one cigarette. ments of Medicine and Surgery, Hope It is known that no 'fade' in secretory Hospital (University of Manchester Schzool response occurs in these circumstances. The of Medicine), Eccles Old Road, Salford) volume rate of true gastric secretion (Vg) We have previously shown that intra- Are the parietal cells of patients with duo- fell significantly after smoking: VgC 145-8 oesophageal balloon inflation elicits denal ulcers more sensitive than those of to 112-2 ml/h (23%) p<0(05, VgDU 237-6 abnormal reflexes in primary oesophageal normal subjects?' to 175-2 ml/h (26%) p<002 (Wilcoxon's motility disorders. We now compare motor rank-sum). The effects of smoking on responses and sensory thresholds in reflux J C ROXBURGH, P F WHITFIELD, AND M HOBSLEY pyloric loss and duodenogastric reflux were and primary motility disorders (PMD). (Department of Surgery, University College not significant. Thus acute cigarette causes Graded ((-3() ml) balloon distension was and Middlesex Hospital Medical School, not an apparent fall, through changes in performed in nine volunteers and 76 London) There is controversy as to whether pyloric loss or duodenogastric reflux, but a patients (reflux 32; PMD 44), after conven- the parietal cells of duodenal ulcer patients real fall in gastric secretion. This factor tional manometry. Reflux was documented (DU) have a greater sensitivity to histamine could explain the increased parietal cell by pH recording. Motor and sensory thres- than controls (C). Most investigators have mass of chronic smokers via the gastrin holds were recorded together with the type studied small numbers of patients each with feedback mechanism. of response to inflation - for example, several doses. By contrast we have studied spasm. large numbers using a 'maximal' (130 nmol/ Eight (88.9%) volunteers had a normal kg/h) after one other dose of histamine (14 peristaltic reflex in contrast to 32 (43.4%) of ,maximal', n=55, l/8 'maximal', n=18). patients (p<0)01). There was no significant Analysis (Hofstee plot) of the volume rates OESOPHAGOGAS'I'RODUODENAL POSIERS difference in the type of response between of secretion at these doses showed no patient groups. Initial stimulation of significant difference in sensitivity: the two Can oesophageal pH determine bile reflux in motility occurred at similar volumes in each calculated doses required to produce 50% Barrett's oesophagus? group. First awareness of distension occur- of the calculated maximal secretion (km red at similar volumes in volunteers and K LENDRUM, D F EVANS, C S ROBERTSON, D H with PMD (median 10 ml). Patients values) were, C=12-83, DU=12-61 nmol/ patients http://gut.bmj.com/ kg/h. Regression analysis of secretion rates TAYLOR, AND M ATKINSON (Department of with reflux were aware of distension at at fractional doses against the correspond- Surgery, University Hospital, Nottingham) significantly lower volumes (5 ml median; ing secretion rates at maximal stimulation Non-acid reflux has been implicated in the pperistalsis limit the duration patible with the theory that the parietal cells were analysed by HPLC during fasting, of gastro-oesophageal reflux? of DU patients or chronic smokers are more postprandial and nocturnal periods in order sensitive; any tendency for increased secre- to correlate the presence of oesophageal L J HANKIN, M MARPILES, AND J BANCEWICZ tion is explained by the larger parietal cell bile with its effect on pH. (University Department of Surgery, Hope mass in such patients. There was significantly higher BAC in the Hospital, Salford) The role of secondary Barrett's patients than in controls both post- peristalsis in oesophageal clearance remains prandially (Barrett's median 166 FtM controversial. We have assessed the (range 55-997) (95% CI 114-496)) (control relationship between secondary peristalsis, Effect of acute cigarette smoking upon median 17 FM (13-519) (95% Cl -46- provoked by infusion of saline and acid gastric secretion 276)) (p=0.025) and nocturnally (Barrett's during a Bernstein test, and the results of 24 median 270 FM (20-735) (95% CI 179-435)) hour pH recording. The number of second- J C ROXBURGH, P F WHITFIELD, AND M HOBSLEY (control median 11 FM (2-391) (95% CI ary peristaltic contractions was measured (Department of Surgery, University College - 128-176) (p=0-025). before and during infusion of 0()1 M HCI and and Middlesex Hospital Medical School, A significant correlation (p=0.05) was normal saline in 22 patients with docu- London) Chronic smoking is associated also seen between a nocturnal oesophageal mented reflux. with increased maximal gastric secretion. Is pH>5-8 and raised BAC at night in the The infusion of HCI and saline increased there any acute effect of acute cigarette Barrett's patients. No correlation was found the number of secondary peristaltic contrac- smoking that helps explain this phenome- between gastric pH and BAC at any time. tions in 12 patients (mean 0(1 1/min at rest; non? The acute changes in gastric secretion We conclude that a nocturnal oeso- HCI 0t65/min; NaCI 0(55/min: p5-8 may be indicative of This group had the shortest average studied in eight patients with duodenal significant bile acid reflux in patients with duration of reflux episodes (5.7 min) ulcers (DU) and eight controls (C); all 16 Barrett's oesophagus. (p<0-05) during 24-hour recording. Five Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A728 The British Society ofGastroenterology had no increase with either infusion and had pharyngeal ulcers (one died before endo- in the patient and control group at all the longest average duration of reflux scopy could be performed). but the second pH levels examined. We conclude that episodes (8.19 min). Five had an increase also had a single atypical ulcer 3x8 mm in increased activity can significantly effect the with saline and not with acid (average the mid-oesophagus. Two further patients results of pHM. duration 7-1 min). had solitary elliptical ulcers 3x8 mm and These results suggest that the initiation of 5x 15 mm respectively, whilst the remaining secondary peristalsis is important in limiting patient had multiple ulcers from 26 cm to 36 Oesophageal ulceration, NSAIDs, and the duration of episodes of gastro- cm ranging in size up to 3 x 6 mm. In all cases hiatus hernia oesophageal reflux. the ulcers were deep with irregular under- mined edges, and in two cases taking the 1 M SHALLCROSS, J I WYAI-I, AND R V HEAlLEY biopsies was very painful. Subsequent histo- (Departments ofMedicine and Pathology, St Effect of cisapride on the oesophageal pro- logical examination of the biopsies from James s University Hospital, Leeds) The use pulsive force and manometric pressure these unusual ulcers showed koilocytosis/ of NSAIDs is associated with benign oeso- waves multinucleation (five), parakeratosis phageal strictures. A number of drugs are (three), individual cell keratinisation known to cause oesophageal ulceration, but N BRIGHT, G WHELAN, AND C RUSSELL (three), and epidermal thickening (hyper- surprisingly, NSAIDs have been reported (Monash and Melbourne Universities plasia) (two). There were no features of infrequently in this context. Departments ofSurgery and Medicine, Mel- herpes simplex virus, and CMV as a cause Consecutive patients undergoing gastro- bourne, Australia) We aimed to assess the was excluded. scopy at a dyspepsia clinic were studied. effect of cisapride on oesophageal propul- These features are highly suggestive of Oesophageal ulceration (diagnosed endo- sive force as measured by a linear strain viral infection of epithelial cells and are very scopically, or on biopsies from areas of gauge transducer. similar to the histological features described oesophagitis) was found in six of 55 patients Simultaneous measurements of mano- in oral hairy leukoplakia which has not been (mean age 58 yr) who had been taking metric pressure (MP) and propulsive force previously reported in the pharynx or oeso- NSAIDs regularly within four weeks of (PF) in five normal volunteers were made at phagus of HIV positive patients. endoscopy. but in only one of 86 patients three sites - 5, 10, and 15 cm above LOS, (mean age 46 yr) who had not used NSAIDs and in response to dry 5 ml and 10 ml for over one month (p=0-03, Fisher's exact boluses before and after 10 mg iv cisapride Effect of activity on the reproducability of test). If ulceration diagnosed histologically (C). All recordings and analysis were made ambulatory intra-oesophageal pH monitor- is excluded, a significant difference remains on computer (Maclab). Pre and post C ing (pHM) with frequencies of four of 55 and none of 86 values compared by paired t. respectively (p=0.04). Three of the six MP wave - absolute p increased at all S J WALKER, S HOLT, C J SANDERSON, AND patients with ulcers in the NSAID group http://gut.bmj.com/ three sites (p<0-002) and in response to all C J STODDARD (University Department of were also taking oral prednisolone for bolus types (p<0.01); area under curve Surgery, Royal Liverpool Hospital, PO Box rheumatoid arthritis. increased at 5 and 10 cm sites (p<0.000) and 147, Liverpool) Carefully performed pHM Eight of the 55 patients in the NSAID in response to all bolus types (p<0.002). is a reproducible investigation. Clinical group had an endoscopically diagnosed PF wave - absolute F increased in 10 cm experience suggests that reflux symptoms hiatus hernia and five of these also had sites only (p<0.000) and in response to may occur more frequently with exercise. oesophageal ulceration compared with one dry and 5 ml boluses (p<00()(3); area The aim of this study was to investigate the of the 47 without a hiatus hernia under curve increased at 5 and 10 cm sites effect of activity on the reproducability of (p<0.0002). on September 24, 2021 by guest. Protected copyright. (p<0.004) and in response to 5 and 10 ml pHM. We studied 35 patients (20 men) with Patients taking NSAIDs appear to be at boluses (p<0.05). reflux symptoms, mean age 44 years (range increased risk of oesophageal ulceration, In the smooth muscle portion of the 21-70) and five asymptomatic controls particularly if they also have a hiatus hernia. oesophagus cisapride increased absolute (three men), mean age 33 years (range 21- values of MP and PF. The area under the PF 42). All subjects underwent standardised wave ('impulse' in g/seconds) is a measure pHM during normal activity at home Twenty four hour ambulatory oesophageal of 'effort'. Cisapride increased the 'effort' in (period 1). Repeat pHM was performed manometry: a new diagnostic tool the smooth muscle portion of the oeso- between five and 28 days later (mean phagus in response to wet swallows. 10) with all subjects maximising their A P BARLOW, T L NORRIS, C S BAIL, ANI) daily activity (period 2). All exercise A WAISON (Department of Surgery, Royal was recorded during both periods. We Lancaster Infirmary, Lancaster) Conven- Pharyngo-oesophageal leukoplakia in HIV examined six standard parameters of reflux tional manometric assessment of oeso- positive patients at 5 pH levels (3f-05.0) by 22 hour pHM phageal motility is based on a limited (Ormed Ltd). Statistical analysis was by the number of swallows obtained under R P H LOGAN, V S KITCHEN, R J POLSON, N D Wilcoxon's signed-rank test. unphysiological conditions. It is unclear FRANCIS, J R W HARRIS, A J PINCHING, AND J H Activity was increased in all subjects how reliable this is, especially in patients BARON (Department of Gastroenterology, during period 2 compared with period 1. who complain of intermittent chest pain of Histopathology, and GU Medicine, St Patients had more acid reflux than controls non-cardiac origin. Twenty four hour Mary's Hospital, London) Investigation of (p<005, period 1, pH<4). The results of all ambulatory oesophageal manometry was five HIV positive patients presenting with parameters were increased during period 2 evaluated in 10 patients with atypical chest dysphagia and/or chest pain revealed but this only reached statistical significance pain and two asymptomatic volunteers. atypical pharyngo-oesophageal ulceration in the patient group (pH<4). Motility was sampled at two levels in the in each. Two patients had solitary A similar pattern of results was seen oesophageal body and recording was either Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A729) automatic or could be triggered at set times benign Barrett's group with moderate or Influence of fatty acid composition of enteral or during episodes of chest pain. severe dysplasia were all Cp negative. diets on intestinal fat absorption in patients Eight patients experienced symptoms Campylobacter pylori status did not corre- with moderately impaired gastrointestinal during manometry, yielding 105 swallows/ late with the presence of acute inflammation function patients for analysis. Swallowing frequency (26.5%) or chronic inflammation (27.7%) increased during triggered events compared nor was it altered by antireflux surgery R G P REKS, W R HARK, J J PAYNE.-JAMES, AND to automatic events. Non-propagated con- (33% Cp positive postoperatively). 1) B A SILK (Department of Gastroenterology tractions became more prevalent at night, Campylobacter pylori is associated with and Nutrition, Central Middlesex Hospital, with an increase in wave amplitude. In Barrett's oesophagus. The Cp status is Acton Lane, London, and Department of patients exhibiting high amplitude or pro- always negative in association with Nutrition, Institute of Zoology, London) A longed simultaneous contractions abnor- moderate or severe dysplasia or carcinoma. recent study, in which 10 malnourished malities were more prevalent at night. patients with moderately impaired gastroin- Seven patients had gastro-oesophageal testinal function received enteral feeding reflux on pH monitoring, without abnormal with two diets whose nitrogen (N) sources motility during reflux episodes. were composed of either oligopeptides (diet Ambulatory oesophageal manometry, SMALI. BOWEI A) or whole protein (diet B), demonstrated especially with pH monitoring, is of value in no significant differences in N absorption or the diagnosis of atypical chest pain. Record- Effects of T lymphocyte activation on small balance. Although isocaloric, the two diets ings may be targetted to episodes of chest intestinal glycoprotein biosynthesis differed in their fatty acid (FA) contents pain and, in some patients, motility dis- and composition. In the present study, we orders become more prominent during J E CRABTIRE, R V HEAITIY, AND M S investigated the influences that these differ- sleep. Many patients with non-cardiac chest LOSOWSKY (Department of Medicine, St ences had on quantitative and qualitative pain have GOR without evidence of associ- James's University Hospital, Leeds) aspects of FA absorption. Diet A (Reabilan) ated motility problems, even on prolonged Evidence from animal models suggests that supplied 87-7 g fat/d, medium chain fatty monitoring. T lymphocytes can influence goblet cell acids (MCFA) 31-7%, saturated fatty acids differentiation and activated T lymphocytes (SFA) 16.7%, oleic acid 8.6%, linoleic acid have been implicated in small intestinal (LA) 36.8%, gamma linolenic acid (GLA) Campylobacter pylon and Barrett's enteropathy. We have examined the effects 2.4%). Diet B (Clinifeed 4()0) supplied mucosa: an association of prognostic of T lymphocyte activation on small 60(3 g fat/d (SFA 39.4%, oleic acid 27.0-%, significance intestinal glycoprotein biosynthesis as T LA 22-6%, negligible MCFA and GLA). cell abnormalities may well be responsible After two days of enteral feeding, five day R C STUART, R HENIHAN, J MCKENNA, N for the abnormal mucus synthesis and collections of faeces were analysed for total http://gut.bmj.com/ NOLAN, T F GORKEY, G MCEN1EE, C 0 MORAIN, release observed in coeliac disease. fat and FA content. Although total fat AND P J HENNESSY (Departments ofSurgery Endoscopic duodenal biopsies from absorption from diets A (means (SD)) (91.9 and Pathology, St James's Hospital, Dublin patients with histologically normal mucosa (7.6)%) and B (86.5 (10.7)%) was similar, and Department of Gastroenterology, were cultured in vitro for 24 hours and the absorption of MCFA (99.5 (1.4)%) was Meath Hospital, Dublin) Oesophageal incorporation of 3H glucosamine into tissue significantly greater than that of olcic plus mucosal biopsies of 153 patients in four and secreted trichloracetic acid precipitable palmitic and stearic acids (83-3 (14.2)%, groups (1) Benign Barrett's oesophagus glycoproteins was measured (DPMx 10'/mg p<0-01). LA and GLA are both essential

(n=82); (2) adenocarcinoma of the oeso- protein). Endogenous intestinal T lympho- FA. Gamma linolenic acid is the more on September 24, 2021 by guest. Protected copyright. phagus associated with Barrett's mucosa cytes were activated using the mitogenic effective precursor of the regulatory eicosa- (n= 19); (3) reflux oesophagitis (n=40); and monoclonal anti-CD3 antibody (OKT3) noids and 95-1 (8.2)% was absorbed from (4) normal subjects (n= 12); were assessed and an isotype-matched, non-mitogenic diet A. Our data indicate that MCFA and using the Warthin-Starry silver strain for the monoclonal antibody was used as a control. GLA are well absorbed from diet A in presence of Campylobacter pylori (Cp). Culture with anti-CD3 signficantly patients with moderately impaired gastro- Forty five of the benign Barrett's group increased (p<0(0l) the total incorporation intestinal function with improved balance of were complicated by stricture and/or ulcer of glucosamine into tissue and secreted energy and eicosanoid precursors compared and nine had undergone antireflux surgery glycoproteins. Mean values (SEM) for con- with diet B. before biopsy. Nineteen of the 82 benign trol and anti-CD3 stimulated cultures were Barrett's patients (23%) were Cp positive in 185-3 (14.9) and 261 (17.1) (n= 10) respec- contrast with none of the other three groups tively. Addition of cyclosporin A (15 [tg/ Controlled trial comparing a whole protein (p<0.01). Patients with complicated ml), an inhibitor of T cell activation, to anti- and an amino acid based enteral feed as sole Barrett's oesophagus were no more likely to CD3 stimulated cultures prevented the therapy for Crohn's disease be Cp positive (24.4%) (11/45) than uncom- enhanced glycoprotein biosyntheis (192.8 plicated patients (21.6%) (18/37), p=ns. (14.3), n=6). The secretion of glycopro- A H RAOUF, V HILDREY, ANI) JONA1'HAN M When assessed for the presence of dysplasia teins was significantly greater in anti-CD3 RHODES (University Dept of Medicine and or carcinoma a significant negative correla- cultures than in control cultures (p<0001). Walton Hospital, Liverpool) Enteral feed- tion between Cp status and dysplasia/ with 67% of labelled glycoproteins being ing with an amino acid based feed has been carcinoma was detected. No Cp positive medium associated after T cell activation. shown to be effective therapy for Crohn's patient had moderate or severe dysplasia or These results show that activation of T disease; one possible explanation for its carcinoma compared to 26 of 82 Cp -ve lymphocytes in the small intestine enhances efficacy has been hypo-allergenicity due to patients with Barrett's mucosa in the oeso- mucosal glycoprotein synthesis and secre- the lack of whole protein. phagus (p<0.0)1). Seven patients in the tion. Twenty one patients with active Crohn's Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A730 The British Society ofGastroenterology disease (eight ileal, nine ileocolonic, [0.1 1, 4-8 [0.81, 6-2 [151, and 13-0 [1.8] U. A P BARLOW, L R JENKINSON, C S BALL, T L and four colonic) were randomised either Our levels in 59 histologically normal NORRIS, AND A WATSON (Department of to receive amino acid based feed (E028) jejunal biopsies were: maltase 23-4 (6.9) U, Surgery, Royal Lancaster Infirmary, Lan- for three weeks followed by crossover to lactase 5.3 (3-7) U, sucrase 8 4 (3-1) U. caster) Many patients with gastro- casein hydrolysate whole protein feed The finding of adequate disaccharidase oesophageal reflux require antireflux (Triosorbon) for a further three weeks levels in a duodenal biopsy thus appears to surgery following failure of medical treat- (group A, n=11) or to receive triosorbon rule out a specific deficiency without a ment. The duration of this is arbitrary and it followed by E028 (group B, n=-1). No jejunal biopsy being required. A low would be helpful if predictive factors existed alterations in drug therapy were made enzyme level in a duodenal biopsy, to identify patients at an early stage who throughout the trial period. Activity was however, does not necessarily imply that would fail on medical treatment. assessed according to Van Hees and Bristol there will be a low level in the jejunum. Fifty patients with endoscopic oeso- simple index scores. phagitis entered a prospective trial of raniti- Fourteen patients (eight group A and six dine therapy for up to 24 weeks. They group B) were in clinical remission by six Small bowel mucosal morphology and di- underwent endoscopy, manometry and 24 weeks, one withdrew and six failed to saccharidase activity in different ethnic hour ambulatory pH monitoring before improve (three with colonic and three with groups resident in West Birmingham treatment and at eight week intervals. ileocolonic disease). Mean C reactive pro- Follow up was for a mean of 21 months. tein in responders fell from 32 mg/l (range G M WOOD, J LEEK, J KEL LEHER, J GEARTY, AND Thirty six patients (72%) were deemed to 9-82) on entry to 6 mg/I (range 3-19) at six B I COOPER (Gastroenterology Unit and have failed on medical treatment because of weeks. Seven patients relapsed within eight Pathology Dept, Dudley Road Hospital persistent or recurrent symptoms and months of starting solid food (mean 3-7 Birmingham and University Dept of oesophagitis. These patients were more months) while seven are still in remission Medicine, St James's Hospital, Leeds) Many likely to have both a defective LOS and (minimum follow up six months). normal adults living in tropical climates impaired distal oesophageal pump function. This study confirms that a remission can have small bowel mucosal abnormalities Consequently, they had greater acid expo- be achieved with dietary therapy alone in (tropical enteropathy) and low mucosal sure and more advanced grades of oeso- many patients with active Crohn's disease. lactase activity. There are no studies on the phagitis. Twenty patients who failed on The whole protein feed was equally effec- small bowel of immigrants to Britain from medical therapy subsequently underwent tive as the more hyperosmolar and more tropical countries. Distal duodenal biopsies antireflux surgery with a satisfactory result expensive amino acid based feed suggesting were taken from 30 whites, 35 Indians, and in 17 (85%o). that nutrition and low residue may be more 20 Afro-Caribbeans being endoscoped for Patients with a mechanically deficient important than hypo-allergenicity. dyspepsia. Biopsies were orientated and LOS and impaired pump function have assessed by dissecting microscopy; 4 s increased acid exposure and more severe http://gut.bmj.com/ sections were examined morphometrically. oesophagitis. These patients are likely to Measurement of disaccharidases in duo- Biopsies from 18 whites, 21 Indians, and 12 fail on medical treatment and should be denal biopsies obtained at gastroduodeno- Afro-Caribbeans were assayed for lactase, identified at an early stage, providing there scopy sucrase and maltase activity. Indian and are no contra-indications to surgery, as the Afro-Caribbean biopsies were significantly majority will have a satisfactory outcome M J GOODMAN, V LEE, G CROSSLEY, M E HERD, different from whites with respect to dis- after antireflux surgery. I J C PARFIII, AND S D K PERERA (Bury secting microscopic appearances, villous

