Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from

Gut, 1974, 15, 335-348

The British Society of Gastroenterology

The spring meeting was held at the University of Nottingham on 29 and 30 March 1974. The first morning was devoted to informal discussion groups, one of which was on 'Histopathology of the alimentary tract' (Chairman: Professor Ian Dawson) and the other on 'Primary liver cancer' (Chairman: Professor Sheila Sherlock). The whole of Saturday morning, 30 March, was devoted to a symposium on 'Colonic function'. During the afternoon of both days there were sessions devoted to free papers of which abstracts follow.

Death after Partial Gastrectomy for Hospital Admission for Peptic Ulcer and effective in the treatment of gastric Peptic Ulcer-A Long-term Study Acute Gastrointestinal Bleeding in the ulcers'. Their ability to protect the gastric United Kingdom 1958-70 mucosa was assessed in patients with N. A. DIN AND W. P. SMALL(Gastro-Intestinal gastric ulcer or gastritis by measuring Unit and the Gastric Follow-up Clinic, R. C. BROWN AND M. J. S. LANGMAN gastric potential difference (pd) and Western General Hospital, Edinburgh) (Department of Medicine and Therapeu- depression of pd (Apd) caused by 600 After surgery for peptic ulcer, long-term tics, University of Nottingham) Un- mg of aspirin (ASA)2 before and two to survival is decreased. Krause (1958) published figures collected during the four weeks after starting treatment. showed this to be due to pulmonary Hospital Inpatient Enquiry which exam- Eighteen patients were treated with tuberculosis, carcinoma of the stomach ines a 10% sample of hospital discharges carbenoxolone and 11 with gefarnate. remnant, and suicide. and deaths have been analysed to deter- There was no change in pd or 4pd after Westlund (1963) showed the ratio of mine the pattern for gastric and duodenal treatment with gefamate. Carbenoxolone actual to expected deaths to be 1P55:1 in ulcer and for haematemesis and melaena produced no change in pd: -35-6 ± 2-3 males and 1-15:1 in females. between 1958 and 1970. mv before and -35 9 ± 2-6 mv (mean Follow up of 400 patients over 15 years During the period 1958 to 1961 approxi- ± SE) after treatment. However, it and of 1279 patients up to 25 years who mately 33 000 patients with duodenal produced a significant (p < 0 001) http://gut.bmj.com/ underwent surgery for peptic ulcer at the ulcer and 24 000 with gastric ulcer were decrease in zpd: -52-4 ± 3-2% before Western General Hospital, Edinburgh, admitted annually. Though duodenal and 37-3 ± 3-7% (mean ± SE) after confirms an increased mortality in males, ulcer admissions had only fallen very treatment. the ratio being 1-4:1. slightly by 1970, gastric ulcer admissions The pH of gastric contents was moni- The main causes of this increase have fell in the same period by a third. Analysis tored with an intragastric electrode in changed. Carcinoma of bronchus and of the distribution of admissions by nine of the patients, before and after ischaemic heart disease have replaced hospital regions showed a fairly even treatment with carbenoxolone. No sig-

tuberculosis and carcinoma of the distribution for gastric ulcer, but a nificant change was observed. on September 28, 2021 by guest. Protected copyright. stomach. The majority of deaths occur consistent tendency for duodenal ulcer Plasma salicylate levels were measured six to 10 years after surgery. admission to be more frequent in the at intervals during the tests. There was This increased mortality is attributable north with especially high rates being no difference between the levels attained not to the operation but to the effects of recorded in Scotland. in the carbenoxolone-treated and the tobacco and alcohol. While the same By contrast to static or falling overall untreated groups. When zpd was plotted pattern is developing in the general chronic ulcer admission rates, the fre- against plasma salicylate levels, two population, the trend is more advanced quency of admission with haematemesis parallel regression lines were obtained, in the peptic ulcer group and particularly or melaena of uncertain cause has risen zpd being 14-7% lower for those treated in patients submitted to surgery who have by a third during the period under review. with carbenoxolone than for untreated the largest share of bad habits. The cause of this trend, which is particu- patients at any salicylate level (p < There is a need for social re-education larly obvious in younger men, is uncer- 0-00l). in this identifiable high-risk group to tain but it does not parallel national These findings support the hypothesis reduce the mortality from these prevent- aspirin consumption figures which seem that carbenoxolone protects the gastric able diseases. Such a move would make to be falling. mucosa against damage by aspirin. This the ever-increasing refinements of surgical protection does not depend upon any technique for treatment of peptic ulcer The Effects of Aspirin, Carbenoxolone, change in pH or in ability to absorb more meaningful. and Gefarnate on the Gastric Mucosal aspirin. Gefamate, on the other hand, Potential Difference in Man could not be shown to exert the same References protective effect. Krause, U. (1958). Late prognosis after partial A. HOSSENBOCUS AND D. G. COLIN-JONES gastrectomy for ulcer. Acta chir. scand., 114, 341-354. (Faculty ofMedicine, Southampton General References Westlund, K. (1963). Mortality of peptic ulcer Hospital) Carbenoxolone, and to a lesser Langman, M. J. S., Knapp, D. R., and Wakley, patients. Acta med. scand., 174, Suppl. 1402. extent gefarnate, have been shown to be E. J. (1973). Treatment of chronic gastric 335 Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from

336 The British Society of Gastroenterology ulcer with carbenoxolone and gefarnate: Postoperative Duodenogastric Reflux: A Pollock, and Coghill (1966) estimating a comparative trial. Brit. med. J., 3, 84-86. Cause of Gastritis and Symptoms deoxyribonucleic acid in gastric washings Geall, G., Phillips, S. F., and Summerskill, W. H. J. (1970). Profile of gastric potential difference was used. in man. Gastroenterology, 58, 437-443. M. R. B. KEIGHLEY, P. ASQUITH, AND J, Cell turnover rate was measured in 21 ALEXANDER-WILLIAms (University Depart- chronic alcoholic patients, seven patients ment of Surgery, 7he General Hospital, who had consumed an acute excess of Birmingham) Many patients who have alcohol, and eight healthy volunteers who The pH-Dependent Effect of Sodium continued dyspepsia but no recurrent acted as a control group. The results ex- Taurocholate on Increasing Gastric ulcer after gastric surgery have endoscopic pressed as nanograms of DNA-P per Mucosal Permeability evidence of gastritis associated with the minute were as follows: presence of bile in the stomach. In these DESMOND BIRKETT AND WILLIAM SILEN subjects the results of further gastric Group CTR (sponsored by PROFESSOR IAN MCCOLL) surgery are particularly disappointing (Departments ofSurgery, Harvard Medical (Halpern, Hirschowitz, and Moody, 1973) Chronic alcoholics (all) 19-4 + 13-3 School and Beth Israel Hospital, Boston, and it has been suggested that one of the Alcoholics without ulcers 18-4 12-9 Acute effects of alcohol 31-3 12-1 Massachusetts, and Guy's Hospital, Lon- reasons for failure is that their symptoms Controls 13-1 4*9 don) Bile salts increase the gastric are associated with duodenal reflux. To mucosal permeability, but the influence of investigate this hypothesis we studied 30 pH on their action is uncertain. Black has patients one to seven years after 'ulcer Cell turnover rates were significantly shown a mild pH-dependent effect, curative' operations (truncal vagotomy greater after acute exposure to alcohol whereas Davenport showed none. To and pyloroplasty 14; Billroth I gastrec- than in both the control group (p < investigate this further we studied the tomy 6; proximal gastric vagotomy 4; 0005) and the chronic alcoholic group effect of sodium taurocholate (Tch) on the others 6). Twelve had no symptoms, 18 had (p < 0 05). Of the 21 chronic alcoholics, permeability in vitro of rabbit fundic dyspepsia, including 11 with symptoms eight had radiological evidence of peptic gastric mucosa at differing pH values by suggesting reflux. Biliary disease and ulceration, five having duodenal ulcers measuring the mucosal to serosal flux of hiatus hernia were excluded in all sub- and three with gastric ulcers. There was erythritol-C14. At pH 7 0 the trans- jects. Assessment was by a seven-point no significant difference between the mucosal flux of erythritol in normal symptomatic score, measurement of bili- chronic alcoholic group with and without mucosa was 1 85 + 0 25 picomoles/cm2/ rubin and sodium concentrations from ulcers. sec, and 10 and 20 mM Tch increased the 10-minute samples of resting gastric juice, It is concluded that following acute rate to 1'93 ± 0-34 and 5-46 + 0-54 endoscopy, and biopsy. In addition exposure to alcohol the gastric epithelial http://gut.bmj.com/ picomoles/cm2/sec respectively after one fluoroscopic demonstration of reflux CTR is markedly elevated while chronic hour, and 3-18 + 0 53 and 10-10 ± was assessed using a modification of the alcoholism does not significantly alter 1 20 picomoles/cm2/sec respectively after technique described by Capper (1966). Of cell turnover rate. two hours. At pH 3 0 the effect was greater. 11 patients with severe symptoms, radio- The flux rates of 2'5, 5 0, and 10 mM logical reflux and severe gastritis occurred Reference Tch were 3-98 + 1-29, 5-81 4- 1-37, and in six, and heavy bile contamination of Croft, D. N., Pollock, D. J., and Coghill, N. F. 13-52 ± 2-31 picomoles/cm2/sec respec- resting juice in five. In the 12 asympto- (1966). Gut, 7, 333. tively after one hour, and 5-69 + 1V34, matic patients there was no radiographic on September 28, 2021 by guest. Protected copyright. 7.77 ± 1V54, and 23-87 ± 4 97 picomoles/ or biochemical evidence of reflux and the A Morphological and Pharmacological cm2/sec respectively after two hours: 20 presence of gastritis was found in only Study of the Parietal Cells of the Stomach mM Tch at pH 7 0 and 5 mM Tch at pH one. There is a significant correlation in the Dog during Periods of Maximal 3 0 increased the permeability to a similar between the presence of gastritis, dys- Acid Output and after the Gastric Secre- degree; this is a fourfold reduction in peptic symptoms, and duodenal reflux tory Inhibitor UK-9040 dose for a moderate reduction of pH. (p < 0-01). At these pH values Tch is in the ionized, References D. B. HAMER, A. B. PRICE, AND J. H. BARON lipid-insoluble form as they are above its (Department of Surgery, Royal Post- pKa, and thereforeit penetrates themucosa Capper, W. M., Airth, G. R., and Kilby, J. 0. graduate Medical School, and Department to a small extent. This marked pH- (1966). Lancet, 2, 621. Halpern, N. B., Hirschowitz, B. L., and Moody, of Pathology, St Mark's Hospital, dependent effect of sodium taurocholate F. G. (1973). Amer. J. Surg., 125, 108. London) The search for effective medical on gastric mucosal permeability must be treatment of peptic ulceration has led to due to an effect of back diffusion of Gastric Epithelial Cell Turnover after the development of UK-9040 (cis-1- hydrogen ions superimposed on the effect Acute and Chronic Alcohol Ingestion (5 - neopentyl - 2 - thienyl) - 1 - phenyl - 4 - of sodium taurocholate. pyrrolidinobut-1-ene), apowerful inhibitor N. KRASNER, T. J. THOMSON, G. CREAN, AND of gastric acid secretion and an analogue References C. MCNEIL (Gastrointestinal Units, Stobhill of the conventional antihistamines. with fistulae and Black, R. B., Hole, D., and Rhodes, J. (1971). General Hospital and Southern General Four dogs gastric Bile damage to the gastric mucosal barrier: Hospital, Glasgow) The purpose of this Heidenhain pouches were given varying the influence of pH and bile acid concen- study was to investigate the effect of quantities of oral UK-9040. This pro- tration. Gastroenterology, 61, 178 184. excessive alcohol consumption on the duced almost complete inhibition of Davenport, W. H. (1968). Destruction of the gastric mucosal barrier by detergents and urea. rate of turnover of epithelial cells in the pepsin and titratable acidity after doses of Gastroenterology, 54, 175-181. stomach (CTR). The method of Croft, pentagastrin, insulin, histamine, and a Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from The British Society of Gastroenterology 337 standard meal. In the course of these using a scintiscanning method (Heading, These results indicate that metiamide experiments biopsies for light and electron Tothill, Laidlaw, and Shearman, 1971). may be useful in the treatment of noc- microscopy were taken from the lesser Oral administration of 400 mg metianmide turnal symptoms of duodenal ulcer. curve of the stomach with a Wood's tube. 20 minutes before the study retarded No changes were seen with the light emptying in 12 of 14 peptic ulcer patients. References microscope. Electron micrographs con- Metiamide is thus a potent inhibitor of firmed the appearances seen in normal vagally induced gastric secretion and there Black, J. W., Duncan, W. A. M., Durant, C. J., secreting parietal is preliminary evidence that it also delays Ganellin, C. R., and Parsons, E. M. (1972). resting and actively Definition and antagonism of histamine H,- cells. However, the characteristic secre- gastric emptying. receptors. Nature (Lond.), 236, 385-390. tory change of tubulo-vesicular depletion Wyllie, J. H., and Hesselbo, T. (1973). Inhibition was inhibited in the majority of cells after References of gastric secretion in man by metiamide. In the administration of UK-9040. Carter, D. C., Dozois, R. R., and Kirkpatrick, International Symposium on Histamine H,- J. R. (1972). Brit. med. J., 2, 202. Antagonists, edited by C. J. Wood and Prolonged administration of the drug Heading, R. C., Tothill, P., Laidlaw, A. J., and M. A. Simpkins, pp. 371-379. to one dog did not produce tolerance, Shearman, D. J. C. (1971). Gut, 12, 611. acid secretion remaining inhibited. Biop- Wyllie, J. H., Ealding, W. D. P., Hesselbo, T., and Black, J. W. (1973). Gut, 14, 424. sies from this animal when compared with Initial Observations on the Inhibitory those from the short-term experiments Action ofUrogastrone on Gastric Secretory were similar. In all animals withdrawing Responses in Man the drug resulted in a return to a normal Inhibition of Nocturnal Acid Secretion in physiological and morphological response. Duodenal Ulcer by Oral Metiamide This drug arrests the functional and I. E. GILLESPIE, J. B. ELDER, P. C. GANGULI, J. G. WILLIAMS AND G. J. MILTON-THOMPSON H. GREGORY, AND L. GERRING (University morphological secretion of canine parietal Manchester Royal cells. (Royal Naval Hospital, Plymouth) AND Department ofSurgery, D. J. A. JENKINS AND J. J. MISIEWICZ (MRC Infirmary, and ICI Ltd, Alderley Edge, Gastroenterology Unit, Central Middlesex Cheshire) Although the existence of a Effect ofH2-Receptor Blockade on Vagaily Hospital, London) Metiamide is a hista- powerful inhibitor of gastric secretion in Induced Gastric Secretion and Gastric mine H2 receptor antagonist (Black, urine has been known for many years, Emptying in Man Duncan, Durant, Ganellin, and Parsons, only recently has there been available a 1972), shown to be an effective inhibitor small quantity ofextract ofsufficient purity D. C. CARTER, M. WERNER, J. A. H. FORREST, of gastric acid secretion in normals for administration to humans. R. C. HEADING, J. PARK, AND D. J. C. (Wyllie and Hesselbo, 1973). Nocturnal The effects of one-hour iv infusions of

