Gut, 1991,32, A1203-A1260 A 1203 British Society of Gastroenterology Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from

The 1991 Autumn Meeting of the British Society of Gastroenterology was held at the University of Warwick from 9-11 September under the presidency of Professor Sir Robert Shields. Below are printed the 323 abstracts selected by the Programme Committee of the Society for oral and poster presentation.

contraction and anal canal electrosensitivity The results showed that 95% of affected individuals (40/42) were informative with at COLORECTAL: SURGERY, INFLAMMATION AND were not significantly different. one probe (diagnostic accuracy 90-98%). NEOPLASIA Plugs were judged easy to insert (82% of least 45% were informative for flanking or remove (88%) and leakage occurred Some uses) (diagnostic accuracy >99%). during 20% of uses. Eleven patients would use markers Obstructed colon: do metalloproteinases the plug if it became commercially available. Altogether 82% of at risk individuals (27/33) for one or more probes. In 22 have a role in anastomotic dehiscence? plug may have a role in the were informative The anal by bowel management of patients with anorectal incon- cases prior risk had been reduced D L P LACOMBE, F J SAVAGE, R M HEMBRY, P B examination. Only one had the high risk allele. BOULOS (Department of Surgery, University tinence. Success depends on patient preference rather than underlying anorectal physiological Of 11 unscreened individuals, six had the low College and Middlesex School of Medicine, risk allele, three carried the high risk allele, and London and Strangeways Research Laboratory, parameters. two were uninformative. Cambridge) Indirect evidence suggested that In conclusion, DNA analysis can accurately collagenase is a factor in colonic anastomotic Failure of internal sphincter relaxation: the identify high risk family members. In conjunc- leakage. This study examined immunohisto- cause offissure? tion with clinical assessment it can also be used chemically the distribution of collagenase, and to considerably reduce an individual's risk. other metalloproteinases: stromelysin and R FAROUK, G S DUTHIE, D C C BARTOLO, A B This information can be used to reduce the gelatinase and their inhibitor, tissue inhibitor MACGREGOR, R MILLER (Departments ofSurgery, frequency of subsequent bowel screening. In of metalloproteinases (TIMP) in a rabbit Royal Infirmary ofEdinburgh and Bristol Royal our study population, 16/42 families (38%) colonic anastomosis. Infirmary) We carried out ambulatory measure- could benefit from DNA analysis. Develop- An anastomosis was formed after transection ments of internal anal sphincter electromyo- ment of preserved tissue DNA analysis from (group 1 n= 12), after resection of a 3 cm gram (EMG) with anal pressures using a deceased relatives would make a further segment of distal colon (group 2 n= 12) and computerised system to determine whether 16 families potentially informative. Direct after obstruction by a silicone ring placed the failure of internal sphincter (IAS) relaxation mutation probes would be needed for analysis day before resection (group 3 n= 12). Rabbits was the cause of anal fissures. in the remaining 10 families, which comprise of were killed 0 5, one, three, and seven days later Fifteen patients (median age=36 years isolated cases. and tissue taken from the anastomosis (A), (interquartile range 26-40); eight male) with and 3 5 (P1), and 20 (P2) cm anal fissures and 11 normal volunteers (age= 36 distal (D) (P0), mucosal proliferation after ileorec- proximally. years (25-71); six male) underwent fine wire Reduced In all groups, intra- and extracellular enzyme anal sphincter electromyography and anal tal anastomosis in familial adenomatous http://gut.bmj.com/ and TIMP were present at the anastomosis. In manometry. The median (range) IAS EMG polyposis may explain rectal polyp regression group 3 only,intracellular gelatinase occurred frequency was fissure=0-45 Hz (0.31-05), K C R FARMER, RK S PHILLIPS (St Mark's in the submucosa of the resected segment normal=0-41 Hz (0.25-0-44; p<0-01*). Hospital, London and Professorial Surgical Unit, and all postoperative tissue, extracellular Median anal pressures were fissure=118 cm St Bartholomew's Hospital, London) Rectal collagenase, gelatinase, stromelysin, and H20 (89-127), normal=90 cm H20 (60-130; polyp regression occurs in familial adenoma- TIMP were seen in the mucosa of D, A, P0, p<0002*). A direct linear relation between the tous polyposis (FAP) after ileorectal anastomo- and P1 but at seven days they were restricted to IAS EMG frequency and resting anal pressure sis (IRA). Because neoplasia and epithelial cell the anastomosis. was seen in both groups. The median number turnover are related, we determined the effect on September 28, 2021 by guest. Protected copyright. In the obstructed colon changes in the metal- of anorectal sampling episodes per hour was of IRA on rectal mucosal proliferation in FAP. loproteinases are less confined and may justify fissure=2 (1-4), normal=5 (4-6; p<0-01*). Endoscopic biopsy specimens of flat rectal reluctance for primary anastomosis in humans. Fewer episodes of sampling occurred at night mucosa were taken from eight FAP patients in both groups. Anal ultra-slow wave activity before colectomy and 12 FAP patients with an was noted in seven patients with fissures but established IRA. Mucosal proliferation was An analplug for use in anorectal incontinence not in the normal group. assessed by flash labelling proliferating cells The IAS EMG frequency is higher than T J O'KELLY, M SMILGIN HUMPHRIES, N IMCC with bromodeoxyuridine. Labelled cells were anal fissures and corre- MORTENSEN (Department of Surgery, John normal in patients with visualised on paraffin sections using an anti- Radcliffe Hospital, Oxford) We have developed lates directly with higher resting anal pres- bromodeoxyuridine monoclonal antibody. relaxation occurs on a new disposable anal plug for use in anorectal sures. Internal sphincter Twenty crypt columns were analysed. Micro- incontinence. Two tulip shaped designs (large fewer occasions in patients with fissures com- adenomas were excluded. Statistics: Mann- and small) have been trialled. Fourteen incon- pared with controls. Whitney U test. tinent patients (idiopathic 10, post anal surgery *Mann-Whitney U test. The mean labelling index (mean (SD) per- 2, spina bifida 2) median age 61 years (range centage labelled cells/crypt of FAP precolec- 18-82 years) used the plugs for two weeks, Polymorphic DNA probes and predictive tomy patients (13-2 (2.5)%) was significantly keeping a diary ofplug performance. familial adenomatous polyposis: greater than that of FAP patients with estab- diagnosis of lished IRAs (7.0 (1-4)%); (p=00002). Before Patients used more of the small plugs (small a population based study 12-1 (0.9) (mean (SEM)) v large 9-6 (1-0); p= colectomy, more labelled cells were in the 0-046 Wilcoxon signed rank test) but, there D G MORTON, F MACDONALD, M RINDL, middle and upper zones of the crypt was no difference in overall (small 133 (16) hrs R CULLEN, J HAYDON, J GIBSON, C McKEONN, (p<0005); by contrast more labelled cells were v large 97 (15) hrs) or individual plug use time J NEOPTOLEMOS, M KEIGHLEY, M HULTEN in the lower zone after IRA (p<0 005). (small 11.1 (141) hrs v large 10.3 (1.1) hrs). (University Department of Surgery, Regional Colectomy and IRA in FAP is associated There was no correlation between duration of Genetic Services and East Birmingham Depart- with a significant reduction in rectal mucosal plug use and anal canal pressures or sensation. ment of Ophthalmology, Birmingham) The cell proliferation. These findings may explain In the 10 patients who preferred the small plug, putative gene for familial adenomatous poly- both polyp regression in FAP after IRA and maximum resting anal canal pressure (MRP) posis (FAP) has closely linked flanking also the low rectal cancer risk. was lower than in those who liked the larger markers which can be used for predictive plug (small 39 (9.5) cm H20 v 91 (9.0) cm H20; diagnosis, but their value in population based P53 and the adenoma-carcinoma sequence p=0034 Student's t test). Maximum voluntary screening is poorly defined. Therefore, we undertook a study of 42 families (261 N SCOTT, P SAGAR, J STEWART, G E BLAIR, M F individuals) from a circumscribed population DIXON, P QUIRKE (Departments of Pathology, The accuracy of the data in these abstracts is the Surgery and Biochemistry, University of Leeds, responsibility of the authors since the abstracts have not of 5 5 million, using probes I1227, CIIPII, been subject to peer review. ECB27, and YN5. Leeds) p53 is a tumour suppressor gene which A1204 British Society ofGastroenterologv encodes a 53kD nuclear phosphoprotein. colorectal cancers were stained with AUA 1, paque centrifugation, the cells were cultured Mutations in conserved regions of the gene CAM 5.2, Ber EP4, 8.134, PR1A3, PR3B10, with autologous colorectal cancer cells at a ratio however, result in over-expression of a mutant HMFG2, 41.2, ICR2, anti-CEA. AUA1 and of 100:1 tumour cell and 100 U of interleukin 2 protein which acts as a classic oncoprotein. Ber EP4 were selected as both stained the cell for three to four weeks. The tumour cell Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from We have used immunohistochemistry to lines (2/2), colorectal cancer cryostat sections numbers, lymphocyte numbers and lympho- detect mutant p53 in 5% of 38 sporadic adeno- (9/9), malignant ascites (5/5) and were negative cvte cvtotoxicitv were assessed at weekly mas and 44% of 100 adenocarcinomas of the for benign ascites (0/5). intervals. large bowel. We conclude that p53 mutation In 25 patients, 400 ml of normal saline were Control cultures of tumour cells and inter- is a late event in the adenoma-carcinoma instilled into the peritoneal cavity at the begin- leukin 2 alone grew exponentially but in the sequence comparable with chromosome 17p ning and end of the operation, aspirated after mixed cultures all the tumour cells were killed deletions and deletions of the DCC gene. three minutes and malignant cells isolated on a by four weeks. The lymphocyte numbers fell in Analysis of a subset of the adenomas for K-ras histopaque density gradient before cytospin the first two weeks, thereafter increasing 10 to mutations showed a 2 cm diameter benign preparations were stained by an indirect 100 fold. The proportion of cytotoxic lympho- tubulovillous polyp with both a mutated p53 immunoperoxidase technique using AUA 1, cytes increased from 10-24%'o to a maximum of gene and mutation at codon 12 of the ras gene. Ber EP4, and by cytology using the May- 78%'o at three weeks. In separate cultures, the Although this is sufficient in vitro to trans- Grunwald-Giemsa stain. TAK cells were collected, labelled with form primary rat fibroblasts, other changes are Malignant cells were identified in 11 patients II1Indium tropolonate, and then re-injected clearly required in vivo to produce malignant (44%); before and after resection washings in into autologous patients. The patients were transformation in an adenoma. nine and post resection washings in two. Of the scanned at regular intervals to examine the 20 positive samples the antibodies contributed biodistribution of TAK cells in five patients Endogenous hypergastrinaemia stimulates essential diagnostic information in seven (35%). with metastatic colorectal cancer. The images and Immunocytochemistry did assist conven- confirmed a uniform distribution of cells in colonic mucosal polyamine biosynthesis tional cytology in identifying malignant cells each patient, to lung (for four hours only), epithelial proliferation and may play a role in investigating local liver, and spleen, with metastatic lesions being M R GRAY, R S NAGRA, H M WALLACE, J NEMETH, recurrence. visible 24-48 hours after injection. A N KINGSNORTH (University of Liverpool, This work confirms the cytotoxic character- Departments of Surgery and Physiology and Adjunctive intraoperative photodynamic istics of TAK cells, and illustrates their in vivo Departments of Medicine, Therapeutics and therapy for colorectal cancer ability to localise sites of autologous metastatic Pharmacology, Aberdeen) Whether gastrin colorectal disease. stimulates colonic mucosal proliferation is the A M ABUAFI, J T ALLARDICE, R DEAN, M GRAHN, subject of conflicting evidence. Pentagastrin N S WILLIAMS (The Surgical Unit, The Royal Interleukin 2 production in patients with administration stimulates colonic polyamine London Hospital, London) A major source of advanced colorectal carcinoma immunised biosynthesis, a finding often linked to pro- local recurrence of colorectal cancer after with a human anti-idiotypic monoclonal anti- liferative events. Other investigators have ostensibly curative resections (OCR) is micro- body failed to show evidence of mucosal hyperplasia scopic residual disease in the tumour bed. in the colon of fundectomised rats. Twenty one patients (two with Dukes's A, 12 G W L DENTON, R A ROBBINS, I G DURRANT, E B We have measured left colonic mucosal Dukes's B, and seven Dukes's C) who under- AUSTIN, J D HARDCASTLE, R W BAI DWIN (Depart- polyamine content by HPLC, crypt cell pro- went OCR were treated with intraoperative ment ofSurgery and Cancer Research Campaign duction rate by vincristine metaphase arrest, photodynamic therapy (IOPDT), a novel Laboratories, Nottingham University) 105AD7 is and crypt height in four groups of 10 rats. All approach which can destroy malignant cells in a human anti-idiotypic antibody which is an results median (range) were compared by the tumour bed. The tumour bed (surface area internal image of a human colorectal carcinoma Mann-Whitney U. range 95-371 cm 2) in all patients received surface antigen. It is currently being used http://gut.bmj.com/ In rats receiving 200 mmol omeprazole/kg/ doses ranging from 35-70 J cm 2 of green (510 to treat patients with advanced colorectal day postoperative serum gastrin rose 12 fold nm) laser light via specially constructed light carcinoma. Serum interleukin 2 (IL 2) concen- from 23.6 (11-9-37.4) to 255 (173-445) fmol/ delivery systems. Mean (SEM) laser irradiation trations were measured as an assessment of the ml (p<0 01). After 30 days treatment total time was 22.3 (2.6) (range 1155-52.8) minutes. induction of a cellular immune response. polyamine content rose by 74% from 14 6 to There were no postoperative complications Six patients have been treated, with 25.4 nmol/mg protein (p<0 001). Crypt directly related to IOPDT, however, three individual patients receiving up to four height, 2.3 (1.9-2.62) v 2.18 (1 9-2.42) mm, patients developed skin photosensitivity reac- immunisations. Serial weekly serum samples was unaffected. In a separate experiment, crypt tions. Follow up ranged from 3-26 (median 12) taken for six weeks after immunisation have on September 28, 2021 by guest. Protected copyright. cell production rate was increased by 7% from months. Sixteen of 21 tumour specimens had been analysed for circulating IL 2 using a 6 19 (0.0068) CCPH (r=0.989) to 6.61 (0.005) circumferential resection margin (CRM) commercially available IL 2 ELISA (Dupont). CCPH (r=0.988) (p<0 001 Student's t test examined histologically for tumour involve- IL 2 was detected in the plasma of four of the comparison of regression gradient). ment. Eight were positive and eight were six patients, after eight out of nine immunisa- We conclude that colonic mucosa responds negative. Of eight patients whose tumours tions. The response ranged from one to five to endogenous hypergastrinaemia by an involved the CRM who inevitably would weeks (median three weeks) and the peak levels increase in polyamine biosynthesis and a small develop local recurrence, one did so at three of IL 2 detected ranged from 3 to 7 U/ml but significant acceleration in cell turnover. months. Eight patients whose tumours did not (median 4 5 U/ml). No antibody or IL2 related involve CRM and five patients whose tumours toxicity has been observed. The of this amount of endo- in were not examined for CRM involvement production Detection of malignant cells peritoneal remain free of local recurrence. genous IL 2 after immunisation is noteworthy. fluid in colorectal cancer These results suggest that IOPDT is a To obtain similar steady serum levels of IL 2 a A J M LEATHER, C Y YIU, G KOCJAN, W HU, P B feasible and safe approach and does not signifi- therapeutic infusion of exogenous IL 2, with BOULOS, J M A NORTHOVER, R K S PHILLIPS cantly prolong surgery. It may have the poten- attendant toxicity, would be needed. This (ICRF Colorectal Cancer Unit, St Mark's tial of reducing local recurrence. suggests that immunisation has induced a Hospital, London, Department oJ Cvtology, specific T cell response and potentially might induce a mediated anti-tumour response. Middlesex Hospital, London, Departments of In vitro and in vivo characteristics of tumour IAK Surgery, University College and Middlesex activated killer lymphocytes in colorectal School of Medicine and St Bartholomew's cancer Anal smear or microanoscopy to identify anal Hospital, London) The impiantation of malig- intraepithelial neoplasia nant cells in the peritoneal cavity is a likely R I SWIFT, M THOMAS, J GAER, S TEBBUTT, C B cause of local recurrence after curative resec- WOOD (Hammersmith Hospital, London) P S CARTER, A DE RUTTER, C WHATRUP, D KATZ, tion in colorectal cancer. Detection of these Adoptive immunotherapy with Lymphokine G KOCJAN, A MINDEI, J M A NORTHOVFR (ICRF cells by conventional cytology is difficult and activated killer cells. or tumour infiltrating Colorectal Unit. St Mark's Hospital, London, may be assisted by immunocytochemistry. In lymphocytes has produced clinical responses in Academic Departments of G-U Medicine, Histo- this study suitable antibodies were selected and metastatic melanomas. However, the therapy pathologv, and Cvtologv, Middlesex Hospital, used to detect exfoliated malignant cells in requires high doses of interleukin 2, which LIondon) Studies have shown that both homo- patients undergoing colorectal cancer resec- cause unacceptable side effects. We report the sexual men and HIV positive men with anal tion. in vitro development and in vivo characteristics condylomata have a high prevalence of anal Cytospin preparations from two human of tumour activated killer lymphocytes (TAK). intraepithelial neoplasia (28'S in both groups). colorectal cancer cell lines (LoVo, SW480), 10 From 80 ml of venous blood, peripheral blood The first of these two groups is already large ascitic fluids and cryostat sections from nine mononuclear cells were collected by Ficoll (approximately 750000 in the UK) and the British Society ofGastroenterology A1205 second of these two groups continues to Five were studied again four to six weeks later. associated with a 2% two year survival. Other increase in size. The median maximal rectal dose was 55 Gray workers have consistently found the dysplasia

The malignant potential of anal intra- (range 32-64). Dialysis was for two hours using which develops to be gastric in type with a Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from epithelial neoplasia (AIN) is as yet unknown Visking tubing 12 cm by 0.6 cm filled with 10% mixed endocrine cell population. We have but may parallel that of cervical intraepithelial dextran and 0.9% sodium chloride. LTB4 investigated the endocrinology of Barrett's neoplasia with progression through the grades (extracted) and TXB2 were assayed by radio- oesophagus using immunohistochemical of dysplasia to invasive carcinoma in a small immunoassay. methods. percentage of cases. Validation of LTB4 against HPLC gave a Thirteen patients who underwent oesopha- This study has assessed 145 patients for AIN correlation r=0-92 (p=0-015) and of TXB2 geal resection had Barrett's changes around using anal smear and microanoscopy (procto- against GCMS r=0-736 (p=0.037). Radiation their tumours. In five patients in this group scopy using an operating microscope). Ninety increased LTB4 by a median of 0-8 ng/ml with intestinal type dysplasia, as opposed to nine patients had an adequate smear before full (range 0 to 3.78) from median 0 (0 to 0 64) to the more common gastric type dysplasia, we microanoscopic assessment. Cytology on these median 1-01 (0 to 4.0) p=0-0018 (Wilcoxon) detected cell populations for GIP, CCK, 99 patients showed HPV infection in 54 (55%), and increased TXB2 by median 0-78 ng/ml secretin, and motilin, whereas the gastric type AIN in 38 (38%), and only seven (7%) had no (0.05 to 2.72) from median 0-41 (0 to 0 88) to dysplasia expresses gastrin, serotonin, pan- abnormality. Twenty nine (29%) of the 99 1 15 (0-26 to 2.92) p=0-018. Symptom scores creastatin and somatostatin. Neither type patients showed histological evidence of AIN. rose by median 0 5 (0 to 2) points. One month expressed lower small bowel or colonic markers Only 13 of the 29 patients with AIN on after therapy LTB4 values fell in all patients by such as enteroglucagon, neurotensin, or PYY. histology were heralded by AIN on smear (false median -0-64 ng/ml; TXB2 fell by median The carcinomas themselves are generally negative rate of 55%), 25 patients with AIN on -0-21 ng/ml. devoid of endocrine cells. smear had no micro-anoscopic or histological These data are consistent with increased This study indicates that endocrinological evidence ofAIN (false positive rate of 66%). rectal production of LTB4 and TXB2 with typing of Barrett's oesophagus may help in We conclude that the low sensitivity and pelvic radiotherapy. This may contribute to the detecting impending development of oesopha- specificity of anal smear makes it unsuitable as inflammation of early radiation proctitis and geal carcinoma. a screening test for AIN. specific inhibitors may have therapeutic potential. Ileal pouch dialysate is cytotoxic to I-407 and Squamous regeneration in experimental HT-29 cells: bile may be the active factor Barrett's oesophagus: effect of antireflux surgery M N MERRETT, B J CROTTY, N MORTENSEN, D P OESOPHAGEAL DISEASE JEWELL (Gastroenterology Unit, The Radcliffe H LI, T N WALSH, G O'DOWD, P MARKS, P J BYRNE, Infirmary, Oxford) A raised crypt cell produc- S JAZRAWI, T P J HENNESSY (Departments of tion rate (CCPR) has been observed in the ileal Role of smoking and alcohol in metaplasia Surgery and Pathology, St James's Hospital, pouch. This occurs in the first three months and neoplasia in Barrett's columnar lined Dublin) Regression of Barrett's epithelium after ileostomy closure. Our hypothesis was oesophagus after antireflux treatment is disputed. This that a factor in the faecal stream may increase study examined the effect of antireflux therapy ileal CCPR. M R GRAY, R J DONNELLY, A N KINGSNORTH on regression in an animal model. Eight ileal pouches were dialysed in vivo for (University ofLiverpool, Department of Surgery Nine adult mongrel dogs had a 1 cm mucosal four hours using Visking dialysis tubing con- and The Cardiothoracic Centre, Liverpool) We strip defect created in the lower oesophagus taining 10 ml of 10% Dextran in normal saline studied the alcohol and smoking habits of leaving a surrounding 1 cm squamous barrier. http://gut.bmj.com/ (Rheomacrodex). The effect of serial dilutions patients with severe reflux oesophagitis (SRO) A Wendel cardioplasty and hiatus hernia were of dialysate was assessed on I-407 (embryonic (n=24), columnar lined oesophagus (CLO) fashioned and hyperacidity induced by penta- small intestine) and HT-29 (colon cancer) cells. (n=58), and adenocarcinoma arising in CLO gastrin (100 [ig daily). Acid reflux was con- Proliferation assays using 3H uptake showed a (Adeno) (n=23). firmed by two hour intraoesophageal pH dose related fall in proliferation (p=0-0001) for Age (median 65 years) and duration of monitoring. At three months the healing both cell lines. Cytotoxic assays using 51 Cr symptoms (median 10 years) were similar in mucosa was excised leaving further strip revealed dose related cytotoxicity (p=0-0001) each group. CLO median smoking history was defect. An antireflux procedure was performed probably accounting for the antiproliferative 5 pack years (0-45 pack years) which was less and omeprazole (20 mg) was given daily to on September 28, 2021 by guest. Protected copyright. effect. The effect was observed at both dialy- than both the SRO (median 46; 0->100 pack suppress acid secretion. sate pH (mean=5.95) and corrected pH (7.4). years) and Adeno groups (median 54; 0->100 No control animal had columnar mucosa in Limited characterisation showed that the pack years) (p<0-001). Total pack-year the oesophagus. Six of nine animals developed cytotoxic factor has a MW - 1000, is resistant smoking history was similar in SRO and Barrett's mucosa after the reflux inducing to extremes of temperature (-20'C to 100°C) Adeno. Adenocarcinoma patients had smoked procedure but squamous islands were not and pH (2-12), and is significantly inhibited by for more years in total (median 39; 0-54 years) identified. After repeat epithelial stripping and cholestyramine. Furthermore gall bladder bile and started smoking earlier (median age 18) antireflux therapy all five dogs developed is noticeably cytotoxic to both cell lines. than CLO (median 9; 0-55 years) (p<0.001) Barrett's oesophagus. Regenerating islands of These results show that ileal pouch dialysate (median age starting 27) (p<0-001). SRO squamous epithelium were identified, partially is cytotoxic to intestinal epithelial cell lines. exceeded CLO (p<0 002). Of the SRO group replacing columnar epithelium in all five. Thus, stasis within the pouch may result in 50% drank more than 40 units/week whereas This study suggests that a squamous defect prolonged exposure to the cytotoxic factor CLO patients were often non-drinkers (median in the oesophagus is repaired by columnar (probably a bile acid) with subsequent 3; 0-100 units/week) (p<0 02). Adeno median epithelium in the presence of reflux but that epithelial cell loss. In vivo, a response to this alcohol consumption was 10 (0-100 units/ 'islands' squamous regeneration occurs where insult may be an increase in CCPR. week) (p<0-02 v CLO). reflux is adequately controlled. Smoking and alcohol consumption do not to CLO Raised rectal leukotriene B4 and throm- predispose development of metaplastic in patients with severe gastro-oesophageal boxane B2 values after pelvic radiotherapy - reflux but are strongly associated with Oncogenes and oncosuppressor genes in specific targets for therapy? development of adenocarcinoma in Barrett's adenocarcinoma of the oesophagus A T COLE, K SLATER, M SOKAL, B FILIPOWICZ, oesophagus. L KURLAK, C J HAWKEY (Department of Thera- J JANKOWSKI, G COGHILL, D HOPWOOD, K G peutics, University Hospital, Nottingham and WORMSLEY (Departments of Medicine and Differential endocrinology of intestinal and Pathology, University ofDundee) The activation Radiotherapy Department, General Hospital, gastric type Barrett's oesophagus Nottingham) Pelvic radiotherapy often causes of proto-oncogenes has been implicated in the an early proctitis. If eicosanoids mediate this A J RITCHIE, C F JOHNSTON, J McGUIGAN, J R P development and progression of cancer. Their inflammation, specific inhibitors may have GIBBONS, K D BUCHANAN (Department of role in the development of oesophageal adeno- therapeutic potential. We therefore measured Medicine, Queen's University of Belfast and carcinoma is unknown. We studied 15 cases of the effects of radiotherapy on rectal levels of Department of Cardio-Thoracic Surgery, Royal freshly resected oesophageal adenocarcinomas, leukotriene B4 (LTB4) and thromboxane B2 Victoria Hospital, Belfast) Barrett's oesophagus 15 cases of Barrett's oesophagus, and paired (TXB2). is a metaplasia in which a previously squamous biopsy specimens from normal stomach. These Eight patients, aged 57 to 78, were studied epithelium develops into a columnar epithe- specimens were all snap frozen and subse- by rectal dialysis before and immediately after a lium with up to 240 times increased risk of quently stained with monoclonal antibodies to four to six week course of pelvic radiotherapy. developing oesophageal carcinoma which is the following oncogenes: c-erbB2 (neu and A1206 Bnrtish Society ofGastroenterology

CE-1) (external domain), c-erbB2 (NCL- (NOR) oesophageal tests. All underwent a pathology, Renal Medicine, Royal Postgraduate CB1 1) (internal domain), C-src, c-ras, c-myc, double blind crossover study of oesophageal Medical School, London) It is not known how c-fos c-jun, and the oncosuppressor gene - P53. or 0 9% perfusion with 300 ml of 0-1 N HCI Helicobacter pylonr damages epithelia to cause Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from All tumours were well differentiated adeno- saline on two separate days. A latex balloon on gastritis and ulceration. Neutrophils, attracted carcinomas arising from the lower third of the a manometry catheter and an oesophageal by H pylori, probably damage tissues by releas- oesophagus. Twelve cases showed strong pacing electrode were placed 5 cm above the ing enzymes, superoxide, hydrogen peroxide membranous staining with both c-erbB2 (neu) lower oesophageal sphincter. Graded balloon and bioactive lipids. We considered how H and c-erbB2 (CBL-CB1 1). Seven cases showed distension followed by pacing at increasing pylori attracts these cells. Interleukin 8 (IL8) is strong nuclear staining with P53 oncosuppres- currents with ECG monitoring, were per- a newly discovered highly potent attractant of sor gene. Three cases were positive for c-ras. formed before and after fluid perfusion. The neutrophils. We, therefore, studied the effect In Barrett's epithelium, 10 cases were minimum balloon volume (V) and pacing ofH pylori on its release from antral tissue. positive for c-erbB2 (neu and CBl 1), two cases current (P) reported as painful were recorded. Antral biopsy specimens were taken from were positive for c-ras, and one was positive for Basal V was lower in ABN than NOR (9-2 ml patients with normal endoscopic appearances. c-fos. None of the gastric mucosal biopsy v. 12-2 ml, p<0 05). After acid, mean V H pylori was detected by biopsy urease test and specimens showed any demonstrable oncogene decreased in NOR (12-2 ml to 9-1 ml, histology in 10 patients, but not by either in 15. expression. p<0-001); but not in ABN (9-2 ml to 8-5 ml, Biopsy specimens were each incubated in 2 ml The frequency of positive staining for NS). There were no changes of V after saline, RPMI 1640 culture medium for two hours at c-erbB2 and P53 is very high compared with and no significant differences of P in either 37°C, gassed with 95%O2:5%C02. IL8 was other tumours. We conclude that errors in the group after either fluid. measured in culture media by double ligand oncosuppressor gene P53 and the external and We conclude: (a) ABN have a lower basal sandwich ELISA. Neutrophil infiltration in internal domains ofc-erbB2 may be implicated pain threshold for distension than NOR; (b) the same biopsy specimens was then graded in the progression of adenocarcinoma of the distension but not pacing threshold in NOR is from 0=nil to 3 = severe. Results are expressed oesophagus. lowered by acid, implying acid induced as median (range). receptor sensitisation; and (c) this effect is not Despite normal endoscopic appearances, found in ABN suggesting that nociceptors may neutrophil infiltration was greater in H pylori already be sensitised. +ve patients; 2 (0-2), grade 2 in 63%, than in Diffuse oesophageal spasm - a condition H pylori -ve patients; 0 (0-1), grade 0 in 63% which is missed by the clinician and the (p<005). IL 8 secretion (pg/mg tissue) was 2.5 radiologist Mechanisms of gastro-oesophageal reflux (0-7-1) in H pylori +ve patients; detectable in under ambulant conditions 80%, compared with 0 (0-5.6) in H pylori -ve W J OWEN, A ANGGIANSAH, N F BRIGHT patients; undetectable in 67% (p<0 05). (OesophagealLaboratory, DepartmentofSurgery, In conclusion, Hpylori greatly increases local C P BARHAM, D C GOTLEY, D ALDERSON Guy's Hospital, London) Diffuse oesophageal (University Department ofSurgery, Bristol Royal release ofIL8. This may be the major attractant spasm (DOS) is an uncommon but disabling Infirmary, Bristol) The mechanisms that pre- of neutrophils and thus important in tissue condition. Diagnosis depends on the clinician, in damage by H pylonr. the radiologist, and also on a referral for cipitate gastro-oesophageal reflux (GOR) oesophageal manometry. In order to investi- ambulant patients remain largely unknown. gate problems of diagnosis, 42 patients subse- A portable system has been developed to quently diagnosed as suffering from DOS, study oesophagogastric pressure activity were reviewed in order to establish: immediately preceding the onset of acid GOR Is Helicobacter pylori related hyper- 1 The principal presenting complaints and in normal subjects (group I, n= 10), reflux gastrinaemia due to the bacterium inhibiting n= with cell function? http://gut.bmj.com/ duration of symptoms; 2 The number of patients without (group II, 10) and parietal referrals before the diagnosis was made; 3 The (group III, n= 10) endoscopically proved oeso- phagitis during 24 hours of normal activity. R S CHITTAJALLU, J HARWOOD, C A DORRIAN, accuracy of barium swallow examination. Manometric data were recorded at 5, 10, 15 cm K E L McCOLL (University Department of Twenty three patients (55%) complained above and 8 cm below the lower oesophageal Medicine and Therapeutics, Department of Bio- of chest pain and dysphagia, 14 (33%) of sphincter (LOS) and pH 5 cm above the LOS. chemistry, Western Infirmary, Glasgow) The dysphagia alone, and five (12%) of chest pain A total of 1234 acid GOR episodes were mechanism by which chronic Helicobacter alone. The duration of symptoms varied from motor raises serum is not three months to 30 years (mean duration=6 classified as spontaneous, oesophageal pylonr infection gastrin related, belch associated, stress/strain induced, know. H pylon inhibits parietal cell function in on September 28, 2021 by guest. Protected copyright. years). The number of referrals per patient vitro. We have the that varied from two to 15 (mean number of or unclear. investigated possibility Barium Gastro-oesophageal reflux was more fre- hypergastrinaemia in chronic H pylori infection referrals per patient=3-8). swallow quent during the day than at night in all groups represents a compensatory response to main- examination was reported as normal in 15 (p<0.05*). Belching as a cause of GOR was tain acid secretion in the presence of mild (36%), DOS in 10 (24%), hiatus hernia in six greater in group I than group III (p<0 05). inhibition of parietal cell function by the (14%), strictures in five (12%), diverticulum in Spontaneous GOR were more common in bacterium. The acid response to 45 minute three (7%), and achalasia in three (7%). group III compared with groups I (p<005) infusions of pentagastrin at each of the follow- Thus ODS may evade diagnosis for many and II (p<0 05). Stress/strain induced GOR ing sequential doses ([tg/kg/h) 0, 0 031, 0-062, years despite repeated consultations. The in- became more common as a cause ofreflux from 0-124, and 0.6 was compared before and one accuracy ofradiology in this condition points to group I to II to III but did not reach statistical month after eradication of H pylori in eight the need for earlier referral of suspicious cases significance. duodenal ulcer patients in clinical remission. for oesophageal manometry. Under ambulant conditions, GOR is precipi- The median acid outputs (mmol/h) with the tated by a variety of mechanisms. Belching is respective infusions were 5 0, 13-0, 26-3, 31-2, the predominant mechanism in normal sub- 39 0 when H pylon +ve and similar at 4-6, 7-8, jects, while 'spontaneous' GOR dominates in 25-0, 35 6, 43-3 after eradication. The esti- A clue to the mechanism of abnormal patients with oesophagitis. Future studies to mated dose ofpentagastrin required to produce oesophageal sensory perception in non- determine mechanisms ofGOR should concen- 50% maximal response was similar before cardiac chest pain trate on ambulant patients. (0.054 [sg/kg/h) and after (0-061 [tg/kg/h) *Wilcoxon signed rank test. eradication ofH pylori. The estimated maximal A J MEHTA, J S DE CAESTECKER, T C NORTHFIELD response to pentagastrin (mmol/h) was also (Department of Medicine, St George's Hospital similar before (43.2) and after (43.7) eradica- MedicalSchool, London) Lower pain thresholds tion of the organism. for oesophageal stretch have been reported in This study shows that the parietal cell non-cardiac chest pain (NCCP), but the HELICOBACTER PYLORI response to pentagastrin is unaffected by mechanism is unknown. Gesophageal chronic H pylori infection and that the hyper- mechanonociceptors can be sensitised by gastrinaemia cannot be explained by the noxious stimuli in NCCP (Gut 1991; 32: A599). bacterium inhibiting parietal cell function. Our aim was to test the hypothesis that in those Helicobacter pylori increases release of with an oesophageal cause for chest pain, (ie interleukin 8: a potent attractant of abnormal motility or provocation tests) sensiti- neutrophils sation has already occurred. We studied 20 patients with NCCP; of these R GUPTA, S MOSS, D M THOMAS, F ABBOTT, A REES, Gastrin, gastric acid and pepsin responses eight had abnormal (ABN) and 12 had normal J CALAM (Departments ofGastroenterology, Histo- during intragastric titration in duodenal ulcer British Society ofGastroenterology A1207 patients; effect of suppressing Helicobacter sinogens (PGA 95 (37-164) and 103 (35-273), by interview, examination of hospital records, pylon PGC 34 (24-56) and 35 (20-117), A:C ratio 2.9 endoscopy, and antral biopsy. H pylori was

(1 1-3 2) and 2-3 (1-3-3-3)) before and after confirmed by CLO test, histology, and culture. Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from S MOSS, K AYESU, S K LI, J CALAM (Gastro- treatment, respectively. Histological examina- DNA extraction from pure isolates of H pylon' enterology Unit, Royal Postgraduate Medical tion of gastric biopsy specimens before and was possible in six family members. Strain School, Hammersmith Hospital, London) after treatment showed improvement only in typing was performed by restriction fragment Helicobacter pylori positive duodenal ulcer the patients with eradication of H pylori length polymorphism with 11 endonucleases. (DU) patients have high basal and meal stimu- infection. Southern blotting and DNA hybridisation lated plasma gastrin values and peak acid We conclude that after eradication of H were also performed using a cDNA probe output. After H pylori eradication plasma pylori infection, there is a significant fall of complementary to bacterial rRNA cistrons. gastrin values fall but meal stimulated acid serum PGA and even more pronounced fall of Eight of the nine family members (90%) secretion has not been measured. DU patients serum PGC values accompanied by a rise in were H pylori +ve by CLO test and histology. have been reported to have a specific loss ofthe A:C ratio. Strain typing was successful in six members (at inhibition of acid secretion by luminal acidi- least one member from each generation). Each fication. We therefore used intragastric strain was genetically unique. Four strains titration to measure gastric acid and pepsin were isolated from family members with severe secretion and gastrin responses to the intra- One week's treatment for duodenal ulcer duodenal ulcer disease, the other two strains luminal instillation of 4% peptone at pH 2-5 from members with no disease. and 5 5 in 11 DU patients before and after R P H LOGAN, P A GUMMETT, J J MISIEWICZ, M M In conclusion, DU families may be excep- suppression ofH pylori. WALKER, R J POLSON, N Q KARIM, J H BARON tionally susceptible to H pylori infection. Plasma gastrin values were significantly (Parkside Helicobacter Study Group, Central Members may be colonised by different higher at pH 5-5 compared with pH 2-5, and at Middlesex and St Mary's Hospitals, London) As strains. Family members may develop DU pH 2-5 compared with basal values, both successful eradication of H pylon after healing disease irrespective of the colonising strain of before and after treatment. Gastrin values were of duodenal ulcer (DU) can prevent subse- H pylori. also significantly higher (p<005) in all cases quent recurrence of DU, would H pylon eradi- before H pylori suppression than afterwards; cation alone heal active DU? In patients with median basal 9-2 (range 3.7-23) pmol/1 before DU (>5 mm diameter) H pylon was detected compared with 5-1 (1-7-15) after, at pH 2-5 by histology (H&E/Gimenez stains), CLO test, Do teeth predispose to duodenal ulcer median 11-3 (3.8-29) before and 5.9 (5.7-61) culture (selective/non-selective media), and relapse? after treatment and at pH 5-5 median 15-2 3C urea breath test (13C-UBT, positive result (3.9-32) before and 7-15 (6-1-14) afterwards. =excess 613C02 excretion >5 ppm) before M A K KHANDAKER, A SCOTT, M A EASTWOOD, K R In marked contrast outputs of acid and pepsin treatment with a one week eradication regime PALMER (GI Unit, Western General Hospital, at each pH were not altered by suppression of (Denol tablets 1 qds and amoxycillin 500 mg Edinburgh) Eradication of Helicobacter pylori H pylori. qds for seven days, with metronidazole 2 g from the stomach prolongs remission in duo- We conclude, that suppression of H pylori daily on days five to seven. The 13C-UBT was denal ulcer (DU) disease, but gastric reinfec- decreased gastrin independent of luminal pH. repeated immediately after finishing treatment tion is common and could lead to DU relapse. Outputs of acid and pepsin were unchanged. and a repeat OGD performed to assess ulcer In order to identify the reservoir of H pylon' This suggests that H pylori decreases the healing. Healed ulcers were followed by 13C- infection, tooth pickings were cultured from 18 sensitivity ofthe gastric mucosa to gastrin. UBT alone at one, three, six, and 12 months, dentulous and three edentulous DU patients while unhealed ulcers had a third OGD one and from 21 matched dentulous, non-ulcer month after finishing treatment. control subjects. http://gut.bmj.com/ Twenty seven patients (13 men, seven Fifteen DU patients had H pylori associated Serum pepsinogen A and C values before and smokers, median age 42 years; range 16-70) gastritis, and H pylori was shown by histology. after treatment of Helicobacter pylon with DU were studied and 26 are available for H pylori was cultured in Skirrow's media from infection follow up. Mean pretreatment excess 613C02 tooth pickings in seven and in 18 from antral excretion was 25.6 ppm, which fell to 2-4 per biopsy specimens. Four control subjects had H R A VEENENDAAL, I BIEMOND, A S PENA, mil immediately after finishing treatment. At pylori gastritis and Hpylori shown by histology; J KREUNING, C B H W LAMERS (Department the second OGD (median interval 12 days, two of these had positive cultures from tooth of Gastroenterology-Hepatology, University range 8-30) 17/26 (65%) DUs had healed. pickings and four from antral biopsy speci- on September 28, 2021 by guest. Protected copyright. Hospital, Leiden, The Netherlands) Serum The other nine ulcers were smaller (median mens. H pylon was not cultured from dental pepsingogen A and C values have been shown diameter 3 mm), and two weeks later five of plates in edentulous individuals, nor was it to vary in different forms of gastritis. Since these nine had healed (85%). Only four of the isolated from tooth pickings in individuals who there is a strong relation between chronic 26 patients had unhealed ulcers after four do not exhibit H pylori gastritis. active gastritis and Hpylori infection we studied weeks and in each pre-treatment metronidazole Gastric re-infection by H pylon seems to serum values of pepsinogen A (PGA), pep- resistant H pylori (MR Hpylori) were found. In originate from a reservoir of infection in the sinogen C (PGC), and their ratio (A:C) before two patients whose ulcer initially healed (with teeth and gums. Relapse of DU after triple and after eradication ofH pylori infection. clearance of H pylon), ulcers later recurred therapy for H pylori may be influenced by Twenty one patients with H pylon positive (both had MR H pylon). H pylon was eradi- dental status. gastritis were studied before and three months cated in 15/26 (58%) patients (median follow up after treatment with 'triple' therapy (bismuth 4-1 months, range 1.8-6 2). subcitrate 120 mg qds for 28 days, amoxycillin Eighty five per cent of DUs healed by 500 mg qds and metronidazol 500 mg qds for 10 treating H pylori. The one week treatment days) or 'double' therapy (bismuth subcitrate regime used was successful in eradication and MUCOSAL GROWTH AND PROLIFERATION 120 mg qds for 28 days and tinidazol 500 mg healing only in patients whose H pylon was qds for 10 days). The presence of H pylori was sensitive to metronidazole. evaluated by culture, histology of gastric biopsy specimens, and serological tests before Growth regulatory peptides in gastric mucosa and three months after treatment. Serum con- centrations of PGA and PGC were determined DNA characterisation of helicobacter pylori J JANKOWSKI, H J AL-RAWI, D A JOHNSTON, by sensitive and specific radioimmunoassays, strains in three generations of a duodenal D HOPWOOD, M I FILIPE, G COGHILL, K G validated in previous studies. ulcer disease family WORMSLEY (Departments ofGastroenterology and In the patients (n= 17) in whom H pylori Pathology, Ninewells Hospital, Dundee and infection was eradicated, there was a significant C U NWOKOLO, J BICKLEY, A R ATTARD, R J OWEN, Department of Pathology, Guy's Hospital, decrease of serum pepsinogen A (median I A FRASER Departments ofGastroenterology and London) Epidermal growth factor (EGF) and (range) 61 (27-176) ,ug/ml v 42 (18-93) jig/ml, Surgery, Walsgrave Hospital, Coventry, the related peptide transforming growth factor p<0-01) and pepsinogen C (median (range) 51 National Collection of Type Cultures, Central a (TGFa) have been implicated in the stimula- (12-169) v 16 (6-86) ig/ml, p<0-01) values Public Health Laboratory, Colindale, London) tion of gastric mucosal proliferation. We while there was a significant increase of the The aim of this study was to investigate the assessed the immunohistochemical distribu- serum pepsinogen A:C ratio (median (range) hypothesis that familial duodenal ulcer (DU) tion ofthese peptides and their receptor epider- 1-5 (0-5-3-1) v 2-1 (10-3-8), p<0-01). In the disease may be a cluster infection by a single mal growth factor receptor (EGF-R) in mucosa four patients in whom H pylon infection was putative ulcerogenic strain ofH pylori. from the antrum and body ofthe stomach from not eradicated, there was no decrease in pep- Nine members of a DU family were studied 28 patients. Twenty five of the 56 biopsy A 1208 British Society ofGastroenterology specimens were histologically normal (12 thymidine was injected to label cells synthesis- adaptation of growth hormone transgenic antrum and 13 body) while the other 31 showed ing DNA. mice varying degrees of inflammation. The whole basis ofthe Burlinson assay is that EGF, TGFa, and EGF-R have maximal non-proliferating surface gastric cells can be R H DOWLING, R FULLER, M H ULSHEN, E Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from density of distribution on the basolateral and selectively digested away by controlled diges- ZIMMERMANN, P KAY LUND (Departments of apical surfaces of the superficial epithelial cells tion with proteinase; however, parietal cells Physiology and Medicine, UNC Chapel Hill, but are also expressed to a lesser extent on the and proliferating cells in semiconservative North Carolina, USA) Little is known about neck and body cells of the glandular tissue. DNA synthesis could be shown in the digest the effects of growth hormone on the gut and We also showed that EGF is found in greater on several separate occasions. Scanning nothing is known about the molecular biology concentrations in the epithelial cells of electron microscopy also showed that the of this adaptive response. Therefore, in six inflamed mucosa compared with normal digests selectively denuded patches of mucosa. growth hormone transgenic (GHTG) mice and mucosa (p<0 05). In addition, the expression Analysis of thymidine uptake by quantification six litter mate wild type (WT) controls, we of EGF was associated with the presence of of the number of silver grains over the nuclei measured body, intestinal and abdominal lymphocytes but not neutrophils (p<0 05). showed that there was no increase in low level visceral weights and indices of intestinal We conclude that EGF may be induced by labelling following omeprazole administration, mucosal mass, extracted jejunal, ileal and cytokines released by mocosal lymphocytes indicating that there was no 'unscheduled colonic poly A' RNA and hybridised northern and that epithelial EGF may play a role in DNA synthesis.' blots with cDNA, oligomer, and riboprobes to maintaining mucosal integrity in gastritis. The conclusions of this study are that the glucagon, IGF-I, ornithine decarboxylase assay does not selectively remove surface cells, (ODC), S-adenosyl methonine decarboxylase so that any unscheduled DNA synthesis would (SAM-DC), sucrase/isomaltase, and ubiquitin. be overwhelmed by contamination with cells in Compared with WT controls, the GHTG Measurement of human gastric mucosa pro- regular scheduled DNA synthesis. In addition, animals showed marked increases in body liferation combining histochemistry and flow a different approach, namely grain count weight (mean 88%), in liver (71%), jejunal cytometry analysis, does not support the contention that (45%), ileal (24%), and colonic (57%) wet omeprazole induces unscheduled DNA weights and in intestinal length (17%) with S PATEL, D A REW, A COOPER, I TAYLOR, C S synthesis in the rat stomach. corresponding changes in indices of mucosal POTTEN (University Surgical Unit, Southampton mass, villus height and crypt depth. IFG-I General Hospital, Southampton and CRC mRNA increased from mean (SEM) 2-46 Department of Oncology, Manchester) Bromo- (0.42) arbitrary units in the jejunum of the WT deoxyuridine (BRdU) labels gastric mucosal Trefoil gene expression is induced in intest- to 335 (0-41) in the GHTG and from 5-11 cells in the S phase. Computer aided histo- inal goblet and endocrine cells in Crohn's (1 -49) to 7.90 (1-24) in the colon. There was no chemical analysis shows static indices, includ- disease significant difference in jejunal ODC mRNA ing the crypt labelling index (LI), the peak (2-40 (0-16) v 2-37 (0.29) U respectively) but labelling position, and the crypt growth N A WRIGHT, R POULSOM, G W H STAMP, S VAN colonic ODC mRNA increased from 1-12 fraction. Flow cytometry (FCM) yields the S NOORDEN, P A HALL, R JEFFERY, J LONGCROFT, G (0-11) to 1-66 (0-18). There were no obvious phase duration (tS) of mucosal cells and hence ELIA, C PIKE, M-C RIO, P CHAMBON (ICRF differences in SAM-DC, sucrase/isomaltase, or the crypt turnover time (CTR). Histopathology Unit London, Department of ubiquitin mRNA values. Specimens of histologically normal gastric Histopathology, Royal Postgraduate Medical These results show that growth hormone body (GB, n= 14) and antral mucosa (GA n= School, London, and Laboratoire de Genetique excess not only increases body and liver 10) were obtained from 24 patients with gastric Moleculaire des Eucaryotes, Strasbourg, France) weights but also stimulates increases in gut carcinomas who received a bolus dose of 250 Trefoil peptides share a cysteine rich consensus length and weight and provide the first mRNA mg BRdU before surgery. Mucosal tissue domain which is highly conserved. The data on growth hormone induced intestinal http://gut.bmj.com/ sections were stained by a peroxidase method canonical molecule is pS2, which is highly adaptation. and subjected to detailed counting of 50 longi- homologous to the gastrointestinal peptide tudinal crypts per sample. The length of hormone pancreatic spasmolytic peptide (PSP) convoluted crypts was calculated by a grid and its human counterpart hSP, in which the 5- counting method. Nuclear suspensions were cysteine domain is tandemly repeated. PSP analysed by MFCM to measure tS. inhibits intestinal muscular contraction and INFLAMMATION A significant difference existed between GA also gastric acid section. A further member, and GB mucosa by a number of criteria. The 'intestinal trefoil peptide' (ITP) has been on September 28, 2021 by guest. Protected copyright. median lengths were 137 cells (GB) and 188 identified in the theca of intestinal goblet cells. cells (GA). The median peak labelling positions We have defined an ulceration associated cell Crohn's sera enhance tissue factor expression were cell 25 (GB) and cell 58 (GA) from the lineage (UACL) in the human gut, induced by by endothelial cells mouth of the crypt. The median crypt label- chronic ulceration, which secretes epidermal ling indices were 1-6% (GB) and 2-8% (GA). growth factor/urogastrone (EGF/URO), and M HUDSON, D P CARR, A J WAKEFIELD, A K HALL, The mean tS of GA cells was 7-7 hours and of also shows pS2 and hSP gene expression A M SAWYERR, M SMITH, A P DHILLON, R E GB cells was 10-8 hours. The median CTT was (Nature 1990; 343: 82-5; J Pathol 1990; 162: POUNDER (University Departments of Medicine estimated to be 6-7 days for GB and 2- 1 days for 279-284.) We have demonstrated pS2 gene and Histopathology, Royal Free Hospital School GA crypts. expression in normal intestinal lineages of Medicine, London) Endothelial cell tissue The technique advances the study of prolif- adjacent to the UACL in small intestinal factor (ECTF) is the cellular initiator of the eration in human gastric mucosa, and may be of Crohn's disease; pS2 gene product is present in extrinsic coagulation cascade; it is not normally value in the assessment of the response of the the subthecal cytoplasm of goblet cells, expressed on vascular endothelial cells but is proliferation compartment to certain drugs. apparently in the Golgi apparatus, while in situ inducible by cytokines and bacterial lipopoly- hybridisation showed pS2 mRNA in the same saccharide (LPS). We have studied the effect of area. pS2 protein is also present in the apical human sera on ECTF induction on both cytoplasm of gut endocrine cells, again only in unstimulated and tumour necrosis factor 'Genotoxicity', unscheduled DNA synthesis the vicinity of the UACL, associated with (TNF) stimulated human umbilical vein endo- and omeprazole endocrine cell hyperplasia in crypts adjacent to thelial cells (HUVEC), the sera came from 24 the UACL. hSP gene expression was not Crohn's disease patients (n= 124 tests) and 19 R A GOODLAD, C Y LEE, M R ALISON, C SARAFF, demonstrable. normal subjects (n=68). The results are com- N A WRIGHT (Imperial Cancer Research Fund We propose that EGF/URO secreted from pared with Crohn's disease clinical activity, as Histopathology Unit, London and Department of the UACL induces pS2 gene expression in determined by the Harvey-Bradshaw score Histopathology, Royal Postgraduate Medical goblet and endocrine cell lineages in the (HBS). School, London) It has been claimed that adjacent mucosa. The findings of two trefoil Coincubation of HUVEC with patients sera omeprazole stimulates unscheduled DNA peptides, one in the theca and another (pS2) in (1:5 dilution) for six hours induced signifi- synthesis (UDS) in a rat stomach genotoxicity the Golgi, indicates that these peptides are cantly more ECTF (median 2-6 range (0-120) assay (Burlinson, et al Lancet 1990; 335: 419). important in goblet cell function, and in endo- mU/10' cells) than in normal subjects (median The Burlinson assay (Carcinogenesis 1989; 10: crine cell modulation, in Crohn's disease. 0 range (0-10) mU/105 cells), p<0001). 1425) was applied to PVG rats gavaged with Coincubation of TNF (2 U) stimulated omeprazole or the carcinogen MNNG, with or HUVEC with patients' sera induced signifi- without hydroxyurea (HU) injection to block cantly more ECTF (median 85 (7 6-700) mU/ scheduled DNA replication. Tritiated Small and large bowel mRNA in the intestinal 105 cells) than in normal subjects (median 58 British Society ofGastroenterology A1209

(2-9-210) mU/105 cells), p=0.003. In the standard indirect immunoperoxide technique, control subjectsand patients with inflammatory Crohn's disease patients this correlated signifi- with monoclonal antibodies to ICAM-1, bowel disease (IBD). the macroscopically cantly with the HBS by linear regression; r= ELAM-1, and VCAM-1. IEL were isolated from Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from 0-203, p<005. Pretreatment of HUVEC with Normal mucosa showed expression of normal mucosa of colonic resection specimens Crohn's sera for 24 hours before addition of ICAM-1 by capillary endothelium in the region from nine control (eight carcinoma, one polyp) LPS (2 jig for six hours) significantly enhanced of lymphoid aggregates but not at other sites. and six IBD patients using DDT, EDTA, and ECTF (median increase 200% (130-400%)) The inflamed mucosa showed widespread two step Ficoll density centrifugation. The compared with normal sera. expression of ICAM-1 and ELAM-1 by endo- IEL were cultured for 72 hours with and In conclusion, this study suggests that local thelium within mucosa as well as superficial without 10 sg/ml of PHA, and the culture immune induction of tissue factor at the endo- submucosa. The endothelial cells also showed supernatant harvested. Concentrations of thelial cell surface may account for the systemic altered morphology (swelling). There was y interferon (yIFN) and interleukin 2 (IL2) in thrombogenesis in Crohn's disease. moderate endothelial expression of VCAM-1, the culture supernatants were measured using especially in the region oflymphoid aggregates. an enzyme amplified sensitivity immune assay. The intensity of expression of ELAM-1 Control IEL had a median CD4/CD8 ratio of appeared to correlate with the severity of acute 0-22 (range 0 10-0 33) and IBD IEL 0-20 Antiendothelial cell antibodies in inflam- inflammation as assessed by neutrophilic (range 0.12-0-30). When cultured alone, the matory bowel disease: are they related to infiltrate. median cytokine production by IEL was (con- vascular injury? We conclude that in colonic mucosa, cell trol v IBD): yIFN 0.3 U/ml (range 0-06) and adhesion molecule expression is restricted to 0.5 U/ml (range 0-0 7); IL2 1 U/ml (range T R J STEVENS, D S RAMPTON (GI Science areas of inflammation or immune activity 0-20) and 0 U/ml (range 0-10). After stimula- Research Unit, The London Hospital Medical (lymphoid aggregates). This expression is tion with PHA the median cytokine production College, London) Antibodies against endo- likely to be important in the genesis of inflam- by IEL significantly increased (p<0 05) to thelial cells (AECA) are common in vasculitis. mation and offers targets for therapeutic inter- (control v IBD): yIFN 3 9 U/ml (range 0-9-26) Crohn's disease (CD) may be a chronic vention. and 0 85 (range 0-3-10. 1); IL2 15 U/ml (range mesenteric vasculitis. We have measured 0-30) and 5 5 U/ml (range 0-50). There was no AECA values in patients with ulcerative colitis significant difference in cytokine production (UC) and CD, compared them with circulating between controls and IBD patients. levels of von Willebrand factor (vWF), a "'In whole body retention: a new method for These data show that human colonic IEL can marker of vascular injury, and assessed their quantification ofdisease activity in inflamma- produce yIFN and IL2 after stimulation with ability to mediate endothelial cell (EC) tory bowel disease PHA. This is of particular interest, given the cytotoxicity. fact that IEL do not proliferate in response to AECA were measured in sera diluted 1/25 by MS CARPANI DE KASKI, A M PETERS, D KNIGHT, lectins. There is no difference in production of radioimmunosorbent assay using confluent A W j STUTTLE, J P LAVENDER, H J F HODGSON these cytokines in control and IBD subjects. human umbilical vein EC. vWF values were (Departments ofMedicine and NuclearMedicine, measured in sera diluted 1/40 by ELISA. Royal Postgraduate Medical School, Hammer- Complement dependent EC cytotoxicity was smith Hospital, London) Accurate objective determined by "'1Indium release. quantification of disease activity in patients AECA positivity (>mean+3 SD of control with inflammatory bowel disease (IBD) can be group) was more common in patients with UC achieved by measurement of "'In white cell (15/27: median 43-9 arbitrary units; range faecal excretion (FE). This method, however, GALL BLADDER MOTILITY AND DISEASE

