Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from Gut, 1975, 16, 392-409

The British Society of Gastroenterology

The spring meeting was held at the University of Southampton on 10 to 12 April 1975. On the first morning scientific papers were read at a meeting of the Liver Club and the Council of the British Society of Gastro- enterology met in the afternoon. On Friday morning a symposium on 'Immunology of liver disease' was held jointly with the Liver Club with Professor Ralph Wright in the Chair, and there was a meeting of the Path- ologists' Group in the afternoon. The spring meeting banquet was held at Beaulieu Abbey on Friday evening. Also on Friday afternoon and on Saturday morning there were sessions devoted to scientific papers on 'Coeliac syndromes' (Chairman: Dr M. H. Sleisenger), 'Biliary diseases' (Chairman: Dr K. W. Heaton), 'Stomach' (Chairmen: Dr G. Milton-Thompson and Dr D. Colin-Jones), 'Intestinal transport-polypeptides' (Chairman: Professor C. C. Booth), 'Liver' (Chairmen: Professor Sheila Sherlock and Professor A. E. Read), 'Inflammatory syndromes' (Chairman: Dr S. C. Truelove), 'Oesophagus, stomach' (Chairman: Dr J. Bamforth), 'Pancreas' (Chairman: Mr J. E. Trapnell), 'Stomach hormones' (Chairman: Professor Ian McColl), and 'Colon' (Chairman: Professor J. C. Goligher). Abstracts ofthese papers follow.

Jejunal colonization with enterobacteria in two patients relapsed with high bacterial was only threefold. Protein synthesis, as symptomatic tropical residents without counts. Failure to clear mucosal entero- measured by the incorporation of 14C acute sprue bacteria may with folate deficiency leucine into trichloracetic acid-precipi- predispose to mucosal changes in tropical table protein, was twofold greater in the A. M. TOMKINS, S. WRIGHT, W. P. T. JAMES, residents. coeliacs than in the controls. Subcellular AND B. S. DRASAR (Clinical Nutrition and fractionation experiments on the cultured

Metabolism Unit, Department of Human Use of an improved jejunal culture system biopsies from normal subjects indicated http://gut.bmj.com/ Nutrition, London School of Hygiene and for the study of normal and coeliac mucosa that much of the newly synthesized Tropical Medicine, London, and Bacterial protein was in the cytosol with smaller Metabolism Research Laboratory, Colin- C. L'HIRONDEL, W. F. DOE, AND T. J. amounts in the microsomal and mito- dale, London) Colonization ofthe mucosa PETERS (Department of Medicine, Royal chondrial fractions and only trace amounts and luminal fluid by enterobacteria in Postgraduate Medical School, Du Cane in the brush borders. numbers of 103 to 108 organisms/g appears Road, London) A culture system (Mit- These studies demonstrate striking to lead to the development of the mucosal chell, Mitchell, and Peters, 1974), modified abnormalities of enzyme activities and lesion of acute tropical sprue. Patients by the incorporation of a rotating wire protein synthesis rates in coeliac jejunal on September 28, 2021 by guest. Protected copyright. with less severe symptoms present more mesh, has been used to maintain jejunal mucosa compared with controls when frequentlyin the UK., and their diarrhoea, biopsies from both control subjects and maintained in an in-vitro culture system. sometimes accompanied by malabsorp- patients with untreated coeliac disease for tion, may persist after their return. Two 24 hours. The viability of the biopsies Reference 'control' groups without malabsorption during culture was established by dis- Mitchell, J., Mitchell, J., and Peters, T. J. (1974). were studied. Only two out of eight secting and optical microscopy and by Gut, 15, 805. overland travellers with steadily decreasing autoradiography with tritiated thymidine diarrhoea were found to have low counts and leucine. Before culture the protein Depletion of thymus-dependent lympho- (< 103/g) whereas six of eight long-stay concentration of the control biopsies cytes in adult coeliac disease residents (professional expatriates) with (expressed as mg protein/mg DNA) was persistent diarrhoea had 103 to 105 entero- twice that of coeliac tissue. During culture D. P. O'DONOGHUE, M. LANCASTER-SMITH, bacteria/g. the protein and DNA contents of the AND PARVEEN J. KUMAR (Department of A third group of nine patients with tissue decreased by approximately one- Gastroenterology, St Bartholomew's Hos- tropical enteropathy and decreased folate third but the total amount of DNA pital, London) Although in adult coeliac levels had more marked symptoms, in six (tissue + culture medium) remained disease (ACD) thymus-dependent lympho- were colonized by enterobacteria in constant and it was therefore used as a cytes (T cells) may be involved in the numbers of 103 to 106 per g, and had reference. pathogenesis of the jejunal lesion' and abnormalities in mucosal morphology. A Alkaline phosphatase activity (ex- disturbances of lymphocyte function can fourth group of 10 patients with tropical pressed as mUnits/mg DNA) was four occur", circulating T cells have not been sprue was followed after tetracycline times higher in control biopsies than in measured. therapy: improvement at six months was coeliac mucosa. After culture alkaline A sheep red cell rosetting technique less satisfactory in those six with a few phosphatase levels in controls increased has been used to detect T cells in the remaining mucosal enterobacteria, and sixfold whereas in coeliacs the increase blood of ACD patients and controls. The 392 Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from The British Society ofGastroenterology 393 relative and absolute numbers of T cells ence of grade, at each site and for an An alternative pathway for bile acid were decreased in untreated ACD patients overall difference of grade between the metabolism in cholestasis involving 6oa- compared with controls (p < 0 002) and two sites. hydroxylation treated patients (p < 0 002) who had Twenty-one patients (four with DH) normal values. Total blood lymphocyte showed patchiness, which was more J. A. SUMMERFIELD, C. H. L. SHACKLETON, counts, however, were significantly re- common in the jejunum. There was an AND BARBARA H. BILLING (Department of duced only in the untreated ACD group. overall difference of abnormality between Medicine, Royal Free Hospital, Pond In those patients studied both before and the jejunum and duodenum in 13 patients Street, Hampstead, London, and Division after treatment T cells always increased and in some the duodenum was less of Clinical Chemistry, Clinical Research following a gluten-free diet (p < 001). severely abnormal. Centre, Watford Road, Harrow, Middlesex) There was an inverse relationship between Examples ofpatchiness will be presented Bile acids have been isolated from the both relative (p < 0001) and absolute and the relevance discussed. urine, serum, and bile of eight patients (p < 001) numbers of T cells in the with cholestasis. Using gas liquid chroma- blood and numbers of lymphocytes in the tography and combined GLC-Mass epithelial cell layer of the jejunum but spectrometry lithocholic acid and 3 p- there was no correlation with jejunal Recurrent aphthous ulceration and its hydroxy-5-cholenoic acid were shown to lamina propria lymphocytes. association with coeliac disease bepresent mainlyas sulphates. In addition, The depletion of circulating T cells hyocholic acid (3ox, 6cx, 7a-dihydroxy- might be explained by excess accumulation R. FERGUSON, M. J. BASU, P. ASQUITH, AND 5fl-cholanoic acid) and hyodeoxycholic in the jejunal epithelium and loss of W. T. COOKE (The Nutritional and Intestinal acid (3a, 6a-dihydroxy-5#-cholanoic acid) lymphocytes into the small bowel lumen3. Unit, The General Ilospital, Birmingham) were found in most of the samples from These findings are compatible with in- Although aphthous ulceration has been cholestatic patients but not in those from volvement of T cells in the pathogenesis of considered common in idiopathic steator- normal subjects. Hyocholic acid com- ACD and might also explain the impaired rhoea and coeliac diseasel12, a recent prised up to 12-2% of the total bile acids blast transformation and cytotoxic capa- editorial3 on recurrent oral ulceration did excreted in the urine (mean 41 %). Only city of coeliac lymphocytes2. not mention this association. It seemed trace amounts of hyocholic acid were detected in the serum and bile. Up to References relevant, therefore, to deternmine the incidence of coeliac disease in patients 4.9 %of the urinary bile acids (mean 1 -3 %) 'Ferguson, A. (1974). 2nd International Coeliac with recurrent aphthous ulceration atten- werepresentas hyodeoxycholic acid; mean Symposium. of 2-5 % for serumandO-4 % for bile 2Asquith, P. (1974). 2nd International Coeliac ding the dental and general medical out- values Symposium. were obtained. Since26-hydroxycholesterol

patient departments. Thirty-five consec- http://gut.bmj.com/ 3Wheetman, A. P. (1974). Gut, 15, 823. utive patients with recurrent aphthous sulphate was also detected in the chole- ulceration were studied. Seven patients had static specimens, these findings provide Patchiness of the mucosal abnormality in the 'flat' jejunal biopsies characteristic of support for the hypothesis that an coeliac disease (CD) and dermatitis coeliac disease, and 28 had normal alternative pathway for bile acid meta- herpetiformis (DH) jejunal biopsies. Although the seven bolism may exist in cholestasis, similar subjects had lower mean haemo- to that suggested by Mitropoulos and BRIAN B. SCOTT AND M. S. LOSOWSKY globin (P < 0 01) and serum folate levels Myant (1967) for the rat. This hypothesis (Department of Medicine, St James's (P < 0-01) than the other 28 patients, proposes that side chain cleavage precedes Hospital, Leeds) Although there are symptoms of abdominal discomfort and the ring hydroxylation of cholesterol and on September 28, 2021 by guest. Protected copyright. several reports of patchiness of the diarrhoea were common to both groups. leads to the formation of monohydroxy mucosal abnormality in CD, this does not Cell counts in the jejunal mucosa have bile acids which are then hydroxylated in seem to be generally accepted, whereas been performed. The plasma cell counts the 6 and 7 positions. An enzyme system the several reports of patchiness in DH in the subjects with normal jejunal biop- in human liver microsomes which is seem to be widely accepted and have been sies were significantly greater than those of capable of the hydroxylation of tauro- taken as evidence for different types of controls (P < 0-001) and less than those lithocholate to taurohyodeoxycholate has mucosal lesion in the two conditions. with coeliac disease (P < 0 00001). already been demonstrated by Triulzsch This study was designed to assess patch- The findings of a 20% incidence of et al (1974). iness of mucosal abnormality in the coeliac disease in the patients studied proximal small bowel in both conditions. indicates that jejunal biopsy should be References Three hundred and thirty-four biopsies regarded as obligatory in patients with Mitropoulos, K. A., and Myant, N. B. (1967). were taken with a hydraulic capsule recurrent aphthous ulceration. Biochem. J., 103, 472. (Quinton Instruments Co) from 42 patients Truilzsch, D., Roboz, J., Greim, H., Czygan, P., References Rudlick, J., Hutterer, F., Schaffner, F., and with CD including seven with DH. Popper, H. (1974). Biochem. Med., 9, 158. Biopsy sites were (1) the second part of 'Cooke, W. T., Peeney, A. L. P., and Hawkins, the duodenum and (2) the first part of C. F. (1953). Symptoms, signs and diagnostic Bile acid metabolism in chronic bowel features of idiopathic steatorrhoea. Quart. the jejunum. Specimens were graded both J. Med., 22,59-77. disease: Determinations in gallbladder bile, by stereomicroscopy (as villous, ridged, 'Barry, R. E., Baker, P., and Read, A. E. (1974). portal blood, and peripheral blood convoluted, or flat) and histology (as The clinical presentation in coeliac disease, normal, partial villous atrophy, or sub- pp. 33-69. Clinics in gastroenterology, ed. J. H. SIEGEL, S. BARNES, J. S. MORRIS, AND Cooke, W. T., Asquith, P. W. B. Saunders total villous atrophy). The specimens & Co. Ltd, London. B. N. BROOKE (The Department ofMedicine, were assessed for patchiness, ie, a differ- 'Editorial (1974) Brit. med. J., 2, 757-758. The Royal Free Hospital, Hampstead, and Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from 394 The British Society ofGastroenterology the Department of Surgery, St George's resulting in a high degree of accuracy in We conclude that in patients with Hospital, Tooting) The association be- the classification ofjaundice. radiolucent stones and 'functioning' gall- tween liver disease and chronic bowel 13'I-Rose Bengal is administered intra- bladders, effective gallstone dissolution is disease has not been satisfactorily ex- venously, and count rates during hepatic related to (1) the dose of CDCA per kg plained. Alterations in bile acid metabolism uptake and biliary excretion are recorded body weight, and (2) its ability to produce in such diseases as ulcerative colitis. over the liver, biliary tract, and duodenum an unsaturated bile. Crohn's disease, ileal resection, and using a gamma camera-computer system irradiation ileitis might be responsible. with an electronic light pencil. An uptake- Reference Lithocholic acid has received the most excretion curve ('hepatogram') is ob- 'Mok, H. Y. I., Bell, G. D., and Dowling, R. H attention as the causative agent1 because tained, from which the Ti of uptake and (1974). Lancet, 2, 253-257. of its marked hepatotoxic reactions the excretion quotient are determined. demonstrated in animal experiments2. In The results of the first 64 examinations Bile acids inhibit lysozyme activity the present study, gas liquid chromato- show that by qualitative assessment of the graphic measurements of bile acids in uptake and excretory phases of the Y. GHOOS, G. VANTRAPPEN, AND T. PEETERS portal blood and gallbladder bile were hepatogram, and determination of the Ti (Department ofMedical Research, Univer- performed in nine patients with bowel and excretion quotient, jaundice can be sity of Leuven, Belgium) Lysozyme is disease with no associated liver disease classified with an 86% accuracy in cases one of the factors which control the and compared with a control group. where the cause is not apparent from growth of the intestinal microflora. As Lithocholic acid concentrations did not clinical findings and liver function tests. detergents are known to affect lysozyme exceed 1V2 ,mol/l in portal blood in It is concluded that this technique activity we studied the effect of various diseased patients (controls 0-2-7 uemol/l), enables an accurate classification of bile acids on the lytic activity of lysozyme and no differences in composition or jaundice, and, by permitting quantitative towards Micrococcus lysodeiklicus. concentration of other bile acids were assessment of hepatocellular function in All bile acids tested inhibited the found. Marked elevations (up to 196 the jaundiced patient, allows this to be lysozyme activity. The degree of inhibition ,mol/l) ofbile acid concentrations, mainly studied during and after recovery from depended on the nature and the concen- primary bile acids, were found in the obstructive jaundice. tration of the bile acids. Conjugated bile peripheral sera of 13 patients with liver acids were stronger inhibitors than their disease associated with ulcerative colitis, Factors determining gallstone dissolution unconjugated homologues and sulphata- especially in those with biliary disease, ie, in patients treated with chenodeoxycholic tion of bile acids resulted in an even sclerosing cholangitis. However, there acid (CDCA) greater inhibition, eg, at 0 5 mM: GCDC, were no differences when compared with 52 %; CDC, 11 %; CDCsulph. 