SHEARMAN (Departments of Clinical Sur- pain is a frequent symptom in duodenal 0-125, 025, and 0-5 ,ug/kg on the acid http://gut.bmj.com/ gery and the Gastrointestinal Section of ulceration and overnight secretion of acid responses to continuous iv infusions of the University Department ofTherapeutics, in this disease is often high. We have pentagastrin, 0-2 ,ug/kg/hour, histamine Royal Infirmary, Edinburgh) Conven- studied the effect of a single oral dose of acid phosphate 10 ,g/kg/hour, and single tional antihistamines do not block the 400 mg of metiamide on the overnight subcutaneous injections of soluble insulin, stimulation of gastric secretion. The new acid secretion in 11 patients with duodenal 0-2 units/kg, were observed in 12 normal H.-receptor blocking drug, metiamide, ulcer. Each was studied on two occasions, healthy male volunteers. All three doses inhibits histamine- and pentagastrin- receiving either the drug or placebo ofurogastrone inhibited the acid responses

induced secretion in man (Wyllie, Ealding, according to a predetermined random to pentagastrin in all subjects, the mean on September 28, 2021 by guest. Protected copyright. Hesselboand Black, 1973) but its effects on order. After a one-hr basal period, the reduction in output being 60%, 85%, and vagally induced secretion and the rate of tablets were swallowed with 250 ml of 90% respectively for the 0-125, 0 25, and gastric emptying are unknown. water and the collection of juice was 0 5 pg/kg/hour doses of urogastrone. Less Vagal stimulation was achieved by discontinued for one hour. The stomach marked inhibition was noted in the continuous insulin infusion (0 03 units/kg/ was then emptied: measurements of secretion of intrinsic factor and of pep- hour) (Carter, Dozois, and Kirkpatrick, residual metiamide showed that 80-100% sin. Serum gastrin concentrations were 1972) in six healthy male volunteers. The of the dose had left the stomach. Gastric not affected. volume and acid concentration were secretion was collected continuously for The inhibitor effect of urogastrone reduced by simultaneous iv infusion of a further six hr and half-hourly samples was less on the secretory responses to 200 mg metiamide/hour. The mean were analysed in the usual way. Plasma histamine and to insulin. pLAO of 6'22 + SD 3-7 mmol/hour was gastrin was measured before and two hr Throughout each experimental run significantly lower than in paired control after the drug. repeated measurements were made of tests (20-9 + SD 6-4 mmol/hour: P < Ten of the 11 patients responded to pulse, blood pressure, and temperature, 0O001). Paired tests were also performed metiamide. There was a striking and highly and blood was taken before, during, and at in four peptic ulcer patients, using 0 04 significant reduction of acid output and 24 and 36 hours after the infusions for units insulin/kg/hour as a vagal stimulus. rise in pH (P < 0-01 to 0-05), which estimations of Hb, WBC, film, platelets, The mean pLAO during simultaneous persisted for six hours after the drug. In urea, and electrolyte concentrations and metiamide infusion (9.3 4+ SD 8-1 mmol/ five patients the pH remained above 5 liver function test. Apart from transient hour) was again significantly lower than for five hr after the drug. Eight patients headache in two subjects with only the in control tests (29-1 + SD 13-0 mmol/ were anacidic for periods ranging from largest dose of urogastrone, there were hour: P < 0 01). The effect of metiamide one to seven hours. Plasma gastrin levels no side effects or alterations in any on gastric emptying was determined by were unchanged. There were no side haemotological or biochemical measure- paired measurements of emptying rate effects. ment. Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from