16-5-100) than CD (6/29: 27-0; 13.5-66.2) or is cumbersome and has practical difficulties http://gut.bmj.com/ controls (1/16: 18-5; 106-42.0). AECA values which limit its routine application. We evalu- were higher in UC (p<00001) and CD ated the quantification of "'In whole body (p<0005) than control but were unrelated to retention (WBR) as an alternative method in Non-adrenergic non-cholinergic inhibitory disease activity or treatment. AECA occurred patients with IBD. After the reinjection of innervation in human gall bladder muscle in both IgG and IgM fractions of sera. AECA "1'In labelled granulocytes the patient stood in values were directly related to serum vWF front of an uncollimated y camera and counts M McKIRDY, C D JOHNSON (University Surgical concentrations in UC (R=0-42, p<005) but were collected over two minutes. After Unit, Southampton General Hospital, South- not CD (R=-0-25; pL=02). AECA positive approximately 96 hours, the patient was ampton) Non-adrenergic non-cholinergic on September 28, 2021 by guest. Protected copyright. serum were not cytotoxic to EC with or without recounted and the % of "1'In counts retained (NANC) inhibitory nerves are present added complement. was calculated. Results were expressed as % of throughout the gut in man and in the gall In conclusion, raised serum AECA values injected counts that had been excreted (100- bladder of several species, but they have not are common in UC and CD. The correlation WBR, normal value . 10%). been found in human gall bladder. We have between AECA and vWF in UC suggests an Thirteen patients underwent white cell scan- sought evidence for NANC nerves in strips of association between endothelial cell injury and ning and measurement of FE and 100-WBR. A gall bladder muscle from gall stone patients AECA. However, the inability of AECA to good correlation between WBR and FE was undergoing cholecystectomy. mediate complement dependent cytotoxicity of found (r=0-96; n= 13; p<0 05). In 45 studies Gall bladder muscle strips were suspended in endothelial cells makes a major pathogenic role 100-WBR was compared with gradings of an organ bath and subjected to repeated for AECA in IBD unlikely. abnormalities of image: 100-WBR was electrical field stimulation (EFS: supramazimal 7-8+4-9% in five normal scans, 9-8+16% in voltage, 10 Hz, 0-3-0.5 ms pulse width for 5 the 15 (+) scans, 21-4+7-9% in the 17 (++) seconds) which depolarises nerves but not scans and 57±16% in the 8 (+++) scans. In muscle. Adjacent strips of gall bladder muscle Increased expression of cell adhesion five cases 100-WBR results were not concor- were given a multifactoral histological score for molecules in active ulcerative colitis dant with imaging, supporting the notion that fibrosis (0-4) and inflammation (0-15). for detection of IBD imaging is more sensitive All 30 strips responded to 15 nM CCK by M BALSITIS, Y MAHIDA, C J HAWKEY (Departments than WBR and FE. increased tone. Twenty one strips contracted of Pathology and Therapeutics, University However, our results indicate that when after EFS; non-responders had high histo- Hospital, Queen's Medical Centre, Nottingham) quantification of disease activity is required, logical scores and low response to CCK. Interaction between endothelial cells and WBR is an accurate, reliable alternative to FE. Responsive strips were exposed to atropine (1 leukocytes via cytokine activated cell adhesion tmol/1), CCK8 (50 nmol/l) and guanethidine molecules is an important event in the develop- (1 [imolll). EFS produced relaxation in nine ment of inflammation. Since we have pre- strips in these conditions. L-nitro-arginine (10 viously shown increased mucosal production of Cytokine production by human colonic [tmol/l) was added to four strips showing interleukins 1 and 8 in active ulcerative colitis, intraepithelal lymphocytes in controls and NANC relaxation. The NANC persisted in we investigated whether expression of inter- inflammatory bowel disease three. cellular adhesion molecule-i (ICAM-1), We have shown NANC inhibitory innerva- endothelial leukocyte adhesion molecule-i H R DALTON, P HOANG, H J DE SILVA, D P JEWELL tion in human gall bladder muscle. Inflam- (ELAM-1), and vascular cell adhesion (Gastroenterology Unit, The Radcliffe Infirmary, mation and fibrosis impaired the neurally molecule-i (VCAM-1) was increased in active Oxford) The function of human intraepithelial mediated responses to EFS, including NANC ulcerative colitis. Cryostat sections from lymphocytes (IEL) remains enigmatic. The relaxation. Neural mechanisms may help uninflamed colonic mucosa (8) and from active aim ofthis study was to determine the cytokine regulate gall bladder filling and emptying in ulcerative colitis (6) were stained using a production profile of human colonic IEL in man. A1210 British Society ofGastroenterology

Effect of hyperglycaemia on gall bladder postprandial residual gall bladder volume was (WGTT) was measured in all consenting sub- motility and plasma hormone secretion increased (21-7 (2-1) v 9.0 (0.9) ml). After jects whom we discovered to have gall stones treatment with octreotide, gall bladder fasting (n= 54) in an ultrasound survey of the popula-

S Y DE BOER, W F LAM, M C W JEBBINK, A A M volume was not significantly increased (45 0 tion, and in age matched controls. Two con- Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from MASCLEE, J B M J JANSEN, CB H W LAMERS (3.0) v 33-6 (2.7) ml). Octreotide did not secutive stools were x rayed after oral ingestion (Department of Gastroenterology-Hepatology, significantly alter maximal gall bladder empty- of multiple, differently shaped, radio-opaque University Hospital, Leiden, The Netherlands) ing, but the rate of emptying was reduced and pellets. Acute hyperglycaemia has been shown to postprandial residual gall bladder volume Overall, WGTT was similar in cases and suppress oesophageal and gastric antral further increased (36-8 (3.9) v 21 7 (2 1) ml, control subjects. However, in the 10 non-obese motility. The aim of this study was to investi- pduodenum. In (p<0 05) reduced compared with those during gastroenterostomy the duodenum is bypassed euglycaemia (22±1% and 60±6%, respect- and this could affect gall bladder motility, CHRONIC LIVER DISEASE ively). Plasma CCK levels after MSF remained predisposing to gall stones and maldigestion. unchanged. The integrated CCK secretion Gall bladder contraction and gastric empty- after feeding during hyperglycaemia (29+5 ing were measured simultaneously in seven pM.60 minutes) was significantly (p<0 05) patients who had undergone gastroenteros- Natural history of autonomic neuropathy in reduced compared to that during euglycaemia tomy without vagotomy (group 1) for peptic chronic liver disease (58-± 10 pM.60 minutes). The MSF and feed- ulcer and in seven matched control subjects ing induced PP secretion during hyper- (group 2). Gastric emptying was assessed using M T HENDRICKSE, P J THULUVATH, D R TRIGER glycaemia (235+90 pM.90 minutes and a dual labelled test meal with liquid (water) and (Department of Medicine and Pharmacology, 1040±270 pM.60 minutes, respectively) were solid (omelette) components. Gall bladder con- University ofSheffield) To examine the natural

also significantly (p<0.05) reduced compared traction was measured by ultrasound. history of autonomic neuropathy in chronic http://gut.bmj.com/ with that during euglycaemia (430±70 pM.90 Mean (SEM) liquid T was 9 (2) minutes liver disease we have evaluated 60 patients (19 minutes and 1960±220 pM.60 minutes, in group 1 and 19 (2) minutes in group 2 alcoholic, 18 primary biliary cirrhosis, 23 respectively). (p<005). The mean lag phase for solid empty- chronic active hepatitis; 57 Child's A, three We conclude that gall bladder motility and ing was only 6 (5) minutes in group 1 compared Child's B) using standard cardiovascular tests, secretion of CCK and PP in response to sham with 35 (7) minutes in group 2 (p<005). In and followed them prospectively for a median and regular feeding are related to blood glucose contrast, the subsequent mean linear phase of of 50 months. Somne 45% (27/60) had vagal values. Hyperglycaemia impairs MSF and gastric solid emptying was very similar in both neuropathy on initial testing. Ten patients died

feeding induced gall gladder contraction and groups, 0.37 (0-1) and 0.40 (0-08)%/minutes. (eight liver related, one cerebrovascular, one on September 28, 2021 by guest. Protected copyright. CCK release. Hyperglycaemia reduces plasma Gall bladder contraction began in both groups respiratory death), eight of whom had vagal PP values suggesting impaired vagal- as soon as food entered the stomach. Emptying neuropathy. Life table analysis showed a cholinergic activity during hyperglycaemia. had two linear components, in group 1 the significantly reduced survival associated with mean rate of the first phase of contraction was vagal neuropathy with a 30% v 6% four year significantly greater than that seen in group 2, mortality in those without vagal neuropathy 2.5 (0.8) compared with 1 (0-4)%/minute (p<002). There was no significant difference Impaired gall bladder motility in acromegaly (p<005). The second phase of gall bladder in hepatic function or aetiology of liver disease emptying was identical at 0 54 (0-4)%/minute between the two groups. Patients who died had a number of abnormal S M CATNACH, J V ANDERSON, G M BESSER, J A H in both groups. significantly higher WASS, P D FAIRCLOUGH (Departments of Gastro- Rapid gastric emptying in gastroenteros- cardiovascular tests (p<0002), and a lower enterology and Endocrinology, St Bartholomew's tomy is principally due to loss of the lag phase Valsalva ratio (p<0028), deep breathing heart has been and this defect is not a result of vagal denerva- rate change (p<0033), and lying standing ratio Hospital, London) Octreotide recently seven had used to suppress growth hormone secretion in tion. Gall bladder emptying is increased in (p<0002). Thirty patients repeat It has been that gastroenterostomy, presumably because of tests (mean interval between tests 40.7 months) acromegaly. suggested long had on initial term therapy with this drug is associated with rapid gastric emptying and enhanced jejunal of whom 15 vagal neuropathy an of stone CCK release. testing. Five developed abnormal tests whilst increased prevalence gall formation, to normal on follow possibly due to an inhibitory effect of three reverted up. octreotide on bladder emptying. Using These results indicate that although mild gall cases may be reversible the presence of ultrasound, we have studied gall bladder in liver disease emptying after a standard liquid meal (Ensure, Gall stones in people who are not obese may autonomic neuropathy chronic 250 ml, 250 Kcal) in 30 untreated acromegalic be explained by slow colonic transit is associated with a significantly worse patients and 16 on octreotide. prognosis. In untreated K W HEATON, P M EMMETT, C L SYMES, F E M acromegalic patients, fasting A 0 gall bladder volume was not significantly BRADDON, HUGHES (University Department different to the value in normal subjects (33-6 of Medicine, Bristol Royal Infirmary, Bnrstol) maximal Artificially slowing down intestinal transit Intrahepatic portal occlusion by micro- (2.7) v 26-2 (2.6) ml). However, new model of and the rate of increases biliary deoxycholate and the spheres: a portal hypertension percentage emptying emptying bile in the rat after the meal were significantly impaired cholesterol saturation index of (Gut 1986; % 27: 550). We therefore speculated that slow compared with normal subjects (maximum B R T MATHIE rate constant of transit might be a feature of people with gall V JAFFE, ALEXANDER, (Department emptying 34 (4 0) v 64 (28)%, risk Postgraduate Medical School, emptying -0.011/min v -0 04/min) and the stones, at least of those without the major ofSurgery, Royal factor of obesity. Whole gut transit time London) Available experimental models of British Society ofGastroenterology A121 1 portal hypertension (PHT) are based either on colitis using an alkaline phosphatase tech- cirrhosis or externally applied portal vein (PV) nique OESOPHAGUS constricting devices. These have proved dis- appointing because the models are unstable S K LO, P CUSICK, K A FLEMING, R W G CHAPMAN Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from and the PV pressure increases variable and (Department ofGastroenterology, J3ohn Radcliffe unreliable. We have devised a new method of Hospital, Oxford and Nuffield Department of Twenty four hour ambulatory oesophageal raising PV pressure which uses intraportally Pathology and Bacteriology, University of pH monitoring in uncomplicated Barrett's infused microspheres to block intrahepatic Oxford) We have recently reported the oesophagus portal radicles. The resultant PHT model presence of an anti-neutrophil nuclear anti- would have the advantage of normal liver body in primary sclerosing cholangitis (PSC) C S NEUMANN, R J L HERON, BT COOPER function and a more clinically relevant intra- and ulcerative colitis (UC). The methodology (Gastroenterology Unit, Dudley Road Hospital, hepatic obstruction to PV flow. has been refined to give more specific detection Birmingham) All but one of the five previous Measured aliquots of microspheres (15, 25, of antibody in PSC using an alkaline phos- studies on acid reflux in Barrett's oesophagus 50, and 90 im) or control equivalent volumes phatase method. Normal human neutrophils (BO) concluded that it was greater than in of saline were injected into a peripheral PV were cytocentrifuged, ethanol fixed, and then reflux oesophagitis (RO). These studies came tributary (caecal vein). The resultant changes incubated with coded patients' sera. Rabbit from surgical units, three of five studies in arterial, PV, and splenic pulp pressures were anti-human immunoglobulin conjugated with included Barrett's patients with complications, monitored in a total of 33 rats. Sequential alkaline phosphatase was used to detect the and in two of five studies, BO patients were microsphere injections produced graduated bound antibody. The reaction was visualised older than RO patients. In our study, acid rises in PV pressure up to a mean peak of using fast red. Twenty three of 30 PSC patients reflux in 15 patients with uncomplicated BO 18-9+0-9 mm Hg (9.5±0 9 mm Hg increase) showed positive granular cytoplasm staining from a medical gastrointestinal unit was which declined gradually to a steady state (some in a perinuclear distribution) with fila- compared with that in 21 patients with mild pressure of 13-8±0-3 mm Hg (4.4±0.3 mm Hg ments surrounding the neutrophils (type 1 reflux oesophagitis, 16 patients with more increase). There was no significant difference pattern). Fifteen of 45 UC patients and one of severe reflux oesophagitis, and 10 controls, of between increases produced by differing three chronic active hepatitis patients (CAH) comparable age. All patients had 24 hour microsphere sizes. Splenic pulp pressures, showed a similar staining. The immuno- ambulatory oesophageal pH monitoring though usually damped, closely paralleled globulin class was predominantly IgG. No (Synectics) within one week of endoscopy. those measured in the PV. correlation was found between antibody titre, Results showed that controls differed signifi- PHT can therefore be produced by blocking clinical activity or liver histology within the cantly from the other groups with respect to PV radicles with microspheres. The maximum PSC group. Fourteen other UC patients, two of total % time and the number of episodes >5 pressure achieved, however, is substantially three CAH patients, five of 14 primary biliary minutes that oesophageal pH was <4 over 24 less than that obtained by total PV occlusion cirrhosis, four of 18 alcoholic liver disease hours, but there were no differences between (60 mm Hg). This suggests the existence not patients, six of 32 Crohn's disease patients, one patients with RO and with BO. Within each only ofpressure dependent extrahepatic shunts of two coeliac disease, and three of six large disease group patients >50 years of age had but also functional intrahepatic portal systemic duct obstructive jaundice patients were also more acid reflux than patients <50 years. shunts not previously described in the normal positive but showed a diffuse pattern of cyto- We conclude that severity of acid reflux in liver. plasmic labelling with no surrounding fila- patients with uncomplicated BO is no greater ments (type 2 pattern). than in patients with RO of comparable age. This method of detecting ANA is more Our results suggest that other factors must be Is anaemia a feature of hypertensive specific than those described in recent reports important in the development of Barrett's and may be of diagnostic significance in PSC oesophagus. gastropathy? http://gut.bmj.com/ and of prognostic significance in UC. F GRANAI, H SMART, DR TRIGER (Department of Medicine and Pharmacology, University of Sheffield, RoyalHallamshire Hospital, Sheffield) Although haemorrhagic gastropathy is an Enhanced brain serotonin metabolism, in Treatment of advanced adenocarcinoma of important cause ofbleeding in portal hyperten- human hepatic encephalopathy the oesophagus and stomach with epirubicin, sion, its contribution to the anaemia of stable cisplatin, and continuous 5-fluorouracil chronic liver disease is unknown. We have H ALMARDINI, E HARRISON, P INCE, K BARTLETT, on September 28, 2021 by guest. Protected copyright. studied 72 consecutive patients with portal C 0 RECORD (Gastroenterology Unit, Royal R C MASON, M HIGHLEY, N BRIGHT, M HILL, hypertension undergoing diagnostic endo- Victoria Infirmary and MRC Neurochemical S BARKER, D CUNNINGHAM, P HARPER (Depart- scopy or maintenance sclerotherapy. Seven Unit, Newcastle General Hospital, Newcastle ment of Surgery and Oncology, Guy's Hospital, patients receiving propranolol for previous upon Tyne) An excess of the neuroinhibitory London and Royal Marsden Hospital, London) bleeding gastropathy were excluded from transmitter serotonin could be responsible This study describes our early results with analysis, as were patients with documented for the impaired consciousness in hepatic epirubicin, cisplatin, and fluorouracil (ECF) bleeding varices within the previous 3 months. encephalopathy (HE) and increased brain 5- chemotherapy in 10 assessable patients to date Anaemia (Hb greater than 2 SD below the HIAA has been a consistent finding in various (16 entered) with advanced adenocarcinoma of normal mean), was found in 49% ofthe patients animal models of the condition. the oesophagus and stomach. Patients had (overall median: Hb 12-5 g/dl). Hb was lower In the present study, using HPLC with either locally advanced disease, nodal or liver in more advanced liver disease (Child's A: 12-7 flurometric detection, we have examined brain metastasis confirmed by biopsy specimens g/dl (n=39), B: 11-9 g/dl (n=19), C: 9-7 g/dl serotonin and its precursors and metabolites in which were assessable by computed tomo- (n=7); p<005), but there were no differences 15 patients with HE complicating acute and graphy. All patients had ECOG scores 0-2. according to variceal size, previous variceal chronic liver disease and 13 matched control 5-Fluorouracil was administered by contin- bleeding, number of bleeds, or sclerotherapy subjects. Serotonin was significantly increased uous iv infusion via a minipump and Hickman sessions. The Hb did not differ (p=0.78) in thalamus (p=0-041) while the degradation catheter in a dose of 200 mglm'/day, E-50 mg/ between patients without gastropathy (12-7 product 5-HIAA was increased in thalamus m2 and C-60 mg/m2 were given by iv bolus in a g/dl, n= 17), those with mild gastropathy (p=0-048) globus pallidus (p=0-004), and three weekly cycle. (erythema or mosaic pattern) (12-7 g/dl, n=39) putamen (p=0 002). The tryptamine degrada- Assessment of response was made after three or those with severe gastropathy (cherry red tion product indoleacetic acid was increased in cycles. Response (>50% reduction of all para- spots) (11-7 g/dl, n=9). Median Hb in 22 frontal cortex, caudate nucleus, globus meters on computed tomogram) was seen in Helicobacter pylori positive patients was 11-7 pallidus, putamen, and thalamus (p<0O001) seven (70%) patients, with stasis in one and g/dl compared with 12-6 g/dl in 43 who were The precursor amino acid tryptophan was progression in two. All had symptomatic H pylori negative (p=0 36). increased in globus pallidus (p=0.003), benefit especially with regard to dysphagia, We conclude that although patients may putamen (p=0 009), thalamus (p=0 023), requiring less laser treatment than is usually present with acute bleeding due to severe frontal cortex (p=0-014), and caudate nucleus seen in such patients. The treatment was well gastropathy, it does not seem that portal hyper- (p=0 033) while 5-hydroxytryptophan was tolerated with significant problems seen in less tensive gastropathy is a major cause of chronic also increased in all brain areas studied than 10% of treatment cycles. anaemia in portal hypertension. (

Open access endoscopy for acute dysphagia practitioner because of frequent or daily full oesophageal function tests. Review of in Leicestershire dysphagia. endoscopic video tapes significantly enhances In conclusion, only a small proportion of the accuracy of interpretation.

B TREGASKIS, P NAIR, Y CHUAH, A C WICKS, J F outpatients presented with frequent or severe Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from MAYBERRY (Department of Gastroenterology, oesophageal symptoms; an investigation of LeicesterGeneralHospital, Leicester) In 1990, an oesophageal function in these patients is open access service for people with dysphagia therefore feasible. Even daily and potentially Symptoms dictate the salivary bicarbonate was established. General practitioners in the ominous symptoms are often not reported and acidification district and surrounding areas were invited to become evident only after specific questioning. response to intraoesophageal refer all patients for early endoscopic assess- C M BROWN, B SLEE, L SANDLE, W D W REES ment. Referrals could be made at any time (Hope Hospital, Salford and Trafford General throughout day and night. Outside office Hospital, Manchester) Since swallowed salivary hours, messages were recorded on a telephone Primary immotile oesophagus in young bicarbonate contributes to acid neutralisation answering serice. During the first seven patients within the oesophagus, basal secretion and months of operation 50 patients were referred. response to oesophageal acidification were Their mean age was 64 years (range 16-93). S M ALLEN, D E VAN RAEMDONCK, I P ADAMS, examined in seven healthy subjects. Significant new pathology was detected in 44 H R MATTHEWS (East Birmingham Hospital, A 10 cm segment of oesophagus was per- (86%) cases. Nineteen patients (38%) had Birmingham) Since oesophageal manometry fused with saline (pH=7 0, 5 mt/minute) strictures in the oesophagus. was introduced groups of patients have containing a non-absorbable marker (3H- Oesophageal pathology detected: 11 peptic been identified with disordered motility, for polyethylene glycol). Saliva was collected by strictures (22%); eight malignant strictures example achalasia and diffuse oesophageal continuous dental aspiration, pooled at 15 (16%); eight oesophagitis (16%) (two Barrett's, spasm. minute intervals, and bicarbonate output was three hiatus hernia); three hiatus hernia alone Since 1984 we have seen 14 young patients determined by measurements of volume, pH, (6%); one impacted food bolus (2%); one with loss of oesophageal motility which is and pCO2. Swallowed salivary bicarbonate was pharynx ulceration (2%); one Candida oeso- unexplained in terms ofreflux, neurological, or determined by appearance of amylase in oeso- phagitis (2%); 17 normal structurally (34%). systemic disease. Mean age at presentation was phageal aspirates and marker dilution. After a Of the patients with a structurally normal 33 years (range 20-42) and nine were female. basal period with saline, the oesophagus was oesophagus, only six had completely normal Barium swallow was normal in eight patients perfused with 0 1 N hydrochloric acid. Five endoscopies. One patient had a gastric fundus and showed minor abnormalities in six. The subjects experienced heartburn during acid carcinoma and one pyloric stenosis, two gastric only endoscopic abnormality was minimal perfusion and mean (SEM) salivary bicarbo- ulcers, two duodenal ulcers, one duodenitis, oesophagitis in three patients, and pH studies nate secretion increased from 2848.2 (1480-4) two gastritis, two duodenal polyps. were all normal. Upper oesophageal sphincter to 4362 1 (1393-6) [smol/hour (p=0-017). This We found 19 strictures requiring treatment pressures and cervical motility were normal resulted from an increase in salivary volume (38%) and significant oesophageal pathology except in one patient. Motility in the body of (149-6 (39 2) to 208-8 (44.4) ml/hour, p= responsible for dysphagia in 66% of patients. the oesophagus was severely reduced in all 0 0053), and increased bicarbonate concentra- The service led to early diagnosis and treatment patients with a mean amplitude of 10 mm Hg. tion (14-5 (4.3) to 19-3 (2.4) [tmol/ml, p= and has been well received by patients and Lower oesophageal sphincter resting pressures 0.23). Two subjects with higher basal salivary general practitioners. were reduced in 11 patients, with incomplete bicarbonate secretion did not experience Such a service should now become routine in sphincter relaxation in three. All patients have symptoms during acid perfusion and a reduc- units concerned with an efficient patient orien- been followed up for at least three years tion in salivary bicarbonate secretion occurred tated service. without progression of their symptoms or the with oesophageal acidification (means=53585 development of a secondary cause. Seven to 2882 1 imol/hour). http://gut.bmj.com/ patients have undergone repeat studies with no Symptom perception therefore seems changes in their characteristics. important in enhancing salivary bicarbonate We conclude that there is a group of young secretion in response to oesophageal acidifica- patients who seem to undergo severe primary tion. Oesophageal symptoms in the population: a loss of oesophageal motility for reasons that survey by a group of 50 general practitioners have not yet been identified. on 2200 patients on September 28, 2021 by guest. Protected copyright. L BENINI AND THE VERONA GENERAL Non-cardiac chest pain - is it gastro- PRACTITIONERS STUDY GROUP (Divisione di Oesophageal function assessed by endo- oesophageal reflux? Gastroenterologia, COC di Valeggio sM, scopic video recording Universitd di Verona and Servizio Sanitario A ANGGIANSAH, J CHAMBERS, R COOKE, N F Nazionale, Verona Italy) The prevalence of H TZATHAS, P M SPRINGETT, P E T ISAACS BRIGHT, K SUMBOONNANONDA, W J OWEN oesophageal symptoms in the general popula- (Gastroenterology Department, Victoria Hospital, (Departments of Surgery and Cardiology, Guy's tion was investigated. A questionnaire was Blackpool) An endoscopic assessment of oeso- Hospital, London) Thirty seven patients who completed by 50 general practitioners on 2200 phageal function was made in 72 consecutive had been admitted to the coronary care unit patients over 18 years seen consecutively on patients (41 F, 31 M, aged 23-88 years) with with suspected myocardial infarction were two days to record the frequency, severity, and oesophageal symptoms but no oesophagitis, referred to the oesophageal investigation unit association of oesophageal symptoms with stricture, or other lesion. Scores of lower after detailed cardiological assessment with food, beverages, or smoking. Mean (SD) age oesophageal sphincter (LOS) function, resting normal coronary angiography. and male/female ratio were 48.5 (18-11) years motility (RM), and peristalsis (P) were made at Oesophageal motility was studied with base- and 0-6 respectively. Heartburn was present endoscopy. Video scores were made in 45 line manometry (Aspen Medical). Provocation (P) in 31-1%, frequent (F) or daily (D) in 6-2 patients by 'blind' review of video recordings. testing with hyperventilation, Bernstein acid and 1-9% of all cases respectively. Its severity Scores were compared with function tests - 24 perfusion, and iv edrophonium (80 [sg/kg was moderate or severe in 14-5%. In 29% of hour pH monitoring (PHM) for LOS function BW) was used during manometry in an attempt patients, heartburn was not associated with and perfusion manometry for RM and P. to maximise the diagnostic yield. Following the meals, in 33% it was worse before and in 37% Endoscopic LOS score had a sensitivity of motility studies, all patients underwent 24 hour after meals. A particular food was the cause in 82% and specificity of 61%; video increased oesophageal pH monitoring (Synectics) to 15-7% of cases (wine 8%, spirits 5.5%, coffee sensitivity to 92% and specificity was detect abnormal gastro-oesophageal reflux 9.3%, smoking 3%). Similar data were found unchanged (63%). Endoscopic RM score had a (GOR). for dysphagia (P 22-8% of cases, F 41%, sensitivity of 36%, specificity 98%; video Baseline manometry was abnormal in four D 04%), regurgitation (P 39-2%, F 723%, D increased the sensitivity to 100% and specificity patients (10-8%) (two diffuse oesophageal 0.6%), odinophagia (P 10-7%, F 2-1%, D fell to 81%. Endoscopic P score had a sensi- spasm (DOS), two non-specific motility dis- 0 4%), bolus (P 12-8%, F 3.7%, D 0 7%), and tivity of 48%, specificity 86%; video increased orders (NSMD)). Provocation testing results pain after retching (P 8-8%, F 1-5%, D 0.2%). the sensitivity to 87%, specificity was were as follows: hyperventilation test, five The frequency of dysphagia, regurgitation and unchanged. positive (13.5%) (no manometric changes); odinophagia increased with age but this was not We conclude that simple endoscopic assess- Bernstein acid perfusion test, 12 positive the case with heartburn, bolus, or pain after ment of oesophageal function may easily be (32.4%) (seven GOR, one DOS, one NSMD, retching (analysis of variance). As many as performed during routine endoscopy and pro- and three normal); edrophonium test, four 43% of patients did not contact their general vides data comparable with that obtained from positive (10-8%) (two GOR, two normal). British Society ofGastroenterology A1213

Oesophageal pH monitoring showed that 14 without HH, and that HH had no influence on Medical School, London) Oesophageal acid per- patients had GOR (38%). treatment results in oesophagitis. fusion may cause anginal pain in patients with

In conclusion, oesophageal abnormalities coronary artery disease (CAD). The suggested Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from were found in 18 patients (48 6%) and GOR mechanisms are acid provoked coronary was the commonest finding (38%). The provo- Thoracoscopic enucleation of leiomyoma of ischaemia or confusion of heartburn with true cation tests were found to be non-specific in the oesophagus angina. that the Bernstein acid perfusion test was To distinguish between these possibilities, positive in five patients without GOR and N J EVERITT, M GLINATSIS, M J MCMAHON we studied 15 patients with angiographically edrophonium reproduced symptoms in four (University Department ofSurgery, The General proved CAD (14 men; mean (SD) age 59 (7) patients without motility disorders. NCCP is a Infirmary, Leeds) A 48 year old woman with a years). All had ambulatory 24 hour oeso- complex problem and it may not be caused by a six month history of dysphagia was shown to phageal pH and seven lead ambulatory ECG single aetiological factor. have the characteristic appearances of a monitoring (for ST segment analysis). Six leiomyoma of the mid-oesophagus on barium patients had angina during the study, with a swallow and on endoscopy. median and range of 2 (1-7) episodes, and nine Endoscopic enucleation was carried out had episodes of ST depression >1 mm, with a Intralesional treatment of idiopathic oeso- under general anaesthesia with the patient in median and range of 7 (2-29) episodes. Seven phageal ulcers in AIDS the left lateral position. The right lung was had abnormal acid gastro-oesophageal reflux collapsed and a video laparoscope was inserted (GOR) (% total time pH <4 exceeding 7%). J SMITHSON, B G GAZZARD, (INTRODUCED BY B G through the fifth intercostal space. The lung There were no significant correlations of % GAZZARD) (AIDS Unit, Westminster Hospital, was retracted medially with two 5 mm diameter time pH <4 or number of reflux episodes with London) Idiopathic oesophageal ulcers causing rod retractors. The azygos vein was divided number of ST segment shifts. Of a total of 80 dysphagia and oesophadynia have been des- between catgut ligatures and locking poly- ST shifts, only 11 correlated with reflux cribed in patients with AIDS. We report two dioxanone clips (Absolok - Ethicon). The episodes. An association between anginal pain cases which resolved symptomatically and thoracic oesophagus was mobilised and retrac- and GOR was observed in three patients. In endoscopically after intralesional steroid ted laterally with a sling. Rotation of the these three patients, six ofa total of 10 episodes injection. oesophagus enabled a longitudinal myotomy ofangina correlated with reflux episodes, but in Two HIV positive patients with previous over the posteriorly placed lesion. The only one episode in one patient did GOR, ST AIDS diagnoses and complaining of dys- encapsulated leiomyoma was enucleated intact segment shift, and symptoms coincide. phagia, retrosternal pain, odynophagia, and without mucosal damage. The longitudinal We conclude that in patients with CAD: acid weight loss were found at endoscopy to have muscle was closed with catgut sutures. The GOR and episodes of ischaemic ST depression large oesophageal ulcers. Histology from both patient made a rapid and uncomplicated are uncommonly correlated; the association is ulcers showed non-specific acute and chronic recovery. not increased in patients with abnormal GOR; inflammation with no evidence of viral inclu- Our experience suggests that thoracoscopic in a minority of patients, pain from acid reflux sions, mycelia, or other pathogens on light or surgery has the potential to provide advantages cannot be distinguished from their anginal electron microscopy and immunoflorescent in the treatment of oesophageal leiomyoma pain, and this is the most frequent explanation staining. After two weeks of (foscarnet) anti- similar to those that laparoscopic surgery has for episodes of angina related to reflux. CMV treatment with no endoscopic change, brought to the treatment ofgall stones. the patients were treated with intralesional methyl prednisolone acetate (120 mg in total at three sites along the ulcer). Nifedipine promotes gastro-oesophageal Oesophageal acid clearance before and after There was a noticeable improvement in pain reflux healing ofoesophagitis http://gut.bmj.com/ in both patients within two hours and improve- ment in dysphagia and appetite over the next 24 A J MEHTA, J S DE CAESTECKER, T C NORTHFIELD P SINGH, A ADAMOPOULOS, R H TAYLOR, DG hours. Follow up endoscopies, at two weeks in (Department of Medicine, St George's Hospital COLIN-JONES (Royal Naval Hospital, Haslar, both cases, showed resolution of the ulceration Medical School, London) Nifedipine decreases Gosport, Hants and Queen Alexandra Hospital, with residual scarring only. Both ulcers recur- lower oesophageal sphincter pressure (LOSP), Portsmouth, Hants) We have previously red at the same site within two months and and amplitude (A) and duration (D) of distal reported lack of improvement in oesophageal again responded to intralesional injections both oesophageal peristalsis. This effect should manometric and transit abnormalities after symptomatically and endoscopically. Both promote gastro-oesophageal reflux (GOR), but healing ofoesophagitis. This study investigates on September 28, 2021 by guest. Protected copyright. patients are now maintained on intralesional this has not been studied. the effect of healing of oesophagitis on oeso- steroids every six to eight weeks. Our aim was to assess the effect on GOR of phageal acid clearance. nifedipine and atenolol, two drugs commonly Nineteen patients with endoscopic oesopha- used in ischaemic heart disease (IHD). Patients gitis were studied. Eighteen of them under- with endoscopically proved peptic oesophagitis went 24 hour oesophageal pH monitoring. Of Prevalence of hiatal hernia and its influence (n=8) and healthy controls (n=8) underwent a these, 14 (78%) had abnormal pH profiles. A on gastro-oesophageal reflux and treatment double blind placebo controlled cross over three lumen oesophageal manometry catheter response in patients with reflux oesophagitis study, each on three separate days. One hour and an antimony pH probe were passed via the after treatment (nifedipine 30 mg/atenolol 100 nasal route into the oesophagus and the distal H ZHU, F PACE, 0 SANGALETTI, G BIANCHI PORRO mg/placebo po), oesophageal manometry was tips of both were positioned 5 cm above the (Gastrointestinal Unit, L Sacco Hospital, Milan, performed (rapid pull-through for LOSP, 10 upper border of the previously mapped LOS. Italy) It is still controversial whether the wet swallows for A and D). A standard acid Some 15 ml of0-1 N HCI was instilled into the presence of a sliding hiatal hernia (HH) might reflux test (SART) was then performed after oesophagus using the proximal port of the adversely influence gastroesophageal reflux loading the stomach with 300 ml 0-1 N HCI. catheter so that it arrived 15 cm above the LOS. (GER) and treatment results of patients with Nifedipine, as expected, decreased LOSP in The subject was then asked to swallow every 30 GER. We submitted to oesophagoscopy and patients and controls v atenolol or placebo seconds. Acid clearance time (ACT) was oesophageal pH monitoring 185 patients with (p<000S). Nifedipine decreased A in patients measured in seconds as the interval from the typical GER symptoms. (p<005). SART score was increased with time of instillation of HCI to the time the pH Eighty four patients proved to have neither nifedipine (mean increase in patients 4-3 v came up to 5 and stayed at or above that level oesophagitis nor pathological GER (PhR), 37 placebo, 5-5 v atenolol (p<0005), in controls for 60 seconds. The test was done in sitting and had pathological reflux but no oesophagitis 1-75 v both placebo and atenolol (p<0-01)). supine postures. The procedure was repeated (PR), and 64 had reflux oesophagitis (RE). HH We conclude that nifedipine increases GOR in all the patients after complete endoscopic was found in 19 (29.3%), 11 (16-9%), and 35 in patients with oesophagitis and normal sub- healing of oesophagitis following a course of (53 8%) respectively. GER parameters in the jects. This could be important in patients with omeprazole 40 mg/day for a median duration of three groups were statistically the same. IHD treated with nifedipine, as acid GOR 12 weeks. Twenty two healthy volunteers Patients with oesophagitis were treated for up could mimic or provoke angina. served as controls. to 24 weeks with H2 blockers, at normal or In both patients (P) and controls (C) median double doses: after treatment, no significant ACT was significantly longer in the supine than difference was found in the proportion of Does gastro-oesophageal reflux cause angina in the sitting posture (P: 490 v 420 seconds; healed patients with or without HH. in patients with coronary artery disease? p=004 and C: 369 v 252; p=0 03). Patients We conclude that HH was more frequent in had significantly longer median ACT in both reflux oesophagitis patients, that GER para- A J MEHTA, J S DE CAESTECKER, T C NORTHFIELD supine and sitting postures compared with the meters were similar overall in all groups with or (Department of Medicine, St George's Hospital controls (490 v 369; p=0-013 and 420 v 252; A1214 British SocietyofGastroenterology p=0-026 respectively). There was no correla- patients) in 50 consecutive patients with Chest x ray in the diagnosis of iatrogenic tion between the age, sex, or the grade of obstructing oesophageal or gastric cancer who oesophageal perforation - an audit oesophagitis and ACT. There was no signifi- had either received or were unsuitable for cant change in the median ACT in supine or surgery or radiotherapy. PDT used iv R N M VAN SOMEREN, J JACOMB-HOOD, S MCGEE, Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from sitting postures after healing of oesophagitis haematoporphyrin derivative 4 mg/kg, a D S RAMPTON, J MURFITT, C P SWAIN (Depart- (490 v 640 and 420 v 371 respectively). copper vapour pumped dye laser delivering 630 ments of Gastroenterology and Radiology, The Results from this study suggest that nm light through a guide wire placed endo- Royal London Hospital, London) We have impaired oesophageal acid clearance is an luminal light delivery system designed by us. reviewed the value of the chest x ray (CxR) in integral component of gastro-oesophageal Endoscopic Nd:YAG laser treatment was the detection of perforation occurring during a reflux disease and that it does not improve with delivered by non-contact 50-60 W thermal series of 408 consecutive endoscopic pro- healing ofoesophagitis. method. cedures involving oesophageal dilatation from PDT results were as follows. Quantitative 1989-91. Twelve iatrogenic perforations radiology showed a median lumen diameter occurred (3%), all in patients with malignant (MLD) before treatment of3-9 mm (range 2-2- strictures (nine/366 dilatations, three/42 5) and after treatment of8-6 mm (range 7-11-4) prosthetic placements). In the 48 hours after Results of simultaneous two level oesopha- p<0 05). The median before treatment dys- endoscopy, perforation was diagnosed by geal pH monitoring in patients with gastro- phagia score of 3 rose to 5 after treatment endoscopy (two/12), CxR (seven/12), water oesophageal reflux disease and controls (p<005). The mean number treatment soluble contrast (nine/12), plain abdominal x courses was 1-2. Median survival was 12 weeks ray (one/12), clinical findings (five/12). The 20 P SINGH, A ADAMOPOULOS, R H TAYLOR, DG (range 1-60). NLT results showed a MLD day mortality was 10/12. In all patients, CxR COLIN-JONES (Royal Naval Hospital, Haslar, before treatment of 2-1 mm (range 0-5.2) and was performed within 24 hours of the pro- Gosport, Hands and Queen Alexandra Hospital, after treatment 8-0 (range 3-16) (p<0 05). The cedure. Eleven of 12 CxRs in patients with Portsmouth, Hants) For 24 hour oesophageal before treatment dysphagia score of 2 rose to perforation were available for blind retrospec- pH monitoring, the pH probe is positioned 4 (p<005). The mean number of treatment tive review by two radiologists and an endo- 5 cm above the lower oesophageal sphincter courses was 4-3. Median survival was 18 weeks scopist, these were interspersed with x rays (LOS). This is simply by convention, and so far range (8-40). The perforation rate was '1/26 from patients who had not perforated. there has been no reported attempt to find the (4%) in PDT and 1/24 (4%) in NLT and both Evidence of perforation was mediastinal gas best level for the pH probe to achieve the were guide wire related. Thirteen of 26 PDT (5), hydropneumothorax (1), pleural effusions highest discrimination of acid reflux. We com- patients developed skin photosensitivity (seven (3), some CxRs had more than one abnor- pared the results of simultaneous 24 hour pH mild, five moderate, one severe). mality. One of seven control CxRs was thought monitoring with two probes at different levels Advantages of PDT included smokeless wrongly to show perforation. The endoscopist in the oesophagus. non-thermal nature, ease of treating tightest diagnosed perforation in only four/ 1 patients Thirty one healthy controls and 45 patients part requiring less endoscopic skill and tumour from the CxR. with endoscopically documented oesophagitis selectivity with less danger in treating junctions The post-procedure CxR may detect per- were studied. Two antimony pH probes were between normal and malignant tissue. Advan- foration after the treatment of malignant passed nasally and positioned 5 (distal) and 10 tages of Nd:YAG laser treatment included strictures, particularly if reviewed by a cm (proximal) above the upper border of the superior laser reliability and lack ofskin photo- radiologist. However, we now routinely under- LOS and connected to two separate recording sensitivity. PDT patients required significantly take contrast studies immediately after dilata- devices. The 90th centiles of the values from fewer treatment sessions (p<0 05). Photo- tion or intubation of such strictures. Since no controls were used as the cut off points. Total dynamic therapy seems a promising alternative patients with benign strictures incurred per- % time pH <4 gave the best discrimination at to Nd:YAG laser treatment for patients with foration, CxR in this group seems redundant. both levels with the 90th centile 4-9% for distal obstructing oesophageal and gastric cancer. and 3-9% for the proximal level. This gave an http://gut.bmj.com/ overall specificity of 90.3% separately for both levels, but the sensitivity was slightly higher at the distal level (77.7% v 71-1%). Combining Prevalence of oesophagitis in subjects on with supine and/or upright values or the values Oesophagitis is as important as oesophageal long term non-steroidal anti-inflammatory from the two probes did not improve dis- stricture diameter in determining dysphagia drugs crimination. In controls at distal level, the median % time M DAKKAK, J R BENNETr, S C MASLIN (Hull Royal J D ARNOLD, G L SWIFT, G T WILLIAMS, W E pH <4 was significantly higher in upright than Infirmary, Kingston Upon Hull) It is a common WILKINS, J S MORRIS, J RHODES (Departments of on September 28, 2021 by guest. Protected copyright. in supine position (2-2 v 0 3; p=0 005). In both observation that stricture patients with severe Gastroenterology and Pathology, University groups, there was a strong correlation between dysphagia may have a wide lumen, while others Hospital ofWales, Cardiff) Fifty patients (mean the two probes for all variables (p<0-001). In with a narrow stricture have few swallowing (SD) age 52 (14) years, 28 female) attending a controls, the median total time % pH <4 was complaints. rheumatology clinic were investigated by similar for the distal and proximal probes (1-6 v In 64 patients with benign oesophageal upper gastrointestinal endoscopy and oesopha- 1-8; NS); but in patients, the figure was much stricture the dysphagia score was compared geal biopsy. All had been taking indomethacin higher at the distal level (10-7 v 7.7; p<0-001). with the diameter of the stricture. There was for at least one year. Endoscopic and histo- There was a significant correlation between the a positive association, but the correlation logical findings were recorded and graded. grade of oesophagitis and all pH variables at coefficient (r) was 0 544, suggesting that the Oesophageal lesions were present in 10 both levels with the association being stronger diameter of the stricture is an important, (20%). There were erythema in three, linear at the proximal level (p<0-02 at distal and though not the sole, determinant ofdysphagia. erosions in five, and deep ulcers in two. Gastric <0 0025 at proximal). Stricture diameter explains 29-6% (r2) of the erosions were present in 13 and three had Oesophageal pH monitoring with a probe at variation in dysphagia score. gastric ulcers. Twelve patients had duodenal 10 cm above LOS gives almost the same level of The patients were divided into three groups erythema and or erosions and one patient had a discrimination as the conventional position and according to the severity of oesophagitis (19 duodenal ulcer. Endoscopy was normal in 12 is less likely to give spurious results from probe patients had minimal, 22 moderate, and 23 subjects. Four with linear oesophageal erosions displacement. severe oesophagitis). Analysis showed the had normal biopsy specimens on histology but mean dysphagia scores to be 83, 73, and 59 (out eight others with normal oesophageal mucosa of a maximum possible 90) in each group on endoscopy had inflammatory changes on respectively. The dysphagia score of each histological assessment. Four of the 10 subjects group was significantly different from the with oesophageal lesions noted on endoscopy Comparison of photodynamic therapy and others (Kruskal Wallis test). Relating the dys- had no gastric or oesophageal symptoms. Nd:YAG laser therapy for obstructing oeso- phagia score to stricture diameter for each Asymptomatic oesophageal disease is phageal and gastric cancer group gives correlation coefficients of r=0-379, common in patients receiving long term non- r=0-651, and r=0-583. If both diameter and steroidal anti-inflammatory drugs. M ABULAFI, J ALLARDICE, R DEAN, M GRAHN, N S severity of oesophagitis are included then WILLIAMS, C P SWAIN (The Surgical Unit and 66-0% of the variation in the dysphagia score Academic Department of Gastroenterology, The can be explained. Royal London Hospital, London) We compared We conclude that the degree of oesophagitis photodynamic therapy (PDT) (26 patients) is as important as luminal diameter in Neuronal maturation in the myenteric plexus with Nd:YAG laser treatment (NLT) (24 determining swallowing ability. of human fetal and infant oesophagus British Society ofGastroenterology A1215

R J I HITCHCOCK, A E BISHOP, J M POLAK We conclude that in CD, small bowel and activity comprised complexes of 11-2+1 (Department of Histochemistry, Royal Post- colonic transit are considerably accelerated, minutes (mean+SEM) duration with a fre- graduate Medical School, London) This study and PC capacitance is reduced. Patient quency of 3-4/minute, and amplitude mostly provides the first quantitative analysis of the plasma accelerates GE and SBT in rats; the <60 cm H20. This uncoordinated activity Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from maturation of neurons in the myenteric plexus rat bioassay is a promising method to occurred with equal frequency in channels of the human oesophagus. Oesophageal elucidate the bioactive mediator(s) of CD. proximal and distal to the anastomosis. The samples (eight weeks gestational age to 28 return of bowel sounds was not associated with months of age (n=35)) were immunostained change in activity. However, the first passage for general nerve, synaptic vesicle, glial and of flatus corresponded to the appearance of neuropeptide markers and histochemically Measurement of orocaccal transit time by a aboral migrating complexes (3-2 cm/second) in stained for NADH-diaphorase. Cell fre- new ferromagnetic technique five patients. quency, size, and the immunoreactive Colonic ileus after colectomy may persist for myenteric fraction were computer quantified. R B OLIVEIRA, J R MIRANDA, 0 BAFFA, 60-110 hours. The transanastomotic pressure Neuronal size increased with gestational age N M MATSUDA, L E A TRONCON (INTRODUCED BY gradient rarely exceeds 50 cm H20 during this from 6 im at eight weeks to 20 im at term and D G THOMPSON) (Faculdade de Medicina de time. Passage of flatus corresponds to the 21 ,tm at 28 weeks. The myenteric fraction and Ribeirao Preto, Universidade de Sao Paulo, return to propagating activity. cell frequency peaked at 16-20 weeks and then Ribeirao Preto, SP, Brazil) Current methods *Wilcoxon rank. fell rapidly until the third trimester. The ratio for measurement of oracaecal transit time of glial to nerve protein immunoreactivity (OCTT) have some limitations, such as failure increased throughout. Immature neurons to produce hydrogen (H2) after non-absorbed expressed general nerve and synaptic vesicle sugars have reached the colon or exposure to Measurement ofthe human gastric relaxation protein immunoreactivity by eight weeks. radiation. We therefore investigated the responses to distension and to feeding Neuropeptide immunoreactivity was not seen validity of a new non-invasive ferromagnetic until 13 weeks but an adult-like pattern was technique for measuring OCTT and to detect N K AHLUWALIA, D G THOMPSON, L TRONCON, complete by 15-5 weeks. abnormally rapid OCTT in patients. Experi- J BARLOW, L HEGGIE (University Department of Thus, we have shown that though neuronal ments were carried out in 21 healthy control Medicine, Hope Hospital, Salford) Although maturation continued during gestation, neuro- volunteers and in a group of 11 patients with receptive gastric relaxation to food is well peptide expression was complete and neuron diarrhoea caused by gastric or small bowel recognised, methodological difficulties have frequency maximal at the onset of fetal disorders. After an overnight fast, a standard precluded its accurate measurement in man swallowing at 16 weeks. These findings form test meal containing 5 g ofmagnesium ferrite as and the factors modulating the response remain the basis for an investigation of abnormal a magnetic tracer and 18 g of lactulose was poorly understood. We therefore developed a neuronal maturation in oesophageal atresia. ingested. The arrival of the magnetic tracer to computerised pressure/volume sensor device the caecum was monitored with a magnetic attached to a 1200 ml balloon sited in the detector probe externally applied to the right fundus to measure compliance (pressure/ iliac fossa and end expiratory breath samples volume) responses to graded gastric distension MOTILITY were taken up to three hours after meal inges- during fasting and after food. tion for H2 measurements. Values obtained After an overnight fast 15 healthy volunteers with the ferromagnetic technique were closely ingested the assembly and the balloon was correlated with those observed with the H2 positioned in the fundus. Intrafundal pressure Gastrointestinal transit, colonic capaci- breath test (R=0-74, p<0-001). In the group of was recorded for 30 ml stepwise inflations of

tance, and possible mediators in carcinoid patients with diarrhoea, OCTT values were the balloon from 0 ml to the maximal tolerated http://gut.bmj.com/ diarrhoea faster than in controls either when measured volume and compliance was measured by cal- with the magnetic technique (median: range; culating the slope (x 10 ') of the log trans- M CAMILLERI, G THOMFORDE, D MINSKE, 45:10-125 minutes v 84:40-155 minutes, formed pressure/volume relationship. Three M VASSALLO, S POWERS, L KVOLS (INTRODUCED p<0-01) or with the H2 breath test (42.5:30-95 consecutive inflations were performed during BY S PHILLIPS) (Mayo Clinic, Gastroenterology minutes v 80:40-120 minutes, p=0.02). fasting plus a further inflation after ingestion of Unit, Rochester, MN 55905 USA) The patho- In conclusion, this study suggests that the a 250 ml, 250 kcal standard liquid meal. Seven physiology ofcarcinoid diarrhoea (CD) remains ferromagnetic technique can reliably measure individuals repeated the study on a separate were to motor to assess of the method. unclear. Our aims study gut orocaecal transit time and is effective to detect day reproducibility on September 28, 2021 by guest. Protected copyright. function in CD and the effects of putative abnormally rapid uppergastrointestinal transit. Fasting studies showed that the slope of the mediators on gastrointestinal transit in rats. In initial inflation curve was mean 114-6 (SEM) four unoperated patients with severe carcinoid (10-0) mmHg/ml. On the second pre-meal diarrhoea and 10 healthy controls, we distension, the slope decreased to 83 0 (5.4) measured gastric emptying (GE) and small Return of colonic motility after sigmoid (p<0-01 v first) indicating distension induced bowel transit (SBT) by ""Tc labelled 1 mm colectomy using an ambulatory technique fundal relaxation. No further change in com- pellets in a meal, and colonic transit by "'In pliance occurred during subsequent pre-meal labelled pellets from a delayed release capsule. J P ROBERTS, M BENSON, W W WOODS, distensions (slope: 79-8 (5.7); p>0 05 v Capacitance of the combined ascending and J R ROGERS, N S WILLIAMS (Surgical Unit, The second). Feeding further decreased the slope of transverse regions (proximal colon, PC) was Royal London Hospital, London) Colonic motor the pressure/volume curve to 60-27 (7.7) calculated (Gut 1990; 31: 443-9). In anesthe- activity in the postoperative period has been mm Hg/mI (p<0 05 v pre-meal) indicating a tised rats, we measured the dose related poorly investigated. To determine the effect of further increase in fundal compliance. Repeat effects on combined GE and SBT of 'n'Tc colonic resection on pressure activity, six studies showed that the slopes of the three saline by the putative mediators, scrotonin patients undergoing sigmoid colectomy and fasting compliance curves were similar to the (5HT), and substance P (SP), motilin and primary anastomosis were studied using a three initial values (95.29 (16-3), 82-14 (18-4), 81-0 saline (controls), and plasma from one channel microtransducer probe (CTO-3, (16-2), p>0 05; coefficient of variation= 14%). patient (normal plasma SP and urinary Gaeltec Ltd) positioned across the anastomosis In conclusion, increasing distension of the 5HIAA) and one healthy control. In separate and connected to a solid state recorder (Gaeltec human fundus induces a progressive and repro- studies the effects of 5HT, motilin, and 7MPR). Anaesthetic agents and postoperative ducible relaxation response which is modulated plasma on GE in the rat were assessed by analgesia were standardised. Probe position by distension itselfand by food, both serving to dynamic scintigraphy. was verified radiologically. Traces were increase gastric accommodation for a given The results showed that: (1) In CD, PC analysed quantitatively, by automated com- nutrient load. emptying and overall colonic transit were puter analysis, and qualitatively. considerably accelerated (p<005); SBT Colonic pressure was measured continuously showed a similar trend (p=0-.07); GE was in each case for 85-108 hours. There was normal. (2) Mean (SEM) PC volume was absence of activity > 10 cm H20 for a variable The response of the human migrating motor lower in CD (793 (63) ml) than in health (1324 period (median 25, range 14-66 hours) after complex to fasting gas and secretion (162) ml; p=0.01). (3) In rats, intra-aortic surgery. The motility index (MI=mean ampli- 5HT and patient plasma accelerated GE tudex% duration activity) increased signifi- D SMITH, B WALDRON, F C CAMPBELL (Depart- (p<005); motilin and control plasma did not. cantly by the third postoperative day compared ment ofSurgery, Ninewells Hospital and Medical Motilin and patient plasma accelerated com- with the first (median 1-4 range 0-05-14-8, v School, Dundee) The interaction of the phases bined GE and SBT (p<005); 5HT, SP and 0-38, 0-7.3, p<0-01*), but there was a persis- of the migrating motor complex (MMC) and control plasma were ineffective. tent loss of normal diurnal variation. Motor intraluminal gas and acaloric secretion is un- A1216 British Society ofGastroenterology known. In this study small bowel perfused tube automated method for measurement of gastric present within three hours in all patients. The manometry was carried out in 17 volunteers and small bowel motor physiology. migrating motor complex (MMC) interval was over four separate three hour intervals each: *ANOVA, two way analysis of variance. markedly reduced for the first 24 hours (mean (i) in the baseline fasting state (BL); (ii) after (SEM) 27-8 minutes (3 0)) but tended to nor- total gas and fluid evacuation (TGFE) from the malise with time. Phase II activity returned

entire upper gastrointestinal tract through a after a mean of 49-4 hours (range: 35-60). Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from perforated orocaecal tube; (iii) after intagastric Comparison of a perfused catheter and a Phase III mean amplitude was decreased (- 10 instillation of gas (IIG) (350 ml air); (iv) after strain gauge assembly in pharyngo-oesopha- mm Hg) or absent in distal duodenum and intagastric instillation of fluid (IIF) (350 ml geal pressure measurement jejunum in five of six patients for 29-6 hours acaloric 0.5% methylcellulose solution). (range 16-54-2). There was no correlation All studies showed fasting motility patterns. J A WILSON, A PRYDE, C C A MACINTYRE, between the return of bowel sounds and TGFE decreased phase II duration (median R C HEADING (Departments ofSurgery, Medicine changes in PSB motility patterns. (interquartile range) 37.9 (30 4 40) minutes and Medical Statistics Unit, University ofEdin- The disparity between EMG and pressure (TGFE) v 54-7 (35-1-67-3) minutes (BL), burgh) Finebore strain gauge assemblies (SGA) data suggests that the SB motor 'programme' is p=0O03) and contraction amplitude (mean are now available for manometric investigation preserved but ineffective during POI. The low (SEM) 16-7 (0.4) mm Hg (TGFE) v 18-5 (0.4) and are increasingly used for pressure measure- amplitude of the pressure changes at the distal mm Hg (BL), p<0-001). Phase III contraction ment in the pharynx and upper oesophageal sensors suggests that contractile forces may be frequency was decreased (median (inter- sphincter (UOS). Other centres continue to use dissipated by luminal distension. quartile range) 7-72 (6-99-9 3) (TGFE) v 10-07 conventional perfused catheters, and the (9-66-10-96), p<0 005). Conversely, IIG in- measurement differences between the two creased both the duration (median (inter- catheter types are unknown. We studied 21 quartile range) 67-3 (604-71-8) minutes (IIG) patients, 9 males, 12 females, aged 25-81 years Oral and intravenous erythromycin has no v 54.7 (35-1-67-3) minutes (BL), p<0 02) and (mean=56) with cervical symptoms (globus, effect on distal human colonic motility the contraction amplitude during phase II dysphagia, hoarseness) using multiple radially (mean (SEM) (0.3) mm Hg (IIG) v 17.6 (0.3) orientated sensors of both a 4-8 mm perfused J S JAMESON, J ROGERS, A H RAIMUNDO, mm Hg (BL), p<0-001). Phase I duration was catheter (Arndorfer) and a 2-8 mm SGA M M HENRY, J J MISIEWICZ (Department of decreased (median (interquartile range) 27-6 (Gaeltec) linked to a GR800 computer recorder Gastroenterology and Nutrition, Central Middle- (25A4-33 3) minutes (IIG) v 37-7 (26.9-56 7) (Aspen Medical). sex Hospital, London) Motilin receptors in the minutes (BL), p<0O05). Phase III contraction The results showed lower LOS RPT lower oesophageal sphincter, stomach, gall frequency was increased by IIG (median (inter- (p<005) and oesophageal body pressures bladder, and small bowel are stimulated by quartile range) 9-88 (9-16-10-67) v 9 3 (8-18- (p<002) with the SGA than the perfused erythromycin and motilin infused at physio- 9 72) (BL), p<0O04). IIF increased phase II catheter (Student's t test). UOS RPT and SPT logical concentrations increases colonic contraction amplitude (mean (SEM) 20-3 (0.3) pressures were also lower with the SGA by an pressure activity. Erythromycin decreases mm Hg (IIF) v 17-6 (0.3) mm Hg (BL), average of30 mm Hg (both p<0-001), pharyn- colonic transit time in humans, but its effect on p<0-001), but not duration (median (inter- geal pressures were considerably lower with the colonic segmental pressure activity is un- quartile range) 58.6 (56-69 4) minutes (IIF) v Arndorfer (4+19 mm Hg) than the SGA known. 54.7 (35- 1-67-3) minutes (BL), p=NS). (96±50 mm Hg, p<0-001). Eight male volunteers were studied on two The phases ofthe MMC appear responsive to In conclusion, the recording of pressures occasions, receiving either 125 mg iv or 500 mg alteration in fasting gut content and may con- consistently lower in the LOS and oesophageal oral erythromycin, or placebo in a single blind tribute to differential transit ofgas and fluid in body with the SGA than the perfused catheter randomised crossover design. Sigmoid the fasting state. is probably due to the smaller stretch/tension pressures were recorded with a four lumen response induced by the narrower SGA water perfused assembly at 50, 45, 30, and diameter (2-8 mm). This response seems to be 15 cm from the anal verge. Pressures were greater in the striated muscle of the UOS. In for index mm Hg/ analysed activity (Al, http://gut.bmj.com/ Development and validation of a micro- contrast, SGA recorded pharyngeal pressures minute) for the 35 cm colonic study segment. computer technique for analysis of gastric were significantly higher, confirming the No significant (MANOVA) difference was and small bowel manometry (fasting and fed greater ability of strain gauges to capture the found in the Als after erythromycin (mean state) steep upstroke (AP/At) pharyngeal waves. (SEM) 498 (43) mm Hg/minute v 765 (44), Laboratories which introduce an SGA must basal) and placebo (588 (39) v 641 (21) given D SMITH, B WALDRON, B E STOREY, M LOUDON, establish normal reference ranges appropriate orally, or after erythromycin (846 (67) v 1091 F C CAMPBELL (Departments of Surgery and to the catheter diameter and transducer (116) and placebo (1135 (57) v 739 (18) given Physics, Ninezvells Hospital andMedicalSchool, characteristics. intravenously. In a further experiment one Dundee) Manual analysis of motility is too subject was given increasing doses of iv on September 28, 2021 by guest. Protected copyright. laborious for routine clinical use. Previous erythromycin (125 mg, 250 mg, and 500 mg) computerised methods have lacked facilities without change in colonic Al. (125 mg: 646 for artifact exclusion, pattern recognition for Proximal small bowel motility is preserved in (297) v 722 (195), basal; 250 mg: 950 (205) v the migrating motor complex (MCC), and the postoperative ileus: fact or fiction? 936 (243); 500 mg: 863 (154) v 660 (322)). validation. This study has developed a new Despite using doses known to affect small microcomputer technique with these features, M J BENSON, J ROBERTS, J ROGERS, W WOODS, bowel and gall bladder motility, neither oral nor and validated it in 24 hour ambulatory studies N S WILLIAMS, D L WINGATE (GI Science Research intravenous erythromycin affected segmental ofgastric, duodenal, and jejunal motility in six Unit and Surgical Unit, The Royal London colonic pressure in the unprepared sigmoid volunteers, against two assessments by two Hospital Medical College, London) Electromyo- colon. These data suggest that motilin skilled observers. graphic data suggest that primate proximal receptors are not stimulated by erythromycin No significant differences* were found small bowel (PSB) contractility is not abolished in the human sigmoid colon and previously between microcomputer (Comp) and observer in postoperative ileus (POI). Using prolonged reported effects of erythromycin on colonic (Obs) analysis in detection of cough artifact, intraluminal manometry, we wished to docu- transit may be secondary to changes in small gastric MMC, duodenal MMC, and MMC ment local and propagated phasic pressure intestinal or proximal colonic function. migration velocity. Interobserver differences changes in the PSB during POI after major in contraction detection during 3 x 30 minute intra-abdominal surgery. We studied six sub- intervals were found (p<005),* whereas no jects (three M/three F; age 49-77 years) under- difference was observed between microcom- going sigmoid colectomy. Premedication, Irritable bowel syndrome and affective dis- puter (total contractions; n=470) and the mean anaesthetic, and postoperative opioid analgesia order: a family history ofboth observers (total contractions; n=457).* were standardised. At operation, a three-sensor There was no significant difference* in mean nasojejunal manometric catheter was intro- P A DEWSNAP, G W LIBBY, M J G FARTHING (SEM) contraction amplitude (Comp=36 (2) duced to locate the transducers in the proximal (Department of GastroenteroloV, St Bar- mm Hg; Obs 1=37 (2) mm Hg and Obs and distal duodenum and jejunum; its position tholomew's Hospital, London) A random sample 2=37-7 (2) mm Hg); contraction duration was checked radiologically at the beginning of 33 outpatients with a clinical diagnosis of (Comp= 3-4 (0O1) secs; Obs 1=3.3 (0-1) secs, and end of the study. Recording continued irritable bowel syndrome (IBS) were evaluated and Obs 2=2-8 (0- 1) secs) or contraction from 30 minute after wound closure until the by questionnaire for gastrointestinal (GI) propagation (Comp: n=41; Obs 1:n=39 and passage of flatus. symptoms including the Manning criteria and Obs 2:n=39) were found. The mean duration of recording was 97-6 discriminatory symptoms of affective disorder This novel technique provides an accurate hours (range: 84-108). Phase III activity was as defined by the Research Diagnostic Criteria British Society ofGastroenterology A1217