General Hospital, Bury, Greater Man- and enterocyte height and mucosal thick- on September 24, 2021 by guest. Protected copyright. chester) Descending duodenal biopsies ness. Interepithelial lymphocyte counts How important is the role of oesophageal were obtained from 49 patients (including were significantly higher in Indians than in manometry? six with known coeliac disease and one with whites. Mucosal abnormalities in Indians Crohn's disease) being investigated for correlated inversely with the time since W J OWNEN, A ANGGIANSAH, M MCCULLAGH diarrhoea, abdominal pain, weight loss, their last visit to India. In 57% of Indians (Department of Surgery, Guy's Hospital, anaemia or folate deficiency. The histology and 83% Afro-Caribbeans. but in no London) The usefulness of oesophageal was normal in 41, showed giardiasis in one whites, studied, sucrase to lactase ratios manometry in the diagnosis of primary and showed varying degrees of villous were >4-5 indicating primary lactase oesophageal motor disorders (OMD) was atrophy in the six known coeliacs and one deficiency. No subject had lactase assessed by comparing the radiological other patient. The 42 non-coeliac patients deficiency as a result of mucosal changes. findings on barium swallow and the mano- had mean disaccharidase levels (SD) as We conclude that the small bowel mucosa of metric findings in a group of patients found follows: maltase 14-1 (6.4) U ([tmol sub- British Indians and Afro-Caribbeans differs to have OMD. strate converted per g of tissue per min), from that of indigenous whites and these In 1984-1988 481 patients presented with lactase 2-3 (2.4) U (with a bimodal distribu- groups commonly have primary lactase chest pain and dysphagia and were investi- tion around 0 and 6-0 U), sucrase 4 9 deficiency. gated firstly by barium swallow and then (3.3) U. For the coeliac patients the mean by oesophageal manometry (Gaeltec) and levels were: maltase 6-7 (5-3) U, lactase 0.6 24 hour ambulatory pH monitoring (0.7) U, sucrase 2-1 (2.0) U. Proximal (Synectics). Eighty six patients (18%) were jejunal biopsies obtained v'ia the Crosby found to suffer from primary OMD and capsule in six of the patients with lactase OESOPHAGUS were classified on the basis of oesophageal levels below 2-0 U gave jejunal lactase manometry. There were 27 patients with levels (corresponding duodenal levels in Can failure of medical treatment be pre- achalasia and barium swallow gave the square brackets) of 0 1 [0.4], 1.0 [0.21, 3.1 dicted in gastro-oesophageal reflux? correct diagnosis in 19 of these (sensitivity= Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A731

70%). There were 48 patients with either C S ROBERISON, B A B MARTIN, AND M maximum two years: symptom free at death diffuse oesophageal spasm or nutcracker ATKINSON (Department of Surgery, from unrelated cause). Even in advanced oesophagus and barium swallow was correct Univ,ersity Hospital, Nottingham and disease laser therapy was useful in short in 26 (sensitivity=54%0). There were 11 Department of Virology, Queen Elizabeth lesions and for overgrown tubes. Longer patients with scieroderma and radiology Hospital, Birmingham) To investigate the lesions had a more variable response and was correct in seven (sensitivity=64%). In possibility that achalasia may be caused by intubation was required in five subjects. the whole group barium swallow examina- neurotropic viral damage to the oeso- tion had a sensitivity of 60% in the diagnosis phageal myenteric plexus sera from 58 of primary OMD. patients and 40 controls were examined for Thus if reliance was put on barium evidence of varicellazoster virus (VZV), swallow examination, the diagnosis of cytomegalovirus (CMV). or herpes simplex GASIRODUODENAL 11 primary OMD would be missed in 40% of one virus (HSV) infection by a complement patients subsequently diagnosed mano- fixation test. Viral serology was positive in Evaluation of methods for detecting metrically as having OMD, and in 7% of the 37 of the 58 patients (63-8%) with achalasia Campylobacterpylori whole group presenting with chest pain and (23 HSV; 19 CMV; 16 VZV) and 19 of the dysphagia. 40 (47-5%) control sera (13 HSV; 11 CMV; M J WEBBERLEY, N HUDSON, P lOWE, J GEARIY, one VZV) but only for VZV was positivity B 1 COOPER, AND V MELIIKIAN (Departments of significantly greater in the achalasia group, Gastroenterology, Microbiology, and Histo- (X2 8 72; p<0.AV05). pathology at Dudley Road Hospital, Does diagnosis of an oesophageal disorder Using in situ hydridisation. oesophageal Birmingham) Campylobacter pylori has improve outcome in patients with non- tissue from nine patients and 10 controls been implicated in the pathogenesis of cardiac chest pain? was examined for HSV, VZV, and CMV antral gastritis and chronic peptic ulcera- nucleic acid. Varicellazoster virus nucleic tion. Several methods have been described J S DE CAESTIECKER, G M BRUCE, AND R C acid was identified in the oesophageal tissue to identify the presence of organisms on HEADING (Department of Medicine, Royal of only one of the nine patients compared gastric mucosa. We have compared the Infirmary, Edinburgh) Postal question- to none of the 10 controls (NS) and no sensitivity of six existing methods, rapid naires were sent to 94 patients with chest evidence of HSV or CMV infection was urease test, Clotest (Delta West Ltd), pain and normal coronary arteriograms and obtained in any tissue samples. acridine orange stain, Gram stain, to their general practitioners. Forty two This study provides only limited support histology, culture, and a newly described (group A) had not undergone oesophageal for the view that VZV, CMV, or HSV are test, diffusion interference contrast micro- manometry or pH tests. Of the rest, the involved in the aetiology of achalasia of the scopy (DIC), on brushings and biopsies oesophagus was normal in 21 (group B) and cardia. taken from the antrum. The presence of http://gut.bmj.com/ abnormal in 31 (group C). All were told Cpylori was established when three or more they had normal hearts; group C patients methods of detection were positive in an were also told their pain was oesophageal. Using the Nd-YAG laser in oesophageal individual patient. Over 90% returned questionnaires. Age, carcinoma: the short, the long, and the Fifty nine patients were studied, 45 were sex distribution and proportions with intubated positive for C pylori (19 antritis, 26 peptic anginal or atypical pain were similar. In all ulcer). Antral brushings (94%) were con- groups, 90% still complained of chest pain. D W BUlI.MORE, C WALL, AND K J A sistently more sensitive than antral biopsy This was unchanged or worse in 46%, 60%, MILOSZEWSKI (St James's Hospital, Leeds) (85%). Rapid detection methods (Gram on September 24, 2021 by guest. Protected copyright. and 46% in groups A, B, and C respectively Forty one patients with very advanced stain (97%), rapid urease (93%)), and (ns). Similar proportions (A: 59%, B: 50%, oesophageal carcinoma were treated with Clotest (89%), were more sensitive than and C: 53%) continued to have time off laser therapy. Half were over 75 years old culture (68%) or histology (80%). work or had given up employment. In group (age range 39-92). Half had had previous Diffusion interference contrast microscopy C, fewer patients (33%) believed they had surgery (10 intubation/dilatation, eight was a rapid and relatively sensitive method heart disease compared with A (44%) and B surgery, three DXR). Eleven had long of detection (86%). (45%), but more were undecided (C: 53% v lesions (>10 cm) and eight overgrown In conclusion, our results suggest that A: 12% and B: 30%; p<0-003). Fewer GPs tubes. Short lesions rapidly improved (one Gram stain and rapid urease test performed felt that pain was cardiac in group C (30%) v to two sessions) so that an adequate solid or on antral brushings are the methods of A (48%) and B (35%) while more felt it was soft-solid diet could be taken but recurrent choice for detecting C' pylori and draw oesophageal in C (68%) v A (15%) and B therapy (3)0006000 joules/session) was attention to the lower sensitivity of culture (20%; p<0-001). Thus, although most GPs required every three to six weeks. Over- and histology. accepted an oesophageal source of pain in grown tubes could be effectively cleared group C patients, four fifths of the patients (although one ignited) but in some did not. pharyngeal dysfunction caused persisting A new angle on campylobacter Diagnosis of an oesophageal abnormality distressing dysphagia and inhalation. In did not improve functional outcome. This long lesions, the anorectic and cachectic J M MARRERO, R T SPYCHAL, P M GOGGIN, C U may be explained by the poor perception by technical patency did not always result in YU, C M CORBISHLEY, S H SAVERYMUTTU, AND the patients of their diagnoses. improved nutritional intake. Intubation is a 1 C NORTHFIELD (St George's Hospital suitable alternative in those not improving Medical School, London) We have shown after three or four laser sessions and those that human gastric mucosa forms a high Possible role of herpes viruses in the with little intraluminal tumour. Survival contact angle with aqueous solutions, aetiology of achalasia of the cardia was generally short (a third at three months, indicating a hydrophobic lining which may Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A732 The British Society ofGastroenterology be important in mucosal defence. Hydro- NUD) were CP negative, mean age of 42, 10 associated with an increasing frequency of phobicity is reduced in peptic ulcer disease. men and 12 women. Patients positive for CP duodenitis. Though Campylobacter pylori (CP) is had median PGE2 of 44, PGI2 of 24, and strongly associated with peptic ulcer, the thromboxane (TXB2) of 34 ng/mg protein, mechanism by which it might lead to ulcer- compared with PGE2 of 35 (p=0. 14, Mann- Campylobacter pylon and soluble gastric ation remains unclear. Whitney test), PGI2 of 15 (p=0.11), and mucus in peptic ulcer disease Our aim was to test the hypothesis that TXB2 of 33 ng/mg protein (p=0- l ), in CP CP is associated with a reduction in gastric negative patients. The differences remained P [ESSARO, F DI MARIO, F VIANELI-O, P L DAL mucosal hydrophobicity even in the absence insignificant after sub-group analysis of GU SANTO, F FARINATrI, AND R NACCARATO (Dept of peptic ulcer. We studied gastric mucosa and NUD patients. Twenty CP positive of Gastroenterology, University of Padua, obtained from non-ulcer dyspeptic patients patients had moderate/severe gastritis Padua, Italy) Campylobacter pylori (CP) (n=56) at diagnostic endoscopy. Contact histologically, against eight CP negatives has recently been proposed as a casual angles (CA) of saline drops were measured (p2-5 had GM. Within each mucus. endoscopy being normal or showing minor sex, GM showed no correlation with alcohol erythema, and with a normal abdominal consumption or smoking. Peptic duodenitis ultrasound. Analgesics, antibiotics, or anti- was present in 0/379, 3/76, 12/23, and 24/40 Inappropriate 24 hour hypergastrinaemia in ulcer agents were not allowed. Patients patients with GM involving none, <5%, asymptomatic C pylori infection were regrouped according to their CP status 5-20% and >20% of the surface epithelium as determined by histology and bacteriology respectively. CP were present in 28 biopsies J T L SMITH, R E POUNDER, D J EVANS, D Y on biopsies taken from the gastric antrum all with >5% GM and duodenitis. GRAHAM, AND D G EVANS (Acad Dept ofMed, and body. Twenty six (16 GU+10 NUD) Small foci of GM are acquired, common Royal Free Hospital School of Medicine, were CP positive, mean age of 40 years, and randomly distributed in the proximal London and Digestive Disease Section, nine men and 17 women; 22 (6 GU+ 16 duodenum. Increasing duodenal GM is Veterans Admin Med Centre, Baylor Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A733

College of Med, Houston, Texas, USA) Similarly dysmotility type symptoms associated gastritis in children. Effect on Simultaneous 24 h intragastric acidity and (nausea, easy satiety, bloating and belch- serum pepsinogen I (PG 1), gastrin, and IgG 24 h plasma gastrin concentration were ing) were equally distributed between both antibody titres measured in 80 healthy subjects. The sub- groups. A previous study found a slightly jects were all male students aged 19-24 increased incidence of heartburn in CP+ G ODERDA, D VAIRA, J HOI ION, C AINI EY, [) years, who had no history of peptic ulcera- patients: we found no associations with DELIOLIO, AND N ANSAIDI (Dept of Gastro- tion and were free from dyspepsia. All heartburn or acid regurgitation. The only enterology, Paediatric Section, University of had a normal physical examination, haema- significant finding was that NSAID inges- Turin and Dept of Gastroenterology and tology, and biochemistry profile. On the tion was commoner in the CP+ group Microbiology, The Middlesex Hospital, day of the study no subject received any (24.7% v 9.2%; p=0 004). We conclude London) The association between CP and form of antisecretory medication. An that in the absence of ulcer disease, infec- gastritis has also been described in children. aliquot of gastric contents was aspirated tion with C pylori does not give rise to a Thirty two children (20 boys, 12 girls, mean hourly via a nasogastric tube, and acidity clinically distinct syndrome. age 12 years, range 6 to 18 years) with non- measured using a glass electrode. Venous specific abdominal pain, and gastritis CP blood samples for plasma gastrin concentra- positive underwent to six week course of tion were taken hourly from 08-24((X) h and Adjuvant metronidazole improves eradica- amoxycillin (50 mg/kg) and tinidazole (20 two hourly from 02.0800 h. One sample of tion of Campylobacter pylori in duodenal mg/kg). Endoscopic biopsies were per- blood was frozen at -20°C until later blind ulcer treated with colloidal bismuth sub- formed from the antral mucosa and after analysis for IgG antibody to C pylori, citrate overnight fasting blood samples were taken measured by a sensitive and specific sero- for the determination of serum PG 1, gastrin logical test (Evans et al, Gastroenterology, T O'RIORDAN, A TOBIN, S BEAT[IE, E SWEENEY, and IgG antibody to CP in all the children in press). C KEANE, AND C O'MORAIN (Dept of Gastro- before treatment and after one month stop- Five of the healthy subjects had serologi- enterology, MeathlAdelaide Hospitals and ping the therapy. Thirty children (94%) cal evidence of an infection with Cpylori: 75 Depts of Histopathology and Microbiology, were cleared of CP and gastritis was healed were negative. The median 24 h intragastric Trinity College, Dublin, Ireland) Persist- in 27 (84%) children and improved in the acidity was 843 mmol.h/l (range: 274-1393) ence of Campylobacter pylori (CP) after remaining five, one month after treatment. for negatives and 654 mmol.h/l (range: 527- duodenal ulcer (DU) healing is associated IgG antibody titres, serum PG I and Gastrin 850) for positives (p=0.079). The 24 h with high rates of ulcer relapse. We com- were significantly decreased after the treat- plasma gastrin concentration was 199 pmol/l pare a number of adjuvant antibiotic ment (p<0-001 respectively). (87-918) for negatives and 398 pmol.h/l regimens designed to achieve optimal CP This study shows the efficacy of combined (range: 354-2254) for positives (p<0001). clearance in patients with DU and an associ- amoxycillin and tinidazole in eradicating CP C pylori-infected healthy subjects have a ated CP positive antral gastritis. as well as healing gastritis, and confirms the http://gut.bmj.com/ significantly raised 24 h plasma gastrin con- All patients had two antral biopsies reliability of IgG antibody titres in evaluat- centration which is inappropriate for their performed before treatment which were ing the response to treatment in children as acidity - an abnormality previously seen in assessed for histological evidence of has already been shown in adults. peptic ulcer patients. gastritis and independently for CP status using Gram stain, culture and Warthin- Starry stain. The patients were allocated to High success rate for eradication of Campy- C pylori is not associated with a distinct five treatment groups. All patients received lobacter pylori infection using a colloidal dyspeptic syndrome colloidal bismuth subcitrate (CBS) 120 mg bismuth subcitrate (CBS) metronidazole on September 24, 2021 by guest. Protected copyright. qid for four weeks. Endoscopy and antral combination G M SOBALA, M F DIXON, AND A T R AXON biopsy were performed four weeks after (Gastroenterology Unit and University finishing treatment. The groups were (1) no J WEIL, G D BELL, P GAN I, P JONES, J TROWELL, Department of Pathology, The General antibiotics n=23; (2) amoxycillin 500 mg tid AND G HARRISON (Departments of Medicine, Infirmary, Leeds) It has been speculated for seven days n= 18; (3) metronidazole 200 Histopathology, Medical Physics and Phls that Campylobacter pylori (CP) may cause mg tid for seven days n=23; (4) metronida- Laboratory, The Ipswich Hospital, Heath symptoms in some patients with non-ulcer zole 400 mg tid for seven days n=20; and (5) Road Wing, Ipswich) Marshall et al (Lancet dyspepsia. We attempted to identify a metronidazole 400 mg and amoxycillin 500 1988; ii: 1437) recently showed that in symptom complex associated with CP in mg tid for seven days n=20. C pylori positive patients a CBS/tinidazole such patients. Three hundred and sixteen Groups 4 and 5 had significantly higher combination eradicated 770% of infections. patients attending an open-access dyspepsia clearance rates of CP than groups 1-3 The duodenal ulcer relapse rate after 12 clinic were given a symptom questionnaire, (p<0-05). We did not benefit a significant months was 21% in patients rendered and CP status was assessed histologically benefit from adding amoxycillin to metro- C pylori negative compared with 84% in from two antral biopsies. Two hundred and nidazole 400 mg tid. No significant anti- those in whom the infection persisted. fifty one questionnaires were returned. The biotic toxicity was encountered during the We have done metronidazole sensitivity questionnaire was able to clearly identify study. tests on 194 C pylori isolates from endo- different symptomatology between the 65 We recommend that metronidazole 400 scopically obtained antral biopsies over the ulcer and 186 non-ulcer patients. In the non- mg tid be used as adjuvant therapy in last 18 months and found 80.4% to be ulcer group, 77 were positive for CP. An duodenal ulcers treated with CBS. sensitive. We have tested 34 patients, whose increasing frequency of CP positivity with C pylori isolate sensitivity was known, with age was confirmed. Ulcer like symptoms CBS (de-Nol - Brocades) - either two (nocturnal pain and relief by food) were, Combined amoxycillin and tinidazole for tablets bd (n= 19) or 5 ml liquid qds (n= 15) however, no commoner in the CP+ group. eradication of Campylobacter pylon (CP) for 28 days in combination with metronida- Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A734 The British Society ofGastroenterology zole 400 mg tds for the first two weeks. The Value of postoperative contrast radiology in Hooded-Lister rats with and without treatment was well tolerated. When the assessment of colonic and colorectal omentectomy. Animals received intra- C pylori status was re-assessed one month anastomotic integrity luminal (IL) injections of 10P MC28 tumour after completing treatment (Lancet 1988; ii: cells or intraperitoneal (ip) injections of 10` 1245) 29/34 (85.3%) were no longer A M AKYOL, D J GALLOWAY, J R MCGREGOR, W R MC28. Animals were killed at 16-18 days infected. The eradication rate of the 32 MURRAY, G BELL, B A SUGDEN, J LOGIE, AND after injection. With IL injection tumour patients known to have metronidazole W D GEORGE (Departments of Surgery, West- occurred at the anastomosis and the sensitive C pylori infection, before treat- ern Infirmary, Glasgow, Inverclyde Royal omentum in 38% and 41 % of animals ment, was 90.6%. Hospital, Greenock, Crosshouse Hospital, respectively in the control group (n=36). Colloidal bismuth subcitrate was well Kilmarnock, and Raigmore Hospital, Inver- After omentectomy (n=35) the values were tolerated and cheaper than the CBS/ ness) The prognostic significance of a 14% and 9% (omental remnant) respect- tinidazole combination used by Marshall et radiological leak from a left colonic or ively (p= 0.02). With ip administration, al (see above) and ought, similarly, to be colorectal anastomosis in predicting a clinic- tumour occurred in 58% of control animals effective in reducing duoudenal ulcer ally detectable anastomotic dehiscence is (n=28) at the anastomosis and in 85% in the relapse in Cpylori positive patients. not clear. The relative safety of radiological omentum compared with 20% and 29% (in assessment has not been established either omental remnant) after omentectomy and may depend not only on the technique (p=0 02). but also the timing of the examination. In this model we have demonstrated a Within the setting of a prospective random- reduced ability of an anastomosis to support COLORECTAL ised comparison of suturing and stapling 'seeded' tumour after removal of the techniques this study set out to examine the omentum. We suggest that the develop- A trial of three v six day haemoccult screen- predictive accuracy of limited contrast ment of local recurrence from peri- ing for colorectal neoplasia radiology after 233 elective and emergency operatively spilled tumour cells may left colonic or colorectal anastomoses. be enhanced by, or dependent on, the W M THOMAS, G PYE, C MANGHAM, AND J D Radiology was carried out between post- proximity of the omentum. HARDCASTE (Department ofSurgery, Univer- operative days 4 and 14 with a median of sity Hospital, Nottingham) Haemoccult postoperative day 7. Twenty three patients (HC), a faecal occult blood test, detects 56- developed clinical evidence of anastomotic Totally stapled abdominal restorative 81% of asymptomatic carcinomas when leakage (9.8%). Forty patients (17 1 %) had proctocolectomy: a retrospective compari- performed over three days. In known radiological leaks and in 28 of these (12%o) son with the sutured technique colorectal cancer patients, it's sensitivity for there was no clinical leak. Thus in the http://gut.bmj.com/ neoplasia is increased by extending the test detection of clinically significant anasto- W A KMIOI, K HOSIE, J Al.EXANDER-Wit.LIAMS, period to six days. We have compared three motic leak postoperative contrast radiology AND M RB KEIGHLEY (Th2e General Hospital, and six day testing in a screening study of yielded figures for sensitivity, specificity, Birmingliam) The advent of stapling techni- asymptomatic individuals. and overall accurary of 52%, 86.6%, and ques has decreased operative time, enabling Thirty five thousand one hundred and 83.2%. The predictive accuracy of a nega- more patients to undergo sphincter saving eighty four age/sex matched individuals tive contrast study was 94.3% while the surgery. We have performed 20 totally were randomised to receive HC over three predictive value of a postive result was only stapled restorative proctocolectomies using or six days. Ten thousand one hundred and 30%. In three cases the contrast enemas a J pouch, comparing hospital morbidity seventy six (57 8%) of 17616 offered three were followed within a few hours by signs with the 20 previously sutured J pouches. on September 24, 2021 by guest. Protected copyright. day HC, and 9461 (53.8%) of 17 568 offered and symptoms of a clinical leak. Age and sex distribution was equal: 28 (16- six day HC completed the tests, a signific- We conclude that postoperative contrast 60 years)* stapled v 28 (11-62 years)* antly lower compliance (p<0-001). enemas rarely give information of any sutured (11 women in each group). An One hundred and thirty one (1 29%) of immediate clinical importance and may well operative loop ileostomy was used in five of the three day HC were positive, signific- be hazardous. the stapled group and 14 of the sutured antly fewer than the 160 (1.69%) positive group. Operating time was shorter in the after six day HC (p<002). Investigation of stapled group: 155 (12(-190 minutes)* than these revealed 20 carcinomas (1. 14/1000 Importance of the omentum in the develop- the sutured group: 220 (17(-300 minutes)* offered, and 1-97/1000 completing the test) ment of intraperitoneal metastases p<() 05**, as was length of hospital stay: 14 in the three day group, and 24 carcinomas (12-104) stapled v, 21 (12-56) sutured (1.37/1000 offered and 2-56/1000 complet- R LAWRANCE, A COOPER, M lOIZIDOU, P p<0.0)5**. There were three operative tech- ing the test) after six day HC (NSD). Al EXANDER, AND I IAYLOR (University nical failures in the stapled group, leading One hundred and twelve adenomas in 76 Surgical Unit, Southampton) Areas of to sutured pouch construction. Early persons were detected after three day HC trauma are preferred sites for metastatic morbidity included excision of one pouch in (4.31/1000 offered and 7-47/1000 complet- tumour growth, and this is thought to each group for ischaemia and a further ing the test). One hundred and twenty three account for the development of local recur- three* patients (stapled group on steroid adenomas in 83 persons (4.72/10()0 offered rence after gastro-intestinal surgery for therapy)* having an ileostomy raised and 8-77/1000 completing the test) were malignancy. In extensive intra-abdominal because of pelvic sepsis. All patients with- detected after six day HC (NSD). recurrence the omentum is invariably out an ilcostomy in the stapled (n= 12) and Extending the test period does not involved. We have investigated the import- sutured (n=5) groups were continent by day significantly increase the yield of neoplasia ance of the omentum in the development of with two patients in each group experienc- in HC screening, but decreases compliance tumours at sites of intra-abdominal trauma. ing soiling at night. Frequency of defeca- and results in a higher rate of colonoscopy. Colonic anastomoses were performed on tion was similar by day: 6 (5-9)* stapled l} 6 Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A735