338 The British Society of Gastroenterology Secretin Release in Man after Intra- pg/ml) compared with normals (mean with adult coeliac disease were examined duodenal Acid 68 pg/ml, P < 0 0025), but the rise of for the presence of basement membrane serum CCK after the meal was slower thickening and collagen deposition. Jejunal S. R. BLOOM AND A. S. WARD (cIo M. than in control subjects, so that by 30 biopsies from patients suffering from other Hobsley, Middlesex Hospital, London) minutes the mean levels in the two groups small intestinal disorders served as con- A sensitive radioimmunoassay for plasma were similar, and peak levels were not trols. secretin has been set up with antibodies significantly different (CD: mean 4274 Biopsies from 45 (31 %) coeliac patients raised to natural and synthetic secretin. pg/mi, controls: 4940 pg/ml, P > 0 050). showed basement membrane thickening Synthetic tyrosinic secretin (1 or 6position) Gallbladder emptying, which began within often associated with deposition of or natural secretin iodine 125 was used 12 minutes after the meal in all of the collagen beneath the basement membrane. as tracer. Changes of 25 pg/ml plasma control subjects (mean 9-2 minutes), was In 11 patients these collagen deposits can be detected with 95% confidence and significantly delayed in patients with CD were dense and in the other 34 patients fasting levels have been found to be below (mean 24-6 minutes, P < 00025), who basement membrane thickening was the 50 pg/ml. appeared to require a greater increment of predominant finding. No basement mem- Secretin release was studied by intra- serum CCK for gallbladder contraction brane thickening or collagen deposits duodenal infusions of 40 ml of 0 1 N HCI to begin. We conclude that at least two were seen in control biopsies. Fatal, over five minutes. In five normal volun- factors contribute to the defective gall- unremitting malabsorption developed in teers plasma secretin peaked at six bladder emptying in patients with coeliac four coeliac patients whose jejunal minutes, with a mean rise of 46 pg/ml disease. First the rise in serum CCK is biopsies showed dense collagen deposition (SE 8'3), and returned to baseline by 15 less steep than normal. Secondly the gall- beneath the basement membrane. minutes. In 11 patients with duodenal bladder appears to be less sensitive to the These findings confirm that collagenous ulceration secretin rose by only 21 pg/mI action of CCK, possibly as a result of the membrane thickening is a frequent (SE 6 4) at six minutes and returned to abnormally high fasting levels. finding in jejunal biopsies from patients baseline by 10 minutes. The duodenal with adult coeliac disease. The presence acid infusion produced an inhibition of References of dense collagen deposits beneath the pentagastrin-stimulated gastric secretion. Chapple, M., Low-Beer, T. S., Nolan, D., Davies, basement membrane, however, may indi- Four subjects, who received an exogenous E. R. (1974). An istotopic method for the cate a poor prognosis. secretin infusion at a dose known to study of gallbladder emptying. (Submitted to Brit. J. Radiology). References produce a small inhibition ofpentagastrin- Englert, E., and Child, V. S. W. (1966). Quantitative stimulated gastric secretion (0 5 U/kg over analysis of human biliary evacuation with a Hourihane, D. O'B,. (1963). The histology of eight minutes) had a mean peak plasma radioisotopic technique. Gastroenterology, intestinal biopsies. Proc. roy. Soc. Mcd., 56, http://gut.bmj.com/ 50, 506-518. 1073-1077. increment of 1045 pg/ml (SE 125). Harvey, R. F., Dowsett, L., Hartog, M., and Rad, Weinstein, W. M., Saunders, D. R., Tytgat, G. N., Thus there appears to be impaired A. E. (1973). A radioimmunoassay for and Rubin, C. E. (1970). Collagenous sprue secretin release in patients with duodenal cholecystok-inin-pancreozymin. Lancet, 2, -an unrecognised type of malabsorption. 826-829. New Engl. J. Med., 283, 1297-1301. ulceration and there is a discrepancy Low-Beer, T. S., Heaton, K. W., Heaton, S. T., between the endogenous and exogenous and Read, A. E. (1971). Gallbladder inertia secretin levels normally produced in and sluggish enterohepatic circulation of The Cellular Infiltrate of the Jejunum in gastric acid inhibition studies. bile salts in coeliac disease. Lancet, 1, 991- Coeliac Patients with Complicating Lym- 994. phoma on September 28, 2021 by guest. Protected copyright. Abnormalities of Cholecystokinin Secretion and Gallbladder Emptying in Coeliac Collagenous Basement Membrane Thicken- R. FERGUSON, P. ASQUITH, AND W. T. Disease ing in Jejunal Biopsies from Patients with COOKE (The Nutritional andIntestinal Unit, Adult Coeliac Disease General Hospital, Birmingham, and the T. S. LOW-BEER, R. F. HARVEY, D. NOLAN, Department of Experimental Pathology, E. R. DAVIES, AND A. E. READ (University R. BOSSART, K. HENRY, WILLIAM F. DOE, University of Birmingham) Although Departments of Medicine and Radiology, AND C. C. BOOTH (Departments ofMedicine there is an increased incidence of lym- Bristol Royal Infirmary, Bristol) In order and Histopathology, Royal Postgraduate phoma in adult coeliac disease, the cause to investigate the abnormality of gall- Medical School, London) Collagenous remains obscure. Decreased immuno- bladder function in coeliac disease basement membrane thickening is obser- logical surveillance has been suggested (CD) (Low-Beer, Heaton, Heaton, and ved in a significant proportion of jejunal as a possible mechanism and in support Read, 1971),we havemeasured gallbladder biopsies from patients with adult coeliac of such a hypothesis lymphocytes from emptying by a radioisotopic technique disease (Hourihane, 1963). In 1970 coeliac patients show impaired PHA (Englert and Child, 1966; Low-Beer, Weinstein, Saunders, Tytgat, and Rubin transformation and altered responses to Nolan, and Davies, 1974), and related it described a condition characterized by EB2 cells. to serum cholecystokinin (CCK) levels malabsorption, a flat jejunal mucosa with Reports quantitating cells in jejunal measured by radioimmunoassay (Harvey, a dense deposit of collagen beneath the biopsies from patients with uncomplicated Dowsett, Hartog, and Read, 1973) in 10 basement membrane, and failure to coeliac disease have shown a marked patients with untreated CD and 10 control respond to a gluten-free diet. They increase in plasma cells and a decrease subjects after a standard fatty 'meal' named this condition 'collagenous sprue'. in lymphocytes in the lamina propria and containing 20 ml arachis oil. To assess the relationship between these an increase in intraepithelial lymphocytes Fasting serum CCK was markedly two conditions, histological sections of (Holmes, Asquith, Stokes, and Cooke, raised in patients with CD (mean 1082 349 jejunal biopsies from 145 patients 1973). To test whether this also applied Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from The British Society of Gastroenterology 339 to patients developing lymphoma, biop- Small numbers of eosinophils and neutro- skin. In 18 clinically fit subjects the mean sies from 18 such patients were studied; in phils were seen but no immunoglobulin pd was 16 mV + 1-48 (1 SEM), lumen six patients two or more serial biopsies or complement-containing aggregates negative. It was lower during the first were available. Results were compared were demonstrated as previously described two weeks after operation (10-86 mV 4: with 15 healthy controls and 30 other in childhood coeliac disease (Shiner and 1'49) but thereafter varied little over 18 coeliacs of whom 15 were on a gluten-free Ballard, 1972). These findings suggest months and did not vary when measured diet. Results in uncomplicated coeliac that the same humoral mechanisms are repeatedly' over a single 24-hour period. disease confirmed previous studies but in important in the pathogenesis of the The pd at 7 to 10 cm deep to the stoma was lymphoma patients, although the cell jejunal lesion in both ACD and DH and lower than at 2 to 5 cm (mean 7-8 mV counts were abnormal, they were signifi- that both IgA and IgM systems are compared with 16 mV) but both these cantly different from other coeliacs. involved. are higher than has been reported in the Changes also tended to be present up to normal terminal ileum (Sachar et al, several years before the lymphoma was Rderence 1969; Turnberg et al, 1970). diagnosed. The results suggest that the Shiner, M., and Ballard, J. (1972). Lancet, 1, 1202 Patients judged clinically and on the immunological status of these patients basis of serum and urine electrolytes to be differs from other coeliacs, that it could Coeliac Disease, Malignancy, and Gluten- dehydrated and sodium depleted had pd represent a primary abnormality and could free Diet values similar to those in fit patients. be relevant to the aetiology and diagnosis There was no correlation between the of lymphoma. G. K. T. HOLMES, P. L. STOKES, R. MCWALTER, Na+/K+ ratio in urine and ileostomy J. A. H. WATERHOUSE, AND W. T. COOKE ejecta or between these ratios and pd. Reference The Nutritional and Intestinal Unit, The These findings suggest that salt-retaining Harris, 0. D., Cooke, W. T., Thomson, H., and General Hospital, Birmingham) An steroids were exerting little influence on Waterhouse, J. A. H. (1967). Malignancy in analysis of 208 coeliac patients, all with ileal ion transport. adult coeliac diseae and idiopathic steat- This simple and reliable technique can orrhoea. Amer. J. Med., 42, 899-912. characteristic jejunal biopsies studied Holmes, G. K. T., Asquith, P., Stokes, P. L., and between 1939 and 1972, has been made of provide useful information about ileal Cooke, W. T. (1973). Cellular infiltrate of the incidence of malignancy and of the function and here the pd was used to jejunal biopsies in adult coeliac disease predict the possibility that the high mean (ACD) in relation to gluten withdrawal. Gut, effect of a gluten-free diet in modifying 14, 429. this. The number of cancer deaths was K+ in ileostomy ejecta (9-06 m-equiv/1, compared with those expected based range 5-2 to 20 3) was due to active K+ Immunological Phenomena following upon the rates prevailing in the local secretion.

Gluten Challenge In the Jejunum of population and calculated using the References http://gut.bmj.com/ at with a Patients with Adult Coeliac Disease and method of years risk midpoint Sachar, D. B., et at (1969). Gastroenterology, 56, Dermatitis Herpetiformis mortality rate for the series taken from the 512. Case-Pearson tables. Statistically signifi- Turnberg, L. A. et al (1970). J. clin. Invest., 49, 557. M. LANCASTER-SMITH, PARVEEN KUMAR, AND cant increases of all cancers, carcinoma M. L. CLARK (Department of Gastro- of the oesophagus, and reticulosarcomas Functional Differentiation of the Human enterology, St Bartholomew's Hospital, were found. The duration of symptoms of Jejunum and Ileum London) The cellular infiltrate of the coeliac disease before those attributed to JOAN P. W. WEBB, ANElTE E. lamina propria is an important feature of reticulosarcoma averaged 22 years and D. B. A. SILK, on September 28, 2021 by guest. Protected copyright. the jejunal lesion in gluten-sensitive for carcinoma 31 years. When men and LANE, M. L. CLARK, AND A. M. DAWSON enteropathy. We have studied the effect of women were considered together those (Departments of Medicine and Gastro- gluten on the jejunal mucosa, using on a normal diet were subject to increased enterology, St Bartholomew's Hospital, histological and immunofluorescent tech- risks of cancer at all sites (P < 0 001) but London) Animal experiments have niques in 10 patients with adult coeliac those treated with a gluten-free diet for at demonstrated a decreased efficiency of disease (ACD) and in seven with derma- least 12 months irrespective of their absorption of sugars and some amino titis herpetiformis (DH); all patients were clinical response were not at greater risk acids in the ileum compared with the on a gluten-free diet and had no abnor- than the population as a whole. In jejunum. In order to investigate the mality or mild partial villous atrophy of contrast, the incidence of reticulo- magnitude of this gradient in man, a the jejunum. Serial biopsies before and sarcoma though less in those on a gluten- perfusion technique has been used after either a single challenge of 25 g of free diet was significantly greater in both (Sladen and Dawson, 1970). Jejunal and gluten or taking a gluten-containing diet groups (P < 0 001). ileal absorption of glucose, glycine, and for seven days were studied. L-alanine as well as glycyl-L-alanine have Comparable changes were found in A Study of the Electrical Potential been studied in six normal subjects. The both ACD and DH. Total cell counts were Difference (PD) across Human Ileostomy correct siting of the perfusion tube in the increased at 24 hours and within 48 hours Mucosa ileum was confirmed by studying bi- there was a rise in both IgA- and IgM- carbonate absorption, for Phillips and containing cells. However, despite this P. ISAACS AND L. A. TURNBERG (Manchester Summerskill (1967) showed that whereas increase, IgA cell numbers remained Royal Infirmary and Hope Hospital, this ion was absorbed in the human within the normal range even after seven Salford) Potential difference was jejunum, secretion occurred in the ileum. days on a gluten-containing diet. This measured across ileal mucosa in patients There was a 45-1% reduction in the contrasted with IgM cells which in all but with ileostomies using a KCI/agar probe mean glucose absorption rate, a 55-5% one case rose to levels well above normal. and a reference electrode attached to the reduction in the mean glycine absorption Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from 340 .The British Society of Gastroenterology rate, and a 17-9% reduction in the mean i 0 5 to 20'6 ± 12 on 1000 mg/day, and Plasma Levels of Amino Acids and Gluca- L-alanine absorption rate between the correlated significantly with dose per kg gon in Patients with Pancreatic Gluca- jejunum and ileum. In contrast, the body weight. Similar results were found gonomas dipeptide glycyl-L-alanine was absorbed when different doses were given to the at comparable rates from the two sites. same individuals. Transiently elevated C. N. MALLINSON, B. COX, AND S. R. BLOOM The results lend further support for the serum hepatocellular enzymes (ICD and (Greenwich Hospital G.I. Unit, Depart- existence of separate mechanisms for SCOT) were found in six of 31 patients ment ofMedicine, Guy's Hospital Medical amino acid and dipeptide transport in on 750-1000 mg CDCA/day but in only School, Department of Clinical Investiga- man because there was an absorptive one of 21 patients on lower doses. These tion, The Middlesex Hospital) At the gradient for the free amino acids between enzymes returned to normal either last meeting of the Society we described the jejunum and ileum which was not spontaneously or on reducing CDCA a syndrome of dermatosis, diabetes, apparent when the dipeptide was per- dosage. Cholesterol solubility in bile anaemia, and weight loss associated with fused. Higher concentrations of free deteriorated in six of eight patients pancreatic islet-cell tumours containing glycine (p < 0102) and free L-alanine (17-3 ± 1-5 to 10-1 4± 10) three months glucagon and high plasma glucagon (p < 01) were aspirated during the ileal after withdrawing CDCA. levels (Mallinson, Salmon, Barrowman, compared with the jejunal dipeptide In conclusion, both cholesterol solubility and Bloom, 1973). It was suggested that perfusions. These differences are likely and the incidence of raised hepatocellular the effect of the glucagon on amino acid to be due to the differential in absorption enzymes are related to dose of CDCA: metabolism could account for the clinical rates of the free amino acids in the once gallstones have dissolved, long-term features. Plasma glucagon (pg) has been jejunum and ileum, rather than to maintenance therapy may be necessary. measured by radioimmunoassay and differences in mucosal peptidase activity plasma amino acids (paa) by ion-exchange because glycyl-L-alanine was hydrolysed chromatography in four patients with the at comparable rates in vitro by jejunal A Malabsorption Syndrome in Overland above clinical features and high plasma and ileal intraluminal peptidases. Travellers to India: Mucosal Colonization glucagon levels, in three of whom a by Bacteria pancreatic glucagonoma had been found. References In exacerbations of the syndrome all four Phillips, S. F., and Summerskill, W. H. J. (1967). A. M. TOMKINS, W. P. T. JAMES, AND B. S. patients showed very high pg and low Water and electrolyte transport during paa levels. Arginine stimulation did not maintenance ofisotonicity in human jejunum DRASAR (Clinical Nutrition andMetabolism and ileum. J. Lab. clin. Med., 70, 686-698. Unit, London School of Hygiene and alter these values. Following surgical Sladen, G. E., and Dawson, A. M. (1970). Further Tropical Medicine, and Bacterial Metabo- 'cure' of the syndrome both pg and paa studies on the perfusion method for measur- lism promptly returned to normal. During http://gut.bmj.com/ ing intestinal absorption in man: The effects Research Laboratory, Colindale) ofa pr6ximal occlusive balloon and a mixing A new group of patients with tropical clinical remission pg and paa were less segment. Gut, 11, 947-954. malabsorption is described. Typically grossly abnormal than in patients in young adults, they develop diarrhoea exacerbation. Successful treatment of the The Effects of Different Doses of Cheno- during an overland journey to the Indian rash with diiodoquine resulted in return deoxycholic Acid and of Withdrawing subcontinent. Thirty-fourpatients, without to normal values of paa. Pharmacological Treatment on Bile Lipid Composition and parasitic infestation, with diarrhoea of suppression for one hour of glucagon and Liver Function in Patients with Gallstones one to nine months' duration, were insulin secretion lowered pg values

