Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

Gut, 1974, 15, 822-841

The British Society of Gastroenterology

The following are abstracts of papers given at the annual meeting held at the University of Birmingham on 19-21 September. On 19 September there was a discussion organized by the Liver Group (Convener, Professor Sheila Sherlock) on 'The carrier of hepatitis B antigen'. In the afternoon there was a symposium shared by the British Society for Digestive Endoscopy on 'Diagnosis of pancreatic disease' (Moderator, Dr Sheila Waller), and a clinicopathological conference on 'Progressive intestinal disease in an adolescent' (Moderator, Dr W. T. Cooke). The Sir Arthur Hurst Memorial Lecture was given by Dr A. F. Hofmann on 20 September. The scientific sessions followed on 20 and 21 September. -A fuller account of the meeting appears in 'Notes and activities' on page 844, together with the names of the officers of the Society and.those of the newly elected Council.

P1 recorded and multiple biopsies taken rhoea, although serum levels of vitamin from different parts of the rectum at each A, D, and E are normal. In contrast to The extent of rectal premalignant change examination, (b) consideration should be the adult, a normal diet usually is indicated In ulcerative colitis given to a policy of colonoscopy with two years after extensive resection ofileum multiple biopsy in all patients with ex- in childhood. R. H. RIDDELL (introduced by B. C. tensive colitis who are statistically at in- MORSON) (St Mark's Hospital, London) It creased risk of malignant change. The P3 has been suggested that in patients with frequency with which colonoscopic ex- ulcerative colitis regular rectal biopsy can aminations should be performed has yet Perianal Crohn's disease be used for detecting premalignant change to be determined. and that this reflects similar changes in J. ALEXANDER-WILLIAMS, D. M. STEINBERG, http://gut.bmj.com/ the proximal colonic mucosa1. To assess Reference J. S. FIELDING, H. THOMPSON, AND W. T. the accuracy of this policy the frequency 'Morson, B. C., and Pang, L. S. (1967), Gut, 8, 423. COOKE (Nutritional and Intestinal Unit, The and extent of premalignant change in the General Hospital, Birmingham) The nat- rectum was measured using an eyepiece P2 ural history and results of surgical treat- micrometer on slides of rectal mucosa ment of perianal disease were assessed in from 56 proctocolectomy specimens. Diet and growth after resection of ileum in 418 patients with Crohn's disease. Forty of these specimens had carcinoma childhood A prospective review was made of 109

(25 rectal and 15 above the rectosigmoid patients initially diagnosed as having on September 30, 2021 by guest. Protected copyright. junction), and a further 16 had premalig- H. B. VALMAN (Northwick Park Hospital perianal Crohn's disease in 1968. All but nant change anywhere in the large intes- and Clinical Research Centre, Harrow, five have been followed and examined tine but no carcinoma. Middlesex) Twelve children who have after five years, following a policy of con- Five out of the 25 patients with rectal survived resection of more than 45 cm of servative management. In the majority carcinoma had premalignant change ileum (eight during the neonatal period (78Y) the disease status was unchanged; around the tumour only and this involved and four later in childhood) have been re- in only 16% had the disease deteriorated less than half of the mucosa examined. In assessed at periods between three and 16 in the five years. Continued or intermit- two out of the 15 patients with cancer in years. Two children received a low-fat, tent symptoms occurred in 35 %. the colon there was no evidence of pre- high-protein diet for nine and 13 years A separate review of 96 local anal malignant disease in the rectum and in a after resection and showed no advantage operations in 68 patients with Crohn's further two patients it involved less than in growth compared with 10 children who disease has shown that the anal lesions are half of the rectal mucosa. Among the 16 had a normal diet two years after resec- not necessarily serious or progressive and specimens without carcinoma premalig- tion. No child had persistent diarrhoea for simple establishment of drainage gave nant change in one patient did not extend longer than two years after resection. The good results in 70 %. Incontinence is to the rectum, and in a further five half weights of individual children are appro- likely to be the result of aggressive surgery or less of the rectal mucosa examined was priate for their heights. Their heights tend not of progressive disease. involved. These changes were least marked to be less than those of their siblings but Even in the presence of underlying in the rectum in four patients and most only one is less than the third centile. Two active bowel disease good results occur in marked in three. children are below the third centile for 54 % and the eradication of proximal In view of these findings it is suggested the height expected from their parents' active disease is not a necessary prerequi- that (a) ideally the site of rectal biopsy to heights. Despite the lack of diarrhoea the site, contrary to the views of Garlock detect premalignant change should be older children still have marked steator- (1967). Some patients may remain in good 822 Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

The British Society of Gastroenterology 823 health with minimal symptoms even in the DOUGLAS (Gastroenterology Group, of Medicine, University of Rhodesia, presence of gross anal stenosis with Department of Medicine, Royal Victoria Salisbury, Rhodesia) The objects of this fissures and fistulae. Infirmary, and Department of Medical study was to demonstrate the existence of Although an occasional indication for Physics, General Hospital, Newcastle upon tbopical sprue said not to occur in Africa. radical surgery, perianal Crohn's disease Tyne) Normal small intestinal epithe- We investigated 38 megaloblastic anae- can be managed conservatively in most lium contains interepithelial lymphocytes mias and three patients clinically thought patients. but their fate is unknown'. The observa- to have malabsorption syndrome. Full tion that in both coeliac disease' and haematological investigation and compre- Reference Crohn's disease2 there is an increase in hensive small intestinal work up was done. Garlock, J. H. (1967). 'Surgery of the small intes- the number of interepithelial lymphocytes Twenty-four patients had tropical sprue. tine' in surgery of the alimentary tract. in the small intestine suggested that in The following details concern only these London: Butterworths. these conditions there may be an increased 24. Clinically they presented typically with P4 loss of lymphocytes into the bowel lumen. anaemia, weight loss, anorexia, abdominal Such a situation is known to occur in pain, and diarrhoea. Of the 21 with mega- The HL-A system and the immunological lymphangiectasia3. We have therefore loblastic anaemia, the mean haemoglobin response to dietary antigens studied the distribution and faecal loss of was 5-4 g; six had a low serum B12 and peripherally harvested lymphocytes label- folate, two a low B12 only, and nine B. B. SCOTT, L. M. SWINBURNE, S. M. RAJAH, led with 51-Cr and reinjected into human either a low serum or red cell folate AND M. S. LOSOWSKY (Department of subjects. Localization of these labelled Twenty-one had severely abnormal jejunal Medicine, StJames's (Universitv) Hospital, lymphocytes has been made by external biopsies. Twenty-two had abnormal D- Leeds) There is ample evidence ofrelation- counting and by counting of faecal, urine, xylose absorption. All 24 had impaired ships between histocompatibility antigens and blood samples daily for five days. The Co57 vitamin B12 absorption. Steator- and immune responses in animals but not distribution of the lymphocytes within rhoea occurred in only eight, perhaps due in man. The close association between the body was different from normal in to inadequate fat-loaded diets, but the HL-A8 and coeliac disease (CD) might patients with coeliac disease. In five tropical sprue group excreted markedly suggest that immunological abnormalities normal subjects enteric loss of lympho- more faecal fat than a control group. in CD are related to the HL-A system. cytes over five days was 0-24% (SD ± Eighteen had malabsorption patterns on High levels of serum gluten antibodies 0-16). In three cases of lymphangiectasia small intestinal radiology. Six had atro- are common in CD and in other condi- the five-day faecal loss was 0 47 %, 0 55 %, phic gastritis and achlorhydria, five tions with damaged gut mucosa and may and 0 95 % respectively. In two untreated superficial gastritis, and 12 hypochlorhy- merely reflect absorption of dietary pro- coeliac patients faecal loss was 0-66 % and dria. There was no statistical difference teins. However, gluten antibodies are not 1-85 % and in two patients with Crohn's between the diets of the patients and http://gut.bmj.com/ found in all such patients and are found disease faecal loss was 1-45 % and 2-11 %. matched controls. Patients were rein- in some patients with chronic liver disease. The results have been correlated with vestigated in three groups. After six The relationship between these immune interepithelial lymphocyte counts in months tetracycline and haematinics, the responses to gluten and histocompatibility mucosal biopsies and with measurement combined regimen; after six months tetra- antigens is not known. of 51-Cr in resected intestine. cycline alone; and some, that subsequently Serum gluten and milk antibodies and Our observations suggest that there is joined one or other of these groups, HL-A-status were studied 'blind' in 124 normally a pathway of lymphocyte re- after two to three weeks' tetracycline subjects with various conditions. Gluten moval into the gastrointestinal tract of alone. To date 15 abnormal biopsies have on September 30, 2021 by guest. Protected copyright. antibody titres were significantly higher in probable importance in lymphocyte mi- been repeated. Eight were treated with the HL-A8-positive subjects (p < 0O0005; gration streams4. The finding of an in- combined regimen and seven with tetra- limit 1/128). If the 23 CD patients are crease in this lymphocyte loss may explain cycline alone; all returned to normal. excluded gluten antibody titres are still some of the immunological abnormalities D-xylose absorption improved in all nine significantly greater (p < 0-005). Further- observed in the conditions studied, and after the combined regimen, six to more more, milk antibody titres tend to be may yield a method of screening for in- then 5 g; in all eight after six months' higher in HL-A8-negative subjects. Thus flammatory bowel disease and coeliac tetracycline, five to more than 5 g and in from both antibodies a discriminant disease. all seven on two to three weeks' tetra- function can be calculated which separates cycline, four to more than 5 g. Vitamin HL-A8-positive and -negative subjects References B12 absorption became normal in seven with a high degree of certainty. of eight on the combined regimen, the These results 'Ferguson, A., and Murray, D. (1971). Gut, 12,988. suggest that in man as well 'Otto, H. F. (1973). Current topics in pathology, other improved; after six months' tetra- as in animals histocompatibility antigens 57, 81. cycline all nine returned to normal; and are related to immune responses. The 3Weiden, P. L., et al (1972). J. clin. Invest., 51, 1319. four were normal and three relevance of these findings to the aetiology 'Yoffey, J. M., and Courtice, F. C. (1970). Lymph, improved on lymphatics and the lymphomyeloid complex. two to three weeks' tetracycline. Faecal of CD will be discussed. Academic Press, London. fat levels improved in all four on the com- P5 bined regimen, in all six on six months' P6 tetracycline, and in four of five on the Enteric loss of lymphocytes in coeliac short course of tetracycline. The mean disease and in Crohn's disease Tropical sprue in Rhodesia weight gain was 9 kg on the combined regimen, 10 kg on six months' tetracycline, A. P. WEETMAN, J. HAGGITH, AND ADRIAN P. G. E. THOMAS, AND D. J. CLAIN (Department and 2-9 kg after two to three weeks' Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

824 The British Society of Gastroenterology tetracycline. Six megaloblastic anaemias Reference Hospital, London) The value and safety achieved a haematological response on Visick, A. H. (1948). Ann. roy. Coll. Surg. Engl., 3, of percutaneous needle biopsy of the liver tetracycline alone, all six haemoglobins re- 266. has been studied in 125 patients with turning to normal. Of four bone marrows mechanical obstruction confirmed at sur- repeated, to date, two have become P8 gery or necropsy. Biopsies were done only normoblastic and two showed minimal on those patients with normal blood megaloblastic change, having been severe- Antibiotics in biliary disease coagulation and adequate platelet counts. ly megaloblastic. Our patients had a Jaundice, of varying degree (in some malabsorption syndrome which responded M. R. B. KEIGHLEY, R. DRYSDALE, D. W. patients > 20 mg//), had been present to conventional therapy for tropical sprue. BURDON, AND J. ALEXANDER-WILLIAMS for from two weeks to two years. We have excluded coeliac disease, abdo- (The General Hospital, Steelhouse Lane, There was no mortality following minal tuberculosis, lymphomas, parasites, Birmingham) In patients undergoing bi- biopsy. One patient developed biliary and diet as alternative causes. We therefore liary operations, and particvlarly those peritonitis and underwent surgery from consider tropical sprue to occur in central who are jaundiced, there is a close corre- which he made an uneventful recovery. Africa and to cause most of our megalo- lation between the presence of micro- Minor complications occurred in seven blastic anaemias. organisms in the bile and the develop- patients and these all responded to medi- ment of wound sepsis and septicaemia. cal treatment. Percutaneous cholangi- P7 To investigate the value of chemotherapy ography with the finding of dilated bile in preventing these sequelae an antibiotic ducts, was performed successfully in 38 Observer variation in the assessment of excreted almost entirely in bile (rifamide) patients only one of whom had a compli- results of surgery for peptic ulceration and one with low bile but adequate serum cation following needle biopsy. concentrations (gentamicin) were com- Histological features of large bile duct F. T. DE DOMBAL, JANE C. HORROCKS, AND pared with controls. obstruction were seen in 83 % of the SUSAN E. CLAMP (The General Infirmary, A randomized trial was conducted in patients and in a further 13 % the biopsy Leeds, and the County Hospital, York) 150 patients who were allocated to re- showed cholestasis. The initial biopsy re- Results of surgery for peptic ulceration ceive rifamide, gentamicin, or no anti- port was misleading in only six patients. are usually graded according to (a) pre- biotic. Infective complications were re- The histological findings were particularly sence or absence of various postoperative corded by an independent observer. Ade- valuable in 17 patients in whom previous symptoms; (b) severity ofthese symptoms; quate antibiotic levels were assumed if the drug ingestion or the clinical history made and (c) an overall grading according to concentration was twice the minimum a diagnosis of biliary obstruction less the classification of Visick (1948). The inhibitory concentration for more than likely. present paper examines the observer varia- 80% of biliary organisms. In patients with large bile duct obstruc- http://gut.bmj.com/ tion inherent in these three assessment In non-jaundiced patients adequate tion, therefore, percutaneous needle bi- methods. bile concantrations occurred in 97 % on opsy of the liver is useful in confirming Some 232 patients were studied (fol- rifamide and 15% on gentamicin but the diagnosis and is of value in the inves- lowing peptic ulcer surgery) presenting to amongst jaundiced patients levels were tigation of the patient with cholestasis of the clinics of the Leeds/York gastric only 10 and 0% respectively. Adequate uncertain cause. The incidence of signifi- follow-up group. Each patient was re- serum concentrations were found only in cant side effects was low. viewed by the usual panel of observers; patients on gentamicin (87 %). Bacter- concomitantly a separate (blind) assess- bilia was significantly reduced only in the Plo on September 30, 2021 by guest. Protected copyright. ment was made by a further panel of non-jaundiced rifamide patients (p < observers, the results being subsequently 0-05). Only in the gentamicin group was Effect of wheat bran on bile salt metab- compared. wound infection and bacteraemia signifi- olism and bile composition A very high degree of observer agree- cantly less than controls (p = 0-05 and ment was recorded between observers and < 0-02 respectively). Also bacteraemia E. W. POMARE, K. W. HEATON, T. S. LOW- between panels both in York and in Leeds was eliminated in the jaundiced patients BEER, AND C. WHITE (University Depart- (95 %) concerning the presence or absence receiving gentamicin (p = 0-05) but not in ment of Medicine, Royal Infirmary, of specific postoperative complaints. Less those on rifamide. Bristol) Feeding bran reduces the en- agreement (under 90 Y.) was recorded con- We conclude that adequate serum anti- trance into the bile of deoxycholate (DC), cerning the severity of symptoms. As re- biotic levels are more important than bile a colonic bacterial metabolite, and in- gards Visick classification, initial agree- levels in preventing septic complications creases the proportion of chenodeoxy- ment was low (64% in York, 68% in of biliary operations, particularly in cholate (CDC) in the bile'. To elucidate Leeds) but rose with experience to over patients with jaundice. the mechanism of these changes we have 80% in both centres. performed kinetic studies, using the iso- These data suggest that the current P9 tope dilution technique after simultaneous degree of observer agreement in the clinics iv administration of 14C-labelled cholate studied is high. However, 'inter-series' Percutaneous needle biopsy of the liver and (C) and CDC, in six healthy subjects with comparisons based on overall Visick large bile duct obstruction cholecystographically normal gallblad- classifications should be viewed with ders (two containing translucent stones). extreme caution. Future comparisons J. S. MORRIS, G. A. GALLO, P. J. SCHEUER, The effects of bran (mean 57 g/day taken should concentrate upon the presence or AND S. SHERLOCK (The Departments of for four to six weeks) were as follows: absence of postoperative symptoms. Medicine and Histopathology, Royal Free DC pool shrank from 1-20 to 0-80 mmoles Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