(RDC). In addition, a detailed family history of resulted in plasma bismuth concentrations that High dose balsalazide compared with GI and affective symptoms among their 145 were below the 'alert' threshold of 50 ng/g. sulphasalazine in the treatment of acute first degree relatives was taken. Where possible, relapse in ulcerative colitis this family history was supplemented by in- Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from formation obtained directly from the relatives J R B GREEN, C H J SWAN, A E ROWLINSON, J A by a similar questionnaire. Twenty five of the Is high dose balsalazide better than sulpha- GIBSON, P BROWN, G D KERR, P C THORNTON 33 probands (75%) met RDC criteria for salazine in initial management of ulcerative (City General Hospital, Stoke-on-Trent, Stafford affective disorder, mainly major depression colitis? General Infirmary, Shrewsbury Hospital, Telford (54%). There was evidence for a family history Hospital, Biorex Laboratories) Balsalazide of IBS in 45% of probands. However, IBS J C MANSFIELD, M H GIAFFER, P A CANN, C D (BSZ) is a sulphasalazine (SASP) analogue and occurred in 22 of the 145 relatives (15%), HOLDSWORTH, D M McKENNA, P C THORNTON has been shown to be well tolerated in high dose comparable with that in the general population. (Royal Hallamshire, Sheffield, Middlesbrough for 12 months (Green, et al 1990). It may be A family history ofmajor depression was found General Hospital, Middlesbrough, and Biorex that the delivery ofa higher concentration of 5- in 19 of the 33 probands (57%) with a preva- Laboratories Ltd, Enfield) We have compared ASA to the colonic mucosa in acutely relapsed lence among relatives of 19%. This is greater balsalazide (BSZ) 6-75 g/day and sulphasala- ulcerative colitis (UC) will increase the ease and than in the general population (approximately zine (SASP) 3 g/day in a double blind random- rapidity of achievement of remission. In a 10% lifetime prevalence) and ofsimilar magni- ised trial in 37 patients with newly diagnosed prospective double blind trial, 40 patients with tude to that found in family studies on ulcerative colitis (UC). Patients were not either acute relapse or first presentation of UC psychiatric patient populations. allowed steroids and were reviewed at two, were randomised to receive either SASP 3 The results show that (i) there is an apparent four, and eight weeks. Sigmoidoscopic appear- g/day or BSZ 6 g/day. Severity of relapse was tendency for IBS to run in families which is ances, rectal biopsy specimens, and symptom stratified into mild (no steroid needed), explained by the high population prevalence of and stool diary records were used to assess moderate (topical steroid needed), or severe IBS, (ii) the high prevalence of depression in response between entry and eight weeks. The (systemic steroid needed) to ensure two com- family members suggests that the affective groups were well matched for age and sex parable patient groups. Patients underwent diagnoses in IBS probands are genuine cases of distribution. sigmoidoscopy at four, eight, and 12 weeks to affective disorder rather than normal reactions Intolerance to therapy, necessitating with- assess progress. to physical symptoms, but, (iii) there is no drawal, was seen in one of 20 patients on BSZ Seventeen of 22 patients (77%) who received evidence to indicate that IBS and affective (rash) and in eight of 17 patients on SASP BSZ were in remission at 12 weeks compared disorder reflect a common familial predis- (three nausea, three severe headaches, one with 11 of 18 (61%) on SASP (NS). Five position. rash, one pancreatitis) (p=0-02 Fisher's exact patients (29%) on SASP were withdrawn from test). Clinical deterioration of the colitis led to the study due to intolerance compared with withdrawal and treatment with steroids in two none on BSZ (p=0-021 Fisher's exact test). patients on BSZ and three patients on SASP This study shows that high dose balsalazide (NS). Assessment of the patients who com- is not only an effective therapy for acutely THERAPEUTICS pleted eight weeks' treatment (BSZ 17 relapsed UC, but is also better tolerated than patients, SASP six patients) shows similar sulphasalazine in these patients. improvements in stool frequency, percentages of unformed and bloody stools, as well as Bismuth pharmacokinetics in healthy male improvements in sigmoidoscopic and histo- subjects after twice daily oral dosing for logical appearances in both groups.

10 days with ranitidine bismuth citrate, In conclusion, high dose BSZ is better Review of non-steroidal anti-inflammatory http://gut.bmj.com/ tri-potassium di-citrato bismuthate (De- tolerated than SASP and thus more successful drugs in general practice Noltab), or placebo in the initial management of UC. G L SWIFT, J RHODES (University Hospital of L F LACEY, N M FRAZER, 0 N KEENE, J T L SMITH Wales, Cardiff) Patients, many of whom are (INTRODUCED BY J MILLS) (Division of Clinical elderly, may receive non-steroidal anti- Pharmacology and Department of Medical Improved maintenance ofremission in ulcer- inflammatory drugs (NSAIDs) for long periods Statistics, Glaxo Group Research Ltd, Greenford, ative colitis by balsalazide 4 g/day compared and in general practice 'repeated prescriptions' In Middlesex) Ranitidine bisriuth citrate (RBC) is with 2 g/day may be obtained without a consultation. a on September 28, 2021 by guest. Protected copyright. a salt of ranitidine with a complex of bismuth general practice with 12 000 patients we have and citric acid. A 10 day repeat dose random- M H GIAFFER, C D HOLDSWORTH, J E LENNARD- identified 315 patients with repeat prescription ised double blind, parallel group, comparator, JONES, C A RODRIGUES, P B McINTYRE, S cards which listed at least one NSAID or and placebo controlled study was conducted. MANJUNATHA, J H BARON, I G BARRISON, R J aspirin in anti-inflammatory dosage. One There were four treatment groups, with 12 POLSON, A M HOARE, G S R DAVIES, P C THORNTON hundred and forty one ofthese also listed drugs subjects per group: RBC (500 mg bd), RCB (Royal Hallamshire, Sheffield, St Mark's for conditions sometimes made worse by (1000 mg bd), De-Noltab (240 mg bd), and Hospital, London, Queen Elizabeth II Hospital, NSAIDs (eg heart failure, hypertension, placebo. Blood and urine samples were Welwyn, St Mary's Hospital, London, Wycombe asthma), and 15 listed drugs with which inter- collected after the last (19th) dose. Plasma and General Hospital, and Biorex Laboratories Ltd, actions with NSAIDs may occur (eg anti- urine bismuth concentrations were determined Enfield) Maintenance ofremission in ulcerative coagulants, sulphonylureas, anti-convulsants). using a validated inductively coupled plasma colitis by sulphasalazine is dose related, but Thirty eight randomly selected patients (age mass spectrometry method. dosage increase is limited by side effects. 27-81 years) with non-rheumatic conditions, RBC was well tolerated and there were no Balsalazide 2 g/day is as effective as sulphasala- taking long term NSAIDs (range three months serious adverse events. After the last dose, zine at the same dose for remission mainten- to 17 years) agreed to try an alternative geometric mean (range) bismuth Cn., for RBC ance treatment and this drug is usually well analgesic - paracetamol, codydramol, (500 mg bd) was 5 (2-19) ng/g, for RBC (100 tolerated in high dosage. We therefore com- coproxamol, or cocodamol. After one month, mg bd) was 12 (4-42) ng/g, and for De-Noltab pared in 133 patients with ulcerative colitis in 22 had very satisfactory pain relief without (240 mg bd) was 21 (7-247) ng/g. The corres- remission treated with balsalazide 2 g/day (n= NSAID; 16 had resumed therapy but four were ponding trough plasma concentrations were 2 65) and balsalazide 4 g/day (n=68) with regular taking reduced dosage. After four months, 25 (1-5) ng/g, 4 (2-8) ng/g, and 4 (2-20) ng/g, review over one year. ofthe 38 had stopped their NSAIDs (including respectively. The geometric mean AUC over a Relapse was significantly more common on one after haemorrhage from a peptic ulcer) and dosing interval after the last dose were 34 (18- the 2 g dose (53%) than on the 4 g dose (36%) two others were well on reduced dosage. 91) ng.h/g, 71 (27-192) ng.h/g, and 79 (33-436) p<0 01. Six patients (9%) were withdrawn In conclusion, patients' requirements for ng.h/g, respectively. The corresponding because of intolerance at 2 g/day (three dys- NSAIDs should be reviewed regularly; those bismuth urinary recoveries (AeT) over the pepsia, two diarrhoea, one constipation) and with non-rheumatoid conditions may find dosing interval were 97 (62-208 ig, 227 (90- nine (13%) at 4 g/day (four diarrhoea, two equivalent pain relief from safer, cheaper, 990) jig, and 309 (137-1614) itg, respectively. nausea, two flatulence, one epigastric pain). alternative analgesics. When normalised for dose, Cmax and AeT were We conclude that balsalazide 4 g/day is significantly higher (p<005) and Cmax dis- superior to 2 g/day for remission maintenance played a greater degree of intersubject vari- treatment in ulcerative colitis, resulting in a ability with De-Noltab than with RBC. relapse rate very similar to that in another study In conclusion, twice daily dosing with RBC using 3 or 6 g/day but with adverse reactions Role of 5-hydroxytryptamine (5-HT) type 3 for 10 days was safe and well tolerated and more frequent in the present study. receptors in cholera toxin induced secretion A1218 British Society ofGastroenterology

J A DIAS, F H MOURAD, M J G FARTHING (Depart- Is radioimmunolocalisation a feasible tech- complications is eliminated. Conservative ment of Gastroenterology, St Bartholomew's nique for the intraoperative detection of treatment is a safe option in most instances, Hospital, London) Intestinal secretion induced intra-peritoneal deposits of colorectal with a low risk offurther complications, so that by cholera is classically attributed solely to the cancer? we do not recommend elective resection after Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from activation of the adenyl cyclase complex and recovery from an acute attack. increase in intracellular cAMP. However, J W DAWSON, W WADDINGTON, F SAVAGE, W HU, accumulating evidence suggests that the C DEAN, P B BOULOS (Departments ofSurgery and intestinal secretagogue 5-HT may contribute to Nuclear Medicine, University College, London the secretory process via its action on 5-HT2 and Institute Cancer Research, Sutton, Surrey) and 5-HT3 receptors. Radioimmunolocalisation (RIL) has been Anti-neutrophil cytoplasmic autoantibodies We have examined this hypothesis by study- strongly advocated as a method for the peri- directed against cathepsin G in sera from ing the effect of a highly selective 5-HT3 operative detection of subclinical colorectal patients with inflammatory bowel disease receptor antagonist on intestinal water move- cancer. The monoclonal antibody (MAb) ment in cholera toxin (CT) induced secretion. 'B723' labelled with '25Iodine, is claimed to D REUMAUX, J F COLOMBEL, A CORTOT, L H NOEL, Adult male Wistar rats were injected sc with supercede other radiolabelled MAbs because of P LESAVRE, P DUTHILLEUL (Laboratoire the 5-HT3 receptor antagonist (BRL43694/ it's specificity for tumour and low background d'H4fmatologie-Immunologie, CH Valenciennes, Granisetron) 30 or 300 jig/kg, two hours before radioactivity. Clinical and immunohisto- Clinique des Maladies de l'Appareil Digestif, instillation of 75 jig CT for two hours in chemical studies were performed on 28 patients CHU Lille, INSERM U 90, and Departement isolated small intestine. In situ jejunoileal undergoing resection for colorectal cancer to de Nephrologie, Hopital Necker, Paris, France) perfusion was then performed with plasma determine whether sensitivity and specificity of Anti-neutrophil cytoplasmic autoantibodies electrolyte solution (Na 140, K 4, Cl 104, the technique were altered by either the isotope (ANCA) are present in sera from patients with HCO3 40 mmol/l) to assess water and sodium or MAb. inflammatory bowel disease (IBD). Our pre- transport. Patients were injected with the MAb 'ICR2' liminary results suggested that ANCA could be CT induced net water secretion (median, labelled with 100 MBq of either "'Indium or directed against cathepsin G (a constituent of -50.1 Rl/min/g (interquartile range -59.5 to 125Iodine and probed at laparotomy, three days neutrophil primary granules) in IBD. The aim -29.8)). Prior treatment with BRL43694 30 ( 1 'Indium) or 10 days (125Iodine) later. A ratio of the study was to assess the specificity and tg/kg reduced the secretory state (-13-5 of counts from tumour:normal colon (T/NC) sensitivity of ANCA and of ANCA directed (-43- 1 to - 8.7); p<0 03) while at 300 jig/kg it was obtained. Immunohistochemistry was against cathepsin G for ulcerative colitis (UC) was reversed to net absorption (21-8 (14-7 to then performed on each cancer, comparing among patients with IBD. Sixty healthy con- 21-2); p<0 02). Net sodium and chloride B72-3 with ICR2. T/NC ratios did not differ trols, 119 patients with Crohn's disease (CD) movement followed water movement. significantly ("'1Indium, median 1-66, range (52 men, 67 women, mean age 30 years (50 with BRL43694 300 ig/kg had no effect on basal 0.9-2.13:125Iodine, median 1-75, range 1 1- active and 69 quiescent disease)), 53 patients net water and sodium movement in normal rat 5.8). Immunohistochemical staining of all with UC (24 men, 29 women, mean age 33 small intestine. cancers using B72-3 was no more specific to years (34 with active and 19 quiescent disease; Our findings provide further evidence that 5- tumour than ICR2. 7 proctitis, 19 left sided, 14 pancolitis, and 13 HT is involved in CT mediated secretion and We conclude that probing is not impaired by colectomised)) were studied. IgG ANCA were imply that inhibition at 5-HT3 receptors alone using a high energy radionuclide; detection of investigated using an indirect immunofluore- can prevent CT induced secretion. tumour is determined by the specificity ofMAb scence technique on ethanol fixed leukocytes. for tumour. Immunohistochemistry ofB72-3 is The cytoplasmic (c-ANCA) and perinuclear no more specific to colorectal cancer than ICR2 (p-ANCA) patterns were determined. The and we remain sceptical of results achieved presence of anti-cathepsin G antibodies was COLORECTAL elsewhere. tested by ELISA (positive values: >4 SD above http://gut.bmj.com/ the mean for controls). Among patients with IBD, the presence of p-ANCA and of ANCA directed against Ultrastructural appearances of the pelvic cathepsin G was 93% and 91% specific and 43% ileal reservoir mucosa and 47% sensitive for UC respectively. Likelihood of recurrence after an acute The UC associated p-ANCA has a high D L BRUCE, B F WARREN, P DURDEY, M LUCKETT, complication ofdiverticular disease degree of specificity. The presence of ANCA

N A SHEPHERD (Departments of Histopathology directed against cathepsin G in 47% of patients on September 28, 2021 by guest. Protected copyright. andSurgery, Bristol Royal Infirmary and Depart- S SARIN, P B BOULOS (Department of Surgery, with UC suggests that cathepsin G is a major ment of Histopathology, Gloucestershire Royal University College and Middlesex School of target antigen for ANCA in UC. Hospital) The pelvic ileal reservoir has Medicine, The Rayne Institute, London) Because improved the lifestyle of patients with ulcera- the risk of further complications after either tive colitis and familial adenomatous polyposis. conservative or surgical treatment of an acute With time and in relation to episodes of complication of diverticular disease is not inflammation, pelvic ileal reservoirs may documented, it is difficult to advise appropri- Tuberous sclerosis is a common cause of undergo colonic metaplasia, changing from ately on the subsequent management. There- multiple rectal polyps villous small bowel mucosa to flat pouch fore, all patients admitted with diverticulitis, mucosa with a variable chronic inflammatory haemorrhage, or peritonitis between 1980 and S R GOULD, J B STEWART, L N TEMPLE (Epsom cell infiltrate. There have been no detailed 1987 were reviewed and prospectively followed General Hospital, Epsom, Surrey) Tuberous electron microscopical studies ofthe pelvic ileal up for a median of 48 months (interquartile sclerosis (TS) is associated with epilepsy, reservoir mucosa. In this study, we have range of 30-65). The main outcome measures mental retardation, and a variety of other examined mucosa from a resected pouch and were hospital readmission with further compli- stigmata but rarely with clinically recognised five pouch biopsy specimens in individuals cations and survival. gastrointestinal manifestations. Fifteen with and without pouchitis. The ultrastruc- Some 72 of 86 patients (84%) with diverti- patients with TS were examined to determine tural changes seen include villous flattening culitis responded to antimicrobial drugs and the incidence of rectal polyposis. All under- and the appearance of basal bodies adjacent to intravenous therapy with a readmission rate of went sigmoidoscopy; 10 patients were also the microvilli, both of these being features of 2% per patient year. With haemorrhage, 10 of examined by colonoscopy. Eleven of 15 normal colonic mucosa, and adding further 37 (27%) required a median blood transfusion patients (73%) had rectal polyps. The polyps weight to the concept of colonic metaplasia in of 4 (IQR 2-6) with no mortality and there was could be detected by careful rectal examination pouch mucosa. In distinct contrast to pouches a readmission rate of 5% per patient year. in five patients. These polyps were asympto- showing only chronic inflammation, the Patients who required staged colonic resection matic. They were small (3-4 mm), usually reservoirs with pouchitis have almost complete and anastomosis for peritonitis, obstruction, or sessile, and frequently multiple. They were absence of microvilli. This may well account for diverticulitis which failed medical treat- typically of maximal density just above the for much of the symptomatology of this idio- ment had a total inpatient mortality of 12% and anorectal junction, often in clusters, and some- pathic relapsing condition of the reservoir. no further readmissions. The long term times confluent. Their appearance was fre- Our studies provide further evidence that survival rates of those who had surgery and quently sufficiently distinctive to differentiate pouch mucosa acquires some of the character- those treated conservatively were the same. them from other types of rectal polyp. In one istics of colonic mucosa and that pouchitis has The indications for emergency surgery patient presenting with irritable bowel syn- many clinicopathological similarities to ulcera- therefore should be strictly defined as there is a drome the presence of these polyps pointed to tive colitis. high mortality, although the risk of further the diagnosis of unsuspected TS. Histology British Society ofGastroenterology A1219 indicated that these polyps were micro- CCPR from a control value (n=8) of3-62 (0.59) counts greater than 2% (2-3, 4.5, 4.7%) and hamartomata; adenomatous or malignant to 7-33 (0 90) cells/crypt/hour (p<0.01). The each of these was studied in an acute relapse. changes were not seen. presence of the EGF receptor was confirmed All Crohn's disease patients had cell counts less In the population studied, characteristic histologically in each section. Hence, EGF than 2%. A relation was present between spleen Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from rectal polyps were common and may be a increases rectal epithelial proliferation in FAP size and pitted cell count for the patients previously unrecognised and useful marker of and could help promote neoplastic change. with inflammatory bowel disease (r=-0-73, TS. p

(p<0 001). The results suggest that the pre- experimentally induced tumours are found at preparations. Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from viously observed changes in SCFA pattern are sutured compared to 'sutureless' colonic There is much unnecessary NSAID pre- secondary to neoplasia rather than a primary anastomoses. scribing. Many patients can stop NSAIDs cause. Due to the interactions of carbohydrate without adversely affecting joint symptoms. and bile acid metabolism, the findings may Few have recurrent abdominal symptoms once have implications for the interpretation of off NSAIDs. Many patients with CPUD are abnormal duodenal bile acid profiles in taking OTC aspirin or NSAIDs (often in colorectal cancer patients and those with FAP. GASTRODUODENAL combination). The contribution of these drugs to CPUD could be reduced by improved patient education. Anastomotic cancer: do sutures matter? Value of 14C urea breath test and urease slide test (CLO test) to diagnose Helicobacter J L McCUE, J P SHEFFIELD, C UFF, RK S PHILLIPS pylon in uraemic patients Evidence for an interaction between alcohol (StBartholomew'sHospitalandICRFColorectal and certain H2 receptor antagonists Unit, St Mark's Hospital, London) Local recur- A M EL NUJUMI, P ROWE, C A DORRIAN, K EL rence of colorectal cancer after resection may MCCOLL (University Department ofMedicine and S HOLT, M GURAM, C W HOWDEN (University of be partially explained by enhanced anastomotic Therapeutics, Western Infirmary, Glasgow) As South Carolina, Columbia, SC, USA) Some H2 carcinogenesis. This study employs a novel the diagnosis of Helicobacter pylori infection receptor antagonists (H2RA) have been technique of 'sutureless' colonic anastomosis is often based upon measurement of the reported to inhibit gastric alcohol dehydro- to explore the relative role of sutures and organism's metabolism of urea, we have genase (ADH) resulting in increased blood the healing colonic wound in experimental investigated the reliability of these tests in 16 alcohol concentrations (BAC) and ethanol bio- colorectal carcinogenesis. uraemic patients on maintenance dialysis treat- availability after ingestion of small doses of One hundred and sixty six male F344 rats ment. Eight of them were confirmed to have ethanol (0- 15 or 0 3 g/kg). received 12 consecutive weekly subcutaneous H pylon' infection on the basis of histological To examine interactions between anti- injections of azoxymethane (AZM) (10 mg/kg! antral gastritis associated with H pylon' like secretory medication and alcohol, six healthy week). Either: (1) a sham procedure; or a 5 mm organisms and positive serology and culture. male physicians (mean age 34 years) ingested transverse colotomy repaired with (2) four The other eight patients had normal antral alcohol (0.75 g/kg) after a meal in the evening, interrupted 5/0 sutures of either (a) silk, histology and negative serology and culture. on six separate occasions following pretreat- (b) polyglactin (Vicryl), or (c) stainless steel; or The mean (range) serum urea concentration in ment, in random order, with cimetidine (800 (3) a 'sutureless' technique were performed. the infected patients was 21 (12-31) mmol/l mg OD), ranitidine (300 mg OD), or nizatidine Animals were killed 28 weeks after the first compared with 23 (11-32) mmol/l in those not (300 mg OD), famotidine (40 mg OD), or dose of carcinogen. infected. In each of the infected patients endo- omeprazole (20 mg OD) for seven days before Animals with anastomotic tumour were scopic antral biopsy specimen was positive each study. Pretreatment with cimetidine or found in 46% of the sham group, 41% of the using the urease slide test (CLO test) at five nizatidine caused a significant increase in peak 'sutureless group', and 68% in the sutured hours whereas it remained negative in each of BAC compared with control (100±3 9, group (p<005 cf sham, x2=44; p<0 02 cf the uninfected subjects at 24 hours. The 20 90.3+3.4, and 75-9+3-4 mg/dl, respectively, 'sutureless', X2 =635). The corresponding minute values for the 14C urea breath test in the p<0 02). Cimetidine, nizatidine, and figures for anastomotic cancer were 9%, 22%, H pylon' positive patients ranged from 61-801 ranitidine increased ethanol bioavailability http://gut.bmj.com/ and 38% (p<0 002 cf sham, Fisher's exact (mean 204) kg percentage dose/mmol CO2 x compared with control (UC at 120 minutes, test). 100 and showed no overlap with the values for 8934+484, 8556+289, 7821+410, and No significant differences in tumour yield the H pylori negative patients (01 1-8, mean 7) 7122±407, p<0 05, respectively). were noted between silk, Vicryl and steel. All (p<0005). The enhancement of mean BAC by cimeti- sutures seem to enhance anastomotic tumour The breath test values in these uraemic dine or nizatidine are of medicolegal import- formation and we suggest that 'sutureless' patients are similar to those in patients with ance, and increased ethanol bioavailability due anastomosis may diminish this risk. normal renal function in whom we take a to certain H2RA may be undesirable. These

positive test as greater than 40 and a negative findings are relevant to the selection of anti- on September 28, 2021 by guest. Protected copyright. test as less than 20. This study indicates that secretory drugs that are used frequently in uraemia does not reduce the value of the urease patients who drink alcohol. Cellular proliferation at colonic anastomoses slide test or 14C urea breath test in diagnosing H pylon infection. J L McCURE, R K S PHILLIPS (St Bartholomew's Hospital, London) Enhanced anastomotic Eradication of Helicobacter pylon - meta- carcinogenesis is well recognised experiment- analysis to determine optimal therapy ally and may be due to accelerated cellular Patient understanding of non-steroid anti- proliferation. As cancer yield is enhanced by inflammatory drugs and ulcer complications: N CHIBA, J W RADEMAKER, B V RAO, R H HUNT suture materials, the influence of different a need for improvement (Division of Gastroenterology, McMaster sutures in an anastomosis and also a suture- University, Hamilton, Canada) Multiple anti- less closure on anastomotic crypt cell produc- G SALEEBY, C W HOWDEN, S HOLT (University of biotic regimens are used to treat Helicobacter tion rate (CCPR) were explored. South Carolina, Columbia, SC, USA) The link pylon infections, with varied success reported. Eighty male F344 rats were used. A 5 mm between non-steroid anti-inflammatory drug Eradication of H pylori has been shown to transverse colotomy was created which was (NSAID) use and complicated peptic ulcer decrease duodenal ulcer relapse and is recom- repaired with (1) four interrupted 5/0 sutures of disease (CPUD) is known by doctors, but mended for refractory ulcers. We have there- silk, stainless steel, or polyglactin 910 (Vicryl) patient understanding may be poor. We con- fore performed a meta-analysis of published or (2) a 'sutureless' closure. Five animals in tacted 39 patients six to 12 months after trials to determine the optimal combination each group were killed after one week, one hospital discharge following CPUD related to therapy. month, three months, or six months. CCPR NSAID use. All had been told to avoid further A computerised and fully recursive search of was assessed by the stathmokinetic technique. aspirin or NSAIDs but only 10 remembered published reports in English up to October At each time interval the number of metaphase the advice. Thirty five said they were not taking 1990 retrieved 167 articles and 74 abstracts. A figures in 20 crypts were counted and plotted NSAIDs (three were); four said they were (two total of 26 studies (11 papers and 15 abstracts) against time. The CCPR was derived from the were not). Recurrent problems were rare met all the predetermiend selection criteria and slope of the regression line. although one patient had had a further provided extractable data. Heterogeneity and In the sutured animals, anastomotic CCPR haematemesis. Only 11 were taking any anti- differences between groups were tested by x2 was significantly greater than adjacent ulcer medication. Nineteen were taking para- Pooled eradication rates for triple therapy descending colon CCPR for at least three cetamol instead of NSAIDs; none had any (79%) were significantly (p<000005) better months postoperatively. By contrast, there was worsening of joint symptoms. than both single (19%) and double (48%) no significant elevation of the CCPR at the Of 311 patients admitted with CPUD, 194 therapy. No differences were found between sutureless anastomosis compared with the (62%) had been taking NSAIDs (compared bismuth and amoxicillin single therapies. For adjacent colon at any time point. with 19% of controls; p<0001). Of these 194, double therapies bismuth + metronidazole British Society ofGastroenterology A1221

(55%) was significantly (p<0 05) better than 1 1-2; and III, 21-3. Patients underwent Commercially available enteral feeds were bismuth+amoxicillin (44%). Triple therapy endoscopy within two hours of the functional administered through a fluoroscopically with bismuth+metronidazole+tetracycline assessments, and the endoscopist was not positioned nasoduodenal tube. Ranitidine or (93%) was significantly (p<0.0005) better than aware of the functional scores. saline was infused iv using the Gastrojet (MIC Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from bismuth+metronidazole+amoxicillin (73%). A total of89 patients were studied: 23 males, Ag, Solothurn) which incorporates a pH data- We conclude that the combination of 66 females, median age 55 years. Ulcers were logger with a small volume peristaltic pump, bismuth+metronidazole+tetracycline is cur- found in 36 patients (36/89, 40%); they were allowing feedback control ofintragastric pH by rently the best regimen available and results in distributed as follows: 15/22 (68%) in func- individualised drug dose titration to maintain an eradication rate of93%. tional group III, compared with 9/28 (32%) in a predetermined pH which was set at 5 0. group I (X2=5-2, p<0 02), and 12/39 (31%) in Ranitidine infusion maintained a median pH group II (X2=7-24, p<0 01). 6-2 (range 5-6-6.7) compared with placebo pH In conclusion patients with debilitating 1-3 (1-2-2-1) p<00001. Intragastric pH was Immunomodulatory effects of histamine H2 arthritis seem to have a higher prevalence of maintained above pH 3 for 92% (75-98) of the receptor antagonists in healthy volunteers NSAID related peptic ulceration. This finding time with ranitidine and for 7% (1-33) with may be relevant to the process of selecting placebo p<0 0001. Ranitidine maintained P H NICHOLS, G V MILLER, C W RAMSDEN, J N patients for prophylactic anti-ulcer therapy. intragastric acidity above pH 4 and pH 5 for PRIMROSE (Department of Surgery, St J3ames's 89% (65-97) and 86% (58-96) of the total time University Hospital, Leeds) The immunological respectively. The median dose of ranitidine effects ofa week's therapy with three histamine used was 207 mg (140-316). H2 receptor antagonists were investigated in 11 Gastric and duodenal mucosal blood flow in Gastrojet infusion of ranitidine with intra- healthy male volunteers. The parameters patients receiving non-steroidal anti- duodenal nutrition can maintain a raised intra- measured included natural killer (NK) and inflammatory drugs - influence of age, gastric pH suitable for stress ulcer prophylaxis. lymphokine activated killer (LAK) cell smoking, ulceration and Helicobacter pylori function; T lymphocyte proliferative capacity, and interleukin 2 (IL 2) production; peripheral A S TAHA, W ANGERSON, H BtEKMAN, C MORRAN, lymphocyte subset analysis for markers CD3, N HUDSON, C J HAWKEY, R D STURROCK, R I Effect of non-steroidal anti-inflammatory CD4, CD8, CD16, and CD25. RUSSELL (Departments of Gastroenterology, drug induced gastric mucosal injury on intra- Cimetidine (400 mg bd) enhanced both NK Rheumatology and Surgery, Royal Infirmary, gastric pH and gastrin profiles in healthy cell number and function after 24 hours Glasgow and University Hospital, Nottingham) volunteers (p<005 Wilcoxon test) and also increased the Animal studies have suggested that non- percentage of peripheral CD8+ (cytotoxic/ steroidal anti-inflammatory drugs (NSAIDs) J W RADEMAKER, T J MCDONALD, N CHIBA, R H suppressor) cells (p<0 02), with a concomitant can suppress gastric blood flow which in turn HUNT (McMaster University, Hamilton, fall in the expression of the soluble IL 2 might lead to ulceration. The situation is not Ontario, Canada and University of Western receptor (p<0 02). These differences were not clear in patients on long term NSAIDs who Ontario, London, Ontario, Canada) Both non- apparent at any other time during therapy. could have other factors that might alter blood steroidal anti-inflammatory drugs (NSAIDs) Ranitidine (150 mg bd) had no effect upon flow. Also, little is known about duodenal and Helicobacter pylon' cause gastropathy pre- NK cells, but caused a reduction in LAK cell blood flow in such patients. Using laser dominantly affecting the antrum. H pylon' function (p<0 02), a depression ofthe lympho- Doppler velocimetry, we measured gastric and increases gastrin secretion by unknown mecha- cyte in vitro blastogenic response to mitogen duodenal mucosal blood flow in 70 arthritic nisms. stimulation with concanavalin A (p<0005), patients (23 males, 47 females, median age 54 The effect ofantral gastric mucosal injury by and a decrease in the lymphocyte production of years), who took NSAIDs for longer than four indomethacin (50 mg tid for seven days) on the IL 2 (p<0 01). These effects, together with an weeks, and studied the correlation with demo- 24 hour pH and gastrin profiles was studied in http://gut.bmj.com/ increase in the percentage of CD4+ (helper/ graphic factors, ulceration, and Hpylori. Blood 10 H pylori negative healthy male volunteers. inducer) peripheral lymphocytes (p<001), flow was measured in healthy looking mucosa Endoscopy before and after treatment deter- were consistent throughout treatment before in the gastric antrum and first part of duo- mined H pylori status and gastric mucosal returning to baseline within a week of stop- denum. H pylori was detected by histology and injury. 24 hour pH was measured using con- ping. Famotidine (40 mg mane), the most bacteriology in antral biopsy specimens. tinuous ambulatory pH monitoring and potent H2 antagonist, had no significant effect The median duodenal mucosal blood flow multiple blood samples (30) for plasma gastrin upon any of the immunological parameters. was 150 perfusion units in smokers (n=29) measured by radioimmunoassay. Therefore, histamine H2 receptor antago- compared with 175 in non-smokers (p=0-024, Median (range) gastric mucosal injury score on September 28, 2021 by guest. Protected copyright. nists have diverse immunological effects but Mann-Whitney U test), 123 units in patients increased significantly from 0 to 3.5 (1-11) and this activity is unlikely to be mediated via with duodenal ulcers (n= 12) compared with predominantly affected the antrum. No change specific interaction at the H2 receptor. 160 in those without duodenal ulcers (p= occurred in mean 24 hour pH before 2-15 0.020), and 135 units in patients with H pylori (0.45) and after 2-42 (1-17) treatment. The 24 (n=30) compared with 168 in patients without hour and meal stimulated integrated gastrin H pylori (p=0 033). There was no correlation profiles (ng.h/l) were also unchanged; mean Arthritic joint dysfunction as a predictor of with age or sex. Gastric blood flow was not (SD) 24 hour and meal stimulated integrated non-steroidal anti-inflammatory drug peptic influenced by any of the above variables. gastrin secretion before and after treatment ulceration In conclusion, duodenal, but not gastric, were 516 (168) and 86 (31), and 467 (188) and mucosal blood flow is reduced in NSAID 77 (40) respectively. A S TAHA, C MORRAN, N HUDSON, C J HAWKEY, patients who smoke, or those with duodenal We conclude, that in contrast to H pylori, R D STURROCK, R I RUSSELL (Departments of ulcers or H pylori. NSAID induced gastric mucosal injury does Gastroenterology and Rheumatology, Royal not alter acid or gastrin secretion. Mucosal Infirmary, Glasgow and University Hospital, inflammation and mediators other than prosta- Nottingham) Patients with deformed or poorly glandins appear to alter the regulation of functioning joints could, in theory, be at a Gastrojet infusion of ranitidine and intraduo- gastrin secretion in H pylori. greater risk of developing non-steroidal anti- denal nutrition: a more rational prophylaxis inflammatory drug (NSAID) related peptic for stress ulceration? damage, as advanced arthritis might need more aggressive therapy. To test this hypothesis, we D G MORGAN, N j V BELL, C JAMES, R H HUNT assessed the extent of joint dysfunction and the (Department of Gastroenterology, McMaster SMALL INTESTINE endoscopic findings in a group of arthritic University, Hamilton, Ontario, Canada) H2 patients receiving NSAIDs for a minimum of receptor antagonists, often prescribed for four weeks. The patients' functional assess- stress ulcer prophylaxis in the intensive care ment involved inquiring about their ability to unit, cannot easily overcome meal stimulated 14C breath tests and problems of using an perform various daily activities, and whether acid secretion. Furthermore, enteral nutrition assumed carbon dioxide output aids or devices were needed. A standardised alone may reduce stress ulceration. To assess health assessment questionnaire was used, and the effect of an intravenous infusion of raniti- A DUNCAN, A CAMERON, M S STEWART, R CARTER, the overall response was graded on a (0-3) dine on gastric pH while receiving intraduo- R I RUSSELL (Gastroenterology Unit, Respiratory scale: 0, fully independent; and 3, highly denal nutrition, we performed a randomised Unit, and Institute of Biochemistry, Royal Three main functional cross over study in eight healthy volunteers. Infirmary, Alexandra Parade, Glasgow) dependent person. 14C test results an groups were then identified: I, scoring 0-1; II, Each underwent two 24 hour studies. In the calculation of breath A1222 British Society ofGastroenterology assumed value of 9 mmol/kg/hour for carbon R J CORSON, S T O'DWYER, I S PATERSON, B G CHIARIONI, C SCATTOLINI, F BONFANTE, E dioxide output (CDO) is invariably used. OPPENHEIM, N Y HABOUBI, R A LITTLE, C N BARDELLI M T BRENTEGANI, L BENINI, I VANTINI To test the validity of this assumption we MCCOLLUM (University Hospital ofSouth Man- (Division of Gastroenterology at Valeggio sIM, measured CDO in 55 fasting patients on whom chester, North Western Injury Research Centre, University of Verona, COC Valeggio sIM Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from a 14C triolein breath test was performed. CDO University ofManchester) Multiple organ failure Verona, Italy) Nifedipine has been showed was measured in triplicate or quadruplicate after aortic surgery is poorly understood, but to inhibit small bowel motility in animals, following collection of breath into Douglas may be due to gut damage. We investigated the but human studies are lacking. This study was bags. The respiratory quotient (r) was also effects of hind limb ischaemia and reperfusion a randomised, double blind, comparison of measured to detect those patients with a high r upon gut permeability and systemic endotoxin the effect of nifedipine (30 mg) and placebo who hyperventilated. Nineteen patients (35%) concentration, using anaesthetised rats. Three on orocaecal transit time of a liquid meal in had elevated r and four (8%) had low r values groups were studied: three hour bilateral hind nine healthy volunteers. After an overnight and so these results were excluded. In the limb ischaemia followed by two hour reperfu- fast, each subject had a single oral dose of patients with high r values the intraindividual sion (n=6); three hour hind limb ischaemia nifedipine 30 mg (three capsules, 10 mg each) variability of CDO was high (CV= 14.7%) and without reperfusion (n=6), and controls anaes- or placebo, and 30 minutes later ingested a the CDO was significantly higher than those thetised for five hours without ischaemia liquid meal comprising 300 ml of an enteral with normal r values (p<0-001). (n=6). Hydration was maintained with iv diet (Nutridrink 1.5 cal/ml, Nutricia) with In the 32 patients with normal r values the saline, and body temperature was maintained lactulose 20 g. Blood samples were taken before intraindividual variability of CDO results was at 37 5°C. Horseradish peroxidase (HRP) was nifedipine administration and at 30 minute good (CV=6.7%). There was no significant instilled into the isolated ileocaecal loop 15 intervals for determination of the nifedipine difference between the 24 controls and eight minutes before killing to measure transmucosal concentration. End expiratory breath samples malabsorbers who made up this group. The permeability of HRP beyond intercellular tight for H measurement were collected at 10 minute mean CDO was 8-66 mmol/kg/hour which junctions by electron microscopy. Endotoxin intervals for 30 minutes fasting and after the agrees with previous studies, but the results values were measured using the chromogenic meal. The orocoecal transit time was taken showed a large degree of variation (range Limulus amoebocyte lysate assay before as the time for a sustained increase above 5-12-4 mmol/kg/hour, interquartile range tourniquet application, tourniquet release, and mean fasting levels of at least 10 ppm 7.55-9 86). In extreme cases this could cause two hours after reperfusion. of H. overestimation of results by 80% and under- One animal in the control group and Nifedipine significantly increased the transit estimation by 27%. ischaemia alone group showed increased time compared with placebo (mean (SEM) 131 When an assumed value for CDO is used permeability, however reperfusion lead to all (16) minutes v 104 (15) minutes; p<0 05, to calculate results of 14C breath tests such as six animals showing HRP permeability Wilcoxon's test for paired data). Nifedipine 14C triolein, 14C xylose or 14C cholylglycine (Fisher's exact test p=0-015). No statistical plasma concentrations expressed as the area tests, a sizeable error may be introduced which difference in endotoxin values was noted under the curve showed a positive correlation could cause false positive and false negative between the three groups. with orocaecal transit time (r=0.92, p<0 004, results. These results show that hind limb ischaemia regression analysis). and reperfusion damages the gut, but are not In conclusion, nifedipine 30 mg prolongs the associated with systemic endotoxaemia. mouth to caecum transit of a liquid caloric meal in normal subjects. This effect is correlated to Coeliac disease is primarily associated with plasma drug concentration. the DQA1*0501 DQB1*0201 heterodimer

M R TIGHE, M A HALL, E CARDI, K I WELSH, A potential method of reducing graft versus

P J CICLITIRA (Rayne Institute, St Thomas's host reactivity in small bowel transplantation http://gut.bmj.com/ Hospital, Molecular Immunogenetics, UMDS, Epidemiology of Crohn's disease and Guy's Hospital, and The Children's Hospital, C L INGHAM CLARK, P W CRANE, P A LEAR, R F M abdominal tuberculosis in Bangladeshis and Rome, Italy) In northern Europeans, coeliac WOOD (INTRODUCED BY RK S PHILLIPS) (Pro- Europeans in Britain disease is associated with the DR3 DQw2 fessorial Surgical Unit, St Bartholomew's (DQA1*0501 DQB1*0201) haplotype. Hospital, West Smithfield, London) There is C S J PROBERT, V JAYANTHI, K KING, H COCK, Linkage disequilibrium does not allow identi- extensive migration of graft cells to host D POLLOCK, S I BAITHUN, C SHELDON, N BARNES, fication of the susceptible allele in DR3 indi- lymphoid tissues after small bowel transplanta- J F MAYBERRY, D S RAMPTON (Leicester General

viduals. In southern Italy, there is a high tion (SBT) with cyclosporin A (CsA) immuno- Hospital, Leicester, London Chest Hospital and on September 28, 2021 by guest. Protected copyright. incidence ofDR3 negative patients with coeliac suppression. This study examines the effect of Royal London Hospital, London) The incidence disease. delaying the start of CsA treatment on subse- of Crohn's disease (1972-89) and abdominal This study investigated 43 patients with quent graft cell emigration. SBT was carried tuberculosis (1985-89) in a defined Bangladeshi coeliac disease from Rome, Italy together out in rats from PVG donors to DA recipients community was studied in an East London with 39 ethnically matched controls. in three groups; no immunosuppression Borough (population 164 000 with 28 000 DRB, DQA, and DQB alleles were identi- (n=5), CsA (15 mg/kg/d) from day 0 (n=6), Bangladeshis). From a review of about 3000 fied using the polymerase chain reaction and CsA (15 mg/kg/d) from day 4 (n=6) after potential cases there were 99 of Crohn's and sequence specific oligonucleotide transplantation. On day 7 tissues were har- disease, including five Bangladeshis resident in probes. vested and stained with strain specific mono- the borough at diagnosis. The incidence in At the DRB locus, 51% ofpatients were DR3 clonal antibodies (OX27 vv PVG, MN4 vv DA) Bangladeshis was 1 3/105/year in the 1970s and (10% controls), 42% DR5 (26% controls), and using an immunohistochemical technique. 2.2/105/year in the 1980s compared with 34/ 77% DR7 (36% controls). No patients were Histological changes of acute rejection were 105/year and 4.2/105/year in Europeans, and homozygous for DR7, but were heterozygous seen in the group receiving no treatment but 4 6/105/year and 54/105/year in West Indians, for DR5/7 (42%), DR3/7 (39%), or DRw6/7 not in either of the CsA treated groups. Host respectively: none of ethnic group differences (15%). cell migration to graft tissues was reduced in in incidence or the changes with time was At the DQ loci, 91% of patients possessed both CsA treated groups. Graft cell migration significant. There were 13 cases of abdominal the DQA1*0501 allele (51% controls) and to host tissues was much greater in the group tuberculosis, of whom eight were Bangladeshi. 98% the DQB1*0201 allele (41% controls). receiving CsA throughout than in the rejecting The incidence in the Bangladeshi community The combination DQAl*0501 DQB1*0201 group or the group receiving delayed start CsA. was 7.7 cases/105/year, which was significantly was found in 91% patients v 18% controls Delayed CsA treatment successfully pre- higher than that in Europeans (0.32/105/year, (p=0 00005, X2=32 16, RR=38-0, EF= vents macroscopic graft rejection yet reduces Z=5-8, p<0.001, relative risk 34 950o 88 7%). the coincidental survival of graft leukocytes CI 4-271), but was not significantly different These results support the hypothesis that within host lymphoid tissues. Such strategies to that of Crohn's disease (X2 = 0. 5, coeliac disease is primarily associated with the may be ofvalue in obviating GVHD after small NS). presence of DQA1*0501 DQB1*0201 in both bowel transplantation. The similarity of incidence of Crohn's DR3 positive and negative populations. disease in Bangladeshis and Europeans con- trasts with other findings in South Asians in Britain. The high incidence of intestinal tuber- culosis indicates that it whould be given at least Hind limb ischaemia-reperfusion damages Effect of nifedipine on orocaecal transit in equal weighting with Crohn's disease when the gut but is not associated with systemic normal subjects: correlation with plasma reaching a diagnosis in Bangladeshis with endotoxaemia drug concentration abdominal symptoms. British Society ofGastroenterology A1223