investigated. Mean 24-hour stool weights markedly but had no effect on paa. These on September 28, 2021 by guest. Protected copyright. H. Y. I. MOK, G. D. BELL, AND R. HERMON on a standard 97-105 g fat diet were results are consistent with the hypothesis DOWLING (Departments of Medicine, 394 i SEM 57 (range 180-1421 g). that amino acid metabolism is an inter- Royal Postgraduate and Guy's Hospital Twenty-nine of 31 patients on the diet mediary in the pancreatic glucagon Medical Schools, London) Although had steatorrhoea; all except one had syndrome. relatively large doses of chenodeoxycholic xylose malabsorption and 11 of 12 had Reference acid (CDCA) dissolve gallstones, recent B,, malabsorption. Jejunal morphology animal studies suggest that it may be was always abnormal with a more severe Mallinson, C. N., Salmon, P. R., Barrowman, J., lesion in with and Bloom, S. R. (1973). The association of hepatotoxic. Since previous doses of those protracted diarrhoea; a specific skin lesion with islet-cell tumours CDCA were chosen empirically and the decreasing folate levels related to duration of the pancreas. Gut, 14, 827. effect of withdrawing therapy is unknown, of symptoms. "IC glycocholate breath we studied bile lipid composition and tests were negative in 11 of 11 patients. A Prospective Survey of the Treatment of liver function in patients with gallstones Simultaneous samples ofjejunal mucosa Acute Pancreatitis after smaller doses of CDCA and exam- and luminal fluid were cultured for aero- ined cholesterol saturation of bile after bic bacteria in nine patients. All nine had C. W. IMRTE, A. S. WHYTE, AND L. H. cessation of treatment. significant contamination of the mucosa BLUMGART A prospective study of 78 The biliary cholesterol solubilizing itself with 103-107 bacteria per g. Luminal cases of acute pancreatitis documented (bile acid + phospholipid fluid tended to have fewer bacteria but over two years is presented. Regular i still > 103 organisms/ml. Successful follow up of 94% of patients has been capacity t cholesterol in- treatment led to an elimination of mucosal achieved. creased from 11-6 + SEM 1P3 to 17-0 + bacteria and histological improvement. Thirty-nine patients (50%) had un- 1-7 on 250 mg CDCA/day; from 12-3 ± Mucosal colonization by bacteria appears equivocal evidence of biliary disease. 1-0 to 19 0 + 2-3 on 500 mg; 12-7 ± 1 1 to be of significance in maintaining the Alcohol-associated acute pancreatitis to 19-7 ± 2-8 on 750 mg and from 12-1 mucosal lesion of tropical sprue. occurred in 20 cases (26%) of whom all Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from The British Society of Gastroenterology 341 but one were male. Two cases occurred the other 17 propositi who had HB-Ag- Liver Disease in Healthy Blood Donors in association with pancreatic carcinoma. positive chronic liver disease. Thirteen Associated with Presence of Hepatitis B No associated aetiological factor could be contacts had HB-Ab and three HB-Ag in Antibody implicated in seven patients. their serum. Positive serological findings Neither Trasylol (aprotinin) nor gluca- were more common among the sleeping B. E. BOYES, I. L. WOOLF, J. S. WHIrTAKER, gon were part of the management regime. partners of the propositi than among the E. TAPP, D. M. JONES, P. H. RENTON, The mortality for the 67 patients managed relatives. F. STRATrON, R. MCSWEEN, AND I. W. by conservative regime was 6%. However, Similar studies performed on age- and DYMOCK (Departments of Medicine, Path- in the remaining 11 cases early surgery sex-matched control households showed ology andBacteriology, University Hospital was performed, usually on uncertainty of all samples to be HB-Ag and HB-Ab of South Manchester, The National Blood diagnosis, and five of this group died. Of negative. Transfusion Service, Manchester, and the the patients with proven biliary disease, These results demonstrate the transient University Department of Pathology, 29 were submitted to elective biliary nature of the HB-Ab following hepatitis. Western Infirmary, Glasgow) In a pre- surgery and only one sustained a further Interhousehold spread of the HB-Ag is vious communication to this Society we major attack of pancreatitis this being more evident amongst the close contacts reported on the occurrence of liver related to a retained common bile duct of subjects with chronic liver disease than disease in asymptomatic blood donors stone. HB-Ag carriers. who were carriers of the hepatitis B The overall mortality for the series was antigen (HB-Ag). In addition to this 11V5%. The results of this study compare routine testing of donor blood for HB-Ag favourably with reports on the use of Studies on Carriers of Australia Antibody all donations have been screened for the Trasylol (Trapnell, Rigby, Talbot, and hepatitis B antibody (HB-Ab). In the Duncan, 1973) and glucagon (Condon, E. D. FAIRCLOUGH, G. SLAVIN, E. WILLIS, T. period from December 1970 95 donors Knight and Day, 1973) and underline the P. CLEGHORN, M. DENMAN, AND A. J. LEVI who were HB-Ab positive and HB-Ag necessity for further carefully controlled (Northwick Park Hospital and Clinical negative have been referred for clinical clinical trials before accepting these Research Centre and North London assessment at the Liver Clinic. agents as beneficial in the treatment of Blood Transfusion Centre) Six persistent All 95 were asymptomatic. In each acute pancreatitis. Australia antibody carriers were studied. instance a careful history was taken All were clinically well, without stigmata to elicit a possible exposure to HB-Ag. References of liver disease or a history of jaundice. Thirty of the donors had been in close Trapnell, J. E., Rigby, C. C., Talbot, H., and Dun- Routine haematological parameters were contact with hepatitis patients but none can, H. L. (1973). Abstract. Gut, 14, 828. had themselves been jaundiced. Twelve Condon, J. R., Knight, M., and Day, J. L. (1973). normal except in one alcoholic. Frequent http://gut.bmj.com/ Brit. J. Surg., 60, '09. enzyme estimations over periods up to were tattooed, 12 had previously re- two years showed minor elevations in ceived blood transfusion, and nine were SGOT and SGPT in two out of three hospital staff members. None of the 95 Serological Findings amongst Domestic non-alcoholic subjects. had any stigmata of liver disease but 15 Contacts of Persons with Transient and Liver biopsies showed multiple sarcoid- had abnormal routine liver function tests. Persistent Hepatitis B Antigenaemia like granulomata in one subject and Liver biopsies were obtained from 11 marked portal inflammation in a second. donors. Only three biopsies were normal, the remainder showing focal parenchymal

PH. GATEAU, JENNY HEATHCOTE, AND SHEILA These two patients had the highest levels on September 28, 2021 by guest. Protected copyright. SHERLOCK (Department ofMedicine, Royal of HB-Ab. A focal lymphocytic infiltrate necrosis in five and chronic persistent Free Hospital, London) Serum hepatitis was seen in one biopsy. Three patients had hepatitis in three. B antibody (Hb-Ab) has been sought, by biopsies normal to light microscopy. It is concluded that the presence of the passive haemagglutination technique, Electron microscopy demonstrated a large HB-Ab may sometimes be associated with amongst the domestic contacts of 39 excess of mitochondrial crystals in the liver changes similar to those found in hepatitis B antigen (Hb-Ag)-positive patient with granulomas and in the HB-Ag carriers. subjects. patient with the marked portal inflamma- Monthly serum samples were obtained tion. The alcoholic subject showed Cell-mediated Immunity to Hepatitis B from 10 patients with acute type B hepa- unusual cytoplasmic crystals. No intra- Antigen in Antigen-negative Active Chronic titis during their convalescence. Five had nuclear particles of the type associated Hepatitis HB-Ab detected transiently. Six of their with Australia antigenaemia were seen. 23 contacts, studied similarly, had anti- Lymphocyte studies in vitro showed W. D. REED, W. M. LEE, A. L. W. F. EDDLE- body detected, most commonly three normal distribution of T and B cells, STON, C. G. MITCHELL, A. J. ZUCKERMAN, months after the propositus suffered normal K cell function, but significantly AND ROGER WILLIAMS (The Liver Unit, hepatitis. Three were blood relatives. depressed responses to mitogens. King's College Hospital, London, and Fifty-nine household members of 29 Carriage of HB-Ab may be associated London School of Hygiene and Tropical persistently HB-Ag positive individuals with significant hepatic histological chan- Medicine) Eighteen per cent of a series were tested for both HB-Ag (by counter- ges, without clinical evidence of disease. of 94 patients with active chronic hepatitis immunoelectrophoresis) and HB-Ab. HB-Ag was not demonstrated in serum or (ACH) were found to have hepatitis B Twelve subjects were healthy carriers of liver biopsy specimens to account for the antigen (HB-Ag) in the serum. However, the HB-Ag; only two of their 21 contacts persistence of the antibody. Its signifi- apart from an increased frequency in hadHB-Ab and nonewereHB-Agpositive. cance in the spectrum of hepatic disease males and those born overseas, no signifi- Thirty-eight contacts were traced from is not clear. cant differences were found in clinical Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from

