Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

Gut, 1977, 18, A940-A990

The British Society of Gastroenterology

The 38th annual main meeting of the British Society of Gastroenterology (under the Presidency of Dr. Geoffrey Watkinson) and the 6th annual main meeting of the British Society for Digestive Endoscopy (under the Presidency of Dr. W. Sircus) were held at York University from 22 to 24 September last, preceded by a Teaching Day organised by The British Society of Gastroenterology. The social programme included receptions at the Guild Hall and Castle Museum together with both societies' annual dinners. The Plenary Scientific Session included the Sir Arthur Hurst Lecture given by John S. Fordtran entitled 'Food and acid secretion'. The size ofthe programme necessitated four simultaneous sessions for the remainder of the meeting. Abstracts of all papers given at the meeting are reproduced below.

ENDOSCOPY Bacterial contamination of fibreoptic endo- References scopes 'Shull, J. H., Greene, B. M., Allen, S. D., Dunn, G. Neuroleptanalgesia versus diazepam as a W., and Schenker, S. (1975). Bacteraemia with premedication for upper GI tract endo- M. NOY (introduced), LYNNE HARRISON upper gastrointestinal endoscopy. Annals of (introduced), G. K. T. HOLMES, R. H. SAGE Internal Medicine, 83, 212-214. scopy "Axon, A. T. R., Phillips, J., Cotton, P. B., and (introduced), AND R. COCKEL (Selly Oak Avery, S. A. (1974). Disinfection of gastro- C. BIRT, GILLIAN DAVIES, AND B. STERRY Hospital, Birmingham) The clinical rele- intestinal fibre endoscopes. Lancet, 1, 656-658. ASHBY (General Hospital, Southend) vance of bacterial contamination of upper Neuroleptanalgesia using phenoperidine gastrointestinal endoscopes is controver- Varieliform gastritis or superficial hyper- and droperidol has been the standard sial despite reports of bacteraemia after trophic gastritis medication for endoscopy at Southend for many types of endoscopyl and fatal some years. In a clinical trial to assess this Pseudomonas septicaemia after fibre-optic C. ANDRE, R. LAMBERT, B. MOULINIER, AND method 150 patients were allocated by oesophagoscopy in leukaemia. The latter B. BUGNON (Centre d'Endoscopie, Pavillon random numbers to receive phenoperidine group was rendered liable to infection by H, Hospital Edouard Herriot, Lyon, and droperidol or phenoperidine and granulocytopenia. We have encountered France) Ninety cases of varioliformhttp://gut.bmj.com/ diazepam or diazepam alone. three previously healthy patients who, after gastritis have been observed. This disease In the endoscopist's assessment cases endoscopy, developed severe infections deserves its place in the field of inflam- with anatomical difficulties were excluded with Pseudomonas of type identical with matory gastropathies on morphological, leaving 41, 45, and 40 patients respectively that on the endoscope. All were examined clinical, and physiopathological grounds. in the three groups. Both phenoperidine as emergencies before surgery for acute 1. Gastritis attacks the fundus. The top and droperidol and phenoperidine and haemorrhage. of the nodules is ulcerated, hence the name diazepam received higher scores for A quantitative survey of bacterial varioliform gastritis or even erosive

patient tolerance than diazepam and contamination of endoscopes and acces- gastritis. on September 28, 2021 by guest. Protected copyright. showed a lower incidence of movement, sories showed that the insertion tubes were 2. On the clinical level, the main retching, salivation, hiccough, gagging, easily cleaned but simple washing was symptoms and signs are epigastric pains and coughing during endoscopy. inadequate to disinfect channels within often of an atypical ulcerous nature, At the follow-up 15 patients failed to instruments. Irrigation of channels with dyspeptic problems with nausea and return, leaving 46, 48, and 41 patients in Savlon left 12% heavily contaminated, gastric intolerance, and weight loss. the respective groups. Forty per cent of rising to 50% by the next endoscopy ses- Radiographs show large longitudinal folds patients who had received diazepam com- sion. Thorough irrigation with activated in the fundus and characteristic rosette plained of thrombophlebitis and 20 % had glutaraldehyde (±detergent) virtually images in the antrum. Endoscopy shows complete amnesia for the whole procedure. eliminated vegetative organisms; pro- the topography of the lesions: ulcerations Approximately 50% of those receiving longed immersion appeared unnecessary2. at the top of the swellings. The disease is diazepam had fully recovered the same day The most important time for disinfecting characterised by acute episodes, the compared with only 15 % ofthose receiving instruments is immediately before use. symptoms lasting several weeks, and droperidol and 90% and 80% respectively This was shown by a study of oral flora relapses are quite frequent. Anatomical the following day. The diazepam group before and after endoscopy. Of 124 recovery always takes place later than showed the least number of adverse effects patients from 25 sessions, 19 became clinical recovery. and the highest number of patients who colonised by bacteria from the endoscope 3. The percentage of plasmocyte IgE is were prepared to return for a repeat (usually Pseudomonas aeruginosa); 18 were from 12 % in the fundus and 11 % in the procedure. first on the list. Since routinely disinfecting antrum when it remains normal in com- We conclude that neuroleptanalgesia is instruments and accessories with glu- mon inflammatory gastritis. Treatment by *best for the endoscopist but diazepam is taraldehyde before use, oral colonisation a stabiliser of mast cells (sodium cromo- jpreferred by the patient. has been eradicated. glycate) may be advised, because it often A940 Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A941 coincides with a clinical improvement. In gastric cancers' were found in neighbour- condition. ERCP provides a good surgical seven subjects the IgE plasmocytes were ing hospitals and at York District map, but the outcome is mainly dependent measured before and after the treatment: Hospital. Their clinical, morphological, on removal of the initiating cause. their percentage changed from 14 to 4. and histological characteristics were com- pared with those of Japanese 'early Routine endoscopic biopsies: a new and ac- Assessment of observer error in upper gastric cancers'"2'3 and revealed a remark- curate tool to investigate gut endocrinology gastrointestinal endoscopy able similarity. The results of this study suggested that a higher proportion of M. G. BRYANT, S. R. BLOOM, J. M. POLAK, R. J. HOLDEN AND G. P. CREAN (Gastro- British gastric cancer could be diagnosed S. HOBBS, W. DOMSCHKE, S. DOMSCHKE, P. intestinal Centre, Southern General Hos- at an 'early' stage by more intensive MITZNEGG, H. RUPPIN, AND L. DEMLING pital, Glasgow) There are few assessments investigation of dyspeptic patients using (introduced by S. R. BLOOM) (Depart- of the error inherent in endoscopy. In this up-to-date radiological techniques, fibre- ments of Medicine and Histochemistry, study two experienced observers have optic endoscopy, and endoscopic biopsy. Royal Postgraduate Medical School, independently and sequentially examined London, and Medizinische Universitats- the oesophagus, stomach, and duodenum References klink, Erlangen, W. Germany) The tissue of 31 patients attending a routine endo- concentrations of intestinal hormones in 'Nakamura, K., Sugano, H., Takagi, K., and scopy clinic. Each observer assessed the Fuchigami, A. (1967). Histopathological study alimentary disease has hitherto been presence or absence of 16 features in the on early carcinoma of the stomach. Gann, 58, studied only in surgical specimens, and the oesophagus, 29 in the stomach, and 15 in 377-387. information is therefore of little diagnos- the duodenum. To each feature assessment 'Murakami, T. (1972). Pathomorphological diagno- tic value. This sis, in Early Gastric Cancer, pp. 53-58. Gann study was therefore under- a probability value was attached using the Monograph II. Edited by T. Murakami, Uni- taken, firstly, to determine whether the gut probability scale 0-1. versity Park Press: Tokyo. hormones can be reliably measured in Agreement was present in 97.4% of the 'Mochizuki, T. (1972) Method for histopathological extracts of small mucosal biopsies and, 496 oesophageal assessments, 91 5 % ofthe examination of early gastric cancer, in Early Gastric Cancer, Gann Monograph II, pp. 57-62. secondly, to establish from this normal 883 gastric assessments, and 85-46% ofthe Edited by T. Murakami. University Park Press: reference values and distribution pattern. 405 duodenal assessments. Agreement Tokyo. Parallel biopsies were taken from the about the normality or abnormality of the antrum, duodenum, and jejunum of nine oesophagus, 93%; stomach, 87%; and ERCP and surgery in recurrent acute patients for analysis of protein and DNA duodenum, 89%; and agreement about pancreatitis content and quantitative immunocyto- the presence or absence of focal chronic chemistry. A specially adapted micro- lesions (ulcer, tumour) greater than 93 %, P. B. COTTON AND J. R. CROKER (Gastro- radioimmunoassay was used to measure was high. Disagreements about lesser intestinal Unit, The Middlesex Hospital, hormonal content. Gastrin was maximal signs were much greater-for example, London) ERCP performed on 135 in the antrum (280 ± 68 pmol/g; 251 ± 78 http://gut.bmj.com/ gastric mucosal redness, 42% disagree- patients between recurrent attacks of cells/mm2). VIP was widely distributed but ments; gastritis 25% disagreement. acute pancreatitis showed normal pan- was highest in the duodenal bulb (96 ± 25 The probabilities attached to discordant creatography in 43% of 123 successful pmol/g; 52 ± 11 cells/mm2). Secretin, assessments of chronic lesions were low studies, major diffuse changes in 14 %, and GIP, and motilin were maximal in the (< 0 9) indicating uncertainty by both obstruction, pseudocyst, or stricture in descending duodenum (128 ± 52, 70 ± 8, observers. Disagreements over lesser signs 32%. Three patients had cancer and 11 63 ± lOpmol/g; 16 ± 4, 30 8, 60 10 were more strongly expressed-for exam- important congenital duct anomalies. cells/mm2 respectively), while enteroglu- ple, 69% of disagreements over mucosal Retrograde cholangiography showed cagon was detectable only beyond the redness were given probabilities of > 0 9 stones in 13 patients with previous ligament of Treitz (13 ± 4 pmol/g; 10 ± 1 on September 28, 2021 by guest. Protected copyright. by each observer. An awareness of such negative radiology. The 63 patients studied cells/mm2). error should influence the writing and in 1971-74 were reviewed at two to five This methodology at last allows study of interpretation of endoscopy reports. years. Progress had been excellent in 32, the physiology of the non-circulating hor- good in 11, and bad in 11; three patients mones found in the gut paracrine system. Comparison of 'early gastric cancer' in had died (two of unrelated conditions), Investigation of the level of mucosal Britain and Japan and six could not be traced. Surgical proce- endocrine hormones and their cell dures based on the ERCP findings had pathology in routine endoscopy clinic D. M. D. EVANS, J. L. CRAVEN, F. MURPHY, been performed in 31 patients: cholecys- biopsies should provide an important new AND B. CLEARY (Llandough Hospital, tectomy (nine), sphincter procedures tool for the preoperative diagnosis of Penarth, and York District Hospital. (seven), pseudocyst drainage (six), left alimentary disease. Introducer: J. L. CRAVEN, York District hemipancreatectomy (seven), total pan- Hospital) Before the introduction of createctomy (two). Cholecystectomy alone Endoscopic Celestin intubations for inoper- endoscopy, four out of 720 cases of gastric gave excellent results even when pan- able malignant dysphagia: a new use for the cancer at Llandough Hospital were diag- creatography was abnormal. Subsequent Foley catheter nosed before the cancer had breached the drinking habit in patients with alcohol muscularis propria, an incidence of 0 5 %. abuse (28/49 men; 2/14 women) was the E. W. GILLISON, J. KHAN, AND J. M. ELLIOTT Using endoscopy and endoscopic biopsy, major determinant of prognosis with or (Department of Gastroenterology, Kidder- 10 out of 101 cases of gastric cancer were without surgery. Only one patient made minster General Hospital) In complete diagnosed at this 'early' stage, an inci- good progress despite continuing to drink. agreement with Ferguson and Atkinson' dence of 101%. Four additional 'early Relapsing acute pancreatitis is a benign concerning the high mortality of laparo- Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A942 The British Society of Gastroenterology tomy and pull-through for malignant Eleven patients with biopsy-proven Highly specific antibodies to CCK have dysphagia, an attempt was made to active coeliac disease, 13 patients with recently become available and we were emulate their results using the endoscopic coeliac disease on gluten-free diet with therefore able to investigate the state of method they described to dilate and insert good clinical and histological response, and the CCK producing cells in coeliac disease. Celestin tubes. 13 age- and sex-matched normal subjects Jejunal biopsies were taken from seven Earlier experience of perforation of the were studied with a standardised break- children with coeliac disease and five oesophagus without radiographic control fast. controls with suspected malabsorption but prompted a study using the image Plasma levels of gastrin, motilin, pan- normal mucosa. Quantitative immuno- intensifier in the X-ray department for 13 creatic polypeptide, VIP, and entero- cytochemistry using an automatic tele- consecutive dilatations in nine patients glucagon were measured. Plasma entero- vision image analyser computer showed with malignant dysphagia. Seven dilata- glucagon in controls rose from 28 ± 7 that the number of CCK cells in the coeliac tions and intubations were performed for pmol/l to 45 ± 11 pmol/l at 180 minutes. biopsies increased by 37% (mean 7T9/mm2 advanced carcinoma of the oesophagus, Patients with active coeliac disease had ± 1-98) (normal mean 5-7 ± 0-82). The three for carcinoma of the gastric cardia, raised basal levels (94 ± 31 pmol/l), CCK cells were also larger than normal and three for constriction of the oesopha- which rose dramatically to 263 + 62 and strongly immunofluorescent, indicat- gus by advanced bronchial carcinoma. pmol/l at 180 minutes (p < 0 005). ing high storage of hormone. This One of the bronchial carcinomas had pro- Patients with treated coeliac disease had indicates that CCK release, like secretin, is duced a fistula into the oesophagus which normal enteroglucagon levels. There were impaired in patients with coeliac disease. was sealed by the Celestin tube. no significant differences in the levels of Only one patient died in hospital the other hormones. References secondary to myocardial insufficiency and Thus, measurement of the gut hormone 'Di Magno, E. P., Go, V. L. W., and Summerskill, the remainder went home after two days. profile demonstrates the specific defect in W. H. J. (1969). Pancreozymin secretion is By employing a gauge 28 Foley catheter the diseased small intestine and a con- impaired in sprue. Gastroenterology, 56, 1149. 2Polak, Julia, M., Pearse, A. G. E., Van Noorden. over the flexible Eder-Puestow system, siderable compensatory increase of the Susan, Bloom, S. R., and Rossiter, Mary, A. each Celestin tube could be inserted into ileal hormone, enteroglucagon. This pat- (1973). Secretin cells in coeliac disease. Gut, 14, the malignant stricture and beyond. Dis- tern of change appears to be highly 870. 'Bloom, S. R., Patel, H. R., and Johnston, D. Z. location of the tube had occurred in four specific to coeliac disease and may serve as (1976). Failure of secretin release in coeliac of the patients and all were successfully a convenient new diagnostic test. disease. Gut, 17, 812. extracted by inflating the balloon of the catheter against the inner wall of each Reference Inhibition of leucocyte migration by a- Celestin tube. Replacement tubes were 'Bloom, S. R., Patel, H. R., and Johnston, D. I. gliadin in patients with gastrointestinal inserted using the same technique. (1976). Failure of secretin release in coeliac disease: its specificity with respect to a-