(4-8)* sutured and by night I ((03)* stapled although all had non-specific histological mum increase in Al occurred 20 min after v (0(2)* sutured. All patients could defer inflammation. Microbiology uncovered a FD in both studies and was significantly defecation comfortably for 30 minutes cause of diarrhoea in 17 (cryptosporidium (p<0.05) higher with ranitidine compared despite fluid stool, the above data confirms nine, giardia and campylobacter six, to placebo (835 (150) mmHg/min v 517 the similarity of early functional result in atypical mycobacteria two); rectal histology (160)). both groups. *Median range, **Mann- in 17 (CMV colitis nine, HSV one, Kaposi's The cephalic phase of the colonic Whitney U Test. sarcoma six, and non-Hodgkin's lymphoma response to food is not secondary to one). Three had CMV and crypto- increased gastric acid output. Indeed, the sporidium. Sigmoidoscopic appearances presence of gastric acid may be inhibitory. Successful restorative proctocolectomy were abnormal with macroscopic inflamma- is related to reduced pouch activity on tion or Kaposi's sarcoma in all these ambulatory manometry patients except those six with crypto- Anismus does not adversely affect the out- sporidiosis as their only pathogen. Colono- come of colectomy and ileorectal anastomo- R MILLER, D C C BARTOLO, W ORROM, AND N J scopy provided additional information in sis for slow transit constipation MCC MORIENSEN (University Department of only one individual with CMV ulcers of the Surgery, Bristol Royal Infirmary, Bristol) transverse colon and barium enema was G S DUiHIE, D[C C BARIOLO, R MILL ER, N J M(C High pressure ileal contractions have been abnormal in only seven patients (three of MOR'FENSEN, AND) J VIRJ.FF (University associated with poor function after ileal J nine with CMV, two of seven with KS and Department of Surgery, Bristol Royal pouch construction. We measured ambula- two of six with giardiasis and campylo- Infirmary, Bristol) To determine whether tory anal and rectal pressures after ileoanal bacter) and in no case provided additional anismus adversely influences the outcome W pouches in 15 patients (age 42 (28-52). 12 information. of colectomy and ileorectal anastomosis men, three women) and compared them Neither barium enema or colonoscopy (IRA) for slow transit constipation (STC) with 15 normal controls (age 52 (29-80), 10 add usefully to rigid sigmoidoscopic biopsy we analysed the results after the procedure men, five women). and stool microbiology in HIV positive in 30 patients. Preoperative proctography Mid-anal sphincter (SP) and 'rectal' patients with diarrhoea. or electromyography demonstrated pressures (RP) were measured with a anismus with failed evacuation of contrast micro-transducer catheter for 2 7 hours. in 50%. The remainder showed normal The signals were digitalised and recorded in Cephalic phase of the colonic response to inhibition and evacuation of contrast. Sixty a portable electronic memory for later com- food is not secondary to increased gastric five per cent failed to spontaneously puter display, and analysis. The system acid output evacuate a rectal balloon. Follow up was for allowed the study of patients with minimal a median of 2 25 years (range 0(8X4.9). Two http://gut.bmj.com/ constraints and whilst fully ambulant. J ROGERS, ANA H RAIMUNDO, AND J J patients have since been converted to ileos- Compared with the highly dynamic MISIEWICZ (Department of Gastroenterology tomies for incontinence. The median stool nature of the anorectum in normal control and Nutrition, Central Middlesex Hospital, frequency is 2 5/day (range 1-10). Only patients the W pouch patients had very little London) To determine whether the three have stool frequencies of greater than activity. The sensation of pouch filling was cephalic phase of the colonic response to three/day. Sixty five per cent of patients always associated with multiphasic pouch food was related to gastric acid secretion have occasional pain or bloating although contractions with rises in pouch pressure of eight normal subjects (one female, mean only 20% with regularity. No patients con- >20 mmHg. One patient with minor noc- age 20(6 yr (0.7) SD) were studied on two tinued their laxative use. Ninety per cent of turnal soiling demonstrated frequent high occasions. Subjects took ranitidine 12()( patients were very happy with the outcome on September 24, 2021 by guest. Protected copyright. pressure pouch contractions (>35 mmHg, mg, or placebo in four divided doses 14 h of surgery (even those converted to ileosto- frequency > 1 per hour). before study. Order of medication was mies). Although half the patients exhibited The results suggest that ileo-anal W randomised. Colonic pressures were anismus on their preoperative proctograms pouches are generally quiescent and that measured with a four lumen perfused tube and 65% failed to pass a rectal balloon this incontinence in this group is related to high assembly in the unprepared sigmoid colon. finding did not influence the outcome. pressure pouch contractions. After a 30 min basal period food discussion We conclude anismus is not a contraindi- (FD) was used as a cephalic stimulus for cation to colectomy and IRA in STC. 30 min. Pressure records were computer Value of barium enema and colonoscopy in analysed in 10 min epochs for activity index HIV positive patients with diarrhoea (Al=area under curve) for the study seg- Rectopexy is an ineffective treatment for ment (sum of all four channels). Constant obstructed defecation G M CONNOLLY, ALASTAIR FORBES, AND BRIAN gastric aspiration by NG-tube was done in GAZZARD (Departments of Medicine, St ranitidine studies to measure gastric acid R MILLER, W J ORROM, D C C BARTOLO, N J MCC Stephen's and Westminster Hospitals, output and sham-aspiration with intermit- MORTENSEN, AND A M ROE (University London) The value of double contrast tent 1 ml samples to measure gastric pH in Department of Surgery, Bristol Royal barium enema and colonoscopy was com- the placebo studies. Acid output was com- Infirmary, Bristol) The symptoms of pared to rigid sigmoidoscopy, rectal biopsy, pletely blocked with ranitidine in contrast to obstructed defecation have been attributed and microbiological examination of stool the acid pH of placebo. In ranitidine studies to rectal intussusception so rectopexy has specimens in 58 HIV infected patients with total AI during FD period (30 min) was been advocated in the surgical manage- diarrhoea (three liquid motions/day >one significantly (p<0.04, paired t test) higher ment. In this study, patients with obstructed month). than basal (2313 (473), mean (SEM) defecation underwent manometry and No cause was found in 26 (17 with HIV mmHg/min v 1189 (296)) in contrast with proctography before and after rectopexy. constitutional disease rather than AIDS) placebo (1315 (397) v 879 (267), NS). Maxi- Seventeen patients (16 women and one Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A736 The British Society ofGastroenterology man, mean age 51.6 years) were studied. incremental volume (AV=maximum toler- ERCP in acute biliary pancreatitis Eleven underwent anterior and posterior ated volume-volume of first sensation; cc) fixation of the rectum and six had posterior from 50 (16) to 243 (47) cc (p<0.05). This G I BELL, R J C SiEELE, S C S CHUNG, J W C fixation only. Preoperatively five patients effect was only found in group B. I.EUNG, AND A KC Li (Combined Endoscopy demonstrated rectoanal and six rectorectal We conclude that, by an increase of Unit, Prince of Wales Hospital, SSliatin, NT intussusceptions. Fifteen had significant incremental anal pressure and incremental Hong Kong) ERCP was undertaken in 140) pelvic descent. No significant change in rectal volume, posterior rectopexia offers a patients with acute biliary pancreatitis (45 maximum resting pressure (MRP), maxi- 75% chance of regaining full continence, an men, 95 women). Mean age was 58 years mum voluntary contraction (MVC), pelvic additional 10% of improvement, and a 15% (range 2(-93). Forty six patients had urgent descent (PD), or anorectal angle was seen chance of stabilisation of partial faecal ERCP (within 72 hours) and 90 early ERCP postoperatively. In the initial follow up, incontinence. (3-30 days). Forty four patients had CBD many patients had significant amelioration stones with no significant differences in of symptoms. On longer follow up, however detection with urgent v early ERCP. Seven- (mean 13-4 months), only two had longterm teen cases of CBD stones were associated improvement. The remainder had a poor with GB stones and five with IHBD stones. clinical result in spite of complete resolution PANCREATICOBIL IARY AND INFLAMMATIORY Twenty two other patients had parasites in of rectal intussusception. Many reported a BOWEL DISEASE the biliary or pancreatic ducts. worsening of symptoms as reflected by an ES was performed in 35 patients in whom increase in tenesmus and stool frequency Acute phase protein responses during prog- bile duct stones were seen at ERCP, and (preop 12 stools/week, postop 27/week) nostically severe acute pancreatitis and their stone extraction was achieved in 33. ERCP (p<005 Wilcoxon's signed-rank test for modification by high volume fresh frozen failed to show the biliary tree in 14 cases and pairs). In the two cases with a satisfactory plasma therapy the PD in 21 (no difference between severe result, both could empty the rectum com- v mild disease). Filling of the PD had no pletely and demonstrated rectoanal intus- -r LEESE, C HAL I A A'FI'ARD, M HOILILIDAY, J P significant effect on the course of the susception on preoperative evacuation NEOPTOLEFMOS, M WATKINS, AND M THOMAS disease. No serious complications were proctography. In those with poor results, (Department of Surgery, University of encountered and there were no deaths in four had complete emptying and three had Leicester, Leicester) Fresh frozen plasma this series. Twenty nine patients had severe rectoanal intussusceptions. In conclusion (FFP) therapy may improve survival in pancreatitis. rectopexy is an ineffective treatment for acute pancreatitis. The proposed mecha- ERCP is a safe and reliable means of obstructed defecation in most patients. nism is the replenishment of specific pro- detecting biliary and pancreatic pathology