Opioid immunoreactivity in myenteric long periods oftime in some patients with IBD. (6-3 (0.9) v 3-7 (0.6), p=0 04). Histology of neurons of the guinea pig small intestine Bone densitometry should be considered in all perfused gut was unremarkable. patients with inflammatory bowel disease, par- In conclusion, iron status is a significant P A STEELE, M COSTA (INTRODUCED BY D L ticularly those with high risk factors so that modulator of intestinal uptake of radiolabelled Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from WINGATE) (Centre for Neuroscience, Department prophylactic measures can be taken where heme. As heme iron is not chelatable by dietary of Physiology, Flinders University of South indicated. ligands, this should augment iron availability Australia, GPO Box 2100, Adelaide 5001, in iron deficient states. Australia) Exogenous opioid compounds have profound effects on intestinal motility and yet the role of endogenous opioids in enteric Cortical bone loss in patients with inflamma- neurons is not known. The aim of the present tory bowel disease: an eight year longitudinal Effect of5-Hydroxytryptamine (5-HT) type 3 study was to identify functional classes of study receptor antagonism on water absorption opioid immunoreactive neurons in myenteric during intestinal anaphylaxis ganglia on the basis of their morphology, D CLEMENTS, R M MOTLEY, W D EVANS, R J distribution, neurochemistry, and projections. COLES, A HARRIES, J RHODES, J E COMPSTON F H MOURAD, J A DIAS, L J D O'DONNELL, M J G Whole mount preparations of the myenteric (Departments ofMedicine and Medical Physics, FARTHING (Department of Gastroenterology, St plexus were prepared from control tissue and University Hospital of Wales, Cardiff) The Bartholomew's Hospital, West Smithfield, from tissue where intrinsic and extrinsic neural prevalence of osteoporosis is increased in London) The intestinal secretagogue 5-HT, pathways had been interrupted. Tissue was patients with inflammatory bowel disease present in mast cells and enteric neurons, may double labelled with antisera raised against (IBD), but there have been few longitudinal be a mediator ofwater and electrolyte secretion proenkephalin derived peptides or prodynor- studies of bone loss in these patients. In this in intestinal anaphylaxis. We have studied the phin derived peptides combined with antisera study we have measured bone mineral density effect of a highly selective 5-HT3 receptor raised against other neurochemicals known to at the junction of the distal one third and antagonist on water absorption in sensitised label certain classes of myenteric neurons. proximal two thirds of the radius using single rats during rechallenge with a food allergen. These experiments showed that opioid photon absorptiometry in 50 patients with Adult male Hooded-Lister rats (200-250 g) immunoreactivity in cell bodies of myenteric IBD. Thirty three had Crohn's disease and 17 were inoculated ip with 10 ,ug ovalbumin (OA) neurons coexisted with immunoreactivity for ulcerative colitis; 25 were women. The mean and alum adjuvant. Fifteen days later rats calretinin, neurofilament protein triplet, age was 45 years (18-70). All the patients were received either a 5-HT3 receptor blocker neuropeptide Y, substance P, or vasoactive traced and the measurements repeated in 39, (BRL43694/granisetron) 300 jig/kg sc, or intestinal peptide. The projections of these after a mean follow up period of 7 9 years saline and two hours later a 15 cm segment of neurons was established by interrupting nerve (range 7-1 to 8.2). jejunum was perfused in situ with either pathways and examining the consequent In female patients the annual change in plasma electrolyte solution (PES) or PES+OA change in fibre distribution in the targets. radial bone mineral density was -0 74% (range (20 mg/l). Successful sensitisation was con- Together these experiments indicated that -3.44 to + 1-03) (p=0 022), the greatest bone firmed by specific IgE titres of > 1 in 8. opioid immunoreactivity is found in several loss occurring in postmenopausal women Net water absorption after exposure to OA functionally distinct classes of myenteric (mean 1-1%/year). In male patients the mean (median 25 (interquartile range 21-33) d/ neurons: inhibitory and excitatory motor- rate of bone loss was -0 07% (range - 1 10 to min/g; n=6) was significantly reduced com- neurons to the circular muscle, orally and + 1-63) (p, NS). Patients with abnormally low pared with PES (72 (60-82); n= 10; p<0 05). anally directed interneurons in the myenteric values at the first measurement remained Pretreatment ofsensitised rats with BRL43694 plexus, interneurons to the submucous osteopenic at the second measurement while partially reversed the decreased water absorp- ganglia, and motorneurons to the muscularis some others with normal values initially tion after PES+OA (46 (36-65); n=10; mucosae. showed increased rates of bone loss and had a p<005), but remained less than in the http://gut.bmj.com/ subnormal bone mineral density after the untreated control group (p<005). The profile follow up period. of net chloride movement followed that of These results indicate increased rates of water. BRL43694 had no effect on basal trans- Rate of spinal bone loss of patients with cortical bone loss in some patients with inflam- port in non-challenged controls. inflammatory bowel disease: four year matory bowel disease and emphasise the need Thus, decreased water absorption during longitudinal study to monitor bone mass in these patients so that intestinal anaphylaxis is partly due to activation prophylactic measures can be instituted. of neuronal 5HT3 receptors but their blockade R J MOTLEY, D CLEMENTS, W D EVANS, E 0 prior to antigen exposure does not entirely on September 28, 2021 by guest. Protected copyright. CRAWLEY, C EVANS, J RHODES, J E COMPSTON prevent the intestinal transport changes, (Departments of Medicine, Medical Physics, implying that other mechanisms are involved. Radiology and Pathology, University Hospital of Iron status modulates heme uptake by small Wales, Cardiff) The prevalence of oesteoporo- intestine sis is increased in patients with inflammatory bowel disease (IBD) and vertebral fractures S K ROBERTS, G P YOUNG, R HENDERSON (INTRO- Differential effects offasting and semistarva- occur in some relatively young patients. In this DUCED BY B COLLINS) (Department ofMedicine, tion on the kinetics of Na dependent glucose study we have made serial annual measure- University ofMelbourne, The Royal Melbourne uptake by rat jejunal brush border membrane ments of bone mass in the lumbar spine over a Hospital, Vic 3050, Australia) Ingested heme is vesicles four year period in 70 patients with IBD (41 claimed to be a significant source of iron, yet women, aged 20-81 years). Bone mineral heme must be taken up intact for the iron to be E S DEBNAM (Department of Physiology, Royal density was measured in the first three lumbar available. The aims of this study were to Free Hospital School of Medicine, London) A vertebrae using quantitative computed tomo- determine whether iron status modulates reduced food intake produces complex effects graphy. The combined in vivo/in vitro intestinal uptake ofheme. on intestinal glucose uptake and one complicat- precision of the technique is 2-3%. ['4C]Heme was prepared by incubating ing factor in the interpretation of results using The mean percentage annual change in [14C]6-aminolevulinic acid with rat reticulo- intact epithelium is a reduced enterocyte spinal bone mineral density was -2-1% for cytes (activity 0.4 [tCi/[mol). Six Sprague- number. In order to study rmembrane adapta- men (range -8-1 to +3.8) and -2% for women Dawley rats made iron deficient (ID) by dietary tion per se, brush border membrane (BBM) (range -7- 1 to +3-1). The heterogeneity in means and six controls were perfused with vesicles have been prepared from jejunal rates of loss was statistically significant 1 FimoWl ['4C]heme through cannulated 10 cm mucosal scrapes using control, three day fasted (p<0001). There was no significant correla- segments of jejunum. Heme uptake was (F, 18% weight loss), and eight day semi- tion between rates of spinal bone loss and derived from "4C-radioactivity in perfusate, starved (SS, 25% food intake/day, 16-5% patient age, height, weight, disease duration or infusate, and mucosa after correction for weight loss) rats. Vesicles were incubated for duration of corticosteroid treatment. In men, recovery ofthe marker, [57Co]cyanocobalamin. four seconds with 5-6-980 [iM [3H]-D-glucose however, there was a significant positive corre- ID rats had a microcytic anaemia: haemo- in the presence of a 100 mM NaSCN gradient lation between the amount of corticosteroid globin 92 (8) v 160 (2) g/l in controls. Mucosal implying a similar electrochemical driving ingested during the study and the rate ofspinal uptake of [14C]heme was significantly greater force in the three preparations. Uptake was bone loss (p<005). Rates of bone loss were in ID rats (19-3 (2.8)% v 108 (1 1)%,p=0-031, expressed as nmol/min/mg total membrane comparable in patients with Crohn's disease t test). Mucosal I4C:57Co ratios confirmed protein. and those with ulcerative colitis. [14C]heme extraction from infusate in both Hofstee analysis revealed two transporters These results indicate that high rates of groups (p<0-01); the mucosal to infusate (TI: high affinity, low capacity, T2: low spinal bone lce . are maintained over relatively '4C;57Co ratio significantly greater in ID rats affinity, high capacity). Fasting induced a A1224 British Society ofGastroenterology higher Vmax of TI (+98%, p<0-01) and T2 (47). EMA was positive in 100% of patients tered to female random hooded rats and at (+52%, p<0-01) but no change in Kt. SS with UCD, 1-2% GFD, and 47% NS-GFD; all various time points animals were killed and (i) vesicles had a reduced Vmax of TI (-52%, other patient groups were negative. Other tests the number of visible ulcers throughout the p<0O005) and T2 (-26%, p<005) together were positive in 76-92% of UCD, 9-28% on SMI counted, (ii) infiltration by inflammatory Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from with a decreased Kt of TI (-65%, p<0-001) GFD, and 39-75% on NS-GFD; false positives cells determined histologically (score: 0-=none, and T2 (-27%, p<0 05). were also seen but not with the ARA-IgA test. 1=little, 2=mild, 3=moderate, 4=marked, One explanation of these differential effects The sensitivities and specificities were EMA 5=severe), and (iii) haemorrhage (measured as is that in F rats, the absence of food may spare (100%, 98 8%), AGA-IgA (90 5, 85 4), AGA- peroxidase activity) into the small intestinal the BBM glucose carrier at the expense ofother IgG (76-2, 89), and ARA-IgA (90.5, 98 7) contents assessed. The effect of misoprostol membrane proteins. For SS rats however the respectively. Jejunal mucosa was obtained and sulphasalazine (administered 30 minutes presence of luminal nutrient, albeit at a lower from 18 UCD, 32 GFD, and 13 NS-GFD. All before and six, 24, and 30 hours after indo- level, will require the retention of a wide array UCD patients had subtotal villus atrophy methacin) on ulceration was also investigated. of BBM proteins. (SVA) and positive EMA; all GFD patients Indomethacin induced a time dependent with normal mucosa were negative. The corre- increased in (i) the number ofvisible ulcers (six lation was not 100% with PVA or SVA in the hours=5 (3); 24 hours= 103 (7); 48 hours = 141 NS-GFD/'GFD' groups. (15)), (ii) inflammatory cell infiltration score In conclusion the new EMA is more specific (six hours=1-0 (0.4); 24 hours=2-0 (0.7); 48 peroxidase activity SMALL INTESTINAL DISEASE and sensitive than other current antibody tests hours=3-8 (1-3)), and (iii) for diagnosis ofCD. (six hours=1-9 (0.7); 24 hours=8.7 (1.2); 48 hours=7.7 (1-4) EU/g) (results are mean (SEM), n=8). Misoprostol (ED50 0054 mg/kg Low plasma cystine is a sensitive indicator of po) and sulphasalazine (ED50 42 mg/kg po) small bowel disease Localisation of increased intestinal perme- significantly reduced the number of visible ability in coeliac and Crohn's diseases ulcers. W DICKEY, G ROBERTS, K G PORTER (INTRO- Thus, indomethacin-induced ulceration of DUCED BY J S A COLLINS) (Department of K TEAHON, T SMITH, I BJARNASON (Clinical the rat small intestine has remarkable similarity Medicine, Queen's University ofBelfast, Belfast Research Centre, Harrow and King's College to that found in man in terms of inflammatory City Hospital and Department of Clinical School ofMedicine and Dentistry, London) The cell infiltration, haemorrhage, and suscept- Chemistry, Royal Victoria Hospital, Belfast) differential urine excretion of orally adminis- ibility to drugs. Although the small bowel is important in tered test substances shows increased intestinal amino acid metabalism and transport, few have permeability in patients with coeliac and studied plasma amino acid values in small Crohn's diseases. A technique has been bowel disease. We measured fasting plasma developed to localise precisely the site of the Relevance of intestinal bacteria, prosta- concentrations of 19 amino acids in nine permeability changes. glandins, and pro-drug administration to patients with subtotal or total villous atrophy, Subjects fast from midnight for 36 hours. At non-steroidal anti-inflammatory drug nine patients with small bowel Crohn's disease, 7 am an iv drip is set up followed by im vitamin (NSAID) induced increases in gut and 22 control subjects with normal jejunal B12. At 8 am subjects drink a 100 ml test permeability biopsy and small bowel radiology. solution containing 3-o-M-D-glucose (2-5 g) as Only plasma cystine was significantly related a jejunal marker, 57Co vitamin B12 (5 ,tCi) as an G R DAVIES, D S RAMPTON (Gastrointestinal to small bowel disease. Values (mean (SEM)) ileal marker, sulphasalazine (3 g) as a caecal Science Research Unit, The London Hospital were 26 (6.4) [tmol/l (range 9-31) for villous marker (s-sulphapyridine), and 51CrEDTA (1 Medical College, London) NSAID induced atrophy, 26 (7.9) [smol/1 (range 13-38) for [tCi) as the permeability probe with subse- increases in gut permeability are thought to http://gut.bmj.com/ Crohn's disease, and 47 (13-4) limol/l (range quent measurement of serum values for 24 reflect altered mucosal function and precede 24-80) in controls. The difference between hours. the NSAID enteropathy (intestinal blood and values in patients with small bowel disease and Analysis of serum appearances of the test protein loss, inflammation, and ileal dysfunc- in controls was highly significant (p<0-001). probes (peak or 50% of plateau value etc) show tion) that affects 70% of longterm users. Low plasma cystine (<35 [tmol/1) had a sensi- that the jejunum is the main site of 5'CrEDTA Permeability changes have been prevented in tivity for small bowel disease of 94% (17 of 18) permeation in normal subjects (n:5). Patients short term open volunteer studies by high dose and specificity of 86% (19 of 22). Five patients with untreated coeliac disease (n:5) have prostaglandin supplementation, and metro- 5 with previous villous atrophy which had increased jejunal permeability to CrEDTA, nidazole has reduced NSAID induced on September 28, 2021 by guest. Protected copyright. resolved on a gluten free diet had mean plasma while patients with ileocaecal Crohn's (n:5) intestinal inflammation. cystine of49 ,tmol/l (range 37-77). had increased permeation of 5 1CrEDTA To investigate these observations further we Thus, low plasma cystine is a sensitive corresponding to the appearance of the ileal used a randomised, placebo controlled, cross- indicator of small bowel disease and may aid and caecal markers. over, double blind study design; healthy monitoring of response to therapy, although its In conclusion, a technique for the localisa- volunteers underwent a combined 5`Cr-EDTA clinical significance is unclear. tion of increased intestinal permeability has (2 MBq) and mannitol (5 g) oral permeability been validated in patients with coeliac and test before and after one week's treatment with Crohn's diseases. With minor modification it indomethacin (50 mg tds) and either (a) miso- can be used to localise the site of absorption of prostol (200 [sg qds) or (b) metronidazole (400 Is the endomysial antibody the best screening most orally administered compounds. mg bd). test for coeliac disease The 24 hour 51Cr-EDTA permeability increased after one week's indomethacin (1-2% M FERREIRA, S LLOYD-DAVIES, M G BUTLER, M L (0-11) (mean (SEM)) before and 2.37 (0-18) CLARK, P J KUMAR (St Bartholomew's Hospital, Indomethacin induced small intestinal after; n=15, p<0-001). Co-administration of London) There is no reliable non-invasive damage in rats resembles NSAID induced metronidazole prevented this effect (1 07 screening test for coeliac disease (CD). Endo- enteropathy of the human small intestine (0-15) before and 1-51 (0 21) after; n=8, NS) mysial antibody (EMA) is a recently described but misoprostol did not (1 37 (0.27) before and antibody found on the basement membrane M A TREVETHICK, N CLAYTON, P STRONG, 3 26 (0.40) after; n=7, p<0 005). No drug around smooth muscle fibres of monkey I HARMAN (INTRODUCED BY K T BUNCE) (Depart- regimen altered mannitol permeability. oesophagus. We have compared the sensitivities ments of Gastrointestinal Pharmacology and In conclusion (1) if related to its anti- and specificities of the anti-gliadin antibody Pathology, Glaxo Group Research Ltd, Ware, bacterial activity, the results with metronida- (AGA-IgA, AGA-IgG using ELISA), AGA, Herts) Non-steroidal anti-inflammatory drug zole suggest that anaerobes facilitate and anti-reticulin antibody (ARA-IgA) and (NSAID) induced enteropathy of the human indomethacin induced increases in perme- EMA using immunofluorescence, and also small intestine (SMI) is associated with inflam- ability. (2) In contrast to previous work, we correlated the results with jejunal morphology. matory cell infiltration and haemorrhage, found that misoprostol did not reverse indo- Sera of patients with untreated CD (UCD which can be reduced by misoprostol and methacin induced permeability changes; n= 21), disease treated with a strict gluten free sulphasalazine. We now report that indo- prostaglandins may either be unimportant in diet (GFD n=87), or a non-strict GFD (NS- methacin (Indo) induced damage to the rat the pathogenesis of this phenomenon, or GFD n= 19) were compared with a GI disease SMI is also associated with inflammatory cell alternatively, misoprostol in therapeutic control group (Crohn's disease (21), ulcerative infiltration and haemorrhage and can be dosage may fail to maintain mucosal prosta- colitis (10)), a non-GI group (rheumatoid limited by misoprostol and sulphasalazine. glandin values in the face of one week's arthritis (20), SLE (33)), and normal subjects Indomethacin (15 mg/kg po) was adminis- exposure to indomethacin. British Society ofGastroenterology A1225

Intravenous aprotinin protects agaisnt celi 20-153). The incidence of abdominal tubercu- whom were symptomatic. Six of 12 EBV loss during reperfusion of ischemic small losis in South Asians decreased significantly positive patients developed reactivation with intestine from 27 cases/105/year during the 1970s to 8-9 fourfold increase in titres but no clinical cases/105/year in the 1980s (X2=42, p<0 001). symptoms. Chronic persistent hepatitis (CPH) Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from LE A FILEZ, R KERREMANS, W STALMANS, The mean incidence during the study was 15-2/ developed in two children with CMV and in K GEBOES, F PENNINCKX (Departments of 105/year in Hindus, 12.3/105/year in Sikhs, and three with EBV infection. Eleven children had Abdominal Surgery, Biochemistry, and 5-81/105/year in Muslims. The relative risk to coinfection with both CMV and EBV. One of Pathology, Catholic University of Leuven, Hindus and Sikhs is 2-1 greater than that for these developed CPH and two chronic active Belgium) The present study aimed to delineate Muslims (2-6 and 2-1 respectively), a finding hepatitis progressing to chronic rejection the role of proteases in the pathogenesis of similar to that in pulmonary tuberculosis. requiring retransplantation in one child. reperfusion damage. The influence of intra- Abdominal tuberculosis is still not an After Tx, CMV and EBV infections are luminal proteases was evaluated by intra- uncommon diagnosis amongst migrants and common in childhood and may be associated luminal aprotinin - a protease inhibitor and clinicians should remain alert to the diagnosis with the development of chronic hepatic stabiliser of proteoglycan polymers - and/or by in South Asians. disease. intraluminal wash out, whereas the intra- cellular and serum proteases were inhibited by iv aprotinin. In four groups of cats the whole small intestine was isolated on its vascular Natural history of cryptosporidiosis in HIV Bacterial infections capable of causing diar- pedicle. Then the superior mesenteric artery infection rhoea in HIV infected patients was occluded for one hour, followed by reper- fusion for another two hours. At the moment of C BLANSHARD, S DAVIES, M NELSON, G M M R NELSON, D C SHANSON, B G GAZZARD reperfusion, the cats were subjected to: group CONNOLLY, V McDONALD, D C SHANSON, A M (INTRODUCED BY B G GAZZARD) (AIDS Unit, I: no treatment (control); group II: intra- JACKSON, N FRANCIS, B G GAZZARD (AIDS Unit, Westminster Hospital, London) This study luminal wash out with 11 physiological solution Westminster Hospital, London) Cryptosporidio- aimed to assess the incidence, clinical presenta- at 37°C; group III: wash out with the same sis was always thought to produce severe tion, and rate of relapse of shigella (Sh), solution containing aprotinin 110 U; group chronic diarrhoea in HIV infected patients but salmonella (Sa), and campylobacter (C) infec- IV: aprotinin 30 000 U/kg iv. Before occlusion this is not always so. We analysed the case tions in HIV positive patients. and at one hour intervals several mucosal records of 121 HIV seropositive patients with All HIV antibody positive patients who had enzymic activities were determined, as well as cryptosporidiosis. blood or stool cultures showing species of the ratio of mucosal/muscle protein and the Since 1985, cryptosporidiosis has been diag- Shigella, Salmonella, or Campylobacter were histologic aspect. nosed in 5% of all patients with HIV infection identified from three separate sources. Compared with the control group, the total and 21% of those with AIDS. In 19% of the Between January 1985 and December 1990, lactate dehydrogenase and maltase activities patients with persistant cryptosporidiosis it 2048 patients were diagnosed as HIV antibody (expressed as a % ofthe prereperfusion activity was their first AIDS diagnosis. The incidence positive at our unit. Five hundred and twenty in U/g muscle protein; means (SEM)) are has apparently increased each year since 1985, four were investigated for diarrhoea. In this significantly better preserved after one hour as and seasonal variation occurs. Four patterns of period seven patients had infections with Sh well as after two hours of reperfusion in group disease were identified: transient (24%), (33 septicaemias, one relapse), 32 Sa (12 septi- IV only. Lactate dehydrogenase: one hour of chronic persistent (58%), fulminant (14%), and caemias, 10 relapse), and 28 C (three septi- reperfusion: 78-8 (7.4)% in group IV v 28-7 asymptomatic (4%). The course of disease was caemias, four relapse). (2.3) in the control group; two hours of reper- unrelated to CD4 count, P24 antigenaemia, In conclusion (1) the incidence of Sa and C is fusion: 62-8 (5.3) v 45-8 (4.3). The other histology, or treatment although those with increased when compared with the homosexual enzymic activities (aldolase B, maltase, gluta- fulminant disease more commonly had lost >7 population as a whole, but the incidence of Sh http://gut.bmj.com/ mate dehydrogenase) gave similar results. kg and had other concomitant infections. is not. (2) Patients with Sa and C have lower Microscopical analysis showed a significantly Treatment with AZT, macrolide antibiotics, CD4 counts than those with Sh and are more better mucosal preservation only in group IV as diclazuril, and interleukin 2 did not affect the likely to have had a previous AIDS diagnosis. well. mean survival which was 7 5 months from (3) Patients presenting with possible enteric In conclusion (1) intraluminal protease diagnosis in those with chronic diarrhoea, 15 infections should always have blood cultures elimination has no effect on the mucosal reper- months in those with transient infection, and taken, as difficulty may be found in isolating fusion damage. (2) The mnechanical effect ofthe 40 days in those with fulminant disease. the organism from the stool. (4) Relapse is wash out seems to promote epithelial cell In conclusion cryptosporidiosis in HIV common in infections with Sa and life long on September 28, 2021 by guest. Protected copyright. shedding. (3) Aprotinin iv at the moment of infected individuals is a heterogeneous disease. prophylactic treatment may be needed. reperfusion prevents mucosal cell loss, the major phenomenon ofreperfusion. Significance ofcytomegalovirus and Epstein- An algorithm for the investigation of Barr virus infection in children after liver diarrhoea in HIV infection transplantation C BLANSHARD, B G GAZZARD (AIDS Unit, West- GUT INFECTION AND IMMUNODEFICIENCY O O ADEODU, M S MURPHY, N GREEN, J BUCKELS, minster Hospital, London) About 50% of D A KELLY (The Liver Unit and Department of patients with symptomatic HIV infection Pathology, Children's Hospital, Ladywood develop diarrhoea, commonly due to infection Middleway, Birmingham) The association of the upper or lower gastrointestinal tract. Abdominal tuberculosis in Indian migrants between cytomegalovirus (CMV) and Epstein- Previous algorithms have not included routine and the indigenous population in Leicester Barr Virus (EBV) infection and clinical out- investigation for microsporidia. come in 37 children (age range 0-3-15 years) Since August 1990, all patients with AIDS or C S J PROBERT, V JAYANTHI, A C WICKS, D L CARR- after liver transplantation (Tx) has been ARC presenting with chronic diarrhoea have LOCKE, P GARNER, J F MAYBERRY (Leicester studied. Microbiological methods included had six stool specimens examined (including General Hospital, Leicester and Brigham and serological evaluation at eight week intervals, methods for ova, cysts, parasites, crypto- Women's Hospital, Boston, USA) A retrospec- viral cultures, and histological examination sporidia, blastocystis, and AFB) sigmoido- tive, epidemiological study of abdominal annually or when clinically indicated. Ten of29 scopy with three rectal biopsies, endoscopy tuberculosis was performed from 1972 to 1989. CMV negative patients seroconverted between with microscopy of duodenal aspirate and Potential cases were identified from hospital seven and 22 (median 4) weeks after transplan- examination of six duodenal biopsies and a departments of medical records and endo- tation. Nine of these children received a CMV Crosby capsule jejunal biopsy by light and scopy, in addition to the county notification positive liver with acyclovir prophylaxis. One electron microscopy. register. The city population includes over of eight CMV positive patients developed Of 71 patients, 49 (69%) had one to four 75000 South Asians. There were 146 cases reactivation after Tx. Three patients developed infections: 21 cryptosporidiosis, 13 giardiasis, in South Asians and six in Europeans, four fever, hepatitis, ascites, one of whom 12 microsporidiosis, 10 CMV, two salmonella, of whom were British. The incidence in developed pneumonitis which responded to two campylobacter, one shigella, three MAI, Europeans has risen to 0 16/105/year, but they treatment with DHPG (Gancyclovir) and CMV one MTB, two spirochaetosis, one entamoeba have significantly less abdominal tuberculosis hyperimmune globulin. Eleven of 25 EBV histolytica, two blastocystis. The diagnostic than South Asians (Z= 14-5, p<0-001 and negative patients seroconverted between seven yield of a single stool specimen was 26%, six relative risk=55.4, 95% confidence interval and 78 (median 26) weeks after Tx, four of stools 40%, duodenal aspirate 4%, rectal biopsy A1226 BnitishSocietyofGastroenterology

17%, and duodenal or jejunal biopsy 41%. All and 30 months after ERCP (median 2 months); required dilatation and laser therapy and of cases ofmicrosporidiosis were detected by light 14 had their chc-cystectomy within three these, seven eventually required an endo- microscopy. Examination of three stools gives months. There were no postoperative deaths. prosthesis. Overall, 22 patients (26%) required 38% ofall diagnoses; duodenal biopsy increases Most patients with common bile duct stones intubation. Endoprosthesis related mortality Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from the yield to 83%, rectal biopsy to 96%, and can be safely and effectively managed by endo- was two (11%), both related to perforation staining three further stools for crypto- scopic removal, and cholecystectomy will not compared with a laser related mortality rate of sporidium to 99%. be required in the majority. Operation, when 3.5%. In conclusion, duodenal biopsy is essential in necessary, is safe. We recommend that Endoscopic laser therapy can palliate a the evaluation of HIV related diarrhoea. cholecystectomy need not be routinely per- majority of patients with inoperable oesopha- formed after endoscopic CBD clearance. geal malignancy, but is limited by the high dysphagia recurrence rate and need for repeated therapy. Laser therapy and endo- prosthesis insertion should be used as comple- Why does endoscopic injection therapy for mentary techniques. ENDOSCOPY bleeding peptic ulcer sometimes fail?

C RAJGOPAL, K R PALMER (GI Annexe, Western water General Hospital, Edinburgh) The prognosis of Controlied trial ofendoscopic injection treat- Smali bowel enteroscopy with ulcers with insufflation - the first 80 cases patients presenting with bleeding peptic ulcer ment for bleeding from peptic is improved by endoscopic injection therapy visible vessels A J MORRIS, L WASSON, R H R PARK, J F (EIT), but failures occur and delay ofdefinitive MACKENZIE (Gastrointestinal Investigation Unit, surgery caused by unsuccessful EIT could R B G OXNER, N J SIMMONDS, D J GERTNER, J M D adversely affect outcome. NIGHTINGALE, W R BURNHAM (Department of Royal Infirinaty, Glasgow) Per nasal Sonde- Romford, type enteroscopy using water or saline insuffla- We have attempted to identify factors pre- Gastroenterology, Oldchurch Hospital, dicting failure of EIT in 122 patients treated by Essex) All patients with acute upper gastro- tion and preservation of peristalsis has been were endo- performed in 80 patients. The median distance a single endoscopist for serious peptic ulcer intestinal bleeding over 26 months bleeding. All patients had either active bleed- scoped within 24 hours by an experienced enteroscope insertion was 190 cm (range 90- had an 250 cm). The caecum was entered in three ing (n=34) or stigmata of recent haemorrhage endoscopist (n=4). Ofthese, 79 patients associated with at least one other risk factor ulcer with a visible vessel (60 non-bleeding, 15 patients. The technique allows views of fine randomised mucosal detail and has shown newly described from: age over 60 years, Hb less than 100 g/l, or oozing, four spurting) and were mucosal 'red-spot' lesions,' ulceration, and, in clinical shock. EIT comprised 4-10 ml of to injection or standard treatment alone. 1:100000 adrenaline and 1-2 ml 5% ethanola- Injections of 1/10000 adrenaline (2 ml) were one case, a mucosal diaphragm with appreci- the ulcer. able luminal narrowing, as described by mine. placed at three to four sites around Awkward access or torrential haemorrhage Adrenaline and ethanolamine oleate 5% (1-2 Bjarnason et aP' in patients on longterm NSAID directly into the vessel. treatment. Some 56% of these patients had one prevented EIT in 10 patients (8%). Overall ml) were then injected success for control of active bleeding (30 of 34 The medical team managing the patient was or more mucosa abnormalities. A total of 37% treatment. with other obscure gastrointestinal blood loss cases) and for prevention of rebleeding (99 of unaware of the endoscopic 118 cases) was excellent. Uncontrolled bleed- The two groups were similar for age (injected had small bowel lesions, and 10% ofall patients initial haemoglobin referred for enteroscopy were found to have ing in four patients and rebleeding in 19 65-5; control 70 4 years), and duo- patients necessitated surgery, and bleeding was concentration (9-63 v 8-87 g/dl), shock (21 out lesions in oesophagus, stomach, of 38), and ulcer site. Major denum to account for their blood loss. invariably due to erosion of a major artery. of 41 zv 24 out Factors associated with failed EIT were rebleeding (7 v 18; p=0 008) and transfusion http://gut.bmj.com/ Preservation of peristalsis during examina- v 8 units; p=0-011) were tion allowed retrieval of lost ground during inaccessibility, torrential bleeding, and the requirement (5 combination of spurting haemorrhage from a significantly reduced in treated patients. The withdrawal. Small bowel perforation occurred also had lower mortality (4 v 8), in two patients. There were no significant nose visible, protuberant vessel (p<005). Other treated group small factors were not significantly more frequent in requirement for surgery (4 v 7) and reduced bleeds. An estimated 20-30% of the v 9 5 days). intestine slips past the tip during examination - failures. These included increasing age, shock, hospital stay (mean 7-1 anaemia, NSAID usage, ulcer type (GU or These preliminary results suggest that endo- a steerable tip may help to reduce this percent- treatment in this high risk age ofunexamined bowel. DU), ulcer position, a protuberant non- scopic injection bleeding vessel, and adherent blood clot or group significantly reduces rebleeding rate and on September 28, 2021 by guest. Protected copyright. 1 Morris AJ, etal. Lancet 1991; 337: 520. spots. transfusion requirement and may have other 2 Bjarnason IT, et al. Gastroenterology 1988; 94: Clinical factors do not predict the success of benefits. 1070-74. EIT but patients presenting with the combina- tion of active bleeding from a protuberant vessel should be considered for early surgery. Experience with new percutaneous biliary Cholecystectomy - a rare occurrence after endoscopes in the gall bladder and bile duct endoscopic removal of common bile duct stones The shadow at the end of the tunnel: R H T LOKE, P I CRAIG, A R W HATFIELD, S P LAKE limitations of laser treatment for malignant (Department of Gastroenterology, Middlesex M RHODES, M LAVELLE-JONES, G CARLSON, dysphagia Hospital, London) We report our experience I LAVELE, C W VENABLES (Departments ofSurgery with two prototype biliary endoscopes and Radiology, Freeman Hospital, Newcastle E SHMUELI, M F MYSZOR, D BURKE, C 0 RECORD, (Olympus; 10 and 12FG) over the past 10 upon Tyne) Endoscopic removal of common K MATTHEWSON (Gastroenterology Unit, Royal months. Twenty five patients (19 females; six bile duct (CBD) stones is safe and effective. Is Victoria Infirmary, Newcastle upon Tyne) Eighty males), median age of66 (range 28 to 88 years), subsequent cholecystectomy always necessary? six patients (mean age 72-9 years) with malig- underwent percutaneous cholecystoscopy (14) We present the results of a 10 year prospective nant dysphagia that was considered inoperable or choledochoscopy (11) under minimal seda- study in 212 patients with common bile duct were treated by endoscopic Nd YAG laser tion. Of the 14 gall bladder patients, two had stones (mean age 76 years, range 25-96) treated therapy. During therapy patients received a retained stones after conventional percu- by endoscopic duct clearance without mean of 2-6 laser sessions, and were in hospital taneous cholecystolithotripsy and 12 were cholecystectomy. a median of eight days. After therapy 58 (67%) examined after percutaneous rotary cholecy- The CBD was successfully visualised in 210 patients could eat a normal diet and 10 (12%) stolithotripsy, six of whom had retained gall patients (99%) and duct clearance achieved in could manage some solids. In eighteen (21%), bladder stones. The gall bladder and cystic 173 (82%). Some 33 of these patients were lost treatment was unsuccessful, and in eight this duct were cleared in all eight patients, two of to follow up. The remaining 140 patients with was because of complications (two tracheo- whom needed direct contact lithotripsy (3 FG successful CBD clearance were followed up for oesophageal fistulae, three perforations, and electrohydraulic probe). a median of 47 months (range 6-124). Twenty three pneumonia). Nine had an endoprosthesis Eleven patients had choledochoscopy (eight five patients (17%) required cholecystectomy inserted. Forty four of the 65 initially success- T-tube, three transhepatic); of these, four had for: biliary colic (n=15), acute cholecystitis fully palliated had recurrent dysphagia after a stones above a stricture and five had previous (n=7), empyema (n=l1), recurrent jaundice mean of 7-8 weeks. Nine were well palliated surgical or endoscopic duct drainage. Stones (n= 1), and ascending cholangitis (n= 1). with further laser therapy alone and six were successfully removed in 10 of the 11 Cholecystectomy was performed between 0 required an endoprosthesis. Twenty seven patients, four needing percutaneous biliary British Society ofGastroenterology A 1227 dilatation and electrohydraulic lithotripsy. using endoluminal ultrasound. PDT was A BAXTER, C J CAMPBELL, N M CLAYTON, J W The one failure needing later ERCP and carried out using (630 nm) light doses of 50J CLITHEROW, A A MCCOLM, R STABLES (INTRO- sphincterotomy. (100 mWx500 s) at each treatment site, with DUCED BY K T BUNCE) (Glaxo Group Research Patients tolerated the procedures extremely one treatment site for each cm2, up to a Ltd, Ware, Herts and Greenford, London) The Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from well with no major morbidity or mortality. maximum of seven treatment sites (treatment novel compound, ranitidine bismuth citrate This offers an exciting new treatment option time one hour). Light from an argon ion (RBC), was evaluated for gastric antisecretory, for retained stones after percutaneous gall pumped dye laser was delivered using a plane mucosal protective, anti-pepsin and anti- bladder procedures and difficult bile duct tip fibre inserted 1-2 mm into the tumour. Helicobacter pylori properties. In Heidenhain stones, particularly those above strictures. Follow up was by endoscopy at one week and pouch dogs RBC and ranitidine hydrochloride one month after PDT, and at one month, dosed orally at 0-1 and 0.3 mg ranitidine/kg, endoluminal ultrasound and biopsy were also produced similar dose related inhibitions of performed. histamine induced gastric acid secretion. In A study of microwaves for haemostasis and Local necrosis was achieved in 21 of 22 rats dosed orally with 1 ml ethanol, RBC tumour destruction in gastroenterology patients. When maximum tumour depth was inhibited the resultant gastric mucosal damage measured, the mean depth of tumour removed with an ED50 of 9-3 (3.2-27) mg/kg po, A KALABAKAS, A PORTER, M BIRCH, C P SWAIN was 6 mm. Only tumours <2 cm in mucosal whereas ranitidine hydrochloride was inactive (Departments of Medical Physics and Gastro- extent were eradicated - three carcinomas and at 100 mg/kg po. The activity of four human enterology, The Royal London Hospital, London) three adenomas - with local disease free pepsin isoenzymes, determined in vitro at pH We designed, built, and tested a prototype intervals ranging from nine to 40 months. With 1-7, was inhibited by RBC at a concentration microwave generator and delivery system for rectal carcinomas, little change in symptoms equivalent to 1 mM bismuth as follows: pepsin use in gastroenterology. Using a 650 W, 2450 was noted if much tumour remained. Healing 1 by 81 (5)%; pepsin 2 by 37 (8)%, pepsin 3 by MHZ magnetron, 0-160 W was generated via a was by regeneration of normal mucosa if 18 (4)%, and pepsin 5 by 32 (2)%. Ranitidine waveguide from the tip of a 180 cm flexible tumours were eradicated. Only two complica- base had no significant activity at 1 mM. RBC coaxial cable. We studied non-contact, contact, tions occurred - a mild sunburn and a lower GI inhibited Helicobacter pylori in vitro with an and interstitial thermal effects of microwaves bleed requiring transfusion of 2 units of blood. MIC (range) of 8 (4-32) [sg bismuthlml, but on necropsy liver and stomach. Using thermo- We conclude that endoscopic interstitial ranitidine hydrochloride had negligible couples, temperature gradients were measured PDT is a safe therapeutic modality with the activity. Ferrets naturally infected with the at points distal to thermal contact. Microwave potential for cure of small lesions <6 mm in related bacterium H mustelae were dosed for power was monitored by radiofrequency power depth and <2 cm in mucosal extent, in patients four weeks with vehicle or RBC at 24 mg/kg bd meter and correlated with calorimetric in whom surgery is inappropriate or, perhaps, and their H mustelae status was assessed at measurements. Maximum temperature as primary treatment in patients with early or intervals by gastric biopsy. All control animals achieved in the stomach was 60°C on serosa at superficial tumours, particularly those located remained colonised with H mustelae at two and optimal haemostatic settings (160°C compared in strategically important areas, such as four weeks, but in 60 ferrets treated with RBC with Nd:YAG laser p<005). We established sphincters. apparent clearance ofH mustelae was produced predictable relations between energy and in 42% at two weeks, and 69% at four weeks. thermal injury using non-contact, contact, and Longer term eradication was seen in 10% ofthe interstitial methods. Two methods ofachieving animals. haemostasis with microwaves were identified This profile ofaction suggests that ranitidine in the studying standard bleeding canine ulcers. (1) PHARMACOLOGY AND THERAPEUTICS bismuth citrate should be evaluated Contact method: inserting coaxial needle core treatment of peptic ulcer disease in man. into tissues and heating slowly until bleeding stopped. (2) Non-contact method: microwave http://gut.bmj.com/ induced sparking (dielectric breakdown) - tip Enalapril and sclerotherapy of oesophageal held 1 mm from tissue - was more rapidly varices A two week eradication regime for effective and caused less tissue damage. Micro- metronidazole resistant Helicobacterpylori wave coagulation was significantly superior to P SVOBODA J OCHMANN (INTRODUCED BY polidocanol 1%+adrenaline 1:10000 injection R SHIELDS) (Institute for Research of Special R P H LOGAN, P A GUMMETT, N Q KARIM, M M stopping. 20/20 v 0/20 standard bleeding ulcers Surgery 662 50 Brno, Czechoslovakia) The WALKER, J H BARON, J J MISIEWICZ (Parkside (p<005) and 10/10 v 0/10 iesenteric and haemodynamic effects of longterm (three Helicobacter Study Group, Central Middlesex serosal vessels (p<0 05). months) treatment with enalapril, a potent and St Mary's Hospital, London) In the UK, on September 28, 2021 by guest. Protected copyright. Microwave field depth is better controlled angiontensin converting enzyme inhibitor, 20% of Helicobacter pylori strains are resistant than radio frequency current and is less likely were studied in 12 randomly selected patients to metronidazole (MR Hp). We have pre- to be obstructed by smoke, bubbles, and blood with portal hypertension and previous episode viously shown that presence of MR Hp causes than endoscopic laser therapy. Microwave of haemorrhage from oesophageal varices. All the failure of eradication by conventional systems should cost 10 times less than lasers. patients had injection sclerotherapy of varices therapies. At present there is no accepted Microwaves look promising for haemostasis at weekly intervals. There was a control group effective treatment for MR Hp. This study and tumour destruction at flexible endoscopy. of 13 patients treated only with injection determines the eradication rate with a new two sclerotherapy and placebo. week eradication regimen consisting of After three months, the wedged hepatic omeprazole 40 mg mane and amoxycillin 500 venous pressure (25.5 (4.8) v 21-3 (4.8) mm mg qds for 2 weeks (days 1-14), with De-nol Role ofendoscopic interstitial photodynamic Hg) and the wedged free hepatic venous tablets 1 qds (days 1-7), and ciprofloxacin 750 therapy in gastrointestinal neoplasia pressure gradient (17-0 (6.0) v 12-6 (3.4) mm mg bd (days 7-14). Hg) were significantly lower than the basal In 19 patients (11 men, median age 35 years, P T CHATLANI, H BARR, N KRASNER, S G BOWN values (p<0-01) in the group treated range 17-72) with DU (n= 15) or NUD (n=4) (National Medical Laser Centre, The Rayne with enalapril. In the group treated with H pylori was detected by antral histology Institute, UCL, London and Walton Hospital, sclerotherapy+placebo this pressure reduction (H&E/Gimenez), culture (selective/non- Liverpool) Although we primarily treat patients was not observed. Systemic haemodynamics selective media), and positive '3C-urea breath referred for palliation of upper and lower and liver function tests did not change during test ('3C-UBT, positive result=excess gastrointestinal (GI) tumours with endoscopic the treatment. 6'3C02>5 ppm). All patients had failed a one 22 with We conclude that enalapril lowers portal week eradication regimen and were known to Nd:YAG laser therapy, patients Mast tumours thus treated were also treated with pressure in patients with portal hypertension have MR Hp by simple disk testing (5 [ig photodynamic therapy (PDT) with a view to (although not in all of them) and may be used sensitivity disks) before starting treatment. - five with good effect to manage patients with oeso- Clearance was determined by '3C-UBT at the local eradication of their tumours upper end of treatment and eradication by '3C-UBT GI carcinomas, 12 lower GI carcinomas, and phageal varices in combination with sclero- five sessile rectal villous adenomas. therapy. at one, three, and six months. To confirm Sensitisation was with 2 5 mg HpD, intra- eradication, endoscopy and biopsy were done venously, 48 hours before tumour assessment one month after the end of treatment. and PDT. Immediately before PDT, mucosal H pylori was cleared in 16 of 19 (84%) dimensions or length of segment of gut Ranitidine bismuth citrate, a novel patients at the end of treatment and success- antisecretory, fully eradicated one month after finishing involved were measured endoscopically and, compound possessing gastric '3C- with colorectal carcinomas, when possible the mucosal protective, anti-pepsin and anti- treatment in 14 of 19 (74%). Negative maximum depth of tumour was measured Helicobacter properties UBT's were maintained for a median follow up A1228 British Society ofGastroenterology of 2-4 months (range 1 5-6 months). The (15-7) and from 84-8 (6-1) to 141-2 (10-2), cells (an adenocarcinoma of colonic origin treatment was well tolerated. The five patients respectively (both p<0 05, Wilcoxon signed syngeneic to the BDIX rat), groups of 12 rats in whom MR Hp was not eradicated complied rank test). 10-3M SASP inhibited this received either octreotide 2 [tg bd or saline with the treatment. These results suggest that upregulation of CD1 lb and CD18 by 66 (20)% (control). At four weeks there was a significant Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from two week's treatment with this regimen can (p<005) and 94 (8)% (p<0-01), and 10-4M reduction (Mann-Whitney U, p<0-001) in the achieve a 74% eradication rate ofMR Hp. SASP by 91 (15)% (p<0-01) and 95 (7)% number oftumour nodules in the treated group (p<001), respectively. TNF increased mean (median 3 (range 7-0) compared with controls MFI ofCD1 lb and CD18 on monocytes (1 14-4 median 21 (range 33-24)). Furthermore no (25 5) to 202 (28 2) and 116-3 (11-3) to 279-2 tumour was present in four of 12 livers in the SHT3 antagonists: a role in irritable bowel (31-0), respectively; both p<0-01). 10-3M treatment group. syndrome and non-ulcer dyspepsia? SASP inhibited this upregulation by 65 (20)% These results indicate that octreotide signifi- (p<005) and 90 (18)% (p<0-01) respectively, cantly inhibits growth and development of D G MAXTON, C G HAIGH, P J WHORWELL while 10-4M SASP inhibited CD18 upregula- hepatic adenocarcinoma ofcolonic origin in the (University Hospital of South Manchester, tion by 89 (28)% (p<0-01), but had no effect on rat and may be of benefit in the treatment of Didsbury, Manchester and Glaxo Group CD1 lb data. 10-5M SASP did not affect hepatic metastases in man. Further studies are Research, UK) 5HT3 antagonists affect gut CD1 1/CD18 expression. required to evaluate this hypothesis. motility and visceral sensitivity and may be of SASP at concentrations found in blood in therapeutic benefit in irritable bowel syndrome vivo appreciably inhibited cytokine induced (IBS). Ondansetron, a selective 5HT3 antago- upregulation of CD1lb and CD18 molecules nist, was therefore evaluated in IBS. on monocyte and granulocytes. Thus, SASP Gall stones and longterm treatment with Fifty IBS patients (age: 22-65 years, 1 IM may reduce cellular recruitment in IBD by octreotide 39F) were randomised into a double blind, inhibiting adhesion molecule expression. placebo controlled crossover trial. A two week J V ANDERSON S M CATNACH, P D FAIRCLOUGH, baseline was followed by two treatment periods G M BESSER, J A H WASS (Departments of Endo- offour weeks separated by a two week wash out crinology and Gastroenterology, St Bartholomew's phase. Active treatment was ondansetron 4 mg Immunological effects of elemental diet in Hospital, London) Octreotide is used long term tds. Efficacy was assessed by recording changes inflammatory bowel disease - a prospective in the management of acromegaly, to suppress in abdominal pain, distension, bowel habit, study growth hormone secretion. Its use has been and a variety of 'non-colonic' features. associated with an increased prevalence of gall Stools became firmer in 21 patients on O MWANTEMBE, A FERGUSON (Gastro-Intestinal stone formation, although the prevalence of ondansetron compared with only four on Unit, University of Edinburgh and Western gall stones in untreated acromegalics is placebo (p<0-001). The effect was primarily in General Hospital, Edinburgh) Elemental diets unknown. We have performed gall bladder diarrhoea predominant patients where stool are as effective as corticosteroid therapy in ultrasound scans on 39 acromegalic subjects consistency improved in 13 of 28 on active inducing remission in Crohn's disease but the before octreotide therapy. treatment compared with two on placebo beneficial mechanism of these diets remains to Six of these had gall stones, no more than (p=0i002), with daily bowel actions also be elucidated. Patients were treated with would be expected in a normal population of decreasing (2-9 (2-1) v 2-0 (1-4), mean (SD), elemental diet (eo28) for a period of at least similar age and sex. We studied 25 of these p=0 04). Ondansetron did nqt adversely affect seven days and 15 remitted. Blood and saliva patients after treatment with octreotide and 12 bowel habit in patients with constipation. were collected in 22 patients and in seven cases further patients who had not had a pretreat- Ondansetron led to a pronounced improve- intestinal secretions were collected before and ment scan. Fifteen of these 37 patients had gall ment in upper gastrointestinal symptoms such after treatment. Antibodies to B-lactoglobulin, stones, significantly more than those on no as postprandial discomfort (p=0 008), flatu- ovalbumin, and gluten in the IgA, IgG, and treatment. http://gut.bmj.com/ lence (p=0 02), and heartburn (p=0(003). IgM classes were measured in all specimens by The mean length of treatment with Abdominal pain, distension, nausea, tiredness, ELISA. In nine patients, the values of cell free octreotide in those with stones was 21-7 (4.8) and back pain were unchanged. interleukin 2 receptor in serum and lavage months compared with 16-3 (2.7) months in In conclusion, ondansetron may improve before and after treatment were also measured. those who did not have stones (p<001). There bowel function in diarrhoea predominant There was no significant change after seemed to be a linear relation between duration IBS. The effects on upper gastrointestinal elemental diet in titres offood antibodies in any of treatment and incidence of stones. In 'stone symptoms also suggest a role in non-ulcer of the specimens before and after the diet and formers', the stone burden increased rapidly dyspepsia. there were no significant changes in the num- once stone formation had started. on September 28, 2021 by guest. Protected copyright. bers of antibody secreting cells (ELISPOT). In conclusion, octreotide therapy is associ- Conversely, a dramatic fall in the levels of cell ated with gall stone formation in acromegalics, free interleukin 2R in lavage was found in the and the incidence of stones is related to the Inhibition of leukocyte adhesion molecule patients who improved. duration of treatment. expression: a novel mechanism of action of The striking reductions in cell free inter- sulphasalazine leukin 2R suggests that elemental diet may work by down regulating T cell activity (IL-2R S M GREENFIELD, A S HAMBLIN, N A PUNCHARD, is a marker of T cell activity). This is the first R P H THOMPSON (Gastrointestinal Laboratory evidence of a possible mode of action of NUTRITION: APPETITE AND SATIETY and Department of Immunology, St Thomas's elemental diet in inflammatory bowel disease. Hospital, London) Sulphasalazine (SASP) may reduce inflammation in inflammatory bowel disease (IBD) by inhibiting leukocyte recruit- Fat induces small intestinal satiety at a lower ment into the bowel. Recruitment depends Octreotide inhibits the growth of liver caloric threshold than carbohydrate or upon leukocyte adhesion to vascular endo- adenocarcinoma in an animal model of liver protein thelium, a process in which the adhesion metastases molecules CD1 1/CD18 may play an important J G GEOGHEGAN, D C LAWSON, C A CHENG, T N role. We have investigated the effects of SASP N DAVIES, J YATES, B A TAYLOR, S A JENKINS PAPPAS (INTRODUCED BY P B COTTON) (Duke upon TNF-induced upregulation of leukocyte (University Department ofSurgery, Royal Liver- University and Veterans Administration Medical CD11/CD18. pool Hospital, Liverpool) The treatment of Centers, Durham, North Carolina, USA) TNF (160 pg/ml) was incubated for 30 metastatic liver cancer remains poor, the Nutritive substances in the small intestine minutes with 0 5 ml heparinised blood from six majority of patients dying within one year of cause satiety signals that probably regulate the healthy volunteers±SASP (10-5-10-3 M). diagnosis. Adenocarcinoma is the commonest intermeal interval. This study investigates the Leukocyte suspensions were obtained and the cancer metastatic to the liver. Octreotide, a relative potency of carbohydrate, fat, and binding of monoclonal antibodies against long acting analogue ofsomatostatin alters liver protein in induction of small intestinal satiety. CD1la, CDl1b, CD11c, and CD18 was deter- blood flow, stimulates reticuloendothelial Six dogs were prepared with oesophageal mined by flow cytometry. The intensity of system activity, and inhibits a wide variety of and gastric fistulas. Isovolumetric nutrient antigen expression was measured as mean trophic hormones. We have investigated its infusions were given over two hours through fluorescence intensity (MFT). effects on the growth and development of duodenal catheters passed through the gastric TNF increased mean MFI (SEM) ofCD1 lb hepatic adenocarcinoma induced by intra- fistula. Each nutrient was given over a range of and CD18 on granulocytes compared with portal inoculation of tumour cells. caloric levels to identify its satiety threshold. controls (no TNF) from 100-4 (11-0) to 135 After intraportal injection of 1 x 107 K12/Tr Satiety was measured by sham feeding at the British Society ofGastroenterology A 1229 end of each infusion. Intraduodenal fat conventional weight reducing diets. It has been much as he or she wanted. In the lean volun- infusion significantly suppressed sham feeding suggested that the release of cholecystokinin teers, the BBS experiment was repeated with a with just 5% of the total 24 hour caloric (CCK) may be involved in the induction of background infusion of LOX (25 mg/kg. 150 requirement. For carbohydrate and protein satiety after a meal. Therefore we have studied minutes). Feelings of hunger and fullness were Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from infusions the thresholds for suppression of the release of CCK in response to a very low scored on visual analogues scales. sham feeding were 10% and 20% of total 24 calorie diet (Modifast) and we have compared Bombesin significantly decreased food hour caloric requirement respectively. these results with those obtained with a normal intake in lean volunteers from 602 (68) (mean In conclusion, (1) small intestinal satiety can 410 kcal meal. (SEM)) g to 482 (74) g (p<0 01). Loxiglumide be produced by a small fraction of the 24 hour Seven otherwise healthy obese subjects (five did not affect the reduction of food intake caloric requirement. (2) The three classes of F, two M; mean age 34 years, range 23-44) induced by BBS (365 (69) g). Hunger and macronutrients have different caloric thres- with a body mass index of40 (range 32-50) kg/ fullness feelings were also significantly influ- holds for small intestinal satiety. (3) Fat has the m participated in a 10 week study on the effect enced by BBS (p<0 05), but not altered by lowest threshold, followed by carbohydrate of 3 dd 80 kcal Modifast on weight reduction, LOX. In obese volunteers food intake during and then protein. Small intestinal satiety may CCK-release, and hunger scores. They all had saline infusion (499 (88) g) was not significantly be mediated by mucosal chemoreceptors normal total serum T4 values and responded reduced by BBS (431 (60) g). Hunger and sensitive to specific nutrients and not post- adequately to 1 mg ofdexamethasone given the fullness feelings in these obese volunteers were absorptive calorie dependent mechanisms. previous evening at 23.00 (morning cortisol also not significantly affected by BBS. In both <0-08 [smol/l). Hunger scores were measured lean and obese volunteers BBS infusion with 10 point visual analogue scales during resulted in comparable plasma BBS and CCK three consecutive days before every meal and values. before the night. The sum divided by 12 is the In conclusion, these data indicate that BBS Intragastric lipid administration dose hunger score. CCK release was studied in reduces food intake and hunger feelings and dependently increases gastric compliance response to a normal 410 kcal meal (protein 19 induces fullness in healthy lean volunteers. responses to distension E%, fat 59 E%, carbohydrate 22 E%), a 387 Obese volunteers are less sensitive to the kcal of commercial liquid food meal (13 E% satieting effects of BBS. The BBS induced L TRONCON, D G THOMPSON, N AHLUWALIA, J protein, 31 E% fat, 55 E% carbohydrates) and effects are not mediated by CCK. BARLOW, L HEGGIE (Department of Medicine, an 80 kcal Modifast (55 E% protein; 2-6 E% fat, Hope Hospital, Salford) The proximal stomach 42-3 E% carbohydrates) meal. Plasma CCK responds to distension by increasing its compli- (antibody T204) was measured by a sensitive ance, which allows volume accommodation and specific radioimmunoassay at -10, 0, 10, Vertical gastric stapling without a band for without substantial rise in intragastric 20, 30, 40, 50, and 60 minutes after the meals. morbid obesity pressure. It has also been suggested that com- for significance increased by food, although the Differences were tested pliance may be employing the Wilcoxon signed rank test. D WILKINSON, H SUE-LING, D JOHNSTON nutrient component responsible is uncertain. During the 10 week treatment course with (University Department ofSurgery, The General In the present study we assessed the effects on Modifast, mean body weight was reduced from Infirmary, Leeds) Vertical banded gastroplasty compliance of a series of meals varying in lipid 122 (9) kg (mean (SEM)) to 99 (7) kg (p<002). is an effective operation for morbid obesity but concentration. Hunger scores decreased from 3 8 (0.7) to 0.9 the band is associated with complications. An Thirteen healthy volunteers underwent 36 (0.3) (p<0 05). The integrated CCK response alternative procedure has been developed in experiments. After an overnight fast a 1200 ml from 0-60 minutes to a Modifast meal was 138 which no band is used. A longer stomach tube balloon attached to a gastric tube and con- (21) pM.h. (After 10 weeks of Modifast treat- is fashioned, starting at the angle of His and nected to pressure sensors was positioned in the ment 100-8 (19-1).) These results were not emptying adjacent to the crow's foot into the gastric fundus. Gastric compliance was significantly different from the CCK-response antral mill. Is this operation effective? http://gut.bmj.com/ assessed by measuring intragastric pressure to the normal meal (86 (13) pM.h) or the liquid Twenty patients (four M, 16 F, mean age 37 during stepwise balloon distension both fasting food meal (93 (14) pM.h) containing about five years, range 26-55) have undergone this opera- and after the test meal. Six isomolar meals (250 times more calories. tion. Mean preoperative weight was 147-9 kg ml) were given in random order. Meals were In conclusion, the relatively high release of (range 108-222) and mean body mass index 280 mOsm saline and 1-25, 2.5, 5.0, 10-0, and CCK in response to only 80 kcal of Modifast (BMI=weight/height2) was 53-6 kg/M2 (range 20% Intralipid diluted in saline. The results may be involved in the satiety effects induced 42-87). Eighteen patients have been followed were expressed as slope values (x 10- 5) of log by a very low calorie diet. up for a mean of 21 months (range 12-36), two transformed volume:pressure data. patients have been lost to follow up. on September 28, 2021 by guest. Protected copyright. Saline did not affect gastric compliance Mean postoperative weight was 109 kg (fasting v fed, median: range 105: 80-118 v (range 76-193) and mean BMI was 39-3 kg/M2 104: 43-185, p>0-10) not did the 1-25% (105: Bombesin reduces food intake in lean but not (range 28-53), often this took over one year to 86-124 v 113: 66-122, p>005) or 2.5% (108: obese man achieve. Mean percentage weight reduction 60-129 v 82: 30-125, p>0 05) fat emulsions. was 26- 1 % (range 10-39), 12 patients lost more to 5.0% (90: 59- Increasing fat concentration R J LIEVERSE, J B M J JANSEN, A VAN DE ZWAN, than 25% oftheir body weight. Fifteen patients 203 v 32: 17-115, p<0 05), 10-0% (91:62-106 L SAMSON, AA M MASCLEE, C B H W LAMERS are pleased with the results of their surgery and v 43: 20-48, p<0 05) and to 20-0% (66: 46-96 (Department of Gastroenterology-Hepatology, three are disappointed. Two patients have v 25: 15-57, p<0 05) resulted in significant University Hospital, Leiden, The Netherlands) begun to increase their weight, after an initial increases in gastric compliance. A positive The mechanisms that induce satiety are not fall. correlation was found between lipid concentra- clear. Studies in a variety ofspecies have shown This method of vertical gastric stapling, tion and the intensity of the gastric compliance that both bombesin (BBS) and cholecystokinin without the use of a band, is an effective effect in the range of 1-25 and 5.0% fat (CCK) are able to induce satiety. Since BBS is a operation for morbid obesity. concentration (R=0-62, p<005). potent stimulus of CCK release, the effects of In conclusion, these results indicate that BBS on food intake may be mediated by the lipid ingestion enhances gastric compliance release of CCK. The availability of the potent through a pathway sensitive to lipid concentra- and specific CCK receptor antagonist tion which is likely to make a major contribu- loxiglumide (LOX) has enabled investigation LIVER DISEASE: PREVENTION AND TREATMENT tion to the gastric emptying delay known to be of the role of CCK in BBS induced satiety. In induced by lipid meals. the present study we have examined the effect of BBS on food intake in lean and obese man. Nine healthy lean volunteers (four M, five F; Experience with a pre-S containing mean age 25 years (range 22-36)) with a median recombinant HBV vaccine: safety and Plasma cholecystokinin response to a very body mass index of 22 (range 20-25) kg/mi2 and immunogenicity studies low calorie diet nine otherwise healthy obese volunteers (nine F; mean age 40 years (range 30-59)) with a I YAP, R GUAN, S H CHAN (Departments of R J LIEVERSE, J B M J JANSEN, A P VAN SETERS, C B median body mass index of 40 (33-49) kg/mr2 Medicine and Microbiology, National University H W LAMERS (Departments of Gastroenterology- were studied. In a double blind fashion they of Singapore, Singapore) The only means of Hepatology and Endocrinology, University received either saline iv or BBS (375 [sg/kg lean preventing the spread and subsequent chronic Hospital, Leiden, The Netherlands) Very low body mass. 150 min iv). Sixty minutes after the sequalae of chronic HBV infection is by active calorie diets cause more extensive weight loss start of the infusions an identical meal was immunisation. Recent studies suggest that with less hunger feelings when compared with presented and each subject was free to eat as inclusion of all HBV envelope polypeptides (S A1230 British Society ofGastroenterology and pre-S) may increase the vaccine immuno- clearance has not been clarified. Ten patients evidence ofarrested growth on longer follow up genicity. (eight M, two F) enrolled in a clinical trial with (median=6 months) in five. We studied the safety and immunogenicity recombinant aIFN (raIFN) for chronic viral ILH is a safe and simple technique produc- of a novel recombinant HBV vaccine contain- hepatitis (eight HCV related and two HBV ing radiological evidence of necrosis in small Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from ing the pre-S components. Healthy volunteers related) were studied. Blood samples were metastases and is worthy of further evaluation. with no previous HBV infection were random- taken immediately before, and at six and 24 ised to receive three intramuscular doses of hours and 15 and 30 days after parenteral either 5 [ig (48 subjects) or 10 ,ug (49 subjects) injections of raIFN (3 MU, three times a ofthe vaccines at month 0, 1, and 6. One month week). aTNF was assayed by ELISA (Q-E- Does a interferon priming enhance the after the third injection, 100% of the vaccinees TNF, Nuclear Laser Medicine); peripheral efficacy ofsubsequent a interferon therapy in seroconverted; 92% of the 5 [sg group and lymphocyte phenotypes (CD2, CD3, CD4, chronic hepatitis B virus infection? 100% ofl0 [tg group had anti-HBs titre greater CD8, DR, CD20, T-DR, CD16, CD45RA, than 10 iu/l and the seroconversion rate did not CD29)were tested by specific fluorescentmono- A P CATTERALL, R KING, J Y N LAU, H M DANIELS, change at one year after vaccination. The clonals (Ortho, Coulter) and then measured G J M ALEXANDER, I M MURRAY-LYON, ROGER geometric mean titres (GMT) of anti-HBs with a flow cytometric fluorescence technique WILLIAMS (Institute of Liver Studies, King's values at months 7 and 12 were similar in the (Ortho-Cytoron). College School of Medicine and Dentistry, two groups; 2162, 2687 iu/l (month 7) 734, 970 The mean baseline value of serum aTNF London and Department of Gastroenterology, iu/l (month 12) in the 5 and 10 ,tg groups was 23-9 (5.5) pg/ml, which was not statistic- Charing Cross Hospital, London) a Interferon respectively. Some 96% of the 10 pg group ally different from that observed after six and (aIFN) is an established treatment for chronic were seroprotected (GMT 182 iu/l) before the 24 hours and 15 and 30 days of raIFN treat- HBV infection but only 30-50% of the patients third injection, and nearly 70% of all vaccinees ment. No differences were observed in any respond successfully in terms of e-seroconver- had an anti-HBs value more than 1000 iu/l at PBL subpopulations except for NK (CD16+ sion and sustained loss of serum HBV DNA. month 7. No unwanted effects were observed. cells) with regard to the percentage and the To determine whether a priming course of This vaccine seems to be safe and rather absolute number, comparing baseline values aIFN enhances the efficacy of subsequent immunogenic. (12-1 (7.6)% and 319-8 (188)) with those at 30 therapy, we conducted a randomised trial to days (8-2 (8.2)% and 201-8 (189)), p<0 009. compare aIFN priming (aIFN for one month, No correlation was found between aTNF no treatment for one month) followed by serum values and PBL subpopulations. standard aIFN therapy (aIFN for three In conclusion, these data suggest that raIFN months) with standard aIFN therapy (aIFN Endoscopic intravascular oesophageal can induce an early viral challenge with subse- for three months) with standard aIFN therapy variceal pressure measurements: response to quent mobilisation of NK population from alone (lymphoblastoid aIFN 10 MU thrice metoclopramide peripheral blood to the liver where they prob- weekly). ably play a role in the cytolitic response. Some 35 patients seropositive for HBsAg C CIJEVSCHI, M STAN, E SANDULESCU, G BALAN, (>12 months), HBeAg and HBV DNA, and M FRASIN (University ofMedicine andPharmacy, with histological evidence ofactive liver inflam- IInd Medical Clinic Gastroenterology, 6600 Iasi, mation, were recruited. They were all sero- Romania) Pharmacotherapy with intravenous negative for markers of HDV but seven were metoclopramide (M) has been reported to be Interstitial laser hyperthermia: a percutane- seropositive for HIV. Twenty nine patients effective in the control of acute variceal bleed. ous therapy for inoperable liver metastases attended at least eight months' follow up; 16 This study reports the effects of M on intra- received aIFN priming and therapy and 13 (IEVP) vascular oesophageal variceal pressure A A C STEGER, W R LEES, K M received aIFN therapy alone. Side effects in patients with alcoholic cirrhosis. There were MASTERS, WALMSLEY, S G BOWN (Departments of Surgery (pyrexia, fatigue) were mild and well tolerated http://gut.bmj.com/ 12 patients (10 men, two women), aged 35-68 andRadiology, University College andMiddlesex and were the same in both groups. years with oesophageal varices caused by School ofMedicine, London) There is a need for These data suggest that a short priming alcoholic cirrhosis. Six patients had recently a simple and safe palliative treatment for course of aIFN may augment the development bled from their varices. The IEVP was inoperable discrete hepatic metastases. of anti-HBe achieved with the standard three measured by endoscopicajly guided fine needle Interstitial laser hyperthermia (ILH) is a new month course of aIFN therapy. puncture of the variceal columns 5 cm above technique, simple in concept. A thin flexible the cardia. The needle was continuously per- laser fibre tip is inserted percutaneously into a fused with sterile saline (0.9%) and attached to