80 %). http://gut.bmj.com/ previous series of patients with liver J. ISER, H. Y. I. MOK, G. D. BELL, AND R. H. The inhibition increased with increasing disease. Lithocholic acid was present in DOWLING (Departments ofMedicine, Guy's concentration of bile acids. At the critical very low concentrations which did not Hospital and Royal Postgraduate Medical micellar concentrations, determined spec- exceed 1 umol/l. Bile acid concentrations School, London) Analysis of results in trophotometrically with Rhodamine 6G, in 10 patients with inflammatory bowel 70 gallstone patients treated with CDCA there was a drop of inhibition. This disease with no evidence of liver disease over three and a half years shows that phenomenon was not observed with were within the normal range. Thus, no gallstone dissolution only occurs in sulphated bile acids. Analysis of uv evidence has been found in this study to patients with radiolucent stones in difference spectra suggests that the on September 28, 2021 by guest. Protected copyright. support the concept that abnormal bile 'functioning' gallbladders. However, stone inhibition is caused by distortion of the acid metabolism is responsible for the size, dose, and duration of CDCA and tertiary structure of lysozyme. These liver disease associated with chronic bowel the resultant changes in bile lipid com- observations illustrate the complex inter- disorders. position all influence the chance ofsuccess. actions of bile acids and intestinal micro- References In 25 patients with radiolucent stones flora. As bile acids are known to inhibit "Carey, J. B., Jr. (1964). Gastroenterology, 46, 490. treated for more than six months small lipase activity and preliminary studies 'Holsti, P. (1960). Nature (Lond.), 186, 250. (< 5 mm) stones dissolved in six out of indicate that they inhibit amylase activity seven by one year (five complete, one as well, it seems possible that, by virtue The radioisotope hepatogram in the partial) and in eight of ten by two years of their enzyme-inhibiting properties, diagnosis ofjaundice (seven complete, one partial). In contrast, they play a hitherto unrecognized role in no large stones (> 10 mm) had changed intestinal physiology. A. WATSON, D. E. BONE, H. J. TESTA, AND by one year but five out of 10 showed BRUCE TORRANCE (Departments of Gastro- dissolution after two years on CDCA. Postoperative symptoms and gastric empty- enterology and Medical Physics, Man- In 16 patients showing gallstone dissolu- ing of solid foods chester Royal Infirmary) The distinction tion, the dose of CDCA (14-4 ± SEM between 'medical' and 'surgical' jaundice 1.0 mg.kg BW-' day-') and the resultant C. PEREZ-AVILA, P. HOWLETT, D. BARBER,. is often difficult, due to the lack of biliary cholesterol saturation index' (0-78 H. J. SHEINER, AND H. L. DUTHIE (Depart- specificity of liver function tests, and ± 0 05) (> 1 supersaturated; < 1 under- ments of Surgery and Medical Physics, difficulty in assessing hepatocellular func- saturated) were both significantly different Sheffield Royal Infirmary) Twenty-five tion and biliary tract patency in the from the corresponding values in nine patients were assessed clinically for post- jaundiced patient. We present a non- patients whose stones did not change size prandial symptoms six months after invasive isotopic technique which gives after six to 33 months on CDCA (10-6 truncal vagotomy and pyloroplasty (TVP) reliable information on these parameters, 1-2 mg and 1-15 i 0-04 respectively). (12) or highly selective vagotomy (HSV> Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from The British Society ofGastroenterology 395 (13). Gastric emptying of a solid meal provided discriminants with an accuracy cytologically, but radiology and histology labelled with radioactive Indium (1l3mIn) of 94 and 85% respectively. The were negative. They have remained well was also measured at this time using a accuracy of the blind computer prediction so far. gamma camera (Howlett, Duthie, and based upon these two discriminants was Although suspicious cytological appear- Ward, 1974), the results being expressed 86 and 91 %. ances may occur in a small proportion of in terms of the half emptying time (TO) of These initial results have shown that benign cases, these results suggest that multiple component analysis and of the symptoms can be used to distinguish brush cytology, which is clinically easy to initial emptying phase. No correlation reflux gastritis from recurrent peptic perform, gives a higher diagnostic rate was found between symptoms and the ulceration. The individual questions that for gastric cancer than multiple biopsy. overall emptying rate expressed by the Ti. differentiated these groups will be presen- Component analysis, which shows the ted. The pathophysiology of duodenitis shape of thepattern ofemptying, indicated Reference -a possible change in the early stages after Halpem, N. B., Hirschowitz, B. L., and Moody, 1. A. DONOVAN, G. GREEN, P. W. DYKES, the meal. This was confirmed when a F. G. (1973). Amer. J. Surg., 125, 108. CAROLINE OWENS, B. G. CLENDINNEN, AND relationship was found between the J. ALEXANDER-WILLIAMS (Department of incidence and severity of dumping and The value of brush cytology in the diagnosis Surgery, The General Hospital, Birming- diarrhoea after TVP and the initial ofgastric cancer ham, and University of Bristol) The emptying phase (r = 0-875; p < 005): concept that duodenitis represents an the more diarrhoea and dumping the ALISON SMITHIES, D. LOVELL, S. HISHON, early stage or is a variant of duodenal faster the initial emptying phase. T. D. KELLOCK, J. J. MISIEWICZ, CHARMIAN ulcer disease is attractive (Cotton, Price, NEWTON, R. E. POUNDER, AND L. M. Tighe, and Beales, 1973). However, there Reference BLENDIS (Departments of Histopathology is evidence to suggest that it is a distinct Howlett,P. J.,Duthie, H. L., andWard, A. S. (1974) Gastric emptying after vagotomy. Proc. roy. and Gastroenterology, Central Middlesex disease entity (Cheli, 1968). Comparison Soc. Med., 67, 836-838. Hospital, Park Royal, London) The value of the pathophysiology of duodenitis with of brush cytology as an additional routine that of duodenal ulceration and with A symptomatic discriminant between two investigation in the differentiation of normal physiology should help to evaluate important causes of dyspepsia following benign from malignant gastric ulcers has this problem and to formulate rational gastric surgery been prospectively assessed. One hundred treatment. and thirty-three consecutive unselected In 14 symptomatic patients with M. R. B. KEIGHLEY, JANE HORRACKS, F. T. patients in whom gastric ulceration was duodenitis diagnosed endoscopically and DE histologically, the peak acid output (mean DOMBAL, A. M. HOARE, P. ASQUITH, P. diagnosed or suspected radiologically http://gut.bmj.com/ .DYKES, AND J. ALEXANDER-WILLIAMS (The were endoscoped. Multiple biopsies fol- PAOpg 26-9 m-equiv/hr) was significantly General Hospital, Birmingham, and the lowed by cytology brushings were per- lower (P < 0 015) than in 50 patients with University Department of Surgery, Leeds) formed on all the lesions and assessed by duodenal ulceration (mean 39 4 m-equiv/ Because the clinical presentation of bile the histopathologist and the cytologist hr). However the duodenitis values did reflux gastritis may mimic recurrent peptic independently. Eight numbered smears not differ significantly from those in a ulceration, it is important to distinguish were made from each brushing and group of 20 normals (mean PAOh 21-6 these, particularly as the results of further screened in numerical sequence. Results m-equiv/hr) investigated by Baron (1963). in with were Basal serum gastrin values in 10 gastric resection patients gastritis of all the tests recorded as benign, on September 28, 2021 by guest. Protected copyright. are so disappointing (Halpern, Hirscho- suspicious, or malignant. duodenitis patients (mean 21-8 pico- witz, and Moody, 1973). The diagnostic In 33 patients cancer was confirmed by grams/ml) were significantly lower than accuracy of radiology to detect recurrent histopathological examination of the in 56 duodenal ulcer patients (mean 30 ulceration is poor when compared with resected stomach, or at laparotomy by the picograms/ml). The duodenitis values the results of endoscopy. However, an surgeons in cases which were found to be were not significantly different from those experienced endoscopist may not always inoperable. In these 33 patients, the in 62 normals (mean 18-6 picograms/ml). be available. diagnosis of malignancy was established In view of the constancy of the peak This study has examined the possibility or suspected in 21 radiologically, in 30 on acid output in any individual, these results -that certain symptoms might distinguish endoscopy, and in 21 histologically. In suggest that duodenitis is unlikely to be a -these groups. Questionnaires were sent to 28 cancer was established by cytology, variant of duodenal ulcer disease. The 76 patients who had been investigated for and in all but one of these the diagnosis 'normality' of acid output and gastrin recurrent dyspepsia by barium meal, was apparent after examination of the levels in duodenitis patients should dis- endoscopy, cholecystogram (all cases), first four of the eight smears. In three of courage surgical treatment aimed at acid and acid studies (46 cases). Patients with the 33 patients the diagnosis was estab- reduction. gallstones were excluded and all recurrent lished by cytology alone. ulcers were confirmed by operation. In the remaining 100 patients the References The enquiry was retrospective in 40 radiological appearances were suspicious Baron, J. H. (1963). Studies of basal and peak acid output with an augmented histamine test. patients, in whom the diagnosis was of malignancy in 15, seven of whom were Gut, 4, 136-144. already confirmed, and prospective in 36 also suspicious on endoscopy. However, Cheli, R. (1968). Duodenitis and duodenal ulcer. where the diagnosis was later established. histology and cytology were both negative Digestion, 1, 175-182. Questionnaires were a in all these seven who have Cotton, P. B., Price, A. B., Tighe, J. K., and Beales assessed using patients, J. S. M. (1973). Preliminary evaluation of small computer by a Bayes analysis and remained well for 18 months or longer. duodenitis by endoscopy and biopsy. Brit. weighted tables. The retrospective replies In five patients cancer was suspected med. J., 3 430-433, Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from

396 The British Society ofGastroenterology Abnormalities of gastric morphology and initial study. After a two-hour basal shown that rates of incorporation of acid secretion in patients with dermatitis collection period 1 mg of GH-RIH was N - acetyl[3H]glucosamine, [3H]glucos- herpetiformis given as a 75-minute intravenous infusion. amine, ['4C]galactosamine, N-acetyl[14C]- No side effects were noted. Plasma gastrin neuraminic acid, and [3H]fucose into M. LANCASTER-SMITH, D. P. O'DONOGHUE, fell from initial mean individual basal glycoproteins of gastric mucus are reduced AND PARVEEN J. KUMAR (Department of values of 273, 147, 119, and 76 p mol/l in following treatment with indomethacin, Gasiroenterology, St Bartholomew's Hos- the four patients to 82, 43, 64, and 20 phenylbutazone, or spironolactone, but pital, London) Gastric parietal cell anti- p mol/l respectively at the end of the are increased after treatment with the bodies have been previously reported' in GH-RIH infusion; mean basal gastric ulcer-healing drug, carbenoxolone. some patients with dermatitis herpeti- acid production for the group (± SEM) Similarly, patients with diseases of the formis (DH). Recently, abnormalities of fell from 16-6 ± 2-9 m mol/hr to 0 5 + stomach, such as gastritis, gastric ulcer, gastric secretion have also been noted2 0-2 m mol/hr; and gastric juice pH rose or gastric carcinoma, showed a reduced but no correlation has been made between from 1-75 ± 0-3 to 7-5 ± 0-5. rate of incorporation of N-acetyl [3H]- these findings and morphological changes. Four dogs were also studied on two glucosamine into glycoproteins of the Thirty-three patients with DH have been occasions with either a saline or 0-5 mg gastric mucosal biopsies. Following treat- studied. Gastric parietal cell antibodies GH-RIH infusion during insulin hypo- ment with carbenoxolone, the rate of have been found in five patients; four of glycaemia. On the control day the mean incorporation of N-acetyl[3H]glucosamine these had achlorhydria and gastric fall in plasma glucose was 3-4 ± 0 4 was restored to normal. Ulcerogenic atrophy whilst one patient had overt m mol/l and rise in gastrin 31 ± 15 p mol/l drugs may thus impair the synthesis of pernicious anaemia with intrinsic factor while during GH-RIH glucose fell 3-6 ± glycoproteins of gastric mucus whereas, antibodies and B,2 malabsorption. Ten of 0 7 m mol/l but gastrin rose only 4 ± 4 conversely, carbenoxolone restores glyco- the remaining patients with negative p mol/l. Total gastric acid production protein synthesis, and mucus, to normal. gastric parietal cell antibodies also under- was reduced 80 ± 8 % by the GH-RIH References went gastric biopsies and pentagastrin (12-1 ± 1-4 m mol/hr control, 2-7 ± 1-3 stimulation tests. Two of these patients m mol/hr GH-RIH). Allen, A., and Snary, D. (1972). The structure and function of gastric mucus. Gut, 13, 666-672. had achlorhydria with gastric atrophy and Growth hormone release inhibiting Lukie, B. E., and Forstner, G. G. (1972). Synthesis a further two had hypochlorhydria, one hormone is thus a potent inhibitor of of intestinal glycoprotein incorporation of of whom had an abnormal biopsy. All gastrin and gastric acid production and a (1-14C) glucosamine in vitro. Biochim. patients were correlated with age- and useful therapeutic agent in Zollinger- Biophys. Acta, 261, 353. sex-matched controls for the acid studies Ellison patients. (P = < 0 002). Metiamide therapy in the Zollinger- http://gut.bmj.com/ These findings suggest that morpho- Reference Ellison syndrome logical and functional abnormalities of Bloom, S. R., Mortimer, C. H., Thorner, M. O., gastric mucosa in patients with DH are Besser, G. M., Hall, R., Gomez, Pan A., M. H. THOMPSON, C. W. VENABLES, I. T. Roy, V. M., Russell, R. C. G., Coy, D. H., relatively common. This lends further Kastin, A. J., and Schally, A. V. (1974). MILLER, J. D. REED, D. J. SANDERS, E. R. support to the suggestion that DH is Lancet, 2, 1106. GRUND, AND E. L. BLAIR (The University of associated with widespread immuno- Newcastle upon Tyne) Total gastrectomy logical abnormalities. The effects of ulcerogenic and ulcer- remains the recommended therapy for the healing drugs on gastric mucus Zollinger-Ellison syndrome. This is, on September 28, 2021 by guest. Protected copyright. References however, associated with considerable 'Fraser, N. G. (1970). Brit. J. Derm., 83, 600-613. 