teins, particularly alpha2 macroglobulin in biliary pancreatitis. ES should be first line http://gut.bmj.com/ (A2M) - a centrally important antiprotease. treatment for removal of bile duct stones in Prospective study on the effect of posterior In a multicentre trial, patients with prog- this condition. rectopexia on faecal continence, anal nostically severe pancreatitis (three or more pressure and rectal capacity adverse Glasgow prognostic criteria) are randomised to receive 24 units of FFP or a How good is methyl tert-butyl (MTBE) for J B V M DELEMARRE, A MAAS GEESIiERANUS, similar volume of human albumin solution common bile duct (CBD) stone dissolution? R SOEBHAG, H G GOOS/EN (INJRODUCED BY (colloid control) during the first 72 hours. C B H W LAMERS) (University Hospital Antiproteases and other proteins are J P NEOPTiOLEMOS, C HALL, W R MURRAY, J Leiden, Department of Surgery, P0 Box measured on days 1, 3, and 7. To date 220 O'CONNOR, AND D 1i CARR-iOCKE (Depart- on September 24, 2021 by guest. Protected copyright. 9600, 2300 RC, Leiden, The Netherlands) patients with pancreatitis have been refer- ments of Surgery and Gastroenterology, Twenty three patients with complete rectal red of which 40 with prognostically severe Dudley Road and Queen Elizabethz prolapse or internal intussusception, were disease were randomised. There were four Hospitals, Birmingham and Western included in a prospective study to analyse deaths in the colloid control group (21%) Infirmary, Glasgow and Leicester Royal the effect of posterior rectopexia on faecal and three in the FFP group (14-3%). The Infirmary, Leicester) The place of MTBE continence. Before operation, five patients concentrations of proteins showing a therapy for CBD stone dissolution is poorly were fully continent (group A), 10 were positive acute phase response (C-reactive defined because of limited experience. We continent for solid stools only (group B) and protein, alpha, antiprotease alpha, antichy- report the results in 33 cases treated in nine eight patients were fully incontinent (group motrypsin, fibrin degradation products, D- different units throughout the UK. C). Patients in group A remained fully dimer) were not influenced by FFP therapy. The median age was 77 (range 53-92) continent; nine of 10 patients in group P The exception was plasma fibrinogen, con- years. Major medical risk factors were regained continence and in one continence centrations of which were higher on day 3 in present in 28. A nasobiliary catheter was was not altered; in group C, three patients the FFP group (p<0t)2). The concentra- inserted endoscopically in all 33 cases; 31 regained full continence, two became conti- tions of proteins which showed a negative also had an endoscopic sphincterotomy nent for solid stools only, and three patients acute phase response (A,M, antithrombin (ES) considered to be inadequate in five. were still fully incontinent. No patient Ill, Fibronectin) were increased by FFP Between 30 ml and 72 1 MTBE was infused experienced adversely affected faecal conti- therapy so that on day 3 concentrations or cycled for between 90 minutes and 40 nence. were higher in the FFP group (p<0.01, hours. MTBE was useful in 12 (36% ) cases: Clinical data were correlated to anorectal <0 05, <0.05). The confirmation that FFP in seven, spontaneous stone passage occur- manometry and rectal capacity measure- therapy supplements declining concentra- red during MTBE infusion and in five there ment. In group B, incremental pressure tions of negative acute phase proteins was cholangiographic evidence of partial (A P=squeeze-basal P; mmHg) increased including A2M may be important. The trial stone dissolution (22% to 66%) allowing from 20 (9) to 63 (8) mmHg (p<0-02) and will continue to see if clinical benefit results. extraction by repeat ES. MTBE was not Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterologv A737 useful in the other 21: four patients sponta- Effect of the novel cholecystokinin-receptor London, General Infirmary, Leeds, General neously passed stones after MTBE was antagonist loxiglumide on basal and Hospital, Birmingham, St Barthlolomew's stopped. six had duct clearance by repeat bombesin stimulated gall bladder contrac- Hospital, London, Northtwick Park ES without evidence of stone dissolution. tion and plasma cholecystokinin in man Hospital, Harrow, and Guy's Hospital, seven required surgery and four had no London) In an observer variation study 10 further treatment of whom one died from B R DOUGLAS, J B M J JANSEIN, R T 0 IHON A histopathologists with a special interest in cholangitis. There were no significant dif- IHAM, AND C B H W LAMERS (Department of inflammatory bowel disease independently ferences in treatment periods or volumes, Gastroenterology and Hepatology, Univer- coded the same 76 colorectal biopsies (34 between those having a successful outcome sity Hospital, Leiden, The Netherlands) with ulcerative colitis, 24 with Crohn's, and and those who did not. Complications Cholecystokinin (CCK)-receptor antagon- 18 'normals). Eleven important discrima- occurred in 20 patients including drowsi- ists have been used in various in vitro and in tory features were identified, depending on ness (n=12), pain (n=5), nausea (n=5), vivo animal studies. Studies on the efficacy their respective frequencies in the three anorexia (n=4), and hypotension (n=2). In of these therapeutic agents in man are, classes of subjects, and the extent of agree- conclusion, although MTBE therapy for however, very limited. In five normal sub- ment between the observers on the report- CBD stones was useful in some cases the jects we have studied gall bladder volumes ing of the features. These comprise neut- overall results were disappointing. (ultrasonography) and plasma CCK levels rophilic infiltration, epithelial granulomas, (radioimmunoassay) every 10 minutes for crypt architectural abnormalities, mucin one hour during the following randomly depietion, cosinophils, paneth cell meta- Can pretreatment gall bladder stone performed infusions (1) 75 ng/kg 30 min plasia, diffuse inflammation, villous characteristics predict the fragmentation bombesin, (2) loxiglumide in a dose of 2-5 mucosal configuration, crypt dilatation, and response to extracorporeal shock wave mg/kg in 10 min followed by 5 mg/kg/h, focal inflammation. After determining the lithotripsy? (3) the combination of bombesin and presence or absence of each of the 11 loxiglumide, and (4) saline control. features recorded by cach observer on all 76 J R F WALTERS, K A HOOD, A KEIGHIIEY, C N Control saline did not significantly biopsies, two multiple regression analyses MALIINSON, AND R H DOWLINC (Castro- influence gall gladder volumes and plasma were carried out. The first provided scores enterology Unit, Guy's Campus, UMDS and CCK-levels. Infusion of bombesin induced for differentiating 'normals' from patients London Bridge Hospital, London) In a gall bladder contraction of 69 (17)% with inflammatory bowel disease, and the patients with gall bladder stones, extra- (p<0.01) accompanied by an increase of second to distinguish Crohn's from ulcera- corporeal shock wave lithotripsy (ESWL) is plasma CCK from 1-3 (0.7) to 9-6 (2.8) pM tive colitis. The results show that the sensi- safe and well tolerated but in our experi- (p<0-02) Infusion of loxiglumide alone tivity and specificity of the scoring system in ence, it does not always fragment the induced a relaxation of the gall bladder to detecting inflammatory bowel disease are stones. To see if pretreatment stone 204% of basal volume (p<.0O1) without 74% and 98% respectively. In detecting http://gut.bmj.com/ characteristics could predict fragmentation significantly affecting plasma CCK levels. Crohn's and ulcerative colitis, the sensitivi- response, in a subset of 39 patients treated Loxiglumide inhibited bombesin- ties are 28% and 40(% respectively and the with a piezo-ceramic machine (Wolf stimulated gall bladder contraction from 69 specificities 99% and 911% respectively. In Piezolith 22(X)/2300), we related fragmenta- (17)% to 19 (17%)% (p<0-05) while conclusion we hope that prospective testing tion to stone number (single l} multiple) and increasing bombesin-stimulated plasma of such a scoring system could lead to correlated number of shocks given to CCK levels to 18 3 (3-2) pM (p<0-005), increased consistency and discrimatory achieve fragmentation with: (i) maximum a level significantly higher than during ability in histological classification. stone diameter and (ii) CT-density bombesin alone (p<0.01). on September 24, 2021 by guest. Protected copyright. (Hounsfield units, HU). All 39 patients had (1) Basal gall bladder volume is under opacifying gall bladders by cholecysto- control of plasma CCK, (2) CCK plays a New ulcerative colitis activity index (UCAI) graphy (OCG) with one to three stones major role in bombesin stimulated gall which predicts endoscopic findings measuring 1(-30 mm that were lucent by bladder contraction, and (3) loxiglumide plain x-ray, OCG and CT (<100 HU). increases bombesin stimulated plasma A IOBIN, Y SUZUKI, E ILEA'N, I O'RIORDAN, ANI) After treatment with up to 50()) shocks/ CCK levels. C O'MORAIN (Dept of Gastroenterology, session and up to five sessions, 30 patients MeatlilAdelaide Hospitals and Dept of (77%) had 'complete' (arbitrarily all frag- Histopathology, Trinity College, Dublin, ments <10 mm), three 'partial' (fragments Ireland) There is no universally accepted >10 mm), and six no fragmentation. activity index for ulcerative colitis. An Complete fragmentation occurred more INFLAMMAJ'ORY BOWEL DISEASE objective index based on readily available often (p<0-05) with single than with clinical and laboratory information would multiple stones. Although stone size did not Scoring system based on histopathological be useful to standardise assessment of predict success or failure, there were posi- features for identifying Crohn's and ulcera- disease activity and therapeutic response in tive correlations between the number of tive colitis clinical studies and individual patient shocks given to achieve complete fragmen- management. tation and: (i) the maximum stone diameter D J SPIEGEILHALTER, A 'IHEODOSSI, J JASS, J The aim of this study was to correlate a (r=0 54, p<0-05) and (ii) CT-density of the FIRTH, M DIXON, M LEADER, D I.EVISON, R simple activity index with endoscopic and stones (r=0-58, p<0-02). LINDLEY, FIIIPE, A PRICE, N A SHEPHERD, S histological findings. Twenty three UC ESWL works best in patients with single THOMAS, AND H IHOMPSON (MRC Biostatis- patients who underwent 33 colonoscopies stones: small stones and those of low CT- tics Unit, Cambridge, Mayday Hospital, over an 18 month period were studied. Nine density require fewer shocks for complete Croydon, Depts of Pathology, St Marks were assessed in both active and quiescent fragmentation. Hospital, London, Westminster Hospital, phases. Patients kept seven day diaries of Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A738 The British Society ofGastroenterology stool frequency and form, pain, bleeding, Primary sclerosing cholangitis: an on recurrence after resection of small bowel and general well being. important and prevalent complication of Crohn's disease. Sixty patients underwent At interview any weight loss, fever, or Crohn's disease resection of small bowel Crohn's disease extra-intestinal symptoms were noted and between 1973 and 1986. Follow up ranged blood drawn for full blood count and B MCGARITY, D A F ROBERISON, D S BANSI, AND from 6-175 months (median 42). Thirty two biochemistry. A score was calculated by H SHEPHERD (University of Southampton, patients did not receive perioperative blood adding weighted values of each variable. Dept of Medicine II, Level D, South Lab transfusion, whilst 28 patients received 1-8 Colonoscopy was performed within a week & Path Block, Southampton General units (median 3) of blood perioperatively. of interview and findings graded using a five Hospital, Tremona Road, Southampton) There was no difference in the age of the point scale. Serial biopsies were taken for Primary sclerosing cholangitis (PSC) is a patients, length of history or pre-operative histological examination. well recognised complication of ulcerative albumin between the two groups. Trans- Statistical analysis using the Spearman colitis occurring in up to 5% of patients. The fused patients had significantly (t test) lower Rank correlation showed that this UCAI association with Crohn's disease (CD) is not mean haemoglobin, however, (11-2 v' 12.5 was a sensitive predictor of endoscopic well established and we have studied 125 g/dl, p<005), and greater length of bowel (r=0.9, p<0.001) and histologic (r=0.71, patients with CD to determine the preval- excised (46.5 v 67 cm, p<005) than non- p2 x Lee-Desu statistic on SPSS-X showed that We conclude that this disease activity normal) were found in 10 patients, and recurrence (proven by radiology + index is a valuable tool in the management investigated by endoscopic retrograde histology) was significantly lower (p=0-.006) of patients with ulcerative colitis. cholangiography (ERC) and liver biopsy. in the transfused patients. At five years, Primary sclerosing cholangitis was diag- cumulative recurrence rate in transfused nosed by typical changes on ERC and/or patients was 19% and in non-transfused Fish oil modifies neutrophil (PMN) function liver histology. Crohn's disease was con- patients 59%. This study shows that in ulcerative colitis (UC) firmed using standard radiological and perioperative transfusion is associated with histological criteria. marked decrease in postoperative recurr- A B HAWTHORNE, T EDWARDS, B FILOPOWICZ, One patient had autoimmune chronic ence in Crohn's disease, which warrants T K DANESHMEND, AND C J HAWKEY (Dept of active hepatitis, one had primary biliary further study. Therapeutics, University Hospital, Notting- cirrhosis, but PSC was present in eight ham) Active UC is characterised by PMN patients (abnormal ERC seven, abnormal infiltration. Increased leukotriene (LT)B4 is liver histology five), a prevalence of 6.4%.

the main chemotactic stimulus in the Four had small bowel CD, all had colonic http://gut.bmj.com/ mucosa, and is also associated with PMN disease. There was no relationship between BASIC SCIENCE degranulation. By enhancing membrane CD activity and presence of PSC: one eicosapentaenoic acid (EPA), to provide an patient was asymptomatic, but had granulo- Difference in antigenic expression between alternative lipoxygenase substrate, fish oil mas on rectal biopsy. Liver histology ascending and descending colon reduces production of LTB4. In a controlled showed cirrhosis in three cases, cholestasis trial in UC of 'Hiepa' oil (4 g EPA daily), we with periductal inflammation in two and was N D ROTHNIE, S U HUICI, N ROONEY, C B WOOD, have measured these changes and investi- normal in one case with typical ERC R C N WILLIAMSON, D CC BARIOLO, N A HABIB gated whether PMN activity, measured as changes. (Department of Surgery and Histopath- on September 24, 2021 by guest. Protected copyright. ,3-glucuronidase release from lysosomal Liver disease was symptomatic in four ology, Bristol Royal Infirmary and Depart- granules, after in vitro stimulation, is patients: three had oesophageal varices, ment of Surgery, Royal Postgraduate reduced after two months' treatment. one pruritus and jaundice, and one had Medical School, Hammersmith Hospital, Eicosapentaenoic acid incorporation was bacterial cholangitis. London) Monoclonal antibody C466 raised measured in red cells by extraction, and gas Primary sclerosing cholangitis is the against human colorectal carcinoma cell chromatography, and rose from a baseline commonest cause of persistently abnormal line SW 620 has been shown to bind strongly value of 0-4 (0.1) (mean (SEM)) to 3-0 liver function in CD, and is at least as to H type 2 oligosaccharide side chains of (0.4)% total lipids, p<0-001, n=32. prevalent as in ulcerative colitis. the structure: aL Fuc(I-2) ,B D Gal(1-4) P Isolated peripheral blood PMN, 2x 107/ml D GlcNAc which is expressed in a large were stimulated with 1*25 FM A23187 number of colonic cancers. Previous studies ionophore, and LTB4 (measured by Perioperative blood transfusion protects have shown this antigen to be present in the reverse-phase HPLC) fell from 80-8 (10-7) against recurrence in Crohn's disease normal colon on the right side of secretors, to 47-0 (7.0) ng/107 cells, p<0-01, n= 16. p- but to be absent on the left, and have glucuronidase release from PMN in J G WILLIAMS AND L E HUGHES (Department of suggested that this is due to bacterial action response to 5 FM A23187, measured by a Surgery, University of Wales College of degrading the antigen. standard spectrophotometric assay, fell Medicine, Heath Park, Cardiff) Heterolo- We have performed immunohisto- from 17 3 (8.6-23.7), (median (interquar- gous blood transfusion produces immune chemical studies using the avidin-biotin tile range)) to 8-9 (5-9-13.4) units/10' cells, suppression in the recipient and is associ- peroxidase method on paraffin sections of p

The British Society ofGastroenterology A739) absent in the left. All the rats and mice were Dublin, Ireland) Human epidermal growth (0.61) (SE) cm', GRA 1-62 (0.45), and positive on the right and negative on the factor (hEGF) is a single 53-amino acid GRA+G17 2.21 (0.46). Immediately after left, with an abrupt cutoff in staining occur- peptide which influences the differentiation stopping GRA growth became exponential ring two-thirds of the way along the colon. and proliferation of a wide variety of cell in three animals. Even by day 31 mean The distribution of antigen with an abrupt types. In the small intestinal mucosa of resected tumour weight was: C 5.01 (1.04), cutoff between right and left colon may be patients with coeliac disease, a marked GRA 3 24 (0.79), GRA+G17 3.73 (0.9). because there is a difference in antigen increase in the proliferation of crypt epithe- Gastrin receptor antagonist can inhibit in expression between midgut and hindgut, lial cells had been noted. This raises the vivo growth of gastrin sensitive tumours. and may have important implications for possibility that hEGF may be involved in Administration of exogenous G17 can the appearance of oncofetal antigens. the pathogenesis of coeliac disease. In the partially reverse this effect. present study this possibility was explored. hEGF was measured by radioimmunoassay Effects of nutrient HCO3 on restitution of (RIA) in jejunal aspirates of untreated Reduced blood flow to the proximal colonic mucosa in vitro coeliac patients; coeliac patients treated duodenum in an experimental model of with a gluten free diet; disease controls; and duodenal ulceration Q ZHANG, P H ROWE, C HANLEY, R C MASON, normal controls. Disease controls were AND I MCCOLL (Department of Surgery, patients with duodenitis or duodenal ulcer. R H K GOMPERTZ, R I'MAiHIE, A MICHALOWSKI, Guy's Hospital, UMDS, St Thomas Street, Significant differences in the levels of hEGF J H BARON, AND R C N WILLIAMSON (Depart- London) We have previously reported measured were observed (a) between ment of Surgery, Royal Postgraduate restitution to occur in colonic mucosa in untreated coeliacs and normal controls Medical School and MRC Cyclotron Unit, vitro after injury by sodium deoxycholate (p<0-01) and (b) between disease controls Hammersmith Hospital, Ducane Road, (DOCA). We investigated the effects of and normal controls (p<0.03). The levels in London) Changes in gastroduodenal blood different nutrient [HCO3I on restitution of treated coeliacs were found to be inter- flow have been implicated in the pathogene- colonic mucosa after injury by bile salts. mediate between those in untreated sis of duodenal ulcer. Unlike other models, Using chambered bull frog colonic mucosa coeliacs and normal controls. duodenal ulcers induced by lower mediasti- exposed to 10 mM DOCA in the luminal Thus, in jejunal aspirates of coeliac nal irradiation in mice are suitable for blood chamber exhibited an immediate fall in patients, hEGF levels seem to correlate flow measurements. Female CFLP mice potential difference (PD) and resistance with the histological lesion. This is consis- (n=45) weighing 25-35 g were randomly (R) and severe mucosal injury with denuda- tent with a pathogenetic role for hEGF in allocated to one of three groups. Group 1 tion of the basal lamina. Following 10 coeliac disease. The finding of significantly (controls) were not irradiated. Group 2 minute DOCA exposure and replacement low levels in patients with. duodenal path- (irradiated controls) received 18 Gy 250 Kv of DOCA with standard luminal solution, ology may, however, indicate that this x rays to the upper mediastinum, which http://gut.bmj.com/ the nutrient solution (N) was replaced with effect is not specific for coeliac disease. does not cause duodenal ulceration. Group N containing different [HCO31: 48 mM 3 (ulcer group) received the same dose of (n=7), 18 mM control (n=11), HCO3 free irradiation to the lower mediastinum, which using HEPES buffer (n=9). All tissues were L365.260 (gastrin receptor antagonist) induces typical chronic duodenal ulcers in allowed to recover for four hours. In tissues significantly inhibits in vivo growth of a 45% of animals. Mice were studied seven with 18 mM HCO3 in N, there was histo- gastrin responsive adenocarcinoma days later, using 15 im microspheres label- logical restitution of the surface epithelium led with Sn113 injected into the aortic arch and PD and R returned within four hours to D L MORRIS, S A WATSON, AND L. G DURRANI 90 seconds before death. Validation studies on September 24, 2021 by guest. Protected copyright. values not significantly different from PD (Departments of Surgery and Cancer showed satisfactory mixing of spheres with a and R before injury. In tissues with 48 mM Research, University of Nottingham, minimum number of 40)0 spheres per probe. HCO3 in N, this process occurred signific- Nottingham) Many human gastric and Proximal duodenal blood flow was reduced antly faster in two hours. In contrast, tissues colorectal cancer cells have gastrin by 40% in the ulcer group (4.5 v 8-4 ml/g with no HCO3 in N exhibited no electrical receptors and can be shown to be stimulated tissue/min: p<0 05, Mann Whitney U test). recovery or restitution with evidence of a by gastrin at least in in vitro culture. AR42J No other significant differences in blood severe mucosal injury. is a rat pancreatic adenocarcinoma which flow were observed, and organ wet weights We conclude HCO3 is necessary in the has 2x 104 gastrin binding sites/cell and were unchanged. Thus the absolute duo- nutrient solution to facilitate the process of reliably responds to gastrin in in vitro denal flow rate was also reduced in the ulcer restitution in vitro. The exact mechanism culture (200% of control). L365.260 (MSD) group. Within the ulcer group there was no remains to be determined but maintainence is a new potent specific gastrin receptor difference between mice with ulcer (n=5) of chloride bicarbonate exchange at the antagonist (GRA). and those without (n= 10). Therefore basolateral membrane and a stable intra- Twenty nude mice with xenografts of reduced duodenal blood flow is associated cellular pH is a possible explanation. AR42J were randomly allocated to: control with duodenal ulceration but may not (C), oral GRA 5 mg/kg twice daily and explain individual susceptibility. GRA+ G 17 10 [sg/mouse/day for 14 days by Quantification of human epidermal growth pump. Gastrin receptor antagonist treat- factor in jejunal aspirates in coeliac disease ment was for 22 days of the4j1 day experi- Sequential gastric emptying in the rat: a new ment. Tumour diameter was measured technique MICHAELJ MURPHY, CIARAN P KELLY, CONLETH daily. F FEIGHERY, DONALD G WEIR, AND RICHARD B Tumour growth was significantly A D HOUGHTON, P lIEPINS, S ALLEN, S CLARKE, GALLAGHER (Departments of Immunology (p<001) inhibited by GRA. Mean tumour AND R MASON (Departments of Surgery, and Clinical Medicine, Trinity College cross sectional area at day 22 was: C 3.3 Nuc-lear Medicine and Radiological Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A740 The British Society ofGastroenterology

Sciences, Guys Hospital and Medical of DMPGE2 with pepsin pH 1.0. Increased stomach has a hydrophobic lining which School, London) To date the only reliable prostaglandin induced mucosal perme- may be important in mucosal defence. method of assessment of gastric emptying in ability to ['HI-inulin was maintained in the The aim of this study was to check the rat involves killing the animal after presence of pepsin. whether this property is attributable to intragastric instillation of radioistope. This These results show prostaglandins miti- mucus. We studied gastric mucosa from pigs study describes a technique by which liquid gate pepsin induced gastric mucosal damage immediately after slaughter (n= 18). and solid gastric emptying can be investi- preventing mucosal bleeding. This could be Contact angles (CA) of saline drops were gated over a long time period without the mediated through a combination of measured using a goniometer as an index of need to kill the animal. increased mucus barrier thickness and non- hydrophobicity. We compared CA of Intragastric instillation of either I ml of parietal secretion. mucus obtained from different areas with OnTc-labelled tin colloid or W'Tc-labelled that of the corresponding mucosa, and CA Dowex resin in bran was performed under a of mucus spread on hydrophylic surface short general anaesthetic a rat endo- using Human pepsins: mucolytic and proteolytic (glass, inherent CA= 17°) with the same scope. Rats were then placed over a gamma activities sample on hydrophobic surface (poly- camera in a purpose built rat holder. propylene, inherent CA=94°). The effect Sequential images over two hours showed a of mucus thickness on CA was also linear pattern of solid emptying and a liquid J P PEARSON, A BLACKBURN, A ALLEN, R M investigated. emptying of monoexpoenential pattern. COAN, K PEEK, N ROBERTS, W TAYLOR, AND C W The CA (mean (SEM)) of mucosa and The results were found to correlate VENABLES (Departments of Physiological well Sciences and Surgery, Medical School, overlying mucus respectively were: 63 (4) with the standard technique of intragastric and 60 9 (3.7) for antrum; 44-6 (4.2) and 54 instillation followed death University of Newcastle upon Tyne and by (r=0.91, Department of Chemical Pathology, Royal (4.4) for body; 48.2 (3) and 49 (4.2) for p<0O-OO1). fundus. The CA of mucus correlated with This study shows that it is to Liverpool Hospital, Liverpool) Human possible gastric contains at least seven different that of mucosa (r=0.76 p<0001, n=15). study gastric emptying in the rat in a sequen- juice The CA of mucus samples (n=6) was the tial manner a camera and pepsins of which pepsin 3 and 5 are the using gamma major components. Pepsin 1, normally a same on glass as on polypropylene (56.9 without the need to kill the animal. This (8.2) v 52 (8.3) NS) and the results corre- method is further minor component, is raised up to five fold in enabling studies on the peptic ulcer disease and has enhanced lated (r=0 9 p<0.01). Mucus samples pathology and manipulation of gastric (n=18) of two different thicknesses (1(X) disorders and the mucolytic activity against pig gastric mucus. emptying effect of surgical Proteolytic activity of pepsin 1, 3, and 5 [tm and 1000 Fm) had similar CA (69.8 procedures on gastric emptying. (purified by HPLC) and unfractionated gas- (4.7) v 72-1 (5.6) NS) and were correlated tric juice was not significantly decreased (r=0.9 p