The British Society of Gastroenterology 825 (p < 0025), CDC pool expanded from their activity by tryptic digestion suggest A2 1-72 to 2-19 mmoles (p < 0 05), while C that the active material is polypeptide in pool and total bile salt (BS) pool were not nature. Cell-mediated immunity to hepatitis B significantly altered. Synthesis of CDC Pancreotone is suggested as the appro- antigen in blood donors with persistent increased from 0-46 to 057 mmoles/day priate name for this pancreatic inhibitor. antigenaemia or high titre antibody (p < 0 025) but that of C was unchanged. Its relation to GLI will be discussed. Total BS synthesis was 1V24 and 1-46 W. M. LEE, W. D. REED, CHRISTINE G. mmoles/day before and after bran (0 05 Reference MITCHELL, A. L. W. F. EDDLESTON, IAN DYMOCK, AND ROGER WILLIAMS Liver < P < 010). The half-lives of C and CDC Crick, J., Harper, A. A., and Raper, H. S. (1950). (Thie were unchanged, indicating that bran has J. Physiol., 110, 367-376. Unit, King's College Hospital, London) little if any bile salt-binding action. The continued presence of either hepatitis In six subjects with radiolucent gall- B antigen (HBAg) or antibody to HBAg stones, bran feeding (mean 48 g/day for Al in the serum of asymptomatic blood four to six weeks) consistently reduced donors implies a faulty immune mecha- the cholesterol saturation of bile. Molar Cholestyramine therapy in cholestatic liver nism and a specific defect in cellular percentage of cholesterol fell from 14-1 ± disease of children immunity to HBAg has been proposed. 3-2 to 10-6 ± 2-7 (p < 0-0125). In the present study 43 antigen-positive These findings suggest that bran, like R. NELSON, G. M. MURPHY, SUSAN EDKINS, blood donors and 28 with persistent anti- fed chenodeoxycholic acid, reduces choles- SHEILA NUTrER, AND CHARLOTTE M. ANDER- body were investigated for cellular im- terol secretion into bile. A high fibre diet SON (Institute of Child Health, University munity to HBAg using the leucocyte may have a place in the prevention and of Birmingham) Six children aged from 4 migration test. even treatment of gallstones. months to 8 years with persistent chole- An abnormal migration index was static liver disease from early infancy have found in 12 (28 %) of the antigen-positive Reference been treated for up to 10 months with group. In an additional 13 subjects, 'Pomare, E. W., and Heaton, K. W. (1973). Brit. cholestyramine 6-12 g daily. In five of titres of HBAg in serum were higher than med. J., 4, 262. these, the response to treatment was that used in the migration test chamber assessed in terms of (i) circulating liver and sensitization could also have been P11 function tests, (ii) liver histology, (iii) bile present in some of these. However, in 18 acids in duodenal aspirate. subjects with low titres of HBAg the Inhibition of external pancreatic secretion In four patients there was improvement migration indices were normal. Serum by extracts of ileal and colonic mucosa in the following liver function tests, transaminase elevations and abnormal whose mean values before and after appearances on liver biopsy were present http://gut.bmj.com/ A. A. HARPER, A. J. C. HOOD, J. MUSHENS, cholestyramine were: serum bile acids in the majority of those with evidence of AND J. R. SMY (School of Pharmacy, 135 ± 130 and 29 ± 32 ,umols/litre cellular immunity to HBAg but were in- Sunderland Polytechnic, Chester Road, (p < 0 05); serum bilirubin 4 2 ± 3-3 and frequent in those with normal migration Sunderland) Instilling oleic acid into the 1-2 ± 1-4 mg/I 00 ml (ns); serum alkaline indices. In the antibody-positive group, colon or lower part of the ileum of anaes- phosphatase 79 ± 22 and 37 ± 18 KA only five (18%) showed sensitization to thetized cats inhibits pancreatic secretion, units/litre (p < 0-05); SGOT 201 ± 56 HBAg and one of these had chronic stimulated by secretin and pancreozymin. and 95 ± 43 iu/litre (p < 0-05) and persistent hepatitis. Hage, Palasciano, Tiscornia, and Sarles serum cholesterol 318 ± 72 and 202 ± 77 The increased frequency of liver on September 30, 2021 by guest. Protected copyright. (Biomedecine: in the press) have also mg/100 ml (p < 0-05). Histological evi- disease in those carriers with evidence of observed inhibition with oleic acid in the dence of cholestasis was considerably re- cellular immunity to HBAg is consistent colon of chronic dogs, but found that oleic duced. with the hypothesis that liver cell injury acid in the lower ileum stimulated the Duodenal bile acid output (jpmols/10 is mediated by sensitized lymphocytes. pancreas. min/kg body weight) measured following As the inhibitory effects in cats can be intravenous pancreozymin was signifi- A3 elicited after cutting the vagal and splan- cantly higher in six controls (mean 19 ± chnic nerves, it seemed likely that the in- 11) than in the patients with cholestasis The effects of portacaval shunting and hibition was humorally mediated. We (4 ± 3) (p < 0-05). Following cholestyr- portacaval transposition on serum gamma- have therefore extracted the terminal amine therapy, output in all four children globulin levels in the rat ileal and colonic mucous membrane of (mean 34 ± 39) increased and was not pigs and cats by a modification of the then significantly different from that of I. S. BENJAMIN, C. J. RYAN, A. L. C. MCLAY, method for preparing secretin and pan- the controls. With the increase in bile C. H. W. HORNE, AND L. H. BLUMGART creozymin (Crick, Harper, and Raper, acid output the proportion of glycocholic (University Departments of Surgery and 1950). Intravenous infusion of the extracts acid increased and that of monohydroxy Pathology, Glasgow Royal Infirmary, and inhibits the volume and enzyme output bile acids fell. In one, all liver function University Department of Pathology, of pancreatic secretion. Gallbladder con- tests have remained normal since stopping Foresterhill, Aberdeen) The aetiology of traction in response to pancreozymin pre- cholestyramine two months ago. hypergammaglobulinaemia in liver dis- parations is also inhibited. The inhibitory Of the other two patients, one showed ease is uncertain (Lancet, 1972). Since effect is not secondary to a reduction in no improvement in any of the features circulating antibody in the normal animal blood flow. The behaviour of the extracts studied and, in the other, studies are not is thought to be determined largely by on millipore filters and the abolition of yet complete. intestinal flora, its elevation may reflect Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

826 The British Society of Gastroenterology increased stimulation by intestinal antigen alcoholic liver disease and chronic active RTA. In nearly all of a group of patients which has failed to be sequestered by hepatitis. It is suggested that the elevation with other liver diseases and in a control Kupffer cells (Inchley and Howard, 1969) of antibody titres directed against the group of normal subjects, results were due either to incompetence of these cells intestinal bacteria is secondary to a failure within normal limits. In addition, using an or to intra- or extrahepatic shunting of of the liver to sequestrate these bacteria, immunofluorescent technique with rabbit blood past the cells (Bjorneboa et al, 1972). but since elevated titres to measles antibody to human Tamm-Horsfall glyco- Male rats (250-350 g) were subjected to and rubella have only been described in protein, it was possible to demonstrate operation as follows: chronic active hepatitis, the possibility of the presence in human liver cell membrane an aetiological association of these viruses of material reacting immunologically as Group I: 11 animals Portacaval anastomosis to this disease has arisen. We have inves- Tamm-Horsfall. Group II: 11 animals Portacaval transposition tigated the incidence of high titres of These findings suggest that the develop- Group III: 19 animals Laparotomy with dissection antibody to Gram-negative intestinal ment of an immune response to this glyco- of portal vein and vena cava bacteria and viruses in primary biliary protein, initiated by release of cross- cirrhosis (40 cases) and other forms of reacting antigens from damaged hepato- Serum levels of y2-globulin were esti- chronic liver disease. cytes, could be the mechanism underlying mated weekly by radial immunodiffusion The patients with primary biliary the occurrence of RTA in some patients assay up to five weeks, when the animals cirrhosis had significantly elevated titres with autoimmune liver disease. were sacrificed. to Gram-negative intestinal bacteria. The After the first week, y2-globulin rose titres were similar to those found in B1 progressively in all groups. Group III patients with other forms of chronic liver showed an increase by five weeks of 40 %, disease. This is further evidence of a The production of lysozyme by the Paneth consistent with normal age changes functional reduction in the phagocytic cell (Horne and Ferguson, 1972). Groups I capacity of the liver in all forms of chronic and II rose together, increasing by 98% liver disease. G. R. VANTRAPPEN, AND T. L. PETERS (Uni- and 124% respectively by five weeks. Antibody titres to measles were elevated versity ofLeuven, Leuven, Belgium) The Groups I and II were never significantly in chronic active hepatitis (p < 0.001) and function of the Paneth cell in normal and different, but differed from group III at primary biliary cirrhosis (p < 0 001) but pathological conditions is still largely un- two weeks (p < 0-05) and at three, four, were normal in alcoholic liver disease. known. In previous cell fractionation and and five weeks (p < 0 005 - p < 0 001). Titres to rubella were elevated in chronic histochemical studies we demonstrated Evidence is presented that portacaval active hepatitis but not in the primary that the Paneth cell granules contain transposition achieves portal-systemic biliary cirrhosis or alcoholic liver disease lysozyme. Based upon this observation we http://gut.bmj.com/ shunting with little change in hepatic groups. This suggests that these viruses developed a method to study Paneth cell function. It is proposed therefore that have a special association with the auto- secretion, using immunofluorescence and hypergammaglobulinaemia in this situa- immune liver diseases. intestinal perfusion techniques. Lysozyme tion may be a result of shunting of portal was isolated from the small intestine of blood past the reticuloendothelial cells of A5 mice and antibodies prepared against it in the liver, and that hepatocellular damage rabbits. The antiserum was used to stain may not play a major role in this process. Cell-mediated immunity to human Tamm- cryostat-cut, alcohol-fixed tissue slices

References Horsfall glycoprotein in autoimmune liver with the indirect antibody technique. In on September 30, 2021 by guest. Protected copyright. disease associated with renal tubular fasting mice fluorescence was largely con- Bjorneboa, M., Prytz, H., and Orskov, F. (1979). Lancet, 1, 58 acidosis fined to the secretory pole of the Paneth Horne, C. H. W., and Ferguson, J. (1972). J. cells. After the intravenous administra- Endocr., 54, 47 D. C. TSANTOULAS, I. F. MCFARLANE, B. tion of 4 mg of pilocarpine the fluor- Inchley, C. J., and Howard, J. G. (1969). Clin. exp. PORTMANN, A. L. W. F. EDDLESTON, AND Immunol., 5, 189 escence in the crypts was abolished, but Leading aticle (1972). Lancet. 1, 80 ROGER WILLIAMS (The Liver Unit, King's streaks of fluorescent material granular in College Hospital, London) Renal tubular appearance could be seen between the acidosis (RTA) occurs in about 30% of villi. Ten minutes after the stimulation the A4 patients with active chronic hepatitis or fluorescent material had reached the top Viral and bacterial antibodies in primary primary biliary cirrhosis, and immunolo- of the villi. Perfusion studies confirmed biliary cirrhosis and other chronic liver gical abnormalities have been implicated these findings. A 15 cm segment of the disease in this association. ileum was perfused with physiological In this study, we have used the leucocyte saline at a constant rate of 4 0 ml/hr. The H. C. THOMAS, R. HOLDEN, J. IRONSIDE, AND migration test to investigate cell-mediated concentration of lysozyme during the R. G. SOMERVILLE (University Department immunity to a protein known as the control period was 0 1-0-2 jig/ml, and was ofBacteriology and Immunology, Glasgow Tamm-Horsfall glycoprotein, which is sharply increased after the intravenous University, and Virology Department, present in normal human urine and is administration of 4 0 mg of pilocarpine. Belvidere Hospital, Glasgow) Increased produced within the tubules of the kidney Much smaller doses were also effective: a antibody titres to measles and rubella at the principal sites of acidification. statistically significant rise was still viruses have been described in chronic Abnormal responses were found in 91 % obtained with a dose of 0-01 mg (peak active hepatitis and increased antibody of patients with active chronic hepatitis or rate 0-8 ,ug/ml). Amylase and acid phos- titres to the Gram-negative intestinal primary biliary cirrhosis associated with phatase were determined concomitantly; bacteria have been demonstrated in RTA, but in only 19% of those without their initial concentration was 5-6 Somog- Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