'Heading, R. C., et al (1974). Amer. J. dig. Dis., DENNIS V. PARKE, W. EDWARD LINDUP, morbidity and a high mortality risk. 704-708. AND JOHN S. SHILLINGFORD (Department of Metiamide (an H2 antagonist) blocks the Biochemistry, University of Surrey, Guild- effects of exogenous pentagastrin upon Inhibition of gastrin and gastric acid by ford, Surrey, England) AND MICHAEL J. gastric secretion and so might be beneficial growth hormone release inhibiting hormone SMITH (St Luke's Hospital, Guildford, in this condition. Surrey) The mucus of the gastrointes- Three cases, exhibiting recurrent ulcera- S. R. BLOOM, R. C. G. RUSSELL, A. A. J. tinal tract is a protective barrier shielding tion (confirmed endoscopically), gastric BARROS D SA, J. H. BARON, G. M. BESSER, the epithelial lining against chemical and hypersecretion, and basal hypergastrin- R. HALL, D. H. COY, A. J. KASTIN, AND enzymic damage. Pathogenesis of peptic aemia, which rose with exogenous A. V. SCHALLY (Departments of Medicine ulcer may thus be considered in terms of secretin (all features of the Zollinger- and Surgery, Royal Postgraduate Medical reduced defence by the gastric mucus. Ellison syndrome), have recently been School and Department of Surgery, St Gastric mucus consists largely of glyco- treated with metiamide. Mary's Hospital, London) We have proteins, containing more than 70 % All three were treated initially for two previously shown growth hormone release sugars as hexoses, hexosamines, and months. inhibiting hormone (GH-RIH) to be a fucose (Allen and Snary, 1972). Recent Repeat endoscopy showed that in two powerful inhibitor of gastrin release but developments in the molecular pathology patients the ulcers healed: the third has have not investigated its effects on gastric of peptic ulcer have included studies on residual stenosis not admitting the acid secretion. Although GH-RIH is quite the effects ofulcerogenic and ulcer-healing endoscope, but remaining very well. easy to synthesize there is very little drugs on the composition and rate of One patient relapsed after six months. material available tested for use in humans synthesis of gastrointestinal mucus (Lukie Re-investigation showed that drug ab- and thus four patients with proven pan- and Forstner, 1972). sorption had changed markedly, but on creatic gastrinomas were chosen for Our studies on rats and ferrets have intravenous administration metiamide Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from The British Society ofGastroenterology 397 remained a potent secretory inhibitor. has an inhibitory activity similar to present mortality (4-14%)1,2 from acute Increasing the dose caused remission of metiamide2, which has been shown to be upper gastrointestinal bleeding. Sixty-four symptoms and re-healing of the ulcer. of potential clinical use3. such deaths occurred in Edinburgh Royal The fasting serum gastrin fell in all Infirmary over a 24-month period. These three patient over the first month by 22, References were divided into five groups: oesophageal 40, and 25 % respectively. 'Fordtran, J. S., and Walsh, J. H. (1973). J. clin. varices (20), gastric ulcers (8), duodenal The mean basal acid output fell by 55 % Invest., 52, 645-657. 2Mainardi, M., Maxwell, V., Sturdevant, R. A. L., ulcers (13), miscellaneous and unidentified with treatment: maximal acid output to and Isenberg, J. I. (1974). New Engl. J. Med., (12), and terminal disease (11). Most pentagastrin by 53% and to insulin by 5 %. 291, 373-376. patients were elderly, especially those Metiamide appears to be a potent 3Pounder, R. E., Williams, J. G., Milton-Thompson, with gastric ulzers (mean, 78 years). The G. J., and Misiewicz, J. J. Brit. med. J. In therapeutic agent in the Zollinger-Ellison press. overall average age (67 years) was reduced syndrome. It appears to reverse the by 12 alcoholic cirrhotics (mean 54 years). parietal cell hyperplasia ind by Eight deaths followed sudden ex- chronic hypergastrinaemia and it may also Non-ulcer dyspepsia and surgery sanguination within 24 hours ofadmission. affect gastrin release. Sixteen occurred while bleeding con- A. M. HOARE, M. R. B. KEIGHLEY, C. HAW- tinued; 12 patients had advanced hepatic New histamine H,-receptor antagonist KINS, J. ALEXANDER-WILLIAMS, AND S. G. failure with bleeding varices, one (gastric inhibits food-stimulated gastric acid se- ELKINGTON (The General Hospital, Bir- ulcer) was 81 years old, two (duodenal cretion mingham) One hundred patients with ulcers) had severe uraemia, and in one symptoms following gastric operations (duodenal ulcer), with accelerated hyper- R. E. POUNDER, J. G. WILLIAMS, R. G. C. have been studied. A definite cause for tension, bleeding was underestimated. RUSSELL, J. J. MISIEWICZ, AND G. J. MILTON- their symptoms was found on endoscopy Twenty deaths followed surgery for THOMPSON (Medical Research Council in 39 patients: 29 ulcers, six carcinomas, bleeding; six patients had advanced Gastroenterology Unit, Central Middlesex and four pyloric stenosis. No abnormality cirrhosis, 10 severe concomitant disease, Hospital, London, Royal Naval Hospital, or gastritis alone was found in the three had major postoperative complica- Stonehouse, Plymouth, Devon, and St remainder. tions, and one an ulcer eroding through the Mary's Hospital, London) The effect on Details of the original operation were aorta. Nine deaths were from severe food-stimulated gastric acid secretion' of available in 81 patients. There was no concomitant disease, and in a further 11 a new histamine H2-receptor antagonist evidence of an ulcer on preoperative bleeding ended an already terminal illness. (cimetidine, SK&F 92334) has been radiology or at operation in 19 patients. Only two deaths appear to have been studied in normal volunteers. None had a lesion on endoscopy to avoidable with 'ideal' managenment. Our Fasting subjects were intubated with a explain their persisting symptoms. Analy- experience suggests that too much should http://gut.bmj.com/ double-lumen nasogastric tube. A stan- sis of the symptoms of these patients not be expected from such diagnostic dard homogenized meal of roast beef, showed that they were significantly techniques as endoscopy. bread and butter made up to 450 ml and different from those of the patients with adjusted to pH 5-5 was instilled into the definite organic lesions. In particular the References stomach. Gastric contents were mixed by patients without ulcers complained of 'Cotton, P. B., Rosenberg, M. T., Waldram, R. P. L., the withdrawal and re-introduction of continuous upper abdominal pain not and Axon, A. T. R. (1973). Brit. med. J., 50 ml of the meal every 15 seconds relieved by alkalis, food intolerance, 2, 505.

'Johnston, S. J., Jones, P. F., Kyle, J., and Needham, on September 28, 2021 by guest. Protected copyright. throughout the study. Acidity of gastric vomiting without weight loss, and symp- C. D. (1973). Brit. med. J., 3, 655. contents was measured every two minutes toms unrelated to the gastrointestinal and the pH maintained at 5-5 by adjust- tract. They date their troubles from the Effect of food intake and the pituitary on ment of intragastric infusion of sodium first operation, but their symptoms are in intestinal structure and function after small bicarbonate. Acid output was expressed fact usually identical to those present bowel resection in the rat in terms of sodium bicarbonate added before that operation. Three-quarters had every 16 minutes'. Venous blood was had a second operation, but none were BRYCE TAYLOR, GERARD M. MURPHY, AND sampled at 16-minute intervals to assay improved by it. R. HERMON DOWLING (Department of gastrin and cimetidine concentrations. The 'phantom ulcer syndrome' is Medicine, Guy's Hospital and Medical Each subject was studied twice, receiving proposed to describe these patients, who School, London) The influence of the cimetidine or placebo in random order. have had gastric operations for 'non- pituitary on the intestinal adaptation In three subjects, 200 mg of cimetidine existent' ulcers. These findings suggest which occurs after small bowel resection taken with the meal inhibited acid se- that operations on patients without a is not known. We therefore examined cretion by 54-60% during a two-hour definitely proven ulcer should be avoided, jejunal and ileal structure and function period when compared with placebo. and further operations should not be after 50% proximal or distal small bowel Plasma gastrin levels showed no con- performed. resection in three groups of male Wistar sistent changes and there were no adverse rats: (1) 26 normally fed controls, (2) 29 reactions. In further experiments, the Can earlier diagnosis reduce mortality in hypophysectomized animals, (3) 28 rats effect of administration of the drug at acute upper gastrointestinal bleeding? pair-fed with group 2. Each group was different times in relation to food is being subdivided into sham-operated controls explored and the results will be related to R. F. A. LOGAN AND N. D. C. FINLAYSON and resected animals. blood concentrations of the drug. The (Royal Infirmary, Edinburgh) Emergency Results obtained four weeks after results to date indicate that cimetidine endoscopy has been advocated to reduce intestinal surgery showed a consistent Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from 398 The British Society ofGastroenterology pattern for all the variables studied. In the role for cholinergic innervation in the Release of secretin from S cells of porcine intact intestine, the reduced food intake control of ileal ion transport. duodenum and jejunum by acid and of both the pair-fed hypophysec- References tomized animals led to a comparable S. N. JOFFE, S. R. BLOOM, JULIA M. POLAK, reduction in mucosal mass/cm length 'Florey, H. W., Wright, R. D., and Jennings, M. A. AND R. B. WELBOURN (Royal Postgraduate (1941). Physiol. Rev., 21, 36. (wet weight, protein, and DNA), di- "Tidball, C. S., and Tidball, M. E. (1958). Amer. Medical School, London) An experiment saccharidase activity, villous height, crypt J. Physiol., 193, 25. was designed to test the hypothesis that depth, and galactose absorption from a infusion of the upper small intestine with 64mM solution perfused in vivo. Following Alveolar H2 in the diagnosis ofcarbohydrate acid releases secretin from the S cells into resection, however, the magnitude of these malabsorption the portal, and thence the general cir- adaptive changes (which were more culation, and stimulates secretion of marked in ileum than in jejunum) was G. L. METZ, L. M. BLENDIS, AND D. J. A. J. pancreatic juice. In seven anaesthetized significantly less after hypophysectomy JENKINS (Department of Gastroenterology pigs, 0 1 N HCI (11 ml/min) was infused than after pair-feeding and in turn this and the MRC Gastroenterology Unit, for 30 min into the isolated duodenum was less than that in normally fed controls. Central Middlesex Hospital, London) and proximal 20 cm of jejunum. Secretin It is concluded that the pituitary does Breath tests are proving useful in studying concentrations in the blood were measured influence intestinal adaptation after re- small intestinal function because of their by radioimmunoassay. Basal levels were section since the effects of hypophysec- simplicity but most require radioisotopes'. 30 (SEM ± 5 5) pg/ml in portal and tomy on mucosal regeneration cannot be Measurement ofnon-radioactive hydro- arterial blood. Peak levels after 15 explained by reduced food intake alone. gen produced from carbohydrate fermen- minutes were: portal blood 221 + 35, tation and measured in expired air by arterial blood 174 + 20 pg/ml. Thirty closed circuit2 or total collection3 tech- minutes after the end ofinfusion the levels Human ileal ion transport in vitro: The niques has indicated a potential diagnostic were 59 4 13-6 and 43 ± 8 pg/ml re- influence of acetylcholine use for H2 estimation in carbohydrate spectively. malabsorption. However, a simple method The volume ofjuice from the cannulated P. E. T. ISAACS, C. L. CORBETT, A. RILEY, for breath sampling is needed for its pancreatic duct increased concomitantly AND L. A. TURNBERG (Department of clinical application. from 0-15 L 004 ml/15 min (basal) to Medicine, Hope Hospital, Salford) The We have investigated end-expiratory 3 9 ± 0 74 ml (0-15 min) and then 9 4 i possibility that the parasympathetic sampling (EES) using a simple Haldane- 2-6 ml (15-30 min). The concentrations nervous system may influence intestinal Priestly tube and compared it to the more and outputs of bicarbonate and tryptic ion transport is suggested by several early complicated methods mentioned. End- activity rose similarly. http://gut.bmj.com/ experimental observations in animals' .2 expiratory sampling H2 concentration, Intestinal S cells were identified in We investigated this possibility further in followed for three hours after ingesting samples of mucosa by indirect imnmuno- human intestine by assessing the effect of lactulose, was compared with simul- fluorescence. Their mean secretin content, acetylcholine (AcCh) on transport across taneous H2 produced per minute by closed measured by TV image analysis of the isolated ileal mucosa. Pieces of stripped circuit (eight subjects) or total collections cell/background ratios, fell by 59 % during mucosa obtained at laparotomy were (seven subjects). The correlation coeffi- acid stimulation, and the mucosal mean mounted in perspex flux chambers and cients were greater than 0-89 in every case extractable secretin, measured by radio- bathed in oxygenated, stirred isotonic (p < 0 01). The reproducibility in EES of immunoassay, fell by 42 %. Acid infusion on September 28, 2021 by guest. Protected copyright. glucose Ringer's solution at 37°. Acetyl- 61 paired samples (at H2 concentrations did not alter the appearance or hormone choline added to both sides of the mucosa from 5 to 360 ppm was 11 -6 % (r = 0 95). content of cells containing gastrin, (n = 6) caused a rise in mean potential A group of 19 patients with diarrhoea motilin, or gastric inhibitory polypeptide. difference (pd) (8-8 to 12-3 mV, P < 0 002) (five with suspected milk intolerance) and These findings are consistent with the and short circuit current (SCC) (290 to five controls were studied by 50 g oral hypothesis. 