The British Society ofGastroenterology A741 increased almost five-fold within five Endoscopic balloon dilatation, a therapeutic children, aged two to 60 months (median minutes of the addition of prostaglandin E2 option for Crohn's strictures 10). In the one child who had two examina- 10 4. After 30 minutes, MGT had returned tions, the indication was pancreatic disease, to pretreatment levels. A J K WILLIAMS AND K R PALMER (University but in all other cases biliary disease was Gastric mucus secretion is best measured Department of Gastroenterology, Western suspected (seven neonatal jaundice/ by changes in the thickness of the adherent General Hospital, Edinburgh) Intestinal cholestasis, one gall stone, one choledochal layer and scanning electron microscopy on strictures as a result of Crohn's disease are cyst). Examinations were carried out under freeze-fractured tissue may be the tech- usually treated by resection. or stricturo- general anaesthesia (eight) or sedation nique of choice plasty, but surgery may be difficult, has (three) and cannulation was achieved in 10 significant morbidity and recurrence is of 11 attempts. Pancreatic and biliary ducts common. An alternative novel approach is were cannulated in eight cases each. The endoscopic balloon dilatation which is two neonates with normal pancreatic ducts accepted therapy for fibrous or peptic stric- but no biliary cannulation were proved to ENDOSCOPY POSTERS tures but has not been reported in Crohn's have extrahepatic biliary atresia (EHBA) at disease. laparotomy. In three neonates, EHBA was Ethanol induced tumour necrosis (ETN) for Balloon dilatation was attempted in disproved by the demonstration of patent palliation of malignant dysphagia seven patients with Crohn's disease under extrahepatic ducts (two biliary hypoplasia, consideration for surgery. One patient had one intrahepatic biliary atresia), obviating J J PAYNE-JAME.S, R C SPILLER, JJ MISIEWIC7, gastric outflow obstruction caused by the need for laparotomy. In one 13 month AND D B A SILK (Department of Castro- duodenal stenosis, five patients had inter- old boy, sclerosing cholangitis was seen. No enterology and Nutrition, Central Middlesex mittent small bowel obstruction because of complications ensued. Hospital, Acton Lane, London) Palliation recurrent disease at an ileo-colic anasto- In experienced hands ERC in neonates is of dysphagia secondary to obstructing misis and one had a short stricture in the safe, and aids diagnosis in neonatal choles- oesophagogastric malignant strictures descending colon. tasis. In agreement with one other report, remains a difficult management problem. Endoscopic balloon dilatation was cannulation of the pancreas but failure to fill Eleven patients (73-5) (SEM 3-1 years) with attempted under intravenous sedation. All the biliary tree implies EHBA. inoperable, unresectable, or recurrent patients tolerated the procedure well, and tumour at anastomosis causing dysphagia were discharged within 48 hours. have undergone per-endoscopic injection of After four dilatations the patient with tumour with dehydrated alcohol to induce duodenal stenosis is asymptomatic and been Patient progress after negative OGD exami- local tumour necrosis (ETN). Mean stric- well for seven months. Balloon dilatation nation - a preliminary study ture length was 5-7 cm (range 1-1i) cm). was only possible in three of the patients http://gut.bmj.com/ Dysphagia scores (range 0, normal swallow- with anastomotic disease. These cases are I T DE DOMBAL, B BROCK, C PASSANI, S TEIiLiFER, ing to 5, unable to swallow saliva) were asymptomatic over two to 10 month follow AND A G MORGAN (Clinical Information assigned to each patient. Patients under- up. The patient with an isolated colonic Science Unit, Leeds University and Airedale went upper GI endoscopy under diazepam stricture was dilated and has been well for District Hospital, West Yorkshire) Recent and pethidine sedation. Dilatation was six months. BSG studies have estimated 260( (X) OGD's undertaken with Celestin dilators if obstruc- Endoscopic balloon dilatation of intest- are performed annually in England and tion was not complete. Dehydrated alcohol inal strictures caused by Crohn's disease is Wales, and emphasised their value in reduc- was then injected in 0-5 ml aliquots with a safe, effective and may overcome the need ing hospitalisation and surgery. Neverthe- on September 24, 2021 by guest. Protected copyright. variceal needle into macroscopic tumour for surgery. less, a substantial proportion of OGD until blanching occurred. In those patients examinations are negative, and the subse- where dilatation could not be achieved quent progress of such patients has been (n=4), tumour was injected and re- Endoscopic retrograde cholangiography little studied. endoscopy and dilatation undertaken a (ERC) in the investigation of cholestasis in We therefore followed a consecutive week later. One patient required one infants series of 2(X) patients newly referred with further endoscopy. After treatment the undiagnosed dyspepsia from general prac- patients were allowed free fluids after six M L WILKINSON, D P DRAKE, C BALL, G MiELl- tice to a special dyspepsia clinic during the hours and discharged the following morn- VERRGANI, AND A P MOWAI (Gastroenterology period January 1987 to April 1988 in whom ing. They were instructed to contact the unit Unit, UMDS of Guy's and St Thomas' OGD yielded negative visual and biopsy if symptoms recurred. Eight patients have Hospitals, London and Department of results. Patients were traced through subse- since died with a survival after first treat- Paediatrics, King's College School of quent hospital records, and through their ment of 121 (31-2) days. No treatment Medicine and Dentistry, London) Neonatal GP's. A 99% follow up was achieved. related complications were recorded. cholestasis presents formidable diagnostic In 41 of 198 traced patients, (20)-7), Dysphagia scores were significantly problems. Unlike adults and older children, organic conditions (warranting treatment) improved from pre-treatment scores after infants are not amenable to ERC with had been established by the time of the the first treatment (p=0 005) and when standard instruments. Initial experience survey. The most common conditions estab- considering subsequent best scores with a prototype paediatric duodenoscope lished were gall stones (22 cases) and diver- (p=0(-(X)3). (Olympus PJF 7.5), with an external dia- ticular disease (11 cases). Most organic We conclude that ETN has considerable meter of 7 5 mm but which lacks a bridge/ conditions were diagnosed within the first potential as a cost-effective therapeutic elevator mechanism, is described. Eleven six months of negative endoscopy, and choice in the management of malignant ERCs have been performed by one would not have been detected by OGD. dysphagia. operator using this instrument in 1t) Subsequent therapy proved effective: Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A742 The British Society ofGastroenterology

94 10% of patients were symptom free at one S DOMSCHKE, P MALFERTHEINER, M BUCHLER, saline alone and were killed at similar time year review. H G BEGER, AND W DOMSCHKE (Dept of Med, intervals served as controls. Pancreatic Had these 200 patients simply been refer- Univ of Erlangen, and Dept of Med and biopsies were taken at the above time red for open access endoscopy rather than Surg, Univ of Ulm, FRG) In acute pan- intervals and prepared in standard fashion (as was the case) to a dyspepsia clinic, one in creatitis, free fatty acids (FFA) might be for transmission electron microscopy. five might have been returned to the com- involved in an early phase of pathogenesis Dilatation of the endoplasmic reticulum, munity with (undiagnosed) organic disease. (Virchows Arch 1986; 409: 791). development of large cytoplasmic vacuoles, We conclude the situation warrants further In 20 patients with acute necrotising pan- and reduction in the number of zymogen (larger scale) study. creatitis (ANP) pancreatic and peripancrea- granules were seen as early as 15 min and tic fat necrosis was verified upon operation these changes progressed over the study and/or by contrast enhanced computed period. No demonstrable changes were Endoscopy and AIDS: an evaluation of the tomography. For comparison, 20 patients seen in the microvasculature at 15 min but risk of cross infection with acute oedematous pancreatitis (AOP), thereafter capillaries of pancreatitis animals assessed clinically, by plasma lipase and by showed a marked increase in the number of PJ V HANSON, D GOR, M V CHADWICK, J CLARK, computed tomography/ultrasonography, transport vesicles, irregularity of the G NICHOLSON, B GAZZARD, H GAYA, N SHAH, were examined. Plasma FFA were assayed endothelial lining and a marked increase in D J JEFFRIES, AND J V COLLINS (Brompton, St by a colorimetric ultramicro method on the the number of fenestrae. Microvascular Stephen's and St Mary's Hospitals, London) day of admission and subsequently. changes in CIP are preceded by ultrastruc- Twenty gastroscopes were sampled after Although in AOP plasma concentrations tural changes in the acinar cell itself and, use on patients with AIDS. Suction biopsy, of FFA were increased in the beginning therefore, are a consequence not a cause of air and water channels were irrigated with (0.78 (0.09) (SEM) mmol/l), higher pancreatitis in this model. viral medium and the insertion tube swab- (p<0.03) FFA concentrations were found bed. Sampling was repeated after washing in ANP (1.14 (0.12) mmol/l). In the later (Keymed auto-disinfector) and after two course, FFA remained raised in ANP (0-86 Pylorus preservation and gastric emptying minutes disinfection in 2% alkaline (0.13) mmol/l on days 5- 1), while FFA during pancreatoduodenectomy glutaraldehyde (Cidex, Surgikos). Poly- values normalised in AOP within one week merase chain reaction (PCR) and Southern (days 2-4: 0 52 (0.11; days 5-11 0(40 (0.13) M J COOPER AND R C N WILLIAMSON (Depart- blotting for nucleic acid were used to detect mmol/l). ments of Surgery, Royal Devon and Exeter HIV and hepatitis B surface antigen Plasma concentrations of FFA seem to Hospital, Exeter and Royal Postgraduate (HBsAg). Human immunodeficiency virus reflect the severity of acute pancreatitis. In Medical School, London) Preservation of and HBsAg antigen assays and HIV cul- AOP, the initial peak may correspond to the antrum and pylorus during pancreato- tures were also performed. Viral examina- the disease outburst itself and unspecific duodenectomy should permit better gastric http://gut.bmj.com/ tion included cultures and immunoflouresc- stress. In ANP, the continuous rise of FFA function and reduce side effects, but ence (IF) for cytomegalovirus; myxovirus may predominantly mirror the ongoing pan- delayed gastric emptying (GE) is commonly cultures and haemadsorption. Samples creatic parenchymal and extrapancreatic fat reported. A personal series of 52 pts with were cultures quantitively for fungi and all necrosis. Binding of possibly toxic FFA with conservative (pylorus preserving) pan- bacterial flora including Cpylori and myco- intravenous albumin appears logical. creatoduodenectomy (PPP) between 1981- bacteria. Using PCR, the most sensitive 88 included 33 men and 19 women with a assay available, HIV nucleic acid was found median age of 44 yr (range 22-81). Indica- on seven or 20 unwashed scopes and HBsAg Correlation of ultrastructural acinar cell tions for PPP were chronic pancreatitis in 27 on September 24, 2021 by guest. Protected copyright. on one. Commensal bacteria were found on changes in caerulein pancreatitis with local and malignancy in 25 (pancreas nine, all scopes, C albicans on six, S aureus on five microvascular abnormalities ampulla two, duodenum six, biliary two, and P aeruginosa on five. Washing alone endocrine six); resection involved total pan- removed all detectable organisms from 66 D KELLY, C DELANEY, G P MCENI7EE, D createctomy in 11 cases. Four patients of 68 contaminated sites, achieving a mean COrTELL, K MCGEENEY, AND J M FllZPATRICK (7.5%) required early re-exploration reduction of 3-18 loglO organisms, (range (Department of Surgery, Mater Hospital, (abscess one, leak one, bleed one, jaundice 17-8.0). Only Neisseria spp were recovered Dublin and Depts of Electron Microscopy, one) and two died (3-8%; leak one, liver after washing (twice, from the air channel) and Medicine and Therapeutics, University failure one). In 43 of the remaining 46 but not after two minutes in Cidex. College, Dublin, Ireland) Caerulein nasogastric extubation occurred within Human immunodeficiency virus con- induced pancreatitis is associated with gross seven days, and of the three with delay (14- taminates 35% of gastroscopes used on distortion of the local microvasculature 35 days) none had residual symptoms. AIDS patients. Cleaning removes HIV and early in the disease process and micro- Gastric emptying was assessed in 23 pts virtually all contaminants, reducing the vascular changes have been implicated in (benign 12, malignant 1i1) using radio- need for lengthy periods of disinfection. the pathogenesis of the disease. The aim of labelled scrambled eggs (solids) and milk this study was to correlate changes in the (liquid) and counting over three hours. local microvasculature with ultrastructural Gastric emptying was normal (< 110 min for changes in the acinar cell. Caerulein pan- solids) in nine, delayed (up to twice normal) creatitis was induced in eight Sprague- in 10 and grossly delayed in four. During PANCREATIOBILIARY POSFERS Dawley rats by a two hour intravenous follow up (median 12 mo, range 3-65) three infusion of Caerulein (5 [tgIkg/h). Two patients needed reoperation for delayed Higher plasma concentrations of free fatty animals were killed at 15 min, 30 min, one GE (one inertia at 15 mo, two recurrent acids in acute necrotising than in oedema- hour, and two hours respectively. Four cancer at five mo). Ten of 15 patients having tous pancreatitis animals who received similar volumes of a BIDA reflux scan had a competent Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. 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The British Society ofGastroenterology A743 pylorus. Gastric emptying is often abnormal Age-sex specific rates have therefore been (n= 1), false negative catheter cholecysto- after PPP but is seldom a clinical problem. compared over time. grams (n =2). In men aged 5(-59 GD rose from 6-8% When successful. MTBE is dramatically (n=148) in the first three years to 18-1% quick but GB cannulation is invasive and Do gall stones obstruct the pancreatic duct? (n=138) in the last three years (p<0_01 X2 complications are frequent - at least while test). In men aged 60-69 GD rose from acquiring experience. 11.66% (n=370) to 19-7% (n=366, p<0.01). J P NEOPIOLEMOS AND D L CARR-LOCKE (Departments of Surgery and Gastro- In the last three years the female to male enterology, University of Birmingham and ratio of GD prevalence for ages 50-59 was Are abnormal bile duct anatomy and bile Leicester Royal Infirmary, Leicester) Whilst 1-3 and for ages 60-69 was 0.8. duct stones associated? it is recognised that common bile duct For those aged 50-59 and 60-69 the (CBD) stones obtruct the CBD it is not female to male ratio in the first three years C C AINLEY, S J WILLIAMS, A R W HATHIEL.D, D) known if they obstruct the pancreatic duct fell from 4:1 and 2:1 respectively to about VARIA, AND J F DOWSr'II (Department of 1:1 in the last three years. Gastroenterology, The Middlesex Hospital, (PD). We therefore examined ERCPs in The of 405 patients: 229 had gall stones (103 with prevalence gall stones at necropsy Mortimer Street, London) It has been our in men over 50 is increasing and is clinical impression that a short common bile CBD stones), of whom 100 had acute pan- approaching that found in women. duct (CBD) is associated with bile duct creatitis; 145 were 'normal' controls; and 31 stones, and this is supported by a recent had acute pancreatitis without gall stones. The CBD and PD diameters were report (Br Med J 1988; 297: 31-2). In the strongly correlated (r=0-382, p<0-001). present study bile duct anatomy in cholan- Each correlated with age (r=0.367 and Risks and benefits of methyl tertiary butyl giograms obtained at cholecystectomy or ether (MTBE) treatment for gall bladder ERCP was studied. 0(394 respectively both p<0-001) and of and remained so after partial correlation analy- stones (GBS): initial experience The total length the bile duct sis (rijk=0-278, p<0-00l). Stepwise logistic length of the CBD (ampulla to cystic duct regression revealed that the CBD diameter S RAJAGOPAI, A KEIGHTLEY, M MAGHSOUDLOO, insertion) were measured in a consecutive G M MURPHY, AND R H DOWLINu (Gastro- series of 1(X) patients with bile duct stones was independently related to CBD stones enterology Unit, UMDS of Guy's and St (BDS) and compared with 100 patients with (T-ratio= 12-61), age (6-86), female sex Thomas' Hospitals, Guy's Campus, stones confined to the gall bladder (GBS) (3.68), and gall stones (3.39) (all p<00()1; London) Percutaneous GB cannulation and and 10() patients with normal cholangio- R-sq=52%). Similarly the PD diameter was MTBE related to instillation of has been advocated as grams (NC). independently age (T-ratio= a safe and effective treatment for dissolu- The mean age of BDS was greater than

7-45, p<0.001) (R-sq= 19.4%). http://gut.bmj.com/ These original observations have tion of cholesterol GBS. To date, experi- GBS or NC (69-5, 57- 1, and 57.4 yr respec- important implications: (1) Clinical ence with this approach is limited. We, tively). Total bile duct length was similar in therefore, report results in our first 10 the three groups (BDS 85() (13.5), GBS decisions based on CBD or PD diameters NC 82.7 but alone have to be because of patients. 82-6 (13'2), (13.8)), CBD circumspect patients length was reduced in BDS (42.7 (16-2)) interdependence on several factors. (2) Symptomatic unwilling/ unsuitable for surgery with 3-> 100 radiolu- compared with GBS (50.5 (12.0), p<)-(X)() Gall bladder stones (as well as CBD stones) cent are (cholecystogram+CT scan) GBS (3-20 and NC (51.1 (13.0), p<0)001). The CBD associated with CBD obstruction (3) mm Patent was mm in CBD stones cause obstruction of the PD in diameter). cystic duct: nine; 40 40% of BDS compared with blocked: one. 12% of GBS and 10% of NC (X2= 11-4, on September 24, 2021 by guest. Protected copyright. patients with and without acute pancreati- + stone to not Intravenous sedation/analgesia local p<0.0Ol), and a CBD <40 mm was found tis; gall obstruction the PD is a the mechanism involved in acute anaesthesia. GB imaged for puncture with left sided cystic duct entry in 28% of causing (transhepatic in six and transcoelomic in BDS compared with 4% of GBS and 2% of pancreatitis. four) with ultrasound+fluoroscopy (n=9); NC (x2=41 5. p<0001). Duodenal diverti- CT (n= 1). Catheter 5/6 F; 30/70 cm. Sub- cula were present in 7% of BDS, 1% of spill vols (3-12 ml) of MTBE instilled/ GBS, and 2% of NC, but were not associ- Prevalence of gall stones in men is increasing aspirated (2(-30 sec cycles) with solution ated with a low or left sided cystic duct changes every three to 15 min and choles- entry. I BATES, MARGARET HARRISON, AND D LOWE terol recovery in aspirates checked (crystals A short CBD, due to a low site of entry of (The William Harvey Hospital, Ashford, on evaporation) and measured. Catheter the cystic duct which is also frequently left Kent) In a prospective study of gall stone cholecystograms every one to three hours. sided, is strongly associated with bile duct disease (GD) in a single Health District Gall bladder punctured in 10, cannulated stones. 8628 necropsies were carried out over a 10 in nine, perfused in seven. Stones dissolved year period up to July 1988. In men the partially in three and completely in four, prevalence of GD (gall stones or cholecy- with up to 18 g cholesterol removed, over '7Tc-IODIDA in the dynamic assessment of stectomy) increased from 15% in the first 2-5-13-0 h. hepatobiliary function in biliary obstruc- three years to 21% in the last three years. In Side effects: no anaesthesia, haemolysis tion. women the rate remained static (27% v or cholangitis. Bile leak necessitating 26%). cholecystectomy (n= 1); catheter dislodge- S J WILLIAMS, PH JARRI'I-I', A R W HATIIFID, C C' These trends are partly the result of a ment (n=2), pain (despite sedation) on GB AINLEY, AND P J ELL (Department of Gastro- gradual increase in the age of the necropsy cannulation (n=4), burning sensation on enterology, The Middlesex Hospital and The population which influences the overall pre- MTBE instillation (n=2), drowsiness Institute of Nuclear Medicine, UCMSM, valence rate in men more than women. (n=4), transient biliary colic/cholestasis London) Imaging (ultrasound (U/S), Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A744 The British Society ofGastroenterology