solid organ tumour with absorption of emitted on September 28, 2021 by guest. Protected copyright. a Statham gauge and the pressure values were laser light as heat producing an area of tumour Ursodeoxycholic acid treatment in active recorded on a Beckman writer. IEVP was necrosis which subsequently heals by cirrhosis with or without hepatitis C virus calculated taking the pressure in the oesopha- regeneration/fibrosis. Experimental studies in antibodies geal lumen as zero reference. IEVP was liver have shown ILH to be effective 10 intravenous normal measured before and after mg and safe. In a pilot clinical study, the feasibility F LIRUSSI, A BECCARELLO, L OKOLICSANYI M. and safety of this technique for inducing (Institute of Internal Medicine, University of Metoclopramide caused a reduction in IEVP necrosis in hepatic metastases was studied. Padua, Italy) Ursodeoxycholic acid (UDCA) in 10 of 12 patients; overall, there was a fall in Ten patients (aged 46-78 years) with a total improves liver function tests (LFTs) in chole- IEVP from 21-4 (3.5) mm Hg to 14-6 (2A4) mm of 18 metastases (diameter 2-0-6.5 cm) and no static disorders. However, little is known about Hg (p<005). There were no complications extrahepatic disease were treated on 31 its effect in patients with established cirrhosis related to the variceal puncture. occasions using a Nd:YAG laser. Some 70% of of different aetiology. We therefore gave In conclusion, intravenous M, which metastases had arisen from the colon/rectum. UDCA (600 mg/day) to 17 anti-HCV positive increases lower oesophageal sphincter Under intravenous sedation, three to four (+ve) and 12 (eight with previous HBV infec- pressure, significantly decreases IEVP in hollow 19 G needles were inserted per- tion, four alcoholics) anti-HCV-ve patients cirrhotic patients. However, to prove that M is cutaneously in juxtaposition into a selected with Child's A cirrhosis plus chronic active a useful agent for the control of acute variceal metastasis under ultrasound control (US). A hepatitis for 13-3±0-7 months (range 8-20) bleeding, further studies are warranted. 200 i laser fibre was inserted down each fibre and 10-2±1-3 months (range 6-18) respect- so the tip lay within the tumour, which was ively. Treatment efficacy and safety were irradiated using a power of 1-5 to 2-0 watts assessed by six monthly changes in routine applied for 500 seconds. There were no com- LFTs, galactose elimination capacity (GEC), Modifications of serum TNF and peripheral plications and all patients were discharged and antipyrine clearance (APCL) as compared blood lymphocyte (PBL) subpopulations within 24 hours of treatment. Real time US with pretreatment values. during recombinant a interferon treatment monitoring during treatment showed conver- In anti-HCV-ve cirrhosis, ALT decreased sion of the metastases from a predominantly from mean (SEM) 138 ull (32) to 79 (12) F DE LAZZARI, G DE SILVESTRO, P FABRIS, mixed echogenic appearance to a hyper- (-43%), AST from 97 u/l (16) to 63 (8) M BORTOLAMI, A FLOREANI, C VECCHIATO, echogenic pattern. Follow up computed (-35%), and y-GT from 111 u/l (27) to 63 (16) C VENTURI, M CHIARAMONTE (Department of tomography at six to eight weeks showed (-43%). In the anti-HCV+ve group serum Gastroenterology and Blood Bank, University of radiological evidence of at least partial necrosis transaminase values were slightly reduced (12- Padova, Italy) Recombinant a interferon in 10 of the 18 metastases. Of smaller meta- 14%), whereas y-GT values dropped from 135 (ctINF) is an effective treatment for chronic stases (diameter -3-0 cm, n=9), seven showed u/1 (34) to 57 (14) (p<0 05). Mean serum viral infections, but up to now the specific the largest percentage necrosis by volume (30- alkaline phosphatase and total bilirubin values, involvement of T and B cell responses in viral 100%) with biochemical and radiological which were normal before therapy, changed British Society ofGastroenterology A1231 little after UDCA treatment. Similarly, GEC of 20 aminotransferases became normal. All months with necrotising enteritis in which and APCL, which were considerably impaired five patients with ascites showed no response. there was dilatation and discolouration of the at entry, showed only modest changes through- Fifteen of 20 relapsed after a mean of three whole bowel together with extensive mucosal out the treatment period. months. All responded to a second three month sloughing. The response was assessed by Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from In conclusion, in patients with anti- course and are maintained so far with further jejunal mucosal morphology and estimation of HCV-ve active cirrhosis, UDCA was well courses upon reactivation. Five of 20 had a crypt cell kinetics before EGF infusion (day 0) tolerated and improved some indices of liver permanent biochemical response, all with low and days 2, 4, and 7 thereafter. Total villus injury. By contrast, the 'activity' of chronic anti-e titres. Two patients died from variceal atrophy and crypt destruction (day 0) were liver disease associated with HCV infection was bleeding at two and four years. No occular side followed by crypt hyperplasia on day 2 not influenced by UDCA treatment, though effects were noted. Liver biopsy at one year in although villus atrophy persisted. By day 4, y-GT values returned, on average, to normal seven of 20 showed inactive cirrhosis. however, villus height had increased in associa- values. In conclusion, (1) hydroxychloroquine is a tion with a significant (p<0-01) increase in safe, very cheap, and effective drug for active crypt mitotic activity. On day 7 the mucosa cirrhosis. Relapses of disease respond equally looked normal. Histological repair was accom- well. (2) Piecemeal necrosis disappears during panied by gradual clinical improvement and Aprotinin improves renal function in remission. (3) Patients with high titres ofanti-e the patient made an uneventful recovery. cirrhosis with ascites tend to relapse. The drug is not active in These results show a significant increase in patients with ascites. crypt cell proliferative activity in association A J MACGILCHRIST, A CUMMING, K CRAIG, I A D with noticeable recovery of the surface BOUCHIER, P C HAYES (University Department of epithelium during EGF infusion and it is Medicine and Gastrointestinal/Liver Service, probable that the rate ofrecovery exceeded that Royal Infirmary, Edinburgh) Several vaso- which would be expected during normal dilators have been found in increased amounts PAEDIATRIC SECTION mucosal regeneration after injury. Further in cirrhosis and have therefore been implicated studies should be undertaken to establish the in the arterial vasodilatation which may trigger value of stimulated crypt regeneration in sodium retention in these patients. However, acquired enteropathies. none has proved causal due to a lack of studies Aztreonam prevents necrotising enterocolitis employing appropriate antagonists. We have in premature neonates previously shown that the plasma kallikrein- kinin system is activated in cirrhosis (Gut 1989; P M MACKAY, M R MILLAR, M I LEVENE, Transient precocious sucrase activity in 30: A1505). This potent vasodilator system can V LANGDALE, N WILD, j W L PUNTIS (Department rotavirus infected neonatal rats be inhibited by aprotinin ('Trasylol'). ofPaediatrics and Child Health, Leeds General We measured renal function (including Infirmary, Leeds) Previous work has implicated M SHAHRIER, M W SMITH, M J G FARTHING, clearance of inulin and para-amino hippurate) bowel colonisation with enterobacteriaceae in j A WALKER-SMITH (The Medical College of St and systemic haemodynamics (including the pathogenesis of necrotising enterocolitis Bartholomew's Hospital, London and Institute of cardiac output by thermodilution) in eight (NEC), a major cause of morbidity and Animal Physiology and Genetics Research, cirrhotics with ascites before and during an mortality in the premature newborn. We have, AFRC, Cambridge) It has been proposed that intravenous infusion of aprotinin. Patients therefore, examined the effect of aztreonam, neojnatal rotavirus infection results in more were on no diuretics and 40 mmol of sodium/ an antibiotic with selective activity for entero- rapid maturation of small intestinal epithe- day. Renal blood flow increased from mean bacteriaceae, on bowel flora and the incidence lium. To study this we infected 6 day old (SEM) 454 (54) to 663 (65) ml/minute, p<0 05 of NEC. Infants <32 weeks gestation were neonatal rats with group B rotavirus and and glomerular filtration rate increased from 72 randomised to receive treatment with intra- measured sucrase and maltase activity by bio- http://gut.bmj.com/ (10) to 121 (19) ml/minute, p<0 05. Renal venous aztreonam and vancomycin (group A, chemical, histochemical, and microdensito- sodium excretion increased in seven patients by n=72), or gentamicin and vancomycin (group metric techniques at 6, 12, 24, 120, 265, and a mean of 151%, and plasma renin fell in all B, n=7 1) in the event of suspected infection at 360 hours post-infection (HPI). patients from 10.0 (2.9) to 5.9 (1.9) (both a postnatal age >7 days. Stool samples were There was no measurable sucrase or maltase p>0 05). Aprotinin increased systemic collected prospectively from birth. Forty seven activity in infected and control animals up to 24 vascular resistance and lowered cardiac output (65%) of group A and 52 (73%) of group B HPI. At 120HPI there was increased sucrase in five of the six patients with low baseline subsequently received antibiotics. Entero- activity (median 26.5, interquartile range 0-59 values. bacteriaceae disappeared from the bowel pmol/min/g) in rotavirus infected rats com- on September 28, 2021 by guest. Protected copyright. Thus, aprotinin improves renal function in within four days of treatment with aztreonam pared with controls (2 5, 0-6 5; p<0 05). cirrhosis with ascites, associated in most cases but were not affected by gentamicin. Group A Sucrase activity was then undetectable in with a reduction in systemic vasodilatation. had a lower incidence of bowel colonisation by infected and control rats at 264HPI (17 days This study supports the arterial vasodilatation enterobacteriaceae than group B at all ages >7 old) but reappeared at 360HPI (21 days old) theory of ascites and implicates the plasma days. There was no difference between groups rats at similar levels. Maltase activity was kallikrein-kinin system in its pathogenesis. in colonisation with yeasts, anaerobes, or increased in rotavirus infected rats at 120HPI enterococci. Eight infants in group B (200, 151-242 v 72, 47-122; p<0-01) and developed NEC, while none in group A were remained at this level up to 264HPI. Histo- similarly affected. Enterobacteriaceae were chemical and microdensitometric assessments Treatment of active cirrhosis B with hy- present in the stools of all the six patients with paralleled the biochemical assays. droxychloroquine: longterm follow up of an NEC from whom stool samples were collected The precocious increase in sucrase and open study in the 48 hours before diagnosis. maltase activity confirms the earlier maturation These findings suggest that aztreonam pre- of intestinal epithelium during rotavirus infec- E A KOUROUMALIS (Academic Department vented the development of NEC in premature tion but the subsequent discordance between of Gastroenterology, University Hospital, infants by suppressing bowel colonisation with these activities indicate differential effects of Heraklion, Crete, Greece) Treatment of active enterobacteriaceae. rotavirus on enzyme expression. cirrhosis in HBsAG +ve anti-HBe +ve patients is controversial. Interferon does not seem to be indicated. Hydroxychloroquine, a lysosomotropic agent, was found to be effective Therapeutic use of epidermal growth factor Seroepidemiology of Helicobacter pylori in reducing spontaneous cytotoxicity in an in necrotising enteritis infection in early childhood vitro system, in a dose dependent manner. P G C A Twenty patients, all with active anti-HBe P B SULLIVAN, M J BRUETON, Z B TABAR, R A J-E THOMAS, R B DOWNES, LUNN, cirrhosis, entered an open study receiving 200 GOODLAD, C Y LEE, N A WRIGHT (Westminster NORTHROP-CLEWES, L T WEAVER (MRC Dunn mg hydroxychloroquine tid for three months Children's Hospital and Imperial Cancer Nutrition Unit, Keneba, The Gambia and Cam- with regular monitoring of liver function tests. Research Fund, London) Epidermal Growth bridge, UK) Helicobacter pylori infection is They have been followed up for 3-6 years Factor (EGF) stimulates epithelial cell pro- common in West Africa. Longitudinal studies (median 4.5 years). Five patients with ascites at liferation in the intestinal mucosa, although in Europe suggest that spontaneous resolution the time ofpresentation were also included. these properties have not found any notable of established infection is rare, but is not All 20 patients responded after one month of application in enteric disease. Intravenous known whether acute infection in early child- treatment with reduction of aminotransferases human recombinant EGF (100 ng/kg/hour hood inevitably causes chronic disease. and improvement of prothrombin time. In 17 infused for six days) was used in a girl aged 8 A total of 134 children (aged 1-15 months), A1232 Bnrtish Society ofGastroenterology from three Gambian villages were studied over neoplasia in the first degree relatives of and University of Calgary, Alberta, Canada) two years. Specific IgG and IgM antibodies to patients with colorectal cancer Conventionally, endoscopic biliary stents are H pylon (Hp-IgG, Hp-IgM) were measured placed with the tip in the duodenum. This may monthly, using a previously validated ELISA B M STEPHENSON, V A MURDAY, D T BISHOP, P J promote accumulation of biological material Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from technique. FINAN (INTRODUCED BY D JOHNSTON) (Imperial leading to stent occlusion. This study investi- Twelve (9%) had high Hp-IgG values at one Cancer Research Fund, Genetic Epidemiology gates whether stent placement completely month, which then declined. Forty four (33%) Laboratory, University ofLeeds and the Depart- above, rather than across the sphincter ofOddi subsequently had diagnostically raised Hp- ment ofSurgery, Leeds General Infirmary) First (SO) reduces the occlusion rate. IgG, and 21 (15%) also showed a briefHp-IgM degree relatives (FDRs) of patients presenting Twelve dogs were randomised to receive a response. In 33 children (24%), raised Hp-IgG with sporadic colorectal cancer are at increased 7 FG biliary stent either across or above the SO. values returned to normal, although many risk of developing colorectal neoplasia. Stents were placed at laparotomy through a became reinfected later. Only 21 (15%) had Although screening of FDRs has been pro- duodenotomy, and fixed with a tape ligature established chronic infection by the end of the posed, the methods used remain debatable. We around the common bile duct (CBD). The study. There were no nutritional differences report the results of a screening study using stents were removed one month later. Stent between cases and controls at seroconversion. faecal occult blood tests and endoscopy in one weight, patency, and serological and macro- In a separate study in the same community, surgical practice. scopical indicators of biliary obstruction were 13C urea breath tests showed that 46 of 50 The endoscopic technique depended on the assessed. (92%) 3-5 year olds were strongly positive for empiric risk value for developing colorectal Five of six stents placed across the sphincter H pylori. cancer based upon family histories - FDRs occluded; all six placed above the sphincter In conclusion, H pyloii infection is common with risk <1:10; flexible sigmoidoscopy and remained patent (p<0 05). Stent weight, CBD in The Gambia from an early age. Most risk > 1: 10; colonoscopy. Screening was diameter, bilirubin, and alkaline phosphatase children can eradicate their first infection, but offered to FDRs with risk <1:10 aged 50-75 were all significantly increased when stents established infection is normal by 5 years. years and risk >1:10, from 10 years younger were placed across rather than above the SO. Clearing infection does not protect from than their affected relative. In conclusion, biliary stents occlude earlier further disease, and undernutrition does not One hundred and thirty three FDRs of 151 in dogs ifthe distal tip is in the duodenum. This predispose to H pyloni infection. patients were contacted. Compliance for FDRs may be due to reflux of duodenal contents into was 69%, compared with 46% for spouse the stent. Human studies comparing standard control group (p<0-001). Sixteen of 92 (17%) placement of biliary stents with placement FDRs had adenomatous polyps (mean size: 1 above the SO are indicated. Vitamin E deficiency, lipid peroxidation, and cm, range: 0-5-2- 1 cm) compared with three of small intestinal function in the Wistar rat 28 spouses (11%). Median age of FDRs with polyps was 54 years compared with 66 years in K J LINDLEY, M A GOSS SAMPSON, D P R MULLER, spouses. Faecal occult blood tests were unhelp- An endoscopy simulator for teaching P J MILLA (Medical and Membrane Biochemistry ful in detecting polyps. Although no cancers colonscopy Units, Institute of Child Health, London) were detected, two are known to have occurred Increased concentrations of free radicals have since the study started (one in a non-compliant C B WILLIAMS, D F GILLIES, A HARITSIS (St been implicated in the cycle of malnutrition FDR and one in a FDR >75 years). Mark's Hospital, London and Department of malabsorption and infection leading to pro- These results suggest that FDRs provide a Computing, Imperial College, London) Accurate tracted diarrhoea of infancy. Infection can high risk group who are more compliant and manipulation of endoscope controls, logical produce an oxidising stress in malnourished accept more invasive screening techniques. hand-eye coordination while tracking through children with low antioxidant defences. bends, and empiric responses in controlling Vitamin E is the most important chain break- shaft loops are all fundamental to insertion of a http://gut.bmj.com/ ing antioxidant in biological membranes. colonoscope, but slow to learn and difficult to Unstripped jejuna from fasted 12 month old Improved assessment ofsmall bowel Crohn's teach. vitamin E deficient and sufficient male Wistar disease using Sonde enteroscopy We have developed a graphics program for a rats were studied in an Ussing chamber. Basal standard PC microcomputer (with graphics short circuit current (Isc) was higher in A J MORRIS, L WASSON, R H R PARK, J F and voice synthesis boards) interacting with a deficient animals (deficient 91 pA/cm2 (95% CI MACKENZIE (Gastrointestinal Investigation Unit, dummy video endoscope and an electronic 80-101) v control 73 gA/cm2 (67-79), n=40, Royal Infirnary, Glasgow) Eight patients with 'patient' box. It produces a screen image which p<005). Tissue resistances were comparable suspected active small bowel Crohn's disease responds realistically to steering, twisting, or on September 28, 2021 by guest. Protected copyright. (72 Q/cm2 (67-78) v 77 Q1cm2 (68-86)). 10 mM were examined using the new technique of push-pull movements as well as to inflation/ mucosal and serosal aminophylline produced small bowel enteroscopy. The patients (four deflation and lens washing and also allows greater responses in deficient rats (56 ItA/cm2 M: four F) with median age 32 years (range 28- coagulation of polyps in the simulated colon. (40-72) v 34 pA/cm2 (25-43), n= 14, p<0 05), 64) all had a normal upper gastrointestinal Screen help messages or audible instructions as did mucosal Escherichia coli heat stable toxin endoscopy. Seven patients had previous small guide the beginner, and overinsufflation or (STa), 60 mU/ml (55 pA/cm2 v 31 iA/cm2, bowel resections for Crohn's disease and prior clumsy manoeuvres result in patient protests, n= 10, p<0-01). Serosal bethanecol (1 mM) to enteroscopy had no evidence of active as well as recording an appropriate score. produced similar changes in both groups (34 disease on small bowel radiology (SB enema Preliminary results suggest that handskills pA/cm2 (26-44) v 32 pA/cm2 (23-41)). four patients; barium meal and follow through and basic confidence in colonoscopy are rapidly Thiobarbituric acid reactive substances three patients). The indication for enteroscopy acquired, with little involvement ofteacher and (TBARS) an index of lipid peroxidation, were was undiagnosed significant blood or protein none of patient. Simulators could make higher in mucosal scrapings from deficient loss in four patients, suspected recurrent small practicable the widespread teaching of jejuna (1-93 (1-38-2-48) v 1-01 (094-1 09) bowel Crohn's disease in three patients, and sophisticated flexible endoscopy to medical or nmol/mg protein, n=6, p<0-01). A positive PVO in one patient. In four patients, small nurse practitioners, with the added possibility correlation was found between TBARS and Isc bowel enteroscopy identified active disease of objective assessment of an individual's (r=0.803, p<0 005). which had not been identified radiologically. In ability. Lipid peroxidation in vitamin E deficient these four cases, information obtained by rats correlated with increased basal and cyclic enteroscopy led to changes in patient manage- nucleotide mediated secretion. This may be of ment and subsequent clinical improvement. relevance of the pathogenesis of protracted We suggest that significant additional Needle knife spincterotomy: an ill deserved diarrhoeal disease in malnourished popula- clinical data can be obtained enteroscopically in reputation? tions. some patients with Crohn's disease. P CURLEY, M J MCMAHON (University Department of Surgery, General Infirmary, Leeds) Needle knife sphincterotomy (NKS) is a technique Placement of biliary stents above the used to gain access to the bile duct at ERCP in sphincter of Oddi prolongs stent patency in the 10% ofpatients in whom cannulation of the ENDOSCOPY dogs ampulla proves difficult. It has, however, been associated with a high incidence of complica- J G GEOGHEGAN, M S BRANCH, J W COSTERTON, tions. T N PAPPAS, P B COTTON (Duke University Over a two year period, NKS was used to Endoscopic screening for colorectal Medical Center, Durham, North Carolina, USA gain access to the bile duct in 37 cases, which British Society ofGastroenterology A1233 represents 12% of ERCP examinations computer graphics simulation of lower gastro- and fibronectin in Hirschsprung's disease: an performed. Five out of 37 cases had diagnos- intestinal endoscopy to test the hypothesis that immunohistochemical study tic ERCP performed, while endoscopic endoscope handling skills can be learned with- sphincterotomy and stone clearance was out using patients. Our simulator consists of D H PARIKH, P K H TAM, D VANVELZEN, D EDGAR Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from possible in 26 cases and placement of a biliary three elements: (1) a desk top microcomputer (INTRODUCED BY A KINGSNORTH) (Department of stent achieved in two cases. Five patients (IBM-386 clone running at 33 MHz) boosted Child Health, University of Liverpool, Royal had unsuccessful therapeutic manoeuvres by a graphics processor, (2) a novel computer Liverpool Children's Hospital, AlderHey, Liver- attempted after NKS giving an overall success programme, which creates a 3-D representa- pool) Previous in vitro studies have suggested rate of89%. The mean age was 67-64 years with tion of the colon using a polygon mapping that successful neural crest cell migration could a range of 46-91 years. Despite high reported technique, and (3) a 'dummy' endoscope, a be influenced by the composition of the extra- complication rates, there were no deaths in this highly modified Olympus duodenoscope which cellular matrix components, tenascin and series and no case of haemorrhage after NKS. converts mechanical input into electrical fibronectin in the developing gut. We aim A single patient had a recurrence of acute signals that drive the simulation. The 'dummy' to gain insight into the pathogenesis of pancreatitis after NKS and ES. One reason for endoscope is advanced and withdrawn through Hirschsprung's disease (HD) by studying the this lower complication rate may be the use ofa a sensing device that provides variable resis- distribution of tenascin and fibronectin in 50% lower diathermy current than previously tance to simulate wall collisions and looping. bowel specimens of patients with HD. reported. The simulation provides both verbal and Immunohistochemical examination was We believe that this technique compliments written feedback. Speed and sound synthesis carried out in specimens from 10 HD patients use of the Classen-Demling sphincterotome allow the computer to 'talk' to the trainee, and (eight aganglionic, five transitional, and 10 and enables safe and efficient diagnostic and a record is maintained of each 'procedure' normoganglionic zones) and 18 age and site therapeutic examinations in technically performed. A multicentre prospective, ran- matched controls from other gastrointestinal difficult cases. domised trial of computer simulation versus surgery. standard training in flexible sigmoidoscopy is The distribution oftenascin was restricted to being undertaken in the United States in 1991. the basement membranes of smooth muscle, vasculature, around neuronal ganglia, and Guidewires in gastroenterology along nerve fibres in all the controls and 10 proximal normoganglionic HD specimens. Do clinical and biochemical features of J More intense tenascin immunofluorescence J H JACOMB-HOOD, R N M VAN SOMEREN, M cholestasis predict choledocholithiasis in BENSON, C P SWAIN (Departments of Radiology was observed in the smooth muscle basement patients with gail bladder stones? A prospec- membranes of the muscularis externa of eight and Gastroenterology, The Royal London tive ERCP study including the effects of Hospital, London) Gastroenterology units, aganglionic and five transitional zones of HD. sphincterotomy on natural history unlike other hospital departments, re-use Widespread distribution of fibronectin was guidewires. Kinks in guidewires may increase found in all the basement membranes as well as J P M ELLUL, M L WILKINSON, I MCCOLL, R H The expense of an admis- in the lamina propria and submucosa of all risk of perforation. DOWLING (Gastroenterology Unit and Depart- a would buy a lot of control and 10 normoganglionic HD sections. sion for perforation ment ofSurgery, Guy's Campus, United Medical We re-usage in More intense immunofluorescence with fibro- guidewires. analysed guidewire andDentalSchools, London) Although common 15 London hospitals, examined the frequency nectin was observed in all the layers of eight duct stones (CDS) cause more problems than in our own department aganglionic and five transitional zones of HD of kinks in guidewires gall bladder stones (GBS), the prevalence of the manoeuvres to cause specimens. and studied required CDS is too low to justify ERCP in all GBS in necropsy tissue. Our findings suggest that the extracellular perforation gastrointestinal patients. Therefore, we need to define a sub- Fifteen of 15 endoscopy units contacted in the matrix constitution is inappropriate in the group of GBS patients in whom routine ERCP http://gut.bmj.com/ London area re-used guidewires but most, affected bowel and may be responsible for the is justified. pathogenesis of HD. including our own, said that kinked guidewires We hypothesised that: (i) in patients with were discarded. We examined 30 reused guide- GBS, clinical and biochemical markers of two of 30 reused wires in our unit. Only cholestasis predict the presence ofCDS and (ii) guidewires had no kinks. Some 106 kinks were Measurement of gastric emptying in infants in those with CDS, sphincterotomy plus stone using applied potential tomography found in 28 of 30 guidewires, most frequently extraction improve the natural history. in first cm. In 160 studies of transendo- the 10 Selection criteria were as follows: sympto- scopic guidewires, penetration/perforation S NOUR, Y MANGNALL, A G JOHNSON, J A S

matic GBS plus: (i) history of cholestasis, (ii) on September 28, 2021 by guest. Protected copyright. using new and re-used guidewires and DICKSON (Subdepartment of Paediatric Surgery, back pain, and/or (iii) raised serum alkaline The Children's Hospital, Sheffield and Depart- necropsy tissue we showed: (1) It was difficult phosphatase, bilirubin, and GT. to normal necropsy ment of Surgery, The Royal Hallamshire perforate gastrointestinal When CDS were found, sphincterotomy and with unkinked (2) Tip Hospital, Sheffield) Applied potential tomo- tissue guidewires. stone extraction were performed and symp- kinked guidewires penetrated mucosa deeper graphy (APT) is a non-invasive, non- toms were reassessed within four weeks and at radiological method used to measure gastric and split tissue more than unkinked wires. (3) three month intervals. Mucosal penetration is easier than muscularis emptying by creating tomographic images of Of 96 patients with symptomatic GBS, 23 tissue resistivity which has been used success- propria: unexpectedly serosa offered greatest (24%) fulfilled the selection criteria and under- resistance to perforation (except small bowel). fully in adults. went ERCP. Of these, CDS were confirmed in APT was validated by gastric aspiration and (4) Some patient specimens proved resistant to six and suspected (ragged/patulous occurred with (25%) used to measure gastric emptying in infants perforation. (5) Perforation only papillae) in two (total 35%). In these six, held bowel. Perforation under 3 months old (30 term, 53 preterm, 49 endoscope against (6) predictive factors were: history of dark urine occurred easily using the wrong end of the infantile hypertrophic pyloric stenosis (IHPS), (sensitivity 83%, specificity 29%), jaundice and 12 with vomiting). guidewire. (7) Perforation of the bowel always (67%, 33%), back pain (67%, 27%), and raised caused kinking of the guidewires. In term infants, milk emptied more slowly serum alkaline phosphatase (17%, 13%). After than Dioralyte mean (SEM) 41-33 (3.09) We recommend careful inspection of re-used sphincterotomy, four of the six (67%) had (T½/2: a towards v 22-0 (1-84), p<0-001) and preterm infants guidewires and support trend dispos- persistent symptoms and underwent chole- able use. had similar results (44.45 (3.08) v 21-78 cystectomy; the other two remain well after 8-0 (2-31)). Gestation, postnatal age, birthweight, (4.2) months. investigation weight, volume, mode, and type In conclusion, clinical and biochemical of milk feed had no detectable influence on features of cholestasis predict CDS in up as a gastric emptying. The IHPS infants had little Computer graphics simulation training to 35% of GBS patients and justify ERCP. and colono- or no emptying before surgery but postopera- tool for flexible sigmoidoscopy Sphincterotomy and stone extraction prevent scopy tive studies at day two, four, and seven showed continuing symptoms only in a minority. gradual return to normal at seven days. between J BAILLIE, P JOWELL, H EVANGELOU, W BICKEL, Statistical significance was noted pre- P B COTTON (Duke University Medical Center, operative and all postoperative studies. Ten of Durham, North Carolina, USA) Basic endo- the 12 vomiting infants had normal findings, a scopy training requires the acquisition of hand- PAEDIATRICS result significantly different from the preopera- eye coordination skills. Until now these have tive investigations of the IHPS infants. been developed by performing procedures on APT is a safe and simple method which can patients; these procedures are often prolonged be used to study gastric emptying of infants at and uncomfortable. We have developed a Extraceliular matrix components, tenascin the bedside. A1234 British Society ofGastroenterology

Gastro-oesophageal reflux disease in cystic (60% (6.7)) than in the caecum (17% (2.8), fibrosis: evaluation with combined oesopha- COLORECTAL p<0-001). Platelet activating factor (PAF, 50 geal and gastric pH monitoring nM serosal, n=7-11 pairs) decreased Rt in distal colon (27% (3.3), p<0-001) and caecum Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from C A MCGIBNEY, P J BYRNE, P LAWLOR, B DENHAM, (14% (4), p=0-007), and the difference T P J HENNESSY (National Children's Hospital, Site of platelet activating factor action on between the segments was significant (p= Dublin and University Department ofSurgery, St colonic mucosa 0.026). Mannitol flux increased from 5-2 to 7-3 Jfames's Hospital, Dublin, Ireland) Prevalence pmol/cm2/hour in distal colon after 50 nmM rates for gastro-oesophageal reflux disease S P L TRAVIS, B CROTTY, D P JEWELL (Gastro- PAF and decreased from 5.2 to 3-4 in six paired (GORD) in cystic fibrosis (CF) vary according enterology Unit, The Radcliffe Infirmary, controls (p=0-013). In caecum, mannitol flux to selection criteria and diagnostic techniques Oxford) Serosal platelet activating factor (PAF) increased from 30.5 to 40.4 pmol/cm2/hour employed. To evaluate the true prevalence of decreases transepithelial resistance (R,) and after 5 nM PAF, and from 23-6 to 26-0 in 10 the disease and its possible aetiology, 24 hour stimulates anion transport in the distal rabbit paired controls (p=0-021). Both ionomycin dual channel (oesophageal and gastric) pH colon. The site of action within the mucosa has and PAF stimulated anion secretion in distal monitoring was carried out in an unselected been investigated using mucosal segments of colon, but not in caecum. group of children with CF: n=20; median age rabbit descending colon mounted in Ussing In conclusion, the basal permeability of the 10, range=4-15 years. chambers. Two human colonic epithelial cell rabbit caecum is greater than the distal colon, Seventeen of 20 children had abnormal lines (T-84 and HT-29) were also used to assess but the distal colon may be more susceptible to oesophageal acid profiles - only two of whom whether PAF has a direct action on epithelial agents that increase mucosal permeability. were symptomatic. Greater oesophageal acid cells. exposure times, including % time oesophageal Serosal PAF (5OnM) decreased R, by mean pH <4 and duration of reflux episodes, par- (SEM) 23 (3)% in mucosal segments (n= 11 ticularly in the supine position, were associated pairs, p<0-001), with a twofold increase in Total mesorectal excision and local recur- significantly with those who had severe mucosal:serosal 14C-mannitol flux (n=6 pairs, rence: a study of tumour spread in the bronchospasm (SB) and those with poor p=0-013) relative to paired controls. This is mesorectum distal to rectal cancer growth profiles (PGP); p<0-01, p<0.01 consistent with an increase in paracellular respectively. Intragastric pH, assessed for the conductance. Net ion transport was monitored N SCOTT, P JACKSON, P J FINAN (INTRODUCED BY supine period and at all pH intervals, was by changes in short circuit current (dSCC, FA/ M F DIXON) (Department of Pathology and significantly greater at the pH < 1 level, in the cm2, mean (SEM)). The two phases of the SCC Surgery, University of Leeds, Leeds) Local two subgroups. response to PAF were completely inhibited by recurrence is a common cause ofmorbidity and In conclusion, GORD is underestimated in indomethacin (10-6 M, serosal): dSCC mortality after 'curative' surgery for cancer cystic fibrosis. With dual channel pH monitor- control=30 (3) (phase 1) and 11 (5) (phase 2), of the rectum. Very low rates of recurrence ing, diagnosis of GORD can be made, risk compared with 0 (1) (p=0-001) and -6 (3) (p= are reported by Heald who practises total groups for GORD (those with severe broncho- 0.047) with indomethacin (n=4 pairs), respect- mesorectal excision (TME), suggesting that spasm or poor growth profiles) and exacerbat- ively. Tetrodotoxin (10-7 M, serosal), which incomplete excision of carcinoma in the distal ing factors such as suppine position can be inhibits neurally mediated changes in ion mesorectum is an important source of recur- ideptified. A combined aetiology - poor transport, had no effect on the SCC response to rent tumour. oesophageal clearance and gastric hypersecre- PAF (n= 8 pairs). We have examined the mesorectum distal to tion - is also suggested. Monolayers of T-84 cells mounted in Ussing 20 rectal cancers removed by AP or anterior chambers showed no change in SCC or Rt after resection combined with TME. The fixed 5 or 50OnM PAF, whether added to the serosal mesorectum from each case was sliced at 1 cm or mucosal surface (n=2-5 pairs). Chloride intervals and inspected for tumour deposits http://gut.bmj.com/ secretion in the T-84 monolayers could be and lymph nodes. Alternate slices were pro- shown by a rise in SCC after ionomycin (10-5 cessed whole for microscopic examination. M, n=5 pairs), which was inhibited by serosal We found distal spread of carcinoma in 20% frusemide (10-4 M, p<0-01), or ouabain (10-4 COLORECTAL of cases, extending between 1 and 3 cm from M, p<001). Receptors for PAF, investigated the luminal tumour. Spread was via mesorectal by binding studies with 3H-PAF, could not be lymphatics in three cases and by direct exten- detected on T-84 or HT-29 cells. sion in three.

are with an indirect on September 28, 2021 by guest. Protected copyright. Sexual dysfunction among women with The results consistent We conclude that local tumour spread action of PAF on the colonic epithelium, Crohn's disease: a hidden problem involving the distal mesorectum is not an probably through release of eicosanoids. The uncommon event in rectal cancer, and that in role of enteric nerves in the response of rabbit G MOODY, C S J PROBERT, E SRIVASTAVA, order to minimise local recurrence at least 3-5 colon to PAF needs further investigation. J RHODES, J F M MAYBERRY (Leicester General cm of mesorectum should be excised distal to Hospital, Leicester and University Hospital of the luminal cancer. Wales, Cardiff) The sexual problems of 50 women with Crohn's disease were investigated by structured interview and compared with age matched controls (mean ages 34-7 and 33-6 Regional differences in colonic permeability Serum cholesterol is increased in patients years respectively, t=0-92 NS). The patients with colorectal adenomas had been married significantly longer than S P L TRAVIS, D P JEWELL (Gastroenterology Unit, controls (t=2 1 p<0.005) and the divorce rate The Radcliffe Infirmary, Oxford) Segmental G I MANTZARIS, E PANAGOU, A HATZIS, G was similar (Fisher's p=0 09 NS). Patients had heterogeneity in electrolyte transport, motility, GEORGIOU, P KONTOGIANNIS, N RAPTIS, G significantly more sexual problems. The fre- and response to some secretagogues has been TRIANTAGHILLOU (Gastroenterology Clinic A, quency of intercourse was less in patients than shown in mammalian colon, but regional Evagelismos Hospital, Athens, Greece) Patients controls (mean 1-9 and 2-3 respectively t=4 1 differences in colonic permeability are poorly with hypercholesterolaemia may be at p<0-001). Indeed there was a significantly defined. increased risk for developing colorectal larger proportion (24%) of patients who had no Transepithelial resistance (R,) and 14C- adenomas and carcinomas. The aim of this intercourse at all (X2=8.3 p<0 005). The mannitol flux were used to assess colonic prospective study was to correlate fasting reasons for this included abdominal pain permeability in mucosal segments of rabbit serum cholesterol concentrations and colono- (24%), diarrhoea (20%), and fear of incontin- caecum and distal colon, mounted in Ussing scopic findings in 196 patients undergoing first ence (14%). Dyspareunia was more common in chambers. Basal R, (ohm.cm2, mean (SEM)) colonoscopy. Patients with colorectal cancer, patients (X2=6-5 p<0-01), this was irrespective was 124 (6) (n=30) in caecum and 403 (25) in inflammatory bowel disease, polyposis of the site of Crohn's disease (small bowel v distal colon (n=30, p<0-001). This was con- syndromes, and colorectal cancer in 1st controls X2-=63 p<0-01, large bowel v con- sistent with a greater mucosal:serosal mannitol degree relatives were excluded. A total of 101 trols X2=9.4 p<0-005 and large v small bowel flux (pmol/cm2/hour) in the caecum (27-0 (2.7), adenomas were found in 66 patients (42 men, X2=0.85 NS). Vaginal candidiasis was more n=20) than in the distal colon (5.4 (0.6), n= 24 women, mean age 63-6 years) whereas no common in patients ('2=58 p<0 02). 14), p<0-001). Regional responses to a calcium adenomas were found in 130 patients (87 men, Women with Crohn's disease experience ionophore and a lipid inflammatory mediator 43 women, mean age 65-1 years). Some 44 considerably more sexual problems than con- were then examined. Ionomycin (10-5 M adenomas were found in the rectum, 36 in the trols. They need sympathetic investigation and serosal, n=4-5 pairs) caused a greater decrease sigmoid, 12 in the right colon, and nine in other management. in Rt relative to paired controls in distal colon sites of the colon. Twenty seven of 101 (26.7%) British Society ofGastroenterology A1235 had a villous component. A significant differ- necessary in three cases. This was not associ- patients had a further laparotomy and end ence was found between cholesterol values in ated with recurrence. colostomies fashioned. Among the last 52 the adenoma and the control groups (mean The mean size of non-recurrent desmoids patients, three radiological leaks have also (SEM) 253.3 (6.0) mg/dl v 220 (4.8) mg/dl and recurrent desmoids were 7-2 cm and 12-2 occurred, none of which required any further Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from respectively, p<0 05). Considering cholesterol cm respectively (0O2>p>0 1, Mann-Whitney surgical management. Perioperative mortality values :200 mg/dl as normal, significantly U test). was 4% within the anterior resection group; more patients with adenomas than controls had Extra-abdominal desmoids can be success- one death was attributable to anastomotic serum cholesterol concentrations above upper fully treated surgically in the majority of cases. dehiscence and sepsis whereas the other three normal (55 of 66 (83%) v 81 of 130 (62%), Recurrences often remain static. Smaller deaths were due to unassociated medical pro- p<0-Ol). desmoids may be associated with lower recur- blems. Our results show similar leakage and These results support the hypothesis that rence rates. These findings suggest that aggres- mortality rates to published studies where hypercholesteroaemia is a risk factor for sive surgery can be curative in desmoid disease anterior resection is frequently performed with developing colorectal adenoma, a known pre- in FAP. Earlier diagnosis with intra-abdominal a defunctioning colostomy. cursor for colorectal carcinoma. desmoid disease before vascular encroachment These results indicate that the routine use of is advanced may similarly permit curative a defunctioning colostomy at anterior resection surgery. is not warranted.

Effects of selenium and vitamin E supple- mentation on colonic celi proliferation in patients with adenomatous polyps Palliative surgery for intra-abdominal High rectal pressure waves in rectal prolapse desmoid disease in familial adenomatous are associated with internal sphincter polyposis R J CAHILL, KR O'SULLIVAN, P M MATHIAS, inhibition B CORRIDAN, S BEATTI, C O'MORAIN (Sir Patrick Dun Research Laboratories, Trinity College K C R FARMER, R K S PHILLIPS (St Mark's R FAROUK, G S DUTHIE, A PRYDE, D C C BARTOLO, Medical School, St_James's Hospital, Dublin 8, Hospital, London andProfessorialSurgical Unit, R MILLER (Departments of Surgery and Gastro- Ireland) Cell kinetic studies have shown St Bartholomew's Hospital, London) Visceral intestinal Liver Service, Royal Infirmary of that patients with adenomatous polyps have and vascular encroachment of advanced intra- Edinburgh and Bristol Royal Infirmary) increased colonic crypt cell proliferation com- abdominal desmoid tumours have lead to the Recovery of continence frequently accom- pared with patients with no colonic disease. current policy ofreserving surgery for the relief panies rectopexy for prolapse. We propose that Recent studies suggest that dietary selenium of severe symptoms or complications. the prolapse causes reversible rectoanal and vitamin E, as antioxidants, may be protec- We have examined the course of 12 patients inhibition resulting in faecal incontinence. tive against colorectal cancer. (five males, seven females) with advanced To investigate this, 12 patients (10 female; This study assessed the effect of oral disease underoing 13 procedures for palliation age median (IQ) 72 (56-77) years) with com- selenium and oral vitamin E supplementation to determine whether this type of surgery is plete rectal prolapse (CRP), 15 patients (11 on colonic crypt cell proliferation in patients worthwhile. female; age 68 (46-72) years) with neurogenic with a history of adenomatous polyps. Nine- Small bowel obstruction, perforation, or faecal incontinence (FI), and 11 normal con- teen patients were recruited, 10 received 200 fistula were indications for surgery in nine trols (five female; age 36 (25-71) years) under- [ig of selenium daily and nine received 160 mg patients. Ten attempted palliative procedures went computerised ambulatory anorectal ofvitamin E daily. Supplementation continued included partial excision (n=7) and/or seg- manometry. for one month. Patients were and mental small bowel resection (n= 3) and/or The median resting anal pressure was CRP= colonoscoped enteric bypass (n=4). There were three intra- 26 cm.H20 ((9-60); p<0 002; Mann-Whitney biopsy specimens were taken before and after http://gut.bmj.com/ treatment. In vitro labelling for S phase colonic operative deaths from exsanguinating haemor- U test v normals*), FI=42 cm.H20 ((26-66); crypt cells was performed using the mono- rage. Median duration of symptom relief in p<0-01*) and normals=90 cm.H20 (60-130). clonal antibody to bromodeoxyuridine survivors was 2 years (range 2 months-13 Median resting rectal pressures were CRP= 15 immunohistochemical technique. The mean years). No patient experienced accelerated cm.H20 ((6-31); p>0.1*), FI=18 cm.H20 number of proliferating cells as a ratio percent growth of desmoid tissue. ((10-26); p>0-01*) and normals= 10 cm.H20 to total cells per crypt was analysed as the Three patients with ureteric obstruction had (5-16). The median number of anorectal labelling index percent (LI%). In this short uretero-ureterostomies. Obstruction has not sampling events per hour were CRP=7 ((6-9); reccurred with follow up of 3-8 years; two p<0.002*), FI=7 ((5-8); p<0.002*) and term study vitamin E supplementation did not on September 28, 2021 by guest. Protected copyright. decrease the LI% whereas selenium supple- patients experienced desmoid regression after normals= 5 (4-6). High pressure rectal waves mentation did so significantly (p<0.0001). postoperative medical treatment with sulindac. (median=110 cm.H20 (82-134); p<0-001 These results show that supplementation Palliative operations for desmoid disease in Rank Wilcoxon test) associated with sphincter with 200 Fg of selenium daily for one month FAP may be associated with a satisfactory inhibition, lasting 20-30 seconds were seen in decreases colonic crypt cell proliferation in period of relief of symptoms but surgery for 11 patients with CRP. The remaining patient in with adenomatous major intestinal involvement carries a 30% this group was continent. These were not seen patients polyps. mortality. in normals or FI. We suggest these high pressure rectal waves represent the prolapse entering the rectum resulting in rectoanal inhibition. The surgical management of desmoid Is anterior resection without a defunctioning disease in familial adenomatous polyposis colostomy safe? K C R FARMER, R K S PHILLIPS (St Mark's K MEALY, P BURKE, J HYLAND (Department of Faecal proteinase activity; raised values in Hospital, London andProfessorial Surgical Unit, Surgery, St Vincent's Hospital, Dublin, Ireland) patients with ulcerative colitis St Bartholomew's Hospital, London) Many The need to defunction the anastomosis at intra-abdominal desmoids are inoperable at the anterior resection remains controversial. As H J SAMSON, A ALLEN, J P PEARSON, W J time ofdiagnosis because ofvascular encroach- our policy has been not to perform a defunc- CUNLIFFE, M RHODES, J RHODES (Department of ment in the small bowel mesentery. tioning colostomy during anterior resections, Physiological Sciences, Medical School, New- We have examined the results of surgical we examined the outcome of our last 100 castle upon Tyne and Department of Gastro- management of extra-abdominal desmoids in consecutive anterior resections, all without a enterology, University Hospital of Wales, familial adenomatous polyposis (FAP) to covering colostomy. During this period, 20 Cardiff) Faeces contain substantial amounts of establish whether aggressive surgery leads to abdominoperineal resections (15%), five proteinase activity which data suggest is raised low recurrence rates. Hartman's procedures (4%), and two resec- in inflammatory bowel disease. Here we report Of 24 desmoids completely excised, 18 tions with coloanal anastomosis (2%) were also a detailed study on the proteinase activity of (75%) are free of recurrence (mean follow up performed. Sixty two patients were men and faecal extracts in healthy controls and patients 13-8 years, range: 2-40 years) although four the mean age was 62-5 (36-93). Thirty eight of with ulcerative colitis. patients required two excisions and one the resections were high and 62 low, defined as Proteinase activity was measured by free required three. Ofthe six patients with residual completely above or below the peritoneal amino group formation with succinyl albumin recurrent disease, four are static, one died from reflection. Clinical anastomotic dehiscence substrate, in supernatants prepared from faecal an intra-abdominal desmoid, and the other has occurred in six patients - all in the low anterior slurries (1:10 dilution of faeces in pH 7*5 insufficient follow up. resection group (6% of total group or 9-8% of phosphate buffer). Proteinase activity Prosthetic repair of the abdominal wall was the low anterior resection group). All of these measured in weekly samples over 10 weeks in A1236 British Society ofGastroenterology

healthy volunteers (expressed as mean (SEM) were higher in group A (maximum resting been demonstrated to be a weak stimulant of units of mmol N terminals/min/g dry weight) pressure 90 v 55 cm H20; maximum squeeze SST secretion in rats. In this study the role of was 3-51 (1.5) units (n=7) in menstruating pressure 110 v 95 cm H20 (NS)). Rectal circulating gastrin on fundus and antrum SST women. This was significantly higher than that sensation was comparable in both groups. concentrations during peptone stimulation was Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from in postmenopausal women (0-71 (0-19) units, Preoperative anal canal length, anorectal angle, studied with and without immunoneutralisa- n=4 p<0 05) but not significantly higher pelvic floor position, and perineal position as tion ofcirculating gastrin with a specific gastrin than that in men (2.72 (1-36) units, n=5). assessed by dynamic videoproctography at antiserum. Proteinase activity for ulcerative colitis patients rest, during maximum pelvic floor contraction, Twenty six conscious male wistar rats (mean (8-15 (1-18) units, n=69) was threefold greater and attempted defaecation did not differ body weight 291±2 g) equipped with gastric than that for the mean ofall healthy volunteers between the groups. However, patients who fistulas and jugular and portal vein cannulas, (2-61 (0 80) units, n= 16 p<0 005). did not deteriorate were shown to have a were studied. Rabbit anti-gastrin serum (60 These studies show (i) wide variation in significant increase in anal canal length, a jl) or normal rabbit serum (60 il) were faecal proteinase activity from different sub- reduced anorectal and less pelvic floor descent injected into the jugular vein 30 minutes before jects; (ii) faecal proteinase activity in men- after operation. Those whose quality of con- a 30 minute intragastric peptone stimulation struating women is significantly higher than tinence deteriorated with time had increasing period. At the end of the study period portal that of postmenopausal women; (iii) faecal perineal descent after operation suggesting that serum and fundic and antral tissue were proteinase activity is significantly higher in they continued to strain. collected for determination of free gastrin patients with ulcerative colitis than healthy These data suggest that persistent perineal binding sites or serum gastrin concentrations in subjects. Faecal proteinase activity has been descent and straining is associated with serum and tissue SST concentrations respect- shown to degrade the colonic mucus barrier deterioration after postanal repair. ively. Differences were tested for statistical and its elevation may be significant in the significance by Mann-Whitney U test for pathophysiology ofulcerative colitis. unpaired results. Peptone stimulated portal gastrin values from 384±59 to 572±62 pg/ml (n= 18; p<005), antrum and fundus SST concentra- Anal transition zone and the distribution of GASTRODUODENAL tions were respectively 892±136 ng/g and neuroendocrine cells in the anorectum 737±113 ng/g. After gastrin antiserum injection serum gastrin values were no longer G CHATTOPADY, M NEWBOLD, D KUMAR detectable while antrum and fundus SST con- (Department of Surgery, The Queen Elizabeth Inhibition of nocturnal gastric secretion is centrations were significantly (n=8; p<0.05) Hospital, Birmingham) The presence of neuro- unnecessary for ulcer healing: further con- higher than during control experiments endocrine cells (NEC) in the anorectum is well firmation (1688±192 ng/g and 1181±249 ng/g, documented. However, the density of the respectively). endocrine cells in different regions of the anal M LAZZARONI, F PARENTE, G BIANCHI PORRO In conclusion, immunoneutralisation of canal has not been determined. The aim ofthis (Gastrointestinal Unit, L Sacco Hospital, Milan, circulating gastrin resulted in increases in study was to determine the distribution of the Italy) Current ulcer treatment with H2 antral and fundus SST concentrations during NECs in different regions of anal canal receptors is based on the inhibition of peptone stimulation. These data suggest that epithelium. nocturnal gastric secretion. However, recent peptone stimulates directly or indirectly the We have studied anal canal epithelium in 14 reports have shown similar rates of healing of production of SST in both antrum and fundus blocks in seven specimens from patients under- duodenal ulcer (DU) regardless of whether the and indicate that circulating gastrin may going abdominoperineal resection. Sections H2 receptor antagonists were administered in inhibit the production of SST in antrum and were stained with haematoxylin and eosin and the morning or at night. The experience is, fundus. http://gut.bmj.com/ also by argyrophil technique. NECs were however, very limited. The aim of this study counted in the epithelium and glandular crypts was to compare the DU healing and analgesic in every 2 mm of visual field at an image effects of morning v single bedtime doses of magnification of 125. Anal transition zone famotidine. Two hundred patients with active (ATZ) was only present in three of seven DU were randomly assigned to a double blind Durations of complete focal mucosal specimens studied. None of the 14 blocks therapy with famotidine at 08.30 am (F om) ischaemia required to produce gastric ulcera- exhibited NECs in the squamous lined anal and 10 pm (F on) for up to eight weeks. tion at low acidity canal. However, melanocytes could be identi- The therapeutic efficacy parameters were on September 28, 2021 by guest. Protected copyright. fied in this region. ATZ, when present, con- endoscopic healing and antacid consumption. C PIASECKI, C THRASIVOULOU (INTRODUCTION tained a relatively small number ofNECs. The The patients were matched for age, sex, BY R POUNDER) (Department ofAnatomy, Royal density of NECs showed a gradual increase smoking, and drinking habits, previous com- Free Hospital School ofMedicine, London) We from the squamocolumnar junction upwards plications, duration ofdispeptic symptoms and recently showed that most mucosal arteries in for approximately 10 mm. Helicobacter pylori antral infection. One the guinea pig are end arteries. Here we used a These data show that the ATZ is absent in hundred and ninety six patients (98 in each snare to temporarily occlude single mucosal about 50-60% ofsubjects. Also, NECs are only group) completed the study. At four weeks, arteries repeatedly. Each vessels's end artery present in columnar lined anal canal. This may ulcers had healed in 60/98 (60%) in the F om status was ascertained by noting the reduction be important in operations on the anorectum as group and 64/99 (64%) in the F on group (p= in mucosal perfusion after occlusion. (A only columnar lined anal canal is likely to be 0-72, odds ratio 0-863, 0-464-1-604). At eight preliminary study, showed that 92 to 97% affected by peptidergic modulation. weeks the corresponding healing rates were 81 reduction indicated non-viability, whilst 50 and 87% respectively (p=0-30, odds ratio to 86% meant survival n=14; p=0-001.) 0-602, 0-24-1-45). The weekly consumption of Occlusions of increasing severity showed that antacids was similar in both groups. after four, five minute occlusions repeated at Cause of deteriorating continence after The equivalent efficacy of the morning and five minute intervals, circulation began not to postanal repair bedtime famotidine administration raises re-establish itself due to coagulation at the site further doubts as to the predominance of of occlusion (p=0 025 between one and 10 J ORTIZ, M OYA, T BACELAR, G CHATrAPADY, nocturnal gastric acidity in the pathogenesis of minute occlusions, n=20). Full thickness B PANAGAMURA, M R B KEIGHLEY (Department DU. necrosis in underlying mucosa was seen at of Surgery, Queen Elizabeth Hospital, sacrifice three hours later, but no necrosis in Birmingham) Twenty patients who initially surrounding areas with undisturbed circula- improved after postanal repair for neuropathic tion. pH of secretions during experiment was faecal incontinence were interviewed and 5.8 to 6 6. This acid will have caused necrosis assessed by anal physiology measurements. In Effect of circulating gastrin on antral and in areas rendered ischaemic. nine patients (group A) the quality of con- fundic somatostatin concentrations in rats It is known that contraction of muscle tinence deteriorated with follow up resulting in layers can completely obstruct perforating incontinence to solids: in the remaining 11 F J VAN DE BRUG, J B M J JANSEN, I J KUIJPERS, arteries. Thus, repeated obstructions of end patients the postoperative continence was C B H W LAMERS (Department ofGastroenterology- arteries, each lasting only five minutes are maintained (group B). The groups were similar Hepatology, University Hospital, Leiden, The likely to initiate ulceration via endothelial for age (53 years and 59 years), but duration of Netherlands) It has been suggested that coagulation mechanisms. Obstruction could incontinence was longer in group A: 36 months somatostatin (SST) acts as a paracrine inhibitor occur from vasospasm or spasm of muscularis v 24 months (NS). Preoperative anal pressures of gastrin release. In return, gastrin itself has mucosae. British Society ofGastroenterology A1237