The British Society of Gastroenterology 827 yi units per ml for amylase and 2-6 The management of this group of been examined in all the first-degree mU/ml for acid phosphatase. The con- infants and young children, together with relatives of all the propositi. centration of these two enzymes decreas- the hypothesis that acute antecedent GE We have investigated all first-degree ed during the perfusion and was un- may lead to prolonged small intestinal relatives of 15 newly diagnosed coeliac affected by the injection of pilocarpine. damage, will be discussed. children. Families known to contain Our results demonstrate the presence of another coeliac patient were excluded. lysozyme in the Paneth cell granules, and B3 Investigations included detailed clinical the ability of lysozyme to serve as a history, anthropometry, andjejunal muco- marker of Paneth cell secretion. Continuing gluten ingestion and its detec- sal biopsy; measurement of haemoglobin, tion in treated coeliac patients serum iron, red cell and serum folate; the B2 HLA status and, in children under 30 kg, P. G. BAKER AND A. E. READ (University a one-hour blood xylose test. Small intestinal mucosal morphology in a Department of Medicine, Bristol Royal Mucosal appearances typical of coeliac group of infants and young children with Infirmary) In order to assess the inci- disease were found in two of the 30 delayed recovery after acute diarrhoea and dence and effects of continuing gluten in- parents (6-6%) and two of the 42 siblings vomiting gestion in patients with coeliac disease, we (4 8%)-an overall incidence of 5 5% of have studied 51 patients after a period of 72 first-degree relatives. Both children M. J. BOYCE, N. E. FRANCE, AND J. A. four to 132 (mean 63) months on a were in one family and thus three of 15 WALKER-SMITH (Queen Elizabeth Hospital prescribed gluten-free diet. Each patient families (20%) contained another coeliac for Children) Acute gastroenteritis (GE) completed a dietary questionnaire, under- member. is usually a self-limiting illness with a low went a repeat jejunal biopsy and had In none of the four was the history mortality, although the morbidity may be serum taken for gluten antibody estima- frankly suggestive nor were any of the considerable (Gribbin et al, 1974). Duo- tion (tanned erythrocyte method). tests other than biopsy uniformly reliable denal mucosal damage, sometimes severe, The questionnaire showed that 30 (60 %) for screening. is common during the acute illness al- had failed to eliminate dietary gluten The incidence of 'asymptomatic' af- though on the basis of a few serial biop- completely. Of these nine were taking fected first-degree relatives was 5 5 % with sies it is suggested that mucosal recovery large amounts, and 21 were taking small one of five families containing more than is rapid (Barnes and Townley, 1973). A amounts. one affected member. Studies where all necropsy study of 10 children who died All nine of the patients taking large propositi are children may give results at variable intervals after acute GE re- amounts of gluten showed subtotal villous different from those where adult cases vealed an abnormal mucosa in seven atrophy on repeat jejunal biopsy com- are used. No test other than intes- (Walker-Smith, 1972). pared with only four of 20 patients taking tinal biopsy was shown to select with http://gut.bmj.com/ Twenty-two infants and young children no gluten (P <0-01). certainty the individuals previously un- with acute antecedent diarrhoea who sub- Similarly, all nine patients taking large suspected. sequently either failed to gain weight amounts of gluten had antibodies to satisfactorily or continued to lose weight gluten in the serum compared with only B5 despite adequate caloric intake were four of the 20 patients apparently taking subjected to small intestinal biopsy. Some no gluten (P < 0-01). Ileal function in patients with coeliac infants showed signs of severe malnu- Nine of 10 patients with both subtotal disease trition. All biopsies were expected to villous atrophy and gluten antibodies on September 30, 2021 by guest. Protected copyright. assist diagnosis and management. were still ingesting large amounts of D. B. A. SILK, PARVEEN J. KUMAR, M. L. Biopsies were performed not less than gluten. CLARK, AND A. M. DAWSON (Medical Unit, three weeks after the acute antecedent ill- These findings suggest that many Department of Gastroenterology, St ness and in some cases as late as three patients with coeliac disease continue Bartholomew's Hospital, London) In ani- months. Seven biopsies were considered to ingest gluten despite initial dietary mals after jejunal resection the remaining histologically normal. The remainder (15) instruction, and that patients with both ileal mucosa becomes hypertrophied and showed variabled egrees of abnormality, subtotal villous atrophy and circulating ileal function enhanced (Dowling and which, on the basis of villous architecture, gluten antibodies are almost certain to be Booth, 1967). Untreated coeliac disease epithelial cell changes, and infiltration of still taking large amounts of gluten. might be compared to this experimental the lamina propria with inflammatory model because the mucosal lesion is more cells, were graded into mild (7), moderate B4 marked in thejejunum than the ileum, and (5), and severe (3). The severe changes some patients absorb vitamin B12 to a were similar to those seen in coeliac Family study of coeliac disease greater extent than normal subjects (Elias disease. et al, 1973). Generalized disaccharidase depression C. J. ROLLES, T. 0. KYAW MYINT, WAI-KEE In the present study the possibility of occurred in association with abnormal SIN, AND CHARLOTTE M. ANDERSON (Insti- enhancement of other aspects of ileal morphology. In two instances disacchari- tute of Child Health, University of function in patients with untreated coeliac dase depression also occurred despite Birmingham) The reported incidence of disease has been investigated by studying normal morphology. Only two children coeliac disease amongst the patient's absorption during ileal perfusion of an developed sugar malabsorption on rein- first-degree relatives varies from under isoosmotic electrolyte solution containing troduction of cow's milk formula after 1 % to over 15 %. However, in none of the 50 mM glucose and 25 mM bicarbonate. rehydration. reports has the small intestinal mucosa The differential handling of bicarbonate Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

828 The British Society of Gastroenterology by the jejunum and ileum was used to and 2-6 % and the cationic exchange A. M. MACKAY, JEAN K. RITCHIE, AND H. G. confirm the correct positioning of the capacities 1-2 m-equiv and 0-7 m-equiv STURZAKER (St Mark's and the Central perfusion tube in normal controls, and per gram. After milling both brans to the Middlesex Hospitals, and the Chester applying the same criteria to the coeliac same particle size, the advantageous Beatty Research Institute, London) The patients ileal positioning was satisfactory characteristics of the coarse bran were aim of this study was to investigate levels in five out of seven subjects studied. Three lost. of plasma CEA in patients with ulcerative of these patients had enhanced ileal func- It is concluded that the water-holding colitis, particularly inthosewith carcinoma tion as shown by increased absorption of capacity of coarse bran is a function of or especially liable to malignant change. either glucose, sodium, chloride or water particle size, and that these two factors CEA was measured by a double compared with any of the respective are related to motility changes. antibody radioimmunoassay method absorption values observed in eight con- (Laurence et al, 1972), the upper limit of trol subjects. C2 normal being taken as 12-5 ng/ml based on These findings indicate that enhanced measurements in 60 healthy control sub- ileal function, in addition to the recently Effects of bile acids on the motility of the jects. described colonic adaptation (Phillips colon CEA levels above 12-5 ng/ml were and Giller, 1973), may explain why some found in 11 of 25 patients with non- coeliac patients with known jejunal W. 0. KIRWAN, A. N. SMITH, W. D. inflammatory bowel disease or minor secretory states do not have diarrhoea. MITCHELL, AND M. A. EASTWOOD (Wolfson anal conditions, originally intended to act Gastrointestinal Laboratories, Western as a hospital control group. References General Hospital and Department of One hundred and fifty-two patients with colitis attending St Mark's or 'Dowling, R. H., and Booth, C. C. (1967). Structu- Clinical Surgery, University of Edinburgh) ulcerative ral and functional changes following small Bile was reported by Horral (1938) and the Central Middlesex Hospitals between intestinal resection in the rat. Clin. Sci., 32, Harvey et al (1939) to stimulate intestinal November 1972 and May 1974 were 139-149. motor activity, but specific effects on the studied, including seven with severe 'Elias, E., MacKinnon, A. M., Short, M. D., and Dowling, R. H. (1973). Factors controlling motor function of the colon have not yet dysplastic changes in the rectal mucosa ileal adaptation after proximal small bowel been described. The effects of bile acids and six with established carcinoma. resection and in coeliac disease. Eur. J. clin. on the colon have therefore been examined CEA levels above 12-5 ng/ml were found Invest., 3, 226. 152 with colitis; no 'Phillips, S. F., and Giller, J. (1973). The contribu- in acute and chronic experiments in the in 53 of the patients tion of the colon to electrolyte and water rabbit and in the human. relationship between actual levels and conservation in man. J. lab. clin. Med., 81, In acute experiments in 14 rabbits bile activity, duration, or extent of the disease 733-746. acids were infused into the caecum in con- could be found. Eight of the 13 patients centrations 2 mM-16 mM. Concentration with either dysplastic or carcinomatous C1 in the range 2 mM-4 mM produced the changes showed levels above normal ( four http://gut.bmj.com/ Actions of bran on colonic motility related greatest motor activity (p < 0-0125) in each group). Only two of the 152 to its physical properties starting at 10 minutes. In 12 chronic ex- patients (one in the dysplastic and one in periments bile in the caecum produced the carcinoma group) had levels above W. 0. KIRWAN, A. N. SMITH, A. A. maximal motor stimulation (p < 0-0125) 40 ng/ml, a level usually associated with MCCONNELL, W. D. MITCHELL, AND M. A. after a delay of 30 to 45 minutes. When carcinoma. EASTWOOD (Department ofClinical Surgery bile was introduced into the sigmoid, the This study highlights the problem of the and Wolfson Gastrointestinal Laboratories, effect took place in 10 minutes. Trhere was selection of controls for CEA estimation General a significant correlation between the moti- and suggests that CEA levels do not con- University of Edinburgh, Western on September 30, 2021 by guest. Protected copyright. Hospital, Edinburgh) The effectiveness lity response and the concentration used tribute to the management of patients of two different bran preparations in (r = 0 98). Bile introduced into the human with colitis. lowering intraluminal colonic pressure sigmoid had a similar effect. and decreasing intestinal transit time has In patients with cholerrhoeic entero- Reference been assessed in 14 subjects given fine and pathy the motility responses correlated Laurence, D. J. R., Stevens, U., Bettelheim, R., coarse bran over one month. Coarse bran well with daily bile acid excretions (r = Darcy, D., Leese, C., Tuberville, C., 0-58). It is suggested that bile can act as Alexander, P., Johns, E. W., and Munro given to nine patients lowered intraluminal Neville, A. (1972). Role of plasma carcino- pressure motility indices significantly: stimulant of colonic motility. embryonic antigen in diagnosis of gastro- and bronchial carci- basal 892-8 + 196 to 648-7 + 339; after References intestinal, mammary, food 1513-2 ± 456 to 446-1 ± 130 (P < noma. Brit. med. J., 2, 605-609. Haney, H. F., Roley, W. C., and Cole, P. A. (1939). 0-01); after prostigmine 2120 + 405 to The effect of bile on the propulsive motility 1216'8 + 398 (P < 0 01), and transit time of Thiry-Vella loops in dogs. Amer. J. C4 93.4 hours + 13-8 to 57*9 hours ± 8-0 Physiol., 126, 82-88. (P < 0-01): fine bran had no such effects. Horral, 0. H. (1938). Bile: its toxicity and relation Immunosuppressive consequences of the Patients first given fine bran and later to disease. University of Chicago Press. treatment of ulcerative colitis with azathio- changed to coarse bran also showed signi- prine ficant change. The water-holding capacity C3 of the two brans differed markedly: CEA estimation in ulcerative colitis with J. M. SKINNER, A. C. CAMPBELL, CATHERINE 6'15 g and 2 36 g of water per g bran for and without malignant change WALLER, JANET WOOD, AND I. C. N. the coarse and fine preparations respect- MaCLENNAN (Nuffield Department of Clini- ively. The lignin content of each was 4-1 % J. B. DILAWARI, J. E. LENNARD-JONES, cal Medicine and Nuffield Department of Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

Thne British Society of Gastroenterology 829 Pathology, Radcliffe Infirmary, Oxford, trial was of a double-blind crossover maximum of two to three times normal at introduced by Dr S. C. Truelove) Stud- design in which patients received active or 36 hours. Elevated levels were main- ies were made of lymphoid subpopula- placebo treatment in a randomized order, tained for at least four days, but returned tions in the blood and rectal mucosa of 40 each for a period of four weeks. Patients almost to normal at seven days, when the patients who were taking part in a double- recorded symptoms on a diary card, and a liver approaches its estimated preopera- blind trial of continuous treatment with sigmoidoscopy with rectal biopsies was tive weight. azathioprine, the clinical results of which performed initially and at the end of each The present data suggest an appropriate are reported by D. P. Jewell and S. C. treatment period. functional relationship between collagen Truelove. In addition to blood leucocyte On the basis ofchange in symptoms and synthesis and hepatocyte and mesenchy- and differential counts, the following and sigmoidoscopic appearance, 11 pati- mal cell proliferation in regenerating assays of lymphocyte function or sub- ents improved during the DSCG period; liver. Further studies of this relationship populations were applied: mitotic re- this improvement was marked in nine. may be of value in studying the mecha- sponse to phytohaemagglutinin (T cell Five patients improved during the placebo nisms not only of liver regeneration but function), staining for surface immuno- period and the improvement was marked also of liver pathology. globulin (B cells), and cytotoxicity against in two. Four patients showed no change antibody-sensitized target cells (K cell during either period and a further four References activity). In some cases T cells were also were withdrawn because they failed to Higgins, G. M., and Anderson, R. M. (1931). Arch. identified by their capacity to form rosettes complete the trial satisfactorily. The Path., 12, 186. with sheep red blood cells. Plasma cells of number of eosinophils in biopsy speci- McGee, J. O'D., Patrick, R. S., Rodger, Marion C., specific class were identified in the lamina mens varied from 0 to 115 per five high- and Luty, Caroline L. (1974). Gut, in press. propria of rectal biopsies by an immumo- power field. Five patients with less than 10 peroxidase technique and were quanti- eosinophils/5 hpf did not respond to intal; D2 tated. From the blood leucocyte counts eight of 10 with more than 10 eosinophils/ the only change attributable to azathio- 5 hpf responded to the drug. The results Adenocarcinoma of the bile ducts: Rela- prine was a slight and gradual fall in suggest that DSCG may be of value in the tionship of anatomical location to clinical lymphocyte count. The lymphocyte assays treatment of proctitis. The findings may features showed that azathioprine had little effect also be important in relation to the on the major T and B cell subpopula- pathogenesis of this disease. DAVID A. INGIS AND RICHARD G. FARMER tions. Patients on azathioprine did, how- (Department of Gastroenterology, The ever, show a highly significant depression Dl Cleveland Clinic Foundation, Cleveland, of K cell activity. After 12 months' treat- Ohio, USA) An unusual, but not rare, ment, this lymphocyte cytoxicity was Prolyl hydroxylase activity in regenerating cause of obstructive jaundice is carcinoma http://gut.bmj.com/ almost immeasurable in several patients. rat liver of the bile ducts. It was postulated that The assays of plasma cells in the rectal lesions at the hepatic duct bifurcation lamina propria revealed that these cells 1. S. BENJAMIN, J. O'D. MCGEE, THAN THAN, represent a clinical entity separate from were markedly depleted by azathioprine MARION C. RODGER, AND L. H. BLUMGART those arising elsewhere in the bile ducts. treatment. (University Departments of Surgery and This review of23 cases ofcarcinoma ofthe Pathology, Glasgow Royal Infirmary) bile ducts (1960-1974) compared carci- C5 Most investigations in the field of liver noma of the hepatic ducts and common regeneration have focused on the kinetics bile duct regarding clinical presentation, on September 30, 2021 by guest. Protected copyright. Treatment of chronic proctitis with di- and mechanisms underlying the cellular treatment, and prognosis. There were 14 sodium cromoglycate proliferative response. This paper is con- patients with hepatic duct lesions and nine cerned with the collagen productive re- with common bile duct carcinoma. Age, R. V. HEATLEY, B. J. CALCRAFT, J. RHODES, sponse in regenerating liver, since collagen sex, presenting symptoms, physical ex- E. OWEN, AND B. EVANS (Department of is the main extracellular product which amination, and laboratory findings were Gastroenterology, University Hospital of provides structural support for a pro- similar regardless of location of carci- Wales, Cardiff) Mast cells and eosino- liferating cell population in vivo. Activity noma. Location did not influence whether phils are commonly found in the rectal of prolyl hydroxylase, a key enzyme in the correct diagnosis was made at the mucosa of patients with ulcerative colitis collagen biosynthesis, was used as an initial operation, only 25 %. Percutaneous and proctitis. The mast cells are often index of collagen production. The tissue cholangiograpby, operative cholangio- degranulated during disease activity and level of this enzyme in general parallels graphy, and endoscopic retrograde cho- may play a role in the pathogenesis. Since the rate of collagen synthesis in tissues langiopancreatography were equally suc- disodium cromoglycate (DSCG) stabilizes (McGee et al, 1974) and preliminary data cessful in making the diagnosis in both mast cells in bronchial asthma, it may be using labelled precursors indicate that the locations. Pathologically, the hepatic of therapeutic value in proctitis. relationship is valid in the present model. duct carcinomas were scirrhous and distal We have examined DSCG in 24 patients Sixty-eight per cent hepatectomy lesions were adenocarcinomas. Location with proctitis. All had active symptoms (Higgins and Anderson, 1931) or sham influenced operative feasibility; resection and inflammatory changes on sigmoido- operation was performed in male rats. At was possible with common bile duct scopic examination; the barium enema intervals after surgery, hepatic concentra- lesions. Survival was less than one year was normal in all patients. DSCG was tion of prolyl hydroxylase in the regen- for both locations, and unaffected by 5- given by enema (200 mg twice daily, and erating posterior lobes was measured. fluoracil or radiation. Since prognosis orally 100 mg three times daily). The Activity of the enzyme increased to a is so poor, attention must focus on means Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