ERCP, PTC) is highly accurate in delineat- predisposes to stone formation in the CBD AA POI.YDOROU, E M (HISHOLM, AA ROMANOS, ing the level and nature of biliary obstruc- itself. J F DOWSE1I, S WILLIAMS, P B COIlON, A R W tion. After biliary decompression, Periampullary diverticula were found in HAIFIFID, AND R C G RUSSEIL (Gastro- however, s bilirubin (bili) may not fall 46 of 362 patients undergoing diagnostic enterology Unit, The Middlesex Hospital, immediately and even with excellent U/S, it ERCP (12.7%o). Cholangiography was Mortimner Street, London) Adequate pallia- may be difficult to assess success of decom- successful in 41 patients with diverticula. tion of jaundice in patients with HBO can pression. Using "Tcn-IODIDA, we calcu- Thirty four patients with diverticula were be achieved by drainage of >25% of the lated hepatic extraction fraction from jaundiced (74%) compared with 164 with- liver parenchyma. Endoprosthesis place- blood, initial washout time and time to 50% out diverticula (52%, p<0.01). Common ment into a single dilated ductal system only clearance from computer-analysed time bile duct stones were found in 21 patients in type II or IIl HBO (Bismuth's classifica- activity curves over 60 min as a non-invasive with diverticula (46%0) and 65 of those tion) can achieve this. It could be postulated evaluation of hepatobiliary function in 23 without (21%, p<0-001). Seventeen that as the secondary ducts of the LHD are pts (10 men, 13 women; mean age 70 yr (44- patients with diverticula and CBD stones involved late by tumour, LHD EP insertion 89)) with biliary obstruction (ca pancreas had previously undergone cholecystectomy will be preferable to RHD EP insertion. We 16, cholangio ca seven) before and five to (77%0) compared with 41 patients with CBD report our four year experience of single EP seven days after either endoscopic (18 pts) stones and no diverticula (63%, NS). placement in either RHD or LHD in 151 or surgical (five pts) biliary decompression. The results confirm the association patients with type 11 (64) or III (87) HBO. When IODIDA was not seen in the small between periampullary diverticula and Median age was 73 years (35-92). Eighty bowel at 60 min, a four hour film was taken. choledocholithiasis. The majority of eight patients were women. Ninety one Biochemistry and U/S were also performed patients with CBD stones and diverticula, patients had EP placed in RHD (II 45, 111 at the same time interval. however, had previously undergone 46) and 41 in LHD (II 15, III 26) with Before treatment, mean s bili was 320 cholecystectomy. This suggests that most overall successful EP placement 87% (132/ [tmol/1 (range 79-540) and U/S was consis- CBD stones in patients with diverticula do 151). Endoprosthesis failed in 19 patients. tent with biliary obstruction. Hepatic not migrate through a dilated cystic duct but Successful drainage was defined as a reduc- uptake of IODIDA was satisfactory in all have formed de novo in the CBD. tion by 30(% of total serum bilirubin within pts. Eighteen pts had complete (ie no bowel seven days combined with ultrasound activity at four hours) and five pts partial evidence of biliary decompression. The obstruction. Five to seven days after treat- Infected common duct bile is not associated results related to successful drainage, com- ment, (a) s bili fell by 50% in 16 pts, U/S with bilirubin deconjugation in man plications, 30 day mortality, EP changes, confirmed decompression and extraction mean survival in weeks and median survival and clearance of IODIDA improved G ALOJ, S K 11, C BIANCO, AND I S BENJAMIN in weeks are recorded in a Table held by the markedly. (b) In seven pts, s bili failed to (Department of Surgery, Royal Post- authors. The principal complication was http://gut.bmj.com/ decrease. In three pts, U/S suggested graduate Medical School, Hammersmitlh cholangitis occurring in 15 (1 1%) patients decompression and the IODIDA scan Hospital, London) Primary common bile requiring second EP insertion in the showed biliary patency. These pts had pro- duct (CBD) stones are frequently associ- undrained duct in seven (5%0) patients (11 4, longed cholestasis and s bili normalised ated with stasis and sepsis. On the basis of in 111 3), the remainder settling on conserva- within one mo. In four other pts, the vitro studies this has been attributed to tive treatment. IODIDA scan suggested continued deconjugation of bilirubin by bacterial There was no advantage statistically of obstruction, which in two was not predicted betaglucuronidase, but this has not been LHD stenting compared with RHD stent- by U/S. ERCP confirmed stent blockage widely confirmed by clinical studies. We ing, with equally successful drainage on September 24, 2021 by guest. Protected copyright. requiring stent change (two pts) and poor have performed cultures and assays of achieved. An EP should therefore be drainage requiring a second stent in two pts. betaglucuronidase (BG), conjugated (CB), inserted into the most accessible duct Hepatic uptake of IODIDA is good in pts and unconjugated bilirubin (UB) in CBD system to achieve adequate palliation. with high s bili levels IODIDA scanning bile from 64 patients undergoing biliary shows biliary patency after biliary decom- tract surgery. There was no significant pression and is useful in the evaluation of correlation between the levels of BG and Gall bladder vasculature in acute acalculous pts who fail to improve clinically and UB or percent UB in the whole group, nor cholecystitis biochemically after decompression. in patients with or without positive bile culture. Levels of BG, UB, and CB did not B L WARREN (INiROUCEI) BY D C' CARTER) differ significantly between 26 patients with (Departmnent of Surgery, Tygerberg Periampullary diverticula predispose to positive culture (16 with CBD stones) and Hospital and the University of Stellenbosch, primary rather than secondary stones in the 38 with negative culture (13 with stones). Tygerberg, 7505, Soutll Africa) Specimen common bile duct Results from dogs with experimental biliary arteriography of the gall bladder was stricture showed a similar pattern. These utilised in this study to evaluate the com- R I HALL, C J INGOLDBY, AND M E DENYER observations do not support bacterial parative patency of cystic artery run off in (Department of Surgery, St James's deconjugation as the principal mechanism acute acalculous cholecystitis. Radiographs University Hospital, Leeds) Periampullary of primary CBD stone formation. of the freshly-excised, unopened gall blad- diverticular and common bile duct (CBD) der were obtained after cannulation of the stones are known to be associated. It is not cystic artery and injection of sodium iotha- clear, however, whether the diverticulum Comparison of right (RHD) versus left lomate 70% m/v 0( 1 and 0 25 ml per centi- causes retrograde biliary hypertension with (LHD) hepatic duct endoprosthesis (EP) metre of gall bladder length. dilatation of the cystic duct and migration of insertion in malignant hilar biliary obstruc- The findings in six histologically verified a gall bladder stone into the CBD or if it tion (HBO) cases of acute acalculous cholecystitis were Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A745 compared with those in non-inflamed gall and regurgitation and this was associated London) Small intestinal bacterial over- bladders after elective cholecystectomy and with poor oesophageal body clearance and growth (SBBO) has been implicated in in acute gall stone associated cholecystitis. abnormal acid reflux. In the remaining encephalopathy, malnutrition, and endoto- The typical arteriographic appearance of patients minor degrees of lower oeso- xaemia complicating hepatic cirrhosis. We non-inflamed specimens was that of a series phageal sphincter and body motor abnor- have studied lactulose hydrogen breath test of irregular arterial arcades connecting the malities were seen but were not associated profiles to assess intestinal transit times and main longitudinal branches of the cystic with abnormal acid reflux or symptoms. prevalence of SBBO, as judged by the artery. These vessels remained patent in These results suggest that in spite of injec- presence of an early peak - that is, within 30 acute gall stone associated cholecystitis and tion sclerotherapy and transection for minutes. Nineteen patients with biopsy there was, in addition, evidence of early bleeding varices oesophageal function is proven cirrhosis (13 with encephalopathy, capillary and venous filling. In contrast, generally maintained. six well compensated) and 10 healthy sub- variable but marked degrees of arterial jects received 15 g lactulose after an over- occlusion were evident in all specimens of night fast. Twelve of 13 patients with acute acalculous cholecystitis, including Omeprazole in the management of staple encephalopathy had an early pulmonary three in which no overt necrosis had occur- line erosion of the oesophagus after EEA gun hydrogen excretion peak. In contrast, this red. transection for variceal bleeding was present in two of seven compensated Radiographic small vessel occlusion is a cirrhotics and 1/10 controls (p<(.(X)l; X). prominent feature of acute acalculous G L KAYE, S SIRINGO, P MISIRY, P A MCCORMICK, The intestinal transit time of lactulose was cholecystitis and appears to be an early K E F HOBBS, AND A K BURROUGHS (Academic prolonged in cirrhotics (113 (8) v 80 (9) event in the evolution of this disease. Intra- Departments of Medicine and Surgery, minutes, mean (SEM); p<0.0l). The operative quantification of gall bladder Royal Free Hospital and School of severity of liver disease among study sub- perfusion may yield useful clinical and Medicine, Pound Street, Hampstead, jects was variable (Child's score 5-14) investigative information. London) Bleeding after staple transection which correlated with baseline hydrogen for variceal haemorrhage in cirrhotics is excretion (r=0(49, p<0.05). frequently caused by erosion at the transec- These results are consistent with the con- tion line. The bleeding is usually minor in cept that intestinal motility is reduced in nature and is occasionally caused by metal cirrhotics and SBBO seems to be a constant I.IVER POSI[-RS staple eroding the mucosa, but it is not feature of hepatic encephalopathy. These known whether acid reflux, local ischaemia abnormalities may be related to the severity Does transection after injection sciero- and/or portal hypertension contribute to of liver disease. therapy for varices adversely effect oeso- this erosion. In 58 cirrhotics transected as an phageal function? emergency 24 (42%) have rebled from http://gut.bmj.com/ staple line erosions with 52 episodes com- Safety of extradural intracranial pressure S J WALKER, S A JE-NKINS, S ELLENBOGEN, C J pared with 13 others who have rebled from monitors in fulminant hepatic failure STO[)DARD, AND R SHIELDS (University varices or other lesions, with 14 episodes. Department of Surgery, Royal Liverpool Seventeen patients with persistent staple R KEIAYS, G J M ALEXANI)ER, A DARKINS, R Hospital, Liverpool) First line management line erosions were treated with standard GUI L EN, AND ROGER WvILLIAMS (Liver Unit, of bleeding varices by transection alone may doses of ranitidine and/or sucralfate for at King's College Hospital and Dept of Neuro- effect the lower oesophageal sphincter. The least two months to try to heal the lesion - surgery, The Maudsley Hospital, London) effect of transection after previous sclero- none did so. After this high dose ranitidine Treatment of cerebral oedema in fulminant on September 24, 2021 by guest. Protected copyright. therapy on oesophageal body function and (300 mg bd) and sucralfate (1 g qds) were hepatic failure requires paralysis and con- acid reflux is unknown. used for one month. Repeat endoscopy only trolled ventilation and clinical recognition We investigated five patients (four men), showed healing in four patients. Nine of further episodes of cerebral oedema is mean age 44 years (range 30-59) who had patients had bleeding whilst on low or high based on rises in systolic blood pressure and undergone oesophageal transection and dose ranitidine. The 13 patients with persis- abnormal pupillary responses. These signs reanastomosis using a stapling gun on aver- tent erosion at the staple line were then may be absent or late in the course of age 27 months (range 2-60) before this treated with 40 mg omeprazole daily for one cerebral oedema. Monitoring of intra- study. Transection was performed because month. All had healed erosions at repeat cranial pressure allows early recognition of life-threatening haemorrhage uncontroll- endoscopy. When omeprazole was stopped and treatment of cerebral oedema but able by repeated injection sclerotherapy seven rebled from the erosion within two the severe coagulopathy of fulminant with ethanoline oleate. Symptoms were months. This suggests acid contributes to hepatic failure has discouraged this assessed by a modified Visick score. the development of staple line erosion after approach because of the risk of intra- Manometry of upper and lower sphincters transection of the oesophagus. Omeprazole cerebral haemorrhage. We have reviewed and oesophageal body was performed using is more effective than ranitidine in healing our experience in 36 consecutive patients a triple-lumen perfused catheter. Ambula- these erosions and may prevent bleeding. with fulminant hepatic failure in grade IV tory oesophageal pH was monitored over 22 coma who had Ladd extradural intracranial h (Ormed system) and the results analysed pressure monitors inserted through a at 5 pH levels for percentage reflux time and Lactulose hydrogen breath test profiles in frontal burr-hole. The aetiology was para- reflux episodes. All investigations were per- patients with hepatic cirrhosis cetamol overdose in 26 cases and viral formed without complication even though hepatitis in nine and the mean age 30. The varices were still present in three of P MISIRY, H CHESTA, H WADHWANI, K SRAI, median prothrombin time at operation was five patients. No patient complained of AND 0 EPSTIIN (Academic Department of 85 seconds (control 15, range 27-204) and dysphagia. One patient had daily heartburn Medic.ine, Royal Free Hospital, Pond Street, the median platelet count 142x 1OW1 (range Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A746 The British Society ofGastroenterology

52-443). Monitors remained in situ for three M-H TSUI, P J SCHEUER, N MCINTYRE, AND B integrating the areas under the curve of the days (mean, range 1-9). Fourteen patients DICK (Academic Departments of Medicine, beta-ATP peak in the spectra. After the survived; in two abnormal neurological Radiology, and Histopathology, The Royal initial drop in ATP level to 40% due to the signs became evident during convalescence Free Hospital School of Medicine, London) fructose challenge, during 24 h preservation and a CT scan indicated cerebral infarction Transjugular and percutaneous plugged with EC a further decrease to 20% is adjacent to the monitor in one and a deep liver biopsy with gelfoam plugging of the observed while with UW solution the ATP unrelated abscess in the other. In both, needle track have recently been introduced level is stable after 24 h and recovers during eventual outcome was satisfactory. Post- for use in patients with impaired blood the next 24 h to within 78% of the initial mortem examinations were performed in clotting. As the two techniques have not value in Krebs. After reperfusion with 18/22 who died: in none was there evidence been previously compared we report the Krebs-lactate at 37°C the UW preserved of haemorrhage and 11 had cerebral preliminary results of a randomised control- liver recovered more rapidly from a fructose oedema. Complications of ICP monitoring led trial. Patients requiring liver biopsy challenge than did the liver preserved in are relatively few in fulminant hepatic entered the trial if the platelet count was less EC. These data show that liver preservation failure despite severe coagulopathy. than 80000: and/or the prothrombin time using UW results in a better maintainance was more than three seconds prolonged of the intracellular ATP level and a faster compared to control despite vitamin K. appropriate metabolic response to a Colchicine improves hepatic excretory Over a 15 month period 45 patients were fructose challenge, when compared with failure in primary biliary cirrhosis (PBC) randomised; 23 to the plugged and 22 to the EC. transjugular group. Age, sex, liver func- T W WARNES, B P ROWAN, A SMIIH, AND C tion, platelet counts, and prothrombin BABBS (Liver Unit, Manchester Royal times were similar in the two groups. Cholesterol accumulation in renal cortical Infirmary, Manchester) Colchicine treat- Twenty one of 23 patients in the plugged brush border membranes of biliary ment appears to be beneficial in PBC. group had biopsy performed (one patient obstructed rats increases Na-dependent D Conventional liver function tests (LFT's), refused biopsy, one had a transjugular at glucose uptake however, are inadequate tools to monitor physician's request). Liver tissue was response to treatment and new therapeutic obtained in all 21. Two patients had compli- Y IMAI ANI) J S OWEN (SPONSORED BY N endpoints are needed. Galactose elimina- cations after the procedure; one sub- MCIN lYRE) (Academic Department of tion capacity (GEC:mg/min/kg) reflects capsular haematoma, one hypotension Medicine, Royal Free Hospital and School hepatic functional cell mass and may predict requiring blood transfusion. Transjugular of Medicine, Pond Street, Hampstead, survival in PBC; in addition PBC is charac- biopsy was performed in 19/22 patients (one London) Renal dysfunction, particularly terised by severely impaired hepatic excre- refused biopsy, one died before biopsy, and excessive Na is a common and