Changes to mucus glycoproteins in gastric reduced at the ulcer edge (p<001) and These results confirm the idea that altera- cancer opposite wall (p<0 05), and at the scar of tions in the p53 gene affect tumour behaviour. healed DU (p<0 05). R L SIDEBOTHAM, N K DHIR, L HOUGH, (LATE) J This reduction in mucosal tPA may pre- Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from SCHRAGER (INTRODUCED BY J H BARON) (Depart- dispose patients to ulcer disease and suggests a ment of Surgery, Royal Postgraduate Medical vascular involvement in ulcer pathogenesis. Transforming growth factor (a expression in School, London and Department of Chemistry, normal gastric epithelium, intestinal meta- Kings College, London) Immunochemical and plasia, dysplasia, and gastric carcinoma lectin studies show that carbohydrate bio- synthesis of mucus glycoproteins is altered in Early gastric carcinoma: correlation of DNA MM NASIM, D M THOMAS, M R ALISON, M I FILIPE gastric carcinogenesis. To extend these obser- ploidy, tumour types and prognosis (Departments of Histopathology, Hammersmith vations we have compared the content and and Guy's Hospital, London) Transforming distribution of carbohydrate in mucus glyco- M J BRITO, M I FILIPE, J ROSA, G WILLIAMS, growth factor ax (TGFa) is a mitogenic and polypeptides (MG) from non-malignant H THOMPSON, G ORMEROD, J TETLEY, R MORRIS morphogenic polypeptide structurally related mucosa (16 specimens; individuals with benign (Departments ofHistopathology, Guy's Hospital, to epidermal growth factor (EGF) and sharing peptic ulcer, or disease free necropsies), and UMDS, London; IPO Lisbon; University of the same cell surface receptor. There is from uninvolved mucosa in patients with Wales; Central Hospital, Birmingham; ICR, evidence that over expression ofTGFa may be stomach cancer (14 surgical specimens). The Sutton; and Public Health, Guy's Hospital, directly involved in the series of pathological number of carbohydrate residues associated UMDS, London) DNA ploidy and S-phase events leading to malignancy. Using a mono- with representative core segments of equal fraction of 92 early gastric carcinomas were clonal antibody (GF10; Oncogene Science) and length decreased by 12% (p=0 02) in MG from studied by flow cytometry using formalin immunohistochemistry on formalin fixed, uninvolved mucosa. Also, carbohydrate was fixed, paraffin embedded material. The paraffin embedded tissue sections we have distributed differently in MG from uninvolved tumours were classified according to Kodama: assessed the expression of TGFa in normal mucosa. Numbers of carbohydrate chains (0- 36 small mucosal (Mucosa (M)-26; submucosal gastric mucosa, in precancerous gastric lesions, elimination analyses) declined from a mean of (SM)-10); 33 super mucosal (M-15; SM-18); and in cancer of the human stomach. TGFa 448 to 332 chains per 1000 amino acid residues 8 Pen A and 15 Pen B. immunoreactivity was predominantly cyto- (p<0001), with significant decreases of Fifty seven tumours were diploid (62%) and plasmic with occasional membrane staining. serine and threonine in the polypeptide core. 35 aneuploid (38%). No significant difference Expression was observed within the differen- Structural units per carbohydrate chain in ploidy was found between mucosal and tiated compartment of the normal mucosa (n= increased from a mean of 5.7 to 6-9 (p=0 005), submucosal tumours or between those with 20) (that is, in surface epithelium and in cells with significant increases in ratios of N-acetyl and without lymph node metastases. However, deep in the gastric gland, particularly parietal glucosamine or galactose to N-acetyl the majority (63%) of the Pen A tumours, cells). Overexpression of TGFu was seen in galactosamine. considered as carrying a worse prognosis, were 70% of mucosal samples exhibiting intestinal Comparative analyses of(1) MG from disease aneuploid. metaplasia (n= 38); in 60% of dysplastic free antrum and duodenum (necropsies) and DNA ploidy was significantly different epithelium (n= 10) and in 60% of gastric (2) MG from non-malignant antrum before and between small mucosal (M,SM) and super- carcinomas (n=24). Interestingly, while 93% after structural modification by partial 1B- mucosal (M,SM) types (p=0-01). Signet ring of intestinal type carcinomas showed strong elimination suggested that the above changes tumours (n=20) were predominantly diploid immunoreactivity, only 30% of diffuse type are attributable to biosynthesis of intestinal (88.5%) compared with 55 8% in the tubular carcinomas were similarly stained. mucus glycoproteins within metaplastic type (n= 52) (p=0 002). We suggest that TGFa may be involved in mucosa, or decreased biosynthesis of neutral Preliminary data offollow up (between three the pathogenesis of gastrointestinal metaplasia relative to sulphated mucus glycoproteins by months and eight years) in 81 patients show and neoplasia as well as in the maintenance of http://gut.bmj.com/ gastric mucus cells. three local recurrences and four related deaths, the integrity of the normal gastric mucosa. all in cases belonging to super or Pen A subtypes. In conclusion, aneuploidy was more often seen in tumours known to be associated with Effect of acid suppression and gender on Mucosal tissue-type plasminogen activator worse prognosis (tubular, Pen A and super gastric emptying using applied potential activity in peptic ulcer disease types). Thus DNA ploidy may play a role in tomography preoperative assessment of tumour behaviour. on September 28, 2021 by guest. Protected copyright. M A WODZINSKI, K D BARDHAN, P COOPER, J W WRIGHT, D F EVANS (Department ofSurgery, J T REILLY, F E PRESTON (Northern General Queen's Medical Centre, Nottingham and GI Hospital, Sheffield, District General Hospital, Science Research Unit, The Royal London Rotherham, and Royal Hallamshire Hospital, Mutant p53 expression in gastric carcinomas Hospital Medical College, London) Gastric Sheffield) Impaired fibrinolytic activity (FA) is a prognostic indicator emptying (GE) can be measured using applied may lead to occlusion of the rich vasculature of potential tomography (APT), an impedance the gastroduodenal mucosa causing tissue M I FILIPE, M H MARTIN, D P LANE (Department of imaging technique, but acid secretion is necrosis and ulcer formation. To examine this, Histopathology, UMDS Guy's Hospital, London thought to alter the resistivity of the stomach FA was studied in patients with benign gastric and Cancer Research Campaign, The University, and modify the results obtained. Acid inhibi- ulcer (GU) (n=6), active duodenal ulcer (DU) Dundee) Abnormalities of the p53 gene have tion is therefore recommended. (n=9), healed DU (n=6), and normal controls been identified in many malignancies with We have used APT to measure GE of 500 ml (n= 11). Multiple biopsy specimens were taken reports of aberration in over half of colorectal, Oxo and 500 ml porridge in 16 volunteers (10 at gastroscopy from the stomach and duo- lung, breast, and hepatocellular carcinomas. male, six female) without acid suppression and denum, and in GU and DU cases from ulcer The normal gene acts as a recessive oncogene after 400 mg cimetidine and 40 mg omeprazole. edge or scar (DU) and opposite wall. Tissue while mutations change the apparent function Interpretable results were obtained without type plasminogen activator (tPA) activity was to that of a dominant oncogene. acid suppression and there was no difference in assayed spectrophotometrically in biopsy In this investigation a three layered immuno- liquid emptying between different treatments specimen homogenates and expressed as mIU/ peroxidase technique was applied to routinely or between men and women. In the female mg protein. The mean (range) tPA in controls fixed and paraffin embedded tissue sections porridge group GE was significantly acceler- was: stomach 2970 (2030-3840) and duodenum from 125 gastric carcinomas, using a polyclonal ated after omeprazole compared with controls 4320 (3120-6260). In GU, tPA at ulcer edge anti-p53 antibody. (83 mean (SEM) (8.6) minutes (50% emptying) was 1220 (220-2820) and opposite wall 2210 It was found that 57% of these carcinomas v 148 (14.6) minutes, p=0 001). There was no (1310-4440). In active DU, tPA at ulcer edge expressed the mutant p53 protein (positive difference in solid emptying in men. was 2170 (730-5130) and opposite wall 3170 nuclear staining). Survival table analysis The men emptied significantly faster than (1760- 5120), while in healed DU, tPA at the showed a strong association between p53 status women in both the control (100 3 (8.4) minutes scar was 3200 (1760-5180) and opposite wall of the tumour and patient survival time after v 148 (11.9) minutes, p=0.01) and the cimeti- 3810(1390-6090). diagnosis (p<0 02-Mantel-Cox test). The five dine groups (74.7 (7.2) minutes v 130 (18.3) These results show control duodenal mucosa year survival of patients with mutant express- minutes, p=0 03). The omeprazole group did has higher tPA than gastric mucosa (p<001). ing tumours was 24%, compared to 56% with not reach significance. Compared with controls, in GU tPA is notice- non-mutant expressing tumours (the median In conclusion, acid suppression accelerated ably reduced at the ulcer edge (p<0.01) and survival times were 13, and 102 months GE of solids in women. Acid suppression is opposite wall (p<005); in active DU tPA is respectively). unnecessary when using APT to measure A1238 British Society ofGastroenterology gastric emptying. A gender difference in solid inhibited phase 1 (by 36%, p=0-014) and antigens is uncommon in foveolar, surface and gastric emptying has been shown. completely inhibited phase 2 (p=0.005). The gland cells.

chloride channel blocker diphenylamine Using proliferating cell nuclear antigen Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from carboxylic acid (2x 10-4 M, mucosal, n=5 (PCNA) as a marker ofcellular proliferation we pairs), had a similar effect (phase 1 p=0-016; used a computer aided image analysis system to phase 2 p=0-012). No phase 2 response was quantify objectively gastric body immuno- CELL BIOLOGY apparent with bilateral chloride free Ringer's staining. Two groups of 10 male Wistar rats (n=8 pairs), although there was no change in were treated with omeprazole 400 ltmol/kg/ the ,hase 1 response. Serosal DIDS (10` and day for 30 days. Controls received vehicle. All 10- M, n=4 pairs), an anion exchange data are expressed as median (range) and Proliferative assessment by computer aided inhibitor, increased baseline SCC, but did not compared by Mann-Whitney U test. image analysis - a new technique for consistently alter either phase of the response Mean serum gastrin in omeprazole treated objective quantification of gastrointestinal to PAF. rats rose 10 fold from 75 fmol/ml (19-170 fmol/ proliferation In conclusion, PAF has a specific effect on ml) to 750 fmol/ml (450-850 fmol/ml) ion transport in the colonic mucosa, which (p<0-001). Oxyntic mucosal thickness was M R GRAY, J A HUNT, R W IRLAM, D F WILLIAMS, becomes desensitised after initial exposure. increased 15% from 4-9 mm (4-42-5- 11 mm) to A N KINGSNORTH (Departments of Surgery Stimulation of chloride secretion by PAF 5.69 mm (54-7 05 mm) (p<0-001). Mucous and Bioengineering, University of Liverpool) seems to explain partially phase 1 of the SCC neck cell labelling increased 33% from 500/ Immunocytochemistry can selectively stain response and to be totally responsible for mm2 (200-600/mm2) to 670/mm2 (488-820/ proliferating cells using monoclonal anti- phase 2. mm2) (p<0*001). Gland cell labelling increased bodies. PC10 is a monoclonal antibody specific 300% from 62/mm2 (36-88/mm2) to 200/mm2 for proliferating cell nuclear antigen. Objective (144-377/mm2) (p<0 001). quantification of immunostaining, which The number of cells expressing PCNA is reflects proliferative rate, is difficult as staining Vertical and longitudinal gradients of trans- appreciably increased in the mucosa of the intensity varies between sections, large forming growth factor a expression indicate hypergastrinaemic rat. Increased expression of numbers of cells need to be counted, and selective differentiation programmes in the proliferation associated antigens is more complete blinding of observers is impossible rat colon noticeable in the oxyntic gland compartment because the histology is coincidentally than in the mucous neck cells. apparent. D J AHNEN, G ELIA, N A WRIGHT (Imperial Cancer We have used a technique coupling PCIO Research FundHistopathology Unit, London and immunostaining with computer aided image Denver Department of Veterans Affairs Medical analysis. Staining of conventionally fixed Center, Denver, Colorado, USA) All the neces- SV40 T antigen allows resumption of celi tissues was carried out with PC10 using a DAB sary components oftransforming growth factor division in the small intestinal vUllus of chromogen without counterstain. Slides were a (TGFa) mediated autocrine or paracrine transgenic mice read at x 200 magnification by a Hitatchi solid growth regulation are present in the colon state CCD camera and fed to an image analysis (TGFa and its receptor are synthesised by R A GOODLAD, C Y LEE, G SCHMIDT, S HARRIS, E S system of a Joyce-loebl mini-magiscan. Images colonocytes, colonocyte proliferation is stimu- REES, S HAUFT, J GORDON, D J AHNEN, N A were manipulated using Genius software to lated by TGFa). We have used immunoperoxi- WRIGHT (Imperial Cancer Research Fund Histo- adjust for staining intensity, subtract back- dase immunohistochemistry to examine the pathology Unit, London; Department ofGenetics, ground, and artifact and separate overlapping expression of TGFa in normal, preneoplastic, Glaxo, Greenford, Middlesex; and Washington 1mm2 were School cells. Twenty fields scanned for and neoplastic rat colonic mucosa. Appreciable University of Medicine, St Louis, http://gut.bmj.com/ each data point. vertical (maximal expression in upper crypt, Missouri, USA) An unique pattern ofprolifera- Repeated scanning of the same field of none at the crypt base) and longitudinal tion is reported from the intestine of a strain of PCNA stained gastric body absolutely repro- (maximal expression in the caecum; a progres- transgenic mice. The SV40 large T antigen was duced nuclear counts without variation. sive decrease distally) gradients of TGFct linked to an intestinal fatty acid binding Multiple counts on the saime section compiled immunoreactivity are present in the colon. protein (IFABP) promoter and the antigen was from 20 observations showed a standard Refeeding of48 hour fasted animals resulted in expressed in the villi of the more proximal deviation of 2-7%. This represents an unprece- increased proliferation in all colonic segments regions of the small intestine. Mice were dented degree of reproducibility which can be and decreased TGFa immunoreactivity in the injected with tritiated thymidine and on September 28, 2021 by guest. Protected copyright. applied to assess objectively the proliferating distal colon (no change seen in the proximal). vincristine. While the pattern of proliferation fraction in histological sections. Dimethylhydrazine treatment (25 mg/kg in the crypts was conventional, proliferating weekly for up to 16 weeks) resulted in increased cells were observed on the villi, especially in the proliferation but no apparent alteration in duodenum, where the labelling index (LI) for TGFa immunoreactivity in the non-neoplastic the villus was 11-6±0-26%. The LI of the Colonic ion transport and platelet activating mucosa (at 10, 15, or 20 weeks). DHM induced crypts was 33-4+4-3%. The density of label- factor tumours consistently had less TGFa expression ling (grain count) however, was significantly than the adjacent mucosa. (p=0O007) less (28-3±1-7 v 52 5±4.55). Few S PL TRAVIS, D P JEWELL (Gastroenterology Unit, These observations show that TGFa expres- labelled cells were seen in the basal part of the The Radcliffe Infirmary, Oxford) Distal colonic sion is regulated both during differentiation villi or in the top fifth, most activity was in the ion transport exhibits a biphasic response to and regionally within the colon; they suggest mid zones of the villus. Cell division was also platelet activating factor (PAF), a lipid that in the distal colon TGFa is secreted in shown by positive proliferating cell nuclear mediator derived from membrane phospho- response to (and thus could mediate) a physio- antigen (PCNA) immunostaining, and by the lipid. The ionic basis of the increase in short logic stimulus to proliferation (refeeding); that presence ofmitotic figures. circuit current (SCC) has been investigated in TGFa expression is decreased in neoplastic Thus, the IFABP linked expression of the isolated mucosal segments ofrabbit descending mucosa; and that the altered proliferation of large T antigen produced unique patterns of colon, mounted in Ussing chambers, and preneoplastic colonic mucosa may not be intestinal epithelial cell proliferation; in which bathed in Ringer's solution containing 0-25% mediated by major alterations in TGFa cells on the villus recommenced proliferation. albumin. Serosal PAF (50 nM) stimulated an expression. These mice offer a powerful model system for initial rise in SCC (mean (SEM) [tA/cm2 of 28 assessing the effects of proliferation on (3) (phase 1, maximal at 2-3 minutes), then epithelial cell differentiation programs that are remained 12 (6) above baseline SCC (phase 2, normally expressed during translocation along maximal at 15-30 minutes), compared with Localisation and quantification of gastric the crypt to villus axis. changes in controls of 0 (1) and -5 (2) respec- body proliferative compartment in omepra- tively (n= 11 pairs, p=0-012). The PAF meta- zole treated rats using computer aided image bolite, Iyso-PAF, had no effect and both analysis phases were inhibited by a PAF analogue Calretinin and calbindin-D28k immuno- inhibitor. Restimulation with PAF 30 minutes M R GRAY, J A HUNT, R W IRLAM, D F WILLIAMS, reactivity in human gastrointestinal nerves after initial exposure did not alter the SCC. A N KINGSNORTH (Departments ofSurgery, Bio- and endocrine cells Mucosal amiloride (10-4 M, n=7 pairs) engineering, and Physiology, University ofLiver- abolished baseline SCC, but did not alter either pool) The proliferative compartment of the J R F WALTERS, A E BISHOP, P FACER, D E M phase of the response to PAF. Serosal oxyntic mucosa is confined to the mucous neck LAWSON, J H ROGERS, J M POLAK (Departments of frusemide (1.0-4 M, n=6 pairs) partially cells. Expression of proliferation associated Medicine and Histochemistry, Royal Post- British Society ofGastroenterology A1239 graduateMedical School, London; Department of A method for the isolation ofviable epithelial ing the existence of other cytokines capable of Biochemistry, King Saud University, Riyadh, cells from human colonic biopsy specimens modifying growth responses after partial hepatectomy. Saudi Arabia; and the Physiology Laboratory, Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from Cambridge) Calretinin and calbindin-D28k are J MEENAN, C O'FARRELLY, P W N KEELING, two high affinity Ca2' binding proteins having C FEIGHERY, D G WEIR (Departments ofClinical 58% sequence homology. They have been Medicine and Immunology, Trinity College, localised to the cytoplasm of different specific Dublin) Attempts to isolate human colonic NEOPLASIA central neurones including those involved in epithelial cells from endoscopic biopsy speci- neurodegenerative disorders. We have studied mens have been hampered by low yields, the immunocytochemical distribution of these lamina propria contamination, and the toxicity two proteins in the human gastrointestinal of mucolytic agents. We describe a method for An autocrine role for gastin/cholecystokinin tract. the isolation oflarge numbers ofepithelial cells peptides in pancreatic tumour cell growth Unlike calretinin, calbindin immuno- with high viability and long survival. reactivity was found in some endocrine Four biopsy specimens were taken at 30 cm M BLACKMORE, B H HIRST (Department ofPhysio- cells including gastric enterochromaffin like from each of 14 normal colons. Specimens were logical Sciences, Medical School, Newcastle upon and D cells, and small intestinal S cells. put directly into 1 mM Dithiothreitol in Ca21/ Tyne) A role for gastrin as a growth factor in In both the submucosal and myenteric ganglia, MG21 free Hank's buffered salt solution (CMF gastric and colonic tumour cells has been a proportion of nerve cell bodies were HBSS) supplemented with 0 3% bovine serum proposed. We have examined the effects immunoreactive for calbindin (in duodenum, albumin (BSA), penicillin, and streptomycin. of gastrin/cholecystokinin (CCK) receptor 13% in submucosal and 37% in myenteric) After four hours at room temperature the antagonists on the growth of the AR4-2J rat or calretinin (24% and 23% respectively), or biopsy specimens were transferred into 1 mM pancreatic tumour cell line. The antagonists both proteins (8% and 4%). In nerve pro- EDTA with CMF HBSS/0-3% BSA and in- proglumide (IC50=1 3x 10-3 M), benzotript cesses, calretinin was generally more abundant cubated for one hour at 37°C on an inclined (IC50=4x10-4 M), CR1409 (IC50=1 5x10-5 than calbindin, particularly around blood rotating table. The supernatant was washed in M), and CR1505 (IC50=2.5x10-5 M) com- vessels. Calretinin was localised to submucosal CMF HBSS at 75 g for 10 minutes. Assessment peted with '25IhG17-1 for binding to gastrin ganglion cells which were also immunoreactive of cell numbers and viability were performed receptors on AR4-2J cells and inhibited AR4- for vasoactive intestinal peptide, neuropeptide using ethidium bromide/acrodine orange label- 2J proliferation over a four day period (as Y, galanin, or substance P and to myenteric ling in a haemocytometer. Cell identification assessed by the MTT and neutral red assays) at cells with substance P immunoreactivity. was by FACscan analysis using the monoclonal similar concentrations. The inhibition ofAR4- Calbindin was colocalised with fewer pep- antibodies DAKO-Ber-EP4, CD3, and CD19. 2J proliferation by these gastrin/CCK receptor tides, being found with vasoactive intestinal Median cell count was 2-1 million (1(0- antagonists could be partially reversed by peptide or galanin in submucosal cells. Dis- 8.35). Mean viability 85% (70-100). FACscan addition of 5 x 10 ` M gastrin two hours before crete neuronal localisation for both proteins analysis showed 94% epithelial cells with 6% the antagonists. Anti-gastrin immunoglobulins was found by eight weeks of fetal develop- intraepithelial lymphocytes. Samples with low also inhibited AR4-2J proliferation when com- ment. viabilities were incubated in a nylon wool pared with a control immunoglobulin prepara- Both calretinin and calbindin may prove column. This procedure increased cell viability tion. useful in determining Ca2+ mediated actions in counts by 6-14%. After 72 hours in RPMI These results are consistent with an autocrine the enteric neuroendocrine system in normal (10% fetal calf serum) at 4°C mean viable count growth factor role for gastrin in AR4-2J rat and diseased states. was 1-64 million. pancreatic tumour cells and imply that gastrin/ In summary, this method allows for the CCK antagonists may be useful in therapy ofviable cells from against gastrin receptor positive tumours. In harvesting oflarge numbers http://gut.bmj.com/ human colonic biopsy specimens. It introduces contrast to the other gastrin/CCK antagonists a novel method for increasing the percentage investigated, much greater concentrations of Induction of adhesion molecultes by viability of cell suspensions and broadens the L365,260 were required to inhibit AR4-2J cell cytokines (interferon y, interleukin I, tumour use of the FACscan. proliferation (IC50=6-5 x 10-5 M) as compared necrosis factor a, interleukin 6) on the with its ability to compete with '25IhG17-1 surface of HT 29 and i407 cells binding (IC50=2x 10-8 M). The anti-tumour activity of L365,260 is, therefore, unlikely to S L BLOOM, D P JEWELL (INTRODUCED BY D P be mediated by gastrin receptors. JEWELL) (Gastroenterotogy Unit, The Radcliffe Effects of recombinant cytokines on EGF- on September 28, 2021 by guest. Protected copyright. Infinnary, Oxford) In view of evidence suggest- induced hepatocyte DNA synthesis ing a role for adhesion molecule ligand pairs in immune recognition and cellular cytotoxicity, A C WOODMAN, H J F HODGSON (Gastroenterology we examined basal and cytokine induced Unit, Royal Postgraduate Medical School, Oestrogen and progesterone receptors in expression of eight adhesion molecules on London) The coordinated control of liver colorectal cancer tissue and five colon cancer intestinal epithelial cells using a panel of eight regeneration requires both growth stimulation cell lines monoclonal antibodies. and inhibition. We have shown that condi- Cells from a colonic (HT 29) and an tioned medium from hepatic non-parenchymal C W HENDRICKSE, C E JONES, I A DONOVAN, embryonic small intestinal cell line (i407) were cells (NPC) after 70% partial hepatectomy J P NEOPTOLEMOS, P R BAKER (Department of exposed to cytokines at various doses, stained inhibits epidermal growth factor (EGF) Surgery, Clinical Research Block, University at times from seven hours to seven days later induced hepatocyte proliferation in vitro. To of Birmingham and Dudley Road Hospital, with monoclonal antibodies, and then analysed investigate the potential role of Kupffer and Birmingham) The finding of oestrogen receptor by FACscan. endothelial cell derived factors, we have (ER) mRNA in colonic tumour and normal Results showed: (1) A high constitutive assessed the effects ofrecombinant interleukin mucosa is consistent with a role for sex steroids expression of class 1 antigen with some I a (ILla) IL1fi, TNF, and TGFO, on EGF in colorectal cancer. Using EIA we quantified further induction by interferon y (IFNy) but induced DNA synthesis, assessed by [3H]- ER and progesterone receptors (PgR) in 17 not by interleukin I (ILI), tumour necrosis thymidine incorporation into primary adult rat carcinomas (11 F; 6 M) with paired normal factor a (TNFa) or interleukin 6. (2) Consti- hepatocyte cultures. mucosa in 10 and in five colon cancer cell lines. tutive expression of ICAM 1 varied from 5 to IL1P (0.001-1 ng/ml) and TGFI31 (0-001- ER and PgR (fmol/mg) were detected in 15 and 30% with a trend to higher expression on HT 1 ng/ml) considerably reduced the response to 17 cancers respectively: median (range) ER 1-3 29 cells than i407 cells. (3) ICAM 1 is induced 10 ng/ml EGF (15644 (991) dpm/20000 (0-113), PgR 3.9 (0-3-10-2). Values in paired on both cell lines by IFNy and TNFa but hepatocytes for ILIB, 7531 (311) for TGFP1, cancer and mucosa tissue were not significantly not by IL6 or ILl, unlike other tissues. cf 38 758 (2943) for EGF alone; mean (SEM), different but ER correlated with PgR in cancer (4) CD66, a member of the CEA family, is n=8), whereas TNF (0.01-1 ng/ml) and ILla tissue (tau=0 551, p<0005) and ER in expressed on HT 29 cells but not i407 cells (0-01-10 ng/ml) had no effect. The specificity mucosa (tau=0-533, p<005). These relations and is not induced by cytokines. (5) Other of the IL1 P and TGFf31 effects were confirmed exhibited significant linear log correlations (r= adhesion molecules (ELAM, VCAM) were not by abrogation of inhibition by the respective 0-678, p<0 003; r=0-669, p<0 03 respect- expressed. specific neutralising antibodies (anti-ILIl, ively). Mucosal PgR did not correlate with These results support the hypothesis that 2 [ig/ml; anti-TGFf3i, 250 ng/ml). cancer PgR nor ER in mucosa. ER 3-5 (1-2- inducable ICAM 1 expression may play a role Neither antibody however inhibited the 11-8) and PgR 24-3 (9 1-63.2) were detected in in leukocyte-epithelial cell interaction in the effect of NPC conditioned medium on hepato- all cell lines (HT-29, LS-174T, SW-620, gut. cyte DNA synthesis induced by EGF, indicat- LOVO, Colo-320). In all cell lines PgR was A1240 British Society ofGastroenterology greater than ER; oestradiol (10 nM) did not tumour bearing MNNG-treated hamsters occasions after injection of 3-5 ml radiolabelled seem to down regulate ER or induce PgR. (1-18, 0.641-42, p=0 003). These differences (40 MBq 131-I) lipiodol, with CT overlay This study indicates that oestrogen receptors were largely accounted for by a reduction of images to confirm site and size of metastases. are a feature of colonic mucosa and that in cholic acid derivatives (3a, 12a-, 3a, 70i, 120-, Significant activity was detected only in the Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from carcinomas they seem to regulate PgR suggest- and 12-oxo, 3a-hydroxy-5¶ cholanoic acids; liver and lungs. ing oestrogen responsiveness. p<001 at least). The beneficial tumour:liver ratios suggest The metabolic abnormalities of FBA in that a potentially tumouricidal dose of targeted tumour bearing animals supports a previous radiotherapy may be safely administered suggestion that human tumours absorb more to selected patients with colorectal liver Secretion of pancreatic secretory trypsin deoxycholic acid and may partly explain incon- metastases. inhibitor by Capan 1 pancreatic tumour cell sistent findings of FBA in case control studies line is not influenced by cholecystokinin or of CRC. This is therefore a suitable model to gastrin investigate this further. Survival after surgery for colorectal cancer is R J PLAYFORD, P H DEPREZ, J WOODBURN, as good in district general hospital practice as J CALAM (Department ofMedicine, Rayal Post- in teaching hospital practice graduate Medical School, London) Secretion of Bile and DNA damage in an animal model pancreatic secretory trypsin inhibitor (PSTI) R D KINGSTON, S WALSH, J JEACOCK (INTRO- by normal pancreatic acinar cells is increased A D SPIGELMAN, D K SCATES, S VENITT, RK S DUCED BY R D KINGSTON) (Department ofClinical by cholecystokinin (CCK) or gastrin. PSTI has PHILLIPS (St Mark's Hospital, Royal Marsden Studies, Trafford General Hospital, Manchester) also been shown to be a growth factor for the rat Hospital andStMary's Hospital, London) Many We aimed to analyse the short and long term pancreatic AR4-2J tumour cell line. We deter- carcinogens react with individual DNA bases results of treating patients with colorectal mined if the human pancreatic tumours Capan to form DNA adducts. Adduct values are cancer admitted to teaching and non-teaching 1, MiaPaCa-2, and PANC-1 secreted PSTI and greater in the duodenum of patients with hospitals. ifthis secretion was under the influence ofCCK familial adenomatous polyposis (FAP) than in A total of 567 patients admitted to district or gastrin. the duodenum of controls, and are greater in and teaching hospitals in the north west were About 5 x104 cells of the various cell lines the duodenum than in the stomach of FAP entered to the study. Altogether 295 patients were incubated in 10 ml of normal growth patients. This pattern of adducts mirrors the were treated in a teaching hospital and 272 medium (RPMI 1640), containing 10% fetal distribution of foregut tumours in FAP patients in a district hospital. Demographic, calf serum, for 72 hours. In addition to these patients. Possible explanations include pre and postoperative details and pathological samples, the various cell lines were incubated delivery of carcinogens to mucosa by bile or data were entered onto a computer compatible under identical conditions but with the defective DNA repair mechanisms. form and input to a mainframe computer. addition of CCK or gastrin in the medium at a We collected gall bladder bile at surgery Patients were followed up annually for a mini- final concentration of 10-6 to 10-12 M. At the from FAP and control patients and gave it by mum of five years and patients' status and any end of the 72 hours the medium was collected gavage to Fischer rats (FAP bile, 6 rats, control evidence of recurrence were recorded on a and assayed for PSTI by radioimmunoassay bile, 7; dose: 0.5 ml bile/100 g body weight, follow up form. The data were analysed using using antiserum T4. thrice weekly for nine weeks). Adduct values SPSSX and survival analysis performed on the Medium from Capan 1 cells which had not were measured in small bowel DNA by 32p- follow up data using program PIL on BMDP had CCK or gastrin added contained 170 nglml postlabelling/chromatography. package. of PSTI-like immunoreactivity. Similar con- DNA adduct values (adducts/109 nucleo- There was no significant difference in the centrations of PSTI-LI (140-190 ng/ml) were tides) were significantly higher in rats treated number ofoperative mortalities. The incidence also found in the medium from Capan 1 cells with FAP bile than in rats treated with control of postoperative complications was similar. http://gut.bmj.com/ which also contained CCK or gastrin. No bile (FAP bile: median 23-5, range 12-40; Patients' hospital stay was slightly longer in PSTI-LI was found in the media from control bile: median 10 range 2-27; p=0 004). non-teaching hospitals and there was a greater MiaPaCa2 and PANC-1 cell lines±CCK or These results suggest that the distribution of proportion of more elderly patients. There was gastrin. adducts found in the FAP foregut is a result of no difference in the survival rates. In conclusion, Capan 1 cell lines secrete large carcinogens in bile rather than of defective In conclusion, complication rates, operative amounts ofPSTI, but unlike normal pancreatic DNA repair. This is consistent with the idea deaths, and five year survival rates in the two acinar cells, the secretion is autonomous and that bile is important in foregut tumour study groups were similar. not influenced by CCK or gastrin. development in patients with FAP. on September 28, 2021 by guest. Protected copyright.

Perioperative heparin - a successful adjuvant Increased secondary faecal bile acids in a Lipiodol as a vehicle for targeted internal to surgery in colorectal cancer new hamster model ofcolorectal cancer radiotherapy in liver metastases R D KINGSTON, J W L FIELDING, M PALMER C H E IMRAY, T MINOURA, A DAVIS, S RADLEY, R E HIND, S PERRING, J FLEMMING, V BATrY, (INTRODUCED BY RD KINGSTON) (Department of K M NEWBOLD, M LAVELLE-JONES, A M LAWSON, S BIRCH, I TAYLOR (University Department of Clinical Studies, Trafford General Hospital, P R BAKER, J P NEOPTOLEMOS (Departments of Surgery and Departments of Nuclear Medicine Manchester) We aimed to evaluate the effect on Surgery, University of Birmingham and Dudley and Radiology, Southampton General Hospital, survival of perioperative subcutaneous heparin Road Hospital, Birmingham, and Clinical Southampton) Lipiodol, an iodinated derivative when given as an adjuvant to surgery. Research Centre, Middlesex) We argued that the of poppy seed oil, has been shown to be Extensive data were collected from a pro- hamster would be a more suitable model for selectively retained within primary liver spective study of 601 patients with colorectal studying faecal bile acids (FBA) and colorectal tumours. We have studied the biodistribution cancer undergoing curative surgery. Patients cancer (CRC) since its hepatic metabolism is of lipiodol in patients with colorectal hepatic were followed up every three months until much closer to humans than that of other metastases after hepatic arterial injection, and death, or for five years. Time to recurrence and rodents. assessed dosimetry for possible treatment using duration ofsurvival was calculated from date of Four groups of 12 hamsters had twice weekly 13II labelled lipiodol. resection. intrarectal instillation of a locally acting Fifteen patients underwent selective angio- Factors influencing survival were identified carcinogen, MNNG at doses of 1, 4, and 8 mg graphy before treatment for colorectal hepatic by multiple regression analysis using Cox's Kg- 1 or vehicle (DMSO) alone for four weeks. metastases, when 3 ml radiolabelled (2 MBq method. Survival and event free curves were Sacrifice at 15-40 weeks showed CRC in all 131-I) lipiodol were injected. At subsequent calculated using the Kaplan-Meier method. animals at the higher MNNG doses and one laparotomy biopsy specimens of tumour and Results suggest a small but significant adenoma at the lowest. FBA analysis was normal liver were taken and subjected to well improvement in survival at five years or equiva- performed by gas chromatography mass counting, allowing tumour:liver ratios to be lently a reduction in the risk of death. This spectrometry and showed 9 FBA in the con- evaluated. Two patients had low ratios in large effect as apparent is not explained by demons- trols (no tumours) which were remarkably (> 10 cm) metastases. Of the remainder, at 24 trable differences between heparin and non- similar to the FBA profile of 10 healthy hours the median ratio was 1-5 (1 1-2.5; n=6), heparin patients in the distribution of known humans. The median (range) FBA ([tmols.g-' at three to nine days (n=8) the ratio was 2 75 prognostic factors. Adjustment of these factors faeces) of cancer bearing animals (0.52, 0 46- (1-64). slightly increased the apparent magnitude of 0 84) was lower than controls (1-08, 0-95-1-65, Ten patients have undergone whole body the beneficial effect. p=0-008; two tailed Mann-Whitney U) or non- counting and SPECT imaging on at least two The magnitude of survival and event free British Society ofGastroenterology A1241 survival is similar to that reported by Moertel scintigraphy. The rats were studied at 2, 4, 6, increased arachidonate (20:4, n-6) and after one year of adjuvant cytotoxic therapy. and 21 days after intraportal administration of docosahexaenoate 22:6, n-3) values in In conclusion, perioperative subcutaneous viable or dead Walker cells. colorectal cancer but is controversial. There- heparin has a small but significant effect on five Micrometastases were present histologically fore, we assessed fatty acid profiles in both Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from year survival. four days after inoculation. The hepatic perfu- phospholipid and neutral lipid fractions sion index (HPI) at four days (51-8+±168) was separated by column chromatography in the significantly greater (p<0-0001 Mann- cancer tissue, transition zone mucosa, (3 cm Whitney U test) than in controls (33-78+± 1-77). from the cancer), and normal mucosa in 10 Do smokers and drinkers have an increased The increase in the HPI four days after inocula- patients with colorectal cancer. Analysis was by risk of colorectal adenomas? tion was accompanied by a significant increase capillary gas liquid chromatography (pmol in the mean renal transit time (3-95± 118 sensitivity). R F A LOGAN, J LITTLE, I D TURNER, J D seconds) compared with controls (2-28±0-48 The results were as follows: (1) Total mean HARDCASTLE (University Departments of Public seconds). Conversely, the renal blood flow was (SD) mg/g wet wt fatty acids in cancer tissue, Health and Epidemiology, and Surgery, significantly reduced in animals with micro- 5-96 (0.56) was significantly increased com- University Hospital, Nottingham) Recent metastases (7-32±2-81 ml/minute) compared pared with both transition zone mucosa, 4-76 studies have suggested that smoking and with controls (14-02±3-42 ml/minute). These (1-15) and mucosa, 4-32 (0.97) (both p<0 05, alcohol intake are important and possibly inter- changes in HPI, renal transit time, and renal AOVO). (2) Total fatty acids in the neutral active risk factors for developing colorectal blood flow were maintained at six and 21 days lipid fraction were reduced in cancer tissue, adenomas (Kikendall et al, Gastroenterology after inoculations. 1-68 (0.6) compared with transition zone 1989, Cope et al, Gut 1991). We have enquired These results suggest that renal blood flow is mucosa, 4.7 (3.7) and normal mucosa, 3-87 about these factors in subjects participating in a reduced during the early stages of growth and (2 09) (both p<0 05). (3) In the phospholipid large trial of faecal occult blood (FOB) screen- development ofhepatic tumour. Furthermore, fraction of cancer tissue, 20:4, n-6 was 0.57 ing for colorectal neoplasia. FOB +ve adenoma since renograms with a flow phase are techni- (0-18) and 22:6, n-3 was 0-13 (0.06), both cases (n= 147), FOB -ve age and sex matched cally easier to perform in man than estimations higher than in normal mucosa, 0.44 (0- 16) and controls (n= 153) and FOB +ve patients with- of the HPI, determination of renal blood flow 0.07 (0.04) respectively (both p<0 05); values out adenomas (n= 176) were interviewed at may be of value in the detection of occult liver in the transition zone were intermediate for home two years after investigation. Uncon- metastases. 20:4, n-6, 0-51 (0-14) and for 22:6, n-3, 0.09 ditional logistic regression has been used to (0.05) (NS). estimate relative risks (RR) and 95% con- In conclusion: (1) This study supports pre- fidence intervals (CI) adjusted for age, sex, and vious findings of increased 20:4, n-6 and 22:6, social class. Urgent admission and subsequent surgery n-3 in colorectal cancer. (2) The increase was The RR ofcolonic adenoma for ever smokers for colorectal cancer has a poor prognosis? most noticeable in the phospholipid fraction and those smoking 15+/day respectively (never and is of relevance since this fraction is meta- smokers RR=1) were 0-78 (0-5-1-3) and 0-82 R D KINGSTON, J JEACOCK, S WALSH (INTRO- bolically labile, indicating active roles for 20:4, (0-3-2-1) for FOB -ve controls and 0-87 (0 5- DUCED BY RD KINGSTON) (Department ofClinical n-6, the precursor of putative tumour promot- 1-5) and 1.1 (04-2 8) for FOB +ve controls Studies, Trafford General Hospital, Manchester) ing prostaglandins and 22:6, n-3 suggestive of with no association evident between total pack We aimed to analyse the short and long term reduced lipid peroxidation implicated in cancer years of smoking and risk of adenoma. Based results of treating patients with colorectal growth. on current consumption there was a weak cancer admitted as emergencies. association between adenomas and total alcohol A total of 733 patients admitted to one intake: using FOB -ve controls the RR of district general hospital for colorectal cancer adenoma was 1-3 (0 7-2.5), 1-4 (0.7-2.8), and were included in this study. Three main groups http://gut.bmj.com/ 1-7 (0 8-3.6) for increasing tertiles of alcohol were identified, patients admitted electively, intake compared to non-drinkers (RR= 1) patients admitted as emergencies and operated NUTRITION (Trend X2=2-1) and using FOB +ve controls on within 24 hours ('urgent'), and other the RR being 1-2 (06-2.2), 1-6 (0 8-3.2), and emergency patients as defined by admitting 1-8 (0.9-3.8) (Trend X2=3.2). Adenoma pre- surgeon. Demographic, pre- and postoperative valence was not related to the type of alcohol details were recorded on a standard form for Zinc sulphate supplementation modifies the consumed. computer input and analysed on a mainframe long chain fatty acid metabolism in patients For both exposures, relations did not vary using a standard statistical package (SPSSX). with Crohn's disease on September 28, 2021 by guest. Protected copyright. significantly when analysed by adenoma size, Data included symptoms, surgical and patho- site or histological type. These results indicate logical data, complications, and follow up A BELLUZZI, C BRIGNOLA, M CAMPIERI, L that alcohol intake, but not smoking, is weakly information. Survival analyses on the follow up PIRONI, P GIONCHETTI, F RIZZELLO, P IANNONE, associated with the prevalence ofasymptomatic data was performed using program P1L of the M MIGLIOLI, L BARBARA (INTRODUCED BY C J colorectal adenomas. These results are consist- BMDP package. HAWKEY) (Clinica Medica e Gastroenterologia, ent with recent metaanalyses of smoking and Patients admitted as emergencies had a Farmacologia Clinica e Terapia Medica, alcohol in colorectal cancer which show only a significantly poorer performance status. The Policlinico S Orsola, University of Bologna, weak relation between cancer and alcohol operative mortality in the urgent group was Italy) Patients suffering from Crohn's disease intake and no relation with smoking. more comparable with the elective group; 11% (CD) can develop a zinc deficient status. Since and 9% respectively. The other emergency zinc is involved in long chain fatty acid (FA) group showed an operative mortality rate of metabolism, we used gas chromatography to 21%. Five year survival for the elective patients investigate the FA profile of red blood cell Do alterations in renal haemodynamics was 31% compared with 18% for both phospholipid (RBC-P) before and after supple- predict the presence of hepatic micro- emergency groups. mentation with zinc sulphate (ZnSO4) (200 mg metastases? In conclusion urgent surgery for emergency daily for six weeks) in 15 patients with CD in cases does not necessarily result in a higher clinical remission. D M NOTT, J YATES, J S GRIME, S A JENKINS operative mortality or wound infection rate, RBC-P FA profile was measured since it is (University Department ofSurgery, Royal Liver- but has a lower probability of curative resec- less susceptive than the plasma P FA profile, pool Hospital, Liverpool) We have previously tion. Five year survival for all emergency to short term, meal related changes. We shown that the increase in the hepatic perfusion patients was worse than for elective patients. investigated the same FA profile in 15 healthy index (HPI) in the presence of overt tumour in controls (HC) without any alteration of zinc the rat is accompanied by a significant decrease metabolism. in renal blood flow. Since there is little informa- The plasma zinc values were 72 (8) [tg% tion on the temporal relation between altera- Fatty acids in the phospholipid and neutral before the treatment and increased to 114 (10) tions in renal blood flow and the growth and lipid fractions in colorectal cancer [tg% afterwards (arith.mean (SEM)). Before development of hepatic tumour, we have supplementation the two main saturated FAs, undertaken such a study in the rat. Male Fisher C W HENDRIKSE, S RADLEY, A DAVIS, I DONOVAN, palmitic and stearic (16:0, 18:0) and oleic rats received an intraportal injection of P BAKER, M KEIGHLEY, J P NEOPTOLEMOS (18:1) were significantly increased (p<0-001) 1 6x107 Walker cells. Control animals were (Department ofSurgery, Clinical Research Block, while linoleic (18:2), arachidonic (20:4), and dosed with the same number of dead cells. University of Birmingham and Dudley Road w3 (20:5, 22:5, 22:6) FAs were reduced Renal and hepatic blood flow were measured by Hospital, Birmingham) Previous experimental (p<0-001) in CD patients compared with HC. the microsphere method and by dynamic studies in the rat and man have suggested Treatment with ZnSO4 abolished these differ- A1242 Bnrtish Society ofGastroenterology ences so that there were no significant differ- polyurethane 2). Some 84% of patients needed gelatine capsules, as an isotonic glucose electro- ences between CD patients and HC at the end only one silastic catheter for the duration of lyte (280 mOsm/kg, 30 kcal) solution and as a of the treatment. their feed, and 90% needed only one poly- glucose polymer (Maxijul) solution (280 In conclusion, patients with CD have zinc urethane catheter. mOsm/kg, 200 kcal). The daily stomal output Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from deficiency which affects FA metabolism and This study confirms the value of fine bore remained constant for each patient during the membrane composition. catheters for the delivery of full intravenous four test periods but varied between patients nutrition via a peripheral vein. The poly- from 0U60 to 2-84 kg (daily intestinal fluid urethane catheter used was shown to have a balance 074-2-61 kg). Without a salt supple- superior lifespan compared with the silastic ment, three of the patients lost more sodium Role of felbinac gel in the prophylaxis of one. from the stoma than they took in by mouth peripheral parenteral nutrition related (-25, -94, -101 mmol/day) and the mean thrombophlebitis sodium balance for all six subjects was - 16 mmol (range -101 to 79) daily. Extra salt was J S PAYNE-JAMES, S KAPADIA, M J BRAY, S RANA, Comparison of radiological and endoscopic absorbed with each form of supplement D MCSWIGGAN, D B A SILK (Department ofGastro- methods for percutaneous gastrostomy and (p<005); no patient was in negative balance enterology and Nutrition, Central Middlesex jejunostomy with the glucose electrolyte solution (mean 96, Hospital, London) The aetiology of peripheral range 0 to 226 mmol), one patient with the vein thrombophlebitis (PVT) associated with N SATHANANTHAN, J MURFITT, H FAWCETT, glucose polymer solution (mean 96, range -25 peripheral parenteral nutrition (PPN) is multi- N VAN SOMEREN, J POWELL-TUCK, P SWAIN to 164 mmol) and two with the salt capsules factorial. This study determined whether (Departments ofRadiology, Gastroenterology and (mean 66, range - 8 to 145 mmol). Two local application of a non-steroidal anti- Clinical Nutrition, The Royal London Hospital, patients vomited with the salt capsules. There inflammatory gel (felbinac 3% - Traxam, London) We compared radiological (R) was only a small increase in energy absorption Lederle Laboratories, UK) could reduce the with endoscopic (E) methods of placing per- (mean 115 kcal) with the glucose polymer incidence or delay onset of thrombophlebitis. cutaneous gastrostomy (PG) and jejunostomy solution as compared with the glucose- Fifty healthy volunteers had a peripheral (PJ) in 24 patients requiring long term enteral electrolyte solution. vein cannula (Vasculon 2, Viggo AB, Sweden) feeding unable to tolerate nasogastric tubes. A sipped glucose electrolyte solution seems inserted in each forearm for five days. Both Twelve patients had radiologically placed to be the optimal mode of sodium replacement forearms were randomised to receive either (a) gastrostomies/jejunostomies (Fresenius PG in patients with a high output jejunostomy. twice daily application of 1 g of active gel (A), n=2, Cook: Carey-Alzate-Coons PJ n= 10) and or (b) 1 g of inactive placebo gel (I) on skin 14 patients had attempted endoscopic overlying the cannula. Twelve hourly observa- gastrostomies/jejunostomies (Fresenius n=6, tions of cannula sites were made recording the Abbott n=2, Caluso n=2, Bard n=2) PG n= Ultrafine bore catheters for intravenous development of (a) redness, (b) swelling, (c) 10, PJ n=2). (R) PG/PJ were placed in 12 of 12. nutrition - peripheral venous nutrition with- hardness (each measured as <2 cm or >2 cm in (E) PG/PJ were placed in 12 of 14. Poor out thrombophlebitis? length), and (d) presence or absence of pain. transillumination prevented endoscopic place- Three sites were examined: (i) site of insertion ment in two which were subsequently placed M MADAN, D j ALEXANDER, M j MCMAHON of cannula, (ii) mid-point of cannula, (iii) by a combined radiological and endoscopic (University Department of Surgery, General cannula tip. Cannulas were removed ifany sign method. Radiological PG/J diagnoses: CVA Infirmary, Leeds) Intravenous nutrition (IVN) was >2 cm in length at any site or if pain was (6), head/neck/oesophageal cancer (4) short can be administered via a peripheral vein but excessive. bowel (1), scleroderma (1); endoscopic PG/J the high incidence of thrombophlebitis limits (A) had significantly fewer episodes of pain diagnoses: CVA (9), motor neurone disease (3). the osmolality of the feed. Osmolality can be at the insertion site (p<005). (A) had signifi- No major complications occurred with either reduced by limiting the amino acid or glucose http://gut.bmj.com/ cantly fewer cannulas with signs >2 cm at each technique. Mean duration of percutaneous content but this also reduces the nutritional time point. For (A) and (I) respectively at each feeding was (R) 7/12 (2-17), (E) 5/12 (0-13). value of the feed. In this study a feed providing time point these values were (% cannulas); 12 Minor complications were initially observed 1800 kcal per day (800 kcal as glucose), with an hours, 0 v 2; 24 hours, 4 v 10; 36 hours, 6 v 10; more commonly (p<0t05) with radiological osmolality of 1250 mmol/kg was administered 48 hours, 10 v 20; 60 hours, 12 v 22; 72 hours, methods: mild peristomal infection 5 (R), through a peripheral vein via a standard 20 G 15 v 28; 84 hours, 17 v 30; 96 hours, 20 v 34; 2 (E), late tube migration 4 (R), 0 (E), but were Teflon cannula or a fine bore (23 G) silicone 108 hours, 22 v 45 (p<0 05). reduced by antibiotics and earlier tube change. catheter.

We conclude that topical felbinac gel may Diarrhoea was commoner with PJ than PG, Patients in both groups were fed for a median on September 28, 2021 by guest. Protected copyright. have a significant role in reducing the incidence 3 (R), 1 (E) (NS). offive days. The incidence ofthrombophlebitis and delaying onset of the changes of PVT, and We conclude that radiological placement is was significantly higher in the Teflon group, thus may be appropriate for the prophylaxis of effective and safe and allows long term enteral 2-04 episodes v 0.07 episodes per patient. The thrombophlebitis in patients receiving PPN. feeding in patients with head/neck/oesophageal median life span of a silicone cannula was cancer in whom peroral endoscopic gastro- significantly higher than that of a Teflon stomy placement was not possible and was cannula, 128 v 36 hours. technically superior to endoscopic methods for These results suggest that a low incidence of Fine bore silastic and polyurethane catheters placing jejunal tubes. Combined radiological thrombophlebitis can be obtained by the use of for the peripheral venous delivery of intra- and endoscopy allowed placement in patients fine bore silicone catheters thus avoiding the venous nutrition: a randomised study where endoscopy alone failed to indicate safe need for central venous access in most patients apposition of stomach and abdominal wall. who require IVN. N J EVERIIT, M MADAN, D J ALEXANDER, M J Radiological methods extend the usefulness of McMAHON (University Department of Surgery, less invasive percutaneous feeding techniques. The General Infirmary, Leeds) A randomised prospective study compared the efficacy of Effects of osmolality and heparin with hydro- silastic (23 g Epicutaneo Cava Katheter - cortisone on thrombophlebitis in peripheral Vygon), and polyurethane (22 g Secalon Oral salt supplements to compensate for intravenous nutrition Hydrocath - Viggo) fine bore catheters for jejunostomy losses: comparison of sodium the delivery of intravenous nutrition via a chloride capsules, glucose electrolyte M MADAN, D J ALEXANDER, M J MCMAHON peripheral vein. Fifty patients were fed for a solution, and glucose polymer electrolyte (University Department of Surgery, General median duration of nine days with a 2-5 l feed solution Infirmary, Leeds) Intravenous nutrition, (osmolality 1250 mOsm/l, 13 g nitrogen, 1800 administered via the central route, incurs both kcal). Twenty five patients received a silastic J M D NIGHTINGALE, J E LENNARD-JONES, E R the risks of catheter insertion and catheter catheter and 25 a polyurethane catheter. WALKER, M J G FARTHING (St Mark's Hospital, related sepsis. Peripheral intravenous nutrition The rate of thrombophlebitis was similar in London) Six patients with jejunostomies and is associated with a high risk of thrombo- each group (silastic 0-018 episodes/patient day residual jejunal lengths of 105 to 250 cm took phlebitis. We investigated the incidence of v polyurethane 0-015 episodes/patient day). the same food and water each day for eight thrombophlebitis caused by the infusion of (a) Silastic catheters had a shorter median lifespan study days. In random order, three methods of a ready to use mixture with an osmolality of (silastic 172 hours v polyurethane 201 hours, salt replacement were tested, each over 48 1130 mOsm/kg, (b) this mixture plus heparin p=003 Mann-Whitney). Silastic catheters hours, against a period without added salt. and hydrocortisone, and (c) a feed, with an were more prone to occlusion without the During the three test periods the patients took osmolality of 700 mOsm/kg, with heparin and development of thrombophlebitis (silastic 9 v 120 mmol of sodium chloride daily, as salt in hydrocortisone to investigate the effects of the British Society ofGastroenterology A1243 addition ofheparin and hydrocortisone and the The incidence and aetiology of acute pan- Reversal of transforming growth factor a effect of osmolality on the incidence of creatitis (AP) has been examined in a mixed stimulated pancreatic cancer growth in vivo thrombophlebitis. urban and suburban population of 1.5 million by somatostatin analogue RC-160 The addition ofheparin (500 U/1) and hydro- served by eight hospitals in the North West Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from cortisone (5 mg/l) to feed (a) significantly Thames Health Region over a period of 38 P KAPUR, N M DAVIES, J GILLESPIE, A V SCHALLY, reduced the daily risk of thrombophlebitis months. The criteria for AP were amylase P J GUILLOU, G J POSTON (Academic Surgical from 0 43 to 0-11 episodes per patient, p<0 05. >1200 iu/l with abdominal pain and signs of Unit, St Mary's Hospital, London; Department A reduction in the osmolality resulted in a peritoneal irritation, or computed tomogram, ofMedicine, Tulane University and VA Medical further fall in the incidence of thrombo- laparotomy, or necropsy evidence of Center, New Orleans, USA) Transforming phlebitis to 0.04 episodes per patient with a pancreatitis. Some 487 cases have been growth factor a (TGFa) is an autocrine growth significant increase in the median life span of documented, giving an overall incidence of factor for pancreatic cancer in vitro and is the cannula from 26 hours to 86 hours, p<0 02. AP of 103 per million population per trophic to these tumours when administered in These results show that a low incidence of year. vivo. The purpose of this study was to examine thrombophlebitis can be achieved by the use of In 376 cases (77%) an aetiology was found. the effect of the somatostatin analogue RC-160 a low osmolality feed with heparin and hydro- Alcohol and gall stones (155 (32%) and 140 on TGFa stimulated pancreatic cancer growth cortisone thus the peripheral route is ideal for (29%) respectively) accounted for most of the in vivo. short term intravenous nutritional support. cases. Iatrogenic causes accounted for 9% Some 24 male Syrian golden hamsters were (ERCP (20); postoperative (18), and drugs (6)). inoculated in both cheek pouches with H2T Other causes included trauma (3), viral (2), and hamster ductal pancreatic cancer cells and then tumour (2). Indications for ERCP were; biliary equally randomised to four equal groups: stones (12), pancreatic investigation (5), and saline; RC-160 (100 pg/kg); TGFa (10 pg/kg), PANCREAS non-stone causes ofobstructive jaundice (3). In and RC-160+TGFa each at the same dosage as five patients the pancreatobiliary system was the other regimens. Treatment was given three never visualised and a further five patients had times a day for seven weeks by intraperitoneal diagnostic imaging alone. Only 10 had a injection. Tumours were measured weekly; at Effect ofpancreastatin on insulin release and therapeutic procedure performed, which was sacrifice tumours were weighed and analysed secretin stimulated exocrine pancreatic successful in seven. for DNA content. secretion AP following ERCP had a significant From week four until sacrifice TGFa signifi- morbidity in that median hospital stay was 11 cantly promoted tumour growth, while RC- J V SCHONFELD, M K MULLER, M RUNZI, H days (range 4-101). 160, alone and in combination with TGFa, GOEBELL (INTRODUCED BY D WINGATE) (Depart- significantly inhibited tumours (p<0-01 by two ment ofGastroenterology, Medical Clinic, Essen, way ANOVA). At sacrifice, tumour weights Germany) Pancreastatin, a 49-amino-acid followed this trend, as did tumour DNA con- C-terminal amidated peptide, was isolated tents which were significantly different. from porcine pancreas in 1986. It has since Natural and unnatural course of chronic In conclusion, RC-160 abolishes the growth been shown to inhibit insulin release and pancreatitis based on a long term follow up of stimulatory effect of TGFFa on pancreatic cholecystokinin (CCK) stimulated exocrine a medical surgical series cancer in vivo, in addition to having a direct pancreatic secretion in vivo. There are, how- tumour inhibitory role. These findings support ever, very few studies on pancreastatin and I VANTINI, G CAVALLINI, G ANGELINI, B VAONA, the therapeutic use of somatostatin analogues secretin stimulated exocrine pancreatic secre- G TALAMINI, M FILIPPINI, G CATAUDELLA, A in the treatment of patients with pancreatic tion, and these have rendered contradictory FIORETTA, G CASTELLANI, P BOVO, M GUIOTTO cancer. results. (Ist Clinica Medica e Div Gastroenterologia http://gut.bmj.com/ The arterially perfused isolated pancreas of in Valeggio sIM Universita di Verona, Italy) male Wistar rats was used. The exocrine During 1970-89, 637 patients with chronic pancreas was stimulated submaximally by pancreatitis (CP) (549 M; 88 F) were observed. secretin (100 pg/ml), insulin release was stimu- The data were submitted to statistical analysis Photodynamic therapy on the pancreas and lated by glucose (16-8 mM). The pancreatic (also for censored data). In 81-7% the aetiology adjacent normal tissues in the hamster duct was cannulated by a polyethylene tube. was alcoholic (M>F, p<0-001), in 2-2% The volume of and amylase content in 10 familial, in 5-7% idiopathic (F>M, p<0-001) P J 0 NUUTINEN, P T CHATLANI, J BEDWELL, A J

minute samples of pancreatic juice and insulin and in 6-3% there were other causes. Some 542 MACROBERT, S G BOWN (National Medical Laser on September 28, 2021 by guest. Protected copyright. concentration in 60 second samples of the CP patients were followed for 11±6-5 years. Centre, The Rayne Institute, University College, effluent were measured. Then 20 pM and 200 Cumulative survival was 76% at 15 years. London) Photodynamic therapy (PDT) is based pM pancreastatin were tested in two subse- Causes of death (known in 91 of 119) were on the interaction of light with a previously quent 10 minute intervals (n=8; p