421 ,uA/cm2, P < 0.01) maximal at a dose lactose tolerance tests. All the five controls of 10-4 M but still observable at 1O-5 M; and 10 diarrhoeal patients had a glucose The correlation between bioassay and these effects were enhanced by neostigmine rise of > 20 mg % and a two-hour radioimmunoassay of serum cholecysto- and blocked by atropine. Isotopic flux hydrogen rise of < 4 ppm (including two kinin determinations with 22Na and 36C1 revealed with previously suspected 'milk intoler- that the rise in SCC was attributable to a ance'). A hydrogen rise of > 20 ppm A. G. JOHNSON, C. E. MARSHALL, LYNDA change from a small mean net Cl absorp- (m 82 SD 45) was recorded in all nine DOWSETT, AND R. F. HARVEY (Department tion (+ 0 6) to a net Cl secretion (-4-3 patients with a glucose rise of < 20 mg%. of Surgery, Charing Cross Hospital ,.equiv/cm2/hr, P < 0-001) due to an In conclusion, we have found EES to Medical School, and University Department increase in the serosa-to-mucosa uni- be a reliable method of breath hydrogen of Medicine, Bristol Royal Infirmary) directional flux of Cl (10-6 to 14-4 measurement and a satisfactory and simple Bioassay and radioimmunoassay are p-equiv/cm2/hr, P < 0-05). Unidirectional test for the diagnosis of hypolactasia. complementary ways of measuring poly- and net Na transport were unaffected. peptide hormones, each having advantages These effects ofAcCh were not mediated References and defects. In order to compare these by cAMP since cAMP levels were not 'Newman, A. (1974). Gut, 15, 308. two methods for cholecystokinin (CCK), increased in mucosa incubated with "Bond, J. H., and Levitt, M. D. (1972). J. clin. blood samples were obtained from Invest., 51, 1219. fasting AcCh. 'Calloway, D. H., and Murphy, E. L. (1968). Ann. six normal subjects, eight patients with These observations support a possible N. Y. Acad. Sci., 150, 82. chronic pancreatitis, and two patients Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from The British Society ofGastroenterology 399 with other conditions. Samples were also present in the tumours and plasma GIP of intestinal urease may govern the extent obtained from four normal subjects after levels were normal. Patients suffering of urea hydrolysis, but that the mechan- ingestion of substances such as milk or from other types of watery diarrhoea, isms for reclamation of urea N returning magnesium sulphate in order to provide including eight with a typical history of via the enterohepatic circulation are a wide range of CCK levels. The serum pancreatic cholera but no causative influenced by multiple factors not the was separated immediately and stored at tumour at laporotomy, had plasma VIP least of which is the fraction of gut intra- -20°C and each assay performed without levels in the normal range. Thus measure- luminal nitrogen derived from urea. knowledge of the other's results. The ment of a single fasting plasma VIP methods have been described in detail concentration in patients without obvious Reference elsewhere' 2. cause for the severe watery diarrhoea Varcoe, R., Halliday, D., and Tavill, A. S. (1974). A highly significant correlation was should result in earlier diagnosis and Gut, 15, 898-902. found between the two assays when the improved prognosis in the Verner- results were plotted logarithmically (r = Morrison syndrome. Free fatty acids and unconjugated hyper- 0-791; p < 0 001) but the regression line bilirubinaemia did not pass through zero, 1 pg/ml on References radioimmunoassay being equivalent to Kraft, A. R., Tompkins, R. K., and Zollinger, R. M. R. E. COWAN, J. KAYE, AND R. P. H. 28 mlvy dog units/ml on bioassay. This (1970). Amer. J. Surg., 119, 163. THOMPSON (Gastrointestinal Laboratory, Verner, J. V., and Morrison, A. B. (1974). Arch. may be due to a non-specific 'serum blank' intern. Med., 133,492. St Thomas' Hospital, London) Little is in the bioassay. The straight plot produced Bloom, S. R., Polak, J. M., and Pearse, A. G. E. known of the mechanism of the uncon- a clear asymptotic regression curve with (1973). Lancet, 2, 14. jugated hyperbilirubinaemia of fasting the medium range of bioassay results but free fatty acids (FFA) could be higher than expected compared with The role of the enterohepatic circulation of involved since their concentration in blood radioimmunoassay. This could mean that urea nitrogen in hepatic albumin synthesis also rises with fasting. highly biologically active CCK fragments in man After repeated overnight fasts serial are being detected by bioassay but not by blood levels of bilirubin and FFA of two radioimmunoassay. A. S. TAVILL, RAE VARCOE, D. HALLIDAY, of the authors were measured during the The study also confirmed that the high P. RICHARDS, AND E. R. CARSON (MRC following day when the mean plasma levels of immunoreactive CCK in patients Clinical Research Centre, Harrow, Middle- total bilirubin rose steadily at 05 with chronic pancreatitis represent bio- sex) The relationship between endo- 4mole/litre/h for seven and a half to eight logically active hormone. genous urea metabolism and albumin hours, and serum FFA at about 45 has been studied following the ,tmole/litre/h. Intravenous infusion of References synthesis http://gut.bmj.com/ single intravenous administration of [14C] insulin (0 04 units/kg/h) for one hour 'Johnson, A. G., and McDermott, Susan J. (1973). during an identical fast reduced bilirubin Lancet, 2, 589. urea, [I5N] urea, and [1251] albumin. 2Harvey, R. F., Dowsett, Lynda, Hartog, M., and Deconvolution of the biosynthetic [15N] by 2-0 ,mole/litre/h, and FFA by 390 Read, A. E. (1974). Gut, 15, 690. albumin dynamics enabled calculation of ,umole/litre/h. Conversely, a fat meal the absolute rate of urea nitrogen utiliza- (60 g corn oil) increased bilirubin by Vasoactive intestinal peptide and the tion for albumin synthesis. The possible 1-2 umole/litre/h, and FFA by 102 Vemer-Morrison syndrome roles of the plasma urea concentration, jtmole/litre/h, compared with rises of dietary protein intake, and albumin 0-5 i&mole/litre/h and 26 ,umole/litre/h S. R. BLOOM (Department ofMedicine, The synthetic rate in the regulation ofintestinal during the same period of uninterrupted on September 28, 2021 by guest. Protected copyright. Royal Postgraduate Medical School, Lon- degradation of urea and the efficiency of fasting. don) The mean time from onset of hepatic utilization of released nitrogen for Free fatty acids also rise after myo- symptoms to diagnosis in the Verner- albumin synthesis have been investigated cardial infarction. We therefore studied Morrison syndrome (pancreatic cholera) in 10 patients with chronic uraemia and 29 postinfarction patients without cardio- is three years (Kraft, Tompkins, and four normal volunteers. Although the genic shock, and 17 developed uncon- Zollinger, 1970) by which time many of mean absolute rate of urea degradation in jugated hyperbilirubinaemia (17 ,umole/ the tumours have metastasized (Verner uraemics (3 7 m mole h-1) was higher litre or more) in the first three days. and Morrison, 1974) and the patients then than in normals (2.3 m.mole h-1) there We suggest that FFA interfere with succumb to torrential diarrhoea. Vaso- was no significant correlation with plasma hepatic bilirubin metabolism and may active intestinal peptide (VIP) has been urea concentration. Nevertheless, the cause the unconjugated hyperbilirubin- suggested as the causative agent of this absolute utilization of urea nitrogen for aemia of fasting and myocardial in- syndrome (Bloom, Polak, and Pearse, albumin synthesis was very much higher farction. 1973). in uraemics (83.8 u.mole h-1) than in Plasma VIP has been measured by normals (6-4 p.mole h-'), while the Interference with sympathetic function and radioimmunoassay in 17 patients with the efficiency of utilization was about sixfold catecholamine responsiveness in liver classical Verner-Morrison syndrome and greater and was enhanced by a restricted disease was greatly elevated, ranging from 232 to protein intake. A significant negative 2100 pg/mI (normal < 100 pg/ml). In 10 correlation was noted between efficiency K. K. MANGHANI, JEAN GINSBURG, S. P. cases where tumour was available the of utilization and the albumin synthetic NEWMAN, A. G. BERNARD, M. R. LUNZER, VIP content ranged from 0 9 to 108 ug/g rate. These data and those obtained in the AND SHEILA SHERLOCK (Departments of wet wt (detection limit < 0001 ,ug/g). stagnant loop syndrome(Varcoe, Halliday, Medicine, Obstetrics, and Physics, Royal Gastric inhibitory peptide (GIP) was not and Tavill, 1974) indicate that the supply Free Hospital, London) Chronic liver Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from 400 The British Society ofGastroenterology disease may be associated with clinical quantitatively by direct measurement of patients restudied during the recovery signs of peripheral vasodilatation and a liver parenchymal cell uptake of 1311 Rose phase, cytotoxicity was decreased from a hyperdynamic circulation. Hypertension Bengal using a gamma scintillation mean of 63 to 15%. In the remaining is rare in cirrhosis. Baroreceptor-mediated camera with a digital store and retrieval seven who had a biopsy performed, there sympathetic responsiveness has been system is described. Eighty-two studies was only minimal parenchymal inflam- shown to be impaired in liver disease and have been performed on 73 patients and mation, and cytotoxicity was observed this has been suggested as an explanation the results compared with the histological in only one case. for the above cardiovascular changes'. appearances on liver biopsy and the Blocking experiments indicated that the In order to determine the site and extent clinical outcome. Patients studied in- cytotoxic reaction was directed against of this defect we have measured the effects cluded patients with normal liver biopsy LSP as in chronic active hepatitis, and it of both reflex sympathetic and exogenous (14); obstructive jaundice (12); primary is possible that alcohol or the associated catecholamine stimulation in healthy biliary cirrhosis (9); acute and con- hyaline necrosis may initiate this auto- subjects and patients with cirrhosis. valescent hepatitis (15 studies on 10 immune reaction which eventually could The effect of applying ice to the fore- patients); alcoholic liver disease (32 lead to cirrhosis. head, of stressful mental arithmetic, of studies on 28 patients, including 18 with lower body negative pressure and of the cirrhosis, five with alcoholic hepatitis, Reference intravenous infusion of catecholamines five with fatty liver). 'Thomson, A. D., Cochrane, A. M. G., McFarlane, forearm flow was measured by correlation I. G., Eddleston, A. W. L. F., and Williams, on blood The results show a good Roger (1974). Lymphocyte cytotoxicity to venous-occlusion plethysmography2. The between the rate of liver uptake of 1311 isolated hepatocytes in chronic active effect of these manoeuvres on pulse rate Rose Bengal and the histological changes hepatitis. Nature (Lond.), 252, 721. and blood pressure was also measured. on biopsy, as well as a good correlation Reflex vasoconstriction in response to with clinical prognosis measured in terms ice and lower body negative pressure was of clinical improvement or deterioration 14C-ethanol breath test in alcoholic liver significantly impaired in cirrhosis as was to death. The rate of liver uptake is a disease the reflex vasodilatation during mental better index than the clearance of radio- arithmetic. Peripheral vascular responses isotope from the blood and is superior to B. DORDONI, R. P. H. THOMPSON, AND to exogenous noradrenaline were also conventional biochemical investigations ROGER WILLIAMS (Liver Unit, King's College significantly impaired in patients with in both icteric and anicteric patients. It is Hospital and Medical School, London) cirrhosis, but responses to exogenous suggested that this technique may be a The aetiology of alcoholic hepatitis is adrenaline and angiotensin were similar in safe and sensitive method of assessing the unknown, but may be due to impairment

both groups. severity of liver disease in addition to by large doses of alcohol of its own http://gut.bmj.com/ These results suggest that patients with monitoring the clinical progress, parti- metabolism. chronic liver disease have impaired cardio- cularly in situations where liver biopsy We have studied the hepatic metabolism vascular responses to both reflex sym- may be unreliable or hazardous. of alcohol by the excretion of 14CO2 in pathetic stimulation and exogenous nor- the breath after an intravenous tracer dose adrenaline, indicating a defect of the of 14C-ethanol in patients with alcohol efferent and possibly central and afferent Lymphocyte cytotoxicity to isolated hepato- liver disease, and compared them to pathways in the sympathetic nervous cytes in alcoholic liver disease patients with viral hepatitis. In six normal