830 The British Society of Gastroenterology of earlier diagnosis, but separation into Analysis of the necropsy findings in 95 (1973). Bile salt metabolism and the colon. Scand. J. Gastroent., 8, 425-431. distinct clinical entities based on location patients showed cerebral oedema to be a 'Pomare, E. W., and Low-Beer, T. S. (1974). The of the lesion is artificial. striking feature in 36, and in 20 it was selective inhibition of chenodeoxycholate associated with brain herniation. Major synthesis by cholate metabolites in man. Gut, in press. D3 gastrointestinal bleeding was responsible 3Northfield, T. C., and Hofmann, A. F. (1973). for death in 26 patients, 10 died of various Biliary lipid secretion in gallstone patients. Cholelithiasis: A metabolic consequence of infections, and in five there was acute Lancet, 1, 747-748. ileostomy pancreatitis. In the remaining 21 cases, death appeared to be due to severe hepatic D6 WILLIAM S. J. MAIR, GRAHAM L. HILL, AND failure without these complicating factors. JOHN C. GOLIGHER (Department ofSurgery, When the area of surviving liver paren- The effect of florantyrone (Zanchol) on the The General Infirmary, Leeds) All ileost- chyma was assessed by a morphometric composition of T-tube bile omists attending a large clinic were technique on necropsy liver biopsies, this submitted to cholecystography to de- gave a value of less than 12 % (normal J. R. KIRKPATRICK, M. A. EASTWOOD, AND termine the incidence of gallstones and about 85%) in all the patients in whom W. D. MITCHELL (The Department of to determine the factors governing this. hepatic failure was the cause of death, Clinical Surgery and the Wolfson Gastro- Of 67 patients studied to date, four whereas in those cases with sepsis as a intestinal Laboratories, Western General have had cholecystectomy performed and major cause of death and in half the cases Hospital, University of Edinburgh, Edin- a further 14 have developed stones since with cerebral oedema or bleeding, the burgh) In 1956 McGowan described ileostomy. The overall incidence of stones hepatocyte volume fraction was between changes in common duct bile resulting is thus 28 % and for the 28 patients over 25% and 55%. from the use of a new choleretic floran- 50 years of age, 13 (46%) have gallstones. Thus, better understanding and manage- tyrone. The results in the physical proper- Detailed operative and pathological ment of these complications is necessary ties of the bile suggested that this drug data are available for each patient, and, if the survival rate is to be improved even should be useful in the treatment of of the many risk factors studied, only age, further. biliary disease. Recent emphasis on the sex, and ileal resection were significant. value of altering bile composition promp- Eleven out of 18 over 53 years of age D5 ted a new study of this drug. developed stones compared with 12 out Four patients were studied following of 49 under 53 (p = < 0-0025). Thirteen Effect of administration of a colonic cholecystectomy and choledochotomy. out of 18 women developed stones com- metabolite of cholic acid on cholesterol T-tube bile was collected for three days pared with 25 out of 49 men (P = < levels in bile and blood before and three days during therapy with 0005). 250 mg of florantyrone (Searle) adminis- http://gut.bmj.com/ The mean length of ileal resection in E. W. POMARE AND T. S. LOW-BEER (Univer- tered thrice daily orally. Within 24 hours those who developed stones was 18-3 in. sity Department of Medicine, Bristol there were changes in the bile, both in compared with 6-3 in. in those who did not Royal Infirmary, Bristol) Cholic acid is colour and chemical composition. The (p = < 001). metabolized by colonic bacteria to deoxy- principal change was in the bile acid con- Of 23 patients with a resection < 4 in. cholic acid (DC)'. This metabolite centration from 4-8 ± 1-8 mM to 8-9 + nine had stones. None of those without administered at doses up to 150 mg daily, 3-2 mM, particularly in the cholic acid stones were over 53 years of age. selectively suppresses hepatic synthesis fraction (3-2 ± 1-3 to 5 9 + 1 9 mM) and It is concluded that there is an in- and pool size of chenodeoxycholate in phospholipids (570 ± 77T6 mg% to on September 30, 2021 by guest. Protected copyright. creased incidence of gallstones in ileos- (CDC), without altering total bile salt 142 i 134-0 mg%). tomists, particularly in women, those pool size2. CDC, when used for dissolving There were also significant but less with an ileal resection, and those who are gallstones, decreases the cholesterol con- striking increases in the concentration of over 53 years of age. tent of biliary lipids by decreasing choles- cholesterol and in dry weight and osmolal- terol secretion into bile3. We anticipated ity of the bile. The changes in the deter- D4 that DC administration would increase gent content of the bile might well be the cholesterol content of bile lipids. exploited in studies and management of Fulninant hepatic failure: Histological Sixteen healthy volunteers received 100- biliary problems. quantitation of surviving liver parenchyma 150 mg DC dailv for two weeks. The in the evaluation of the cause of death cholesterol content of biliary lipids in- Reference creased significantly (p < 0-0125) and McGowan, J. M. (1956). Surg. Gynec. Obst.. 103, B. PORTMANN, B. G. GAZZARD, I. M. MURRAY- reversibly (p < 0-025), and this was 163. LYON, AND ROGER WILLIAMS (Liver Unit, accompanied by a significant fall in serum King's College Hospital, London) Since cholesterol to 88 % of baseline levels. El 1968, 130 adult patients with grade III or These results suggest that populations IV encephalopathy due to fulminant in whom there is a high colonic absorp- Ion transport characteristics of human hepatic failure (FHF) have been seen. tion of bacterially metabolized cholate, jejunal and ileal mucosa in vitro Only 12 of the first 99 patients survived, ie, DC, have an increased predisposition although a more encouraging figure (45 % to cholesterol gallstones. P. ISAACS AND L. A. TURNBERG (Division of survival) has been obtained in a recent Gastroenterology, Manchester Royal Infir- series of 31 patients treated with charcoal References mary, and Department of Medicine, Hope column haemoperfusion. "Morris, J. S., Low-Beer, T. S., and Heaton, K. W. Hospital, Salford) In-vivo studies of ion Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

The British Society ofGastroenterology 831 transport demonstrate differences between EA (2 5 mg/kg), administered in jejunal intravenously, the mean water absorption human jejunum and ileum. To investigate lumen prior to PGE1 (0 9 ,sg/kg/min), in five subjects (± SEM) fell from 1 99 ± these differences at the mucosal level we significantly reduced (p < 0 001) the net 0-87 ml/minute to -0O81 ± 1-49 ml/ have studied ion transport in human in- secretory effect of intraluminal PGE1 by minute. Similar results were obtained with testinal mucosa in vitro. Pieces of stripped an average of 4-8 ml/min/25 cm for water electrolyte absorption. In three subjects, mucosa from fresh surgical specimens and 632 pequiv/min/25 cm for sodium; net secretion of water and electrolytes were mounted in Ussing-type flux cham- EA suppressed the PGE1-induced increase occurred after frusemide. bers and bathed in oxygenated glucose- in plasma to lumen unidirectional flux of These findings may account for the Krebs-Ringer solution at 37°. There were sodium. Intravenous or intraluminal diarrhoea which has been reported in clear differences between the behaviour aspirin (25 to 45 mg/kg) did not modify some patients when high doses of fruse- of short circuited jejunal (n = 8) and PGE,-induced secretion nor control ab- mide are used, especially in patients with ileal (n = 9) mucosa. Net Na- absorption sorption rates. No significant changes in chronic renal failure. In addition, this (netNa+) was greater in ileal than jejunal systemic plasma level of PGE occurred inhibition of absorption in the small intes- mucosa (12-8±1.2 against 4-0±1.1 ,uequiv/ during the different periods of study. tine may affect the absorption of other cm2/hr) due to a greater mucosa to serosa These results suggest that aspirin, which drugs which may be given together with unidirectional flux (Jm); serosa to mucosa inhibits prostaglandin synthesis in vitro, frusemide. Modification of the dosage flux (Jm) was similar in the two tissues. and reduces cholera secretion in animals2, regimes of such drugs may be necessary JnetCl- was near zero in jejunum but has no effect on the intestinal fluid move- when frusemide is administered in large ileal mucosa absorbed 5 4 ,uequiv/cm2/hr ments induced by preformed PGE1. doses. of Cl-. Electrical characteristics are shown Conversely, they indicate that EA inhibits in the table. in man PGE.-elicited jejunal secretion, an Reference effect of EA similar to that observed, in 1Phillips, S. F., Summerskill, W. H. J. (1966). PD (m V) Resistance SC Current animals, on cholera and cyclic AMP- Occlusion of the jejunum for intestinal per- (Q/cm') (Aequiv/cm2/ fusion in man. Proc. Mayo Clin., 41, 224-231. hr) mediated secretion3. Jejunum 9 0 t 05 17-0 2-3 6-3 1 0 References E4 Ileum 9-1 03 11-6 1-6 93 09 'Matuchansky, C., and Bernier, J. J. (1973). Effects of ethanol on small intestinal Gastroenterology, 64, 1111-1118. Theophylline (10 mM) had no effect on 'Finck, A. D., and Katz, R. L. (1972). Nature absorption netjejunal ion transport while in the ileum (Lond.), 238, 273-274. it increased, Jsmcl-producing a net secre- 3AI-Awqati, Q., Field, M., and Greenough, W. B. N. KRASNER, K. M. COCHRAN, C. G. tion of 2 0 uequiv/cm2/hr and JnetNa+ (1974). J. clin. Invest., 53, 687-692. THOMPSON, H. A. CARMICHAEL, AND R. I. was slightly reduced to 9-6 /Aequiv/cm2/hr. E3 RUSSELL (Gastroenterology Unit, Stobhill http://gut.bmj.com/ These results demonstrate that ileal General Hospital, Glasgow, and Depart- mucosa absorbs more Na+ per cm2 than The effect of frusemide on small-intestinal ment ofGastroenterology, Royal Infirmary, jejunal mucosa and that while the ileum absorption of water and electrolytes Glasgow) It is well established that absorbs Cl- actively the jejunum does not. chronic alcoholic subjects may exhibit Differences in response to theophylline J. F. MaCKENZIE, K. M. COCHRAN, AND R. I. malabsorption1. In the present study, the also suggest cyclic AMP stimulatedo in RUSSELL (Department of Gastroenterology, absorption of water, electrolytes, and transport processes are probably different RoyalInfirmary, Glasgow) Although diu- glucose by the jejunum was measured in in these two regions. retics are widely used, little is known of 10 chronic alcoholic patients using a on September 30, 2021 by guest. Protected copyright. their effects on the movements of water triple-lumen tube perfusion system2. A E2 and electrolytes in the small intestine. malabsorption screen was also performed We have studied the effect of frusemide on each patient. The influence ofethacrynic acid and aspirin on small intestinal absorption of water Jejunal histology was normal in every on water and electrolyte secretion induced and electrolytes using a jejunal perfusion patient and only isolated biochemical by prostaglandin E1 in the human jejunum system in man. An isomotic solution con- abnormalities were found in individual taining sodium, potassium, chloride, and patients. However, the mean absorption C. MATUCHANSKY, J. Y. MARY, J. C. bicarbonate in glucose and using phenol- of water in the alcoholic subjects (50 0 ± RAMBAUD, AND J. J. BERNIER (Groupe de sulphonphthalein as a water-soluble 21-3 ml/hr) was significantly lower (p < Recherches sur la Physiopathologie de la marker, was perfused using a double- 0 001) than the mean value in 14 healthy Digestion, INSERM, Hopital St-Lazare, lumen tube with proximal occluding control subjects (205.0 ± 15-9 ml/hr). Paris, France) Intraluminal prostaglan- balloon". After a steady state had been Alcoholic patients also showed a signifi- din E1 (PGE1) promotes a copious jejunal achieved and baseline collections ob- cant reduction (p < 0 001) in the absorp- secretion ofwater and electrolytes in man.1 tained, frusemide was given intravenously tion of sodium (7-5 ± 2-9 m-equiv/hr) To investigate further this secretory effect, in doses of either 20 mg or 40 mg and the when compared to control subjects (23.1 the action of ethacrynic acid (EA) or effect on intestinal absorption determined. ± 1-3 m-equiv/hr); chloride absorption aspirin upon basal jejunal absorption and After 20 mg of frusemide the mean water showed a similar trend. PGE1-induced secretion of water and absorption (± SEM) in five subjects fell Since the availability of adenosine tri- electrolytes was studied in 25 healthy from a baseline of 3-15 ± 1 01 ml/minute phosphate (ATP) plays a significant role volunteers using an intestinal perfusion to 1-39 ± 1-97 ml/minute. Similar falls in the active transport of Na+ and K+ technique (proximal occlusive balloon were obtained with electrolyte absorption. across the intestinal cell membrane, an and glucose-saline isoosmotic solution). After 40mgof frusemidewasadministered in-vitro model was set up to study ATP Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