disease. Gut, 17, 812. gliadin and coeliacs http://gut.bmj.com/ Reference 'Ferguson, R., and Atkinson, M. (1976). Endo- Cholecystokinin abnormalities in coeliac P. ASQUITH AND M. R. HAENEY (Frazer- scopic insertion of the Celestin tube in patients disease Squire Metabolic Research Unit, East with inoperable carcinoma of the cardia. Gut, Birmingham Hospital and, Department of 17,832. J. M. POLAK, M. V. MCCROSSAN, C. M. Experimental Pathology, University of TIMSON, D. R. JOHNSTON, D. HUDSON, M. Birmingham) Specific leucocyte migra- ABSORPTION/MALABSORPTION AND COELIAC SZELKE, A. G. E. PEARSE, AND S. R. BLOOM tion inhibition (LMI) is generally regarded DISEASE (Departments of Histochemistry and the as an in vitro test of cell-mediated on September 28, 2021 by guest. Protected copyright. Endocrine Unit RoyalPostgraduate Medical immunity. LMI to gluten has been Coeliac disease: diagnostic hormone pro- School, London, and Department of reported in patients with adult coeliac file Paediatrics, Nottingham Medical School) disease'2. We have evaluated the test In coeliac disease there is a diminished with particular regard to antigen and H. S. BESTERMAN, J. STEWART, S. GUERIN, secretion ofboth bicarbonate and enzymes disease specificity. R. MODIGLIANI, C. N. MALLINSON, AND S. R. by the pancreas. This is seen in response to LMI to a-gliadin, a-lactalbumin, BCG, BLOOM (Royal Postgraduate Medical a normal meal, to intraluminal acidifica- and PPD has been estimated in four School, Hammersmith Hospital, London, tion (known to release secretin), or to groups of subjects: normal-diet coeliacs West Middlesex Hospital, Isleworth, intraluminal aminoacid perfusion (a (15), gluten-free diet coeliacs (11), patients Hopital Saint-Lazare, Paris, France, and stimulant of CCK release)". However, the with other gastrointestinal diseases (20), Greenwich District Hospital, London) pancreatic secretion is normal after and age- and sex-matched healthy controls Coeliac disease is underdiagnosed and this intravenous injections of CCK and (26). LMI to BCG and PPD was similar in may be due to the absence of a simple secretin, thus indicating that the pancreas all four subject groups, confirming that screening test. We have previously itself can function normally but lacks the the potential cellular responsiveness of demonstrated a marked impairment of appropriate hormonal signal (CCK- coeliac patients is normal. secretin release', as this hormone is secretin) from the gut. We have previously Leucocyte migration in the presence of localised to the area of maximal mucosal shown that the S cells in coeliac disease a-gliadin was significantly inhibited in pathology. In view of the increased cell are hyperplastic and have increased hor- treated coeliacs compared with untreated tumover in coeliac disease, we have now mone storage2. This fits with the func- coeliacs, healthy controls, and patients investigated the release of the trophic tional failure of secretin release after with other intestinal diseases, but no hormone, enteroglucagon. intraduodenal infusion of acid3. significant inhibition was seen in untreated Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A943 coeliacs compared with the control The reasons for this are unknown but the organism to pig intestine, and that is groups. In contrast, no significant dif- have clear implications in patient care. an important virulence determinant. We ferences were found in the response to a- have previously shown that a human lactalbumin in any of the four groups. Reference EPEC (serotype 026K60H11) can adhere Significant inhibition to a-gliadin was 'Morris, J. S., Aidukiewicz, A. B., and Read, A. E. specifically to the mucosa of human foetal observed in 9/11 coeliacs on a gluten-free (1970). Neurological disorders and adult coeliac small intestine'. Now we have evidence diet, 5/15 untreated coeliacs, 1/26 healthy disease. Gut, 11, 549-554. that this adherence is mediated by a controls, and 1/20gastrointestinal patients. transmissible plasmid. Inhibition to a-lactalbumin occurred in Distribution of neurotensin in man: a Strain 026K60Hl1 was grown in liquid 2/11 treated and 3/15 untreated coeliacs, peptide hormone affecting carbohydrate culture to label its DNA uniformly with 3/26 normal subjects and 3/20 patient metabolism 3H-thymidine. Sarkosyl-lysed cells were controls. subjected to ethidium bromide-caesium LMI to a-gliadin appears specific for A. M. J. BUCHAN, J. M. POLAK, S. SULLIVAN, chloride buoyant density centrifugation. adult coeliac disease and occurs more S. R. BLOOM, AND A. G. E. PEARSEN (Depart- Almost 30% of the DNA banded at the frequently in treated than in untreated ments of Histochemistry and Medicine, density characteristic of plasmid DNA. coeliac patients. Royal Postgraduate Medical School, Lon- Analysis of this material in neutral don) Neurotensin (NT) is a tridecapep- sucrose density gradients showed that it References tide originally isolated from bovine hypo- comprised a larger plasmid species with a 'Bullen, A. W., and Losowsky, M. S. (1976). Cell- thalamus. Recent studies have suggested molecular weight of 50-60 megadaltons, mediated immunity (CMI) to gluten fraction III that neurotensin-like immunoreactivity and two smaller species. (GF I1I) in adult coeliac disease (ACD). Gat, 17, may be present in the rat gut in quantities We transferred the adherence charac- 813. 'Douwes, F. R. (1976). Gluten and lymphocyte larger than those found in the nervous teristic by bacterial conjugation from the sensitisation in coeliac disease. Lancet, 2, 1353. system. Neurotensin has a wide spectrum EPEC strain to 15 % ofa recipient strain of of actions including production of hypo- E. coli K12. Analysis of the DNA of Increased prevalence of epilepsy in coeliac tension, gut contraction, increased vascu- adherent clones of K12 showed that 9% disease lar permeability, haemoconcentration, was in the plasmid form, identical with the hyperglycaemia, and hyperglucagonaemia. plasmid of 50-60 megadaltons in the donor J. M. LAIDLOW, R. G. CHAPMAN, D. G. We report the results of studies into the EPEC. COLIN-JONES, 0. EADE, AND C. L. SMITH distribution and localisation of NT in We conclude that this plasmid (that we (Gastrointestinal Clinics, The Royal and human intestine. The study involved radio- have designated pLG101) mediates mu- Queen Alexandra Hospitals, Portsmouth, immunoassay and immunocytochemistry cosal adherence in some strains of human and the Professorial Medical Unit, South- of fresh surgical and endoscopic samples. EPEC, and is likely to be an important ampton) A number of neurological dis- The intestinal distribution shows the determinant of virulence. orders may occur in association with highest concentration in ileal mucosa (16-2 http://gut.bmj.com/ coeliac disease1, but an increased preva- pmol/g: 31 cells/mm2) a significant Reference lence of epilepsy in this condition has not amount in jejunum (2-82 pmol/g: 1-10 'McNeish, A. S., Tturner, P. J., Fleming, J., and cells/mm2) with traces present in other Evans, N. (1975). Mucosal adherence of human previously been documented. In view of a enteropathogenic Escherichia coli. Lancet, 2, strong clinical impression that the preva- areas. Wehaveestablishedtheexactcellular 946-948. lence is increased, the following survey was origin of NT in the gut by the semithin- carried out. thin technique. The morphology ofthe cell Studies in primary hypomagnesaemia: One-hundred-and-eighty-fivetreatedpre- is characteristic of a typical endocrine cell evidence for a defect in carrier-mediated sumed coeliac patients who were mem- with a connection to the lumen via micro- transport of magnesium on September 28, 2021 by guest. Protected copyright. bers of the Coeliac Society in Hampshire villi and the storage granules grouped at were sent a questionnaire inquiring about the basement membrane. The identifying P. J. MILLA, 0. H. WOLFF, AND J. T. HARRIES the occurrence and frequency offits, black- feature is the electron dense, uniformly (The Hospital for Sick Children, Great outs, and other medical conditions: 165 round large (300 nm) secretory granules. Ormond Street, and Institute of Child patients returned the questionnaire. Nine The cell has been named the N cell as it Health, London) In comparison with patients were considered to be epileptics, was previously undescribed. The circum- other divalent cations, the intestinal giving a prevalence of 5*45%. A further scribed localisation to the lower small absorption of magnesium (Mg++) has not six patients were considered to be possible intestine suggests that NT may be been widely studied. Primary hypo- epileptics. In seven out of nine cases the important in the post-digestive process. magnesaemia is a rare disorder which is epilepsy was temporal lobe in type. inherited in an autosomal recessive The national prevalence of epilepsy of Mucosal adherence of human entero- fashion, and which is associated with all types is approximately 0 5 %. In order pathogenic E. coli (EPEC) is mediated by a defective absorption of Mg++. The precise to confirm this figure, 165 age- and sex- transmissible plasmid site and nature of the transport defect has matched controls were circulated with a not been defined. similar questionnaire. Of92% who replied A. S. MCNEISH, P. H. WILLIAMS, N. EVANS, We have investigated such a patient by there was one possible case of epilepsy, P. TURNER, AND R. H. GEORGE (University means of metabolic balances as well as by giving a prevalence of 0-6%. of Leicester and Birmingham Children's a steady-state perfusion technique. Meta- These results show that there is a higher Hospital) In pigs, virulent strains of bolic balance studies showed net mal- prevalence of epileosy in coeliac disease EPEC possess the plasmid-coded surface absorption of Mg++ during infancy. At (x2 = 4-47, p < 0-05). antigen K88 that promotes adherence of the age of 3 years perfusion of the proxi- Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A944 The British Society of Gastroenterology mal jejunum with Mg++ (1 and 2 mM) References References showed secretion of Mg++, compared with mean control values of 0019 and 'Walser, M., and Bodenlos, L. J. (1959). Urea 'Calloway, D. H., and Murphy, E. L. (1968). The 0-025 ,tmol/min/cm respectively; at 10 metabolism in man. Journal of Clinkal Investiga- use of expired air to measure intestinal gas tion, 38, 1617. formation. Annals of the New York Academy of mM absorption occurred at a rate of 0 13 'Sorensen, L. B. (1959). Degradation of uric acid in Science, 150, 82-95. compared with a mean control value of man. Metabolism: Clinical and Experimental, 8, "Metz, G., Gassull, M. A., Leeds, A. R., Blendis, L. 0 15. The kinetics of Mg++ transport were 687. M., and Jenkins, D. J. A. (1975). A simple studied in a small group of control sJones, J. D., and Burnett, P. C. (1974). Creatinine method of measuring breath hydrogen in metabolism in humans with decreased renal carbohydrate malabsorption by end-expiratory children, and the results suggest a saturable function: Creatinine deficit. Clinical Chemistry, sampling. Clinical Science and Molecular mechanism at low concentrations (Km 3-7 20, 1204, 1212. Medicine, 50, 237-240. mM; Vmax 0-078 pmol/min/cm), with a superimposed diffusional component at Effect of maltose on the absorption of high concentrations. Metabolism of dietary fibre components in glucose in the jejunum in man These results suggest that Mg++ is man, as assessed by breath hydrogen and transported by a carrier-mediated mecha- methane G. I. SANDLE, R. W. LOBLEY, AND R. nism at low concentrations, and that this HOLMES (University Department of is defective in primary hypomagnesaemia. Gastroenterology, Manchester Royal Infir- K. TADESSE AND M. A. EASTWOOD (Wolfson mary) In vitro work suggests disac- Laboratory, Gastrointestinal Unit, Western charidase-linked glucose transport from Urea, uric acid, and creatinine fluxes General Hospital, Edinburgh) If man is maltose in addition to the monosac- through the small intestine of man able to digest dietary fibre, it is by virtue of charide transport system'. his intestinal bacteria. Anaerobic bacterial To investigate this, 20 cm segments of V. S. CHADWICK, J. D. JONES, J.-C. metabolism of oligo- and polysaccharides proximal jejunum were perfused by DEBONGNIE, T. GAGINELLA, AND S. F. results in products including hydrogen and double-lumen tube in six normal subjects PHILLIPS (Gastroenterology Unit, Mayo methane. These gases diffuse to the blood using isotonic glucose-saline solutions Clinic, St Mary's Hospital, Rochester, and are excreted in the expired air, a (flow rate 21 ml/min) containing PEG 5 Minnesota 55901, USA) Radioisotopic sample of which can be measured by gas- g/l. Active glucose transport was tracer studies have shown that approxi- chromatography'. saturated with 166-5 mM glucose and the mately 7 g ureal, 200 mg uric acid2, and up Normal individuals, eating regularly, rates of absorption (mM/20 cm/10 min ± to 700 mg creatinine3 can be degraded by excrete less than 20 ppm of hydrogen. SE) from 222 mM glucose (8-84 ± 0-8) and intestinal bacteria each day. How these There is a regular and typical pattern of 277-5 mM glucose (10-21 ± 0-68) were not metabolites reach the colon is controver- change during the day, with peak pro- significantly different. sial, but as the colon is not very permeable duction in the morning and early after- Four normal subjects were perfused to these molecules it is thought that they noon. Fasting minimises the morning and with isotonic solutions in sequence con- http://gut.bmj.com/ cross into the small bowel lumen and afternoon rise and the variation during the taining 35 mM maltose, 222 mM glucose, enter the colon in ileal fluid. We measured day. Methane excretion is not influenced 35 mM maltose + 222 mM glucose, and daily fluxes of urea, uric acid, and crea- by diet and is typical for the individual. finally 111 mM maltose. Absorption rates tinine through distal duodenum and We have studied the metabolism ofpoly- from 222 mM glucose in the two groups terminal ileum in four normal subjects saccharides (cellulose, hemicellulose, pec- (8-84 ± 0-8 and 10-16 i 0-29) were not using slow perfusion techniques to deter- tin, starch), oligosaccharides (raffinose, significantly different. Absorption from mine input to, and output from, the small lactulose), and lignin. Ten or 20 g of the the maltose + glucose mixture (11-58 + intestine. 906 + SEM 105 mg urea, 112 i substances in water were eaten raw in the 0-3, 0-02 < 2 P < 0-025) and from 111 mM on September 28, 2021 by guest. Protected copyright. 43 mg uric acid and 94 ± 17 mg creatinine morning and the end-expiratory breath maltose (11-33 ± 0-46,0-025 < 2 p < 0 05) entered the small intestine from the duo- hydrogen and methane2 followed during both exceeded that from glucose (10-16 ± denum and 759 + 75 mg urea, 89 + 26 mg the day while otherwise fasting. 0 29). Absorption rates from maltose + uric acid, and 93 + 16 mg creatinine were Raffinose and lactulose increased total glucose and 111 mM maltose were not delivered to the colon daily. hydrogen production and peak values of significantly different. Maltose hydrolysis Concentrations of urea and uric acid in 50-60 ppm were common. Hemicellulose (19.3 ± 1-41) was inhibited by glucose ileal fluid remained constant over the 24 increased total breath hydrogen to a lesser (10-76 ± 1-83, 0-025 < p < 0-05). hours, so that colonic inputs were extent and peak values of 30 ppm were It is concluded that (1) disaccharidase- directly related to the rate of ileal flow. attained by some. The other polysac- linked glucose transport was not confirmed However, creatinine concentrations in- charides and lignin studied had no effect. in vivo in man, (2) increased glucose creased after meals, suggesting conversion Physical properties-for example, particle absorption from maltose + glucose may of dietary creatine to creatinine within the size-did not influence hydrogen pro- be due to diffusion, (3) glucose is absorbed lumen. duction. Methane excretion is not affected more rapidly from 111 mM maltose than We conclude that, as the measured by any of the chemicals. 222 mM glucose, (4) maltose hydrolysis is colonic input of urea, uric acid, and This suggests that, after acute admini- inhibited by high glucose concentrations. creatinine from the ileum accounts for stration, hemicellulose, lactulose, and only a small proportion of their estimated raffinose are metabolised by a mechanism Reference daily intestinal breakdown, large amounts involving hydrogen and methane pro- 'Malathi, P., Ramaswamy, W. F., Caspary, W. F., of these metabolites must be excreted duction, whereas the other polysac- and Crane, R. K. (1973). Studies on the trans- 4irectly into the colon from the blood. charides and lignin are not. port of glucose from disaccharides by hamster Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A945 small intestine in diiro. I. Evidence for a di- StruLctural and hormonal alterations in the meability and we have therefore attempted saccharidase-related transport system. Bio- gastrointestinal tract of parenterally fed rats. chlinica et Biophysica 307, 613-626. to show the same phenomenon in vivo. Acta, Gastroenterology, 68, 1 177-1183. Groups of mice were fed ovalbumin or Factors influencing intestinal mucosal Effect of folate deficiency on mucosal DNA saline for 14 days, rested for 14 days, and hypoplasia during total parenteral nutrition synthesis during recovery from tropical then challenged with intragastric oval- (TPN) in rats malabsorption (TM) bumin. The concentration of ovalbumin in the circulation was measured 45 minutes C. A. HUGHES, A. PRINCE, AND R. HERMON later using a sensitive radio immunoassay DOWLING (Guy's Hospital and Medical A. M. TOMKINS, M. MCNURLAN, AND S. and was lower in those animals previously WRIGHT (Clinical Nutrition and Metabo- fed ovalbumin. As the clearance of 125j1- School, London) During TPN, rat intesti- Hospital for Tropical Diseases, nal mucosa becomes hypoplastic' 2,3 but it lism Unit, ovalbumin from the circulation was not Department of Human Nutrition, London increased in these animals, it is concluded is not known how quickly this occurs nor Medicine) whether it is due to (1) exclusion of luminal School of Hygiene and Tropical that antigen feeding induces immune The importance of mucosal folate de- exclusion by the gut. nutrients, (2) secondary pancreatic hypo- in impairment of epithelial function, (3) reductions in trophic hor- ficiency Further groups of mice were fed antigen regeneration during recovery from TM is in the same dosage for the same length of mones, or (4) changes in bacterial flora. An in vitro system for jejunal We therefore established speed of change uinclear. time, but subsequently challenged with biopsy specimens1 to assess the essential parenteral ovalbumin in complete Freunds in jejunal and ileal structure and function, step of thymidylate syn- pancreatic mass and aerobic + anerobic folate-mediated adjuvant. Mice fed ovalbumin showed a thesis (methylation of deoxyuridine -> reduced antibody response compared with mucosal bacterial counts after three to 15 thymidylate) in DNA synthesis of mucosal days of TPN before studying the effect on controls. The phenomena of immune cells has been used to monitor effects of exclusion and orally induced systemic intestine and pancreas of 40 [cg CCK of TM. octapeptide or 175 units secretin kg therapy tolerance are therefore stimulated simul- Control subjects incorporated 234 l 76 taneously and together would offer an Bw-t day-1 during 10 days TPN. dpm H3Thymidine/ug DNA and TdR/ Jejunal villus height fell from 423 1 effective way of dealing with relatively DNA was suppressed to below 20% by harmless ingested antigens. SEM 51 ,um before to 342 _- 28, 313 the addition of 2 x 10-4 deoxyuridine 19, 301 ± 13, 295 ± 13 at three, six, 10, (dU) via an effect on the folate dependent and 15 days. Apparant Vmax (in vivo de novo pathway. TdR/DNA in seven Reference galactose absorption; 4-64 mM fell from was than controls (607 ± 44 4 to 19-4 2 patients higher 'Walker, W. A., Isselbacher, K. J., and Bloch, K. J. + + mmol/cm intestine-' 86 P < 0-01); dU failed to suppress TdR/ (1971). Intestinal uptake of macromolecules: h-1 but 'carrier affinity' increased so that DNA in six cases, indicating functional effect of oral immunisation. Science, 177, 608- Km fell from 36 7 + 5 to 13 2 ± 1 5 mucosal folate deficiency. 610. mmol/l. Pancreatic weight, DNA, and After four weeks tetracycline TdR/ http://gut.bmj.com/ protein also decreased within three days DNA fell in five cases with mucosal Small intestinal changes induced by an (P < 0001). improvement (261 ± 74 p < 0-05). dU elemental diet (Vivonex) in rats In the doses used, neither CCK nor suppressed TdR/DNA in each and folic secretin prevented intestinal hypoplasia acid (100 ,tg/ml) addition produced no L. M. NELSON, H. A. CARMICHAEL, R. 1. but CCK prevented pancreatic hypoplasia effect. In two cases, mucosal lesions RUSSELL, AND F. D. LEE (Gastroenter-ology (374 ± 8-6 mg/100 g BW without and 568 deteriorated and dU failed to suppress Unit and Department of Pathology, Royal 42-7 with CCK). TdR/DNA. Such changes imply that Infirmary, Glasgow) The importance of Viable bacterial counts mucosal oral rather than intravenous nutrition in (log5o/g mucosal folate deficiency usually recovers on September 28, 2021 by guest. Protected copyright. wet weight) also decreased, jejunal rapidly after antibiotics but may continue maintaining normal gut mass and function anaerobes falling from 6 58 ± 33 before and contribute to persisting mucosal has been demonstrated in rats' and to 4 32 ±- 0-4 after 10 days TPN (p < lesions. dogs2 but the effect of different types of 0-001). oral nutrition, especially elemental diets, In summary, intestinal mucosal hypo- Reference on small bowel structure and function has plasia and hypofunction, associated with not been fully investigated. We have reductions in microbial flora, develop 'Tomkins, A. M., McNurlan, M., and Wright, S. G. investigated the effect of an elemental diet (1977). Folate deficiency and DNA synthesis of within three days of TPN and are pre- jejunal mucosa in tropical malabsorption. Guit, (Vivonex) on the morphology and enzyme vented neither by CCK nor secretin. CCK 18, A 408. activity of normal rat jejunum. prevented the pancreatic hypoplasia of Three groups of rats were studied, with TPN. Absorption of antigen after oral immunisa- similar numbers in each group fed Vivonex tion and the induction of systemic tolerance and normal diet. Groups 1 and 3 (n = 12 References in both cases) were three months and 'Hughes, C., Bates, T., Sabin, E., and Dowling, R. E. T. SWARBRICK AND C. R. STOKES group 2 (n = 9) a one month study. H. (1976). Pancreatico-biliary secretions: are (introduced by A. M. DAWSON) (St. The ratio of crypt height: villus height they trophic to the intestine ? Clinical Science and Molecular Medicine, 51, 3P. Mark's Hospital, London, and The Institute was significantly reduced in the Vivonex 2Levine, G. M., Deren, J. J., Steiger, E., and Zinno, of Child Health, London) In vitro experi- fed rats compared with controls in all three R. (1974). Roll of oral intake in maintenance of ments have suggested that prior feeding of groups (p < 0-01, p < 0 05, p < 0-01). No gut mass and disaccarhide activity. Gastro- intact protein antigens reduces their sub- control rat had a ratio < 0 22 and only enterology, 67, 975-982. 'Johnson, L. R., Copeland, E. M., Dudrick, S. J., sequent absorption1. These in vitro models one Vivonex fed rat had a ratio of > 0-20. Lichtenberger, L. M., and Castro, G. A. (1975). have the disadvantage of altered per- Jejunal protein content, alkaline phos- Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A946 The British Society of Gastroenterology phatase, and disaccharidase activities 3-5%v.39-2±4-1%.n = 6,p = <0005). r6sorption des trav6es osseuses. Pathologie et were measured for rats in groups 2 and 3. Differences in hepatic metabolism may Biologie, 12, 1238-1243. Jejunal alkaline phosphatase activity was play a part, as the plasma half-life of significantly increased in the Vivonex fed intravenously injected paracetamol is STOMACH AND DUODENUM rats. Specific activity increased from 3 52 shorter in the pectin-fed rats (30 0 i 15 + 0 43 to 5-37 0-42 pmol/30 min/mg minutes v. 340 ± 1-2 minutes. n = 6, Statistical analysis of experimental data: protein (mean ± SEM) in group 2 and p = <0 05), though the antipyrine half- evaluation of some common errors with from 3-24 ± 0-21 to 3-88 + 0-25 ,umol/30 lives are the same. reference to gastric secretion studies min/mg protein in group 3 (p < 0-05 in Our results show that fibre affects drug both cases). Total activity per 10 cm seg- absorption and that the effect varies with P. B. BOULOS, P. F. WHITFIELD, R. G. FABER, ment was also increased (p < 0-02, p < the type of fibre. Unexpectedly pectin AND M. HOBSLEY (Department ofSurgical 005). enhances rather than retards drug absorp- Studies, The Middlesex Hospital and These results suggest that the elemental tion. Pectin may also affect drug metabo- Medical School, London) The interpreta- diet Vivonex may increase the mature lism. tion of numerical data usually depends enterocyte population and improve entero- upon statistical evaluation. The 'para- cyte survival in normal rats. This em- Osteomalacia in patients with small metric' tests commonly used are valid only phasises the importance of oral nutrition, intestinal resection if the data are normally distributed. even to the normal small intestinal mucosa. Taking gastric secretion as an example, JULIET E. COMPSTON, L. W. L. HORTON, AND we have analysed the distributions of References B. CREAMER (Gastrointestinal Research histamine and insulin stimulated acid out- Unit, Rayne Institute, and Department of put in 70 control subjects and 124 patients 'Levine, G. M., Deren, J. J., Steiger, E., and Zinno, Surgical Pathology, St. Thomas' Hospital, with duodenal ulcer. Only in some R. (1974). Role of oral intake in maintenance of distribu- gut mass and disaccharidase activity. Gastro. London) The prevalence of histological instances were the data normally entero!ogy, 69, 975-982. osteomalacia after small intestinal ted. For non-normal data non-parametric 2Feldman, E. J., Dowling, R. H., McNaughton, J., resection has been investigated in 25 tests must be used unless the data can be and Peters, T. J. (1976). Effects of oral versus transformed to a normal distribution. intravenous nutrition on intestinal adaptation patients, aged 22-72 years, by quantitative after small bowel resection in the dog. Gastro- assessment of transilial biopsies'. This, indeed, was possible in the examples enterology, 70, 712-719. Eight patients (32%) had histological quoted by taking the square-root of each osteomalacia, severe in five and mild in value; the simple parametric tests could Dietary fibre and drug absorption: the effect three; only one was symptomatic. Definite then be applied. The changed interpreta- of pectin and bran on paracetamol absorp- radiological changes occurred in four of tions were often striking-for example, tion in the rat the eight, but two with severe osteomalacia the lower boundry of maximal acid output