nglkg/hour) and measurement of on September 28, 2021 by guest. Protected copyright. isotopic have shown a cephalic phase ofgastric secretion about their symptoms, preoperatively and one incorporation into secreted enzymes, we have year afterwards. examined pancreatic function in 10 HPN and intestinal flows in response to a food discussion (FD) stimulus. To investigate the The most common preoperative symptoms patients with severe SBS before and after seven were colic fat of SMS effect of cephalic stimulation on pancreatic (89%), intolerance (80%), and days (100 ig tds) exocrine function in the presence and absence nausea (73%). Eleven patients (15%) had The results (mean (SEM)) showed that in jaundice. Postoperatively abdominal discom- comparison with 10 matched sub- of gastric acid, the (FD) stimulus was applied healthy to six normal volunteers (mean age: 26- 1 years fort (39%) and bloating (37%) were the most jects, trypsin, amylase, and lipase SEC was common symptoms. One third of the patients higher (355 (55) Eq/hour v 190 (21) p<0 range: 24-29). Subjects were pretreated with 05), ranitidine 1200 mg (in four divided doses) or developed at least one new symptom. SYN was faster (45 (15) v 71 (15) minutes), but The symptoms best cured by the operation PTO was similar (43 v 36 identical placebo, in random order, 24 hours (20) (10)%/hour) before study. Subjects were intubated with a were jaundice (100%), colic (73%), and fat in SBS patients. After treatment, SYN and intolerance (72%). Overall, 66% graded their SEC returned to normal, but PTO was reduced multilumen tube, and duodenal contents were aspirated continuously with aliquots collected residual symptoms as none or mild, and 77% to 23 (5)%/hour indicating an increase in said they were either completely or well satis- enzyme pool size to 1022 at 15 minute intervals for three hours before (260) Eq (normal and three hours after FD. There was no fied. 528 (48)). In summary, therefore, at least The results that stomal losses significant difference in pancreatic enzyme three suggest high secretion between the 30 minute FD period quarters of patients were satisfied with chole- are associated with adaptational pancreatic cystectomy. Postoperative symptoms were hyperplasia and that SMS results in and the preceding 30 minute basal period in the therapy placebo study: trypsin 63-9 (18-6) IU/1 v 88-4 usually mild and often arose de novo postopera- stagnation of the large intracellular enzyme tively. We thus conclude that despite these Our results the use of SMS (19-3); chymotrypsin 569 (166) IU/1 v 772 pool. support (259); amylase 94458 (37645) IU/1 v 116375 symptoms a high degree of satisfaction can be in suppressing pancreatic secretory losses, achieved. but raise concern over its use in acute pan- (38437); lipase 10535 (2971) IU/1 v 23195 creatitis where intracellular enzyme activation (13 498) or in the ranitidine study: trypsin 704 (for example, crinophagia) of the enlarged (271) v 300 (110); chymotrypsin 2746 (746) v pool of enzymes may exacerbate disease 1330(242); amylase 505916(109 459) v 444 791 activity. (112 249); lipase 77 444 (22 762) v 29 979 (8026) Financial consequences offailing to diagnose (values mean (SEM)). laxative induced diarrhoea These data show that there is no cephalic phase of pancreatic enzyme secretion either in A DUNCAN, A CAMERON, A J MORRIS, M S the presence or in the absence of gastric acid, STEWART, W G BRYDON, R I RUSSELL (Gastro- and do not confirm the previous findings in enterology Unit and Institute of Biochemistry, Influence of growth factors on growth of humans, which used sham feeding as the Royal Infirmary, Glasgow and GI Laboratory, pancreatic cancer in vitro stimulus. Western General Hospital, Edinburgh) Laxative British Society ofGastroenterology A1245 induced diarrhoea (LID) is a well documented chloride channels on both sides. In addition, cause of diarrhoea which is readily diagnosed GASTRIC DISEASE the basolateral membrane appears to contain a by urine analysis. We introduced such a service Na/Cl- symport sensitive to bumetanide to biochemists and gastroenterologists in the (l0-4 M). Like the antrum, the fundic pd was Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from West and Central belt of Scotland. The preval- F237 also shown to be dependent on apical sodium ence of LID was measured in two populations Study of 24 hour gastric pH profiles in channels and basal Na+/H+ exchangers. and found to be present in 2 of 49 (4%) new patients with major upper gastrointestinal However, diphenylamine-2-carboxylate and patients referred to gastroenterology with diar- bleeding from peptic ulcers bumetanide had no effect on pd when added to rhoea, and in 2 of 10 (20%) patients who were either mucosal or serosal side. already being investigated for diarrhoea of A KALABAKAS, R N M VAN SOMEREN, M J BENSON, Our findings indicate distinct regional differ- unknown origin. Of seven patients with LID G R DAVIES, D F EVANS, C P SWAIN (Academic ences in ionic transport processes responsible the diagnosis was suspected in five (71%). This Department of Gastroenterology, The Royal for mucosal pd in the rat stomach. finding and the low rate ofrequests made ofthe London Hospital, London) Gastric acidity might laxative analysis service (eight per annum) be important in the pathogenesis of further suggest that clinical awareness of this diagnosis bleeding from peptic ulcers. Drugs suppress- is low. We have calculated the cost offailing to ing gastric acidity appear to have failed to alter Peptic ulcer disease: the north/south divide? make the diagnosis in eight LID patients outcome following peptic ulcer bleeding. It 1983-1985 diagnosed in Glasgow and Edinburgh GI units, remains probable that available antisecretory in whom laxative ingestion was either drugs incompletely suppress gastric acid in J D O'BRIEN, J ASHLEY, M J S LANGMAN (Depart- unsuspected or only considered late in the patients with bleeding peptic ulcer between ment ofMedicine, Queen Elizabeth Hospital and patient's investigation. An average of £2807 admission and further bleeding. We measured The Office ofPopulation, Censuses and Surveys, (range=£60-£10709) was spent on investiga- 24 hour gastric pH in 13 patients with major London) Examination of hospital admission tions which would have been avoidable had an peptic ulcer bleeding (two had further bleed- data in the past has suggested that peptic ulcer early laxative test been performed. In compari- ing, one died). disease has greater impact in the north than in son, each laxative test costs £24 and so the cost Twenty-four hour recordings were com- the south ofthe United Kingdom. This preval- of screening all GI patients presenting with pleted in 11 (one operated at 11 hours, one ence pattern has not been assessed since a rising diarrhoea was estimated at £600 for each recording stopped at 13 hours). Patients were frequency in ulcer perforation and mortality laxative abuser diagnosed (assuming a preval- given ranitidine (RAN) 300 mg bd or omepra- has been observed in women, nor since data on ence rate of 4%). zole (OM) 40 mg od orally at the time of urgent bleeding and perforated ulcer have been avail- It may be financially worthwhile to perform a endoscopy within 12 hours of admission and able. laxative test on all new GI referrals presenting placement of pH probe. Gastric acidity was We have now examined hospital admission with diarrhoea. measured as % of time below threshold pH rates for bleeding and perforated gastric and values 5 4 and 6.4. At pH 5 4, all clotting duodenal ulcers from 1983 to 1985, which is the functions (PT, PTT, KPTT, and platelet latest period available according to hospital aggregation) are zero and at pH 6-4, PT, PTT, region, using Hospital Inpatient Enquiry A prospective audit of investigations in out- KPTT are fourfold prolonged and platelet (HIPE) samples ofdischarges and deaths. patients with iron deficiency anaemia aggregation 23%. In this study, gastric pH was Duodenal ulcer perforation rates in men <5*4 for 76% OM, and 84% RAN and 72, ferritin ulcers might be reduced by neutralisation of that predispose particularly to ulcer perfora- <20), 43 probable iron deficiency, and four no intragastric pH to values normalising clotting tion. evidence of iron deficiency. Thirty four function has yet to be tested. patients had received NSAIDs. Some 120 causes for anaemia were found in 99 patients, and no cause was found in 12. Upper gastro- Low dose aspirin: an unrecognised cause of intestinal lesions were found at endoscopy in 39 gastric mucosal damage cases and strongly suspected in 24. Lesions Regional variation in the generation ofgastric causing anaemia were no more likely in patients mucosal potential difference N HUDSON, A T COLE, F E MURRAY, P HYMAN- taking NSAIDs than those not taking NSAIDs TAYLOR, L KURLAK, B FILIPOWICZ, C j HAWKEY (11 v 14, p>O-1). Duodenal biopsies in 50 B J NG, F SEOW, M C NGU (INTRODUCED BY D B (Department of Therapeutics, University patients revealed coeliac disease (3), giardia (1), JoNES) (Gastroenterology Unit, Repatriation Hospital, Nottingham) Regular low dose aspirin and alactasia (1). Large bowel pathology (by General Hospital, Concord, NSW 2139, used in cardiovascular prophylaxis is associated barium enema, colonoscopy, and sigmoido- Australia) This study characterises ion trans- with increased risk ofmelaena. Doses as low as scopy) accounted for 20 cases. Other causes port mechanisms responsible for the genera- 75 mg daily are often used. It is not known included other small intestinal disease (3), tion of transmucosal potential difference (pd) whether these doses are less harmful to the menstrual loss (8), haematological abnormali- in gastric mucosa. gastric mucosa than standard therapy. The aim ties (6), malignancies (5), and dietary Measured in vitro (Ussing chambers), fundic of this study was to evaluate gastric damage deficiency (3). In searching for dual gastro- and antral gastric mucosa of the rat showed pd caused by low dose plain aspirin and compare intestinal pathology a colonic cause for anaemia of 31-7±0-5 mV (n=129) and 28.9±0 5 mV this with enteric coated (EC) aspirin 300 mg as was found in only one patient with a gastric (n= 53), respectively. In the antrum, part ofthe Nuseals. ulcer (polyp) and two with oesophagitis (polyp pd was dependent on apical sodium channels as Twelve volunteers each received five days' (1), known colitis (1)) in the 92 patients who shown by a fall in pd when 10-5 M amiloride treatment with: placebo, aspirin 300 mg daily, had upper and lower tract investigations. Thus was present. This concentration of amiloride aspirin 75 mg daily or EC aspirin 300 mg daily, a cause for anaemia was identified or strongly had no effect when added to the basolateral in a double blind, crossover trial. Endoscopy suspected in 90% of cases. side. However, at 10-3 M, amiloride caused was performed on days 0, 1, and 5 for each We conclude that unsuspected dual path- a marked fall in pd, suggesting the presence treatment, and gastric erosions were counted. ology in the gastrointestinal tract was rare of Na+/H+ antiport on the basolateral Results were expressed as median (IQR) (2%). Colonic investigations have a low membrane. The chloride channel blocker, number oferosions at endoscopy. diagnostic yield if patients have no colonic diphenylamine-2-carboxylate (10-4 M), when Aspirin 300 mg caused significantly more symptoms and have a significant upper added to either the apical or basolateral side, mucosal injury after multiple doses 18 (2-26) intestinal cause for anaemia. also reduced pd, indicating the presence of than EC aspirin (p<0-001) and placebo A1246 British SocietyofGastroenterology

(p<0-001). Aspirin 75 mg caused less mucosal necrosis - in this case it attacked foci of mucosa with P (25%), p=0-22. The transfusion injury 1.5 (0-7) than aspirin 300 mg (p<0 6) rendered ischaemic by spasm of muscularis requirements were higher in the P treated but more than EC aspirin 0 (0-1) (p=0-15) or mucosa. group (median units transfused: P=3 units, placebo 0 (0-2) (p=0- 16). There was no differ- This hitherto unseen phenomenon suggests M=2 units, p=0.02). In patients receiving M, Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from ence between damage caused by EC aspirin that stress (anaesthesia and surgery) can induce 4% required surgery compared with 15% in P and placebo (p=0.98). ischaemia mediated by spasm of muscularis patients (p=0.05). In conclusion, aspirin 75 mg causes less mucosa. In the absence of mucosal stimulation Among the 17 patients who received NSAIDs gastric mucosal injury than aspirin 300 mg but (hypomotility), the effect can be prolonged in the two weeks prior to entry there were six more damage than (EC) aspirin 300 mg. Injury sufficiently to cause ulceration. rebleeds (35%) and three required surgery caused by EC aspirin is at placebo levels. (18%); this compared with 18% rebleeds and Enteric coating of aspirin may offer more 8% requiring surgery in non-users ofNSAIDs. 2 gastric mucosal protection than lowering the up of patients with type III intestinal There were three withdrawals (1 M, P) dose. Follow because of abdominal pain. Two patients (3%) metaplasia and increased detection of early receiving M had diarrhoea, one of whom gastric carcinoma withdrew. The five other withdrawals (all in the M group), were for non-compliance (2), Barrier properties of the adherent gastric M I FILIPE, T ROKKAS, G E SLADEN (Department of rash, congestive cardiac failure and non- mucus gel to pepsin Histopathology and Gastroenterology Unit, Hodgkins lymphoma. One patient in the M UMDS Guy's Hospital, London) Early gastric group was excluded from analysis owing to V K HOSEIN, D THAKKER, A ALLEN, J P PEARSON cancer (EGC) is associated with a much better previous major gastric surgery. There were no (Department of Physiological Sciences, Medical prognosis than advanced stage disease and is deaths in either group. School, Newcastle upon Tyne) Pepsin erosion of therefore a valuable diagnosis. Incomplete sul- In conclusion, M significantly reduced the adherent gastric mucus is balanced by new phomucin secreting intestinal metaplasia (type need for surgery and for transfusion in patients mucus secretion thus maintaining a protective III IM) has been related to gastric carcinoma with a recent upper gastrointestinal haemor- gel mucosal layer that excludes pepsin from (GCa) but its malignant potential and value in rhage. Rebleeding was reduced in the M group the mucosal surface. We have tested this surveillance have not been tested in prospective but this did not reach statistical significance. hypothesis in vitro. studies with patient follow up. Here we present A layer of fresh pig gastric mucus gel (2 mm and compare data on the incidence and fre- thick x 2.3 mm diameter), separating two com- quency of EGC detection in two periods: (A) partments, was exposed on one side to pepsin 1976-81 retrospective, no patient follow up; - Reduction in angiogenesis in non-steroidal (2 mg.ml- , pH 2) and on the other citrate (B) 1982-87, prospective patients with type anti-inflammatory drug associated gastric buffer (pH 2). Soluble degraded mucin and III IM on initial biopsy underwent biopsy again ulcers pepsin were measured in both compartments at at six to 12 month intervals. During 1976-87, intervals over four hours incubation at 37°C. 718 gastrectomies for GCa were performed; 24 N HUDSON, M BALSITIS, C J HAWKEY (Depart- The rate of pepsin mucolysis of the mucus were EGC, and six (1-5%) and 18 (6.4%) were ments of Therapeutics and Pathology, University gel was 4-54 mg (0.47) (mean (SEM), n=3) detected in periods A and B respectively Hospital, Nottingham) Non-steroidal anti- degraded mucin over the four hours, equiva- (p 0.01). During 1982-87, 2286 biopsy speci- inflammatory drugs (NSAIDs) are associated lent to a decrease in mucus thickness of mens were examined, of which 4% were type with peptic ulceration. The pathogenesis of approximately 25 im.hr-1. With acid (pH 2) III IM from 80 patients. Of these, 22 patients this action remains unclear. One mechanism alone, pepsin plus polyacrylate carbomer (1 showed coexisting GCA (of which five were may be impaired ulcer healing. Angiogenesis is mg.ml- ) or sucralfate (0-63 mg.ml- 1, 0 57 mg EGC), four had peptic ulcer, and 11 are under a prerequisite for the repair of deep mucosal (0-1) (n=6) of degraded mucin was released. surveillance. The remaining patients were lost ulceration in the stomach. The aim of this http://gut.bmj.com/ Diffusion of pepsin (2 mg.ml-l, pH 2) or to follow up or not yet recalled. The diagnosis of study was to investigate whether NSAID myoglobin (15 mg.ml-l, pH 7) through the EGC arose from the initial gastroscopy in all six therapy inhibits angiogenesis in gastric ulcers. mucus layer over four hours was less than cases of period A compared with period B in Endoscopic biopsy specimens were taken 0-25%.hr-'. which most cases 61% (11 of 18) were diag- from the edge of gastric ulcers in five patients These studies show: (i) pepsin mucolysis nosed as a direct result ofregular follow up. For on longstanding NSAID therapy and seven would cause discontinuities in the mucus layer these 11 patients, the medium time between control patients and fixed in formalin. All in vivo if not balanced by new mucus secretion; first endoscopy and diagnosis of EGC was 25 ulcers were greater than 5 mm in diameter and (ii) the adherent mucus layer is a protective months (range 12-30 months). at least 2 mm in depth. Sections (5 [) were on September 28, 2021 by guest. Protected copyright. permeability barrier against luminal pepsin; We conclude that EGC can be diagnosed stained immunocytochemically for CD31, a (iii) mucosal protective agents, carbomer and with increasing frequency if patients with type specific vascular endothelial cell marker. sucralfate, inhibit pepsin mucolysis of the III IM are closely followed up with biopsy. Vascularity was determined in three separate adherent mucus gel. zones: (1) superficial margin of the ulcer with granulation tissue present, (2) deep margin Double blind comparative study of with granulation tissue present, (3) the Focal spasm of gastric muscularis mucosae misoprostol with placebo in acute upper adjacent superficial area with glandular tissue. can induce focal ischaemia and ulceration gastrointestinal bleeding The parameters of vascularity assessed were: number of vascular buds, number of hollow C PIASECKI, C THRASIVOULOU (INTRODUCED BY G C BIRNIE, G C FENN, M J SHIELD, G C ROBINSON vessels and maximum vessel diameter. R POUNDER) (Department of Anatomy, Royal (Department of Gastroenterology, Western The edge ofNSAID ulcers in the presence of Free Hospital School of Medicine, London) Infirmary, Glasgow and Medical Department, granulation tissue was significantly less While transilluminating guinea pig gastric G D Searle & Co Ltd, High Wycome, Bucks) vascular than controls; number of hollow wall, we noticed foci of partial and complete The effect ofmisoprostol (M) or placebo (P) on vessels mean 11-8 (95% confidence limits: 7-7- compression of submucosal vessels by trans- rebleeding was assessed in 150 patients with 18-1) v 23-1 (15-7-33-9) per high power field verse bands. Mucosal blood perfusion beneath acute upper gastrointestinal haemorrhage con- (p<0-01 Student's t test) and vessel maximum foci, measured by 02 electrode, was 2 to 5% of firmed endoscopically within 24 hours of diameter 16-7 (13-9-20-5) v 29-9 (18-2-49-3) normal. The area involved was shrunk by 27%, admission. Admission criteria required con- (p<0.03). The number of vascular buds was with resulting tortuosity of vessels. We firmation of a significant gastrointestinal also lower in the NSAID patients 9-4 (5 3- attribute this to compression of vessels by haemorrhage (indicated by haematemesis, 16-5) v 16-6 (8-7-31-9) (p=0-11). Vascularity spasm of muscularis mucosa, because these melaena, or hypovolaemic shock) or the in adjacent normal mucosa was not signifi- vessels are embedded in this muscle (external presence of stigmata of recent haemorrhage cantly affected by NSAID treatment; hollow muscle was removed). Arteries and veins (SRH). vessels 7-4 (1.5-36) v 6-4 (4-8-15 5), vessel returned to normal with normal mucosal perfu- In this single centre study patients received maximum diameter 152 (3-1-37-5) v 14-9 sion, either spontaneously within five minutes M 300 [tg qds (n=75) or P (n=75). Endoscopy (3 8-58 5) and vascular buds 2 7 (0 0-23.4) v or immediately following gentle mucosal or surgery was used to confirm suspected 2-6 (0-0-19-3). stimulation. However in five of 15 animals rebleeding during the study period of up to 10 In conclusion, NSAID associated gastric 'spasm' remained for one to three hours, and days. Presence of SRH was associated with an ulcers have reduced vascularity compared with there was full thickness necrosis ofthe underly- increased risk of rebleeding or surgery: with control ulcers and this may inhibit repair ing mucosa. Surrounding areas without spasm SRH=27/98 (28%); without SRH=3/52 (6%). mechanisms. This may explain the high pre- showed no necrosis. pH during the experiment Rebleeding was less common in patients valence of peptic ulcer complications associ- was 5.2 to 6-8. Acid is probably necessary for treated with M (15%) than in patients treated ated with their use. British Society ofGastroenterology A1247

prevented the rise in nucleic acid and protein relative risk ofC in smokers v non-smokers was PANCREAS contents. 1-21. At 17 years 277 smokers (69%) with CP The results confirm the tropic role of CCK developed C compared with only 93 non- after PSBR, and show that CR-1409 prevents smokers (55%). Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from this adaptive growth. In conclusion, in our CP patients only Effect of soybean lectin on pancreatic smokers have an increased risk ofdeveloping C secretion and plasma cholecystokinin (21%).

P H DEPREZ, R J PLAYFORD, J CALAM (Gastro- Immediate prognostic assessment of acute enterology Unit, Royal Postgraduate Medical pancreatitis using assays to quantify pan- School, Hammersmith Hospital, London) Raw creatic zymogen activation soya strongly stimulates pancreatic secretion GUT MOTILITY and growth, and promotes pancreatic neoplasia A M GUDGEON, D I HEATH, A JEHANLI, G PATEL, rat. are in the Soya's trypsin inhibitors thought C W IMRIE, J HERMON-TAYLOR (Departments of responsible, but we found in a pilot study that Surgery, St George's Hospital, London and The these had little effect on secretion compared Royal Infirmary, Glasgow) While prognostic Defining the physiological responses of the with raw soya flour (RSF). Soya also contains a criteria for acute pancreatitis are available 48 human oesophagus to distension potent lectin (SL) which has been reported to hours after admission, there is no simple, stimulate pancreatic growth. We tested its reliable, non-invasive test which can be used on D WILLIAMS, D G THOMPSON, L HEGGIE, J effect on pancreatic secretion. admission. We have developed sensitive BARLOW, J BANCEWICZ (Departments ofMedicine Jugular, pancreatic, and duodenal catheters immunoassays specific for trypsinogen and andSurgery, Hope Hospital, Salford) The aim of were inserted into anaesthetised, atropinised human prophospholipase A2 activation pep- the study was to provide a precise definition of rats (n=6 per group). Biliopancreatic juice was tides (TAP and PLAP) using C-terminally the neurophysiological responses of the normal diverted and protein measured in 15 minute directed antibodies which enable a direct human oesophagus to distension in vivo. Six- collections. Blood samples (0-6 ml), taken measurement of pathological zymogen activa- teen healthy volunteers underwent multiple before and 15 minutes after intraduodenal tion. In 53 patients with acute pancreatitis the (30 second duration) intraoesophageal disten- injection of RSF (30 mg) or SL (1-8 mg; median on-admission urine PLAP concentra- sions at five sites varying from six to 18 cm equivalent to the RSF by hemagglutination tion for those with mild disease (uncomplicated above the lower sphincter using a novel double test), were assayed for cholecystokinin (CCK) pancreatitis) was 1-51 nmol/l (range 0-4.95 balloon technique capable of simultaneously by radioimmunoassay using antiserum A2. nmol/l) and for severe disease (those develop- measuring manometric and propulsive Pancreatic protein output increased rapidly ing one or more major local or systemic compli- responses both above and below the site of (within 15 minutes) from mean (SEM) 33 (6) cation) 4-12 nmol/1 (range 0-2-70 nmoL/l) distension. [sg/min to 116 (23) (p<0*01) after SL and to 97 (p<0.005 Mann-Whitney U test). Similarly, At all sites, inflation ofeither balloon beyond (27) after RSF (p<0*05). Plasma CCK rose there was a significant (p<0.0001) median a threshold of 7 (3-10) ml (median, range) only slightly after SL from 10 (3) to 15 (4) urine TAP increase in severe pancreatitis induced both a distension dependent increase pmol/l (NSD). (mild: 0 nmol/l, severe: 3-21 nmol/l). A in proximal contractile activity (125 (40-190) In conclusion, pure soybean lectin strongly specificity of 100% and sensitivity of 60% for mm Hg/30 sec at 10 ml inflation) and propul- stimulates pancreatic secretion and may be a predicting severe disease was obtained using a sive force (60 (45-72) gm at 10 ml inflation). major factor in the harmful effects of soya on cut off level of 8 nmol/l for combined urine Inflation of the lower and upper balloon the pancreas. The rise in CCK release appeared TAP and PLAP concentrations. together induced a potentiation of the motor insufficient to account for the massive pan- The results indicate that assays quantifying response proximal to the upper balloon, 350 creatic response. zymogen activation provide a simple non- (280-520) mm Hg/30 sec (p<0 01 v upper http://gut.bmj.com/ invasive on-admission prognostic assessment balloon alone), indicating ascending excitation. of patients with acute pancreatitis which may In contrast, inflation of the upper balloon influence management. reduced the propulsive response induced by inflating the lower balloon to 10 ml from 60 (45-72) gm to 12 (8-20) gm (p<0 01) indicat- Pancreatic adaptation to massive enterec- ing descending inhibition. Patterns of response tomy is abolished by the cholecystokinin Is smoking associated with the risk of to inflation showed regional differences in antagonist CR-1409 developing pancreatic calcification in character, with induction ofperistaltic contrac- on September 28, 2021 by guest. Protected copyright. patients with chronic pancreatitis? tions in the upper, but non-peristaltic contrac- P WATANAPA, M EGAN, P H DEPREZ, M R ALISON, tions in the lower, oesophagus. The magnitude J CALAM, R C N WILLIAMSON (Departments of G CAVALLINI, G TALAMINI, B VAONA, P BOVO, of the proximal response also varied regionally Surgery, Medicine, and Histopathology, Royal M FILIPPINI, I VANTINI, A RIELA, L FRULLONI, to similar degrees of distension, from 110 (70- Postgraduate Medical School, Hammersmith V DI FRANCESCO, M P BRUNORI, E TASINI, 165) mm Hg to 10 ml at 6 cm, v 75 (35-120) Hospital, London) Since pancreatic adaptation P PEDERZOLI (Clinica Medica and Clinica mm Hg to 10 ml at 15 cm, above the lower to massive proximal small bowel resection Chirurgica, Policlinico B.go Roma, University of oesophageal sphincter (p<0O01). (PSBR) may be modulated through chole- Verona, Italy) It is unknown whether there is an In conclusion, oesophageal distension cystokinin (CCK) secretion, we tested the association between cigarette smoking (S) and induces both an ascending excitatory and a effect of the CCK antagonist CR-1409 on this calcification (C) in chronic pancreatitis (CP). descending inhibitory neural response which response. We determined if there was an association together result in an aboral propulsion force Male Wistar rats (n=72) weighing 200-225 g between C, S, and other variables including whose magnitude is directly related to degree, were randomised to receive either PSBR or alcohol intake in CP. Some 637 consecutive CP length, and site ofoesophagus distended. transection/resuture followed by saline or CR- patients diagnosed over the period 1973-89 1409 (10 mg/kg daily sc). Rats were killed one, were reviewed (mean follow up 11 ±6-5 years). two, or three weeks postoperatively, when Only patients who had ultrasound or ERCP, or blood was obtained for CCK assay and the both, and computed tomogram and plain film of Nutrient propulsion through the small bowel pancreatic cell proliferation was assessed by the abdomen every three years were included in is modulated via a fi adrenoreceptor pathway three parameters: nucleic acid and protein the study. Onset of C was considered the end content, bromodeoxyuridine (BUDR) label- point of the follow up. The patients were N K AHLUWALIA, D G THOMPSON, D WILLIAMS, ling index, and proliferating cell nuclear divided in two groups: non-smokers and J BARLOW, L HEGGIE (University Department of antigen (PCNA) expression. PSBR increased medium to heavy smokers (. 10 cigarettes/day). Medicine, Hope Hospital, Salford) While P1 plasma CCK concentration by 83-102% at one Of637 patients only 570 fulfilled our criteria. A adrenergic blockade is known to accelerate to three weeks, irrespective of CR- 1409 treat- total of 376 (66%) developed calcifications human upper intestinal nutrient transit and ment. Total pancreatic DNA content increased (CCP), while 64 (17%) had C at the time of may produce diarrhoea, the motor events by 37% at two weeks (p<0 05) and by 93% at diagnosis. C were detected in 266 (71%) ofCCP responsible remain unexplored. We devised a three weeks (p<0005), while RNA content patients at five years and in 365 (97%) at 17 combined intraluminal manometric and force increased by 67% and 180% (p<0-001) and years. Smoking was correlated with the transduction catheter to study both propulsive protein content by 15% and 88% (p<0 05). presence of development ofC (Mantel-Cox test force and propagation of intestinal motility PSBR increased BUDR labelling index and p<0004, likelihood test p<0 0009). The mean with and without atenolol 100 mg to induce P3 PCNA positive staining. CR-1409 completely timefordevelopingC in smokers was eight years adrenoreceptor blockade. abolished this proliferative response and also compared with 12 years in non-smokers. The Ten volunteers participated in the study A1248 British Society ofGastroenterology after an overnight fast. The catheter assembly clinically applicable, accurate means of detect- Anorectal physiology: the effect of acute was positioned in the proximal small intestine, ing accelerated or delayed transit in patients stress and propulsive and manometric activity were with suspected colonic motility disorders. Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from measured simultaneously for 90 minutes before A PRIOR, L A HOUGHTON, P J WHORWELL and 30 minutes after ingestion of a standard (University Hospital of South Manchester, West meal (360 ml; 200 kcal). The study was Didsbury, Manchester) Visceral hypersensitivity repeated on a separate day 60 minutes after Impact ofa late meal on rapid eye movement/ occurs in many patients with irritable bowel ingestion of 100 mg atenolol. non-rapid eye movement sleep activity syndrome (IBS). However, it is more common Control study results are as follows. During in those with high anxiety levels, raising the fasting (phase II) motility, (mean (SEM) 2-7 D KUMAR, G TSANG, R JAMES (Department of possibility that it is merely a reflection of (0 3)) propulsive events/minute were observed Surgery, The Queen Elizabeth Hospital, underlying anxiety. To investigate factors (86% of total motility) generating 24 (4) gm Birmingham, Janssen Research Foundation, influencing visceral sensitivity, the effect of force/minute, in addlftion 0.4 (0-1) non- Grove, Wantage, Oxon) Sleep has previously acute stress on anorectal responses to balloon were After propulsive events/minute noted. been shown to suppress postprandial activity. distension was assessed in 14 healthy volun- food a similar number of propulsive events/ To determine the effect of a late meal on the teers (three male, 11 female; age 24-52). Each minute were observed (3.0 (0.5), p>0 05 v sleep rapid eye movement/non-rapid eye move- subject was studied on three occasions and was fasting (74% of total motility)), generating 17 ment (REM/non-REM) cycle, we have exposed to cold pain, mental stress or control (3) gm force/minute (p>0 05 v fasting), but recorded sleep activity after an early and a late study in random order. non-propulsive activity was significantly meal in eight healthy volunteers. Sleep was Both subjective and objective measures of increased (1-0 (0-2)/minute, p<0 05 v fasting). recorded using the standard electrodes and a stress increased significantly during both stress Atenolol study results are as follows. Fasting portable sleep recorder with eight channels studies (mean (SEM) anxiety level; control 23 propulsive activity was unaffected by 0 (Oxford Medical Systems, Oxon UK). The (2.9), cold 56 (5.4), mental 61 (6.5), p<002; blockade 2-0 (0.4) events/minute generating 21 subjects were required to ingest a standard 600 pulse rate; control 71 (0.5), cold 82 (0.9), (8) gm/minute (p>0.5 v control). After food kcal meal at 6 pm on night 1 and 15 minutes mental 84 (1-2), p<005). However, there were both propulsive and non-propulsive activity before going to bed on night 2. The two nights no changes in rectal sensitivity (volume to were similar in frequency to control study were studied in a random order in all subjects. discomfort (ml); control 190 (14-5), cold 198 (propulsive 2-6 (0.6) events/minute, non- The total sleep times between the two nights (16-9), mental 180 (14-9)), rectal compliance propulsive 1-4 (0-3)/minute, p>0 5) but con- were similar (454 v 460 minutes (mean)). The (ml/cmH2O; control 6-4 (0.6), cold 7 3 (0.9), sistently stronger forces were generated 30 (6) percentage of total sleep time occupied by mental 6 3 (0.7)), or distension induced gm/minute (p<003 v control). REM sleep was also similar for the two nights motility (motility index; control 1405 (376), In conclusion, atenolol uncovers a tonically (mean (SEM) 19-83 (3 32) v 21-2 (2.46), NS). cold 1389 (387), mental 1021 (289)). active 0i adrenoreceptor mediated inhibition of However, REM latency after a late meal was In conclusion, acute stress does not affect intestinal propulsive force in man which significantly shorter (mean (SEM) 81-4 (12-43) anorectal responses to balloon distension in appears to modulate normal intraluminal trans- v 159-17 (56 59) minutes, p<0.01). Stages 2 normal volunteers, suggesting that the abnor- port nutrient passage by preventing precipitate and 3/4 did not differ significantly between the malities in visceral sensitivity noted in IBS are through the upper gut. two nights (stage 3/4 31-03 (6-81) v 28-43 not solely due to anxiety. (3.86), stages 2 45-17 (3.95) v 46 0 (3-19), NS). A late meal followed by sleep seems to reduce Strategy for an inexpensive, non-invasive, REM latency without changing the overall

sensitive test for identification of colonic Small intestinal motility in diarrhoea pre- http://gut.bmj.com/ in proportion of the REM/non-REM sleep cycle. motility disorders clinical practice These data lend further support to the concept dominant irritable bowel syndrome of gut-brain axis and may explain why post- M CAMILLERI, A R ZINSMEISTER (INTRODUCED prandial activity after a late meal immediately D A GORARD, G W LIBBY, M J G FARTHING BY S F PHILLIPS) (Mayo Clinic, Gastroenterology (Department of Gastroenterology, St Bartholo- Unit, Rochester, MN 55905, USA) Although before sleep is significantly shorter. mew's Hospital, London) Abnormalities ofsmall widely used in the assessment of delayed bowel motility have been reported in irrit- colonic transit, the radiopaque marker method able bowel syndrome (IBS). We have studied with a single abdominal radiograph on the small bowel motility using a transnasal catheter on September 28, 2021 by guest. Protected copyright. fourth day appears to be less sensitive for Colonic circular smooth muscle relaxation by incorporating six strain gauges spanning 95 cm detection of accelerated colonic transit. Our leukocyte derived nitric oxide in six patients with diarrhoea predominant IBS aim was to develop a relatively inexpensive, (median age 28.5 years, range 24-53) and six non-invasive, accurate test of fast or slow S J MIDDLETON, J 0 HUNTER (Department of control (C) subjects (25.5, 19-32). Ambulatory colonic transit utilising selected scans taken Gastroenterology, Addenbrooke's Hospital, recordings began in the afternoon, continuing during the first 24 hours after the ingestion of a Cambridge) We have previously shown that rat till the following morning, during which time pH sensitive, methacrylate coated capsule con- distal colonic circular smooth muscle only small amounts of clear fluids were taining 1 l 1In resin pellets. (DCCSM) is extremely sensitive to nitric oxide allowed. We analysed regional colonic transit data (NO). Reduced tone of colonic smooth muscle Ninety nine hours of recording in IBS from three groups: 22 healthy controls; is a feature of ulcerative colitis but its patho- patients and 98 hours in C subjects were 10 patients with functional and four with genesis is unknown. DCCSM from non-fasted analysed. The IBS patients exhibited circadian carcinoid diarrhoea (D); and seven patients male Wistar rats was attached to isotonic variation in migrating motor complex with idiopathic constipation (C). A logistic transducers (Harvard T3) in 2 ml organ baths periodicity at the proximal jejunum; diurnal discriminant analysis compared sensitivity and and perfused with oxygenated Krebs Henselite periodicity mean (SEM) 106 (24) minutes, specificity ofcomplex and simple summaries of at 37°C. Human neutrophils (N) and mono- nocturnal periodicity 63 (6) (p<005). In C, transit. nuclear cells (M) relaxed acetycholine precon- periodicity was 86 (9) diurnally and 73 (9) The results showed that among complex tracted DCCSM (21+19-4%, p<0-01 and nocturnally. There were no differences in summaries, proximal colon emptying rate 18-5±21%, p=0-018). N-G-monomethyl-L- overall, nocturnal, or diurnal periodicities (PCER) (p<0-01 for D only) and geometric arginine (L-NMMA) competitively inhibits between IBS and C. The mean duration of centre of colonic isotope at four hours NO synthase and this, but not D-NMMA, phase III complexes at each recording site (p<0005 for C and D) and 24 hours (p<0O005 reduced relaxation by both N from increased aborally in IBS and C subjects for C only) showed significant differences from 53-2+35-1% to 1-8+10% (p=0-01) and M respectively: from 5.4 minutes and 5.9 minutes healthy controls. Simpler transit summaries from 33+42% to 7*7+30% (p=0 041), an in proximal jejunum, 7-6 and 6 8 minutes in also had significant discriminant value; these effect reversed by the addition of the substrate mid-jejunum to 8 4 and 10.2 minutes in ileum. included ascending (AC), transverse (TC), and for NO production L-arginine (3 mM/l). The durations were not different between IBS descending (DC) colon counts at four hours Haemoglobin 200 nM/1, which binds NO, and C. There were no differences in velocity or (p<0-01 for all); and AC, TC, and stool counts decreased relaxation by N by 70.4% and M by extent of propagation of phase III complexes. at 24 hours (p<005). Receiver operating 76 5%. The number of phase III motor complexes characteristic curves showed that at 90% sensi- NO is released by human leukocytes and starting distally was similar in both groups. tivity, specificity of TC counts at four hours may be an important pathogenetic factor in Clustered contractions occupied 10-5 (2.4)% was identical (79%) to that of PCER. ulcerative colitis where inhibitors of NO (C) and 12-2 (4.4)% (IBS) of total recording In conclusion, quantitation of isotope in synthesase may have a therapeutic time. Orocaecal transit time (OCTT), colonic regions at four and 24 hours provides a role. measured by lactulose hydrogen breath test, British Society ofGastroenterology A1249

was 52 (10) minutes in the IBS group and 77 (6) initially had a loss of their symptoms subse- added to the perfusate reservoir (1200 ng/ml in 10 control subjects (p<0 05). quently (38%). Similar incidence and resolu- concentration of CsA). After an initial 30 Thus, although OCTT is faster, we have tion rates were observed for the other symptom minutes of continuous livers were

perfusion, Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from been unable to show any small intestinal intra- groupings. Adjusting for differences between converted to single pass condition and HRP (25 luminal pressure abnormalities in these diar- responders and non-responders and for the mg) was given as a one minute pulse. After six rhoea predominant IBS patients. established precision of the questionnaire did minutes, the single pass perfusion was con- not significantly alter the results. verted back to recirculating perfusion. Five, 2 While symptoms codipatible with functional minute and 10, five minute bile samples were gastrointestinal disorders are common in collected during the perfusion. Selective affective biasing in recognition middle aged people and overall prevalence is In miglyol and in CsA perfused rats, bile flow memory in irritable bowel syndrome relatively stable, there is substantial variation rates were lower than in control rats but the within individual subjects from year to year. difference was not significant. The first biliary J E GOMBORONE, P A DEWSNAP, G W LIBBY, M J G HRP peak (paracellular pathway) occurred at FARTHING (Department of Gastroenterology, St seven minutes. In CsA rats, it was higher than Bartholomew's Hospital, London) In depres- in miglyol and control rats (44- 1 ± 14- 1, sion, emotionally negative sensory inputs 9 5±3 3, 5-9±2-1 ng/minutes, respectively; establish stronger memory traces than neutral LIVER p<003 ANOVA test). Conversely, the second or positive inputs. That is to say, there is a HRP peak (transcellular pathway) observed at mood-congruent bias in information process- 20 minutes, was similar in the three groups of ing. This bias is now recognised as funda- rats (14-1+±34, 19-3±3-2, 14-9±5-0, respect- mental to the nature of affective disorder. We Different pattern of genomic DNA loss in ively). have explored the relation between IBS and colorectal liver metastasis and hepatocellular In conclusion, CsA increases tight liver affective disorder from the novel perspective of carcinoma junction permeability. This suggests that information processing. hepatic junctions may be involved in CsA We constructed a word recognition memory SHI-FA DING, N A HABIB, JJ DOOLEY, C WOOD, induced cholestasis. task which contained 24 emotionally loaded L BOWLES, J DELHANTY (Department ofSurgery, stimulus words (eight negative, eight positive, Hammersmith Hospital, London, Departments of and eight neutral) which subjects were Surgery and Medicine, Royal Free Hospital required to remember, and later select from a School ofMedicine, London, and Department of Autonomic function tests in cirrhosis word list. We tested randomly selected IBS Genetics and Biometry, University College patients (n=30) and compared results with London) A candidate tumour suppressor gene J F DILLON, J N PLEVRIS, D J EWING, I A D depressed patients (n=28), patients with (TSG) on chromosome 5 for colorectal BOUCHIER, P C HAYES (Department ofMedicine, organic gastrointestinal disease (n=28), and carcinomas (CRC) has been cloned (Kinzler, Royal Infirmary, Edinburgh) Abnormal cardio- normal controls (n= 30), all of comparable age et al, Science 1991; 251: 1366). We previously vascular reflex tests have been reported in and sex. A similar bias to emotionally negative reported allele loss on chromosome 5 in cirrhosis, but their interpretation is unclear. stimuli in word recognition responses occurred hepatitis B virus (HBV) negative hepato- We studied 22 patients (16 male: six female in IBS (93% negative words recalled) and cellular carcinomas (HCC), which might aged mean (SD) 62-3 (14- 1) years) with depressed patients (87%) which was more suggest a TSG loss for HCC (Ding, et al, Gut cirrhosis (15 alcoholic). Patients were grouped common than in normal controls (67%; 1990; 31: A1211). In order to investigate as Child's A (16) and Child's B and C (6). We p<005) and patients with organic disease whether the same gene deletion on chromo- used a standard battery ofcardiovascular reflex (73%; p<0 05). The IBS and depressed some 5 occurs in both CRC and HCC, we tests described and as well (as by Ewing Clarke) http://gut.bmj.com/ patients differed, however, in that the IBS compared allele loss in 11 patients with as RR interval variability for 24 hour ECG group incorrectly over-identified emotionally colorectal-liver metastasis (CLM) with that in tapes, and pupil cycle time (PCT). PCT negative words that were not test stimuli six patients with HBV negative HCC. involves shining a slit oflight on the edge ofthe (p 100 However, when applied retrospectively to the ment. Disappearance of IgM anti-HCV occur- pg/ml. patients in centre B, the model had a specificity red in 8 of9 patients with sustained response to Although detectable TNF was discovered of 100% and a sensitivity of 25%. The latter interferon therapy. in five patients (20-100 pg/ml), ILl in one (13 should be improved with the development of a In conclusion, positivity for serum IgM anti- pg/ml), and IL6 in four (80-1000 pg/ml); dynamic prognostic model. C100-3 correlates with active hepatitis C. In endotoxaemia and plasma cytokines were not treated patients, disappearance of IgM anti- significantly correlated, nor did any parameter HCV seems to predict a sustained response to predict graft function, rejection, or outcome. interferon treatment. The results suggest that endotoxaemia during Surveillance for cytomegalovirus infection OLT does not stimulate cytokine release, and using culture techniques in liver transplant may not be ofclinical importance. recipients Safety of major surgery in acute hepatic M SMITH, DR PILLAY, D CHARMAN, P D porphyria GRIFFITHS, K ROLLES, A K BURROUGHS (Hepato- Intracerebroventricular neuropeptide Y biliary and Liver Transplantation Unit and S R DOVER, L PLENDERLEITH, M R MOORE, K EL stimulates bile secretion in the rat via a vagal Department ofVirology, Royal Free Hospital and MCCOLL (University Department ofMedicine and mechanism School of Medicine, London) Cytomegalovirus Therapeutics and Department of Anaesthetics, (CMV) infection is a major cause of morbidity Western Infirmary, Glasgow) Patients with acute M FAROUK, J G GEOGHEGAN, W C MEYERS and mortality after liver transplantation, but hepatic porphyria are often denied surgery for (INTRODUCED BY P B COTTON) (Duke University,

prophylaxis against CMV is not routinely used. co-existing diseases because of fear that the Durham, North Carolina, USA) The choleretic http://gut.bmj.com/ Serological surveillance is complicated by anaesthetic or stress of surgery will precipitate response to feeding is known to be abolished by modified antibody responses due to immuno- a life threatening porphyric crisis. We have vagotomy. The central mediators responsible suppression, so that strategies for prophylaxis reviewed the outcome of 31 major surgical for this choleresis have not been identified. In require prospective surveillance using culture procedures under general anaesthetic in 20 rats, intracerebroventricular (ICV) administra- techniques. Surveillance was evaluated weekly patients with acute hepatic porphyria. The tion of neuropeptide Y (NPY) potently in 46 consecutive liver transplant recipients procedures included cholecystectomy (6), stimulates feeding. In this study, the effect of using a rapid culture technique (detection early renal transplant (3), cardiac surgery (2), ICV NPY on bile flow was investigated in antigenic fluorescent foci - DEAFF), conven- hysterectomy (3), laparotomy (3), mastectomy, normal and vagotomised rats. tional cell culture, and liver immunocyto- hip replacement, and nephrectomy (1 each). Common bile duct and femoral vein on September 28, 2021 by guest. Protected copyright. chemistry. CMV infection was found in 17 Seventeen of the patients were known to have catheters were placed in urethane anaesthetised (37%) ofwhich 11 (24%) including the only two porphyria preoperatively, and they only rats. Local stimulation of bile flow by gastric seronegative recipients had CMV disease received anaesthetic agents believed to be safe acid was avoided by pyloric ligation and gastric (pyrexia with viraemia or hepatitis or in porphyria. These 17 patients had uneventful diversion. An intravenous infusion of 1-2 FtM/ pneumonitis) which caused four deaths within recoveries with none developing porphyric kg/minute of sodium taurocholate was com- one year oftransplantation. crisis. In six of these patients the urinary menced and bile flow allowed to stabilise for Three independent risk factors for CMV excretion of the porphyrin precursors delta- two hours. A bolus of InM NPY or carrier as infection were: (1) recipient seropositivity aminolaevulinic acid and porphobilinogen was control (0-1% albumin in 0.9% saline) was prior to transplant, in whom donor sero- monitored and none showed a postoperative injected stereotaxically into the lateral positivity conferred increased risk compared to rise. Two of the three patients not known to ventricle. Bile was collected in 15 minute donor seronegativity; (2) increased transfusion have acute porphyria preoperatively, and who samples. Four groups were studied (six rats per of whole blood and fresh frozen plasma; (3) therefore received standard anaesthetics, died group). Vagotomy was performed at the increased use of immunosuppressive drugs. in porphyric crisis in the postoperative period. cervical level. Positive CMV cultures from whole blood and/ This study indicates that patients with acute Mean bile output, observed 30-120 minutes or liver biopsy specimens, but not from urine hepatic porphyria can be subjected to major after injection: control group=mean (SEM) or throat swabs were significantly associated surgery provided appropriate anaesthetics are 1-36 (007), control and vagotomy=1-31 with CMV disease. used. The risk is for undiagnosed cases. (0-18), NPY=-154 (0-1l)*, NPY and This surveillance programme suggests that vagotomy=1-32 (0.13) (units: ml of bile/90 blood cultures are the most important to minutes,* p<0 05 by ANOVA). sample routinely and that CMV prophylaxis This study shows that ICV NPY causes a should be used in the groups at risk. Controlled Endotoxaemia during orthotopic liver trans- significant choleretic effect which is abolished trials should be set up to confirm the value of plantation: a clinically important problem? by vagotomy and the choleretic response to CMV prophylaxis. feeding may be initiated by the release of M LARVIN, S A PERRY, C W RAMSDEN, M I central NPY. ALDOORI, S A SADEK, G R GILES (University Department of Surgery, St James's University Significance of serum IgM anti-hepatitis C Hospital, Leeds) Endotoxaemia occurs during virus (HCV) in chronic HCV infection orthotopic liver transplantation (OLT), but its Indirect utilisation of glucose for the clinical relevance is uncertain. Endotoxic synthesis of hepatic glycogen in man S BRILLANTI, C MASCI, P RICCI, M MIGLIOLI, shock is mediated by cytokines secreted by L BARBARA (Instituto Di Clinica Medica e mononuclear phagocytes on binding endo- R F G J KING, K IBRAHIM, M MADAN, M J Gastroenterologia, University of Bologna, Italy) toxin. The present study investigated whether MCMAHON, D JOHNSTON (University Department British Society ofGastroenterology A1251 of Surgery, The General Infirmary, Leeds) energy x ray absorptiometry of the lumbar (NGA) is a synthetic ligand for the asialoglyco- Hepatic glycogen is synthesised from intra- spine (L2-L4) and femoral neck was per- protein receptor. Uptake of99ITc-NGA allows cellular glucose 6-phosphate. It is often formed (precision <1%). Bone mineral density a functional assessment of receptor concentra- assumed to involve exclusive utilisation of (BMD) was measured in 150 patients (M:F, tion and 99mTc labelling gives simultaneous Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from glucose without rearrangement of the carbon 57:93) - 121 with cirrhosis and 29 after liver hepatic imaging. We have assessed the hepatic ring (direct pathway) but it is now believed 3C transplantation (OLT). Local controls were processing of 99mTc-NGA using the isolated fragments may be used preferentially for used to construct regression equations to deter- perfused rat liver. synthesis (indirect pathway). We have mine age and sex matched normal values. The Forty per cent of a pulse (150 pmol) of addressed the hypothesis that 3 carbon inter- degree of osteopenia was measured by the 99mTc-NGA was taken up first pass. Of this, mediates (such as lactate) are used in the BMD difference from expected values. only 7% was released at the sinusoidal pole, indirect pathway in fasted individuals follow- Patients with primary biliary cirrhosis (n= 41% was excreted in bile, and 51% remained in ing a glucose load. Fifteen patients were given 30) exhibited noticeable osteopenia (mean= the liver. Fractionation on Sephadex G25 an infusion of 20% glucose (79-90 mllhour) -0-115, 95% CI -0-190 to -0040 g/cm2; showed that >85% of biliary 99mTc comprised before elective abdominal operation. All p<0 005) and 18 patients with cryptogenic three small MW metabolites and <15% was received a 2-5 g bolus of 1110 kBq of D-[6-3H] cirrhosis had similar reduction in BMD intact NGA. Pretreatment with leupeptin, a or D-[3-3H] glucose and D-[U-J4C] glucose (-0- 111, -0-161 to -0-060 g/cm2; p<0 005). lysomomal protease inhibitor, abolished out- before removal of a 1 g biopsy specimen of Patients with alcoholic cirrhosis (n=34) put of the small MW metabolites, but not of liver. 3H and 14C were determined in purified showed no significant decrease in spinal BMD. intact NGA. Thus biliary output of small MW glycogen as well as in glucose and lactate from Patients post-OLT had the most severe metabolites of 99mTc-NGA is by the lysosomal samples of peripheral blood. In each case both osteopenia with spinal BMD difference pathway. the ratio and specific activity of 3H and 14C in (-0-158, -0-218 to -0 099 g/cm2, This contrasts with 125I labelled NGA where glycogen were found to be significantly lower p<0-0001) and femoral neck BMD difference most radioactivity is released as small MW than those in administered glucose. By calcula- (-0 095, -0-14 to -0 05 g/cm2, p<0-0001). metabolites at the sinusoidal pole because of a tion 50-90% ofglycogen repletion occurred by No other cirrhotic group showed significant different chemical attachment of the label to indirect pathways and not all of this was from reduction in femoral neck BMD. the ligand. For 99mTc labelled NGA this arte- glucose supplied. These data show that spinal osteopenia is factual anomaly can be used to advantage as an It is concluded that the operation of a direct common in cholestatic and non-cholestatic imaging agent as most of it is confined within pathway in man is not exclusive and that cirrhosis, and that patients following OLT are the hepatobiliary system. significant fluxes for repletion of hepatic at an increased risk for the development of glycogen occur by an indirect route. severe osteopenia.