832 The British Society of Gastroenterology following the exposure of segments of slowly transported as is observed experi- Hospital) Proof that autonomic neuro- guinea pig jejunum to 2% ethanol for mentally. pathy causes gastrointestinal symptoms periods of one hour. ATP levels in seg- References in diabetes is lacking and the site of any ments perfused with Krebs' solution were 'Weir, D. G., Brown, J. D., Freedman, D. S., and such changes is conjectural. A cine radio- significantly higher (p < 0-02) than levels Scott, J. M. (1973). Clinical Science and graphic and manometric assessment of in ethanol-perfused portions. Molecular Medicine, 43, 625-631. oesophageal motor function and the 'Blair, J. A., Johnson, 1. T., and Matty, A. J. (1974). to have These findings suggest that ethanol may J. Physiol., 236, 653-661. gastric secretory response insulin induce changes in jejunal ATP and 'Blair, J. A., and Matty, A. J. (1974). Clinics in been used to study autonomic function in ATPase content which may explain the Gastroenterology, 3, 183-197. a group of 20 diabetics with diarrhoea, inhibition ofintestinal absorption ofwater vomiting, impotence, and bladder symp- and electrolytes found in the chronic E5 toms. alcoholic patients. The electrical measurement of glucose Oesophago-gastric sphincteric tone was low and oesophageal peristalsis although References absorption result- Ilber, F. L. (1971). Alcohol and the gastrointestinal coordinated was of low amplitude tract. Gastroenterology, 61, 120-123. N. W. READ, R. J. LEVIN, AND C. D. ing in delayed oesophageal emptying in 'Cooper, H., Levitan, R., Fordtran, J. S., and HOLDSWORTH (Departments of Medicine the 150 Trendelenburg position. Ingelfinger, M. D. (1966). A method for Bethanecol increased sphincteric tone studying absorption of water and solute and Physiology, University of Sheffield) from the human small intestine. Gastroenter- The active absorption of glucose from the to normal but not to the high levels it ology, 50, 1-7. small intestine is linked to sodium iron does in Chagas disease or achalasia, E5 transfer and is therefore electrogenic. In suggesting that the ganglion cells of the the rat the electrical potential difference myenteric plexus were intact in diabetics. Intestinal absorption of tetrahydrobiop- The Hollander test revealed evidence of terin and pteroic acid in man: A comparison (PD) across the jejunal wall increases with increasing concentrations of luminal glu- complete vagotomy in six of eight diabe- ofmodels for the transport of folates across tics with diarrhoea but was usually the small intestine cose. Plotting PD against glucose con- results in a saturation curve normal in those without. centration a in the J. A. BLAIR, K. RATANASTHIEN, AND R. J. from which the kinetic parameter of These findings indicate lesion LEEMING (Department of Chemistry, Uni- 'apparent Km' can be obtained. In the preganglionic vagal fibres rather than in versity ofAston in Birmingham and General rat this is identical with that obtained by the myenteric plexus which may be an Hospital, Birmingham) (introduced by chemical methods of measuring active important factor in the causation of W. T. Cooke) Biopterin derivatives are absorption. diabetic diarrhoea and could account for present in normal human serum (1-3 ng/ In man the potential difference between the reportedly low incidence of duodenal ml) and urine (1-2 ,tg/ml). When large an intraluminal and a subcutaneous ulcer in diabetics. http://gut.bmj.com/ oral doses of tetrahydrobiopterin are electrode was recorded. Infusion of solu- F2 given to man only slight rises in the serum tions of the same osmolarity and ionic and urinary levels are seen in contrast to composition but containing serially in- Can symptoms or radiographic reflux be the large rises with other tetrahydrop- creasing concentrations of glucose caused predicted by measuring cardiac sphincter terins, eg, 5-methyltetrahydrofolic acid. the jejunal lumen to become progressively pressure? Similarly large oral doses of pteroic acid more negative and a saturation curve was gave no increase in serum and urinary found. The apparent Km in 99 normal J. B. DILAWARI, D. A. W. EDWARDS, AND levels, again in contrast to the substantial volunteers (61-1 mM ± 3-6 SE) was D. H. GIRMES (MRC Gastroenterology on September 30, 2021 by guest. Protected copyright. rises obtained with other pterins, eg, folic significantly higher (p < 0 001) than that Unit, Central Middlesex Hospital, and acid. Thus both compounds are at best found in three patients with malabsorp- Department of Statistics and Computer poorly absorbed through the intestine. tion (23-7 ± 8-0 SE). Science, University College, London) It has been previously suggested' that Kinetic parameters estimated from There is a widespread supposition that human small intestine contains a permease chemical absorption curves are the most low cardiac sphincter pressure is asso- for 5-methyltetrahydrofolic acid which is sensitive method of assessing changes in ciated with reflux and that measurement affected by the stereochemistry at C6 of jejunal function, but are technically diffi- of the pressure indicates whether the the tetrahydropterin ring. These observa- cult in man. This new technique of deter- patient is suffering from reflux. Two hun- tions with tetrahydrobiopterin and pteroic mining electrically the kinetic parameters dred and forty-six subjects with dys- acid suggest that there are no specific of active glucose absorption uses a single peptic symptoms were grouped into carrier systems in the human intestine for lumen tube, is rapid and more clinically 138 with and 108 without symptoms either the tetrahydropterin or pterin ring. acceptable. Because of these features it attributed to reflux. The pressures re- Another model2,3 for the intestinal should find wide application in studying corded by four-channel perfusion mano- transport of folates suggests that they are jejunal absorption function in health and metry of the cardiac sphincter failed to transported as the neutral species through disease. separate the groups. Odds in favour of the the lipoid membrane after conversion to presence of symptoms were calculated; these forms in an acid microclimate at Fl odds better than 19:1 (5 % level of signifi- about pH 3.5. In such a microclimate the Impairment of upper alimentary vagal cance) existed if the pressure was 5 mm concentration of the neutral forms of function in diabetes Hg or less, but only 5 % of all subjects and tetrahydrobiopterin and pteroic acid 9 % of those with symptoms had this would be almost zero and therefore they I. M. STEWART, D. J. HOSKING, B. J. PRESTON, pressure. Two hundred and twenty-one either would not be transported or only AND M. ATKINSON (Nottingham General of the subjects had a standardized Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

The British Society of Gastroenterology 833 radiographic examination for the cap- was 58 %. In contrast the mean reduction F5 acity to herniate the sphincter and for in ulcer profile area in the 27 geranyl radiographic reflux. Reflux of barium farnesylacetate-treated patients was 47 %. The patient's assessment of the result of was seen in 58. The distribution of This difference is not statistically signifi- operation for peptic ulcer sphincter pressures was the same in the cant (p > 01). Side effects occurred in groups with and without radiographic half of the carbenoxolone-treated patients, whereas of the ELIZABETH L. CAY, A. E. PHILIP, W. P. reflux indicating that low sphincter pres- none patients receiving SMALL, M. A. HENDERSON, AND J. NEILSON sure is not the sole cause of radiographic geranyl farnesylacetate developed oedema (Gastric Follow Up Clinic, Western General reflux. Simultaneous herniation of the or electrolyte disturbance. Hospital, Department of Psychological sphincter occurred in those with radio- Medicine, University of Edinburgh, Edin- graphic reflux and this seems the likely References burgh, and Duimfries and Galloway Royal explanation for the failure of the anti- Doll, R. (1964). Scot. med. J., 9, 183. Infirmary, Dumfries) When we seek to reflux mechanism. We conclude that a Newcombe, P. B., Stone, W. D., and Richardson, evaluate a new operation for ulcer, it is random measurement ofcardiac sphincter D. C. (1970). Adv. Abstracts, 4th World in Congress of Gastroenterology, Copenhagen, customary to set up a controlled trial. pressure is unhelpful deciding whether 313. Yet for 15 years or more, controlled a patient has reflux or is suffering from it. trials have failed to distinguish between The use of probability calculations in the various vagotomies, the various decision making of this sort will be drainage procedures, and the various re- discussed. F4 sections and anastomoses. Are there no differences, or have we Effective treatment of gastric ulceration become obsessed with the method and F3 with a Bismuth preparation (De-Nol) neglected the indices on which the judge- ment of success ultimately depends? A double blind trial of carbenoxolone and B. E. BOYES, I. L. WOOLF, R. Y. WILSON, D. J. We believe that doctor-determined criteria geranyl farnesylacetate in gastric ulcer COWLEY, AND I. W. DYMOCK (The Depart- are outdated and too insensitive and that a ments of Medicine and Surgery Univer- new look at what is expected of an opera- P. M. SMITH, G. E. SLADEN, M. J. S. LANGMAN. sity Hospital of South Manchester) Of tion is required. The opinion of the patient AND J. E. LENNARD-JONES (University Hos- drugs known to affect the rate of healing who judges the outcomeofsurgeryin terms pital of Wales, St Bartholomew's Hospital, of gastric ulcers in ambulant patients the of the quality of his life has been largely City Hospital, Nottingham, and University liquorice derivatives are most widely used neglected because it has been thought too College Hospital, London) Carbenoxo- but may produce adverse side effects. difficult to handle 'soft' data of this kind.

lone, a liquorice derivative, has been used Recently a bismuth preparation, tri- But other professions confronted with a http://gut.bmj.com/ widely in the treatment of peptic ulcer potassium di-citrate bismuthate (De-Nol) similar problem have been forced to look since Doll's controlled studies (1964) has been advocated for use in patients at attitudes, and by the use of question- showed that it would significantly in- with gastric ulceration. In order to assess naires have successfully hardened 'soft' crease the rate of healing of gastric ulcer the efficacy of this preparation we have data. in the ambulant patient. Unfortunately, conducted a randomized double-blind From a list of over 100 statements such side effects are common, and we therefore trial of De-Nol in patients with radiologi- as 'everything seems to go straight through decided to compare carbenoxolone with cally and endoscopically proven benign me', 'I wake as fresh as a daisy', used by

geranyl farnesylacetate, a synthetic iso-. gastric ulcers. patients to describe the result ofoperation, on September 30, 2021 by guest. Protected copyright. prenoid extracted from white headed Of the 20 patients admitted to the trial a preliminary inventory of 53 items was cabbage previously shown to aid ulcer 10 received De-Nol and 10 an identical made and tested on 66 postoperative healing (Newcombe, Stone, and placebo. These two groups were com- patients. These patients had been treated Richardson, 1970). parable with reference to age, sex, and in two different centres and had an opera- Fifty-seven ambulant patients were ran- ulcer type at the start of the trial. Seven tive outcome ranging from success to domly allocated to the two groups, one of the 10 patients receiving the active failure. receiving carbenoxolone 100 mg tds and preparation had complete radiological Statistical analysis of their replies shows the other geranyl farnesylacetate 100 mg healing of the ulcer but only two of those that the response to the 53 items can be tds. At entry into the trial the groups were receiving the inert preparation. Endo- accounted for by three underlying factors similar with respect to age and sex, each scopically nine of the 10 treated by De- or dimensions. The first of these draws patient having had a barium meal not Nol healed compared with three in the together statements reflecting psycho- more than five days beforehand. The placebo group. The mean percentage social state after surgery, the second links surface area of the ulcer profile was reduction in the cross-sectional area of the items concerning specific gastric state determinedindependentlybyoneof us, and ulcer asjudged by comparable radiographs after surgery, while the third is a dimen- again four weeks later at the end of treat- was 91 % in the treated group and 36% in sion of general physical well being.; ment. Weekly recordings were made of the control group. None of the patients These preliminary results indicate that blood pressure, weight, and ulcer symp- developed side effects during therapy, and it is possible to assess the quality of a toms. Plasma electrolytes were measured there was no evidence of drug toxicity. patient's life after surgery in a way which at the beginning and end of the trial. This degree of healing with De-Nol is is simple, brief, and open to public Fifty-two patients completed the comparable to or better than that achieved scrutiny. Since these measures obtained by trial. Of the 25 who received carbenoxo- by the most extensively used ulcer-healing means of a self-administered inventory are lone, mean reduction in ulcer profile area agent, carbenoxolone sodium. quantified, their value as indices can be Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