system. subjects the excretion in the first four on September 28, 2021 by guest. Protected copyright. References A. M. G. COCHRANE, A. D. THOMSON, A. hours was 47 l 5 8 % (mean ± SD), and MOUSSOUROS, B. PORTMAN, A. L. W. F. was significantly increased in six alcoholics 'Lunzer, M. R., Newman, S. P., and Sherlock, S. EDDLESTON, AND ROGER WILLIAMS (The with livers alone (67 ± 10%). It was (1973). Skeletal muscle blood flow and fatty neurovascular reactivity in liver disease. Liver Unit, King's College Hospital, also significantly increased in 13 alcoholics Gut, 14, 354-359. Denmark Hill, London) Lymphocytes with cirrhosis (74 ± 19%), although the 'Ginsburg, J., and Cobbold, A. F. (1960). Effects from patients with untreated chronic plasma clearance of antipyrine, an of adrenaline, noradrenaline and isopro- pylnoradrenaline in man. Ciba Foundation active hepatitis (CAH) have been shown indication of metabolism of other drugs, Symposium on Adrenergic Mechanisms, to be cytotoxic to isolated hepatocytes. was significantly slowed (30 ± 23 hours; ed. by J. R. Vane, G. E. W. Wolstenholme, The ability of a liver-specific membrane normal 11-7 ± 3 8). Compared to these and M. O'Connor, pp. 173-189. J. & A. lipoprotein (LSP) to block this reaction alcoholics it was significantly reduced in Churchill Ltd, London. suggested that sensitization to this antigen seven with alcoholic hepatitis (44 4 9%o) was responsible for the hepatocyte des- and less significantly in nine with viral Quantitative assessment of liver function truction'. Using the same assay we have hepatitis (57 ± 13%), even though liver and prognosis using 1311 Rose Bengal investigated 23 patients with alcoholic damage was more severe in those with liver disease, to determine whether auto- viral hepatitis. D. R. TRIGER, T. R. GAMLEN, D. M. ACKERY, immune reactions are involved in its These results confirm that the rate of J. S. FLEMING, R. W. GRANT, R. W. KENNY, pathogenesis as others have suggested. metabolism of alcohol is increased in A. G. MaCIVER, AND RALPH WRIGHT Positive results have been obtained in 12 alcoholics, and show that this persists (Professorial Units ofMedicine andPathol- of 23 patients, and when the findings were even when cirrhosis has reduced anti- ogy and the Wessex Regional Department related to the histology significant cyto- pyrine metabolism. Secondly, the relatively ofNuclear Medicine, Southampton Univer- toxicity was found in nine of 10 patients severe impairment of alcohol metabolism sity Hospitals, Southampton) A tech- with evidence of acute alcoholic hepatitis in alcoholics with alcoholic hepatitis may nique for assessing hepatic function and abundant hyaline. In two of these help to explain this liver lesion. Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from The British Society ofGastroenterology 401 Studies of a viral agent isolated from were weighed weekly: the control rabbits to the caecum and appendix for five patients with Crohn's disease and other gained significantly more weight than minutes at laparotomy, no other procedure intestinal disorders those inoculated with Crohn's or ulcera- being performed. Three animals died tive colitis homogenates. Macroscopically, within 14 days with gross distension of W. L. BEEKEN, K. K. ACHARYA GOSWAMI, eight of 19 of the Crohn's inoculated the caecum. The remaining six all AND D. N. MITCHELL (Brompton Hospital, showed ileal thickening, abscess forma- developed saccular lesions similar to London) In 1974 a small RNA virus was tion, and mucosal ulceration. Two of the those described above, and two showed isolated in the USA from 31 of 44 five rabbits receiving ulcerative colitis mucosal ulceration. patients with Crohn's disease (CD) and homogenate showed mucosal erosion and It is concluded that contact with skin other intestinal disorders1. We report ulceration in the colon. Microscopically, preparation is a potent cause of caecal here the preliminary findings of a search granulomatous changes evolved in nine lesions in the rabbit. This factor should for such an agent in similar patients in of the Crohn's inoculated: four of the five clearly be excluded in animal models of the UK. To identify virus, tissue culture rabbits receiving ulcerative colitis homo- intestinal disease. monolayers of human embryonic lung genate showed granulomatous changes fibroblasts are inoculated with suspen- with the presence of aggregations of Reference sions of intestinal tissue and observed for round cells; these changes were limited to 'Cave, D. R., Mitchell, D. N., Kane, S. P., and a virus-induced effect the colon and were dissimilar those Brooke, B. N. (1973). Further animal cytopathic (CPE). from evidence of a transmissible agent in Crohn's Positive cultures are defined by the seen in the Crohn's inoculated. The disease. Lancet, 2, 1120-1122. development of CPE in one or more histological differences were maintained passages. Viral neutralization studies of on passage from four of the Crohn's and In-vitro synthesis of immunoglobulins, sera are performed against homologous one of the ulcerative colitis donors. The secretory component, and lysozyme by and heterologous viral isolates. Thus results of these experiments confirm our normal and pathological human gastro- far, cultures have been positive in six previous findings in Crohn's disease; intestinal mucosa patients, four with CD, in one with procto- additionally, they provide evidence for colitis, and in one with cancer of the the presence of a transmissible agent frcm D. B. L. MCCLELLAND, R. F. M. LAI A FAT, colon. Neutralizing antibody against the patients with ulcerative colitis. R. van FURTH (Department ofTherapeutics, US been identified in first isolate has Reference Royal Infirmary, and Department of the serum of the first UK patient. Initial Microbial Diseases, University Hospital, electron microscopic studies of the US 'Cave, D. R., Mitchell, D. N., Kane, S. P., and Brooke, B. N. (1973). Further animal Leiden) An in-vitro culture technique agent carried out in London have demon- evidence of a transmissible agent in Crohn's has been used to study protein synthesis strated nuclear and cytoplasmic changes disease. Lanc ?t, 2, 1120-1122. in of normal and biopsies pathological http://gut.bmj.com/ of CPE consistent with those induced by mucosa from oesophagus, stomach, and Picorna virus. Electron microscopic studies Chronic lesions of rabbit bowel due to large and small intestine in patients. of London isolates are in progress. These contact with antiseptic skin preparation Tissues are cultured in the presence of preliminary investigations are currently radioactivity labelled amino acids, and being extended by studies of coded M. M. ORR, D. L. TAMARIND, JOSEPHINE newly synthesized, labelled proteins are biopsies and sera in collaboration with COOK, W. J. FINCHAM, P. R. HAWLEY, J. P. demonstrated by radioimmunoelectro- other London hospitals in an attempt to QUILLIAM, AND M. H. IRVING (Departments phoresis. Normal mucosa from all sites clarify the relationship of these viral of Surgery, Pharmacology, and Clinical has been shown to synthesize secretory isolates to human disease. Pathology, St Bartholomew'sand StMark's IgA in vitro, although the relative amounts on September 28, 2021 by guest. Protected copyright. Reference Hospitals and the Institute ofOrthopaedics, of IgA and secretory component syn- London) Chronic caecal lesions arising thesized differ in different parts of the 'Aronson, M., Phillips, C. A., and Beeken, W. L. in rabbits receiving ileal injections of bowel. IgG and IgM synthesis has also (1974). Gastroenterology, 66, 661. Crohn's tissue homogenate have been been detected in most normal biopsies. attributed to transmissions of the disease'. Lysozyme is synthesized by normal gastric Observations on the transmissibility of We observed similar caecal lesions in 24 mucosa. Synthesis of the C3 and C1 Crohn's disease and ulcerative colitis of 51 rabbits up to three months after components of complement was found in ileal injections of bacterial suspensions, small and large bowel. D. R. CAVE, D. N. MITCHELL, AND B. N. sterile culture media, and Crohn's and Striking changes in the pattern of BROOKE (St George's Hospital, London, non-Crohn's tissue homogenates. The immunoglobulin synthesis were seen in and Brompton Hospital, London) We possibility has been investigated that these inflammatory conditions of stomach and have extended our transmission studies lesions were artefacts due to contact with intestine, such as biliary gastritis, in which of Crohn's disease in New Zealand white the skin preparation, tincture of iodine there was a marked increase in IgG and rabbits' to include the use of fresh ileal or and surgical spirit. IgM synthesis, or active ulcerative colitis colonic tissues from six patients with A series of 30 rabbits were subjected to in which IgG synthesis was greatly in- Crohn's disease (19 rabbits), five patients procedures similar to the above but saline creased. with no evidence of inflammatory bowel packs were used to insulate the bowel from Several recent studies have demon- disease (18 rabbits), four sham controls, the skin preparation during inoculation strated by immunofluorescence that there and two patients with ulcerative colitis of the ileum. None developed large bowel are changes in the numbers of immuno- (five rabbits). Intestinal changes were lesions. globulin-containing cells of each class in assessed by biopsy at three, six, and nine In nine rabbits swabs containing dilute the mucosa in inflammatory bowel disease months and at necropsy. All the rabbits iodine-in-spirit or spirit alone were applied and coeliac disease. Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from 402 The British Society ofGastroenterology The present study provides confirma- the function of the remaining platelets hepatitis B antigen positive and 15 tion ofthese findings using an independent has never been investigated. Using the hepatitis B antibody positive. Of the 28 method, and also provides information Mielke template technique to quantitate spouses tested none were antigen positive about the ability of normal and abnormal capillary bleeding time we found in nine but six were antibody positive. gut mucosa to synthesize other proteins patients an inverse but linear relationship Fifty first-degree relatives of the anti- such as lysozyme which may be involved between bleeding time and platelet count body-positive individuals were available in the physiological functions of secretory (p = < 0001). This differed, however, for testing. None were found to be hepati- antibodies. from that drawn from Shulman's data' in tis B antigen positive but five had positive patients with thrombocytopenia from tests for the antibody. Of the 26 spouses other causes: for any given platelet count tested one was hepatitis B antigen positive Studies on the Peyer's patches of germ-free the bleeding time is significantly (p = < and one hepatitis B antibody positive. and conventional mice immunoglobulin by 0-001) longer in fulminant hepatic failure. In this study the main incidence of synthesis in vitro This is suggestive of defective platelet positive tests was in the first-degree function, and in further studies of platelet relatives (particularly the sibs and parents) D. B. L. MCCLELLAND (Department of sizes using a Coulter counter we found a of the carriers with few positive results in Microbial Diseases, University Hospital, greater reduction of the larger, sticky, the spouses. These results suggest that the Leiden) The Peyer's patches of normal most haemostatically active platelets than risk of transmission of the hepatitis B mice are substantial aggregators of in the smaller ones. Similar measurements antigen by asymptomatic carriers to their lymphoid tissue which lie along the anti- made before and after charcoal haemo- spouses is less likely than to their blood mesenteric border of the small bowel. perfusion used for temporary liver support relatives. They are easily seen with the naked eye showed accentuation of this defect with and have a characteristic architecture further prolongation of bleeding time. when viewed microscopically. The func- Not only will the loss ofsticky platelets Portal hypertension induced by vinyl tion of Peyer's patches is not known, but contribute to the haemostatic defect of chloride they are very much smaller in germ-free fulminant hepatic failure but their animals than in those which have a deficiency may be partly responsible for P. M. SMITH, D. M. J. WILLIAMS, AND I. R. conventional gut flora. the hypotension so characteristic of this CROSSLEY (Department of Medicine, Llan- In this study the ability of Peyer's patch syndrome, since the maintenance of to has dough Hospital, Penarth, Glamorgan) tissue synthesize immunoglobulins normal peripheral vascular resistance is Polyvinyl chloride is a widely used plastic been studied using an in-vitro culture in part dependent on their presence2. in which labelled that has been manufactured from vinyl technique radioactively http://gut.bmj.com/ amino acids are incorporated into newly References chloride monomer in large quantities for which can then be over 40 years. The recent discovery of synthesized proteins, 'Shulman, N. R., Watkins, S. P., Itscoitz, S. B., three angiosarcomas in workers in a identified by radioimmunoelectrophoresis. and Students, A. B. Transactions of Amer- Peyer's patches from conventional mice ican Associations of American Physicians, polyvinyl chloride production plant synthesize IgG, IgA, and IgM, in marked 81, 302-313. (Creech and Johnson, 1974) has led to contrast to the surrounding gut wall, in 'Swank, R. (1968). Ser. Haemat., 12, 146-167. much publicity and the detection of a which only IgA synthesis can be detected further 20 cases across the world. How- this In germ-free animals, ever, non-cirrhotic fibrosis and portal by technique. on September 28, 2021 by guest. Protected copyright. IgG, IgA, and IgM are also synthesized Epidemiological observations on the families hypertension may be a commoner mani- by Peyer's patches, but there is no of hepatitis B antigen carriers and hepatitis festation of vinyl chloride liver damage. synthesis of immunoglobulin by the B antibody-positive individuals Seven vinyl chloride process workers, surrounding gut. Studies of the immuno- aged 32-57, with portal hypertension have globulin synthesis in other organs of JUDITH M. HELLAWELL, I. L. WOOLF, D. M. been seen in one chemical plant, who have germ-free and conventional mice suggest JONES, AND I. W. DYMOCK (Departments been exposed to the chemical for periods that the Peyer's patches may act as a of Medicine and Bacteriology, University of 3-5 to 15 years. Four presented with source of IgA-producing cells when they Hospital of South Manchester) The non- bleeding varices, two were found in a are stimulated by the presence of the parenteral transmission of the hepatitis B survey of workers at risk, and one was bowel flora. antigen (HBAg) by patients with acute discovered to have cirrhosis at laparotomy or chronic hepatitis is now well estab- for a duodenal ulcer. Although oeso- 'Present address: University Department ol lished. However, little is known about the phageal varices were demonstrated by Therapeutics, Royal Infirmary, Edinburgh. transmission within the families of asymp- barium meal or endoscopy, splenic tomatic HBAg carriers or hepatitis B venography has shown only minor changes Defective platelet function with deficiency antibody (HBAb)-positive individuals. In in the intrahepatic branches of the portal of 'sticky platelets' in fulminant hepatic an attempt to elicit this information we vein. In the majority, liver biopsy has failure have carried out an epidemiological study revealed an inconspicuous non-cirrhotic on the families of 40 asymptomatic fibrosis, more apparent on a wedge than a M. J. WESTON, P. G. LANGLEY, AND ROGER hepatitis B antigen carriers and also the needle biopsy. Four patients have required WILLIAMS (The Liver Unit, King's College families of 34 healthy individuals with surgery for bleeding varices, and three of Hospital, London) Although the occur- hepatitis B antibody. these remain alive and well up to seven rence of thrombocytopenia in the bleeding Ninety-three first-degree relatives years later, with little or no evidence of diathesis of fulminant hepatic failure is (parents, sibs, or offspring) of the HBAg encephalopathy. One patient has died well recognized, its cause is uncertain and carriers were studied. Of these nine were from an angiosarcoma. Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from The British Society ofGastroenterology 403 Reference 100 IU/I (one-tailed test, P < 0025). One The relationship of lower oesophageal Creech, J. L., Jr, and Johnson, M. N. (1974). patient in the halothane group showed a sphincter pressure to plasma gastrin con- Angiosarcoma of the liver in the manufac- maximum SGPT of 1800 IU/I and another centration ture of polyvinyl chloride. J. occup. Med., a maximum SGPT of 900 IU/I. Neither 16,150. patient had a symptomatic illness or any C. H. CALVERT, T. G. PARKS, AND K. D. alteration in other liver function tests, BUCHANAN (Departments of Surgery and but liver biopsies showed changes charac- Medicine, Queen's University, Belfast, A controlled prospective trial of the effect teristic of hepatitis. Seven of the patients N. Ireland) It has been suggested by of multiple exposures to halothane on liver given halothane showed a rise in the Grossman (1973) that the response of the function SGPT greater than 20 IU/I while only one lower oesophageal sphincter to circulating patient in the control group showed a gastrin may be unphysiological. RALPH WRIGHT, A. CRAMPTON-SMITH, JOAN rise of 20 IU/I (one-tailed test, P < 0 02). Ten healthy fasting volunteers were TROWELL, MORAG CHISHOLM, MARGARET each given three pentagastrin infusions, HAWKSLEY, 0. E. EADE, BARBARA LLOYD, 0-001 ,g/kg/min, 0 01 /g/kg/min, and J. C. EDWARDS, AND T. M. MOLES (Depart- The mechanism ofaction ofmetoclopramide 0-1 uLg/kg/min for 30-minute periods ments of Medicine and Anaesthetics, respectively while gastric acid output and Southampton University Hospitals, and A. M. HAY (J. SPENCER) (Department of lower oesophageal sphincter pressure Radcliffe Infirmary, Oxford) Over 400 Surgery, Royal Postgraduate Medical were measured. Pentagastrin, 0 01 ug/ patients who had received a halothane School, London) Metoclopramide is kg/min, which was submaximal for acid anaesthetic within the previous year and known to enhance gastrointestinal motility production, resulted in a significant rise who required a further anaesthetic were but there have been few pharmacological in sphincter pressure when compared to allocated at random to be given halothane studies of its mechanism of action. Eisner pressures obtained during saline infusion or another anaesthetic agent, the latter on (1968) and Beani, Bianchi, and Crema (p < 0-05). This sphincter pressure rise, a halothane-free machine. Tests of liver (1970) have suggested that metoclopramide however, was less than that noted when function and eosinophil counts were sensitizes peripheral muscarinic receptors pentagastrin 0-48 ,ug/kg/min was given performed before the anaesthetic and at to acetylcholine. intravenously as a bolus. intervals for two weeks. There was a We have investigated the effects of Six anaesthetized dogs had sphincter significant elevation of the serum trans- metoclopramide on longitudinal strips pressures measured and plasma gastrin aminases in the halothane group com- of guinea-pig stomach mounted in a concentrations assayed at minute intervals pared with the controls, maximal towards modified form of superfusion apparatus following an intravenous injection of the end of the second week. Two patients (Gaddum, 1953). Responses to drugs and synthetic gastrin I at doses ranging from in the halothane group had overt hepatitis transmural stimulation were recorded 15 ng/kg to 500 ng/kg body weight. http://gut.bmj.com/ documented histologically. The relation- under isometric conditions with a tension Sphincteric pressure started to rise at ship ofelevated transaminases to frequency transducer. plasma gastrin concentrations of 50 to and timing of exposure and the nature of Metoclopramide (2 x 10-5 g/ml) 150 pg/ml with a maximum rise at the primary diagnosis will be presented produced a two- to three-fold increase in 1000-3000 pg/ml. Maximum gastrin con- and the significance of these findings amplitude of the spontaneous beats centration after a protein meal in dogs discussed. exhibited by the muscle strip. This was 1 8 ± 22 pg/mI. phenomenon was antagonized by hyoscine These results indicate that some lower (1 X 10-7 g/ml), but not by tetrodotoxin oesophageal sphincter pressure rise occurs on September 28, 2021 by guest. Protected copyright. A controlled trial of repeated halothane (1 X 10-7 g/ml) or hexamethonium towards the upper end ofthe physiological anaesthetics in patients with carcinoma of (5 x 10-6 g/ml). The contractile response range of plasma gastrin concentration the uterine cervix treated with radium to transmural stimulation was similarly but that the peak pressure rise only occurs enhanced by metoclopramide (2 x in the pharmacological range. JOAN TROWELL AND A. CRAMPTON SMITH 10-6 g/ml) as was the response to ex- (DepartmentsofMedicineandAnaesthetics, trinsic acetylcholine. The apparent sen- Reference Oxford) Thirty-nine patients submitted sitization to acetylcholine was, however, Grossman, M. I. (1973). Gastroenterol., 65, 994. to repeated general anaesthetics for prevented by tetrodotoxin and hexa- radium treatment for carcinoma of the methonium, implying that this effect Gastrooesophageal reflux in late pregnancy uterine cervix were randomly allocated to depends upon ganglionic stimulation by anaesthetics which did or did not include acetylcholine. V. M. HEY, D. S. SHARP, D. G. OSTICK, L. halothane. Their serum transaminase These results call for a new interpreta- SKINNER, P. C. GANGULT, AND D. J. COWLEY (SGPT) levels were monitored before each tion of the action of metoclopramide and (Departments of Anaesthesia, Obstetrics anaesthetic. Those patients whose SGPT suggest that it increases the amount of and Surgery, the Patterson Laboratories, rose above 100 IU/I were freed from the acetylcholine released at the post-gang- University Hospital of South Manchester, restriction determined by the initial lionic cholinergic nerve ending. Department of Medicine, Manchester allocation and treated as indicated Royal Infirmary) In pregnancy heartburn clinically. Four of 18 patients in the References is common. In late pregnancy women halothane group had SGPT levels above Beani, L., Bianchi, Clementina, and Crema, C. have an increased risk of inhaling gastric 100 before the third radium treat- (1970). Eur. J. Pharmacol., 12, 320-331. acid during emergency obstetric anaes- IU/I Eisner, M. (1968). Brit. med. J., 4, 679-681. ment. No patients in the control group Gaddum, J. H. (1953). Brit. J. Pharmacol., 8, thesia (Mendelson, 1946). These two (21 patients) developed SGPT levels above 321-326. problems may be related and in this Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from 404 The British Society ofGastroenterology investigation we have sought possible The slides of these biopsy specimens culture medium which was harvested and causes for them. were graded histologically by one pathol- replenished at regular intervals. The The integrity of the lower oesophageal ogist (R.W.) who was working 'blind', enzyme has properties similar to those sphincter was studied in 31 women in late with these slides intermingled with mis- enzymes derived from mammalian skin, pregnancy and in 10 healthy non-pregnant cellaneous slides of biopsy specimens cornea, and synovial tissue in terms of its controls. Pressures were measured with from patients. ability to cleave the tropocollagen molecule perfused open-tipped polyethylene tubes The results show that virtually all the at a specific locus to give three-quarter and transducers. Gastrooesophageal re- gastric biopsy specimens fell within the (TCA) and one-quarter (TCB) length flux ofacid was detected by apH electrode. normal category of the classification of fragments; its pH dependence; and its Fasting serum gastrin and progesterone gastritis of Whitehead, Truelove, and susceptibility to the action of specific were estimated. Gear (1972), which can therefore be inhibitors. Chromatographic studies have Mean gastric pressure was higher in regarded as a satisfactory classification shown a molecular weight of approxi- pregnant women than in controls (p < from the point of view of normal limits. mately 38000, ie, less than that of collage- 0-001). Mean maximum sphincter and By contrast, nearly 50% of the duodenal nase isolated from skin (63 000) but slightly barrier pressures were lower in pregnant biopsy specimens fell into the category of greater than that of collagenase isolated women (p < 0 05). Gastric pressure was mild duodenitis in the classification of from synovium (33000). unexpectedly higher in 13 pregnant Whitehead, Roca, Meikle, Skinner, and women without heartburn (16-8 cm HO) Truelove (1975). This classification there- than in 18 with heartburn (144 cm H20, fore does not appear to define the limits p < 0-05). Maximum sphincter pressure of normality correctly. For future work Pancreatic regeneration following surgical was lower in women with heartburn than on duodenitis, the two categories 0 and I resection in those without or in controls (p < of the classification should be combined 0 025). Barrier pressure was not signifi- to cover the normal range of histological K. W. PEARSON, D. SCOTT, AND H. B. cantly different between women with or appearances. TORRANCE (Manchester Royal Infirmary without heartburn. Free reflux occurred References and the Paterson Laboratory, Christie in eight of II with heartburn, three of 10 Hospital, Manchester) Studies into pan- without heartburn, and in none of 10 Whitehead, R., Truelove, S. C., and Gear, M. W. L. creatic regeneration after surgical resec- controls. Serum and (1972). The histological diagnosis of chronic gastrin progesterone gastritis in fibreoptic gastroscope biopsy tion have given conflicting results: concentrations were similar in pregnant specimens. J. clin. Path., 25, 1. Cameron (1927) failed to show regenera- women with and without heartburn. Whitehead, R., Roca, M., Meikle, D. D., Skinner, tion, Segida (1962) observed regeneration

Serum gastrin did not differ from controls. J. M., and Truelove, S. C. (1975). The http://gut.bmj.com/ histological diagnosis of duodenitis in four months after resection which had Pregnant women with heartburn have fibreoptic gastroscope biopsy specimens. disappeared by 10 months. More recently weaker lower oesophageal sphincters than Lehv and Fitzgerald (1968) observed those without. Significant gastrooeso- pancreatic weight increase commencing phageal reflux may, however, occur in 60 days after resection, in spite of an those without heartburn who thus may Demonstration of a neutral collagenase initial hyperplasia. also be at risk during anaesthesia. from human gastric mucosa Male Wistar rats of body weight 176 ± Reference 15 g were randomly allocated into control Mendelson, C. L. (1946). Anmer. J. Obstet. Gynaec., J. S. TUCKER, G. GREEN, D. WOOLLEY, J. M. and resection groups. Following 90 % on September 28, 2021 by guest. Protected copyright. 52,191. EVANSON, AND I. W. DYMOCK (Department pancreatectomy the residual segment in of Medicine, The University Hospital of the resected animals was compared with The histological state of the gastric and South Manchester) Collagenases, active the corresponding segment in the controls duodenal mucosa in healthy volunteers at neutral pH, are believed to have an at intervals up to 336 days later. important role in the degradation of At all times studied after resection the MARTIN ROCA, S. C. TRUELOVE, AND R. collagen. To date such enzymes have been residual pancreatic segment in the resected WHITEHEAD (Nuffield Department of Clini- identified in the culture medium of a animals was significantly heavier (p = cal Medicine and Department of Morbid variety of human tissues including skin, < 0-001) than the corresponding segment Anatomy, The Radcliffe Infirmary, Oxford) cornea, and the synovial tissue of patients in the controls. Regeneration commenced One of the major problems in the study of with rheumatoid arthritis. during the first 14 days, becomingcomplete gastritis and duodenitis is to be able to Since many pathological conditions of by day 56. Labelling studies using tritiated define the limits of normality. Ten healthy the stomach are associated with break- thymidine showed a significant (p = caucasian volunteers have been studied by down of collagen-containing tissue or, in < 0-001) six-fold rise above control means of endoscopic biopsy in order to the healing process, with marked fibrous levels three days following resection, provide a yardstick. Biopsy specimens tissue formation resulting in stenosis or indicating hyperplasia. Enzyme levels in were taken under direct vision from the stricture formation, we have attempted to the regenerated pancreatic tissue were gastric and duodenal mucosa using the identify collagenase in gastric mucosa. comparable with the controls. Olympus fibreoptic GIF panendoscope or Biopsy specimens taken at routine gastro- Thus the pancreas does regenerate after the Olympus side-viewing JF duodeno- scopy have been incubated at 370 in surgical resection, the primary and pre- scope. The biopsy specimens were taken culture medium containing antibiotics for dominant response being cellular pro- from five standard sites in the stomach periods up to six days. An enzyme with liferation. The regenerated pancreatic and from three standard sites in the the characteristics of a specific neutral tissue is functionally comparable with duodenum. collagenase has been identified in the normal pancreatic tissue. Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from The British Society ofGastroenterology 405 References ment of bicarbonate output by duodenal patients. The morphology of cells in pure Cameron, G. R. (1927). J. Path. Bact., 30, 713. aspiration after secretin stimulation, and juice is excellent and in particular the Lehr, M., and Fitzgerald, P. J. (1968). Amer. J. endoscopic retrograde cholangiopan- presence of typical degenerate cells cor- Path., 53, 513. creatography (ERCP). relate well with the presence of pancreatic Segida, G. V. (1962). Biul. Eksp. Biol. Med., 54, 88. Although a normal scan was good pathology. evidence against chronic pancreatic dis- In 19 cases of pancreatic carcinoma, Antibodies reacting with human exocrine ease, in practice an unequivocally normal ERCP alone was diagnostic in 12 cases pancreas scan was obtained in only 40% of the (63 %), whilst cytology alone was diag- normal patients, the remaining scans nostic in 11 cases (58 %). Endoscopic R. LENDRUM AND GEOFFREY WALKER being unhelpful because of false positive retrograde cholangiopancreatography and (Department ofGastroenterology, StMary's results or interfering conditions. Similar pure juice cytology combined were Hospital, London) Immunological ap- difficulties occurred with the secretin diagnostic in 17 out of 19 cases of car- proaches to problems of aetiology and studies, and the overall screening yield cinoma (90 %). diagnosis in pancreatic diseases have for both these tests was poor. In addition, The dual approach of ERCP and pure received little attention. The evidence for the results of scans and secretin tests did pancreatic juice cytology appears to be a serum antibodies in these conditions is not distinguish between carcinoma and promising approach in the diagnosis of conflicting1'2, while immunofluorescent chronic pancreatitis, However, a high pancreatic cancer. It may also prove of studies in this field have not been reported. proportion of patients with duct obstruc- value in determining the significance of In the present investigation, antibodies tion on pancreatograms showed failure of minor duct changes found at pancreato- to human pancreas were sought using visualization of the pancreatic image on graphy. indirect immunofluorescence. A granular the scan. fluorescent pattern affecting the acinar Pancreatography (ERCP) was more AcutepancreatitisinNottingham 1969-1973: cytoplasm of blood group 0 pancreas discriminating both between normal and A retrospective review was found with sera from 21 of 61 acute abnormal, and between chronic pan- pancreatitis patients. By contrast, positive creatitis and carcinoma, but had a higher J. B. BOURKE (Department of Surgery, sera tested against other tissues did not technical failure rate. This procedure is University of Nottingham, General Hos- produce any characteristic or consistent not yet widely available, nor sufficiently pital, Nottingham) A retrospective re- pattern. Associated conditions among simple to be considered as a screening test. view of acute pancreatitis in Nottingham these 21 subjects included alcoholism, In patients already known to have pan- has been undertaken to determine if the biliary disease, and pancreatic carcinoma, creatic disease, pancreatography provides disease within the Nottingham defined but one-third had no apparent cause. an essential guide to surgical management population area (Miller, Keighley, and Negative results occurred with sera from (Cotton and Beales, 1974). However, the Langman, 1974) is static or changing. http://gut.bmj.com/ patients with relapsing acute pancreatitis problem of investigation of suspected The records of all patients with primary (12), chronic pancreatic diseases (14), and pancreatic disease remains unsolved; the acute pancreatitis (excluding recurrent, pancreatic carcinoma (13). The acinar most pressing need is still for a simple and traumatic, and postoperative pancreatitis) fluorescence was rare among subjects to 1973 were reviewed. There without evidence of pancreatitis, being effective screening test. for 1969 Reference were 145 patients and in 10 of these the found in only two of 80 mixed hospital diagnosis had only been made at necropsy. subjects, one of 78 healthy antenatal Cotton, P. B., and Beales, J. S. M. (1974). Brit. 1,608. The principal associated aetiological med..J., on September 28, 2021 by guest. Protected copyright. patients, and one of 12 healthy adults. factor was gallstones which were present Antibody absorption experiments sug- in 46% of patients. The incidence in the gest that the antigen is associated with the Endoscopic retrograde cholangiopancreato- year and pure pancreatic juice defined population area varied from microsomal and soluble cell fractions, and graphy (ERCP) to year with a peak incidence of 79 per may be pancreas-specific. Other charac- cytology: A combined diagnostic approach million in 1972. In 1969 and 1970 some teristics of this antibody, and its relation- in pancreatic disease patients from Nottingham were included ship to aetiology in pancreatic disease, in the trasylol trial (Trapnell, Rigby, are discussed. A. R. W. HATFIELD, A. SMITHIES, R. WILKINS, 1971, AND A. J. LEVI (Northwick Park Hospital Talbot, and Duncan, 1974). Since References and Clinical Research Centre, Watford the method of treatment has been con- 'Thal, A. P., Murray, M. J., and Egner, W. (1959). servative with careful fluid and electrolyte Lancet, 1, 1128-1129. Road, Harrow, Middlesex) Although management. Duringthisperiod 87 patients 2Metzgar, R. S. (1964). Nature (Lond.), 203, 660-661. ERCP has been firmly established as a to demonstrate the in whom the diagnosis had been made in practical and safe way life were treated with a mortality of 11N4 %. Pancreatic diagnosis: Comparison of pancreatic and biliary systems, difficulties This mortality figure is similar to that endoscopic pancreatography (ERCP), iso- still remain in the interpretation of the reported when glucagon (Condon, Knight, tope scanning, and secretin tests in 62 pancreatogram. Exfoliative pancreatic 1973) and trasylol (Trapnell patients cytology using duodenal aspirates has not and Day, difficulties et al, 1974) are used and contrasts with the found widespread favour due to 25 % mortality in the control group in the P. B. COTTON AND B. A. J. PONDER, J. S. M. in collection and interpretation. trasylol study. BEALES AND D. N. CROFT (The Middlesex At the time of ERCP pure juice can be Hospital, London, andStThomas' Hospital, collected from within the pancreatic duct References London) We investigated 62 patientswith for cytodiagnosis. This combined ap- Condon, J. R., Knight, M., and Day, J. L. (1973). known or suspected pancreatic disease by proach of ERCP and pure pancreatic Glucagon therapy in acute pancreatitis scanning with a gamma camera, measure- juice cytology has been evaluated in 45 Brit. J. Surg., 60, 509-511. Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from

406 The British Society ofGastroenterology

Miller, D. S., Keighley, A. C., and Langman, W. DEVENEY and LAWRENCE W. WAY 200 ml of 50 % glucose by fasting subjects. M. J. S. (1974). Changing patterns in epidemiology of Crohn's disease. Lancet, 1, (University of California School of Medi- This meal was labelled with Indium 113 691-693. cine and Ft Miley Veterans Adminis- and the gastric emptying monitored using Trapnell, J. E., Rigby, C. C., Talbot, C. H., and tration Hospital, San Francisco) Four a Nuclear Enterprises mark V gamma Duncan, E. H. L. (1974). A controlled trial fl camera system. Serial blood samples were of trasylol in the treatment of acute pan- dogs were prepared with a Billroth creatitis. Brit. J. Surg., 61, 177-182. antrectomy and a vagally denervated taken and the plasma enteroglucagon pouch (HP) of the gastric fundus. In- concentration was determined by a radio- Acute pancreatitis: A prospective study and creasing meals of ground liver with 5% immune assay technique. some factors in mortality bone meal were fed to ascertain the A wide range of gastric emptying rates maximum H+ secretion from the HP. was obtained (Ti 4-300 min) for the group C. W. IMRIE, E. M. S. FREW, W. LLOYD Duplicate experiments were then carried as a whole and there were significant JONES, AND L. H. BLUMGART (University out after feeding liver (33 g/kg) and 5% differences between the rates in patients Department of Surgery, Glasgow Royal bone meal to induce the maximal se- who experienced no symptoms during the Infirmary) A prospective study of 213 cretion together with the iv infusion of test and those who did. There was a highly consecutive cases of acute pancreatitis histamine (01 mg/kg-hr) or pentagastrin significant correlation between log Ti admitted to one hospital over a four-year (8 ,ug/kg-hr) or SC infusion of bethanecol and the rate of increase ofplasma entero- period were managed by a careful con- (0<1 mg/kg-hr). Serum gastrin and HP glucagon (r = 0 73, p < 0 001). servative regime which did not include the secretion were measured throughout the Accepting that enteroglucagon is re- administration of trasylol (Aprotinin) or leased by an intraluminal stimulus we glucagon (Trapnell, Rigby, Talbot, and Maximum H+ Secretion from HP conclude that the rate of gastric emptying Duncan, 1974; Condon, Knight, and Day, (pequiv/15 min) determined the magnitude ofthis response. 1973). An overall mortality rate of 10-8% Basal 0 was recorded. There was no significant Liverfeed 266 + 50 Endocrine quantitation of clinical gastric difference in mortality between patients Histamine 650 ± 119 biopsies with biliary pathology (50 % of the Pentagastrin 491 i 107 Bethanecol 307 i 75 patients) and those with alcohol-related Liver feed + histamine 986 + 150 J. M. POLAK, S. R. BLOOM, A. G. E. PEARSE, disease (23% of the patients). Mortality (p < 0-01) AND R. B. WELBOURN (Departments of was high in patients submitted to diag- Liver feed + pentagastrin 1182 i 225 Histochemistry, Medicine, and Surgery, nostic laparotomy in the acute phase of (p < 0-02) Royal Postgraduate Medical School, illness and five of 13 such cases died. Liverfeed + bethanecol 919 ± 288 London) Clinical diagnosis of endocrine (p < 005) http://gut.bmj.com/ Arterial blood gas measurements in 70 dysfunction demands knowledge not only cases revealed 40 % of PO2 levels less than of plasma hormone levels but also of the 60 mm Hg breathing air. Arterial hypoxia experiments. The H+ secretion from the state of the endocrine cells. However the may be a major factor in determining HP after liver started two hours after the question of whether a single small biopsy outcome of the disease and this factor feed and was maximal at four hours, is representative of the state of the endo- may be especially important in the poor while the serum gastrin (radioimmuno- crine cells of the gut mucosa is not yet clinical course of patients submitted to assay) averaging 54 ± 6 pg/ml was known. We have therefore studied the laparotomy. Humidified oxygen (8 litres/ unchanged. correlation between the G cell number, min via Hudson or Ventimask) became The small intestinal phase of gastric density, and area, as delineated by on September 28, 2021 by guest. Protected copyright. routine policy half way through the study secretion occurred late after a meal, was immunohistochemical staining, and the and since its introduction the mortality hormone induced, and independent of gastrin content measured byradioimmuno- rate for comparable groups of patients serum gastrin. This stimulus to gastric assay, in multiple biopsies of the antral over the age of 60 has fallen from 24 to secretion potentiated significantly with region of human stomach. 12%. maximal doses of histamine, pentagastrin, Fresh antra were obtained at operation Acute respiratory insufficiency in acute and bethanecol. from duodenal ulcer patients and evenly pancreatitis requires further investigation spaced biopsy samples were taken by but maybe importantin the elderlypatient, The relationship between gastric emptying means of a specially designed multiple especially if submitted to laparotomy in rate and plasma enteroglucagon concen- punch. Alternate samples (about 40) were the acute phase ofillness. tration stained, each stomach in a single batch, References by an immunoperoxidase method, and D. N. L. S. R. C. LAWSON- area Condon, J. R., Knight, M., and Day, J. L. (1975). RALPHS, BLOOM, cell count, density, and quantified Glucagon therapy in acute pancreatitis. SMITH, AND JAMES P. S. THOMSON (The by an automatic image analysing com- Brit. J. Surg., 60, 509-511. Department of Surgical Studies, The puter (Quantimet 720). The remaining Trapnell, J. E., Rigby, C. C., Talbot, C. H., and Middlesex Hospital Medical School, Lon- samples were extracted and assayed for Duncan, E. H. L. (1974). A controlled trial of trasylol in the treatment of acute pan- don) Enteroglucagon is liberated from gastrin content. creatitis. Brit. J. Surg., 61, 177-182. the intestinal mucosa by the ingestion of A high degree of correlation (r > 0-8, P glucose. This study investigated the < 0-001) was obtained between cell The intestinal phase of gastric secretion in influence of the rate of gastric emptying density, the area occupied by the G cells the dog on the plasma levels of this hormone. and also the total G cell count. Correla- Ninety-nine studies (35 preoperative tion was also obtained with extractable DAVID CAIRNS (Central Middlesex Hospital, and 64 after vagotomy with drainage) gastrin content. introducedby j. j. MISIEWICZ) and CLIFFORD were performed following the ingestion of We conclude that even a small number Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from The British Society ofGastroenterology 407 of biopsy samples will give a good rep- gastric hypersecretion by infusing secreta- serum gastrin of 35 4: 7-1 pg/ml (mean resentative index of the functional state gogues. ± SEM). The response to the standard of the antral G cell, and this technique is Pentagastrin (2 or 4 ,g/kg-min) and meal was biphasic, with peaks at 15 therefore a useful diagnostic tool in carbachol (0 4 or 0-8 pg/kg-min) were minutes (75-8 i 151 pg/ml) and 120 gastric disease. infused subcutaneously into rats for six minutes (91P5 12-3 pg/ml). The inte- to 48 hours. In each group of 30 rats, grated gastrin response (IGR) for each Tissue gastrin in peptic ulceration increased duration of infusion and in- hour was calculated (ng.min/ml), with creased doses ofpentagastrin andcarbachol the IGR for the first hour (173 ± 0-03) J. J. CONNON, J. ARDILL, AND R. J. MC- increased the incidence of duodenal being significantly less than for the third FARLAND (Department ofMedicine, Belfast ulcers, their severity, number, caudad hour (3-32 ± 0 52) (p < 0 01). City Hospital, and The Queen's University distribution, perforation, and death rate In three of the four unoperated mor- of Belfast) Although there have been from peritonitis. With pentagastrin (4 bidly obese subjects the IGR for each many studies of serum gastrin levels in ,Lg/kg-min) and carbachol (0-8 ,ug/kg-min) hour was within 1 standard error of the peptic ulcer disease there is very little for 24 hours, every rat developed a deep mean of the normal controls. information available about mucosal duodenal ulcer with a mean of three ulcers The mean fasting serum gastrin con- gastrin concentration in patients with per animal and a 7 % mortality from centrations in nine operated patients was duodenal ulceration (DU), gastric ulcera- perforation. No control rats infused with similar to the controls (43 0 ± 7 7). The tion (GU), and non-ulcer dyspepsia (NU). saline developed any mucosal changes in response to the meal was again biphasic We have measured the concentration of the stomach or duodenum. with peaks of 119-5 i 24-4 and 149-8 + gastrin (using a double antibody immuno- With this satisfactory duodenal ulcer 26-2 at 15 minutes and 150 minutes assay technique) in mucosal biopsysamples model the gastric secretory inhibitor, respectively. The IGR in the first hour taken at endoscopy from the duodenum, Pfizer UK-9040, an analogue of the (3-62 ± 0-79) was less than in the third antrum, and greater curvature of 31 antihistaminetriprolidine, wasgiven orally, hour (6-29 ± 1-16) (p < 0 05) and each patients suffering from peptic ulceration 10-100 mg/kg, one hour before and at was significantly greater than the equiv- or non-ulcer dyspepsia. The distribution various times during infusion of the alent hour in the controls (p < 0 025). of gastrin followed a similar pattern in secretagogues1. The higher the dose and These findings offer support for the each group, being highest in the antrum the more frequent the dosage, the lower existence of a mechanism by which the 2321 ± 343 pg/g, lowest in the body was the incidence, severity, number, and small intestine influences gastrin responses. 