342 The British Society of Gastroenterology manifestations, autoantibodies, and prog- in the diagnosis of primary liver cell including cirrhosis, but there is no con- nosis between antigen-positive and carcinoma, particularly in the presence of sistent abnormality of small bile ducts. antigen-negative cases (Reed, Eddlestone, cirrhosis. The scan was positive in 22 of Twelve patients have now reached their Stem, Williams, Zuckerman, Bowes, and 24 patients with biopsy proven primary fifth year and four are over 18 years old. Earl, 1973). The latter group has now liver cell cancer whereas no positive been examined further for evidence of results were obtained in 20 scans carried Biocompatibility in a System of Artificial previous infection with hepatitis B virus out on patients with cirrhosis but no Liver Support for Fulminant Hepatic using the leucocyte migration test as a primary liver cell cancer. 67Ga scanning Failure measure of cell-mediated immunity with was also found to be of value in the a column purified preparation of HB-Ag diagnosis of pyogenic abscess, particularly M. J. WESTON, B. G. GAZZARD, P. G. LANG- as antigen. on the edge of the liver where colloid LEY, E. H. DUNLOP, AND ROGER WILLIAMS Positive responses were detected in 24 scan may give an equivocal result. Seven (From the Liver Unit, King's College (63%) of 38 patients with antigen-negative of seven 67Ga scans were positive in this Hospital and Medical School, London) ACH which was significantly higher group. The results obtained in patients Haemoperfusion through activated char- (p < 0-01) than the 30% found in 43 with bile duct carcinoma, secondary coal and ion-exchange resins for the healthy controls. This finding suggests hepatic metastases, other intrahepatic removal of water-soluble and protein- that infection with the hepatitis B virus lesions, and hepatitis are also presented. bound metabolites respectively is a may be of importance in the aetiology of The distribution of 67Ga within the possible basis for an artificial liver the disease in antigen-negative as well as liver in different circumstances has been support system. Unfortunately, platelets antigen-positive cases. Only three (27%) investigated by autoradiography. The and white cells are also adsorbed. Studies of the 11 patients in the antigen-positive findings will be discussed. in vitro showed that coating the charcoal group had evidence of cell-mediated with the polymer 'polyhema' reduced the immunity to HB-Ag and the lack, in References platelet adherence but the thickness of most of these cases, of an appropriate Edwards, C. L., and Hayes, R. L. (1969). J. Amer. this coating and the method of application immune response may underly their med. Ass., 212, 1182. are of critical importance in determining Lomas, F., Dibos, P. E., and Wagner, H. N., Jr. failure to eliminate the infecting virus. 286, 1323. both biocompatibility and the rate of When cell-mediated immune responses (1972). New Engi. J. Med., removal of metabolites. A 4% by weight to a liver cell membrane antigen were coating applied by an encapsulation measured, the frequency of positive The Progress of Children with Intrahepatic technique appeared to be the most reactions in the HB-Ag-negative and Cholestasis suitable for clinical use. -positive cases (51 and 53% respectively) JENNY HEATHCOTE, K. P. DEODHAR, P. J. lIaemoperfusion through charcoal with http://gut.bmj.com/ was similar. This lends further support to SCHEUER, AND S. SHERLOCK (Department a 4% w/w polyhema coating in the dog the proposal that a common autoimmune ofMedicine and Department ofPathology, reduced the platelet count by only 20% process is involved in the pathogenesis of Royal Free Hospital, London) Sixteen over a four-hour period. The biocom- the progressive liver cell damage in both children with prolonged cholestasis have patibility of the coating was also satisfac- groups of patients. been observed. Fifteen presented with tory in other respects. No haemolysis or changes in electrolytes and clotting Reference jaundice, 13 within one month of birth. Three presented later, one at 6 years, with factors were detected. Reed, W. D., Eddlestor,, A. L. W. F., Stem, R. B., were thought clinically to So far 42 treatments have been carried on September 28, 2021 by guest. Protected copyright. Williams, R., Zuckerman, A. J., Bowes, A., pruritis. Nine column and Earl, P. (1973). Lancet, 2, 690. have hepatitis, in five liver histology out using a charcoal perfusion supported this diagnosis and in two others in 13 patients whose condition had 67Ga Citrate Liver Scanning: Evaluation serum rubella antibody in high titre was deteriorated to grade IV hepatic coma of its Use in 80 Patients and Evidence of found. The initial diagnosis was uncertain despite full supportive measures. Seven Intrahepatic Distribution by Autoradiog- in the remaining seven. Two of the 16 are of these patients regained consciousness raphy siblings and the brother of another had during the period of haemoperfusion 'neonatal hepatitis'. Four mothers took which was uncomplicated, with an OLIVER JAMES, J. WOOD, M. MAZE, L. C. progesterone during pregnancy. average platelet drop of only 15% (range GAYOTTO, H. S. WILLIAMS, AND SHEILA Cholestasis persisted in all 16; laparo- 0-30%). All finally made a complete SHERLOCK (Departments of Medicine, tomies were performed on 13 and in 11 clinical and biochemical recovery and Physics, and Pathology, Royal Free operative cholangiography demonstrated were discharged from hospital. Hospital, London) The radionuclide a patent extrahepatic biliary system. '7Gallium has recently been shown to be Two have died before 3 years. The 14 Liver Damage in Patients Taking Methyl- taken up selectively in soft tissue tumours living are mentally normal and only four dopa and inflammatory lesions throughout the are stunted and ill. All but two have body (Edwards and Hayes, 1969; Lomas continual pruritis and 11 have persistent P. J. TOGHILL, P. G. SMITH, PATRICIA Dibos, and Wagner, 1972). or fluctuant jaundice. Survivors have BENTON, R. C. BROWN. AND H. L. MATTHEWS In the present study 67Ga liver scans cholestatic liver function tests, but (Nottingham General Hospital and Derby- have been carried out in 80 patients xanthomas are present in only three. In shire Royal Infirmary) Since 1962 there following 19mTc colloid scan in order to all 10 tested HB antigen is negative and have been sporadic reports of liver evaluate the value of 67Ga liver scanning mitochondrial antibodies are absent. damage in patients taking methyldopa. in the diagnosis of liver disease. Fifty per cent have hepatosplenomegaly. The clinical syndrome has usually resem- The 67Ga scan was found to be valuable Liver biopsies show a variety of lesions bled viral hepatitis with prompt recovery Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from

The British Society of Gastroenterology 343 on stopping the drug (Elkington, Schrei- failure. Serial studies in two patients Experimental Production of Lipoprotein ber, and Conn, 1969) but there have been showed that renal failure developed at the X (LPX) in the Absence of Obstructive some fatalities from hepatic necrosis same time as endotoxin was first detected Jaundice (Rehmann, Keith, and Gall, 1973). Some in the systemic blood. The underlying patients have developed active chronic mechanisms may be related to selective J. A. JAMES, C. H. BOLTON, AND A. E. hepatitis (Goldstein, Lamb, and Mistilis, renal vasoconstriction which endotoxin is READ (University Department ofMedicine, 1973). known to cause. Bristol Royal Infirmary, Bristol) LPX is We have studied 20 patients in whom Although there was renal retention of a unique lipoprotein found in cases of liver damage appeared to be directly sodium in all patients with renal failure, obstructive jaundice whether the obstruc- related to the drug. Six patients have this was also found in 10 of 25 patients tion be intra- or extrahepatic. It contains been seen in Nottingham and Derby with a GFR > 40 ml/min. There was no an abnormally high concentration of Hospitals in the last three years and 14 difference in GFR or renal plasma flow lecithin and a small proportion of litho- have been traced and reviewed after between these patients and those with cholate. Lithocholate is not present in reports to the Committee on Safety of appropriate sodium excretion, but the other lipoproteins and is known to be Medicines. Hepatitis-like reactions occur- sodium retainers had significantly lower hepatotoxic. In the presence of biliary red in 16 patients and in four of these values for free water clearance (p < 0-001) obstruction, both lithocholate and lecithin there was a recurrence of jaundice and potassium excretion (p < 0 005), may be expected to accumulate, as they following a second exposure to the drug. indicating that the site of abnormal are both excreted in the bile. Features suggestive of active chronic sodium retention was the proximal Using the rabbit, we have shown that hepatitis were seen in two patients. There tubule. The mechanism for this is un- when obstructive jaundice is produced was one death from fulminant hepatic certain but hyperaldosteronism is unlikely artificially (by tying off the hepatic ducts), failure and a previously undiagnosed to be important. a lipoprotein similar to LPX is produced cirrhotic died from superimposed hepatic (16 cases). We then administered excess damage. amounts of either lecithin or litho- Histological material was available in Serum Ferritin In Patients with Iron Over- cholate to normal rabbits in order to 10 cases. There was a variable spectrum of load and with Acute and Chronic Liver investigate the effects of these substances. response with, in the main, a mixed Disease When lecithin was infused (into six inflammatory cell portal infiltrate and rabbits) LPX appeared after 24 hours, and cholestasis. The features of chronic J. PRIETO, MICHAEL BARRY, AND SHEILA at no time was there any evidence of aggressive hepatitis regressed after stop- SHERLOCK (The Department of Medicine, hepatic obstruction. Similarly, continuous ping methyldopa. oral administration of lithocholate (four The Royal Free Hospital, London) An http://gut.bmj.com/ References immunoradiometric assay has been used rabbits) produced LPX after six days. to determine serum ferritin in patients There was no hepatic obstruction at this Elkington, S. G., Schreiber, W. M., and Conn, time, although it developed after 10 days. H. 0. (1969). Hepatic injury caused by with iron overload states and in patients L-alpha methyl dopa. Circulation, 40, 589. with liver disease. In iron overload It seems likely that lithocholate and Goldstein, G. B., Lam, K. C., and Mistilis, S. P. disorders serum ferritin was closely lecithin are able to induce the formation of (1973). Drug-induced active chronic hepa- correlated with standard measurements LPX in the absence ofhepatic obstruction. titis. Amer. J. dig. Dis., 18, 177. of storage iron, namely, liver iron We suggest that LPX may be formed as a Rehmann, 0. U., Keith, T. A., and Gall, E. A. mechanism for protecting the body from