834 The British Society of Gastroenterology put to the test by relating them to clinical stitute of Child Health, University of are also found in mice in the course of state and other relevant criteria. Birmingham) The appearance of agglu- local CMI to tuberculoprotein, and in rats tinating antibodies in the duodenal secre- infected with the parasite Nippostrongylus F6 tions was measured serially in a group of brasiliensis (associated with a thymus- 15 infants (aged 1 month to 2 years) dependent immune reaction in the small Long-term effects of truncal, selective, and with enteropathic E. coli (EPEC) gastro- intestine). highly selective vagotomy on gastric secre- enteritis. The specificity of these anti- Local CMI may cause the crypt hyper- ition in man bodies was measured against a panel of plasia of coeliac disease, giardiasis, etc, EPEC, before and after absorption but is unlikely to be the cause of entero- M. J. GREENALL, P. J. LYNDON, J. C. with a suspension of the specific infecting cyte damage in these conditions. It should GOLIGHER, AND D. JOHNSTON (University organisms. The immunoglobulin (Ig) be possible to test this theory by measuring Department of Surgery, The General classes of the antibodies were assessed by secretion of lymphokines by jejunal biop- Infirmary, Leeds) Preservation of the absorption of the intestinal secretions with sies in short-term organ culture. vagal nerve supply to the antrum of the specific anti-Ig antisera. stomach as in HSV allows the antral mill The antibody response in the duodenal References and the pyloric sphincter to be kept intact. secretions was measurable within three 'Ferguson, A., and Parrott, D. M. V. (1972). Side effects of gastric surgery are thereby days of infection, and reached a peak at Clin. exp. Immunol., 12, 477. diminished. However, reports of signifi- 10 to 14 days. IgM antibodies were found 'Ferguson, A., and Parrott, D. M. V. (1973). cant increases in acid output during the early in the response, and were the only Transplantation, 15, 546. first year after HSV and of an increasing detected antibodies in the youngest in- incidence of positive Hollander responses fants. IgA antibodies were found pre- have led to fears that the incidence of re- dominantly in later specimens, obtained G3 current ulceration might be prohibitive towards the peak of the agglutinin re- after HSV. sponse. Histocompatibility antigens in coeliac We compared basal (BAO), penta- In three infants, a poor secretory anti- disease gastrin-'maximal' (PAOPS) and insulin- body response was associated with severe stimulated (PAOI) acid and pepsin out- clinical illness. R. FERGUSON, P. ASQU1TH, AND W. T. puts in patients who had undergone TV + It is concluded that the antibody re- COOKE (The Nutritional and Intestinal P (n = 20), SV + P (n = 15), or HSV sponse of the small intestine in EPEC Unit, The General Hospital, Birmingham) (n = 25) more than four years previously. gastroenteritis may be an important Since approximately 80% of coeliac The three groups were w-ll matched and factor in determining the clinical outcome. patients possess HL-A 81 and histocom- each patient had had a negative insulin patibility antigens are closely linked with http://gut.bmj.com/ test one week after operation. immunological reactions2 the question Mean BAO (± ISE) were: TV, 1I1 G2 arises as to whether coeliacs without (+ 0 4); SV 1416 (± 04); HSV 1P50 (± HL-A 8 are a distinct subpopulation from 04. Tissue damage mediated by lymphocytes in those with HL-A 8 and show a different Mean PAOP" (iSE) were: TV 16-7 local small intestinal immune reactions immunological reaction to gluten. (± 641); SV 13-1 (± 6 0); HSV 23-80 (± To study this possibility the presenting 3 42). ANNE FERGUSON AND T. T. MCDONALD (Uni- clinical features, haematological and bio- Mean PAOI (+ ISE) were: TV 3-5 versity ofGlasgow, Department ofBacteri- chemical status, and morphological param- on September 30, 2021 by guest. Protected copyright. 1-7); SV 1P72 (+ 0 6); HSV 5-21 (± 1-05). ology and Immunology, Western Infirmary, eters of immunological reactivity have None of the differences between groups Glasgow) The villi of mammalian small been compared between 19 HL-A 8 was statistically significant. Pepsin outputs intestine contain lymphoid cells, of which coeliacs and 13 'non-8' coeliacs. The after HSV were also no higher than after only a small proportion are thymus- effect on these factors of gluten with- TV or SV. Eighty-five per cent of patients dependent lymphocytes'. No physiological drawal of at least one year's duration was had Hollander-positive insulin tests after role for intestinal T lymphocytes has yet also examined. Results show a significant HSV but only 60 % were positive after TV been defined. However, experiments in increase in serum globulin levels and a or SV. rodents suggest that a local cell-mediated decreased lymphocyte population in the These findings lend little support to the immune (CMI) reaction may itself con- lamina propria of the jejunum in the idea that the incidence of recurrent ulcera- tribute to tissue damage in small intestinal HL-A 8 group when receiving gluten. No tion will be high after HSV. To date, in disease. such differences are found on gluten Leeds, in 250 patients, the incidence of (a) In rejection of allografts of mouse withdrawal, nor in the other parameters recurrence is nil in a follow-up period of small intestine , T lymphocyte-mediated determined suggesting there may indeed 0 to five and a halfyears. reaction causes crypt hyperplasia and be a difference in immunological reacti- villous atrophy; however, the morphology vity to gluten between coeliacs with and Gl differs from that of human jejunum in without HL-A 8. coeliac disease in that in rejection the Agglutinating antibodies in the duodenal enterocytes appear normal; there are References secretions of infants with enteropathic E. many lymphocytes but few plasma cells in 'Stokes, P. L., Asquith, P., Holmes, G. K. T. coli gastroenteritis the lamina propria, and relatively few Mackintosh, P., and Cooke, W. T. (1972). Lancet, 2, 162-164. intraepithelial lymphocytes. 'McDevitt, H. O., and Bodmer, W. F. (1972). Amer. A. S. MCNEISH, H. GAZE, AND N. EVANS (In- (b) Villous atrophy andcrypt hyperplasia J. Med., 52, 1-8. Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

The British Society of Gastroenterology 835 G4 significantly raised only in those cases in arachis oil (breakfast 3551; SEM 200; severe relapse (p < 001): those in re- arachis oil 2579; SEM 93; t = 2 94, p < Evidence of immunodeficiency in patients mission did not differ from the control 0 02). The breakfast stimulus was re- with coeliac disease group. C, levels in the postcolectomy producible in these subjects on two further group were also significantly elevated tests. P. G. BAKER, J. VERRIER JONES, D. B. (p < 0-01). A similar though less exag- Seven patients who had had a truncal PEACOCK, AND A. E. READ (Departments of gerated disturbance was seen in C3 levels. vagotomy and drainage were then studied. Medicine and Bacteriology, University of These findings suggest: (1) additional The results showed a highly significant Bristol) #X 174 is a potent antigen which support for the role of complement in the difference from normals (normals; IGR = has been used to study antibody produc- pathogenesis of Crohn's disease and 3076 ± 460, vagotomy and drainage: tion in animals and in normal subjects ulcerative colitis; (2) differences in comple- IGR = 6150 ± 804, t = 3-63; P < 0 01). (Peacock et al, Clin. exp. Immunol., 43, ment metabolism between the two diseases These results suggest that a standard 1973). There is evidence for hyposple- when in apparent remission; (3) a persist- 'English' breakfast is the most satisfactory nism in a proportion of patients with ing disturbance of complement metab- stimulus for the initial investigation of coeliac disease, and impairment of anti- olism in some cases of ulcerative colitis patient with equivocal fasting plasma body production has been reported treated several years previously by total gastrin levels. (Pettingale, K. W., Clin. Sci., 38, 1970, colectomy. 16p). H2 Eight patients (two untreated) with References adult coeliac disease were given primary "Doe, W. F., Booth, C. C., and Brown, D. L. (1973). Experimental hypergastrinaemia and an- and secondary injections ofOX 174. Three Lancet, 1, 402-405. tral-gastrin-cell hyperplasia in dogs patients showed gross impairment of 'Ballard, J., and Shiner, M. (1974). Lancet, 1, 402- 403. primary antibody production, and the H. M. JENNEWEIN, P. C. GANGULI, F. secondary response for the whole group WALDECK, R. SIEWERT, J. M. POLAK, AND was significantly lower than that of 40 Hl A. G. E. PEARSE (Pharmaforschung-Biologie, normal subjects. There was a marked C. H. Boehringer Sohn, Ingelheim-Rhein, association between hyposplenism and a Provoking gastrin release-which stimulus? University Department of Surgery, poor secondary response. Royal Infirmary, Manchester, Klinik und This study provides strong evidence for L. P. FIELDING, R. C. G. RUSSELL, AND S. R. Poliklinik fur Allgemeinchirurgie der Uni- impaired antibody production in coeliac BLOOM (Surgical Unit, St Mary's Hospital, versitdt, Gottintgen, Department of Histo- disease. London) (Introduced by J. G. Walker) In chemistry, Royal Postgraduate Medical our experience there is an overlap in the School, London) In order to investigate http://gut.bmj.com/ G5 level of fasting plasma gastrin between the chronic hypergastrinaemia and G-cell Zollinger-Ellison syndrome and the upper hyperplasia in dogs with Heidenhain Serum complement components C, and C4 limit of normal. The response of the pouches, the antrum was separated from in inflammatory bowel disease plasma gastrin to a protein stimulus helps the rest of the stomach by a mucosal to discriminate between these two groups. septum or by complete division. The M. WARD AND M. A. EASTWOOD (Wolfson We have therefore sought to standardize gastroduodenal junction was either left Gastrointestinal Laboratories, Western a 'test meal' of this kind. intact or a pyloroplasty was performed. General Hospital, University ofEdinburgh, Seven fasting subjects were studied Gastric secretion was collected from the on September 30, 2021 by guest. Protected copyright. Edinburgh) The finding of an increased with: Heidenhain pouches and the acid output incidence of serum precipitin reactions to (1) Calcium caseinate was determined by titrating to pH7. complement component C,q in ulcerative lOOg Gastrin levels were measured pre- and colitis and Crohn's disease' and of C, (2) Composite packaged postoperatively by radioimmunoassay. In deposition in the rectal mucosa of patients food 100 g some samples the gastrins were separated with ulcerative colitis2, has raised the (3) Calcium carbonate Made up to according to their molecular size, employ- possibility of a role for complement- 2 g 300 ml with ing a 1 x 200 cm Sephadex G-50 SF binding immune complexes in the patho- (4) Beef extract 25 g tap water column. Between two and four months genesis of inflammatory bowel disease. (5) Milk 300 ml after operation the antra were examined In the present study serum C3 and C4 (6) Arachis oil emulsion for the number of G-ells present (immu- component levels were estimated by radial 100 ml nofluorescence histological technique). immunodiffusion in 30 patients with (7) 'English' breakfast Distinct hypergastrinaemia and acid ulcerative colitis; 13 patients who had Three preliminary blood samples were hypersecretion had developed in dogs undergone total colectomy for ulcerative taken followed by specimens at 15-minute where the antrum was separated from the colitis from two to 14 years previously; intervals for two hours. Plasma gastrin stomach by a mucosal septum leaving the 32 patients with Crohn's disease; and 14 was measured by radioimmunoassay; gastroduodenal junction intact. Gastrin healthy controls. statistical significance was assessed by levels rose to 500 pg/ml (normal 50-80 Significantly elevated C4 levels were paired Student t test. pg/ml). Analysis of the gastrin pattern found in the Crohn's disease group as a The integrated gastrin response (IGR showed a predominance of little gastrin whole (P < 0 01), including those patients = area under curve, pg/2 hr) was the components. The elevated gastrin levels in apparent remission (P < 0 01). In the largest after the breakfast and was signifi- could be suppressed by secretin. Although ulcerative colitis group, C4 levels were cantly different from the next largest, there was a marked hypersecretion in most Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

836 The British Society of Gastroenterology of the dogs with hypergastrinaemia, no antrum in preventing symptomatic duodeno- vity is directly transported from the antral -close correlation between these param- gastric reflux mucosa to the body of the stomach. In the eters was evideWt. In two of three of the second experiment occlusion of all blood dogs with hypcastrinaemia there was a M. R. B. KEIGHLEY, P. ASQUITH, A. HOARE, vessels feeding the stomach arrested the demonstrable G-cell hyperplasia. AND J. ALEXANDER-WILLIAMS (The General transfer of activity from the antrum to the Hospital, Steelhouse Lane, Birmingham) body, in the third experiment division of H3 After gastric operations, dyspeptic symp- the stomach at the antral-body junction toms have been shown to be related to obviated the transfer of activity from the A comparison of basal and stimulated duodenogastric reflux. A prospective antrum to the body but activity was still gastric and pancreatic secretion in patients randomized trial was therefore conducted transferred to the liver. Finally in the in- with and without duodenal ulcer disease to compare the incidence of duodenal tact stomach activity was seen to be reflux after an operation designed to pre- transmitted from the body to the antrum L. V. GUTIERREZ AND J. H. BARON (Depart- serve an innervated intact antro-pyloric of the stomach. ment of Surgery, Royal Postgraduate mechanism: proximal gastric vagotomy In man a similar study has been em- Medical School, London, England) Duo- (PGV) and one in which the antrum and ployed which illustrates the direct transfer denal hyperacidity in patients with duode- pylorus was removed, vagotomy and of radioactivity from the antral mucosa nal ulcer disease may be due to gastric antrectomy (TV + A). to the body of the stomach using a y- hypersecretion and/or decreased duodenal Assessment of 24 patients before and camera. neutralization. Basal gastric secretion and after operation was by a symptomatic A 'portal system' has been demon- the maximum response to pentagastrin score based on a questionaire, measure- strated between the mucosa of the an- (6 ug/kg im) and basal secretion into the ment of the concentration of bilirubin in trum and the body of the stomach through duodenum and its maximum response to four samples of fasting gastric juice, which gastrin could be directly trans- intravenous secretin were measured in 20 endoscopic appearances, gastric biopsy, ported from G cells in the antrum to act (12 male) control subjects (aged 24-69) and a radiological study of reflux. directly on the parietal cell mass before and 10 patients (nine male) with duodenal There was a significant correlation being diluted by the systemic circulation ulcer disease (aged 27-68). between the concentration of bile in the and being excreted in the liver and other In control subjects the volumes (but not fasting gastric juice and radiological re- sites. concentrations or outputs) of stimulated flux (P < 0 01), also betweendyspepsiaand gastric and duodenal secretions were duodeno-gastric regurgitation (P < 0-05). Reference Sapirstein, L. A. (1958). Regional blood flow by the significantly correlated (r = 0-73, p < The relationship between reflux and histo- fractional distribution of indicators. Amer. 01001). In patients with duodenal ulcer, logical gastritis, however, did not reach J. Physiol., 193, 161-166. there were no significant correlations statistical significance (P < 01). Radio- http://gut.bmj.com/ between basal gastric and duodenal secre- graphic reflux was observed in five H6 tion, but after stimulation both volumes (r patients before operation (21 %), in two = 0 85, p < 0 01) and outputs (r = 0'86, patients after PGV (17%), and in seven Protein synthesis and secretion in cultured p x 0101) (but not concentrations) of following TV + A (58 %). rabbit gastric mucosal biopsies gastric and duodenal secretions were We confirm that after ulcer curative significantly correlated. The bicarbonate surgery there are a number of patients D. R. SUTTON AND R. M. DONALDSON secretory capacity in patients with duode- with moderately severe symptoms asso- Hospital) Investiga- (Nottingham General on September 30, 2021 by guest. Protected copyright. nal ulcer (mean 32-2 mmol/h) was com- ciated with duodenal reflux. The re- tion of gastric metabolic function in parable with their gastric acid secretory sults of this trial also suggest that an animal models is limited by inability to capacity (34 5 mmol/h) and similar to the operation designed to preserve an intact isolate the stomach from all extraneous bicarbonate secretory capacity in control and innervated antro-pyloric mechanism influences while culture of gastric tissue subjects (31V8 mmol/h). will protect against duodenal reflux and has only previously been achieved While in control subjects basal acid symptoms. using free cell suspensions which are only output (1P2 mmol/h) was only one and one viable for a few hours. half times the basal bicarbonate output, H5 We report the successful culture of in patients with duodenal ulcer basal acid rabbit gastric mucosal biopsy tissue in output (3 3 mmol/h) was almost seven Is there an antral-body portal system in the which a steady state of protein synthesis times basal bicarbonate output. Thus, the stomach? and secretion was maintained for 24 basal bicarbonate output in patients with hours. Characterization of the secretion duodenal ulcer (05 mmol/h) was only T. V. TAYLOR AND H. BRUCE TORRANCE suggested that most protein was pepsino- half that in control subjects (0-8 mmol/h), (Department of Gastroenterology, Royal gen. Protein synthesis was stimulated by perhaps another example of the failure of Infirmary, Manchester) The direction of pentagastrin while secretion was enhanced the duodenum in patients with duodenal blood flow within the stomach has been by acetylcholine, pentagastrin, secretin, ulcer to respond to a gastric acid load studied in the rat and in man. In four basic and cholecystokinin. These gastro- in spite of the normal bicarbonate secre- experiments carried out on groups of six intestinal hormones only effected secretion tory capacity. rats the transport of the isotope Rb86CI, in the presence of a background of acetyl- which is extracted from the blood stream choline. This type of organ culture allows H4 to the tissues, has been studied (Sapistein, synthesis and secretion of various macro- 1958). molecules to be studied in detail for pro- The importance of an innervated intact The first experiment showed that acti- longed periods. Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