61 ± 15 pg/g, and intermediate in the perforations of duodenal ulcers. duodenum 674 ± 149 pg/g. In control rats plasma gastrins were Comparative effects of codeine and senna Comparisons of tissue gastrin at each low and the gastric G cells full of gastrin on the motor activity of the left colon site between the three groups were made. both on immunofluorescence and electron http://gut.bmj.com/ Body gastrin concentrations were similar microscopy. After gastric secretagogues SHEILA L. WALLER (Medical Research in DU (47 ± 25), GU (32 ± 14), and these measurements did not change. When Council Gastroenterology Unit, Central NU (49 + 17), and although there was a the gastric secretory inhibitor UK-9040 Middlesex Hospital, London) Although tendency towards higher levels of antral was given alone, plasma gastrin was high senna and codeine are effective in con- gastrin in DU (2597 i 531) and GU and the G cells were emptied of gastrin. stipation and diarrhoea, it is not known (2728 ± 908) compared with NU (1639 ± The addition of secretagogues to UK-9040 whether these drugs influence transit by 232), the differences were not statistically did not change this pattern of results. affecting colonic segmenting pressures in significant. However, duodenal gastrin addition to altering colonic propulsion. on September 28, 2021 by guest. Protected copyright. was significantly elevated in DU (931 ± Reference The left colonic segmenting intraluminal 205) compared with NU (429 ± 62) and 'Hamer, D. B. Price A. B. and Baron J. H. (1974). pressures (SP) were recorded at 20, 15, was at an intermediate level in GU (678 i Gut, 15, 336. and 10 cm from the anal margin with three 252). air-filled 10 x 7 mm balloons (Waller, Our results confirm the uneven distri- Gastrin response to a standard meal after Misiewicz, and Kiley, 1972) in eight bution of gastrin in the upper gastro- jejuno-ileal bypass in morbid obese patients diarrhoeal and nine constipated patients intestinal tract and demonstrate a signi- on two separate occasions. No treatment ficantly higher concentration of gastrin JOHN LENNON, G. P. LIDGARD, S. H. TERRY, was given before or during the first test. in the duodenal mucosa of duodenal ulcer AND W. SIRCUS (Wolfson Gastrointestinal Constipated patients took three Sennakot patients. Laboratories, Gastrointestinal Unit, Wes- tablets on the night before, and diarrhoeal tern General Hospital, Edinburgh) The subjects codeine phosphate 60 mg tds for Gastrin, G cells, andgastric acid in rats with small bowel is believed to play a part in the three days before, and 60 mg on the secretagogue-produced and anti-secreta- the regulation of gastrin secretion. Jejuno- morning of, the second test. The drugs gogue-inhibited duodenal ulcers ileal bypass provides an opportunity to were clinically effective inall the diarrhoeal investigate this further. and in seven constipated subjects. Traces S. N. JOFFE, R. GASKIN, A. A. J. BARROS D SA, Serum gastrin concentrations were recorded during the basal half hour, a JULIA M. POLAK, S. R. BLOOM, AND J. H. measured in the fasting state and for standard meal, and the 30-minute post- BARON (RoyalPostgraduate Medical School three hours following a standard meal in meal period were analysed in an analogue Hammersmith Hospital, London) Of the 13 normal controls, four morbidly obese to digital converter and processed by various methods used to produce duodenal subjects, and in nine others with jejuno- computer (Misiewicz, Waller, Healey, and ulcers in animals, one of the nearest to ileal bypass for morbid obesity. Piper, 1968). Differences in SP on and off the clinical situation is the production of The normal controls had a fasting treatment were compared by Student's t Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from 408 The British Society ofGastroenterology test for the following variables: average than expected if potassium were passively ment. The initial results of this trial (40 intensity, percentage duration of activity, distributed across the mucosa. Uni- patients) are as follows: six patients height of pressure peaks, and frequency directional flux measurements, employing developed wound sepsis in the controls and duration ofpressure events. 42K in the tube, showed that the lumen- (Bacteroides were isolated in five), com- Codeine and senna exerted diametrically to-serosa flux was low, that it depended pared with one patient with a wound opposite effects on SP. After codeine the on the luminal potassium concentration infection caused by a Gram-niegative pattern of motor activity in the colon of and was probably passive. The opposite organism in the treated group. In addition diarrhoeal patients resembled that re- flux (serosa-to-lumen) was considerably there were two patients with Bacteroides corded in constipated subjects and vice greater, appearing to include a large septicaemia in the controls, one of whom versa. Codeine increased SP in all leads active secretory component. This com- developed disseminated intravascular co- during the basal and at 15 and 1Ocm during ponent was little affected by altering the agulation from which the patient did not a meal, the effect being greatest at 10 cm luminal sodium concentration but was recover. Septicaemia did not occur in the (p < 0 05; p < 0 01). By contrast, senna considerably increased when other cations treated group. depressed SP during the basal and meal were introduced into the lumen although The early results of this trial indicate periods. The effect was greatest at 20 cm relatively little change in transmucosal pd that Bacteroides is an important cause of (p < 0 05; p < 0 02). The lack ofresponse occurred. Intravenous injection of 42K sepsis after colo-rectal surgery and that to eating in constipation was converted was used to determine the origin of the prophylactic chemotherapy effective to a significant response at 15 and 10 cm secretory component. The results in- against these organisms should probably (p < 0-05). Postmeal activity was un- dicated that it was almost entirely derived be considered in patients requiring large affected by codeine and depressed by from the mucosal epithelium. There was bowel surgery. senna, but not significantly. no evidence for the existence of a signifi- The data suggest that codeine and cant shunt pathway across the epithelium References senna act partly by an effect on colonic in this part of the gut. The methods Leigh, D. A. (1974). Brit. med. J., 4, 225-228. SP and support the hypothesis that SP developed for the present study will be of Okubadejo, 0. A., Green, P. J., and Payne, D. J. H. is an important factor in the mechanisms value in the investigation of changes in (1973). Brit. med. J., 2, 212-214. underlying constipation and diarrhoea. epithelial permeability in inflammatory Problems of a bowel disease. permanent colostomy References References W. D. GEORGE, ANNE EARDLEY, F. N. DAVIS, Waller, Sheila L., Misiewicz, J. J., and Kiley, AND P. F. SCHOFIELD (Departments of Nancy (1972). Gut, 13, 805. 'Edmonds, C. J., and Godfrey, R. C. (1970). Gut, Misiewicz, J. J., Waller, Sheila L., Healy, M. J. R., 11,330. Surgery and Social Research, University and Piper, E. A. (1968). Gut, 9, 232. 2Edmonds, C. J. (1971). Gut, 12, 356. Hospital ofSouth Manchester, and Depart- http://gut.bmj.com/ ment of Surgery, Park Hospital, Man- Potassium transport across distal colonic The importance of bacteroides as a cause chester) Previous workers (Devlin, Plant, mucosa in man of severe sepsis after colo-rectal surgery and Griffin, 1971) have suggested that a permanent colostomy may present many C. SALAS-COLL, J. KERMODE, AND C. J. M. R. B. KEIGHLEY, D. W. BURDON, G. problems to the patient which are not EDMONDS (University College Hospital SLANEY, W. T. COOKE, AND J. ALEXANDER- appreciated by the clinician. The aim of Medical School, London) The observed WILLIAMS (The General Hospital and the this study was to assess the effect of a electrochemical forces across the colonic University Department of Surgery, Bir- permanent colostomy on a patient's life, on September 28, 2021 by guest. Protected copyright. mucosa do not appear adequate to account mingham) It has been suggested that work, and social activities. Sixty-one for the measured potassium concentration Bacteroides fragilis may be an important patients who managed an established gradient arising by passive diffusion'. We cause of wound sepsis and septicaemia colostomy with an appliance were studied, have investigated the problem using a even in patients receiving prophylactic to define areas where significant problems dialysis method2 which involves placing chemotherapy after large bowel surgery. existed, and where further investigation a solution of chosen composition and Patients particularly prone to developing might be required. The main findings are: contained in a dialysis tube in the distal these infections are those with malignant (1) Fifteen of the 61 patients were dis- colon. The tube is mounted on a rubber disease or cases receiving steroids (Oku- satisfied with the advice given on colos- catheter and can be withdrawn after a badejo, Green, and Payne, 1973; Leigh, tomy management. (2) Thirty-eight timed period. Solutions of different initial 1974). patients had difficulties with their original composition were used in the present To determine the pathogenic impor- appliance and 29 were still having study and changes produced by the tance of these organisms we are currently problems. (3) Eighteen of the 61 patients mucosal epithelium observed. Trans- investigating the value of an antibiotic found they had to omit several items of mucosal electrical potential difference effective against Bacteroides but with no their normal diet, and 16 took regular (pd) was also measured. Studies have been influence on Gram-negative bacilli. medication to control the colostomy. done in 18 individuals with normal bowels. Patients requiring excisional surgery There was no correlation between the In the majority, the pd was between 35 for inflammatory bowel disease or cancer degree of dietary restriction, medication, and 45 mV (lumen negative). Using were entered into a prospective random- and the number of movements per day. solutions of varying initial potassium ized controlled trial. Cases were allocated (4) The social life of 22 patients was concentration, composition changes in- into two groups: one receiving Linco- curtailed following operation, and 32 had dicated that the steady-state luminal mycin 600 mg iv eight hourly immediately given up some leisure activity. (5) Of the potassium concentration was 40-50 before and for five days after operation patients employed before operation, the m-equiv/1, a value considerably greater and the remainder who received no treat- majority returned to work and reported Gut: first published as 10.1136/gut.16.5.392 on 1 May 1975. Downloaded from The British Society ofGastroenterology 409 few problems directly attributable to the A survey has been carried out in removal at operation. Weighed samples operation. (6) A majority felt depressed Nottingham in which dietary histories were homogenized in either acid-ethanol following operation and 26 patients were taken from 28 patients with appen- (to determine PG-like content) or Krebs' continue to have periods of depression. dicitis and 27 control subjects, matched solution (to indicate synthetic ability; for age and sex. Crude fibre intakes were Bennett, Stamford, and Unger, 1973). Reference calculated from standard food tables. After extraction the total PG-like activity Devlin, H. B., Plant, J. A., and Griffin, M. (1971). Average crude fibre intake was 4-15 g was assayed biologically against PGE2 Brit. med. J., 3, 413-418. per head per day and no difference in (Unger, Stamford, and Bennett, 1971). intake was found in the two groups. A Normal mucosa and submucosa from the Appendicitis and dietary fibre family history was obtained more fre- same specimens, removed at least 5 cm quently in the group with appendicitis proximal to the tumour, was studied at J. R. COVE-SMITH AND M. J. S. LANGMAN than in the control group. the same time. The results (ng PGE2 (Department of Therapeutics, The City equivalents per g moist tissue i SE) were: Hospital, Nottingham) It has been References normal tissue (acid-ethanol) 42 ± 15; claimed that appendicitis is associated Burkitt, D. P. (1971). Brit. J. Surg., 58, 695. tuniour (acid-ethanol) 89 + 16; normal with lack of dietary fibre (Burkitt, 1971). Robertson, J. (1972). Nature (Lond.), 238, 290. tissue (Krebs') 196 + 121 ; tumour (Krebs) Evidence is based on epidemiological 304 ± 93. Thus, both the PG-like content surveys, mainly carried out in Africa, and and synthetic activity were higher than the rise in appendicitis rates in the late Prostaglandins in human colonic carcinoma normal in cancerous tissues (p < 005; 19th century in Europe, at a time when the Student's t test for paired data). These fibre content of the diet is thought to have A. BENNETT AND M. DEL TACCA (Depart- results support the finding that human decreased. Though dietary surveys in- ment of Surgery, King's College Hospital colonic cancer cells in tissue culture dicate that total crude fibre intake in Medical School, London) Prostaglandins release more prostaglandin-like material Britain has altered little in the past 100 (PGs) have been implicated in various than normal (Jaffe, 1974) and strengthen years (Robertson, 1972), being about aspects of tumour growth including an the possibility that prostaglandins in- 4-2 g per head per day, information from effect on the rate of cell proliferation and fluence tumour growth. the Hospital In-Patient Enquiry and other ability to metastasize in bone. We have sources shows that appendicitis admission measured the PG content and synthesis rates in England and Wales have appar- in four carcinomas from the descending References ently fallen since 1961, whilst admission colon and four from the rectum. The Bennett, A., Stamford, I. F., and Unger, W. G. tumours from 51-72 (1973). J. Pl,ysiol., 229, 349-360. rates for abdominal pain have risen pari patients aged years Jaffe, B. M. (1974). Prostaglandins, 6, 453-461. passu. Figures for Nottingham show the were cut into small pieces and washed Unger, W. G.. Stamford, I. F., and Bennett, A. same trend. with Krebs' solution within 30 min of (1971). Nature (Lond.), 233, 336-337. http://gut.bmj.com/ on September 28, 2021 by guest. Protected copyright.