(1973). Methyldopa-induced sub-massive concentration, DTPA-chelatable iron, and on September 28, 2021 by guest. Protected copyright. hepatic necrosis. Amer. med. Ass., 224, 1390. the storage iron mobilized during quan- the toxic effects of lithocholate. titative phlebotomy. In haemolytic dis- Renal Failure and Site of Abnormal Renal orders, however, serum ferritin levels Primary Liver Cell Carcinoma: Alcohol Retention of Sodium in Fulminant Hepatic were higher, relative to the iron stores, and Chronic Liver Disease Failure than in patients with idiopathic haemo- chromatosis. High ferritin levels were ROSEMARIE LUCIANIN FISHER, P. J. SCHEUER, S. P. WILKINSON, V. ARROYO, H. E. MOODIE, common in patients with both acute and AND SHEILA SHERLOCK (Departments of L. M. BLENDIS, AND ROGER WILLIAMS (From chronic liver disease, normal values being Medicine and Morbid Anatomy, Royal theLiver Unit, King's College Hospital and virtually confined to women and to Free Hospital, London) A correlation Medical School, London) In a consecutive patients with a history of recent haemor- between ethanol ingestion and primary series of 88 patients with fulminant hepatic rhage. In liver disease generally serum liver-cell carcinoma was established in a failure, 61 were found to have evidence ferritin varied with both the transaminase review of 171 patients with primary of considerable renal impairment with a level and with liver iron concentration liver-cell carcinoma at the Royal Free glomerular filtration rate (GFR) of < 25 but correlated well with neither separately; Hospital between 1960 and 1973. Fifty- ml/min. This was indicative of a poor however, an extremely close correlation six per cent were from the United King- prognosis, all the patients dying, whereas was found between serum ferritin and the dom; of these, 51 % hadingestedmorethan in those that survived (21 patients) the product of the serum transaminase x liver 100 g ethanol per day and 41% more than GFR never fell below 40 ml/min. There iron concentration. This is strong evidence 200 g. was a close correlation between the that the ferritinaemia of liver disease is Only 6% of these patients had biopsy development of renal failure and the largely derived from damaged hepatocytes, evidence of alcoholic liver disease. How- occurrence of endotoxaemia. This was the circulating level depending on both the ever, increased ethanol consumption was detected using the Limulus lysate tech- activity of the hepatocellular damage and significantly more common in those nique only in those patients with renal on the parenchymal iron stores. with carcinoma than in a population with Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from

344 The British Society of Gastroenterology vryptogenicoralcoholiccirrhosis alone. No potent inhibitor of PG synthesis. Fourth, opalescent-negative clostridia, are those relationship was established between although antihistamine activity was not most active in degrading sulphasalazine. carcinoma in patients with increased associated with inhibition of PG syn- which is a useful References ethanol ingestion and hepatitis type-B thesis, promethazine, Cooke, E. M. (1969). Gut, 10, 565. antigen. antiemetic, was an inhibitor. Fifth, Drasar, B. S., and Crowther, J. S. (1970). Soc. Carcinoma patients with increased colchicine, whose main side effects are appl. Bact. Technol. Series, No. 5. ethanol ingestion showed longer survival nausea, vomiting and diarrhoea, and Gorbach, S. L., Nahas, L., Plaut, A. G., Weinstein, L., Patterson, J. F., and ILevitan, R. (1968). from onset of liver disease, eg, cirrhosis, apomorphine and morphine stimulated 54, 575. hepatitis, and a longer carcinoma-free PG synthesis. Gastroenterology, period. Survival time from tumour These findings suggest that inhibition A Prospective Follow Up of Outpatients diagnosis was not significantly different by suitable drugs of prostaglandin bio- with 'Total Colitis' in patients with and without increased synthesis in the gut wall may afford symp- ethanol ingestion. tomatic relief in some circumstances and J. E. LENNARD-JONES, J. J. MISIEWICZ, J. A. An unexpected clinical finding was an that the gastrointestinal side effects of PARRISH, JEAN K. RITCHIE, E. T. SWAR- ascitic fluid protein content of less than certain drugs may be mediated by their BRICK, AND C. B. WILLIAMS (St Mark's 3 g % in 79% of the patients with car- stimulating such biosynthesis. Hospital, London) The risks to patients cinoma. with ulcerative colitis involving the whole It appears that the relationship of References colon (Edwards and Truelove, 1963; de primary liver-cell carcinoma and alcohol Bennett, A., Fox, C. F., and Stamford, I. F. (1973). Dombal, Watts, Watkinson, and Goligher, is more important than hitherto suspected. Rheumat. and Rehabilit., in press. 1966; Watts, de Dombal, Watkinson, and Collier, H. 0. J. (1971). Nature (Lond.), 232, 171-19. Eckenfels, A., and Vane, J. R. (1972). Brit. J. Goligher, 1966) have prompted some Effects on Prostaglandin Biosynthesis of Pharmacol., 45, 451.462. workers to recommend colectomy for all Drugs Affecting Gastrointestinal Function such patients (Watts et al, 1966). We have Effects of Sulphasalazine (Salazopyrin) on tended to adopt a more conservative ALISON A. BUTT, H. 0. J. COLLIER, P. J. Faecal Flora in Patients with Inflammatory approach for outpatients with total colitis GARDINER, AND S. A. SAEED (Research Bowel Disease in relatively good health. To assess the Department, Miles Laboratories Limited, results of this policy a long-term follow Stoke Poges, Slough, Buckinghamshire) R. LENDRUM, J. G. WALKER, BERYL WEST, up of these patients was started in 1966. (Introduced by Dr J. J. Misiewicz) AND M. J. HILL (From the Departments of One hundred and seventy-one patients Administration of E or F prostaglandins Gastroenterology and Bacteriology, St have been included, 94 men and 77 (PG) elicits nausea, vomiting, abdominal Mary's Hospital, London) There is con- women, collected from three sources: http://gut.bmj.com/ pain, and diarrhoea. The gut produces siderable interest regarding the mode of (1) 65 patients seen at St Mark's before prostaglandins in response to noxious action of sulphasalazine in producing its 1 January 1966; (2) 70 patients referred stimulation. Such evidence suggests that beneficial effects in ulcerative colitis. One with established total colitis; (3) 36 endogenous prostaglandins may mediate possible mechanism would be an anti- patients whose colitis became total while 'defensive' reactions of the gastrointestinal bacterial effect although previous studies under our care. The mean length offollow tract, such as vomiting and diarrhoea have not supported this (Gorbach, up, so far, is 3-3 years. (Collier, 1971). We therefore tested the Nahas, Plaut, Weinstein, Patterson, and The expected mortality is 4-83; seven effects on prostaglandin biosynthesis of Levitan, 1968; Cooke, 1969). Because of patients have died and the excess annual on September 28, 2021 by guest. Protected copyright. some drugs that affect gastrointestinal recent improvements in anaerobic bac- mortality has been 0 3%. function. teriological technique, it seemed worth- Three patients have developed car- Drugs were tested on (1) synthesis of while re-examining this hypothesis. cinoma. All three had premalignant rectal prostaglandins (mainly PGE2) from ara- Faecal flora were examined by the biopsies and were operated on because of chidonic acid by homogenate of bull methods of Drasar and Crowther (1970) the high risk of developing cancer, though seminal vesicle, with glutathione and in 21 patients with colitis and five with the presence of a tumour was unconfirmed hydroquinone as cofactors; and (2) Crohn's disease affecting the large bowel preoperatively. Two of the tumours were maintenance of resting tone in an isolated during sulphasalazine administration and confined to the bowel wall, and the third strip of rat stomach fundus (Bennett, during control periods. In patients not showed extension through the wall with- Fox, and Stamford, 1973), which is receiving the drug, there were no differen- out lymph node involvement. The patients probably due to intramural generation of ces in flora between those with Crohn's remain well seven, six, and two years after prostaglandin (Eckenfels and Vane, 1972). disease and those with colitis. In the colectomy. Results with the two methods were largely latter condition patients with severe, Twenty-nine patients have undergone in agreement. active disease had many more opalescent- colectomy; seven in an acute attack, the These experiments yielded the following negative clostridia than the less active remainder electively. There have been no conclusions. First, aspirin-like drugs, patients, whose flora were not significantly operative deaths. including paracetamol and quinoline different from normal. The effect of The results suggest that patients with antimalarials, inhibited PG synthesis; sulphasalazine was to decrease the quiescent total colitis can be managed and their potencies overall were not numbers of opalescent-negative clostridia conservatively with relative safety provi- correlated with ability to erode the mucosa. 200-fold, coliforms 40-fold, and eubac- ded that close supervision is maintained. Second, dexamethasone had little or no teria and bacteroides 10-fold. Other References activity. Third, sulphasalazine, which is organisms were unaffected. It is notable Edwards, F. C., and Truelove. S. C. (1963). Gut, 4 useful in ulcerative colitis, was a fairly that the organisms most affected, ie, 299. Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from The British Society of Gastroenterology 345 de Dombal, F. T., Watts, J. McK., Watkinson, mation was obtained about all first-degree were unrelated to tumour extent as G., and Goligher, J. C. (1966). Brit. med. The results J., 1, 1442-1447. relatives and this was subsequently determined at operation. Watts, J. McK., de Dombal, F. T., Watkinson, verified from death certificates or hospital suggest that altered T cell function of G., and Goligher, J. C. (1966a). Brit. med. J., records. specific type is detectable by relatively 1, 1447-1453. The number of deaths due to cancer of simple means in patients with intestinal the large bowel was compared with the cancer and are in broad agreement with Mucin Changes in Colonic Mucosa in number which would have been expected lymphocytotoxicity assays and leucocyte Colorectal Carcinoma by chance, as calculated from the migration inhibition studies (Guillou and Registrar-General's Mortality Statistics. Giles, 1973; Mclllmurray, Gray, and M. ISABEL FILIPE, A. C. BRANFOOT, AND There was a significant increase in the Langman, 1973). B. K. COOKE (Departments of Histopath- number of deaths due to bowel cancer ology and Chemical Pathology, Westmin- among first-degree relatives of index References ster Medical School, London) The large cases compared with the expected inci- Baldwin, R. W., Embleton, M. J., Jones, J. S. P., dence. The index cases were and Langman, M. J. S. (1973). Int. J. intestinal mucosa from surgical specimens also analysed Cancer, 12, 73-83. of carcinoma of the colon or rectum has in respect of age, presence or absence of Guillou, R. J., and Giles, G. R. (1973). Gut, 14, been studied. Histochemical techniques adenomas or other carcinomas in the 733-738. show differences in the mucin composition operation specimen, and a history of Mclllmurray, M. B., Gray, M., and Langman, between histologically normal mucosa previous carcinoma in the large bowel. M. J. S. (1973). Gut, 14, 541-544. far from the tumour and in apparently Early age of onset, the presence of normal mucosa adjacent to carcinoma adenomas or other carcinomas in the An Experimental Animal Model of ('transitional mucosa'). operation specimen, and a history of Crohn's Disease In normal mucosa, sulphomucins are previous carcinoma were all found to be D. R. CAVE AND D. N. MITCHELL (Department predominant in the goblet cell mucus, associated with an increased risk that the of Surgery, St George's Hospital, London, while in 'transitional mucosa' there is a index case would have a positive family MRC Tuberculosis and Chest Diseases decrease in sulphomucins and a marked history. Unit, Brompton Hospital, London) The increase in sialomucins. The relative contributions of heredity terminal ileum or proximal colon of 19 Biochemical analysis reveals a higher and environment to the aetiology of large New Zealand White rabbits (NZW) was content of hexosamines and a higher bowel will be discussed. inoculated intramurally with a 100p or percentage of neuraminidase-sensitive 02p filtrate of homogenate prepared sialic acids in the 'transitional mucosa' Inhibition of Rosette-forming Activity of from fresh human ileal or colonic Crohn's compared with the normal and autoradio- Lymphocytes in Patients with Large disease tissue. When compared with nine http://gut.bmj.com/ graphic studies with 35SOQ show a lower Bowel Cancer by a Colorectal Tumour inoculated controls, the Crohn'sinoculated uptake of the isotope in the 'transitional Extract rabbits gained weight at a significantly mucosa. slower rate (P < 0001 at seven weeks). Mapping of the mucins in the large M. B. MCILLMURRAY AND M. J. S. LANGMAN Macroscopic changes were present in 15 intestinal mucosa along whole specimens (Department of Therapeutics, City Hospi- of 19 Crohn's inoculated rabbits and were resected for carcinoma reveals mucin tal, Nottingham) Thymus-derived lym- independent of the nature or donor of the changes with increase in sialomucins, phocyte (T cell) function has been ex- Crohn's filtrate homogenate or the site of not only in areas adjacent to carcinoma, plored by using the sheep red blood cell inoculation. Positive microscopic changes on September 28, 2021 by guest. Protected copyright. but also in patches of histologically rosette test in standard and modified were present in eight of 19 Crohn's normal mucosa distant from frank forms in patients with large intestinal inoculated rabbits. No macroscopic abnor- tumours. The hypothesis is put forward cancer and in matched controls. malities were present in any of the nine that these mucin changes found in histo- Mononuclear cells were separated from control inoculated rabbits and micro- logically normal mucosa of specimens of blood samples by using a Ficol Triosil scopically all were negative. Successful colorectal carcinoma may represent one gradient and the proportions of rosette- first passages have been achieved from of the features of an early stage in forming cells were determined in the test rabbits given 100, or 0-2,u filtrate of carcinogenesis. and control groups. No differences were human Crohn's homogenate prepared The value and application of these found between them (means and standard from each of five different donors. The findings to rectal biopsies are illustrated. errors of 48-2% ± 2-48 and 49*7% ± results of these experiments provide 189 respectively). further evidence to support the presence Heredity and Bowel Cancer Rosetting of patient and control cells of a transmissible agent from human was then repeated after preincubation Crohn's disease tissue, and illustrate the E. LOVETT (introduced by B. C. MORSON) with an extract prepared from a homo- potential of the NZW rabbit as an experi- (St Mark's Hospital, City Road, London) genate of freshly removed surgical mental model with which to study the There have been many reports in the samples of colonic and rectal tumour aetiology and natural history of Crohn's literature of families with a high incidence tissue. The ratio of rosette-forming cells disease in man. of carcinoma of the large bowel not with and without preincubation (termed associated with multiple polyposis. The the 'rosetting index') was significantly Antibody Production to the Bacterio- family histories of209 patients admitted to reduced in the cancer group but not in the phage 0X 174 in Patients with Crohn's St Mark's Hospital with cancer of the controls (mean and standard errors of Disease colon and rectum during a three-year 0O88 ± 0 05 and 1 01 ± 0-01 respectively). period were investigated in detail. Infor- Differences between patients and controls R. C. BUCKNALL, J. VERRIER JONES, AND. Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from