The British Society of Gastroenterology 837 JA 'in-vivo' dialysis method (Wrong et al, of a single standard chest radiograph. The 1961) in six control subjects, and 12 high count rate obtained with 1as3I-BSP HypercataboHsm of third component of patients with liver disease including six safely allows good gamma camera defini- complement in pimary biliary cirrhosis who had had portocaval shunts. tion of space-occupying lesions and 99mTc- In the patients with shunts, the con- albumin enables blood pool scanning in B. J. POITER, E. ELIAS, AND E. A. JONES centration of ammonia in faecal dialysate these cases. Liver, gallbladder, and gut (Departments of Medicine, Royal Free was similar to that of controls; in patients activity may be seen showing the level of Hospital, London, and University of without shunts, the faecal concentration surgical obstruction. A more accurate Liverpool) Complement-mediated im- of ammonia was raised. In the patients estimate of bile output is obtained than by mune injury is one of the possible mecha- with shunts the concentration of ammonia compartmental analysis of plasma clear- nisms by which small bile ducts may be in the peripheral blood was signifi- ance curves of chemical BSP. In non- damaged in primary biliary cirrhosis cantly higher than those without shunts; obstructive liver disease deconvolution (PBC). Evidence consistent with activa- both were higher than in control subjects. analysis of blood clearance and bile out- tion of the complement system was sought Sodium concentrations in the faecal put curves gives a distribution of BSP by (1) analysing the plasma radioactivity dialysates of patients with shunts were transit times. In seven normal subjects curve and urinary excretion of radio- significantly decreased compared with the first peak of this distribution is narrow activity" after the intravenous administra- those from patients without shunts, or and unimodal with a mean transit time of tion of pure undenatured radioiodinated controls, while the potassium concentra- less than 10 minutes. In cases of intra- C3' and (2) screening sera for conversion tions were increased. These findings hepatic cholestasis, eg, primary biliary cir- products of C3 using Laurell crossed suggest a state of hyperaldosteronism. rhosis, this distribution becomes widened immunoelectrophoresis3 and specific anti- It is suggested that following a shunt and the mean transit of the first peak C3 antiserum. there is an increased absorption of ammo- time greatly prolonged. The metabolism of 1251-C3 was studied nia from the colon into the portal circu- The BSP transit time distribution is a in seven patients with PBC and five normal lation. This increased absorption of promising way of characterizing different control subjects. The fractional catabolic ammonia is one factor contributing to liver diseases and we present results in a rate of C3 was higher in PBC (430% the hyperammonaemia, and possibly variety of disorders. intravascular pool/hr ± 0 94; mean ± hepatoportal encephalopathy, found after 1 SD) than in normals (2-04 ± 020) shunt. J4 (p < 0O0005). There was no overlap between the plasma 1512-C3 disappearance Reference The influence of chronic liver disease on curves in PBC and normals. The synthetic the elimination of anti- Wrong, 0. M., Morrison, R. B. I., and Hurst, P. E. d-propranolol, http://gut.bmj.com/ rate of C3 also was higher in PBC (3-10 (1961). A method of obtaining faecal fluid pyrine, and indocyanine green mg/kg/hr + 1P59) than in normals (105 + by in vivo dialysis. Lancet, 1, 1208-1209. 031) (p < 001). Three of the plasma R. A. BRANCH, J. A. JAMES, AND A. E. disappearance curves of 12SI.-C3 failed to READ (University Department ofMedicine, reveal an early terminal exponential J3 Royal Infirmary, Bristol) Many factors decline, suggesting that some C3 may be can influence drug pharmacokinetics in converted to a metabolic product, pos- An approach to the diagnosis of liver patients with chronic liver disease. This sibly C3d, which is catabolized more disorders using 1231-BSP assesses study the relative importance of on September 30, 2021 by guest. Protected copyright. slowly than C3. In the serum of one drug-metabolizing activity and liver blood patient conversion products of C3 were A. REUBEN, K. NARASIMAH, M. MYERS, T. flow for a rapidly metabolized drug, d- demonstrated. WOOD, AND K. BRrrON (Institute of propranololl, and a slowly metabolized The results suggest that the complement Nuclear Medicine, Middlesex Hospital, one, antipyrine2. Twenty patients with system may be activated in PBC. London, England) The differentiation of stable chronic liver disease and six Referenices 'surgical' jaundice from intrahepatic cho- healthy controls received 40 mg iv d-pro- lestasis, the detection of liver disease pranolol, 1200 mg oral antipyrine, and 'Nosslin, B. (1973). Ciba Foundation Symposium, before biochemical changes in the blood, 0 5 9, 113. mg/kg indocyanine green, to measure 'Nilson, U. R., and Muller-Eberhard, H. J. (1965). and the demonstration of space-occupying liver blood flow (LBF), on separate J. exp. Med., 122, 277. lesions and their pathology are areas of occasions. 'Minchin Clarke, H. G., and Freeman, T. (1968). diagnostic importance. A method of in- The half-life of each drug increases in Clin. Sci., 35, 403. vestigation is described which is appli- chronic liver disease, the increase being cable to each of these problems, using more marked in patients with severe J2 123I-BSP. Blood clearance and hepatic up- liver disease. The serum albumin and take curves, and in addition liver and gall- bilirubin correlated significantly with the The effect of portocaval shunt on colon bladder pictures, are obtained using ex- half-lives of each drug. There were also &Waer of ammonia in cirrhosis of the ternal gamma camera monitoring follow- significant correlations between the half- liver ing a small intravenous injection of lives of individual drugs. A comparison of 1"3I-BSP (< 100 mg) after O9mTc-albumin the intrinsic metabolic clearance, an indi- MAUNG MAUNG SEIN, ANNE HARDY-SMITH, is injected as a background marker. cator of drug metabolizing efficiency AND. R. SHIELDS (Department of Surgery, Jaundice does not interfere with the independent of LBP, was made with University ofLiverpool) Faecal ammonia measurement unlike chemical BSP. The LBF and actual drug clearance; the and electrolytes were measured using an radiation dose is approximately one tenth decreases in actual drug clearance of anti- Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

838 The British Society of Gastroenterology pyrine and d-propranolol are mainly Hepatic lysosomes from iron over- Kl due to a reduction in intrinsic metabolic loaded rats were also shown to be more clearance. However, patients with a fragile than normal. Using sucrose gra- Biochemical studies of pure pancreatic normal serum albumin but a reduced dient centrifugation these lysosomes were juice obtained by duodenoscopic cannu- LBF had a reduced clearance of d-pro- found to be very dense because of accu- lation of the pancreatic duct in conscious pranolol but not of antipyrine. In conclu- mulated insoluble iron compounds within patients sion, the rate of elimination of a drug them. depends more on the drug metabolizing It is suggested that accumulation of P. B. COTTON, M. CREMER, P. ROBBERECHT, activity of a damaged liver than on its excess iron, probably as haemosiderin, AND J. CHRISTOPHE (St Thomas's Hospital, blood supply. However if the metabolic within hepatocyte lysosomes leads to and Middlesex Hospital, London H6pital activity is high, a fall in LBF will decrease disruption of these organelles and this Universitaire Brugmann, and Laboratoire the rate of actual drug elimination. initiates cell damage. de Biochemie, Universite libre de Bruxelles, Belgium) In 27 patients undergoing endoscopy and retrograde cholangio- References J6 pancreatography (ERCP), it has been 'Shand, D. G., and Ragno, R. E. (1972). Disposi. possible to obtain pure secretions from tion of propranolol. Pharmacology, 7, 159. Prolonged survival in the Crigler-Najjar within the pancreatic duct. Intravenous 'Branch, R. A., Herbert, C. M., and Read, A. E. syndrome: Ultrastructural and dietary injection of secretin (Boots, 1 unit/kg) (1973). Determinants of antipyrine half- produced a brisk flow, varying in appa- lives in patients with liver disease. Gut, 14, studies 569. rently normal patients from 2-7 to 8-0 'Rowland, M., Benet, L. Z., and Graham, G. G, J. L. GOLLAN, S. N. HUANG, B. H. BILLING, ml/minute. In patients with definite pan- (1973). Clearance concepts in pharmaco. creatic pathology, the response range was kinetics. J. Pharmacokin. Biopharmacol., 1, AND S. SHERLOCK (Department of Medi- 123. cine, Royal Free Hospital, Gray's Inn 0-94 ml/minute. Further injections of Road, London) Three brothers, who had pancreozymin (Boots 1 unit/kg) or ceru- been deeply jaundiced for over 50 years, lein (20 ng/kg) were given, and collections J5 have been studied. Although their plasma continued each minute for up to 40 min- unconjugated bilirubin concentrations utes. Pancreatic juice sodium and potas- Lysosomal changes in human and experi- (UCB) were greater than 20 mg per 100 sium concentrations remained constant mental iron overload ml they showed no abnormal neurological in each patient. Despite immediate freez- signs. Prolonged exposure to severe Un- ing ofsamples, marked loss ofbicarbonate C. A. SEYMOUR, G BUDILLON, AND T. J. conjugated hyperbilirubinaemia does not occurred unless paraffin was added. In PETERS (Department of Medicine, Royal therefore necessarily increase morbidity. samples so protected, measured bicarbo- nate concentration closely resembled the Postgraduate Medical School, London) Conventional tests ofliver function were http://gut.bmj.com/ Little is known of the mechanism of normal and on light microscopy the only difference between chloride concentra- tissue damage in iron storage diseases. abnormality of liver histology was tion and the sum of sodium and potas- Lysosomal disruption has been implicated occasional bile plugs in undilated bile sium concentrations. The minimal chlor- as a possible mechanism of cell damage. canaliculi. Electronmicroscopy showed ide concentration and maximum bicar- Therefore the lysosomal changes in liver hypertrophy and hyperplasia of smooth bonate concentration were achieved within biopsies from patients with iron overload endoplasmic reticulum with unusual five to 10 minutes of secretin injection. due to haemochromatosis or secondary prominence of the Golgi apparatus. Focal Calculated bicarbonate concentrations haemosiderosis were studied. The specific modification of the cell surface mem- varied little between normal and ab- activities (milliUnits per milligram pro- branes was also evident. These changes normal patients (normals 115-143 m- on September 30, 2021 by guest. Protected copyright. tein) of six acid hydrolases (acid phos- may be implicated in the transport of equivll; definite abnormals 86-133 m- phatase, /-glucuronidase, N-acetyl-fl-glu- unconjugated bilirubin from the hepato- equiv/l). Maximum bicarbonate output cosaminidase, ox-glucosidase, /3-galacto- cyte. ranged from 90 to 1200 4-equiv/minute. sidase, acid diesterase) were two to 10 Dietary restriction for 72 hours to 400 The concentrations of protein and hydro- times higher in biopsies from patients with calories per day produced a dramatic lases (lipase, amylase, chymotrypsinogen) iron overload than in biopsies from con- increase in UCB. The addition of 2400 reached a sharp peak within two minutes trol subjects or patients with other chronic calories by the intravenous administra- of a stimulus. The responses varied con- liver diseases. This suggests an accumula- tion of 50% dextrose did not reduce the siderably between patients, and in rela- tion of undegradable material within the elevated UCB. In contrast, when 2400 tion to bicarbonate secretion. lysosomes. calories was fed as a normal diet the UCB This method of collecting pure pancre- Determination of lysosomal integrity returned to basal levels. While on pheno- atic juice in conscious man provides a new in these biopsies (latent N-acetyl-3-glu- barbitone therapy (which caused a reduc- avenue for research into pancreatic cosaminidase and sedimentable acid hy- tion of UCB to 4 mg per 100 ml within physiology and pathophysiology. drolases) showed that these organelles two weeks) the response to caloric with- were particularly fragile. No such changes drawal and parenteral feeding was similar. K2 were found in biopsies from patients with These results indicate that the hyper- Studies on the nature of cholecystokinin- cryptogenic cirrhosis or other chronic bilirubinaemia of fasting is not just pancreozymin in small-intestinal mucosal liver diseases. After iron was removed by attributable to caloric deprivation and extracts venesection these parameters returned suggests that the type of diet may in- to normal. fluence the degree of hyperbilirubinaemia. R. F. HARVEY, LYNDA DOWSETT, AND A. E. Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