showed no radiological abnormality. in the control group was only 2 5 mmol/h http://gut.bmj.com/ R. C. BROWN, J. KELLEHER, B. E. WALKER, Serum calcium, phosphate, and alkaline by raw data, but 7-3 mmol/h after taking AND M. S. LOSOWSKY (Department of phosphatase concentrations were normal the square root. Medicine, University ofLeeds, St. James's in all three patients with mild osteo- It is well-known that gastric secretion is Hospital, Leeds) Fibre has profound malacia, but alkaline pbosphatase was related to stature'. A method of standard- effects on gastrointestinal function and is raised in the five with severe osteomalacia, isation is to express secretion per unit body known to affect the absorption of nutri- and one of these was also hypocalcaemic. stature2; however, regression analysis ents. It is often given to patients taking Possible precipitating factors were rapid reveals that this method is rarely applic-

drugs but there is surprisingly little infor- bone growth in three young patients, low able. When data are normally distributed on September 28, 2021 by guest. Protected copyright. mation on whether fibre alters the effects dietary vitamin D intake in six, and standardisation should be made by using of these drugs. cholestyramine therapy in one. the appropriate regression formula. In rats fed a basal diet, with 18 % pectin Two patients with severe osteomalacia Application of these statistical con- added, the urinary excretion of paraceta- showed histological improvement after siderations should improve the evaluation mol in the first eight hours after an oral one year of parenteral vitamin D2 therapy of experimental data, and allow fairer dose is greater than in rats fed basal diet Two others with severe osteomalacia were comparison between the results from alone (mean 45 2 ± SEM 4 9% of dose v. treated with oral 1 a-hydroxy-vitamin D, different centres. 20-4 ± 4-3%. n = 6, p = <0-0025). The and 25-hydroxyvitamin D, respectively; cumulative excretion after 72 hours is the both showed a dramatic histological References same. improvement after six months' treatment. 'Baron, J. H. (1969). Lean body mass gastric acid In similar experiments an 18% bran It is concluded that osteomalacia is and peptic ulcer. Gut, 10, 637. diet had no effect. 2Prescott, R. J., Sircus, W., Lai, C. L., and Lam, S. common after small intestinal resection, K. (1976). Failure to confirm evidence for Plasma free paracetamol levels are and bone biopsy is essential for its existence of two populations with dtuodenal raised in pectin-fed rats at 30, 60, 90, and diagnosis. Oral therapy with vitamin D ulcer. British Medical Journal, 2, 677. 120 minutes after oral paracetamol dosage metabolites or analogues can be effective (p = <0-05 at each time) suggesting that and offers possible advantages over Thiocyanate as a marker of saliva in gastric differences in absorption underlie the parenteral vitamin D therapy. juice? more rapid urinary excretion. Further- more, absorption of paracetamol solution Reference P. B. BOULOS, M. DAVE, P. F. WHITFIELD, AND (10 mg/ml) perfused through the small 'Bordier, P. J., Matrajt, H., and Hioco, D. (1964). M. HOBSLEY (Department of Surgical bowel is greater in pectin-fed rats (49 4 ± MWsure histologique de la masse et de la Studies. The Middlesex Hospital and Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A947 Medical School, London) Aspirated gas- later with 690% reduction of PAO. After This non-invasive test of gastric tricjuice contains thiocyanateI. It is known four years 21 % of samples were red)2, the volumes of Vagotomy and intragastric acidity Fifty patients had their maximal consecutive aspirated samples may vary. secretory capacity determined in response Episodic sequestration of portions of the R. F. MCCLOY, D. P. GIRVAN, AND J. H. to pentagastrin (6 ,pg/kg) using a y-camera stomach contents results in a smaller BARON (Department of Surgery, Royal and a non-invasive technique. After 15 aspirate, to be succeeded in the next col- average Postgraduate Medical School andHammer- minutes 99mTc (1 m.Ci intravenously) was lection-period by a larger than on September 28, 2021 by guest. Protected copyright. smith Hospital, London) Gastric acidity given and gastric scans were taken for 30 volume. Post-sequestration samples con- has recently been used to claim that minutes and the intragastric activity was tain juice that has been in contact with the efficacy of an antisecreting drug is determined after subtraction of back- stomach mucosa longer than aspirate dur- comparable with vagotomy', but little is ground. ing the period ofsequestration. They might known of the effect of gastric operations After total gastrectomy no discrete therefore be expected to display the on intragastric pH2. image was formed with no fall-off of back- characteristics of back-diffusion more We studied the effect of truncal (TV) ground activity, indicating that the clearly. and selective vagotomy (SV) on intra- stomach was the only appreciable source During -maximal and maximally- gastric pH in seven patients with duodenal of 9smTc concentration. Pernicious anae- stimulated3 steady-state gastric secretion, ulcer, who were asymptomatic four years mia patients had intragastric counts only 47 pairs of sequestration/post-sequestra- after operation. marginally above background. Twelve tion samples were identified and their Na Twenty-four hourly gastric aspirates duodenal ulcer patients all showed a and H concentration compared. The dif- were performed on two patients (one SV, reduction in activity after vagotomy (mean ferences, A [Na] and A [H] were one TV) immediately before, eight days, reduction 48 4%, p < 0-0005). The mean examined by linear regression. The slope and four years after operation. The TV concentration in duodenal ulcer patients A [H] (y) vs A [Na] (x) was -1-5 (r = patient had 96% of pH samples <2 pre- was 44-2 % higher than in normal subjects -0-88, P < < 0-001). By the back- operatively and none < pH 2 one week or (p < 0-05) and 68-4% higher than in the diffusion hypothesis, this slope should four years after operation, with a 97% gastric ulcer and carcinoma groups com- have been -1-0. However, -1-5 is reduction in peak acid output (PAO). The bined (p < 0-0025). Hiatus hernia, reflux consistent with contamination of gastric SV patient had 41 % of preoperative oesophagitis, and Meckel's diverticula can juice by duodenogastric reflux. samples < pH 2 and 4% < pH 2 eight days be diagnosed using this test. Thus, during stimulated secretion, back- Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A948 The British Society of Gastroenterology diffusion is undetectable, but duodeno- Magensaft secretion. Skandinavisches Archiv fur L. WITZEL (introduced by w. SIRCUS) Physiologic, 66, 225-316. gastric reflux is a plausible source of 2Hollander, F. (1938). Factors which reduce gastric (Gastrointestinal Unit, University Hospital, sodium in gastric juice. acidity. A survey on the problem. American Inselspital, Bern, Switzerland) The in- Journal of Digestive Disorders, 5, 364-372. crease in acid secretion observed in the rat References 3Davenport, H. W. (1964). Functional significance after cessation of prolonged treatment ofgastric mucosal barrier to sodium. Gastro- 'Teorell, T. (1947). Electrolyte diffusion in relation enterology, 47, 142-152. with high doses of metiamidel is greater to the acidity regulation of the gastric juice. than expected from the gain in parietal Gastroenterology, 9, 425-443. Effect of the histamine H2 antagonist cell mass2. Using a perfused rat stomach 2Hobsley, M., and Silen, W. (1969). Use of an inert marker (phenol red) to improve accuracy in cimetidine on gastric mucosal blood flow preparation3 the gastrin dose-response gastric secretion studies. Gut, 10, 787-795. relationship was therefore compared in 3Lawrie, J. H., Smith, G. M. R., and Forrest, A. P. S. E. KNIGHT, R. L. MCISAAC, AND L. P. metiamide and placebo treated animals. M. (1964). The histamine infusion test. Lancet, FIELDING (H. A. F. DUDLEY) (Academic Groups of 10 rats each were sub- 1, 270-273. Surgical Unit and Department of Physio- cutaneously injected during three weeks Does acid back diffusion and dilution reduce logy, St. Mary's Hospital Medical School, with 200 mg/kg metiamide alone (group I) the concentration of acid secreted by the London) Cimetidine is effective in reduc- or in combination with 200 mg atropine parietal cell? ing blood loss in patients with haemor- (II) at eight-hourly intervals. Controls rhagic gastritis caused by liver failure'. were given atropine or saline. M. R. THOMPSON AND M. GIPSMAN (De- This might be due partly to a direct action In acute experiments metiamide led to a partment of Surgery, Manchester Royal on the gastric microvasculature. To prolonged (up to four-fold) rise in serum Infirmary, and V. A. Centre, Wadsworth investigate this aspect we determined gastrin, which was suppressed by atropine. Hospital, Los Angeles) Acid back dif- gastric mucosal blood flow (GMBF) From the acid secretory response to fusion' and neutralisation2 are possible change in response to cimetidine in six graded doses of HG 17 I, 12 hours after explanations for the variation in acid volunteers; using neutral red (NR) the last medication, the calculated maxi- concentration of gastric juice. Both these clearance to estimate GMBF2. mal acid secretory capacity (Vmax) and the mechanisms will result in a decrease in the After nasogastric intubation each sub- ED 50 were established. In both metia- osmolarity of the acid. In order to deter- ject received NR (250 pgkg-lh-') intra- mide treated groups (I + II) Vmax was mine whether these two hypotheses are venously by constant infusion. Gastric twofold higher and the ED 50 only half correct HCI at three concentrations (50, juice (15 min aliquots) and blood (30 min that in both control groups (p < 0 001). 100, and 150 mM made isotonic with samples) were collected. After three basal Thus, in the rat, prolonged metiamide mannitol) was instilled into gastric samples pentagastrin (6 Eugkg-1h-') was medication increases gastrin-sensitivity pouches of four cats and net H+, Na+ and infused intravenously. When acid pro- and maximum secretory capacity of the Cl- fluxes, net volume output, and change duction had reached a plateau, cimetidine parietal cell and endogenous hyper- in osmolarity were measured in the usual (2 mgkg-lh-) was given intravenously for gastrinaemia seems not to be the primehttp://gut.bmj.com/ way3. 30 minutes. NR was extracted from blood mediator. Increasing the concentration of acid and gastricjuice with the non-polar solvent These results underline the necessity of instilled significantly increased (P < 0-05) ether and estimated spectrophotometri- differentiated acid secretory studies in net H+ loss (-27, -75 and -131 ,uEq/30 cally at 540 nm. patients subjected to long term histamine- min), net Na+ gain (+214, +268 and The main result was that cimetidine H2-antagonist treatment. +294 uEq/30 min), net volume output halved gastric mucosal blood flow. Acid (+0 5, 0-9 and 1-2 ml/30 min), and the output was also reduced but the ratio of References change in osmolarity was +12, +3 and GMBF to acid output remained constant. 'Halter, F., and Witzel, L. (1977). Increased acid on September 28, 2021 by guest. Protected copyright. -10 mosmol/l/30 min respectively. These We conclude that the action of cimeti- secretion after sustained metiamide medication data are compatible with either theory",2. dine in reducing blood flow through the in the rat. Gastroenterology, 72, A-6/816. The crucial mucosa to this 'Witzel, L., Halter, F., Olah, A. J., and Hacki, H. factor determining which is gastric may help explain W. (1977). Effects of prolonged metiamide correct is the nature of the increase in drug's beneficial effect in bleeding erosive medication on the fundic mucosa. A secretory fluid output. In further experiments the gastritis. and histomorphometric study in the rat. increase in fluid output stimulated by 150 Gastroenterology, 73, in press. 3Halter, F., Kohler, B., Leuenberger, J., Smith, G. mM HCl continued during the subse- References M., and Varga, L. (1976). The development of a quent instillation of 5 mM HCl. During reliable and sensitive biological assay for gastrin this time the increase in Na+ output was 'MacDougall, B. R. D., Bailey, R. J., and Williams, inbodyfluids. EuropeanJournal ofPharmacology, R. (1977). H2 receptor antagonism and antacids 35, 369-378. matched by an increase in Cl- output in the prevention of acute gastrointestinal (+138 uEq Na+ and +184 ,uEq Cl-). haemorrhage in fulminent hepatic failure. Therefore the decrease in osmolarity is due Lancet, 1, 617-619. Is intrinsic factor really affected by to HCl back diffusion and the increase in 2Knight, S. E., and Mclsaac, R. L. (1977). Neutral cimetidine? Red as an estimate of gastric mucosal blood flow Na+ output is due to the secretion of a in dogs. Journal of Physiology (Lond.), 267, solution of NaCl. 45P. P. C. SHARPE, M. A. HORTON, R. H. HUNT, Thus, acid concentration was reduced JANE G. MILLS, S. H. VINCENT, AND G. J. by H+ back diffusion and dilution with a Effect of prolonged metiamide medication MILTON-THOMPSON (Royal Naval Hos- solution of NaCl. on acid secretory capacity and gastrin pital, Haslar, Hampshire; Clinical Research sensitivity of the rat parietal cell Department, Smith Kline and French References Laboratories Ltd.; Department of Haema- 'Teorell, T. (1933). Untersuchungen uber die F. HALTER, W. H. HACKI, S. K. HACKI, AND tology, St. Bartholomew's Hospital, Lon- Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A949 don) Controversy exists as to the extent tions in 22 of these patients' when no Lancet, 1, 583-586. to which cimetidine reduces output and changes in serum gastrin were found in 18 concentration of intrinsic factor (IF)' . patients but in four patients marked Long-term effects of cimetidine on gastric In order further to evaluate the effects of increases in fasting and stimulated con- secretion cimetidine, seven healthy males were centrations were recorded associated with studied on three occasions. On day 1 resting intragastric pH values of > 6-0. An R. J. HOLDEN, J. B. HEARNS, B. MCKIBBEN, cimetidine 100 mg/h was infused intra- identical Oxo test was performed in each K. B. BUCHANAN, AND G. P. CREAN (The venously for 135 minutes with simultan- patient after completion of one year's Gastrointestinal Centre, Southern General eous infusion of pentagastrin (PG) for the treatment (51x4 ± 13 weeks) in which the Hospital, and the University Department of last 90 minutes. On day 2 PG alone was test solution was instilled through a Ryle's Medicine, Queen's University, Belfast) infused for 90 minutes. On completion, tube, samples of gastric juice were Gastric secretion and serum gastrin levels cimetidine 200 mg intravenously was given aspirated for measurement of pH and H+ were studied serially before, during and followed by 2 g/day for one week, when concentration, and venous blood samples after prolonged treatment with cimetidine. the procedure of day 1 was repeated. were withdrawn for radioimmunoassay Patients with duodenal ulceration were Gastric aspirates were analysed for of their gastrin content. The integrated randomly allocated to treatment with 800 acidity and IF concentration. gastrin response (IGR) was calculated by mg cimetidine daily (n = 6) or 1600 mg Similar results were obtained on days 1 the method described by Ganguli et al. daily (n = 6) for eight weeks; tests were and 3. Compared with day 2, mean peak (1974)2. carried out in the week before starting IF output on days 1 and 3 were reduced by Results before treatment and after three treatment, at weeks 1, 2, 4, and 8 of treat- 49% (p < 005) and 41% (p < 001) and 12 months were compared using a ment, and at weeks 1, 2, and 4 after treat- respectively, while total output after PG Wilcoxon matched-pairs signed-ranks test. ment had ceased. Acid and pepsin out- was reduced by 37% (p < 0 01) on day 1 At one year both peak gastrin concentra- puts were determined from the results and by 30% (NS) on day 3. No effect was tions and IGR were significantly increased obtained in the first hour after 'maximal' seen on IF concentration on either study compared with both pre-treatment and pentagastrin stimulation; serum gastrin day 1 or 3 or on the time course of the three month values (p < 0-01 in every levels were determined from samples response. Mean acid output on days 1 and case) but fasting gastrin concentrations taken in the fasting state. Acid and pepsin 3 was reduced by 70% and 58%, acidity were not significantly altered. Compared outputs were both significantly decreased by 45 % and 35 %, and volume by 45 % and with pre-treatment values, all patients during the treatment period; however, 35 % respectively. except one showed anincreased IGR at one while acid output tended to return to Peak IF output was significantly year. However, stimulated serum gastrin control levels after treatment had ceased, reduced, but this effect was related to the concentrations > 1000 ng/l were found in pepsin output did not. The higher dose of reduction in volume of gastric aspirates. only three patients and this change had cimetidine exerted significantly greater We conclude that treatment with high occurred in the first three months of treat- effects on acid secretion than did the doses of cimetidine for one week does not ment in these patients. All patients except lower dose, but there were no significant http://gut.bmj.com/ affect IF response and that synthesis of IF one had a resting intragastric pH of < 2-0 dose effects with respect to pepsin is probably not altered by cimetidine. immediately before the one year test. secretion. There was no cumulative effect Mean serum gastrin concentration (ng/l) on acid or pepsin secretion with time, at References ± SDs pre-treatment, at three months and either dose level. There were no significant 'Burland, W. L., Mills, J. G., Sharpe, P. C., one year respectively were; fasting 63 ± changes in serum gastrin levels through- Horton, M. A., and Mollin, D. L. (1977). The 27, 102 ± 149, 85 ± 88; peak 259 ± 167, out. effect of cimetidine on intrinsic factor secretion. 459 ± 608 ± IGR 562 ± In Proceedings of the Second International 566, 481; (pg) on September 28, 2021 by guest. Protected copyright. Symposium on Histamine H,-Receptor Antago- 471, 1041 + 1478, 1649 i 1326. Effect of ionic strength on the proteolytic nists, p. 177. Edited by W. L. Burland and M. A. One year's treatment with cimetidine characteristics of human pepsins Simkins. Excerpta Medica: Amsterdam. has therefore produced an approximately 'Fielding, L. P., Chalmers, D. M., Stafford, D. M., I. M. SAMLOFF AND V. DADUFALZA (De- and Levi, J. (1977). Cimetidine and intrinsic three-fold increase in the serum gastrin factor secretion. Ibid., p. 184. response to Oxo (IGR) in this group of partment of Medicine, Harbor General patients. This has not resulted in a rebound Hospital and UCLA School of Medicine, Effect of one year's treatment with cimeti- of acid secretion on discontinuation of Los Angeles) (introduced by J. B. dine on fasting and Oxo-stimulated serum treatment nor in an increased severity of ELDER) The proteolytic characteristics of gastrin in duodenal ulcer patients symptoms in the two patients who have animal and fish pepsins are altered by relapsed to date. changes in the ionic strength of the R. W. SPENCE, L. R. CELESTIN, D. A. incubation mixture1' 2. This study exam- References MCCORMICK, C. J. OWENS, AND J. M. ines the effect of ionic strength on the pro- OLIVER (Department ofGastroenterology, 'Spence, R. W., Celestin, L. R., Owens, C. J., and teolytic characteristics of human pepsin I Frenchay Hospital, Bristol; University McCormick, D. A. (1977). Effect of three (PN I) and pepsin II (PN II) against Departments of Surgery and Medicine, months' treatment with cimetidine on basal and human haemoglobin. The apparent pH Oxo-stimulated serum gastrins in duodenal of PN I and PN II were about 2-2 Bristol Royal Infirmary) Twenty-three ulcer patients. In Cimetidine: Proceedings of the optima duodenal ulcer patients have completed Second International Symposium on Histamine and 3-4 when the ionic strength of the one year's treatment with cimetidine 1-6 g H,-receptor Antagonists. Excerpta Medica: assay mixture was determined solely by of Amsterdam. the concentration of HCl required to daily. Previously we reported the effect 2Ganguli, P. C., Polak, J. M., Pearse, A. G. E., three months' treatment on fasting and Elder, J. B., and Hegarty, M. (1974). Antral obtain a pH gradient of 1 to 5. The Oxo-stimulated serum gastrin concentra- gastrin-cell hyperplasia in peptic ulcer disease. addition of NaCl to maintain ionic Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A950 The British Society of Gastroenterology strength constant at 015 resulted in a incubated with hemicholinium-3. In the differences in gastroduodenal reflux and shift in the pH optimum of PN II to 2 5 hemicholinium-treated strips there was gastric emptying between the two groups and an almost two-fold increase in its complete abolition of the normal of patients. specific activity (A absorbance 280 nm/,pg excitatory response to metoclopramide enzyme). The effects of PN I were minor. (110 ,uM). Only a small reduction in this Effects of proximal gastric vagotomy and At ionic strength 0 025, the ratio of PN I response was detected in strips which were truncal vagotomy and antrectomy on to PN II in a mixture had little effect on incubated with hemicholinium-3 but not gastritis, bile reflux, and acid output proteolytic activity. In contrast, at ionic stimulated, and in which there was no strength 0-15, proteolytic increased pro- significant change in acetylcholine pool A. M. HOARE, I. DONOVAN, AND J. gressively as the ratio of PN I to PN II in size. ALEXANDER-WILLIAMS (The Queen Eliza- the mixture decreased. Studies of gastric The stimulant effect of metoclopramide beth and General Hospitals, Birmingham) juice paralleled the changes found for PN depends, therefore, upon maintenance of A randomised trial has been performed I and PN II. The results indicate that the intrinsic stores of acetylcholine. This find- comparing proximal gastric vagotomy pH optima of PN I and PN II are similar ing lends further support to the hypothesis (PGV) with truncal vagotomy and when ionic strength is maintained at a of increased acetylcholine release. antrectomy (TV and A) in 71 patients physiological level, that the specific with duodenal ulcer. Twelve months later activity of PN It is almost twice that of References endoscopy with gastric biopsies and a PN I, and that the peptic activity of gas- pentagastrin test, including measurement tric juice is determined not only by pH 'Hay, A. M. (1975). The mechanism of action of of bile acids in the fasting aspirate', were metoclopramide. Gut, 16, 403. and total pepsin concentration, but also by 2Hay, A. M. (1977). Pharmacological analysis of the performed. Thirty-five patients had PGV ionic strength and the ratio of PN I to PN effects of metoclopramide on the guinea-pig and 36 TV and A, of whom 58 volun- II. isolated stomach. Gastroenterology, 72, 864-869. teered for postoperative endoscopy and 46 for pentagastrin test. References Bile reflux and gastric emptying in patients Bile reflux was less after PGV than TV 'Schlamowitz, M., and Peterson, L. U. (1961). The with combined ulcer disease and A (p < 0-05). After TV and A six effect of sodium chloride on peptic digestion of patients had more than 120 ,tmol/h reflux bovine serum albumin. Biochimica Biophysica M. J. GOUGH, C. S. HUMPHREY, D. B. of bile acids, and all had symptoms. All Acta, 46, 381-383. FEATHER, AND G. R. GILES (University 40 2Nollis, E. R., and Elam, D. W. (1940). Preparation patients with more than ,umol/h bile and properties of salmon pepsin. Journal of Department ofSurgery, St. James's Univer- reflux had gastric erythema on endoscopy. Biological Chemistry, 134,443-454. sity Hospital, Leeds) The presence of a Gastritis of the distal stomach was more gastric ulcer in a patient with duodenal common after PGV, but was found in the Mechanism of action of metoclopramide: ulceration is usually attributed to gastro- proximal stomach equally commonly after