retention, http://gut.bmj.com/ tory capacity (bromosulphophthalein BSP- one had a plugged biopsy). Liver tissue was important complication of liver disease. k2). The aim of this study, therefore, was to obtained in 16/19 patients. The only compli- The underlying defect is enhanced Na evaluate changes in these dynamic LFT's cation was a neck haematoma in one reabsorption by the proximal tubule, but its during colchicine treatment. patient. In our experience the percutaneous cause is uncertain since many of the pro- Sixty one PBC patients, with a grossly plugged technique appears to be more posed mechanisms seem compensatory abnormal BSP-k2 (<1 5%/min), were effective in obtaining liver tissue in this rather than initiatory. Does plasma lipo- studied during a trial of colchicine treat- patient population and is technically easier. protein induced cholesterol accumulation in ment. GEC and BSP kinetics were deter- renal cortical brush-border membranes mined: BSP-k1 reflecting hepatic blood flow (BBM) cause enhanced Na reabsorption in on September 24, 2021 by guest. Protected copyright. and uptake; BSP-k,, overall function. In the 31p-Nuclear magnetic resonance study of liver disease? placebo group, over three years, BSP-k2 ATP level during liver preservation in rat We measured the cholesterol content of remained grossly abnormal, but improved renal cortical BBM vesicles in rats 1, 3, 8, significantly on colchicine (mean (SD) 0.53 L ROSSARO, C CALDWELL, N MURASE, C HO, I E 15, and 30 days after bile-duct ligation and (0.4) rising to 1.3 (0.9): p=0.015). Overall S1ARZL, D H VAN THIEL, AND R NACCARATO compared their ability to co-transport Na/ liver function, reflected by GEC and BSP- (Cattedra Malattie Apparato Digerente, glucose. Na-dependent D-glucose uptake k,, decreased significantly over three years Universita di Padova, Italy, School of was significantly higher three days after (GEC: 5.1 (1.0) to 3.9 (1.3); p=0 015; BSP- Medicine and Surgery, University of Pitts- ligation compared to non-operated animals k,: 9.2 (5.8) to 4-7 (3.5); p=0.032) in the burgh, and Dept Biological Sciences, (468 (31) pmol/mg protein/4s v 393 (15), placebo group. In contrast the colchicine Carnegie Mellon University, Pittsburgh, p<005, respectively) and was still raised at treated group showed no deterioration. USA) The ATP level of isolated rat liver 30 days (471 (29)). The BBM from ligated Colchicine therefore halted the decline in before, during, and after cold preservation rats were enriched in cholesterol at each overall liver function observed in patients in UW-lactobionate (UW) and Euro- time interval, except 1 day, as indicated by on placebo, and significantly improved the Collins (EC) solutions have been followed small (about 5%) but significant increases characteristic early defect in hepatic non-invasively by phosphorus-31 nuclear (p<0-01) in their cholesterol to phospho- excretory function (BSP-k2). magnetic resonance (3Q'p-NMR) spectro- lipid molar ratio (the main determinant of scopy. A fructose challenge (1.5 mmol) membrane lipid fluidity). There was a during perfusion with Krebs-lactate at 37°C strong positive correlation between Na- Percutaneous plugged versus transjugular was administered and the time course of its dependent D-glucose uptake and the liver biopsy in patients with impaired blood metabolism was studied by lip-NMR both cholesterol to phospholipid ratio (r=0.584, clotting: a controlled trial before and after preservation. Spectra were p<0-001; n=33). Our findings are con- obtained at 81 MHz on a Bruker Biospec II sistent with the hypothesis that Na retention A SAWYERR, P A MCCORMIUK, A K BURROUGHS, (4.7 Tesla). The ATP level is measured by in human liver disease is initiated by Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A747 cholesterol deposition in BBM of the renal causes up-regulation of ER, but the (SEM) to 2 (0.3) mV and resistance (R) proximal tubules. response of AR to testosterone (T) has not from 248 (28) to 30 (13) ohm cm2 and a been investigated. We used a hepatoma cell severe mucosal injury with denudation of line (Hep-G2) to identify the presence of the basal lamina. These findings and the In vitro culture of germinal layer of E AR and determine their response to T. histological injury were similar to those granulosus - effects of albendazole, its meta- Hep-G2 cells were cultured on plastic in observed in tissues not pretreated with bolites, and praziquantel Dulbecco's minimal essential medium PGE, (n= 11). After 10 minutes DOCA (DMEM) with fetal calf serum (FCS) and exposure, and replacement of DOCA with D H IAYLOR AND D L MORRIS (Department of phenol red (PR). The medium was changed standard luminal solution, all tissues were Surgery, University Hospital, Nottingham) to DMEM without FCS and PR (serum free allowed to recover for four hours. In tissues Previous work on in vitro cultures of protos- medium: SFM) for 48 h to avoid the puta- not pretreated with PGE2, there was com- coleces of E granulosus has demonstrated tive oestrogenic effect of PR. The cells were plete histological restitution of the surface the activity of albendazole (Alb) and its then incubated in SFM with 0 nM, 5 nM, epithelium and the PD and R returned to active metabolite albendazole sulphoxide 12-5 nM, 25 nM, 50 nM T. The culture values, not significantly different from the (Alb Sx). We have developed a system medium was aspirated after 48 h and the PD and R before injury. In contrast, which allows us to culture whole cysts and cells were further cultured in SFM for 24 h tissues pretreated with PGE2 did not exhibit therefore allows us to measure the effects (if to wash out T. The cells were then harvested histological restitution of the surface any) of chemotherapy on the germinal layer for assay of AR by the two-tier column epithelium with no significant recovery of of the parasite. Peritoneal cysts removed radioligand binding method (Iqbal et al, PD and R. from gerbils with established infections 1985). Cytosol (C) and nucleosol (N) were We conclude prostaglandins inhibit resti- were cultured in twice weekly changes of assayed separately. The experiment was tution in colonic mucosa in vitro. Drugs that NCTC 135 with 20% FCS and antibiotics for repeated three times. inhibit prostaglandin synthesis may have a 14 and 28 days in the presence or absence of Androgen receptors were detected in C therapeutic role in colonic mucosal ulcera- Alb, Alb Sx, albendazole sulphone (Alb and N, with levels of 136-91.4 fmol/mg sol tion. Sn), and praziquantel (Prazi) with all final protein and Kd of 4-4-17-3 nM, similar to concentrations of 500 sg/l. After culture previously published data. T caused a the cysts were placed into gerbil peritoneal reduction in AR binding at 5 nM and 12.5 Regulation of calcium-pump activity in the cavities (five cysts/gerbil with five gerbils/ nM (physiological levels). Androgen recep- enterocyte by calbindin-D9K culture) for three months before necropsy tor binding returned towards control and assessment. Prazi did not reduce cyst values at 25 nM and 50 nM T. J R F WALTERS (INIRODUCED BY R H DOWLING) survival when compared with controls (C Androgen receptors have been demon- (Gastroenterology Unit, Guy's Campus, 3-8 (0(2), Prazi 3-8 (0(2)). Albendazole and strated in hepatoma cells (Hep-G2) grown UMDS, London) The ATP-dependent Ca' http://gut.bmj.com/ its metabolites significantly (p<0-0() in vitro. Androgen receptor levels were -pump in the basolateral membrane of the reduce cyst numbers (Alb 0 (0), Alb Sx 0-4 reduced at the lower conc's of T, although enterocyte is the energy-dependent step in (0.4), Alb Sn 1 (0.45)). In this system 28 they increased again at 25 nM. There was a the active absorption of dietary Ca". days treatment was in each case more effec- similar trend for both C and N. Absorption of Ca" is dependent on vitamin tive than 14 days, but not significantly so. These findings could be explained by D status and parallels the distribution of The metabolites of albendazole are active in down regulation of AR at physiological calbindin-D9K, the vitamin D-dependent as short a time as 14 days. The excellent conc'1s of T in these malignant hepatocytes Ca"2-binding protein (CaBP). This study protoscolicidal agent, praziquantel, has no in culture. investigated whether the mode of action of on September 24, 2021 by guest. Protected copyright. measurable effect on viability of whole cysts CaBP is to stimulate the activity of the Ca2 - in in vitro culture and therefore its effects on pump. Duodenal basolateral enriched the germinal layer are questionable. membranes were prepared, and ATP- dependent Ca"2 transport by inside-out PLtENARY SESSION POSTERS vesicles was measured as 4'Ca uptake after Response of androgen receptors to testo- the addition of physiological concentrations sterone in hepatoma cell culture Prostaglandins inhibit resitution of colonic (10-60 FM) of bovine intestinal CaBP. mucosa in vitro CaBP stimulated Ca2" transport greatly (a S E J EDMUNDS, A P STUBBS, A A SAN1OS, AND three-fold increase at 30 FtM CaBP), but M L WILKINSON (Gastroenterology Unit, Q ZHANG, P H ROWE, C HANLEY, R C MASON, only in the absence of EGTA as a Ca" - UMDS, Guy's Campus, London) The liver AND MCCOLL (Department of Surgery, buffer. The increased transport was not a is an androgen responsive organ, with pro- Guy's Hospital, UMDS, St Thomas Street, result of any changes in Ca"2 concentration duction of certain proteins and enzymes London) Restitution is restoration of the or 4'Ca specific activity on addition of CaBP. under hormonal control. Also, androgens continuity of the surface epithelium by cell However, Ca2' kinetics in this system were are known to induce hepatic tumours. migration. We have previously described different from those in the presence of Oestrogen and androgen receptors (ER and restitution of colonic mucosa in vitro. We EGTA. The enhanced transport was still AR) have been found in normal liver and investigated the effect of prostaglandins on not saturated at 60 [tM CaBP, and was hepatoma tissue obtained at surgery/ colonic restitution. Using chambered bull unaffected by calmidazolium, a calmodulin autopsy. Androgen receptors have recently frog colonic mucosae pretreated with PGE2 inhibitor. Other proteins that bound Ca2 been found in a hepatoma cell line (PLC/ (10 'M) (n=8) and exposed to 10 mM with similar affinity also stimulated Ca"2 PRF/5) cultured in vivo in nude mice. To sodium deoxycholate (DOCA) in the lumi- transport. This observation, together with date ER but not AR have been discovered nal chamber exhibited an immediate fall in the EGTA-effect, suggested that the Ca2"- in vitro in liver cell cultures. Oestradiol potential difference (PD) from 54 (14) pump may recognise Ca' bound to any such Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A748 The British Society ofGastroenterology high-affinity site. In the enterocyte, CaBP obstruction who were randomised to either labelled proteins were analysed by SDS- concentration is likely to regulate Cal' 10 (53 pts) or 12 FG (53 pts) stents. Patients PAGE and visualised by fluorography. Two extrusion from the cell by the Ca2-pump, were stratified according to whether groups of proteins were observed: (i) those and hence also dietary Ca2' absorption. obstruction of the CBD was above (called present in all isolates including the low MW 'high') or below the cystic duct insertion proteins 22-33 kD and two major bands at (called 'low'). 32 and 81 kD; and (ii) those showing Effects of HMGCoA reductase inhibitors Sixty four patients had 'low' (ca pancreas, differences between isolates (eight bands (HMI) on the lithogenic index of bile (LI) 54; ca ampulla, five; metastases, five) and 42 with MW 30-77 kD). Eight out of 14 isolates patients had 'high' obstruction (cholan- showed unique methionine labelling pro- N HOOGERBRUGGE-VD LINDEN, F W M DE ROOY, gioca, 20; ca gall bladder, seven; meta- files. There was no obvious correlation H JANSEN, AND M VAN BLANKENSTEIN stases, 15). In patients with 'low' obstruc- between [sS]-methionine profile and geo- (Department of Internal Medicine, Univer- tion, 10 FG stents were successfully inserted graphical origin of the isolate. sity Hospital Dijkzigt, Dr Molewaterplein in 31/31 (100%) whereas 12 FG were suc- Biosynthetic labelling of Giardia with 40, 3015 GD Rotterdam, The Netherlands) cessful in only 20/33 (61%). In patients with [S51.-methionine appears to be a highly dis- Treatment of cholesterol gall bladder stones 'high' obstruction, the success rate for 10 criminating system for typing G lamblia by combined extracorporeal shockwave and 12 FG was 95% (21/22) and 35% (7/20) isolates that should be of use in epidemio- lithotripsy and oral bile acid (BA) dissolu- respectively. All 26 patients in whom 12 FG logical studies and in identifying pathogenic tion appears promising. Recurrence rates, stent insertion failed, had a 10 FG inserted strains of Giardia lamblia. however, are likely to be as high as seen successfully. Procedure related complica- after oral BA dissolution alone. HMGCoA tion rates were similar for both stent sizes reductase inhibitors reduce cholesterol (10 FG (12%) v 12 FG (11%)). At time of synthesis, the effect on BA synthesis is death or at at least six months follow up, Effects on ileal output of three peptides unknown. Nine patients with heterozygous stent change was necessary in 27 patients- secreted by tumours associated with the familial hypercholesterolaemia were 21/79 (27%) with 10 FG and 6/27 (22%) watery diarrhoea syndrome (WDS) randomly assigned to either 40 mg prava- with 12 FG. Stent changes were more fre- statin, an HMI, or placebo. Lithogenic quent in 'high' (30%) compared with 'low' J CALAM, Y YIANGOU, G C NIKOU, B J index in duodenal aspirate and four day (20%) obstruction; probably related to the CHRYSANJHOU, J BEACHAM, AND S R BLOOM stool collections for BA excretion, as a increased stent length in the 'high' group. (Departments of Medicine and Chemical measure of BA synthesis, were performed Seven patients are alive at 27-60 wk with the Pathlology, Royal Postgraduate Medical before and after eight weeks of treatment. first stent in situ. Thus 72 patients (68%) School, Hammersmith Hospital, Ducane

After pravastatin mean Ll fell by 21% have so far died with the first stent in situ. Road, London) Tumours associated with http://gut.bmj.com/ (pI change is similar in patients with limited life The aim of this study was to determine HMI's reduce LI and may prove useful in expectancy. which of these peptides is the best marker

preventing recurrence of cholesterol gall for the syndrome. Currently we measure on September 24, 2021 by guest. Protected copyright. bladder stones after non-surgical treatment VIP, but both PHM and PHV are more by decreasing cholesterol secretion without [PSJ-Methionine biosynthetic radiolabelling abundant in plasma in the WDS, and more inhibiting BA synthesis. ofGiardia lamblia: basis for a typing system? potent intestinal secretagogues in the rat. We therefore infused the three peptides at A M CEVALLOS, A M MORRISON, S C ARCHIBALD, 5 pmol/kg/min into six patients with ileo- A randomised trial of 10 v 12 FG endopros- P D BUICHER, AND M J G FARTHING (Depart- stomies for two hours. Mean plateau levels theses for malignant biliary obstruction: ment of Gastroenterology, St Bartholo- of VIP, PHM, and PHV were 163, 1301, Does stent size matter? mew's Hospital, London) The factors that and 2106 pmol/l respectively, and within the determine the severity and duration of range seen in the WDS. J F DOWSE-IT, S J WILLIAMS, A R W HATFIELD, J Giardia lamblia infections are not com- Vasoactive intestinal peptide produced HOUGHTON, T LENNON, AND R C G RUSSELL pletely understood. Parasite virulence is an integrated ileal output of 237 (35-1616) g (Departments of Gastroenterology and likely to be of great importance but in the (geometric mean (95% confidence limits)), Surgery, The Middlesex Hospital and The absence of an accepted system of strain compared with only 15 (2-102) g with PHM CRC Clinical Trials Centre, Kings College typing, differences in pathogenicity and 2 (0.3-16) g with PHV (p= 0.()8). VIP School of Medicine and Dentistry, London) between Giardia isolates cannot be identi- increased chloride (p

The British Society ofGastroenterology A749

C D DEAKIN, C D GOVE, E A FAGAN, J M and endotoxin stimulated production of humoral colonic mucosal defences rela- TREDGER, AND ROGER WILLIAMS (Liver Unit, TNF were measured before and during a- tively immunosuppressed. King's College Hospital, Denmark Hill, interferon therapy in seven chronic HBV London) Paracetamol (NAPA) overdose carriers. Four patients developed a bio- has a high mortality (>50%) in patients who chemical hepatitis associated with perma- Inhibition of peripheral blood natural killer present too late to benefit from N- nent inhibition of HBV replication three to (NK) cell activity by in vivo treatment with acetylcysteine (NAC) and develop acute 12 weeks after commencing treatment. In salazosulphapyridine (SASP) but not with liver failure. Hepatocyte death follows each instance this was associated with spon- 5-aminosalicyclic acid (5-ASA) a rise in intracellular calcium secondary taneous production of TNF (median 190 to influx across the plasma membrane. U/ml, range 116-7()() from levels undetect- M N APARICIO-PAGES, G E CRAMA-BOHBOUIH, Possible beneficial effects of a calcium able before therapy. By contrast spon- H W VERSPAGHT, A S PENA, 1TWETERMAN, ANI) channel blocker, diltiazem, were examined taneous production of TNF was detected C B H W L AMERS (Department ofGastroenter- in vivo late after a hepatotoxic dose of only once in one of three cases unresponsive ology and Hepatology, University Hospital, NAPA. Adult male CDI mice were dosed to ax-interferon at low levels (56 U/ml). Leiden, The Netherlands) Low NK cell with NAPA (450 mg/kg po) followed by Endotoxin stimulated TNF production was activity in patients with inflammatory bowel diltiazem (30 mg/kg ip) at six, nine, or 24 also found to be significantly greater in ai- disease (IBD) has been found in several hours or saline or N-acetylcysteine at two or interferon responsive patients than in studies. In vitro studies with SASP and its nine hours. Mice were killed 30 hours after unresponsive patients (p<0.0()5). metabolites resulted in a decreased NK cell NAPA. When administered at nine hours, These data suggest that TNF production activity. To determine whether the diltiazem decreased liver damage as judged is induced by ca-interferon in those HBV decreased NK cell activity in IBD was by plasma aspartate aminotransferase carriers in whom permanent inhibition of attributable to treatment we studied the activity (mean (SD), control 837 (1060), viral replication is produced. effect of a four week in vivo administration n=18; diltiazem 220 (201), n=18; p<0-05 of 5-ASA (Salofalkl 5(X) mg qid), SASP Wilcoxon's rank-sum test) and N- (10(X) mg qid), and placebo in a randomised acetylgulcosaminidase, coagulation cascade Cigarette smoking and mucosal immunoglo- crossover trial in five IBD patients in remis- proteins (Normotest) and macroscopic liver bulin production in inflammatory bowel sion and four controls. Peripheral blood NK score results. Liver histology showed disease cell activity was determined at the end of mitotic bodies were increased in the each period in a chromium-5 1 release assay diltiazem treated mice compared with con- G F COPE, L PURKINS, L TREJDOSIEWIC7, R V against K-562 targets at a 50:1 effector- trol animals (8.3 v 1-() per high power field, HEAILEY, AND J KELLEHER (Department of target ratio. Natural killer cell activity is n=8 and 7 respectively, p<0-05 Wilcoxon's Medicine, St James's University Hospital, expressed as % cytotoxicity and results rank-sum test). No protective effect was Leeds) Cigarette smoking has received con- evaluated by the Student's t test. http://gut.bmj.com/ seen with diltiazem at six, 12, or 24 hours siderable attention in recent years as a Salazosulphapyridine reduced the NK cell after NAPA. N-acetylcysteine showed opti- possible factor in the pathogenesis of activity compared with placebo both in mal cytoprotection at two hours. Diltiazem inflammatory bowel disease (IBD). Altered patients and controls (respectively 40(2 may provide hepatic protection by decreas- immunoglobulin production has been (18.2) v 74-4 (4-8) and 26.2 (183) v 59-2 ing the degree of hepatocyte damage, associated with inflammatory bowel (5.9)), which restored completely after four enabling cell regeneration. The beneficial disease, and smoking has been shown to weeks placebo. 5-ASA, however, only effect at nine hours in mice occurs later than influence peripheral immunoglobulin marginally affected the NK cell activity that for NAC (up to three hours) and may levels. We measured preformed and newly (patients 52-5 (9-1) and controls 62-5 (6-3)). on September 24, 2021 by guest. Protected copyright. be relevant to the treatment of patients who synthesised IgA, IgG, and IgM by colonic When patients and controls were combined present late after paracetamol overdose and biopsies in organ culture (medians, ng/mg NK cell activity under SASP treatment (34. 1 for whom there is no currently established biopsy protein), from 26 patients with IBD, (12.4)) was lower compared with 5-ASA antidote. and 50 controls. (56-9 (5.7)) and placebo (67-6 (4.4), Separation of patients by current p<005). Sixty seven per cent of all indi- smoking habit showed that smoking had viduals on SASP had NK cell activity levels Spontaneous TNFa production is associated little effect on the preformed levels of all below the lowest placebo value (46.2%) with clearance of hepatitis B virus in inter- three Igs, however smoking had profound whereas on 5-ASA only 22% of them were feron treated carriers effects on the synthesis of immunoglobulins lower. after culture. Thus, IgA synthesis was In vivo administration of SASP reversibly H M DANIELS, G J M ALEXANDER, A MEAGER, reduced in both controls (6-4) and IBD reduces the NK cell activity significantly in a A LW F EDDLESTON, AND ROGER WILLIAMS patients (7-0) who smoked compared with majority (67%) of the individuals tested in (Liver Unit, King's College Hospital, non-smokers (15-8 and 38-8 respectively). contrast to 5-ASA (only 22%). Thus, treat- Denmark Hill, London) Treatment of IgG production increased in smokers with ment with SASP may contribute to the chronic hepatitis B virus (HBV) carriers IBD (25-9 compared with 5.3), while IgM decreased NK cell activity in patients with with ca-interferon is associated with perma- production was greatly decreased in IBD IBD. Moreover, this study indicates that nent inhibition of viral replication in only smokers (0.4 compared with 2.2), but 5-ASA may be the drug of choice for 30% of cases, but the precise mode of action increased in controls who smoked (2.2 longterm treatment of IBD in view of the of a-interferon is unclear as transient inhibi- compared with 0.4). immunological side effects of SASP. tion of viral replication is observed in most Smoking is now regarded as having instances. Tumour necrosis factor (TNF), a possible significance in the pathogenesis of monocyte product, has recently been shown inflammatory bowel disease. This study Right sided colonic response to eating is to have potent antiviral activity in vitro that suggests that smoking has a profound largely non-propulsive is synergistic with both y and ri-interferons. influence on immunoglobulin production by In the present study in vitro spontaneous the colonic mucosa, rendering patients' E K BOHEMEN, K SIEED, J G HARDY, G M Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A750 rThe British Society ofGastroenterology