346 The British Society of Gastroenterology D. B. PEACOCK (Frenchay Hospital, Bristol, These results have been compared with chester) Few follow-up assessments of University Department of Medicine and those obtained by the Hospital Inpatient elastic ligation of haemorrhoids have been Department of Bacteriology, Bristol Uni- Enquiry where similar trends have been published (Clark Giles, and Goligher, versity) The bacteriophage 0X 174 has observed. Comparison with the admission 1967; Groves, Evans, and Williams, 1971). been shown to be a powerful immunogen, rates for ulcerative colitis shows a much Seventy-five patients with symptomatic and a safe tool for investigating antibody- smaller increase over the same period and haemorrhoids have been treated as out- producing capacity in man (Peacock et al, provides no evidence to suggest that patients by rubber band ligation without 1973). There is evidence that cellular transfer of colitis to Crohn's disease anaesthesia using the technique of immunity is impaired in Crohn's disease. diagnoses is the predominant cause of this Barron (1963). Their ages ranged from 25 Serum immunoglobulin levels may be apparent rising frequency of Crohn's to 75 years. Each patient had a sigmoido- raised, but there have been no studies of disease. Furthermore analysis of our own scopy and a barium enema before ligation. the ability to produce antibodies in data shows that the proportion of small On average, three ligations on separate response to antigenic challenge. Ten to large bowel Crohn's disease has not days were required for each patient and patients with Crohn's disease were varied in the time period reviewed. follow up has been from six to 26 months injected intravenously with 3-3 x 109 with an average of 10 months after the PFU of 0X 174, and the level of anti- Oral Lesions in Patients with Crohn's completion of treatment. bodies produced was measured at inter- Disease vals of three to four days during the RESULTS primary response, using the SD50 method M. K. BASU, P. ASQUITH, R. A. THOMPSON, Sixty-five patients returned to work less (Peacock, Jones, and Gough, 1973). One AND W. T. cooKEc (Department of Oral than 24 hours after ligation, eight within patient (C2) had high levels of circulating Pathology and Experimental Pathology, 48 hours, and two at more than 48 hours. antibody before immunization: this has University of Birmingham, Regional Im- During the first week 36 were completely never been observed in normal subjects. munology Laboratory, East Birmingham asymptomatic, 26had minimal discomfort, The remaining patients had primary Hospital,and the Nutritional and Intestinal and 13 had moderate pain with a sense of responses within the normal range. A Unit, The General Hospital, Birmingham) incomplete evacuation in the rectum and second injection of bacteriophage was Oral lesions with characteristic histology some frequency of call to stool in one given on day 28. The patient C2 had no have been described in patients with patient lasting seven days. No patient further increase in titre. The remaining Crohn's disease (Ellis and Truelove, 1972) required hospitalization for either rectal patients developed a normal secondary while a retrospective study of 332 patients bleeding or pain immediately after response. The antibody from the peak of with Crohn's disease showed that 6 1% ligation. the initial response in C2 was of IgG had suffered with oral ulceration (Croft Long-term follow up was possible in http://gut.bmj.com/ subclass. A further group of five patients and Wilkinson, 1972). A prospective 68 of 75 patients, only seven remaining with Crohn's disease was screened for study of 100 patients with Crohn's, 100 untraced. In 60 there was no rectal preimmunization antibody, and all were with ulcerative colitis, and 100 age-, sex- bleeding, in six occasional bleeding, and found to be negative. and denture-matched controls showed in two regular bleeding during defaecation. Our observations show that the depres- that nine Crohn's, two ulcerative colitis', Six patients required and consented to sion in cellular immunity found in Crohn's and one control subject had oral lesions. re-ligation of residual haemorrhoids and disease is not accompanied by a depres- Histologically the Crohn's lesions showed two elected to have a formal haemor- sion of antibody producing capacity. similarities to those seen in the intestine rhoidectomy. on September 28, 2021 by guest. Protected copyright. Reference and could be correlated with activity of We conclude that outpatient ligation bowel disease but not with deficiency of treatment of haemorrhoids is a successful Peacock, D. B., Jones, J. V., and Gough, M. iron, vitamin or folic acid. Changes (1973). Clin. exp. Immunol., 13, 497. B12, procedure, conferring the benefits of were also found in minor salivary glands. early return to work and minimal dis- The Incidence and Prevalence of Crohn's The occurrence of oral lesions might comfort in the vast majority of patients Disease in the Nottingham Area represent a local immunological reaction with a low incidence of recurrence of to oral antigens. In support of this, rectal bleeding. Outpatient waiting time D. S. MILLER, A. C. KEIGHLEY, E. M. BACKETr, changes in salivary IgA production were for treatment of haemorrhoids has been AND M. J. S. LANGMAN (Nottingham) found in Crohn's patients. considerably reduced and hospital beds Applying diagnostic criteria which have References have been freed for other cases. been based upon those used in previous Croft, C. B., and Wilkinson, A. R. (1972). Ulcera- References epidemiological surveys we have examined tion of the mouth, pharynx, and larynx in trends in the frequency of diagnosis of Crohn's disease ofthe intestine. Brit. J. Surg., Barron, J. (1963). Amer. J. Surg., 105, 563. Crohn's disease in the Nottingham area in 59, 249-252. Clark, C. G., Giles, G. R., and Goligher, J. C. Ellis, J. P., and Truelove, S. C. (1972). Crohn's (1967). Brit. med. J., 2, 12-14. the period 1958-1972. The figures have disease with mouth involvement. Proc. roy. Groves, A. R., Evans, J. C. W., and Williams been used to calculate incidence and Soc. Med., 65, 1080. J. A. (1971). Brit. J. Surg., 58, 923. prevalence rates. During this time there has been a marked and consistent The Results of Outpatient Treatment of The Diagnosis of Pseudomembranous increase in the frequency of disease Haemorrhoids by Rubber Band Ligation Colitis by Rectal Biopsy diagnosis with an apparent rise in incidence from 034/100 000/year for men A. P. PANDA, J. M. LAUGHTON, J. B. ELDER, A. B. PRICE AND D. R. DAVIES (St Mark's and 105/100 000/year for women in 1958- AND I. E. GILLESPIE (University Department Hospital, London and St Thomas' Hospital, 61 to 2-61 and 3-73 respectively in 1968-72. of Surgery, The Royal Infirmary, Man- London) (introduced by B. C. MORSON) Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from The British Society of Gastroenterology 347 It is important to make a rapid diagnosis glucosamine, and galactosamine differed values than the other two groups at all in all cases of pseudomembranous colitis significantly from normal in at least one times. as the majority of these patients are specimen. In particular the content of free These findings challenge some of the severely ill. However, clinical and radio- and total sialic acid was distinctly ab- current concepts concerning the aetiology logical distinction from the acute forms of normal (p < 0-05). Using multivariable of postvagotomy diarrhoea. ulcerative colitis and Crohn's disease of discriminant analysis incorporating all the the colon is usually very difficult. Further- data from each patient it was possible to Reference more as conservative management, where distinguish clearly between ulcer patients Fordtran, J. S., and Locklear, T. W. (1966). possible, is the treatment of choice, a and controls with 96-8% accuracy, Amer. J. dig. Dis., 11, 503. quick and accurate assessment is required. whereas differentiation on the basis of the The rectal biopsy appearances of six pentagastrin stimulation test of hydro- The Predictive Accuracy of the Insulin cases of pseudomembranous colitis are chloric acid output was only 53-7%. Test after Vagotomy: A New Interpretation described. The features are characteristic In 12 duodenal ulcer patients who and easily distinguishable from other subsequently came to surgery the pre- R. G. FABER, R. C. G. RUSSELL, J. V. PARKIN, causes of inflammatory bowel disease, operative mucopolysaccharide level was P. WHITFIELD, AND M. HOBSLEY (Depart- especially Crohn's disease and ulcerative abnormal in all cases whereas only five ment of Surgical Studies, The Middlesex colitis. However, in four of these cases the of these had acid levels above the normal Hospital, London) By conventional cri- initial report was given as non-specific range. teria, the postvagotomy insulin test poorly proctitis or 'compatible with ulcerative It is concluded that analysis of the predicts the liability to recurrent peptic colitis'. This indicates the need for more sugar constituents of gastric juice, ulcer. All criteria depend upon compari- widespread recognition of the typical although time consuming, is potentially son between basal and stimulated secre- rectal biopsy appearances of pseudo- an accurate method for the diagnosis of tion (Hollander, 1948; Bank, Marks, and membranous colitis. A confident diagnosis duodenal ulceration. Louw, 1967), but we have shown that can be made by sigmoidoscopy and rectal basal secretion is physiologically variable. biopsy, and we feel biopsy should be Osmotic, Electrolyte. and pH Changes in Therefore in 29 preoperative and 71 performed early in those patients with the Human Jejunum after Truncal Vago- postvagotomy male patients with duo- diarrhoea, in whom pseudomembranous tomy and Drainage denal ulcer, the predictive accuracy of colitis comes into the differential diagno- insulin-stimulated (0-2 units/kg iv) secre- sis; notably diarrhoea associated with