importance of intrinsic sources of acetyl- duodenal reflux and gastric stasis. To both operations. It was unrelated to bilehttp://gut.bmj.com/ choline investigate this problem we have studied reflux or symptoms. Five duodenal ulcers eight patients with combined ulceration were found after PGV, all had peak acid A. M. HAY, W. K. MAN, AND R. F. MCCLOY (DU + GU). The bile content of gastric output (PAO) greater than 20 mmol/h and (introduced by Professor R. B. WELBOURN) juice was measured under basal con- normal mucosa proximally. No ulcers (Department of Surgery, Royal Post- ditions and during maximal pentagastrin were found after TV and A, but PAO graduate Medical School, Hammersmith stimulation and the severity of any greater than 15 mmol/h was associated Hospital, London) Recently published gastritis assessed by the back-diffusion with a normal mucosa proximally (p <

data"2 from this laboratory suggest that technique. Gastric emptying of a 50% 0 02). Successful reduction of acid output on September 28, 2021 by guest. Protected copyright. metoclopramide enhances the contractile glucose meal was estimated by the George by ulcer surgery appears to be associated activity of the guinea-pig antrum by dye dilution technique. The results have with the development of gastritis. increasing acetylcholine release from the been compared with similar studies in 17 post-ganglionic cholinergic nerve ending. patients with uncomplicated duodenal Reference Further studies with longitudinal mus- ulcer (DU). 'Hoare, A. M., Keighley, M. R. B., Starkey, B., cle strips prepared from guinea-pig Basal and peak acid outputs were Alexander-Williams, J., and Hawkins, C. (1977). antrum have revealed an inhibitory inter- similar in both groups. It was only pos- Measurement of bile acids in gastric juice as a test for bile reflux after gastric surgery. Gut, 18, action between metoclopramide and anti- sible to detect bile in the basal secretion of A413. cholinesterase, making conventional tech- two patients with DU -t GU and four niques for the measurement of acetyl- patients with DU. After pentagastrin bile Are prostaglandins deficient in peptic choline release inappropriate. We have, reflux occurred in three patients with DU ulceration? therefore, used an indirect approach to + GU compared with seven patients with test our hypothesis. DU. The mean net loss of H+ ions during R. BAKER, B. M. JAFFE, J. D. REED, B. SHAW, Muscle strips were stimulated repeti- acid instillation was 1-66 mmol H+/15 AND C. W. VENABLES (Departments of tively (200 ,us pulses, 20 Hz, supra- min (-1 19 to 3 67) in the DU + GU Surgery and Physiology, University of maximal current) for two hours in the patients and 199 mmol H+/15 min (0-20 Newcastle upon Tyne, and Washington Uni- presence of hemicholinium-3 (200 ,uM). to 3-52) in the DU group. The mean half- versity, St. Louis, Missouri, USA) It has Pre-treatment in this manner produced a life of the glucose meal was 20-9 minutes been previously shown, in animal studies, mean reduction of 50% in the acetyl- (-1 to 32) in DU + GU patients and 18-6 that there is a positive correlation between choline pool size, when compared with minutes (8 to 43) in DU patients. gastric acid and PGE and PGF secretion'. that in stimulated control strips not These studies failed to show any As duodenal ulceration is associated with Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A951 hypersecretion, it might be expected that 2-8 to 16-5 ± 1-8% (mean ± SEM, P < made from this laboratory2, that fen- changes in plasma PGE and PGF could 001) and an increase in chenodeoxy- fluramine caused a small but significant occur in this disease. Fasting plasma levels cholate, from 30-1 ± 1-6 to 34 9 ± 2-2% decrease in serum cholesterol; and another of PGE and PGF were measured, by (p < 0 01), the changes being the same as report which demonstrated 14%Y. decrease radioimmunoassay2, in 100 patients under- observed previously. Bile was unsaturated in two weeks3. going diagnostic upper gastrointestinal with cholesterol at the beginning and endoscopy. These patients were catego- remained so throughout. The glycine/ References rised into four diagnostic groups. taurine conjugation ratio, body weight, 'Bliss, B. P., et al. (1972). Effect of fenfluramine on It was found that active duodenal and plasma lipids were unchanged. glucose tolerance, insulin, lipid and liproprotein ulceration was associated with a signi- The delay in the action of bran suggests levels in patients with peripheral arterial disease. Postgraduate Medical Journal, 48, 409-413. ficantly raised mean PGE level when that its primary effect is to reduce the for- 'Mekhjian, H. S., and Phillips, S. F. (1970). compared with the other groups (p < mation of deoxycholate, rather than Perfusion ofcanine colon with unconjugated bile 0 01). Plasma PGF did not differ signifi- merely to impede its absorption by acids. Gastroenterology, 59, 120-129. between the various groups. There 'Tomlinson, S. A., et. al. (1975). The effect of cantly physically altering the stools. fenfluramine on obesity and plasma lipids of was wide individual variation in PGE and patients with renal allografts. Postgraduate PGF levels. References Medical Journal, 51, (suppl. 1), 166-170. Plasma PGE and PGF did not alter significantly in 21 patients treated with 'Pomare, E. W., and Heaton, K. W. (1973). Natural history of chronic persistent Alteration of bile salt metabolism by dietary cimetidine 400 mg q.d.s. for 28 days fibre (bran). British Medical Journal, 4, 262-264. hepatitis irrespective of the success, or otherwise, of 2Pomare, E. W., Heaton, K. W., Low-Beer, T. S., therapy. and Espiner, H. J. (1976). The effect of wheat R. G. CHADWICK, J. GALIZZI, E. J. HEATH- In duodenal ulcer patients no correla- bran upon bile salt metabolism and upon the COTE, B. COHEN, P. J. SCHEUER, AND S. lipid composition of bile in gallstone patients. tion was found between plasma PGE and American Journal of Digestive Diseases, 21, 521- SHERLOCK (Academic Department of basal acid output (14 patients), plasma 526. Medicine, Royal Free Hospital, London, PGE and stimulated acid output (17 and the Virus Reference Laboratory, patients), or plasma PGE and serum Bile acid, neutral sterol, and faecal fat Colindale Avenue, London) Twenty-six gastrin (13 patients). Gastric juice PGE excretion in subjects treated with fen- patients (23 men and three women) with output correlated with acid ouput (r = fluramine chronic persistent hepatitis (CPH) have 0 563, p = 0 001), but not with pepsin out- been studied prospectively, clinically and put (five patients), confirming our animal M. S. SIAN AND A. J. HARDING RAINS by serial liver biopsies for six to 192 studies. (Professorial Department of Surgery, months (mean 48 months). In 16 there Cross Medical was evidence of past hepatitis B virus References Charing Hospital School,

London) In view of the excessive wastage (HBV) infection. The aetiology of the http://gut.bmj.com/ 'Baker, R., Jaffe, B. M., Labib, L. A., Reed, J. D., of bile salts during the diarrhoea after others was unknown. Liver biopsies Shaw, B., and Venables, C. W. (1977). Have treatment with fenfluramine, we have showed that in 15 CPH continued, while in prostaglandins a role in the control of secretion studied bile acids, neutral sterols, and three it resolved. Eight developed a mild in the stomach? British Journal ofSurgery, 64, 4. fat excretion in 16 chronic active hepatitis (CAH). These lat- 295-296. faecal healthy subjects 2Jaffe, B. M., Behrman, H. R., and Parker, C. W. before, during, and after administration of ter patients had often presented insidiously (1973). Radioimmunoassay measurement of fenfluramine. and were symptom-free; a rise in serum prostaglandins E, A and F in human plasma. Analysis of variance revealed a statis- transaminase was the only abnormality. Journal of Clinical Investigation, 52, 398-405.