T7he British Society of Gastroenterology 839 READ (University Department of Medicine, SARLES(Unit6de Recherches de Pathologie K4 Bristol Royal Infirmary, Bristol) The Digestive de l'INSERM 46, chemin de la cholecystokinin-pancreozymin (CCK) iso- Gaye, 13009, Marseille, France) In The proximal jejunal mucosa in colonic lated from small-intestinal mucosa by previous studies' , the action of ethanol Crohn's disease and ulcerative colitis Jorpes and Mutt is a 33-amino acid pep- on the dog pancreas was studied in non- tide". In order to determine whether other alcoholic animals and in animals sub- R. FERGUSON, R. N. ALLAN, AND W. T. CCK-like peptides are present in the mitted to short duration consumption of cooKE (The Nutritional and Intestinal small intestine, we have used gel filtration ethanol. Unit, The General Hospital, Birmingham) to study the properties of the CCK in Twelve dogs were provided with chronic Morphological abnormalities of the jeju- small-intestinal mucosal extracts. CCK pancreatic and gastric fistulae (Thomas num have been reported in inflammatory like imrnmunoreactivity was measured by a cannula); six served as control, and six bowel disease1 2. We have studied the sensitive radioimmunoassay, using an were alcohol fed (2-0 g/kg) for two years. mucosal cell population of the proximal antiserum (MS6/72) reacting at the bio- In chronic alcoholic animals, the follow- jejunum in 26 patients with Crohn's logically active (C-terminal) end of the ing changes were observed: disease of the colon and for comparison molecule'. 1 After a test meal, either alone or that in 20 randomly selected patients with During passage through Sephadex associated with 50% intragastric (ig) ulcerative colitis and in 20 normal con- G-50 columns (30 x 500 mm), CCK- ethanol (1 0 g/kg) gastrin blood levels are trols. Our results show that a significant like immunoreactivity separated into higher and better sustained, increase (p < 0-005) in the plasma cell three distinct components. Onecomponent 2 Accordingly, when pancreatic secre- population of the lamina propria occurs 'corresponded in elution position to tion is stimulated by a continuous secretin with both ulcerative colitis and Crohn's Jorpes-Mutt CCK, one had apparently (GIH, 10 CU/kg/h) and CCK-PZ (GIH, disease in comparison to normal controls, a greater molecular weight than this 3 0 CHR U/kg/h) perfusion and gastric even in those cases with previous colec- ('big' CCK), and the third component content is prevented from entering the tomy. In addition, patients with Crohn's eluted in a position similar to that of the duodenum, an acute ig 15 % ethanol disease have significantly higher (p < C-terminal octapeptide of CCK. A administration (1 3 g/kg) elicits a higher 0O05) plasma cell populations than subjects 'little' CCK component, also similar to pancreatic protein secretion, with ulcerative colitis. This increase in the octapeptide in its elution character- 3 Xylocaine spraying of the duodenal plasma cells is not related to the severity istics, could be produced by incubating papilla every 10 min for two h evokes an of illness, extent of disease, nutritional either 'big' or Jorpes-Mutt CCK with increase mainly on the protein pancreatic state, or therapy in Crohn's disease, in trypsin at 35°C for two hours. secretion plateau values. This effect is contrast to patients with ulcerative colitis, As the biological activity of the C- more marked in alcoholic animals, where exacerbation of disease was asso- terminal octapeptide is considerably 4 The increase of the different CCK- ciated with a greatly elevated plasma http://gut.bmj.com/ greater than that of Jorpes-Mutt CCK', secretin-induced pancreatic secretory cell infiltrate. These findings are also these findings suggest that a large part of values elicited by an acute iv ethanol infu- significantly different from the results of the CCK-like biological activity of sion (1 3 g/kg) on the alcohol-fed dogs is we have observed in coeliac disease'. tisssbe extracts may result from the action abolished by atropine (I10 mg/kg/h) but of a relatively small C-terninal fragment, not by a pentolinium perfusion (0-75 mg/ References which is possibly identical with the octa- kg/h): the iv ethanol-evoked stimulation 'Salem, S. and peptide. Such a fragment may be produced ofpancreatic secretion is exerted through a M., Truelove, S. C. (1965). Brit. med. J., 1, 827-831. on September 30, 2021 by guest. Protected copyright. in vivo by enzymes acting on the larger cholinergic mechanism triggered at the 'Hermos, J. A., Cooper, H. L., Kramer, P., and cholecystokinins. hypothalamic bulbar centres on Trier, J. S. (1970). Gastroenterology, 59, and/or 868-873. non-nicotinic receptors of the intrapan- 'Ferguson, R., Asquith, P., and Cooke, W. T. creatic ganglia, (1974). Gut (in press). 'Jorpes, J. E., and Mutt, V. (1973). Secretin, chole- 5 Dose response curves to GIH secre- cystokinin, pancreozymin and gastrin. tin Handbook of Experimental Pharmacology. perfusion (0-5 to 0-8 CU/kg/h) shows K5 vol. 34. Springer, Berlin, pp. 1-179. a higher maximal bicarbonate output than 'Harvey, R. F., Lynda Dowsett, Hartog, M., and in the control. This ethanol-induced Bidirectional sodium flux across the Read, A. E. (1974). Radioimmunoassay of increase in the mass and/or number of intestinal mucosa in Crohn's disease cholecystokinin-pancreozymin. Gut (in press). 'pancreon' units must be related, at least 'Rubin, B., and Engel, S. L. (1973). Some biological in part, to the trophic effects of raised R. N. ALLAN, D. M. STEINBERG, K. DIXON, characteristics of cholecystokinin (CCK-PZ) levels of gastrin and CCK-PZ. AND W. T. COOKE (Nutritional andIntestinal and synthetic analogues. Frontiers in gastro- intestinal hormone research. Nobel Sympo- Unit, The General Hospital, Birmingham) 'sium 16. Andersson, S. Ed. Almqvist and Refwenc We have observed that patients treated Wiksell, Stockholm, pp. 41-56. 'Tiscornia, O., Gullo, L., Sarles, H., Devaux, M. A., by panproctocolectomy and ileostomy for Michel, G., and Grimaud, R. (1973). Diges- Crohn's colitis are more prone to epi- K3 tion, 9, 231-240. Gastroenterology (abstract) sodes offlux than a similarly treated group 62, no. 4, 866 (1972). of patients with ulcerative colitis, even 'Sarles, H., Tiscornia, O., Palasciano, G., Brasca, Panreatic changes induced by chronic A., Hage, G., and Devaux, M. A. (1972). though they are otherwise in good health (two years) ethanol treatment in the Scand. J. Gastroent., 8, 85-96. and there is no radiological evidence of 4Dg recurrent disease in the small bowel. The magnitude of these fluxes resembles that 0.- M. TISCORNIA, G. PALASCJANO, AND H. ofthe fluid loss from the intestinal mucosa Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

840 The British Society of Gastroenterology in cholera where a disturbance of bidirec- suggest that in their natural state, bran centration after urogastrone infusion in- tional sodium flux has been demonstrated (447 g water holding/100 g original creased by 127 to 164% of basal concen- (Love et al, 1972). material), mango (312 g), carrot (208 g), tration. A significant negative correlation We have measured the bidirectional apple (177 g), brussel sprouts (168 g) are between increase in plasma gastrin con- sodium flux in patients with Crohn's better as hydrophilic laxatives than centration and decrease in acid output disease treated by panproctocolectomy bananas (68 g), cauliflower (68 g), pota- was observed (r = 0-72, p < 0-01). with ileostomy and compared them with a toes (49 g), and turnip (37 g). Ulcer pain was relieved 30-60 minutes similarly treated group of patients with Most ofthe fibres act as monofunctional after the beginning of urogastrone infu- ulcerative colitis using a radioisotope weak cation exchange resins; lettuce (3-1 sion. technique with Na22 as a marker, modified m-equiv/g), cabbage, carrot, orange, These results suggest that urogastrone from the method described by Love et al turnip (2-4 m-equiv/g) are in the range of can inhibit the endogenously stimulated (1973). commercially available weak cation ex- acid hypersecretion in Zollinger-Ellison Patients with Crohn's disease have a change resin. patients. The pattern of inhibition is significant reduction in bidirectional When a diet is changed to one with compatible with a competitive action sodium flux which is one reason they are high fibre content then these physical against gastrin for receptor sites on the prone to episodes of flux but also adds characteristics may influence the choice of oxyntic cell. weight to the concept that Crohn's disease vegetables and fruit which are included in is a diffuse disease of the gastrointestinal the diet. Reference tract and may interfere with normal intes- Gillespie, I. E., Elder, J. B., Ganguli, P. C., tinal function even in the absence of mac- Ll Gregory, H., and Gerring, L. (1974). Gut, roscopic or radiological evidence of re- 15, 337. current disease. Effect of urogastrone in the Zollinger- Ellison syndrome L2 References Love, A. H. G., Phillips, R. A., Rohde, J. E., and J. B. ELDER, P. C. GANGULI, I. E. GILLESPIE, The G cell population of the gastric Veall, N. (1972). Sodium iron movement I. DELAMORE, AND H. GREGORY (University antrum, plasma gastrin, and gastric acid across intestinal mucosa in cholera patients. Departments ofSurgery and Haematology, secretion Lancet, 2, 151. Royal Infirmary, and Re- Love, A. H. G., Rohde, J. E., Abrams, A. E., and Manchester, Veall, N. (1973). Measurement of bidirec- search Division, ICI Laboratories. C. M. S. ROYSTON, JULIA M. POLAK, S. BLOOM, tional sodium flux across the intestinal wall Alderley Park, Cheshire) In normal W. M. COOKE, C. R. C. RUSSELL, A. G. E. in man using whole gut perfusion. Clin. Sci., volunteers urogastrone PEARSE, J. H. BARON, J. SPENCER, AND

(0-25 ,ig/kg/hr http://gut.bmj.com/ 44, 267. iv) inhibited exogenously stimulated R. B. WELBOURN (Departments of Surgery gastric secretion but had no effect on and Histochemistry, Royal Postgraduate K6 serum gastrin concentration and produced Medical School and Institute of Clinical no significant clinical side effects (Gillespie Research, Middlesex Hospital) The G Physical characteristics of vegetable et al, 1974). cell populations of gastric antra removed foodstuffs that could influence bowel Four male patients with proven at operation in 20 patients with duodenal function Zollinger-Ellison syndrome have been ulcers were estimated by a modification studied: one had of the method of previously undergone Card and Marks (1960). on September 30, 2021 by guest. Protected copyright. A. A. MCCONNELL, M. A. EASTWOOD, AND four operations including two gastric The G cells were stained by indirect W. D. MITCHELL (Wolfson Gastrointestinal resections, two hadhada truncal vagotomy immunofluorescence (Coons et al, 1955) Laboratories, Western General Hospital, and pyloroplasty, and one remained un- with an antibody to synthetic human gas- University ofEdinburgh, Edinburgh) There operated at the time of study. Informed trin 1. BAO, PAOPG, basal gastrin and is a need to explore physical characteris- consent was obtained. gastrin release by insulin and bicarbo- tics of dietary vegetable fibre that can be Gastric secretion and venous blood nate (Hansky et al, 1971) were measured tested in nutritional studies. This paper samples were collected at 15-minute inter- preoperatively. The mean G cell popula- describes two properties of the fibre of vals after an overnight fast. Following a tion was 19 6 x 106 (SE 3 8), mean BAO commonly eaten vegetables and fruit, 90-minute plateau period of basal secre- 10-3 m-equiv/h (SE 4'4) and mean PAOpG namely water-holding capacity (WHC) tion, urogastrone in the above dose was 46-9 m-equiv/h (SE 7 7). The population and ion exchange capacity. given intravenously for one hour. Sampl- showed no correlation with BAO (r = Twenty-six different fruit and vege- ing continued for a further minimum 0-165), PAOpG (r = 0 253), basal gastrin tables were dried to a powder. The capa- period of one hour after the end of the (r = 0-164) or gastrin release (r = 0 039). city of the powder to hold water was esti- infusion. Measurements of acid, pepsin, There was highly significant correlation mated. Lettuce, carrot, cucumber, celery, intrinsic factor, and plasma gastrin con- between basal gastrin and BAO-(r = and aubergine had the greatest WHC centrations were made in the appropriate 0-673, 0-01 > P > 0-001) but no correla- whereas maize, oatmeal, potato, banana, samples. tion between basal gastrin and PAO wheat, and bran had the least. The water After urogastrone both acid volume (r = 0 283) or gastrin release and PAO adsorptive capacity of any dietary plant and concentration decreased and basal (r = 0-051). is determined by its fibre content and the acid output was reduced by 60 to 82%. The G cells were graded subjectively water-holding capacity of the fibre. The concentrations of intrinsic factor as normal in number or hyperplastic in Estimations of the fibre content of the and pepsin in gastric juice increased by these 20 patients and in four others. original plant and the WHC of that fibre 60 to 300%. Peak plasma gastrin con- Seventeen were 'normal' and had G cell Gut: first published as 10.1136/gut.15.10.822 on 1 October 1974. Downloaded from

The British Society of Gastroenterology 841 populations of 2-3 to 2617 x 106; seven five patients with gastric hypersecretion Therapeutics and Department of Medical were 'hyperplastic' with populations of without pancreatic tumour, and in four Physics, Royal Infirmary of Edinburgh) 18-3 to 45-8 x 10. patients with achlorhydria. Gastric emptying rates for the liquid and In 28 antra the distribution of G cells In the four unoperated patients with solid components of a standard meal have was assessed by examination of about 15 ZES blood gastrin and acid output in- been assessed using a new method by blocks from each and the average numbers creased simultaneously, but in three which both are measured simultaneously. of G cells per 1 mm of mucosa were patients with a total gastrectomy and a The meal contained cornflakes and milk calculated. In 24 cases the distribution remaining endocrine tumour, only one together with 200 tci lismln DTPA was even and in four cases, showing showed an increase in blood gastrin chelate as a marker of the aqueous phase diffuse gastritis, it was uneven. during the infusion of secretin. In four and, as a marker of the solid phase, other patients with a total gastrectomy approximately 30 pieces of filter paper, 3 Refeeces and whose tumours had apparently been mm square, impregnated with 200 ,uci Card, W. I., and Marks, S. (1960). Clin. Sci., 19, completely removed (fasting blood gastrin *9mTc sulphur colloid and coated with a 147. 14-41 pg/ml), a secretin-induced increase thin film of perspex. Sequential scinti- Coons, A. H., Leduc, E. H., and Connolly, J. M. in blood gastrin was observed in two. scanning of the upper abdomen was per- (1955). J. exp. Med., 102, 49. In the five patients with gastic hyper- formed at 25-minute intervals beginning Hansky, J., Korman, M. G., Cowley, D. J., and Baron, J. H. (1971). Gut, 12, 959. secretion without pancreatic tumour 30 minutes after ingestion of the meal (fasting blood gastrin 10-103 pg/ml) (Heading et al, 1971). I3 neither blood gastrin nor acid output In 15 normal subjects emptying of the increased. Blood gastrin decreased after aqueous phase of the meal approximated The secretin provocation test in the secretin in three of the four patients with to a simple exponential process but the diagnosis of Zollinger-Ellison syndrome achlorhydria. solid phase marker apparently emptied These results suggest that the secretin at a constant rate. In almost all patients S. BONFILS, M. MIGNON, AND J. P. ACCARY provocation test is of considerable value this was substantially slower than empty- (Units de Recherches de Gastroenterologie, in the diagnosis of ZES patients with a ing of the liquid phase and the two rates INSERM U-10, HOpital Bichat, Paris) non-operated stomach, and (on the basis correlated poorly, indicating that one (Introduced by Dr J. H. Baron) The of one additional case), for familial cannot be inferred from the other. Some measurement of blood gastrin in fasting screening in the Wermer syndrome. In patients who had undergone gastric sur- patients is a valuable tool for the diagnosis other situations, especially in postopera- gery exhibited particularly fast emptying of Zollinger-Ellison Syndrome (ZES). tive follow up, it seems doubtful whether of the solid relative to the liquid phase. However, increased levels range from the secretin provocation test can reliably The results indicate that measurements twice to more than 20 times normal, so assess the presence or absence of a persis- relating to both the solid and liquid http://gut.bmj.com/ that in some patients provocative tests tent gastrin-secreting tumour. components of a natural meal may be are needed. relevant in defining the specific abnormal- The claim that an injection of secretin 1A ities of emptying which cause symptoms is a paradoxical stimulant for both blood after gastric surgery. gastrin and acid secretion in patients with Gastric emptying rate measurement in ZES has often been made, but the failures man: A method for simultaneous study of Reference of the test are seldom, if ever, mentioned. solid and liquid phases

Gastric acid and blood gastrin were Heading, R. C., Tothill, P., Laidlaw, A. J., and on September 30, 2021 by guest. Protected copyright. measured- before, during, and after the R. C. HEADING, P. TOTHILL, G. P. Shearman, D. J. C. (1971). An evaluation of i'lmindium DTPA chelate in the measure- infusion of GIH secretin 3 Unit/kg/hour MCLOUGHLIN, AND D. J. C. SHEARMAN ment of gastric emptying by scintiscanning. for one hour in 10 patients with ZES, (Gastrointestinal Section, Department of Gut, 12, 611-615.