J. G. TEMPLE, ALMA BIRCH, AND R. SHIELDS tion alone has been investigated. Correc- antibiotic therapy, shock, transfusion (DepartmentofSurgery, Liverpool) Com- tions for pyloric loss (Hobsley and Silen, reactions, subacute colonic obstruction, paratively little is known about the 1969) and duodenal reflux (Fiddian- and chronic cardiac and renal states. composition of the proximal jejunal Green, Russell, and Hobsley, 1972) have http://gut.bmj.com/ Such predisposing factors, in particular content after a meal in health or disease been made to the observed volume, the antibiotic therapy, are discussed in the (Fordtran and Locklear, 1966). resultant true gastric secretion being light of recent publications (McGovern, Fasting subjects ingested a 300 ml designated VG. 1972; Scott, Nicholson, and Kerr, 1973). hypertonic meal (600 mOsm/kg) con- Insulin-stimulated secretion was References taining EDTA 5"Cr as a volume marker. measured for two hours. Before opera- McGovern, V. J. (1972). Rectal biopsy in the Samples were collected at 30-minute tion, the rate during the first half-hour differential diagnosis of colitis. Rendic. intervals for two and a half hours by was much lower than in the subsequent Gastroent., 4, 94-102. siphonage through a single-lumen poly- one and a half hours. Moreover, the on September 28, 2021 by guest. Protected copyright. Scott, A. J., Nicholson, G. I., and Kerr, A. P. was in the timing of the secretion was very (1973]. Lincomycin as a cause of pseudo- vinyl tube whose tip placed peak membranous colitis. Lancet, 2, 1232-1234. proximal jejunum. variable. VG throughout the period half to Three groups of subjects were studied: two hours has therefore been chosen as Gas Chromatographic Measurement of (1) 12 controls, (2) 11 patients without the index of insulin-stimulated secretion, Mucopolysaccharides in Gastric Juice of diarrhoea after vagotomy and drainage, and expressed as mi/hour. The mean Patients with Duodenal Ulceration and (3) 10 patients with postvagotomy preoperative value was 215 ml/hour. diarrhoea. After vagotomy, 54 subjects secreted J. D. DONALDSON, K. D. MACRAE, T. G. Analysis of thejejunal content revealed: less than 116 ml/hour (preoperative mean PARKS, AND H. W. RODGERS (Department (1) There was no evidence that a hyperos- minus twice the standard deviation); of Surgery, Queen's University, Belfast) motic load or excessive dilution was none had a recurrent ulcer. However, of 17 Measurement of gastric acid and pepsin present in the small bowel in patients with subjects secreting more than 116 ml/hour, output is of limited value in the diagnosis postvagotomy diarrhoea. (2) All the post- nine had recurrent ulcer, four had of duodenal ulceration. Possible abnor- vagotomy subjects showed a greater rise recurrent symptoms, and only four (two malities of the mucopolysaccharides in in sodium concentration than the controls within one year of operation) were gastric juice have not been fully explored. in the first hour after the meal. (3) symptom free. This study examines differences in the Subjects with postvagotomy diarrhoea had We conclude that insulin-stimulated sugar constituents by gas liquid chroma- significantly greater sodium concentra- secretion alone predicts recurrent ulcera- tography in basal and pentagastrin- tions than the symptom-free subjects at tion more accurately than any other stimulated juice between 42 duodenal all times after the first 30 minutes. (4) criterion. ulcer patients and 22 control subjects. Chloride concentrations rose slowly In duodenal ulceration the concentra- towards plasma values in each group. References tion of fucose, mannose, galactose, (5) Patients with diarrhoea had higher pH Hollander, F. (1948). Gastroenterology, 11, 419. Gut: first published as 10.1136/gut.15.4.335 on 1 April 1974. Downloaded from 348 The British Society of Gastroenterology Bank, S., Marks, E. N., and Louw, J. H. (1967). Gut, 8, 36. Distance from pylorus (cm) 25 5 10 JIobsley, M., and Silen, W. (1969). Gut, 10, 787. Duodenal APB coordinated Fiddian-Green, R. G., Russell, R. C. 0., and with antral APs 20-91 ± 1 37 21-91 ± 1 57 1955 1.92 Hobsley, M. (1972). Brit. J. Surg., 59, 903. Uncoordinated duodenal APs 1P60 ± 0 27 3 00 ± 0 45 9*79 ± 1.14 Effect of vagotomy on gastroduodenal response to food Characterization of Glucagon Responses to Different Meals in the Dumping Syndrome that bursts of action potentials (APs) Leeds General Infirmary, and Department known as myoelectrical complexes (Szurs- of Medicine, UCLA, California) The F. A. O'CONNOR, K. D. BUCHANAN, E. R. zewski, 1969), which pass down the small hypothesis upon which highly selective 7RIMBLE, J. R. HAYES, AND T. L. KENNEDY intestine of fasting dogs, are disrupted vagotomy (HSV) is based is that the (Departments of Medicine and Surgery, following vagotomy, the extent of these vagally innervated gastric antrum will not The Queen's University of Belfast, Nor- changes being related to the amount of release excessive amounts of gastrin in thern Ireland) High levels of glucagon like vagal denervation (Stoddard and Duthie, response either to vagal or to chemical immunoreactivity (GLI) after oral glucose 1973). The paper reports the alterations stimulation. The response to a test meal have been reported in the dumping that occur in response to feeding after after HSV has been described previously syndrome". In order to decide whether vagotomy. to the Society (Lyndon, Walsh, Johnston, these GLI responses are due to the re- Six Ag-AgCl electrodes were attached and Grossman, 1973). We have now tested lease of pancreatic glucagon or to the to the stomach and duodenum of four the basic hypothesis by measuring serum as yet uncharacterized gut GLI, we have dogs and three-hour recordings of the gastrin levels by radioimmunoassay, and studied the GLI responses to 50 g oral myoelectrical activity made following a gastric acid outputs after vagal stimulation glucose in 20 'dumpers' using two anti- meat meal. Following pyloroplasty and in preoperative duodenal ulcer patients bodies in the glucagon radioimmuno- further testing one dog received a truncal (DU), and in patients who had undergone assay which allow discrimination between vagotomy (TV) and the three others a HSV, truncal vagotomy and pyloroplasty gut GLI and pancreatic glucagon. The highly selective vagotomy followed four (TV + P), or selective vagotomy and GLI responses to a 25 g protein meal and a weeks later by TV. pyloroplasty (SV + P) more than one 50 g fat meal have also been studied in In all tests feeding produced immediate year previously (n = 12 in each group). 'dumpers'. Gut GLI rose in 'dumpers' interruption of the myoelectrical com- The stimulus used was insulin hypo- no matter whether the meal was glucose, plexes and their replacement with gastro- glycaemia. Vagotomized patients were fat, or protein (P<0-005, <0-05,<0-05 duodenal APs. Before pyloroplasty during in good health, and in each the vagotomy respectively) and the rises exceeded that of the first hour after food, 98-82% ± had been shown to be complete soon after http://gut.bmj.com/ control subjects. Abnormalities in pan- 0 50 of gastric pacesetter potentials had operation. creatic glucagon responses to the meals APs which were coordinated with SPs in Mean (± 1 SE) fasting gastrin levels in also occurred in the 'dumpers' in that the proximal duodenum. Other APs not pg/ml were 70 ± 5 (DU), 107 ± 11 pancreatic glucagon paradoxically rose coordinated with antral APs are seen (HSV), 91 + 7 (TV + P), and 91 ± 8 after glucose in seven out of 15 'dumpers' most frequently in the distal duodenum. (SV + P). Mean peak gastrin levels were compared to suppression (P <0-05) in The incidence of gastric APs decreases 81 ± 7 (DU), 114 + 13 (HSV), 114 + 13 control subjects. A rise in pancreatic and uncoordinated duodenal APs increases (TV + P), and 134 + 19 (SV + P). There glucagon to fat was also found in the in the following two hours until normal was no significant difference between the on September 28, 2021 by guest. Protected copyright. 'dumpers' (P<0-05), but in contrast the myoelectrical complexes return. gastrin levels or the acid levels after pancreatic glucagon response to protein Pyloroplasty or HSV do not alter HSV compared with those after TV + P in the 'dumpers' was deficient compared gastroduodenal coordination of APs. On or SV + P. However, the mean peak acid with controls. These abnormalities of the other hand TV was followed by a response in 18 patients more than two pancreatic glucagon and gut GLI release significant increase in duodenal APs which years after HSV (3 7 m-equiv/hr) was in 'dumpers' may have either a compensa- were not coordinated with gastric APs. significantly greater than the peak acid tory or causative influence on the various Preservation of the vagal innervation to response in 37 patients more than two features of 'dumping', including rapid the antro-duodenal segment after HSV years after TV + P (1P40 m-equiv/hr, gastric emptying, diarrhoea, and hypo- maintains normal gastroduodenal co- P < 0-002 by the Mann Whitney U test). glycaemia. ordination of APs. Also, more than two years after operation, 90% of 18 patients after HSV had Hol- Reference References lander positive responses to insulin 'Bloom, S. R., Royston, C. M. S., and Thomson, Stoddard, C. J., and Duthie, H. L. (1973). Gut, 14, compared with 68% of 37 patients after J. P. S. (1972) Enteroglucagonrelease in the 824. TV + P. dumping syndrome. Lancet 2, 789-791. Szurszewski, J. H. (1969). Amer. J. Physiol., 217, 1757-1763. Reference Effects of Varying Degrees of Vagotomy The Influence of the Innervated Gastric Lyndon, P. J., Walsh, J. H., Johnston, D., and on the Gastroduodenal Response to Food Antrum on Gastrin and Acid Responses to Grossman, M. I. (1973). Gut, 14, 824. Insulin Hypoglycaemia in Man C. J. STODDARD AND H. L. DUTHIE (Univer- sity Surgical Unit, Royal Infirmary, P. J. LYNDON, J. H. WALSH, AND D. JOHN- Sheffield) We have previously shown STON (University Department of Surgery,