tically significant increase in bile acid None developed cirrhosis. on September 28, 2021 by guest. Protected copyright. excretion during the drug phase (p < 001) 'e' antigen was present in only one of the LIVER AND BILLARY and during recovery (p < 001). Excretion 15 HBsAg positive patients and this sub- during pre-drug, drug, and recovery phase ject progressed to CAH. Serum antibodies Bran and bile: time-course of changes in was 9 537, 12-766, and 12-032 mg/g dry against nuclei, mitochondria, and smooth normal young men given a standard dose wt. faeces. Increased neutral sterol muscle were not detected. excretion coincided with bile acid elimina- It is concluded that CPH is a benign K. W. HEATON AND A. C. B. WICKS (Uni- tion. There was a lack of correlation condition, predominantly affecting men, versity Department of Medicine, Bristol between faecal fat and drug administra- which may follow HBV infection. 'e' is Royal Infirmary, Bristol) Previously, we tion, and in the three subjects with diar- usually absent. CAH developed in eight of have shown that bran feeding causes signi- rhoea faecal fat and bile acid loss was 26 patients, more often in those presenting ficant changes in bile acid composition and markedly reduced; bile acids excreted insidiously, but this was mild and non- metabolism, and an improved cholesterol were mainly chenodeoxy and cholic progressive. Cirrhosis was not a sequel. saturation of bile in gallstone patients1'2. together with cholesterol as the main These studies used various doses of bran neutral sterol instead of coprostanol. This Chronic lobular hepatitis: a distinct and a single sampling time at four to six is evidence ofreduced 7 a dehydroxylation entity? weeks. We have now fed a standard dose in subjects with diarrhoea. Primary bile of bran (15 g twice daily) to 12 healthy acids have been reported to induce watery S. P. WILKINSON, B. PORTMANN, A. M. G. young men, and analysed duodenal bile diarrhoea in canine colon'. COCHRANE, AND ROGER WILLIAMS (Liver after one, two, four, and six weeks. At six Augmented bile acid and neutral sterol Unit, King's College Hospital and Medical weeks, but not earlier, there was a excretion as reported in this study is in School, London) Three adult male reduction in deoxycholate, from 22-7 ± agreement with the previous observation patients described here presented with the Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A952 The British Society of Gastroenterology characteristic clinical history and bio- DNA binding antibodies; in one patient was no difference. All patients developed chemical changes of an acute viral there was a fourfold rise in the serum alopecia while taking cyclophosphamide, hepatitis, but antinuclear factor was AST. During treatment there was a strik- one haemorrhagic cystitis, three leuco- invariably positive (> 1:160) and one ing fall in the anti-HBc titre, which has penia, and the only male patient developed patient also had a Coomb's-positive been maintained; in one patient the azospermia. haemolytic anaemia. HBsAg was negative. initially high AST level fell to normal. In Therefore we doubt that cyclophospha- Initial liver biopsy was indistinguishable both patients high DNA binding anti- mide aids the management of ACH from acute hepatitis-namely, an acute bodies fell during treatment to normal sufficiently to justify its toxicity, and the inflammatory infiltrate throughout the levels, which have been maintained. trial has been concluded. lobules with relatively little change in the The fall in titre of anti-HBc and DNA portal areas. After two to five months' binding antibodies as a result of inter- Serial changes in plasma tyrosine and observation, when the illness showed no feron treatment has several possible phenylalanine levels in patients with signs of remitting, corticosteroids were explanations: the release of core antigen fulminant hepatic failure treated by given with rapid symptomatic and bio- and DNA, either autologous or viral polyacrylonitrile haemodialysis: relation- chemical improvement. specific from the liver, may complex with ship to coma During follow-up for three, three, and their respective antibodies resulting in a eight years attempts to reduce prednisone fall in titre. Alternatively, interferon R. A. CHASE, M. DAVIES, P. N. TREWBY, dosage below 17 5 mg/day invariably treatment may stop viral replication in the D. B. A. SILK, AND ROGER WILLIAMS (Liver resulted in reappearance of deep jaundice liver with suppression of these markers. Unit, King's College Hospital and Medical and strikingly high values of AST (500 to No significant adverse effect occurred School, London) Previous work in experi- 2000 IU/l). Further biopsies during and these observations should encourage mental hepatic coma has suggested a remission have shown a complete return further trials of fibroblast interferon in causal relationship between rises in levels to normal, but during relapse the changes hepatitis B. of plasma tyrosine and phenylalanine and have always been those initially observed accumulation in the brain of the false with the inflammatory infiltrate confined Controlled trial of cyclophosphamide in neurotransmitters, octopamine and phe- largely to the lobules ('lobular hepatitis'), active chronic hepatitis nylethanolaminel. In the present study we without progression to cirrhosis even after have therefore examined serial changes eight years in one patient. One patient has I. T. GILMORE, R. E. COWAN, A. T. R. AXON, (two to six hourly) in plasma amino acid subsequently died after a staphylococcal AND R. P. H. THOMPSON (Gastrointestinal profiles of 26 patients with fulminant septicaemia. Laboratory, Rayne Institute, St. Thomas' hepatic failure treated by daily four to six These cases, it is suggested, represent a Hospital, London) Azathioprine is an hours polyacrylonitrile haemodialysis2, of distinct entity, with histological features of accepted adjunct to corticosteroid treat- whom 10 regained consciousness and nine acute viral hepatitis, but, clinical and ment in active chronic hepatitis (ACH), (34-6 %) survived. http://gut.bmj.com/ immunological features more in keeping but the value of other immunosuppressive Plasma levels of tyrosine (median 270 5 with chronic active hepatitis, in that long- agents is uncertain. In a controlled cross- [tM, range 78-573) and phenylalanine (318 term corticosteroid therapy seems essen- over trial, cyclophosphamide has therefore ,tM, range 77-716) were raised three- to tial, although progression to that disease been added to prednisolone therapy in four-fold above normal controls on has not been observed, and the term patients with histologically confirmed admission in grade IV coma. Clearances chronic lobular hepatitis is a suitable HBsAg-negative ACH. equivalent to nine pretreatment pools of descriptive one. Activity of the disease was first kept these amino acids were achieved during six