BILIARY TRACT Ursodeoxycholic acid in late primary biliary Effects of octreotide on liver regeneration in cirrhosis: long term follow up the rat

E A KOUROUMALIS (Academic Department N DAVIES, J YATES, B A TAYLOR, S A JENKINS Plasma fatty acids change after cholecystec- of Gastroenterology, University Hospital, (University Department of Surgery, Royal tomy Heraklion, Crete, Greece) Fifteen patients, all Liverpool Hospital, Liverpool) The liver has a women with stage III (9) and stage IV (6) remarkable capacity to regenerate after trauma M W SCRIVEN, J C M STEWART, D F HORROBIN, biliary cirrhosis (PBC), have been or resectioii. Since octreotide inhibits the M CA PUNTIS (Department ofSurgery, University primary http://gut.bmj.com/ followed up for at least two years (24-36 release of a number of hepatotrophic factors of Wales College of Medicine, Cardiff and months) on ursodeoxycholic acid (UDCA). and reduces portal flow we have investigated its Efamol Research Institute, Nova Scotia, Initially, a dosage of 10 mg/kg/BW was used for effect on liver regeneration in the rat. Canada) Surgical trauma causes changes in three months and then 15 mg/kg/BW were Male Wistar rats underwent a 67% hepatec- immune function and thrombotic tendency. administered. Routine liver biochemistry and tomy, followed by treatment with octreotide (2 These changes also occur with abnormalities in immunology were done at regular intervals. At sg bd) or saline (control). Liver regeneration, tissue polyunsaturated fatty acids (PUFA). We one year 7 of 15 had a second liver biopsy. portal pressure, and hepatic haemodynamics thus investigated PUFA perioperatively. The initial dosage was ineffective. Bio- (microsphere method) were determined at 48 The fatty acids in plasma phospholipid were on September 28, 2021 by guest. Protected copyright. chemical improvement started after 30-45 days hours and one and two weeks after the start of measured in 20 patients undergoing chole- on the higher dosage. Normalisation of ALT- treatment in both groups (n= 15). There was no cystectomy (mean age 56, 6 M: 14 F): preopera- AST occurred in 12 of 15 patients and a mean significant difference in the regeneration index tively and for the first two days postoperatively. drop of 30% in alkaline phosphatase and y at 48 hours. However at one week and two Analysis concentrated on the 20 carbon PUFA glutamyl transferase was noticed, without weeks there was a significant reduction (Mann- (c20-PUFA): arachidonate (AA), dihommo- immunological response. Whitney U test p<005) in the regeneration gammalinolenate (DGLA) and eicosapentae- Remission was permanent in only 2 of 15. index in the octreotide group (one week 1-02 noate (EPA). These are metabolised to Reactivation under UDCA occurred in 12 of 15 (0-9-1-1), two weeks 1-23 (0.99-1.36)) com- eicosanoids, which include prostaglandins and after a mean period of 13 months. An increase pared with controls (one week 1-16 (1-0-1-37), leukotrienes. to 20 mg/kg/BW resulted in 7 of 12 having a two weeks 1-36 (1-05-1-67)). Portal pressure There were no significant changes in total partial response. Three of 12 (all stage IV) (mm Hg) was significantly reduced in the c20-PUFA. There were, however, changes deteriorated. Histology at one year showed octreotide group (48 hours 7 5 (3-10), one in individual c20-PUFA. AA rose at day 1 progression to stage IV in 2 of 5 with stage III. week 6 (4.5-9), two weeks 4.9 (3.5-8)) com- (p<005) and this change persisted to day 2 In conclusion, despite good initial bio- pared with controls (48 hours 10-8 (9-12.5), (p<005). EPA and DGLA each fell, at day chemical response, only 13% of late PBC one week 9 (9.5-8.2), and 2 weeks (5.8 1 (p<005) and day 2 (p<001) respectively. patients maintain biochemical remission, while (3.5-9)). There was no significant reduction in The ratios DGLA:AA and EPA:AA showed relapses respond only partially on dosage hepatic arterial flow and portal venous flow in significant depression, on both days (p<0.01). increase and histology does not improve. flow between the two groups. These results show that tissue PUFA, as UDCA treatment does not seem to be helpful in The results of this study suggest that reflected by plasma values, change after chole- late PBC. octreotide inhibits liver regeneration in the rat, cystectomy. There is a shift towards AA which but further studies are required to establish its is metabolised to prothrombotic and immuno- mechanism of action and its effects on the suppressive eicosanoids. There is also a fall in growth of liver tumour after hepatectomy. EPA and DGLA, which have antithrombotic Osteopenia and liver cirrhosis products. These changes may explain some of the responses to surgical trauma. P BRAMLEY, B OLDROYD, S STEWART, A HORSMAN, M SIMPSON, M LOSOWSKY (Depart- Hepatic processing of a novel agent for ment of Medicine, St Jfames's University imaging and assessing hepatobiliary function Hospital, MRC Bone Mineralisation Unit, Laparoscopic cholecystectomy - a compari- University of Leeds, Leeds) In order to deter- W AHMED, A I MORRIS, I T GILMORE, P MALTBY, son with open cholecystectomy mine the degree of osteopenia in consecutive D BILLINGTON (Gastroenterology Department, unselected patients with established liver Royal Liverpool Hospital and Liverpool Poly- K S WYNNE, C M S ROYSTON (Hull Royal cirrhosis, a cross sectional survey using dual technic, Liverpool) Galactosyl neoglycoalbumin Infirmary, Hull) One hundred laparoscopic A1252 BritishSociety ofGastroenterology cholecystectomies are compared with 100 open tions. Use of a laser enables a clean, relatively P MERCER, M HARRISON, F REID, T BATES (The cholecystectomies. Complications occurred in bloodless dissection with minimal tissue William Harvey Hospital, Ashford, Kent) The 12 patients undergoing laparoscopic cholecy- damage. We report our experience of laser reports of 8563 necropsies were reviewed for stectomy, three major (two bile peritonitis, one laparoscopic cholecystectomy (LLC). evidence of an association between gall stones Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from laparoscopic injury causing bleeding), the rest One hundred and fifty consecutive patients or cholecystectomy and the subsequent minor. There were 20 complications from open underwent LLC. In five other patients LLC development of colorectal cancer (CRC). The cholecystectomy, including one death from was attempted but abandoned due to dense 219 subjects with a previous cholecystectomy complications following acute pancreatitis and adhesions (3), cholangiocarcinoma (1), and (CT) were age and sex matched with 219 subphrenic abscess. There were two further absent gall bladder (1). There were 121 women control cases with unoperated gall stones (GS) major complications, the rest were minor. The and 29 men, with a mean age of49 years and a and with 219 cases with a normal gall bladder mean hospital stay following laparoscopic mean weight of 67 kg. Eighteen patients had (NGB). There were 80 men and 139 women, cholecystectomy was 1-77 days. Ninety per postoperative jaundice, eight had ERCP with and only seven subjects were less than 50 years. cent of patients were discharged within 48 four CBD stone extractions. A NdYAG laser Seven of the 219 CT subjects had developed hours. The mean hospital stay following open was used for dissection. The mean operating CRC compared with 8 of 219 (GS) and 7 of219 cholecystectomy was 7-3 days. Eighty per cent time was 29 minutes (range 29-300 minutes) (NGB) controls. The relative risk ofCRC in the were discharged within the first week. Operat- and the mean laser time was 10 minutes (range cholecystectomy subjects compared with the ing time for laparoscopic cholecystectomy 4-35 minutes). Operative cholangiography was gall stone controls was 0-87 (95% CI 0-31- varied between 20 minutes and two hours with performed in 89 patients, not attempted in 41, 2.44). Right sided CRC has been reported in a mean over all operating time of 49 minutes. and cannulation failed in 20. All patients had excess in women after CT but neither of these The average time to return to normal activities gall stones. The mean hospital stay was 3-4 factors showed a positive trend. for patients following laparoscopic cholecystec- days. All had drains inserted, the mean drain- Conversely the 192 subjects with CRC were tomy was 4-5 days. Forty one per cent of those age was 40 ml (3 had 0 ml). The mean omnopon compared with 192 age and sex matched con- working returned to work within one week. requirement was 0 33 mg/kg. trols without CRC. Seven v 10 (3.6% v 5.2%) Following laparoscopic cholecystectomy 31% There were seven complications (5%), three had had CT, 45 v 45 had GD, and 140 v 137 had of patients did not require any analgesics; 91% patients requiring immediate laparotomy NGB. did not require narcotic analgesics. (haemorrhage (2) and gall bladder rupture (1)), This study does not support an association The main advantages of laparoscopic chole- and four requiring subsequent laparotomy between cholecystectomy or gall stones and cystectomy are reduced hospital stay, lack of (slipped cystic duct clip, common bile duct colorectal cancer. However, a preliminary pain from the procedure, early return to damage, duodenal perforation, leaking acces- meta-analysis of the available published normal activities and work, and minimal scar- sory hepatic duct). Ofthe 150 patients who had reports does show positive trends and the ring. uneventful LLCs, all reported an excellent present findings may represent a false-negative cosmetic result and 63% reported excellent study of a population with a low cholecystec- pain control, one had poor control. The mean tomy rate or a publication bias in favour of time to resume normal activity was 9-6 days positive findings. How to minimise failure during exchange of and to return to work was 13-5 days. endoscopic biliary stents These data show that postoperative recovery is excellent after LLC and certainly better than D F MARTIN (Department ofRadiology, Gastro- after 'open cholecystectomy'. enterology Unit, Withington Hospital, University Photodynamic therapy for malignant Hospital ofSouthManchester) When endoscopic tumours ofthe ampulla of Vater

biliary stents become blocked they are http://gut.bmj.com/ normally removed by snaring the stent, remov- Effect of jaundice on N-6 fatty acid induced A M ABULAFI, J T ALLARDICE, R DEAN, N VAN ing it along with the endoscope and then re- SOMEREN, C P SWAIN, N S WILLIAMS, C AINLEY cannulating the papilla and tumour to insert a monocyte tumour necrosis factor production (The Surgical Unit and Academic Department of new stent. Occasionally re-cannulation fails Gastroenterology, The Royal London Hospital, and further endoscopic or percutaneous pro- W G JIANG, M C A PUNTIS (Department ofSurgery, London) Ten patients (55-78 years) with cedures are required for stent replacement. To University of Wales, College of Medicine, periampullary carcinoma who were unsuitable maintain access across the tumour, a guide wire Cardiff) Polyunsaturated fatty acids (PUFA) for resection were treated with photodynamic is inserted through the blocked stent, which is are involved in immune regulation and in this therapy (PDT), an experimental anticancer study we investigated the effect of n-6 fatty on September 28, 2021 by guest. Protected copyright. then withdrawn through a large channel duo- acids on peripheral blood monocyte tumour treatment which is potentially curative for denoscope by a biliary dilatation balloon necrosis factor (TNF) production. From non- small, light accessible lesions. Four tumours (Olbert: 180 cm long 6 Fr catheter, 2.5 cm jaundiced and patients with obstructive were confined to the ampulla, three had long, 4 mm diameter balloon) which is inserted jaundice, cells were cultured with y linolenic localised duodenal spread and three caused over the guide wire into the stent lumen and acid dissolved in ethanol concen- duodenal stenosis. Haematoporphyrin deriva- inflated with water. After withdrawal ofthe old (yLA) (final tive (4 mg kg-') was given intravenously and stent, a new stent is inserted over the guide tration of ethanol less than 0-01%). After 24 activated within tumour at 48 hours by 630 nm wire. hours, culture media were changed and the laser light via a duodenoscope (flat tipped fibre cells stimulated by lipopolysaccharide (LPS) J This technique has been used in 35 patients (10-0 ,ug/ml) for a further 24 hours. TNF 50 J/site/cylindrical diffuser 200 cm- ', inter- to date with success in 31. Three of the four values (U/ml) in the supernatants were stitially, three to four applications), to cause failures occurred early in the series when an measured by the L929 cell line bioassay. yLA selective oxidative necrosis. One to five treat- inappropriately long 4 cm balloon was used. at 10 mM and at 50 mM significantly increased ments were given over a period of two to 16 There has been no complication. Ten or 11-5 control monocyte TNF production from 20-7 months, and were well tolerated. Median Fr stents can be removed via a 4-2 mm channel U/ml (medium only) to 32-0 U/ml and 56-1 hospital stay was 4 days (range 4-10). duodenoscope and although the anchoring U/ml (p<005 by Wilcoxon signed rank test). In four with tumours confined to ampulla, flange of the stent above the tumour everts However, monocytes from jaundiced patients the macroscopic appearances returned to during removal, this does not obstruct with- showed no response to any concentration of normal at six weeks. Biopsy specimens drawal. tested. from two patients, brush cytology from one While the balloon catheter is relatively yLA on anticoagulants taken three to 16 months These data show that the n-6 PUFA yLA can no residual expensive, its use avoids the costs associated potentiate LPS stimulation of monocyte TNF after initial treatment showed with further endoscopic and radiological pro- is lost in tumour but one with a positive biopsy speci- cedures, which are a consequence of failed production; however this sensitisation men developed recurrence at six months. stent re-insertion. jaundice. The serum fatty acids are known to Four with duodenal spread had noticeable be altered in jaundice and we suggest that the endoscopic improvement with reduced tumour PBM membrane fatty acids are similarly mass. Two patients with duodenal stenosis had changed thus modifying the cells response to no significant improvement. Three patients Laser laparoscopic cholecystectomy - our yLA. developed moderate skin photosensitivity first 150 patients reaction but there were no other complications. M J HERSHMAN, RD ROSIN (St Mary's Hospital, PDT produces safe and highly effective London) Laparoscopically performed opera- Relation between gall stones, cholecystec- tumour destruction in most patients with tions cause less postoperative pain and reduced tomy, and colorectal cancer: a necropsy ampullary malignancy and in small tumours hospital stay, compared with 'open' opera- study it may be curative. British Society ofGastroenterology A1253

Biliary ultrasound in the elderly - how 1-98±0-28% despite the reduced RBF suggest- inhibition of mucin glycoprotein synthesis and appropriate? ing renal tubular dysfunction in this elderly secretion over the range 10-5_10-3 M: jaundiced group. control: 35 157 synthesis: (2270) dpmlmg Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from M MACMAHON, T N WALSH, P BRENNAN, Serum concentrations of catecholamines, protein; 10-5 M: 24 418 (1991); 10-4 M: 24406 H OSBORNE, M G COURTNEY (INTRODUCED BY J S renin, angiotensin, aldosterone, kallikrein, and (1460); 10-3 M: 9308 (332); secretion: control: DOYLE) (Departments of Gastroenterology, PGE were normal throughout in all subjects, 21 920 (22802 dpni/mg protein; 10-5 M: 12 335 Surgery and Radiology, Beaumont Hospital, suggesting that the renal abnormalities were (1053); 10` M: 12375 (845); 10-3 M: 7152 Dublin, Ireland and The Royal College of not due to neurohumoral imbalance. (340); p<0 01. Sepharose 4B-column Surgeons in Ireland) Pancreatobiliary disease In elderly jaundiced patients renal blood chromatography confirmed that secretion of poses a diagnostic challenge in all ages but flow is reversibly decreased and tubular the higher molecular weight glycoproteins particularly in high risk elderly patients where function is depressed; this predisposes to the were specifically reduced in a dose-dependent ultrasound (US) is the initial and often only development ofrenal failure. manner by indomethacin. imaging technique used to investigate this In conclusion, indomethacin inhibits both problem, thus avoiding invasive tests. To mucin glycoprotein synthesis and secretion by examine the accuracy of US in an elderly human gall bladder. population, 50 patients (age range 65-94 years) AIDS related sclerosing cholangitis: natural were studied prospectively, comparing US history and influence on overall prognosis findings with endoscopic retrograde cholangio- pancreatography (ERCP) and liver blood tests. G M CONNOLLY, A FORBES, C BLANSHARD, I M Estimation of phospholipid in human gail Indications for ERCP were abdominal pain MURRAY-LYON, M G ANDERSON, B G GAZZARD bladder bile by 'H nuclear magnetic (30), jaundice (19), cholangitis (5), and (AIDS Unit, Westminster Hospital, London) resonance spectroscopy retained stones (1). The procedure was success- Right upper quadrant pain, obstructive liver ful in 46 (92%) of patients, and showed abnor- function tests, variable biliary ultrasound J P M ELLUL, H HUSSAINI, R Z SLAPA, H PARKES, malities in 34 (74%): common bile duct stones abnormalities, and an ERCP indistinguishable G M MURPHY, R H DOWLING (Gastroenterology (22), carcinoma of pancreas (3), cholangiocar- from primary sclerosing cholangitis lead, in the Unit, Guy's Campus, UMDS, London and cinoma (3), ampullary carcinoma (1), pancreas HIV infected, to a diagnosis of AIDS related NMR Unit, Department ofChemistry, Birkbeck divisum (1), haematobilia (1), mucocoele (1), sclerosing cholangitis (ARSC). Its natural College, University ofLondon, London) Conven- and gall bladder stones (2). history and effect on overall prognosis have not tional analytical techniques disrupt the dis- US agreed with ERCP findings in only 21 of been recorded. tribution of biliary lipids between the vesicular 46 (45%) cases. US correlated in only 12 of 34 Nineteen consecutive patients with ARSC and mixed micellar phases. We and others abnormal (sensitivity 35%) and in nine of 12 (positive HIV serology, two characteristic showed that in model bile, 'H nuclear magnetic normal ERCPs (specificity 75%). In patients lesions at ERCP, without ulcerative colitis or resonance (NMR) differentiates non-invasively with ductal obstruction, US agreed with ERCP gall stones) were therefore studied. Median age between cholesterol (chol) and phospholipid in 10 of30 (33%) cases while liver biochemistry at diagnosis was 34 years (range 27-50). HIV (PL) in these two phases, although the changes showed an obstructive pattern in all 30 (100%). serology had been positive for 35 months (2- may be temperature dependent. As a first step Using ERCP, surgery was avoided in 22 (48%). 72). All had abdominal pain; 10 had diarrhoea. we quantitated total phospholipid in native bile There were no complications ofERCP. Alkaline phosphatase (ALP) was >2X normal by NMR. Thus, US was misleading and inaccurate in in 12; bilirubin was raised in two. The median Gall bladder bile was obtained peropera- 25 (54%), while ERCP, despite it's risk poten- CD4 was 58 (7-341). Cryptosporidiosis was tively (n=6). Total bile acid (TBA), PL, and tial, was safe and appropriate. Because of the present in 10, active cytomegalovirus (CMV) in chol concentrations were determined enzy- limitations of US in this age group, it is five. No gastrointestinal pathogen was identi- matically. 'H NMR spectra of unaltered bile http://gut.bmj.com/ recommended that ERCP is a necessary fied in seven. were obtained at 500 MHz, 11-75 Tesla using adjunct to that examination in the investigation Symptoms attributable to ARSC were con- D20 and a reference standard (TSP) in an ofpancreatobiliary disease in the elderly. trolled within eight weeks in surviving subjects external tube at 37°C. The assigned resonance by symptomatic measures (including for the PL choline group at 3 25 ppm and the morphine); evidence that CMV therapy influ- TSP resonance were integrated. Vesicular and enced response is inconclusive. Seven are alive micellar phases of bile were separated by without ARSC symptoms but with persistently sucrose density gradient ultracentrifugation Impaired renal function in elderly patients raised ALP at 10 months (2-28). Twelve have (DGU; n=3) and % PL, chol, and TBA in each with extrahepatic biliary obstruction died at median 5 (1-13) months. The initial phase were determined. on September 28, 2021 by guest. Protected copyright. CD4 was <120 in those dying within six Correlation between NMR and enzymatic A J MACGILCHRIST, A D CUMMING, K CRAIG, I A D months ofthe ARSC diagnosis. It is likely that total PL was 0-887 (p<0 002). Mean PL by BOUCHIER, K R PALMER (Department of ARSC has itself a good prognosis, and is not NMR was 28-8±11-8 and enzymatically PL Medicine, Edinburgh Royal Infirmary and an independent influence on the outcome of was 23-6±8-42. By DGU the vesicular phase Gastro-Intestinal Unit, Western General AIDS. constituted 82-8, 39-6, and 22-6% of the total Hospital, Edinburgh) It is well known that PL respectively. dehydrated patients undergoing surgery for In conclusion, total PL can be detected and relief of obstructive jaundice are at particular accurately quantitated in both the micellar and risk of developing acute renal failure but the Effect of indomethacin on human gail vesicular phases of human bile. pathogenesis of this potentially fatal complica- bladder mucin glycoprotein synthesis and tion is unclear. secretion Renal function was assessed in 16 jaundiced patients with malignant extrahepatic biliary F E MURRAY, B FILIPOWICZ, C J HAWKEY (Depart- Prediction of common bile duct stones: the obstruction. In nine of these it was reassessed ment of Therapeutics, University Hospital, importance of ultrasonic duct visualisation after successful endoscopic stenting. All sub- Nottingham) Gall bladder mucin glycoprotein jects took 150 mmol Na daily and central secretion is essential for gall stone formation, R J C STEELE, K PARK, F GILBERT (Departments of venous pressures were normalised. Mean acting to promote cholesterol monohydrate Surgery and Radiology, University of Aberdeen bilirubin concentration was 365±45 pmol/l at crystal nucleation. Prostaglandins may control and Department of Surgery, University of presentation and 21±7 [tmol/1 after stenting. gall bladder mucin secretion, and non-steroidal Nottingham) One hundred and forty patients In six patients aged less than 65 years renal anti-inflammatory drugs (NSAIDs) prevent admitted for cholecystectomy for uncompli- function was normal at presentation; renal gall stone recurrence in man. The aim of this cated gall stones underwent specific common blood flow (RBF) 543±61 ml/minute, study was to evaluate the effect of indo- bile duct ultrasound scanning during the 24 glomerular filtration rate (GFR) 132±26 ml! methacin on gall bladder mucin synthesis and hours before surgery. In addition, blood values minute, and fractional Na excretion (FENa) secretion in man. of bilirubin, aminotransferase, alkaline phos- 1.22+0.31%. No changes occurred after stent- Gall bladder mucosal explants (n=6 per phatase, y glutamyl transferase, and amylase ing. In the 10 patients older than 65 years (69- group) were prepared from patients under- were determined within the same time period. 82 years) mean RBF was appreciably reduced going routine cholecystectomy for gall stones. At operation, operative cholangiogram was at presentation, 189±18 ml/minute. In stented Mucin secretion in organ culture was measured performed routinely, and 22 patients were patients (n=5) RBF improved from 177 to as incorporated 3H-glucosamine after precipi- found to have common duct stones. 269±59 ml/minute. Mean GFR was modestly tation with TCA/PTA. Results are expressed as Of 10 patients in whom common duct stones reduced, 63±6 ml/minute, and did not change mean (SEM). had been seen on ultrasound, all were found to after stenting. Mean FENa was increased at Indomethacin caused a dose-dependent have such stones, and of 35 other patients in A1254 BritishSocietyofGastroenterology whom an entire empty duct had been visual- destined to die of recurrent disease would help and female non-smokers compared with ised, none were found to have stones. Thus if target these patients for adjuvant therapy. current smokers. Conversely Crohn's disease

stones or the whole length of the common duct The histological specimens of 123 patients (CD) is positively associated with smoking. Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from were imaged, ultrasound attained 100% with newly diagnosed Dukes's B CRC admit- The aetiology of pouchitis in patients with efficiency. ted between 1983 and 1988 were subjected to UC who have had a restorative proctocolec- In the remaining 95 patients, however, a detailed analysis by a single histopathologist. tomy is unknown. It may represent recurrent dilated duct was not very useful having a Histological variables studied included the inflammation similar to the original UC in ileal positive predictive value of only 42%. Like- overall grade and extent of tumour, type of mucosa that has undergone colonic metaplasia. wise, alkaline phosphatase, the best bio- tumour front, presence or absence of inflam- Therefore, it seemed plausible that pouchitis chemical predictor, had a positive predictive mation, mucin, vascular invasion, neural may be related to smoking habit. value of 45%. A combination of these two invasion, necrosis, stromal reaction, Crohn's Patients having a functioning pouch for 1 parameters was better, but only achieved a reaction, peritonitis, the presence ofa papillary year were assessed. Smoking data were collated positive predictive value of 71%. Attempts at pattern to the tumour, signet ring pattern, and via questionnaire or direct interview. Non- improving non-invasive preoperative predic- the number of negative lymph nodes in the smokers included ex-smokers who had ceased tion of common duct stones should focus on specimen. Follow up was between 19 and 87 prior to pouch formation. Patients were improved ultrasonic visualisation of the whole months. The end point was taken as total excluded if (i) original indication was not UC length of the duct. mortality. (n=4), (ii) the excised pouch revealed histo- Using a stepwise Cox regression model, both logical appearances diagnostic of CD (n=2), or neural invasion and necrosis were found to be (iii) data was inadequate (n= 10). Smokers independent variables related to survival. (8 M: 3 F) had a mean follow up of 3-9 years Diarrhoea after cholecystectomy: an under- Patients with neural invasion had an increased (total=43 years). Average cigarette consump- estimated problem? relative risk of 3-02 (p<0-01) while those tion was 10 5/day. Non-smokers (32 M: 18 F) whose tissues displayed necrosis had an had a mean follow up of 3-4 years (total= 170 D PARKER, K W HEATON (University Department increased relative risk of 2-5 (p<0-01). No years). Pouch type was similar in the two of Medicine, Bristol Royal Infirmary, Bristol) other parameter added to these could predict groups being 5 J, 5 W, 1 S, and 20 J, 19 W, Diarrhoea after cholecystectomy, caused by an unfavourable outcome. Neither age nor sex 11 S respectively. type 3 bile acid malabsorption, is generally were significant variables. One smoker has had one episode of thought to be rare but bowel function after In conclusion, the finding of neural invasion pouchitis. Conversely 14 non-smokers have cholecystectomy has not been systematically or tissue necrosis in patients with Dukes's B had 34 episodes (mean=2-1, SD=11) of studied. We have assessed bowel function in 48 CRC heralds a poor prognosis and such indi- pouchitis. The difference in number of of the 51 cholecystectomised subjects in a viduals should be considered for adjuvant episodes was significant (X2 with Yates correc- random population sample (27% men) and, as therapy. tion p<0 02). Pouch 'function' at 12 months controls, 85 ofthe 92 people with ultrasonically (number of bowel actions in 24 hours) was discovered gall stones in the same sample (46% This abstract was alsopublished in the Manchester similar in the two groups being mean=4-1, men, ages similar). Time elapsed since chole- programme, April 1991, but not presented. SD=1-6 in smokers, and mean=5-1, SD= 16 cystectomy was 3 months to 26 years (mean in non-smokers. 7 years). Nearly all the newly discovered gall This study suggests that smoking mav be stones were asymptomatic. Subjects recorded protective against pouchitis. Further larger three defecations on a special form, including Embolisation of superior haemorrhoidal studies are indicated. stool type on a validated six point scale. Symp- artery for severe rectal bleeding toms and bowel frequency were assessed by http://gut.bmj.com/ standard questionnaire. J K DERODRA, J F REIDY, M H JORDAN (INTRO- Unformed stools (types 5 and 6) and liquid DUCED BY R C MASON) (Departments ofRadiology Colonic type mucin occurs in the ileal pouch stools (type 6) were significantly commoner in and Surgery, Guy's Hospital, London) Angio- and small intestinal Crohn's strictures, but the cholecystectomy group (unformed 27-5% graphy is invaluable in localising the site of not in coeliac disease of all stools v 12-4% in the gall stone group, gastrointestinal bleeding, but its role in con- p1 in 4 describe two cases of severe rectal bleeding MILTON, A CAMPBELL, C PRINCE, D P JEWELL defecations) was much more prevalent in the successfully treated by embolisation of (Gastroenterology Unit, The Radcliffe Infirmary, on September 28, 2021 by guest. Protected copyright. cholecystectomy group (35 9% v 5.7%, superior haemorrhoidal artery. Case 1 had Oxford) Colonic metaplasia (adaptation) is well p<0.001). These differences were present in bleeding from a solitary rectal ulcer and case 2 described in the ileal pouch. This has been both sexes (but small numbers precluded after local excision ofrectal villous adenoma. In attributed to stasis and possibly bacterial over- significance in men). No cholecystectomy sub- both cases, conventional surgical procedures growth. However, the mechanism is unknown. ject habitually defecated more than twice daily had failed to control this bleeding. The aims ofthis study were to assess adaptation and in only 5% were all three recorded stools Using coaxial catheter techniques and a 3F of pouch mucin and to determine whether the liquid. Teflon catheter, the superior haemorrhoidal changes are specific to the ileal pouch. In conclusion, unformed stools and urgency artery was selectively catheterised and then Paraffin sections of ileal pouch (9), proximal of defecation are commoner after cholecystec- embolised using Gelfoam particles. This end of resected small intestinal Crohn's tomy but continuous diarrhoea is rare. arrested bleeding in both cases, with no strictures (11), active coeliac disease (7), evidence of bowel ischaemia. In case 1 emboli- ileostomy (1), normal ileum (2), and rectum (4) sation was used as the sole treatment due to the were assessed. Villous height was assessed on patient's poor medical condition. Case 2 had an haematoxylin and eosin stained sections and A-P resection of the rectum once his general the degree of inflammation scored (0-3) for condition improved, after embolisation and both acute and chronic changes. Mucin histo- COLORECTAL cessation ofbleeding. chemistry was performed using high ion Embolisation of superior haemorrhoidal diamine-alcian blue (HID-AB) graded 1 = artery in controlling rectal bleeding has not sialomucin, 2= mixed, and 3=sulphomucin, as been described before and this is a relatively well as with a monoclonal antibody (MMM-17) Histological predictors of poor outcome in easy solution to what can be a formidable against 8-0 acetyl sialomucin (colonic mucin) Dukes's B colorectal cancer problem, especially in poor risk patients. also graded 1-3. The pouch biopsy specimens showed mixed H MULCAHY, M TONER, L DALY, S PATCHETr, D P staining, with a mean grade of 2-0 (HID-AB) O'DONOGHUE (Departments of Gastroenterology, and 2-2 (MMM-17). In Crohn's strictures the Pathology and Epidemiology, St Vincents Smoking and pouchitis grades were 2-2 and 2-6, coeliac disease 1-0 and Hospital, Dublin, Ireland) Dukes's classifica- 1-0, ileostomy 1-0 and 1-0, ileum controls 1-0 tion is a widely used histological prognostic M N MERRETT, N MORTENSEN, M G W and 1-0, and rectum controls 3.0 and 3.0 indicator ofcolorectal cancer (CRC). However, KETTLEWELL, D P JEWELL (Gastroenterology respectively. In pouch mucosa villous atrophy, long term survival of patients with early lesions Unit, The Radcliffe Infirmaty, Oxford) Retro- but not inflammation, seemed to correlate with as staged by this system is by no means assured. spective assessment of smoking habits has the presence of colonic mucin. Some 70% of patients undergoing surgery for shown a reduced risk of ulcerative colitis (UC) In the ileal pouch and proximal to small Dukes's B CRC can expect to be alive at five in current smokers. One case control study intestinal Crohn's strictures, there is a partial years. Identification of the 30% of individuals found overall relative risks of4 and 3-6 for male switch to colonic mucin. No such change was British Society ofGastroenterology A1255 seen in active coeliac disease or in mucosa from M R THOMPSON, P W LEOPOLD, S JACKSON (St lators may therefore excrete more carcinogen in an ileostomy. This suggests that stasis, and not Mary's Hospital, Portsmouth) Since October bile than fast acetylators. of We determined acetylator status in familial villous atrophy or inflammation, is related to 1983, Delormes has been the procedure Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from the mucin changes. choice to treat full thickness rectal prolapse on adenomatous polyposis (FAP) patients (n= an 'all comers, no exclusion' basis. Fifty six 41), sporadic colorectal cancer (CRC) patients patients underwent 60 procedures including (n= 11), and normal healthy controls (n=232). four repeat Delormes. Six patients had After ingestion of 300 mg of caffeine and an Lifetable survival analysis of patients with previously undergone six different procedures eight hour urine collection, urinary metabolites intra-abdominal desmoid disease in familial to treat their rectal prolapses with limited were measured by liquid chromatography and adenomatous polyposis success. None of these procedures precluded metabolic ratios used to determine acetylator Delormes. Mean age was 73 years (range 27- status. The x2 test was used for statistical K C R FARMER, R K S PHILLIPS (St Mark's 83 years) with 44 patients (78%) over the age of analysis. Hospital, London andProfessorialSurgical Unit, 70 (51 female and 5 male). Prolapse history There were significantly more slow acety- St Bartholomew's Hospital, London) Intra- ranged from 1 month to 20 years. Anaesthesia lators in FAP (75%) and sporadic CRC abdominal desmoid tumours encase the used included 53 general, 4 local, and 3 spinal patients (91%) compared with controls (52%) superior mesenteric artery making resection anaesthetics. Length of mucosal stripping (p

patients. The diagnosis of intra-abdominal (>80 at 5 days) and "4In-DTPA (showing http://gut.bmj.com/ disease does not carry a universally dismal (Ist Department ofSurgery, University ofRome, transverse/splenic flexure delay) transit prognosis. 'La Sapienza', Italy) In order to assess the studies), who underwent therapeutic subtotal hypothesis of an altered bile composition in colectomy for this condition and 12 control patients with colorectal cancer, we prospec- specimens removed for neoplastic disease. tively studied 72 subjects. Thirty six of these Samples were taken from both resection Results of restorative proctocolectomy in patients had colorectal cancer (group A), while margins and at 5-10 cm intervals. Histo- patients over the age of 50 years the remaining 36 required a laparotomy for chemical stains and immunochemistry for non-gastrointestinal illnesses (group B, control neurofilament, S-100, and neuron specific population). Bile samples were always taken on September 28, 2021 by guest. Protected copyright. W LEWIS, P J HOLDSWORTH, P SAGAR, D enolase (NSE) antigens were performed. Every JOHNSTON (University Department of Surgery, directly from gall bladder at operation. We region sampled in all specimens from STC The General Infirmary, Leeds) Restorative found, for each biliary salt, the following mean subjects showed an increase in small nerve proctocolectomy (RP) is the operative pro- percentile values: cholate 36-7% in group A v fibres of the muscularis propria: this was not cedure of choice for 'young' patients with 40.7% in group B, chenodeoxycholate 37 9% in seen in any of the controls. No other neural or ulcerative colitis (UC). However, a report from group A v 41-1% in group B, deoxycholate myocyte abnormalities were detected. There the Mayo Clinic that mean bowel frequency 20-9% in group A v 13.4% in group B, litho- was no correlation between distribution of was 11 in 24 hours after RP with J pouch in cholate 3.5% in group A v 4.9% in group B. At histological changes and regional delay in patients over 50, compared with 7 in 24 hours statistical analysis of the standard error of the colonic transit as detected on "I'In-DTPA. - differences between the above reported means, in patients under 50, has together with con- only deoxycholate proved to be significantly These changes are not similar to those siderations of risk to life - tended to limit the higher in the colorectal cancer group compared reported in other gastrointestinal neuropathic use of RP to younger patients. with the controls. conditions. Although definite abnormalities of Between 1986 and 1991, 18 patients aged 50 This study suggests that colorectal cancer innervation occur in the colon in STC, it is not to 66 years (median, 55 years: 9 male) under- patients are carriers of an altered bile only with possible to say whether these represent a went RP with ileoanal anastomosis, end to end regard to deoxycholate, which, alone, should primary defect or an adaptive response to the without mucosal stripping (11 W, 5 J, 2 no, be considered as one the functional abnormality. pelvic reservoirs). The results were compared therefore of possible with those of 18 matched patients (same sex, promoters of colorectal cancer. reservoir, operative technique, follow up) aged under 50 (median 34 years). Measurement of segmental colonic transit Function of the anal sphincters was well in idiopathic constipation using orally preserved in the older patients after RP without Acetylator status: a link between hepatic administered isotope in enteric coated mucosal stripping. The functional outcome metabolism and colorectal cancer capsules was slightly, but not significantly, inferior to the outcome in younger patients. Hence, K C R FARMER, S E OLIVER, A D SPIGELMAN, P N B PANAGAMUA, N TULLEY, A NOTGHI, M OYA, L K 'fitter' patients over the age of 50 need not BENNETT, RK S PHILLIPS (St Mark's Hospital, HARDING, D KUMAR (Department of Surgery, be denied the benefits of restorative London and Professonral Surgical Unit, St Queen Elizabeth Hospital, Birmingham and protocolectomy. Bartholomew's Hospital, London) Bile Department of Nuclear Medicine, Dudley Road influences gastrointestinal neoplasia, perhaps Hospital, Birmingham) We measured segmental by hepatic metabolism of environmental colonic transit using a methacrylate coated carcinogens. The enzyme N-acetyltransferase capsule filled with 2 MBq of" 'In impregnated Delormes procedure for rectal prolapse - a detoxifies gastrointestinal carcinogens and its resin in four healthy volunteers and seven consecutive unselected series activity (fast or slow) is inherited. Slow acety- patients with chronic idiopathic constipation A1256 Bnrtish Society ofGastroenterology

(CIC). Half to three hourly images of the colon histology. Colitis was graded as active or synthesis. We have previously shown that were obtained during a three day period. Time inactive. The other was homogenised in buffer longstanding NSAID therapy is associated

zero was when all activity was seen in the and assayed for alkaline phosphatase activity with increased gastric mucosal leukotriene B4 Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from caecum. The colon was divided into four and related to the DNA content of the biopsy (LTB4) synthesis. LTB4 may promote gastritis regions of interest (ROI) - caecum to hepatic homogenate. by neutrophil recruitment, lysosomal enzyme flexure, transverse colon, splenic flexure, rest A highly significant difference in alkaline release, and changes in vascular permeability. of the colon and rectum respectively. Visual phosphatase activity was found between the The aim of this study was to examine the analysis of images indicated patients with control (0.53+0.2 U/mg DNA) and ulcerative relation between gastric mucosal LTB4 either right sided (group 1) or left sided (group colitis (1-31+0-58 U/mg DNA) groups (p= synthesis and mucosal inflammation assessed 2) delay in transit. Percentage activity in each 0-001). The active ulcerative colitis group histologically. ROI at 6, 24, 32, 48, and 56 hours was (n=9) had higher alkaline phosphatase activity Fifty eight patients on longstanding NSAID measured and mean values in the two groups (1 63+0-56 U/mg DNA) relative to the inactive therapy underwent endoscopy. Two ex vivo were compared with those in the control group (n=15, 1.I2+0.52 U/mg DNA). This antral gastric biopsy specimens were stimu- subjects. difference was significant (p<005). lated by vortex mixing and supernatant Group 1 had mean (SEM) 59-2 (4.9)% The measurement of mucosal alkaline phos- measurements of LTB4 determined by radio- activity retained in ROI 1 compared with 15-8 phatase values may represent an objective and immunoassay, two further biopsy specimens (8.5) in controls (p=0002). Correspondingly, reliable assessment ofdisease activity. were processed for histological assessment. this group had significantly less activity in Microscopy was classified as normal mucosa, ROI 3 (p=0-01) and ROI 4 (p=003) when chemical gastritis (foveolar hyperplasia, compared with controls. Similarly, group 2 had smooth muscle extention, vascular ectasia), or greater activity (32-7 (9 1) v 10-4 (2.0), Does the rectum contract during active chronic gastritis (inflammatory cell p<0-01) in ROI 4. At the end of 48 hours, defecation? infiltrate+architectural distortion). the controls and patients in groups 1 and 2 The results showed that there was a signifi- had evacuated 50%, 5%, and 0% activity A MACDONALD, P J PATERSON, J N BAXTER, I G cant increase in median gastric mucosal LTB4 respectively. FINLAY (Departments of Surgery and Urology, synthesis in NSAID patients with chemical These data show segmental transit delays in Royal Infirmary, Glasgow) During normal gastritis 2.2 pg/mg (IQR.0.4-2.9) compared CIC. This technique allows quantification of defecation the intrarectal pressure is observed with patients with normal mucosa 0-2 pg/mg colonic transit and may be useful in the man- to rise. In the absence ofa reference catheter in (0 0-08) (p<0-01). Patients with active agement ofpatients with CIC. the pelvis, the contribution of abdominal chronic gastritis also had higher LTB4 09 pg/ straining and rectal contraction to the intra- mg (04-3.2) but this did not reach significance rectal pressure rise is unclear. The aim of this (p0 1). leukins, and epidermal growth factor disease. These results demonstrate that significant alterations in the circulating lymphocyte pool W G JIANG, M C A PUNTIS (Department ofSurgery, occur early in the course of a severe attack of University ofWales College ofMedicine, Cardiff) acute pancreatitis. Reversal of these changes In some pathological conditions both the using immunomodulators has potential thera- spontaneous and stimulated (for example, by peutic significance. phagocytosis) secretion of lysosomal enzyme Non-Hodgkin's lymphoma and AIDS: fre- by monocytes is increased. In this study we quency of gastrointestinal localisation in a investigated the effects of several cytokines at large Italian series. different concentrations on this enzyme secre- http://gut.bmj.com/ Spectrum of liver disease in cotton top tion. Peripheral blood monocytes were treated G BIANCHI PORRO, F PARENTE, M CERNUSCHI, tamarin colitis either by culture medium or by cytokine for G RIZZARDINI, L VALSECCHI (Departments of four hours. The lysosomal enzyme, hexo- Gastroenterology andInfectiousDiseases, L Sacco B F WARREN, N K CLAPP (Department of saminidase, released into the supernatant was Hospital, Milan, Italy) Although the close Pathology, University of Bristol, UK and measured colorimetrically and expressed as a association between AIDS and non-Hodgkin's MARCOR, Oak Ridge Associated University, percentage ofthe total enzyme content released lymphoma (NHL) is widely known, no study Oak Ridge, Tennessee, USA) Spontaneous by triton treatment. Interleukins 1, 2, and 6 has evaluated the frequency of gastrointestinal (ILl, IL2, and IL6), tumour necrosis factor colitis of unknown cause is common in new on September 28, 2021 by guest. Protected copyright. (GI) involvement in a large series of AIDS world monkeys. In the cotton top tamarin, (TNF), and epidermal growth factor (EGF) patients with heterogenous risk factors. From most cases bear a close relation to human were studied. June 1985 to May 1990, a total of 70 ulcerative colitis clinically, endoscopically, and The median spontaneous secretion of patients (64 male and 6 female, mean (SD) 32-3 in response to treatment. enzyme was 5-6%. TNF at concentrations (8.6) years) with AIDS associated NHL were One hundred necropsy livers were studied below 125 pg/ml caused no increase but 250 pg/ evaluated at L Sacco Hospital. Fifty three from cotton top tamarins with total severe ml and 500 pg/ml resulted in secretion of 15-6% patients were intravenous drug addicts and ulcerative colitis, negative stool cultures, and a and 22-7% respectively, which was signific- 17 homosexuals. All had B cell lymphomas histological picture resembling human ulcera- antly different from spontaneous secretion. An and the histological subtypes were: high tive colitis. Only 39 livers were normal. In 20 ILl concentration above 62.5 pg/ml increased to grade malignant NHL in 48 cases (69%), there was a mild periportal chronic inflamma- hexosaminidase secretion significantly intermediate grade in 21 patients (30%), and tion, 16 had extensive steatosis, four had 16 1% and up to 70.4% at an IL1 concentration test was low grade in one case (1%). Sixty five patients an appearance resembling chronic active of 500 pg/ml. Wilcoxon signed rank (93%) had evidence of extranodal disease hepatitis, and in four the histology resembled used and p values less than 0.05 were taken and in 22 a GI involvement was ascertained that of sclerosing cholangitis. Other hepatic as significant compared with spontaneous and showed no at necropsy. Of these, 13 had complained pathologies were seen in smaller numbers. secretion. IL2, IL6, EGF of digestive symptoms which allowed us to These changes parallel the liver disease seen stimulatory effects on enzyme secretion. make an antemortem diagnosis: seven in association with human ulcerative colitis. The effects of TNF and ILl on hexo- patients had acute GI bleeding, four patients We believe the cotton top tamarin provides the saminidase secretions may in part explain the complained of recurrent abdominal pain, and first model of liver disease in ulcerative colitis, increased and possibly harmful lysosomal diseases two patients presented with abdominal mass which allows study of the pathogenesis of one enzyme values in inflammatory bowel associated with pain. Three patients had of the extraintestinal manifestations of ulcera- and jaundice for example. radiological and/or endoscopic evidence of tive colitis. lymphomatous disease along the entire digestive tract but, more frequently, isolated involvement of the stomach and/or Education, employment, and inflammatory duodenum (four patients), small bowel bowel disease (four patients), or colon (two patients) was Colitis in the cotton top tamarin - is it a model found. of ulcerative colitis? M K MAYBERRY, C S PROBERT, J F MAYBERRY We conclude that the GI tract is a (Leicester General Hospital, Leicester) Children common site of extranodal NHL in HIV B F WARREN, G R PEARSON, P WATKINS, J PRICE, and their parents are often anxious that chronic infected patients; in 59% of the cases this J W B BRADFIELD, I A SILVER (Department of disease may interfere with their future. The localisation produces severe clinical manifest- Pathology, University of Bristol, Bristol) Con- provision within schools for children with ations. troversy remains concerning the similarity of inflammatory bowel disease was investigated British Society ofGastroenterology A1259 in 70 schools with over 48 000 pupils. Most Oxygen free radical production in acute Specificity of mucosal celi mediated (95%) provided easy access to lavatories infective and inflammatory colitis immunity in inflammatory bowel disease during examinations and told examination boards of a child's medical problem. Most R J CORSON, I S PATERSON, A M HANBURY, P F J R LOWES, J P IBBOTSON, H CHAHAL, J Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from heads (80%) want more information, but few SCHOFIELD (University Hospital of South Man- ALEXANDER-WILLIAMS, R N ALLAN (General have facilities to inform teachers about chester, Manchester) Neutrophil dependant Hospital, Birmningham and Department of chronic illness. oxygen free radical (OFR) production was Medical Microbiology, University of Birming- Eighty three patients with Crohn's disease investigated in patients with acute colitis at ham) There is evidence of activated mucosal diagnosed under 40 completed a questionnaire presentation and at six weeks, using flow cell mediated immune responses in ulcerative about educational and employment experi- cytometric analysis of dichlorofluorescein colitis (UC) and Crohn's disease (CD). It is ences and were compared with controls. The oxidation quantified in fentamoles (fm) of unclear if this is due to a specific pathogen or mean age at survey was 31±5 years. Twenty dichlorofluorescein/cell. Phorbol myristate abnormalities in the mucosal immune system. four patients were diagnosed during schooling; acetate (PMA) acted as a standard second Both enterobacteria and mycobacteria have they lost significantly more schooling than stimulus to access neutrophil responsiveness. been implicated in the aetiopathogenesis of UC controls (X2= 14.3, p<0-001) but had similar Irritable bowel (n= 10) and normal subjects and CD. We have investigated gut associated academic successes. Their current employ- (n= 10) acted as controls. Classification of and systemic cell mediated immunity in ment rate was similar, but significantly more infective (n=9) from inflammatory (n= 12) patients with CD (n= 15), UC (n=6), and patients had experienced long term unemploy- colitis was made retrospectively. controls (n=21) to a panel of antigens. ment (z=2.6, p<0-01), as a result 30% actively At presentation the results were 16±4 fm Mononuclear cells from mesenteric lymph concealed their diagnosis. (35±6 fm PMA) in normal subjects, nodes (MLNC) and peripheral blood Personnel managers at 61 national and 18±6 fm (37±8 fm PMA) in irritable bowel, (PBMNC) from consecutive patients under- 136 local employers, with over 1 000000 112±7 fm* (321±19 fm* PMA) in infective going surgery for UC, CD, or controls (colonic employees, were asked about their attitude to colitis and 126±14 fm* (340±22 fm* PMA) resection, cholecystectomy) were employed in people with inflammatory bowel disease. The in inflammatory colitis (*p<0.01 relative to six day lymphocyte proliferation assays. The attitude was often positive, although 25% controls). By six weeks in infective colitis antigen preparations studied were the 65 kD would not continue to employ people after neutrophil activity returned to 17±5 fm recombinant heat shock protein of Mycobac- diagnosis and 30% would not provide time off (31±7 fm PMA), a level no different to tenum leprae; and heat killed preparations of work to attend clinics. Of the expected 457 controls, but remained raised at 55±10 fm* Salmonella agona; Escherichia coli; Yersinia employees with inflammatory bowel disease, (62±11 fm* PMA) in inflammatory colitis enterocolitica; Influenza; Chlamydia trachomatis; employers were only aware of 61, which con- (*p<0-01 relative to controls). and Candida albicans. firms concealment of their diagnosis. Inflam- OFR production is thus: (1) raised in Responses (PBMNC and MLNC) to all matory bowel disease remains a devastating infective and inflammatory colitis to the same antigens in UC and CD were greater than disease. degree at presentation; (2) returns to normal in controls. The greatest MLNC responses were infective colitis by six weeks; (3) remains raised to antigen preparations from enteric bacteria in inflammatory colitis, a feature which may in UC, CD, and controls. In control sub- explain the continuing mucosal damage seen in jects there was no difference between inflammatory colitis. Y enterocolitica, E coli, and S agona. In CD the IgG subclasses in inflammatory bowel greatest responses were seen to Y enterocolitica diseases and these were greater than responses to E coli (p<005) and S agona (p=0058) (Mann- M A QUADERI, D P JEWELL (Gastrointestinal Unit, Witney U test). There was no evidence of The Radcliffe Infirmary, Oxford) Previous specific sensitisation to mycobacterial antigens http://gut.bmj.com/ studies of immunoglobulin G (IgG) subclass Helicobacter pylori induced gastritis is in patients with UC or CD. concentrations in ulcerative colitis (UC) and not caused by bacterial ammonia produc- These results do not support a mycobacterial Crohn's disease (CD) have reported predomi- tion aetiology for CD or UC, but suggest that nant increases in IgG, in active UC and IgG2 in further study of cell mediated immunitv to active CD. We have measured concentrations K E L MCCOLL, S DAHILL, A EL NUJUMI, J enterobacteria, particularly Yersinia species of IgGI- in patients with UC (19 active, 17 in HARWOOD, P ROWE (University Department of are required. remission), CD (14 active, 20 in remission), Medicine and Therapeutics, Western Infirnary, irritable bowel syndrome (IBS) (15), and Gasgow) Gastric juice ammonium concentra- on September 28, 2021 by guest. Protected copyright. normal volunteers (10). IgG subclass concen- tions and the severity of histological antral trations were measured by radial immuno- gastritis were studied in 16 uraemic patients (8 diffusion. H pylon +ve, 8 -ve) and in 16 patients with Expression of neutrophil receptors CR3, Mean (SD) concentrations ofIgGi were 6474 normal renal function (8 H pylon' +ve, 8 -ve). FcRl, and FcR3 in Crohn's disease mg/I (1706) (UC active), 8481 mg/l (2925) (UC H pylon status was confirmed by microscopy of rem), 4549 mg/I (1757) (CD active), 5504 mg/l antral biopsy, "4C-urea breath test, culture, J C W LEE, C N GUTTERIDGE, D S RAMPTON (St (756) (CD rem), 5358 mg/l (1188) (IBS), and and serology. Histological gastritis was Mark's Hospital and Royal London Hospital, 5303 mg/l (1234) (normal). assessed using a standardised score (polymorph London) Complement receptor 3 (CR3) and Fc Mean (SD) concentrations of IgG2 were infiltrate 0-6, chronic inflammatory infiltrate receptors for IgG (FcR1, FcR3) are leukocvte 2910 mg/l (1228) (UC active), 3158 mg/l 0-2, and mucosal erosions 0-2). The H pylon' surface receptors with roles in vascular endo- (1397) (UC rem), 4690 mg/l (2116) (CD +ve patients with renal failure had consider- thelial adhesion and phagocytosis respectivelv. active), 2454 mg/I (1239) (CD rem), 2574 ably higher intragastric ammonium concentra- Little is known of their involvement in Crohn's mg/I (742) (IBS), and 2793 mg/l (463) tions (mean=24 mmol/1, range 14-43) than disease (CD). We have compared their expres- (normal). Thus, IgG, is raised in UC in those without renal failure (3.4 mmol/l, range sion on peripheral blood neutrophils in healthv remission (p<0-0001) and IgG2 in active CD 1-13) (p<001), yet the mean aggregate controls (n=7) and patients with CD (n= 19) (p<0-0001). IgG3 and IgG4 concentrations gastritis score was similar in the two groups by indirect immunofluorescence and flow were similar in all groups. (5 0, range 3-6 and 5-1, range 3-7 respect- cytometry. We then measured the specific IgG1 response ively). All the H pylori -ve patients had Expression ofCR3 was reduced in CD (mean to vaccination with tetanus toxoid, and IgG2 negligible gastritis (score 0 or 1) in spite of the (SD) 52 (27)% compared with controls (85 (4)% response to pneumococcal polysaccharide in ammonium concentration in those with renal (p<0-01)). Similar results were observed with quiescent UC (n= 15) and Crohn's disease (n= failure (4.4 mmol/l, range 1-12) being similar FcR3 (CD 46 (29)%, control 78 (10)%; 14), IBS (n=6), and normal volunteers (n=5) to that in H pylon +ve patients without renal p<0-01). In contrast, FcRI was increased in using an enzyme immunoassay. All groups failure and being considerably higher than in CD (14 (19)%, control 2 (1)%; p<0-001). FcRl showed a similar post-vaccination rise in the H pylori -ve patients without renal failure expression was directly related to clinical specific antibody levels. (0-6 mmol/l, range001-1 1). disease activity; Harvey-Bradshaw score (R= These data confirm the previously described These findings show that antral gastritis 0 5, p<0-01) and to C reactive protein (R=0-5, pattern of IgG subclass increases in UC and correlates with the presence of H pylori but p<002). FcR3 expression showed converse CD, and suggest that these changes are more is unrelated to intragastric ammonium concen- correlations with these variables (R=-0-5, likely to be due to a response to the nature of trations. p<002; R=-0-4, p<004 respectivel) and luminal antigens rather than a genetic predis- In conclusion, H pylori induced antral was negatively related to FcRI expression (R= position to synthesise individual subclasses gastritis is not due to mucosal damage by -0-45, p<003). preferentially. bacterial ammonia. In conclusion, adhesion of activated neutro- A1260 British Society ofGastroenterology phils to endothelium in inflamed gut could teinases, closely resemble the pattern reported adjuvant. Fifteen days later net water move- account for the reduced expression of CR3 for human Crohn's. Unlike the rat, in which a ment was measured by small intestinal per- and FcR3 in circulating neutrophils in CD. similar model has been developed, rabbit distal fusion for 90 minutes with either plasma Increased FcRl expression in active CD could colon has a mechanical and pharmacological electrolyte solution (PES) or PES+OA (200 Gut: first published as 10.1136/gut.32.10.A1203 on 1 October 1991. Downloaded from be cytokine induced. FcR receptor assay could profile resembling human colon. Additionally mg/l). Serum antigen specific IgE titres were serve as a marker of disease activity in CD. the simplicity, histopathological similarity and measured by passive cutaneous anaphylaxis at its duration make this a suitable model for the end of the perfusion. In rats inoculated evaluating the effects of new treatments on orally with OA no IgE response was detected, pathogenesis. and there was no difference in water absorption Interactions between platelet activating between those perfused with PES (n=9) or factor and eicosanoids and their effects on PES+OA (n=10) (median 92 (interquartile mucosal factors range 84-109) v 79 (71-107) pl/minute/g; NS). Bile modulates genotypic and phenotypic In contrast, rats sensitised by ip route and T D WARDLE, L A TURNBERG (Epithelial characteristics ofGiardia lamblia which developed a positive IgE response had Membrane Research Centre, Department of reduced water absorption on antigen challenge Medicine, Hope Hospital, Salford) In ulcerative P H KATELARIS, T D MCHUGH, S CARNABY, A M (69 (34-73) (n=7) v 23 (6-37) dl/minute/g colitis (UC) inflammatory cells release a variety CEVALLOS, S CHAR, M J G FARTHING (Department (n=4); p<0 05). of mediators which may stimulate intestinal ofGastroenterology, St Bartholomew's Hospital, Thus, neither local nor systemic sensitisa- secretion and contribute to the production of London) Giardia lamblia consume bile salts and tion to a food allergen could be elicited by oral diarrhoea. Colonic mucosal biopsy specimens bile stimulates growth of G lamblia in vitro. exposure during the recovery phase of RV were take'n from 30 patients with active colitis These observations are relevant to the host- infection. This suggests that other variables are and from age and sex matched controls with parasite interaction as G lamblia localise to the involved in the pathogenesis offood allergy. irritable bowel syndrome. Specimens were upper gut where bile is abundant. In this study, cultured (a) untreated; or with (b) platelet the effect of bile on the phenotype and geno- activating factor (PAF); (c) indomethacin and type of 3 isolates (RW6, WB, and GP) was ICI 207968 (cyclo-oxygenase and lipoxygenase examined. G lamblia were cultured in TY1-S- inhibitors); (d) mepacrine (phospholipase A2 33 medium containing 0-6 mg/ml bovine bile Staging and survival of patients with inhibitor); (e) PRA (PAF antagonist); or (f) (TYI+B) for 10-20 passages and compared colorectal cancer: the die is cast at onset of combined (c) and (e). Culture medium was with organisms grown in bile free media with symptoms assayed for PAF, PGE2, and LTD4 and its respect to generation times, morphometrics, effect on short circuit current (Isc) across rat incorporation of [35S]-methionine, expression H MULCAHY, A LOHAN, S PATCHETT, N AFDHAL, distal colonic mucosa in vitro. Results show of heat shock proteins, and biotinylation of D P O'DONOGHUE (Gastroenterology and Liver that PAF was liberated into culture medium by proteins. Genotype was assessed using DNA Unit, St Vincent's Hospital, Dublin, Ireland) inflamed tissue only but PGE2 and LTD4 were fingerprinting. DNA was cut with restriction Early investigation of lower gastrointestinal liberated by control and inflamed tissue. enzymes RSA-1 or PVU-II and probed with (GI) symptoms has been advocated to improve Medium from inflamed tissue generated a the M13 phage genome. the five year survival ofpatients with colorectal higher Isc response than control tissue Generation times in TYI+B were acceler- cancer (CRC). This is based on the assumption medium. The production of PGE2 and LTD4 ated by 32% for RW6 and 31% for WB; mean that a short duration of symptoms confers and the rise in Isc induced by exogenous PAF surface area in stationary phase was increased benefit as regards staging and outcome. Since (10-5 M) were inhibited by indomethacin plus by 16% (p<0.01) for RW6. Neither parameter 1983 all patients in this institution with newly 207968 and mepacrine but not PRA. was significantly altered with GP. diagnosed CRC have had clinical data, includ- ICI, [35S]- http://gut.bmj.com/ Mepacrine produced the greatest attenuation methionine incorporation was diminished in all ing symptom duration, entered on to a in PAF, PGE2 and LTD4 release and the three isolates cultured in TYI+B while expres- computer database. The aim of this study was Isc. Combined indomethacin/ICI 207968/PRA sion of heat shock proteins was unchanged. to examine the relation between duration of reduced PGE2 and LTD4 release and the Isc, The profile ofbiotinylated proteins was altered symptoms and both the extent of disease and but did not influence PAF generation. in all three isolates grown in TYI+B most survival. In conclusion PAF is only produced by notably in the region of 170 kDa. DNA finger- Some 512 patients admitted between 1983 inflamed tisue, its potent secretory effect is printing revealed genomic differences between and 1989 inclusively had a mean duration from mediated predominantly by stimulating isolates grown with and without bile. Most onset offirst symptoms to final diagnosis ofjust eicosanoid release. striking was a band observed at 1-8 kb in WB 16 weeks, considerably shorter than most on September 28, 2021 by guest. Protected copyright. grown without bile which was absent in WB published series. Dukes' D tumours had a grown with bile. significantly shorter duration of symptoms Bile thus affects phenotypic and genotypic (10-5 weeks) than less advanced lesions Model of hapten induced inflammatory expression ofG lamblia in vitro, but the effects (p<0-01). A short symptom duration was bowel disease in the rabbit colon are variable between isolates. This may be predictive of more severe disease (p<0-01), relevant to parasite virulence as enhanced correspondingly fewer advanced lesions being D C ANTONY, F J SAVAGE, R M HEMBRY, PB growth of an isolate with bile may confer found in those with a long duration of symp- BOULOS (Department of Surgery, University survival advantage for the organism. toms. This correlation remained true even College and Middlesex School of Medicine, when Dukes' D lesions were omitted from the London and Strangeways Research Laboratory, X2 tables (p<005) Cambridge) Research on inflammatory bowel Kaplan-Meyer survival curves were con- disease has been hampered by the lack of a Intestinal exposure to food allergen during structed for patients whose duration of symp- simple, yet clinically relevant, animal model. recovery from rotavirus infection: effects on toms was less than 1 month, 1-6 months, or Our results have shown that chronic colitis, IgE production and water absorption upon greater than 6 months. Five year survival was with features similar to human Crohn's disease, rechallenge 22%, 40%, and 46% respectively, all differ- may easily be induced in the rabbit by a single ences being highly significant. When correc- intracolonic instillation of(2-5-50 mg) trinitro- F H MOURAD, J A DIAS, L J D O'DONNELL, M J G tion was made for Dukes' staging this inverse benzene sulphonic acid in a 25% ethanol FARTHING (Department of Gastroenterology, St correlation persisted. No association was found solution. This produced a dose dependent Bartholomezv's Hospital, London) Increased between symptom duration and differentiation inflammation and ulceration, observed by intestinal permeability to antigens has been oftumour. endoscopy, that persisted for at least six weeks; shown during recovery from viral enteritis. In conclusion, these results support the appropriate controls exhibiting no damage. This may play a key role in the development of concept that symptom duration is inversely After two weeks the optimum dose of 40 mg food allergy/intolerance in children. We have proportional to both Dukes' staging and consistently produced skip lesions with a examined the effect ofexposure ofrat intestinal survival. Thus the rapid investigation of the cobblestone appearance, strictures, bowel wall mucosa recovering from rotavirus (RV) infec- colon once symptoms have developed will not thickening, and microscopically there was tion to ovalbumin (OA) on the development of alter the outcome ofCRC. Greater efforts must transmural inflammation, fissuring ulceration, local sensitisation and systemic IgE produc- be directed at earlier diagnosis during the and crypt abscesses. Presence of blood in stool tion. Hooded-Lister (allergy prone) rats aged asymptomatic phase. was detected for three weeks. Our immuno- 15 days infected six days earlier with group B histochemical studies have shown that the RV were inoculated with 100 mg OA by This paper was presented at the BSG meeting in distribution of the metalloproteinases and gavage. A second group of similar aged rats Manchester-April 1991 - but the abstract was not their inhibitor, tissue inhibitor of metallopro- were inoculated ip with 10 ig OA and alum published