LAMONT, D A EVANS, C G WILSON, AND R C 15 underwent surgical resection and two workers believe that CT evidence of SPILLER (Departments of Physiology and were managed conservatively. By contrast enlarged para-oesophageal nodes signifies Pharmacology, Medical Physics and only nine of 45 patients taking neither drug incurable disease and constitutes a contra- Therapeutics, Queen 's Medical Centre, had such complications (p<0(02). Six of this indication to attempted curative resection. Nottingham) Eating stimulates colonic group were managed surgically and three This study was undertaken to investigate motility but what effect does this have on conservatively. There was one death in each the relationship between nodal status and the movement of colonic contents? We have group. Those presenting with inflammatory survival after 'curative' resection. assessed the response of the right colon to a complications were managed with systemic Forty nine patients underwent oeso- 1(XX) kcal meal in eight healthy volunteers, antibiotic therapy without mortality. phagogastrectomy and lymphadenectomy who on separate days took either a high (74) We have found that perforated diverticu- between 1975-81. Follow up has been for a g fat or low (32) g fat version. A pressure- lar disease occurs more commonly in minimum of five years and survival has becen sensitive radio pill and 1 MBq Ind"' DTPA patients taking NSAIDs and conclude that correlated with nodal status. were taken at 10 pm. When the pill and NSAID consumption is associated with a Nodal metastases were present in 72% of Ind"' reached the colon the following day, more severe form of the disease. resected patients. comprising 59% of after one hour basal recordings, the test squamous lesions and 80(% of adenocarci- meal was eaten and recordings made for noma. Overall five year survival was 14.3%, four hours. The motility index used was the Is antireflux surgery appropriate for upright but in patients with nodal metastases was area under the pressure trace. The colonic refluxers? 3.2%. Stratification according to cell type scintigraphic image was divided into seven revealed 10% five year survival in node regions. The geometric centre (GC) of the A P BARLOW, I NORRIS, ANI) A WAISON positive squamous lesions. Four patients isotope mass was calculated from the counts (Department of Surgery, Royal Lancaster had enlarged nodes detected on CT scan- (C0) in each region using the formula: GC= Infirmary, Lancaster) It has been suggested ning which, histologically, showed reactive

Cn x n/total counts. that patients with gastro-oesophageal reflux hyperplasia only. Three of these patients The results: (mean (SEM)) motility index in the upright position fare badly after survived beyond five years. rose from 1 11 (0.30) basal to 2-49 (0-55) antireflux surgery because such reflux is Prolonged survival is possible in the two hours postprandially, n= 16, p<0-02 secondary to aerophagia. Consequently, presence of nodal metastases from (high fat 2-26 (0.51), low fat 2-70 (0(83), some surgeons are reluctant to offer these squamous lesions where five years survival difference NS). There was no significant patients anti-reflux surgery, despite failure is 10%. Enlarged nodes exhibiting reactive movement of right colonic contents during of medical treatment. hyperplasia are associated with a good prog- this period, the geometric centre being 3-33 Of 1(K) consecutive patients who under- nosis. Thus, the CT detection of enlarged

(0.28) initially and 3-50 (0.25) two hours went an antireflux procedure at this institu- lymph nodes is an unreliable prognostic http://gut.bmj.com/ postprandially (diff, NS), again no signifi- tion, 28 were upright refluxers. All had indicator and does not constitute a contra- cant difference between the two meals. Net failed to respond satisfactorily to medical indication to attempted curative resection. retrograde movements occurred in three therapy. Endoscopy, manometry and pH subjects after low fat meal but none after monitoring were performed before and the high fat meal. During 60 h of observa- three months after surgery. Ten patients Sedation for upper GI endoscopy - no room tion only one mass movement occurred. underwent gastric emptying studies. for complacency. The results of a national Contrary to popular but untested belief Preoperatively, 24 patients had oesopha- survey

the pressure waves seen in the right colon gitis, 12 had a defective LOS and nine on September 24, 2021 by guest. Protected copyright. postprandially are largely of a non- ineffective oesophageal motility. Gastric 1 K DANE-SHMEND, R F A LOGAN, AND G DBELL propulsive segmenting type. emptying was normal in nine of the 10 (Dept of Therapeutics, University Hospital, patients. After surgery, 23 patients were Nottinghiam and Dlept of Medicine, Ipswich free of heartburn and regurgitation. Six had Hospital, lpswich, Suffolk) There are few Perforation of diverticular disease is more mild epigastric discomfort or flatulence, but studies of the safety of sedation for upper likely in patients taking non-steroidal anti- there was no gas bloat. LOS pressure G6 endoscopy, but in the US 66 deaths have inflammatory drugs (NSAIDs) improved (11.4 l} 13-7 p<0.05) but motility recently been reported after sedation with was unaffected. Abnormal oesophageal midazolam (Lancet 1988; ii: 140). We R G WILSON, I M C MACINTYRE, AND A N SMITH acid exposure was abolished in 26 (93%) received 665 replies to a survey of 1048 (Department of Surgery, University of which resulted in healing of oesophagitis, at endoscopists. Six per cent never used intra- Edinburgh, Western General Hospital, three months, in 21 (88%). venous (iv) sedation, while 62% almost Edinburgh) Previous retrospective studies Patients with upright gastro-oesophageal always gave a benzodiazcpine: (Diazemuls suggest an association between NSAID reflux fare as well after surgery as other (59%), midazolan (34%)). An additional consumption and the complications of reflux patients. As 90% have an excellent drug, mainly pethidine, was used routinely diverticular disease. A prospective study result from surgery, all who fail medical by 13%. In the previous two years, hypo- has been made of all patients with acute therapy should be encouraged to have anti- ventilation requiring oxygen had been complications of diverticular disease admit- reflux surgery, regardless of the pattern of noted by 40%; respiratory arrest and ted to one hospital over a 30 month period. reflux. cardiac arrest by 3% and 5% respectively. Of 72 patients, 25 were taking NSAIDs (in Supplementary oxygen during endoscopy seven cases combined with systemic corti- was used by 2% more often than once per costeroids), two were taking steroids alone, Is computed tomography (CT) demonstra- month, while 42% never used it. Fifty two and 45 were on neither drug. Only four tion of enlarged nodes a contra-indication to deaths were reported in which sedation, patients taking these drugs had a previous resection in oesophageal carcinoma? endoscopy or both may have contributed. history of diverticular disease. Seventeen of Forty per cent were aware of deaths or the 25 patients taking NSAIDs presented A WAISON (Department of Surgery, Royal cardiorespiratory arrests encountered by with a perforation or peritonitis, of whom Lancaster Infirmary, Lancaster) Some other endoscopists in their own hospital. If Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

The British Society ofGastroenterology A751 these complications are related to hypox- and investigated the relationship to sup- Etodolac causes less endoscopic damagc aemia then greater use of supplementary pression of acidity using correlation and than Naproxen. Naproxen suppressed oxygen should reduce their incidence. Pros- linear regression. gastric PGE2 and duodenal PGE2 and PG I. pective studies are now needed to identify At four weeks, healing rates were signific- Not all NSAIDs suppress gastric or duo- the circumstances and risk factors associ- antly correlated with suppression of 24 hour denal PGs, as shown by Etodolac. ated with such complications. acidity (r=0(76; n=9; p<0-01) but not nocturnal acidity (r=0-45; n= 10; p>0-05). At eight weeks, healing was significantly Elimination of high titre human immuno- correlated with suppression of 24 hour deficiency virus from endoscopes (r=0-81; n=9; p<0-005) and nocturnal P11ENARY acidity (r=0(63; n= 10; p<0-05). P J V HANSON, D GOR, D J JEFFRIES, J V COI.I INS Omeprazole 40 mg daily had the highest Women with intractable constipation have (INTRODUCED BY R ZEEGEN) (Brompton, St healing rates (79-9% at four weeks, 95-9% an abnormality of adrenal steroids Stephen 's and St Mary's Hospitals, London) at eight weeks) and the shortest time to One third of gastroscopes used on patients achieve a healing rate of 50% (estimated at M A KAMM, J E LENNAR[)-JONES, M J G FKARIH- with AIDS are contaminated with HIV. To 2-5 weeks). H2 antagonists healed 82 to ING, A MCI HAN, 1 PERRY, ANI) I CHARD (St study the kinetics of elimination of HIV 90% of GUs at eight weeks, and took three Mark 's and St Barthlolomew 's Ho)spitals, from endoscope surfaces, high titre HIV in to four weeks to reach 50% healing. London) Patients with severe idiopathic serum was aspirated into suction-biopsy Suppression of 24 hour acidity is related constipation are almost exclusively women channels of five GIF XQ20 endoscopes. Air to GU healing rates but not as closely as in of reproductive age, with a high incidence of and water channels of two instruments were duodenal ulcer. Suppression of nocturnal abdominal pain and previous gynaeco- similarly contaminated. Contamination was acidity may be of less importance. Factors logical surgery. To determine whether there measured by irrigating channels with viral other than acid suppression may be is a hormonal or gynaecological abnor- medium, after elution of disinfectant where involved in GU healing. mality present we have examined their sex appropriate, and collecting 3 ml for antigen hormones and pelvic morphology. immunoassay. Endoscopes were cleaned Twenty six women with intractable con- manually in neutral detergent according to Effect of repeated therapeutic doses of stipation (mean age 32, bowel frequency manufacturer's recommendations and dis- naproxen and etodolac on gastric and duo- <1/week) and 21 healthy control women infected in 2% alkaline glutaraldehyde denal mucosal prostaglandins (PGs) in (mean age 33) were studied. Blood samples (Cidex, Surgikos) for two, four, and 10 rheumatoid arthritis (RA) were taken on day 5 (follicular) and days 19, minutes. Contamination was measured 21, 23 for measurement of serum

(luteal) http://gut.bmj.com/ before and after cleaning and after each A S IAHA, S MCLAUGHIIN, P J HOI.LANI), R W FSH, LH, prolactin, oestradiol (E2), pro- disinfection period. Initial contamination KELILY, R D STURROCK, ANI) R RUSSELI gesterone (P), testosterone, androstene- comprised 48xl()4 to 35xlOb picograms (Departments of Gastroenterology and dione, dehydroepiandrosterone sulphate, (pg) HIV antigen per ml. Cleaning in deter- Rheumatology, Glasgow Royal Infirmary 17-OH progesterone, cortisol, and sex gent achieved a reduction to 165 pg/mI and MRC Unit for Reproductive Biology, hormone binding globulin. Pelvis ultra- (99.93%) on one endoscope and to Edinburgh, Scotland) Most studies on the sonography was performed in the follicular undetectable levels (100%) on four. After effect of non-steroidal anti-inflammatory phase to assess ovarian, uterine, and pelvic two minutes in Cidex all samples were drugs (NSAID) on gastric PGs have vein morphology and size. negative and remained negative after the involved giving single doses or short courses There was a significant reduction in on September 24, 2021 by guest. Protected copyright. longer disinfection times. Air and water of aspirin or indomethacin to animals or to patients' luteal E2 (570( v 420 pM, p<0.0l, channels, where contaminated, were tested healthy humans, often without knowing controls v patients, median value, Mann- after 10 minutes disinfection and were base line values. We studied PG synthesis in Whitney U test), follicular P (4-5 v 4-0 nM, negative. 27 patients (mean age of 52 years) with p<0-01), testo (2-3 v 1.8 nM, p<0-l0), Cleaning in detergent reduced high-titre active RA not on NSAID, before and four andro (10.3 v 8 4 nM, p<0(05), DHEAS HIV on gastroscopes by 99-98 to 100%, weeks after taking Naproxen 1000 mg or (5.1 v 3.0 uM, p<0)05), 17-OH Prog (9-7 v reducing the need for long disinfection Etodolac 600 mg/day. Initial endoscopy had 58 nM, p<0-0l), and cortisol (387 v 245 times. to be normal and anti-peptic drugs were not nM, p<0-l0). There was no abnormality of allowed. Biopsies were taken from the gas- FSH, LH, Prol, or SHBG. Pelvic ultra- tric antrum and first part of duodenum. sound showed no abnormality of ovarian, Antisecretory drugs in gastric ulcer (GU): Drug delivery and all assessments were uterine, or pelvic vein size or structure. relationship between suppression of acidity double-blind. Both drugs had equal anti- Women with idiopathic constipation have and healing rates arthritic activity. Seven of 13 patients on a consistent reduction of adrenal steroids, Naproxen (54%) developed endoscopic which may be pathogenically important. C W HOWDEN AND R H HUNT (Gastro- gastric and duodenal damage compared Their abdominal pain and previous surgery enterology Unit, Glasgow Royal Infirmary with three of 14 on Etodolac (21%) whose cannot be accounted for by any pelvic and McMaster University, Hamilton, Lanza scores were lower (p<0-05, Mann- structural abnormality. Ontario, Canada) To see if GU healing Whitney). Naproxen suppressed gastric rates on antisecretory drugs were related to PGE2 from a median of 36 to 14 ng/mg degree of suppression of acidity, we con- protein (p<0-01, Wilcoxon's), duodenal ducted a meta-analysis of 72 published con- PGE2 from 39 to 18 (p<0-05) and duodenal Diagnosis of food allergy by enumerating trolled trials involving H2 antagonists, PGI2 from 62 to 15 ng/mg protein (p<005). IgE containing duodenal cells omeprazole and enprostil. We have calcu- Etodolac did not suppress any of the PGs lated overall healing rates and 95% con- studied (PGE2, PGI2, Thromboxane B2). C AN[)RE, F ANDRE, 1 DESCOS, AND S CAVAGNA fidence limits for different drug regimens Despite equal anti-arthritic activity (Laboratoire d Immunopathologie Diges- Gut: first published as 10.1136/gut.30.5.A704 on 1 May 1989. Downloaded from

A752 The British Society ofGastroenterology tive INSERM, Centre Hospitalier, Lyon- purified from human pancreatic juice after test results. In this study the overall sensi- Sud, Pierre Benite, France) Biopsies were published methods and tested at concentra- tivity of the 13C-urea breath test was 900O obtained during endoscopie examination tions of 10 `-10 ' M for growth stimulatory and the specificity was 98.6%o. The accuracy from jejunum, third portion of duodenum, activity on AR4-2J cells, using both soft was 94.8% with a positive predictive value second portion of duodenum, first portion agarose colony formation and [ HJ- of 98.X2% and a negative predictive value of of duodenum, antrum, and corpus mucosae thymidine incorporation assays. 92O5%. in 120 control subjects and in 220 food Human PSTI stimulated colony forma- In conclusion, the present results suggest allergic patients. None of them was infested tion consistently in three assays. Peak that the 13C-urea breath test is a sensitive by gut parasites. Immunofluorescence activity (range 193-260% of control) was and highly specific method for detection of studies were used to identify mucosal seen with PSTI (10 `-10 "' M). PSTI had Cp. Using a non-radioactive isotope it per- plasma cells. Immunoglobulin containing more effect than that of gastrin (1) "' M). mits repeated longterm follow up in moni- cells were counted according to the tissue PSTI also stimulated incorporation of [`HJ- toring the response to treatment in an easy unit method. thymidine. The maximal effect (83% above and non-invasive way and facilitates epide- The diagnosis of food allergy relied on control; p<0.00l) was seen with 1i) M miological investigations. history taking, skin prick tests, detection of PSTI. This effect was similar to that of IgE anti-food antibodies by the radio- gastrin (10 'M) and EGF (20 ng/ml). allergo-sorbent-test and on a positive Pancreatic secretory trypsin inhibitor did provocation test associated to intestinal per- not stimulate [ H]-thymidine incorporation Direct measurement of an intrinsic oesopha- meability measurement by the lactulose/ in either MKN45 human gastric carcinoma, geal clearance abnormality in patients with mannitol test. MC26 mouse colon carcinoma or EGF- reflux oesophagitis In control subjects, the mean numbers of responsive 3T3 mouse fibroblast cell lines. IgA, IgM, IgG, lgD, and IgE cells were 97, Pancreatic secretory trypsin inhibitor, D WIlLIAMS, D G IHOMPSON, M MARPIES, 17, 8, 1, and 1 in intestinal biopsies. The which is produced by the pancreas, stimu- I O HANRAHAN, AND J BANCE(WICZ (Depart- mean numbers of IgA, IgM, IgG, IgG, and lates growth of the rat pancreatic cancer cell mewnts of Medlicine and .Suurgery, Hope IgE cells were 30, 2, 5, 1, and 1 in the gastric line AR4-2J, and may therefore be involved Hospital (Unit'ersity of Manchlester School tissues. in the pathogenesis of pancreatic cancer. of Medicine), Eccles Old Road, Salforpd) A In food-allergic patients, the mean num- physiological disorder of the intrinsic bers of IgA, IgM, IgG, IgD, and IgE cells oesophageal clearance mechanism has long were 90, 17, 5, 1, and 16 in the intestinal been suggested, but remains unproven, in biopsies. The mean numbers of IgA, IgM, Sensitivity and specificity of the 13C-urea oesophagitis. We report a method for direct http://gut.bmj.com/ IgG, IgD, and IgE cells were 27, 4, 5, 1, and breath test in detecting Campylobacter measurement of intrinsic (non-swallow 3 in gastric tissues. Sensitisation was admit- pyloni related) oesophageal clearance forces, ted if the number of IgE cells for three tissue using a miniature intraoesophageal force units was six or more in the intestine and S DILL, J J PAYNE-JAMES, D MC SWIGGAN, C M transducer attached to an inflatable three or more in the stomach. A significant SCRIMGEOUR, M J RENNIE-, ANI) JJ MISIEWICZ balloon. Normal studies: 15 normal indi- increase of IgE cells was found in all of the (Department of Gastroenterology and viduals underwent manometric study intestinal samples from the 220 food- Nutrition, Central Middlesex Hospital, together with graded intraluminal balloon allergic patients but in only 92 gastric biop- Acton Lane, London) A recent study has distensions (2-12 ml, 1(-25 mm diameter) on September 24, 2021 by guest. Protected copyright. sies from these patients. No control patient shown that the 13C-urea breath test is a at a point 5 cm above the LOS. Above a presented increased number of IgE cells. simple and non-invasive method for detec- threshold of 5 (3-7) ml (median (interquar- Enumerating IgE-containing cells from tion of Campylobacter pyloni (Cp). At tile range)) irregular proximal contractions the duodenum, but not from the stomach, present data concerning specificity and sen- were induced which increased in number may be an efficient method for the diagnosis sitivity of this test are sparse. We report the with increasing distension. Sum of of food allergy in patients without gut evaluation of 134 13C-urea breath tests in contractions/30 sec at 5 ml inflation=20 ( 1(- parasites. comparison with Gram stain, rapid urease 75) mmHg; at 10 ml=60 (40-80) mmHg test (CLO-test) and microbiological cul- (p<0(05 v 5 ml). An increasing aboral tures. The results of the 134 breath tests traction force was also exerted on the bal- Pancreatic secretory trypsin inhibitor were obtained from 69 patients at 134 loon and was directly related to the degree (PSTI) stimulates growth of AR4-2J rat endoscopies. Sixty five patients had a breath of distension. Force at 5 ml inflation= 15 pancreatic carcinoma cells test and endoscopy on two occasions. Using (5-35) g, at 10 ml=30 (15-55) g (p<0.05 l the bacterial culture as gold standard, we 5 ml). I C FREEMAN, B J CURRY, J CALAM, AND J R found 60 Cp positive patients and 54 of Patient studies: 18 patients with varying WOODBURN (Department of Medicine, Royal these had positive breath test results and six degrees of oesophagitis were similarly Postgraduate Medical School, Hammer- had negative tests: five of the six false- studied. The threshold for induction of the smith Hospital, London and Bioscience 1, negative results occurred after four weeks intrinsic response was higher 7 (5-12) ml ICI Plharmaceuticals, Mereside, Alderley treatment with tripotassium dicitrato bis- (p<0-05 v' N) and clearance forces were Park, Macclesfield, Cheshire) Pancreatic muthate with a marked decrease of Cp as consistently weaker, being 0 ((-12) g at acinar cells secrete PSTI which has sequ- shown by the other tests. Four weeks after 5 ml, 8 ((-26) g at 1) ml distension (p<0.0)5 ence homology with epidermal growth fac- drug withdrawal the 13C-urea breath test v N). Patients with oesophagitis thus show tor (EGF). We examined the effects of was positive again in four patients. The fifth deficient intrinsically mediated luminal PSTI on the growth of rat pancreatic acinar patient refused to come back for a third clearance which probably explains the pro- cell carcinoma line AR4-2J. breath test. Seventy four patients were Cp longed postreflux acid residence seen in this Pancreatic secretory trypsin inhibitor was negative and all but one had negative breath condition.