under control (SGOT <2 x normal) for hour haemodialysis, indicating the rapidity on September 28, 2021 by guest. Protected copyright. Treatment of HBsAg-positive chronic at least four weeks with prednisolone, with which they re-equilibrated between active hepatitis with human fibroblast which was then reduced every two weeks tissue and plasma compartments. interferon by 2 mg/day until relapse (SGOT > 3 x Despite removal oflarge quantities (5-17 normal). Prednisolone was then increased mmol tyrosine, 2-81 mmol phenylalanine) J. G. C. KINGHAM, N. K. GANGULY, Z. D. until control had been regained for four of amino acids during six hour dialysis, SHAARI, S. T. HOLGATE, M. J. MCGUIRE, R. weeks, and the patients then randomly there was no relationship between total MENDELSON, T. CARTWRIGHT, G. M. SCOrT, allocated to receive either cyclophospha- removal and final outcome. Serial studies B. M. RICHARDS, AND RALPH WRIGHT mide, 2 mg/kg/day, or placebo for 12 in six survivors showed plasma levels (Professorial Medical Unit, Southampton weeks, while prednisolone was again returning to normal 48 hours in advance General Hospital, Southampton and Searle reduced. After relapse prednisolone was of recovery ofconsciousness in four out of Research Laboratories, High Wycombe) increased, and, after four weeks' control, six patients (phenylalanine) and three out Two patients with HBsAg positive chronic the patients were crossed over. of six (tyrosine). active hepatitis have been treated with Ten patients entered the trial; five This inexact relationship suggests that human fibroblast interferon 107U daily for patients crossed over once and one twice, raised plasma levels of tyrosine and two weeks. Serum hepatitis B markers, providing seven pairs of data for com- phenylalanine are not solely responsible DNA binding antibodies, liver function parison (four patients failed to relapse). In for the encephalopathy in fulminant tests, and haematological parameters have four, a longer control period followed hepatic failure. been tested before, during, and for four cyclophosphamide therapy than placebo, months after treatment. Before treatment two patients having remissions for three to References both patients had high levels of HBsAg six months, but in two a longer control and core antibodies (anti-HBc) and high period followed placebo, and in one there 'Fischer, J. E., and Baldessarini, R. J. (1971). False Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A953 neurotransmitters in hepatic failure. Lancet, 2, Loss of cerebral autoregulation in an rhosis (20), and extrahepatic bile duct 75-80. 'Silk, D. B. A., Hanid, M. A., Trewby, P. N., animal model of liver failure obstruction (18), and completed coding Davies, M., Chase, R. A., Langley, P. G., forms which listed 18 hepatocyte and eight Mellon, P. J., Wheeler, P. G., and Williams, R. P. N. TREWBY, M. A. HANID, R. L. portal tract abnormalities graded 1-4 (1977). Treatment offulminant hepatic failure by MACKENZIE, P. J. MELLON, AND ROGER depending on severity. haemodialysis using a polyacrylonitrile mem- 1-3. WILLIAMS (Liver Unit, King's College With respect to diagnosis, there was brane. Lancet, 2, Hospital and Medical School, London) agreement between the two experienced Two main complications of fulminant observers in 48 of 60 (80%) cases. How- Insulin, glucagon, and amino acid imbalan- hepatic failure are hypotension and ever, total agreement among all three was ces in fulminant hepatic failure cerebral oedema developing in association less (56 7 %). Agreement regarding specific with a raised intracranial pressure. Little histological abnormalities was uniformly is known as to the relationship between distributed among the three observer R. A. CHASE, S. SULLIVAN, S. R. BLOOM, D. B. the 4534 A. SILK, AND ROGER WILLIAMS (Liver Unit, these two and cerebral blood flow and we pairs and occurred in 62-5% of King's College Hospital and Medical have therefore investigated this in a pig comparisons. Minor disagreement (one School, London, and Department of model of surgically induced acute liver grade differences) occurred in 26-4% of Medicine, Royal Postgraduate Medical failure. comparisons. Differences of two grades School, Hammersmith Hospital, London) When normotensive (systolic BP 90-120 occurred in 10-9% of comparisons but Hepatic encephalopathy in patients with mmHg) cerebral blood flow (CBF) was severe disagreement (three grade dif- chronic liver disease is associated with significantly lower in the animals with ferences) occurred in only 0-2% of changes in plasma amino acid patterns- liver failure than in the controls. Induction comparisons. decreased branched chain amino acids of hypotension was associated with a fur- Although the results showing complete (valine, leucine, isoleucine) and increased ther fall, a significant positive correlation agreement about grading of specific aromatic amino acids (phenylalanine, being found between CBF and systolic BP histological abnormalities in two-thirds of tyrosine)' mediated, it is suggested, by a in the animals with liver failure (r = 0 53, cases are reassuring, with regard to reach- reduction of the molar ratio of immuno- P < 0-01). In the controls no such fall in ing a final histological diagnosis, exper- reactive insulin to glucagon from 3 to 12. CBF occurred despite systolic blood pres- ience appears to be of more major These relationships were the subject of sures of as low as 30 mmHg. In the ani- importance. the present study in 25 patients with mals with liver failure but not in the con- fulminant hepatic failure in grade IV trols a raised intracranial pressure further Histocheniical demonstration of liver cop- coma. Branched chain amino acids compounded the fall in CBF. per and copper carrying protein in chronic (BCAA) (354-9 ± SE 38-0 ,pmol/l) were As CBF fell there was a significant fall liver disease normal. Aromatic amino acids (AAA) in cerebral metabolic rate for oxygen were increased three-fold (538-7 ± 50-0), (CMRO2) in the animals with liver failure, S. JAIN, P. J. SCHEUER, BARBARA ARCHER, S. http://gut.bmj.com/ so that the ratio BCAA/AAA was reduced whereas in the controls a fall in CBF was NEWMAN, AND SHEILA SHERLOCK (Depart- (0-74 ±0-08 compared with 3-29 ± 0-26 in accompanied by a compensatory increase ments of Medicine, Histopathology, and controls). Insulin (1094 ± 285 pmol/l) and in oxygen extraction so maintaining a nor- Physics, Royal Free Hospital, Pond glucagon (74-6 ± 10-6 pmol/l) were both mal CMRO2. Street, London) Liver copper concentra- markedly raised and the mean insulin/ This disruption in cerebral circulatory tions can be raised in most chronic liver glucagon ratio was 22-2. Repeat measure- responses, if extrapolated to man, empha- diseases. In Wilson's disease removal of ments in four patients as conscious level sises the importance of preventing the rise excess copper by chelation is essential, and improved (grades 0-IT coma) showed that in intracranial pressure consequent on the same treatment may be of use in on September 28, 2021 by guest. Protected copyright. there was a fall in both insulin (mean cerebral oedema, and promptly treating primary biliary cirrhosis' (PBC). Liver 22-3 %) and glucagon (49-8 %). The mean any reduction in blood pressure if copper concentrations have been mea- insulin/glucagon ratio remained raised secondary hypoxic brain damage is to be sured by neutron activation analysis, and (10-7), however, and the BCAA/AAA avoided. compared with staining for copper by ration (0-96 ± 0-13) was still markedly rubeanic acid and rhodanine, and with reduced. Study of interobserver variation between copper-carrying protein stained by orcein2. These findings strongly suggest that, liver histopathologists The comparison has been made in 69 unlike the situation in the encephalopathy percutaneous liver biopsies; 35 patients of chronic liver disease, the amino acid A. THEODOSSI, R. P. KNILL-JONES, D. B. A. had PBC, 18 Wilson's disease, and 16 changes in FHF are not caused by reduc- SILK, AND ROGER WILLIAMS (Liver Unit, chronic active hepatitis (CAH), HBsAg tions in the ratio. King's College Hospital, Denmark Hill, positive and negative. Liver copper insulin/glucagon London) Relatively little information is concentrations were raised in 31 of the available about interobserver variation patients with PBC, and the degree of References between histopathologists, and the pur- histochemical staining for copper (graded pose of the present study was to assess the 0-3) rose with increasing liver copper 'Fischer, J. E., Rosen, H. M., Ebeid, A. M., James, in J. H., Keane, J. M., and Soeters, P. B. (1976). magnitude of such variation among two levels. Orcein staining was positive 33 The effect of normalization of plasma amino experienced and one senior trainee histo- of the 35 patients. acids on hepatic encephalopathy. Surgery, 80, pathologist. Without knowledge of the All of the patients with Wilson's disease 77-91. each reviewed the same 60 had high liver copper concentrations, but 2Soeters, P. B., and Fischer, J. E. (1976). Insulin, diagnosis, glucagon, amino acid imbalance and hepatic specimens obtained from patients with nine of the 18 had negative histochemical encephalopathy. Lancet, 2. 880-882. acute viral hepatitis (22), alcoholic cir- staining for copper, and 12 were orcein Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A954 The British Society of Gastroenterology negative. Similarly, histochemical stains Foster, G., Kourides, I. A., and Isselbacher, concentration should be performed. gave little indication of the liver copper K. J. (1977). Familial haemochromatosis. New England Journal of Medicine, 296, 1422-1426. References concentration in CAH. Histochemical 'Jacobs, A. (1977). Iron overload-clinical and staining of liver sections is useful in pathological aspects. Semaine Haematologie, 14, 'Bomford, A., and Williams, R. (1976). Quarterly detecting rises in liver copper in PBC, but 89-110. Journal of Medicine, 10, 61 1-612. not in Wilson's disease, where the absolute 'Prieto, J., Barry, M., and Sherlock, S. (1975). 2Feller, E. R., Pont, A., Wands, J. R., et al. (1977). Serum ferritin in patients with iron overload and New England Journal of Medicine, 296, 1422- concentration must be measured. with acute and chronic liver diseases. Gastro- 1426. enterology, 68, 525-533. 'Halliday, J. W., Gera, K. L., and Powell, L. W. References (1975). Clinica Chimica Acta, 58, 207-214. 'Jain, S., Scheuer, P. J., Samourian, S., McGee, J. Diagnosis of early haemochromatosis: O'D., and Sherlock, S. (1977). A controlled trial relative reliability of the serum ferritin, of D-penicillamine therapy in primary biliary serum iron and transferrin saturation Parenteral 1,25-dihydroxycholecalciferol in cirrhosis. Lancet, 1, 831-834. hepatic osteomalacia 2Salaspuro, M., and Sipponen, P. (1976). Demon- stration of an intracellular copper-binding L. W. POWELL, JUNE W. HALLIDAY, ANNA protein by orcein staining in long-standing RUSSO, AND J. COWLISHAW (introduced by R. G. LONG, Z. VARGHESE, E. MEINHARD, cholestatic liver disease. Gut, 17, 787-790. SHEILA SHERLOCK) (Department of Medi- R. K. SKINNER, M. R. WILLS, AND S. SHERLOCK cine, University of (Royal Free Hospital, Pond Street, Value of serum ferritin in the management Queensland, Royal Hampstead, London) The aim of this of haemochromatosis Brisbane Hospital, Brisbane, Australia) The early detection and treatment of idio- study was to assess the use of 1,25- R. G. BATEY, S. HUSSEIN, SHEILA SHERLOCK, pathic haemochromatosis (IHC) is import- dihydroxycholecalciferol (1,25-DHCC) in AND A. V. HOFFBRAND (Department of ant to prevent complications1. Tests cur- four female patients with biliary cirrhosis Medicine and Haematology, Royal Free rently used for screening relatives of and hepatic osteomalacia. Osteoid and Hospital, Hanipstead, London) The role patients are cumbersome and unreliable2. total bone volume proportion was asses- of serum ferritin (FN) in diagnosing The serum ferritin concentration (SF) cor- sed by a computerised technique and para- haemochromatosis is currently being relates closely with body iron stores in thyroid hormone (i-PTH) was measured questioned' as FN metabolism may be normal subjects and in patients with iron by radioimmunoassay. 1,25-DHCC 15-30 abnormal in this disease2. deficiency or transfusional iron overload, micrograms in arachis oil was given intra- We have assessed the value of the test at but the evidence for its diagnostic role in muscularly once a month instead of the diagnosis during venesection therapy and early IHC is conflicting2. We have studied previous monthly vitamin D2 100,000 IU during iron reaccumulation and report 43 families with IHC in order to assess the in ethyl oleate. these results. Liver biopsy iron has been relative values, both singly and in combi- Before treatment with l,25-DHCC all taken as the final determinant of storage nation, of the serum iron, percent four patients had bone pains and severe osteomalacia without osteoporosis. Three iron levels. saturation of serum transferrin (TF), and http://gut.bmj.com/ At diagnosis there was no correlation SF concentration. patients also had a proximal myopathy. between FN and liver biopsy iron (n = 14, Forty-three probands and 199 first or Plasma calcium, phosphorus, magnesium, P > 01). The FN/aspartate transaminase second degree relatives were examined. and serum 25-hydroxyvitamin D levels ratio3 correlated with liver iron values > SF levels were measured by a solid phase were normal. 47-calcium and phosphorus 1000 tsg Fe/100 mg liver (normal < 160 radioimmunoassay3. Increased iron stores absorption was normal in three of the four ,ug/100 mg) but when liver iron was were confirmed by desferrioxamine- patients. No evidence ofhyperparathyroid- between 160-1000 ,ug/100 mg there was no chelatable iron, hepatic iron concentra- ism was found. = Treatment with 1,25-DHCC for one to correlation (r 007). Venesection tion, and by quantitative phlebotomy. All on September 28, 2021 by guest. Protected copyright. resulted in an intial transient rise in FN probands had classical clinical and five months resulted in loss of bone pain in values in two of eight patients but was pathological features of IHC including three patients and resolution of myopathy followed in all by a progressive fall in cirrhosis and gross increase in total body in two patients. Follow up bone biopsy values during therapy. No day-to-day or iron. The serum iron was increased in 37 showed a reduction in osteoid tissue: this diurnal variation was noted in any patient. (90%), the TF saturation in 43 (100%), indicates healing of osteomalacia. Serum FN reached iron deficient levels before and the SF also in all 43 (range 670 to 4100 and urine biochemistry and absorption iron stores had been depleted in three out ug/l) normal ranges 10-150 for females, tests changed little with treatment. of five patients. 20-200 for males). Of the 31 relatives with It appears that 1,25-DHCC has a direct After venesection, FN remained low increased iron stores (16%) the serum iron beneficial effect on bone and muscle despite iron reaccumulation in two out of was raised in 23 (76 %), the TF saturation in hepatic osteomalacia. This response five. in 31 (100%), and the SF in 30 (98%). suggests either a failure of vitamin D Serum ferritin is of limited value in the However, ofthe relatives with normal iron 1-hydroxylation or that hepatic osteo- management of haemochromatosis. It may stores the serum iron was raised in 17 malacia is vitamin D2 resistant. aid in monitoring venesection therapy or (10%), the TF saturation was increased in in diagnosing advanced disease. It pro- 56 (33 %), and SF levels were raised in Induction of remission in hepatocellular vides little help in detecting early disease, three (1-8%). carcinoma with adriamycin iron store depletion, or iron reaccumula- We conclude that the combination of tion in these patients. serum iron and SF concentrations is a P. J. JOHNSON, ROGER WILLIAMS, H. reliable non-invasive screening test for THOMAS, SHEILA SHERLOCK, AND I. M. References significant iron overload. If either is MURRAY-LYON (Liver Unit, King's Col- 'Feller, E. R., Pont, A. Wands, J. R., Carter, E. A. abnormal, liver biopsy and hepatic iron lege Hospital and Medical School, London, Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A955 Royal Free Hospital, London, and Charing Using specific factor assays and quanti- of patients developing wound sepsis one or Cross Hospital, London) This report con- tative immunoelectrophoresis with anti- more of the organisms isolated from the cerns the use of adriamycin (60 mg/M2 bodies raised in rabbits to individual incision were the same as those previously intravenously at three-weekly intervals to a clotting factors, vitamin K responsive identified from gastric juice, and, in these total dose of 550 mg/M2) in 30 patients, all patients were shown to have low pro- cases, the viable counts of the gastric of whom were considered unfit for trans- coagulant activity but normal amounts of juice were > 105 organisms/ml. plantation because of extrahepatic spread, immunologically abnormal precursor pro- These results indicate that patients tumour metastases, or poor general tein. Vitamin K unresponsive patients had likely to develop wound sepsis after gastric condition. Twenty-four had underlying decreased amounts of both procoagulant surgery can be identified by performing cirrhosis. activity and of immunologically normal viable counts on gastric aspirates collected Of 20 patients followed for at least three precursor protein. at preoperative endoscopy. months, eight have shown an undoubted We conclude that in obstructive jaun- response. Four of these are alive and well dice an abnormal precursor protein is References at seven, 10, 14, and 15 months after synthesised. In hepatocellular disease the 'Stone, H. H., Hooper, C. A., Kolb, L. D., Geheber, diagnosis. Repeat angiography in three precursor protein is structurally normal C. E., and Dawkins, E. J. (1976). Antibiotic pro- cases has shown disappearance of pre- but reduced in amount. The modified phylaxis in gastric, biliary and colonic surgery. Annals of Surgery, 184, 443-450. viously extensive tumour circulation and thrombotest detects inhibitory activity of 'Cruse, P. J. E., and Foord, R. (1973). A five year another patient has shown partial clearing PIVKA and can predict response to prospective study of 23 649 surgical wounds. of lung metastases. Within three weeks of vitamin K. the first injection there was a fall of more Aetiology of gastritis occurring after than 50% in alpha fetoprotein levels in Reference surgery for peptic ulcer seven of the 15 alpha fetoprotein positive 'Hemker, H. C., Veltkamp, J. J., Hensen, A., and patients and all of these showed subse- Loeliger, E. A. (1963). Nature of prothrombin A. M. HOARE, H. M. CHAPEL, AND quent clinical remission. In contrast, the biosynthesis: preprothrombinaemia in vitamin K J. ALEXANDER-WILLIAMS (The Queen eight patients in whom values rose died deficiency. Nature, 200, 589-590. Elizabeth and General Hospitals, Birming- within three months from tumour pro- ham, and the Department ofExperimental gression. Failure of alpha fetoprotein CLINICAL SURGICAL Pathology, University of Birmingham) levels to fall within three weeks of Gastritis occurs in the majority of patients instituting therapy is thus of predictive Bacterial flora of the stomach in patients who have had operations for duodenal value. Side-effects were restricted to mild requiring gastric operations ulcer. The aetiology remains obscure, but nausea and reversible alopecia, and the one current theory is that it is caused by present response rate-and, in particular, D. GATEHOUSE, F. DIMOCK, D. W. BURDON, reflux of bile into the stomach'. the of life-are far better than J. ALEXANDER-WILLIAMS, AND M. R. B. quality We have estimated the concentration of http://gut.bmj.com/ those obtained in a previous controlled KEIGHLEY (The General Hospital, Bir- bile in gastric aspirates by the enzymatic trial of multiple cytotoxic therapy and mingham) Gastric resections for ulcer method of Fausa and Skalhegg2. Gastric radiotherapy. and carcinoma are associated with a high biopsies were obtained at endoscopy from incidence ofwound infection' which is pro- the same patients, all of whom had pre- Protein induced by vitamin K absence bably due to disseminating gastrointestinal viously had surgery for duodenal ulcer. (PIVKA) in liver disease: response to IV organisms into the incision at operation2. There was no correlation of gastritis with vitamin K1 therapy We have therefore studied the microflora concentration of bile acids in aspirates of the stomach in normal subjects (n = obtained from the fasting patient (mea- on September 28, 2021 by guest. Protected copyright. F. E. PRESTON, C. D. HOLDSWORTH, AND 11), in duodenal ulcer (n = 30), gastric sured in 105 patients), after pentagastrin R. G. MALIA (Departments ofMedicine and ulcer (n = 12), and gastric carcinoma (measured in 59 patients), or overnight Haematology, Royal Infirmary, Sheffield) (n = 28). Viable counts of aerobic and (measured in 18 patients). Oral anticoagulants compete with vitamin anaerobic organisms have been performed The gastritis occurring after surgery is K and precursor proteins (PIVKA) are on the gastric secretions obtained both by histologically identical with that of produced instead of the normal factors II, preoperative endoscopy and preoperative pernicious anaemia. To exclude immuno- VII, IX, and X'. These have not been nasogastric aspirations. logical factors as a cause of postoperative studied in liver disease. We have measured There was a close correlation between gastritis, immunofluorescent examination PIVKA in jaundiced patients and assessed the bacterial flora of gastric fluid obtained has been performed on gastric biopsies whether it can be used to predict correction at preoperative endoscopy compared with from 20 patients with gastritis after sur- ofprolonged prothrombin time by vitamin operative samples. The mean counts of gery for duodenal ulcer. They contained K1. organisms/ml in gastric juice were as fol- predominantly IgA and no IgG, contrary In seven patients with extrahepatic lows: normal subjects 0 x 10°; duodenal to findings in pernicious anaemia. In some obstructivejaundice mean PIVKA activity, ulcer 1 x 101; gastric ulcer 5 x 102; patients with pernicious anaemia there is assessed by a modified thrombotest, was carcinoma 1 3 x 105. In 53 % of patients cell mediated immunity to gastric antigen, high at 3-7 units/ml (normal 0-1). In these with gastric carcinoma viable counts were as demonstrated by the leucocyte migra- patients prolonged prothrombin times > 105/ml. tion test. We have been able to confirm corrected 24 hours after 10 mg intravenous The incidence of wound infection in this in patients with pernicious anaemia, vitamin K1. In seven jaundiced patients patients undergoing surgery was as fol- but there was no response to gastric with intrahepatic disease, PIVKA was lows: duodenal ulcer 15 %, gastric ulcer antigen in 20 patients with postoperative normal and vitamin K1 ineffective. 29%, and gastric carcinoma 54 %. In 70% gastritis. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A956 The British Society of Gastroenterology Bile reflux or immunological factors are Effect of phenformin on provoked dumping was performed for 'non-correctable' unlikely to be the cause of gastritis occur- in man EHBA. Postoperatively, the stools be- ring after gastric surgery. came bile pigmented in 10. Five, four of W. G. HUMPHREYS, T. G. PARKS, K. D. whom were operated on at 10 weeks, and References BUCHANAN, AND A. H. G. LOVE (Depart- one at 21 weeks, became free from ments of Surgery and Medicine, Queen's 'Bushkin, F. L., Wickbom, G., De Ford, J. W., and jaundice and survive at the age of 6 to 51 Woodward, E. R. (1974). Post-operative alkaline University, Belfast N. Ireland) Dumping months. Four have had cholangitis and reflux gastritis. Surgery, Gynecology and remains a complication of gastric opera- one required oesophageal transection for Obstetrics, 138, 933-939. tions: in the past patients with persistent 2Fausa, O., and Sk&lhegg, B. A. (1974). Quantitative bleeding varices. In a further five patients determination of bile acids and their conjugates symptoms have benefited from treatment operated at eight (two), 11 (two), and 13 using thin layer chromatography and a purified with antidiabetic drugs. This study was weeks, the serum bilirubin fell substan- 3 alpha-hydroxysteroid dehydrogenase. Scandi- undertaken in patients with persistent tially but cirrhosis and its complications navian Journal of Gastroenterology, 9, 249-254. dumping to investigate the effects of developed by 12 months of age. One has the biguanide phenformin on the symp- already died. In the remaining five Combination of proximal gastric vagotomy toms, cardiovascular parameters, and patients operated on at 9, 11, 12, 14, with a rotational posterior gastropexy gastrointestinal hormone release. A dump- and 18 weeks of age, stools remained ing stimulus of 150 ml of 30% glucose was acholic. Four died by 11 months of age. D. M. HANCOCK, M. Y. SANKAR, J. M. OLD, given on separate occasions before and Bile duct to bowel anastomosis in A. A. K. BOSE, F. LOBO, P. TRINDER, AND after 100 mg of phenformin. EHBA is rarely successful. Portoentero- P. L. PUNNER (Department of Surgery, Phenformin was found to decrease the Sunderland, Tyne and stomy performed before intrahepatic General Hospital, induced hyperglycaemia (p < 005), changes are advanced gives the best Wear) We have reduced oesophagal decrease the tachycardia (p < 0 05), and chance of long-term survival. reflux symptoms and insulin reactivity decrease the duration and magnitude of after proximal gastric vagotomy (PGV the fall in diastolic blood pressure (p < Experimental production of white bile in only) by combining PGV with a rotational 0 05). There was no significant change in biliary obstruction posterior gastropexy (PGV/pexy). Thirty- the symptom score or in the decrease in nine PGV only cases are compared with 42 blood volume. Hypertonic glucose stimu- S. J. S. KENT* AND B. T. JACKSON PGV/pexys over a one to six year follow- lated gastrin release (p < 001); however, (St. Thomas' Hospital, London) Rous and up relating postoperative symptoms to the plasma gastrin, insulin, and pancreatic McMaster1 concluded that white bile preoperative state. Our preliminary good GLI (glucagon-like immunoreactivity) formed in biliary obstruction only when results with the pexy procedure have been release were not affected by pretreatment in this series. Gastro- the gallbladder was non-functioning. Our maintained larger with phenformin. The most significant experiments disprove this theory and offer oesophagal competence has also been finding was the enhanced release of intes- testing or an alternative explanation for the forma- http://gut.bmj.com/ assessed by oesophagal pH tinal GLI in response to oral glucose after tion of white bile. aspiration after stimulation with penta- phenformin. meal. The Biliary obstruction was produced in 54 gastrin and a glucose sensitivity These results suggest that phenformin New Zealand white rabbits; 24 having of these tests can be reduced by separating in the 'acute' situation produces objective the two stimuli. complete obstruction, 24 partial obstruc- but not subjective improvement in the tion, and six intermittent complete Reinnervation across nerve gaps should experimental dumping reaction. Intestinal be prevented after PGV/pexy due to obstruction. In half the animals in each GLI is stimulated to a greater degree after group, the gallbladder was excised at the separation of cut nerve twigs. Faber's phenformin, without an appreciable in- same time as the obstruction was pro- on September 28, 2021 by guest. Protected copyright. discriminant (8 mmol H+/h) was used to crease in the severity of dumping. Thus, insulin tests in which duced. define positive (> 8) the role of GLI in the pathogenesis of Nine out of 24 rabbits with complete a 50%. chance of recurrent ulceration has dumping remains uncertain. been reported. Six out of 25 PGV only obstruction formed white bile, while none tests were Faber positive at one year, as of the rabbits with partial obstruction against only one out of 36 PGV/pexys Extrahepatic biliary atresia: results of formed white bile (p < 0-01). White bile (P < 0 05). surgical treatment formation was distributed evenly between Postoperative dysphagia has been those rabbits with the gallbladder intact avoided and heartburn and regurgitation E. R. HOWARD, H. PSACHAROPOULOS, AND (five with white bile) and those in whom reduced after PGV/pexy. The recurrent A. P. MOWAT (King's College Hospital, it had been excised (four with white bile) ulcer rate may also be reduced by this London) Thirty infants with extrahepatic (p > 0-05). Two out of six rabbits with biliary atresia (EHBA) have undergone intermittent obstruction also formed white procedure. laparotomy between June 1973 and April bile. References 1977. In 11 cases direct anastomosis be- It has been shown that the rabbit gall- tween small proximal bile ducts and bowel bladder ceases to concentrate bile in 'Sankar, M. Y., Old, J. M., Trinder, P., Bose, was attempted ('correctable' EHBA). In biliary obstruction2 and these findings A. A. K., Lobo, F., and Hancock, D. M. (1976). The advantages of combining posterior four cases operated on at 10-14 weeks, coincide with the failure of the gallbladder gastropexy with proximal gastric vagotomy. stools became acholic and in two of these to influence the formation of white bile in Chir Gastroenterology, 10, 389-392. the serum bilirubin returned to normal. the experiments now reported. It is sug- 'Faber, R. G., Russel, R. C. G., Parkin, J. V., infants died of liver disease 12 Whitfield, P., and Hobsley, M. (1975). The pre- Eight by gested that white bile may form in com- dictive accuracy of the post-vagotomy insulin months of age. plete or intermittent biliary obstruction test. Gut, 16, 337. In 15 infants hepatic portoenterostomy but not in partial biliary obstruction. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A957

References BADDELEY, N. J. DORRICOTT, M. R. B. fever, chills and rigors, abdominal pain, and 'Rous, P., and McMaster, P. D. (1921). Physio- KEIGHLEY, G. D. OATES, AND G. T. WATTS jaundice and in which the extrahepatic and logical causes for the varied character of stasis (The General Hospital, Birmingham) intrahepatic ducts are frequently dilated bile. Journal of Experimental Medicine, 34, 75- On table 95. cholangiography (OTC) and and contain pigment stones'. It is one of 'Kent, S. J. S., and Segal, M. B. (1975). The effect completion cholangiography have reduced the most common causes of acute ab- of biliary obstruction on the concentrating the incidence of retained stones after dominal emergencies admitted to hospitals activity of the rabbit gallbladder. Journal of biliary surgery' but both techniques are in HongKong'. Information ofradiological Physiology, 251, 33-34. subject to errors of interpretation and changes of the biliary system has hitherto *This work was carried out in the preparation of an MS thesis for London University. technical failures2. Choledochoscopy is an been obtained from operative and T-tube alternative diagnostic technique applicable cholangiograms, which does not represent Clinical significance of white bile in before and after duct exploration.3 the whole spectrum of the disease, as such obstructive jaundice We have analysed the experience of all cholangiograms are performed on patients the general surgeons in our hospital in 101 who require surgery. With the advent of S. J. S. KENT * AND B. T. JACKSON (St. explorations with the rigid choledocho- ERC, study of the biliary system can be ex- Thomas' Hospital, London) Emslie and scope in 90 patients. Forty-two choledo- tended to patients who respond to medical his colleagues1, reporting a small series of choscopies were perforned before con- treatment and in whom surgery is not nine patients, challenged the unproven ventional duct exploration and 59 after. planned. Endoscopic retrograde chol- surgical aphorism that the presence of The findings at pre-exploratory chole- angiograms were studied in 52 patients white bile in the bile ducts of patients with dochoscopy were correct in 39 examina- with RPC. Theearlierchanges of RPC were obstructive jaundice is a sign of liver tions with three false negative results. identified and found to be confined to the failure and poor prognosis. This paper Post-exploratory choledochoscopy cor- intrahepatic biliary tree. The left hepatic reports the results of a study of 69 rectly identified clear ducts in 51 examina- duct was more severely affected than the patients with obstructive jaundice who tions but stones or debris were missed in right hepatic duct and had a higher infest- had white bile and 68 patients (also with eight. The overall accuracy of OTC and ation by clonorchis. The severity of radio- obstructive jaundice and of similar age, completion cholangiography in the same logical changes correlated well with the sex, duration of jaundice, and pre- patients was 85% and 78% respectively. duration ofillness and the need for surgery. operative serum bilirubin) who did not There were three false negative (stones) Gall stones were present in 34-2% of the have white bile. and five false positive (air bubbles). When patients and pancreatic ductal abnor- After operative relief of jaundice, the x-ray was combined with choledochoscopy mality in 7-7%. The decision for surgery rate of decrease in serum bilirubin in the diagnostic accuracy was improved, could be made early and accurately, and patients with white bile, mean 10-3 4+ 1-37 97% before duct exploration and 90% the type of surgery and the assignment of ,umol/l/day was not significantly less than after. surgeons could be planned in advance- the rate in patients who did not have white These preliminary findings suggest that

situations which conventional intravenous http://gut.bmj.com/ bile, mean 15-4 + 2-74 jxmol/l/day (P > choledochoscopy is not a substitute for cholangiograms could not achieve. Chol- 0 05). There was also no difference in OTC but a valuable adjunct. The addition angitis complicated ERC in 23-1 % of the length of survival after relief of jaundice of choledochoscopy should reduce the initial 26 patients without antibiotic cover (allowing for the better prognosis of incidence of retained common bile duct but none of the subsequent 26 in whom patients with benign biliary disease). stones, prevent fruitless search for OTC this was employed. White bile does not appear to indicate air bubbles, and, possibly make obsolete either liver failure or poor prognosis. completion cholangiography. Reference Malignant disease was the cause of References 'Ong, G. B. (1962). A study of recurrent pyogenic on September 28, 2021 by guest. Protected copyright. biliary obstruction in 61 of 69 patients cholangitis. Archives of Surgery, 84, 199-225. with white bile but was present in only 39 'Havard, C. (1970). Operative cholangiography. of the 68 patients who did not have white British Journal of Surgery, 57, 797-807. Single centre double-blind trial of trasylol bile (P > 0-01). This finding might be 2Hall, R. C., Sakiyalak, P., Kim, S. K., Rogers, L. S., and Webb, W. R. (1973). Failure of operative therapy in primary acute pancreatitis expected, as the results of experimental cholangiography to prevent retained common work with rabbits2 have suggested that duct stones. American Journal of Surgery, 125, C. W. IMRIE, I. S. BENJAMIN, J. C. FERGUSON, white bile forms in complete rather than 5 1-63. W. 0. THOMSON, A. J. MCKAY, J. O'NEIL, AND 3Longland, C. J. (1973). Choledochoscopy in partial biliary obstruction. choledocholithiasis. British Journal of Surgery, L. H. BLUMGART (University Department 60, 626-628. of Surgery, Royal Infirmary, Glasgow) References One-hundred-and-sixty-one consecutive 'Emslie, R. G., Thorpe, M. E. C., Colman, J. V. L., Endoscopic retrograde cholangiography patients with primary acute pancreatitis Boughton, C. R., Pritchard, G. R., and Hoy, (ERC) in (Oriental) recurrent pyogenic were admitted to a double blind trial of R. J. (1969). Clinical significance of white bile in cholangitis (RPC) trasylol therapy as a supplement to a the biliary tree. Gut, 10, 530-533. standard conservative 2Kent, S. J. S. (1976). White Bile. MS Thesis, Lon- management don University. SHIU-KUM LAM, KAI-PING WONG, P. K. W. regimen1. The patients were subdivided *This work was carried out in the preparation of an CHAN, H. NGAN, AND G. B. ONG (Depart- into group 1 (those less than 60 years old) MS thesis for London University. ments ofMedicine and Surgery, University and group 2 (age 60 years and over) and of Hong Kong, Queen Mary Hospital, within those groups were randomly Accuracy of operative choledochoscopy Hong Kong and Institute of Radiology, allocated on a double blind basis to Queen Mary Hospital, Hong Kong) RPC either trasylol therapy in a starter dose of A. KAPPAS, J. ALEXANDER-WILLIAMS, R. M. is characterised by recurrent attacks of 500,000 KI units and thereafter 200,000 Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A958 The British Society of Gastroenterology q.i.d. for five days, or to a placebo. urea (p < 0 01), calcium (p < 0 01), high potential difference (PD) across There was an overall mortality rate of potassium (p < 001), bilirubin (p < 0 01), ileostomy mucosa in vivol. 8*7 % with seven deaths in both the trasylol white cell count (p < 0 02) and alkaline We therefore examined the electrical and non-trasylol group. In addition to phosphatase (p < 0-05). characteristics and electrolyte transport there being no significant difference either In five patients lavage correctly pre- activity of ileostomy ipucosal biopsies overall or within either age group, in dicted a severe attack at a time when it searching for evidence ofsuch 'adaptation'. respect of mortality there was also no sig- was thought to be mild on clinical Two suction biopsies of ileostomy mucosa nificant difference in the incidence of the grounds. were taken from each of eight patients (in major clinical complications of acute vivo PD 10-78 ± 2-8 mV) and these were respiratory or renal failure, or the develop- Ileostomy function at home mounted in specially designed miniature ment of pancreatic pseudocyst or abscess. flux chambers and bathed in oxygenated Similarly, factors considered of prognostic N. I. MCNEIL, S. A. BINGHAM, A. M. GRANT, buffer at 370. importance such as severe arterial hypox- AND J. H. CUMMINGS (MRC Dunn Compared with values from our aemia (PaO2 < 60 mmHg), hypoalbumin- Nutrition Unit andAddenbrooke's Hospital, laboratory for normal ileum obtained at aemia (<30 g/l), hypocalcaemia (serum Cambridge) Having an ileostomy is now operation, the PD was higher (5-14 ± 0-5 calcium <190 mmol/l leucocytosis (> considered to be compatible with good mV against 3-3 ± 03 mV) as was tissue 15,000/mm3) were equally distributed health. However, most studies of ileo- resistance (73-1 ± 89 Q Cm-2 against among the patients receiving trasylol and stomists have been carried out in hospital 40 3 i 2-8 Q Cm-2) but the short-circuit those receiving placebo. This study has and little is known about the ileostomist at current was lower (44 5 ± 6-6 tA.Cm-2 shown no benefit in supplementary trasylol home. After a recruitment campaign against 94 ± 7 ,uA.Cm-2). therapy in the treatment of primary acute through the local branch of the Ileostomy Isotopic flux measurements demon- pancreatitis. Association, 36 ileostomists completed a strated a net sodium absorption (2-42 ± 24 h urine and ileostomy collection 1i13 ,uEq.Cm-2.h-1, n = 4) rising on Reference together with nutritional assessment. addition of 10 mM glucose (8-96 ± 3 2 Daily ileostomy output was 760 g + 322 both values being similar Ismrie, C. W., and Whyte, A. S. (1975). A prospec- pEq.Cm-2.h-1) tive study of acute pancreatitis. British Journal of SD with Na 114 mmol/kg, K 8-7 mmol/kg, to 'normal' ileum. Surgery, 62, 490-494. 62 g solids, 5 5 g fat, 6-2 g free sugars, and In three of four tissue pairs no net 0 9 g starch. Ten subjects with Crohn's chloride transport was demonstrated, the Value of diagnostic peritoneal lavage to disease had a significantly higher ileostomy fourth from a patient with ileostomy diar- determine the severity of acute pancreatitis output, 1084 g i 340/day, than the 26 rhoea showed a large chloride secretion. with ulcerative colitis, 635 g ± 215, with We conclude that the high in vivo M. J. MCMAHON, R. L. BLACKETT, AND I. correspondingly greater excretions of ileostomy PD simply reflects a local

PICKFORD (University Department ofSur- electrolytes, fat, sugars, and starch. Nine increase in mucosal resistance and is not http://gut.bmj.com/ gery, The General Infirmary at Leeds) subjects had a raised aldosterone value in due to enhanced sodium absorption. We Effective treatment of acute pancreatitis either urine or blood. have not demonstrated evidence of ileal depends upon early recognition of severe Almost all subjects had normal haemo- 'adaptation'. attacks, although this can be notoriously globin, serum iron, B12, folate, cholesterol, difficult. liver function tests, and plasma Vitamin C. Reference 1 thickness as 'Isaacs, P. E. T., Horth, C. E., and Turnberg, L. A. Diagnostic peritoneal lavage using litre Height, weight, and skinfold (1976). The electrical potential difference across of normal saline was carried out in 27 indices of adequate nutrition were within human ileostomy mucosa. Gastroenterology, 70,

patients with acute pancreatitis as soon as or exceeded published ranges for normal 52-58. on September 28, 2021 by guest. Protected copyright. possible after admission, in order to con- people; all subjects had gained weight firm the diagnosis and establish the since operation. Colonic motility and clinical results after severity ofthe attack. Patients were treated It is concluded that ileostomists main- multiple transverse taeniamyotomy for according to a standardised regime. A tain good nutrition after their operation. diverticular disease severe attack was defined as one requiring However, they lose larger quantities of 14 days hospitalisation, leading to a salt and water than suggested by studies of M. PESCATORI (Institute of Clinical Sur- recognised complication or causing death; hospitalised patients, and are therefore at gery, Catholic University, Rome, Italy) there were 10 severe attacks. continuing risk of electrolyte imbalance, The purpose of our investigation was to There were no complications of lavage. particularly those with Crohn's disease. evaluate the effect of multiple transverse Free peritoneal fluid (> 10 ml) was taeniamyotomy (TTM) on sigmoid mo- recovered from nine of the severe patients Is there small intestinal 'adaptation' after tility and clinical picture of eight patients but only two of the mild ones. The colectomy? A study of transport activity in affected by symptomatic uncomplicated returned lavage fluid was dark straw or biopsies of ileostomy mucosa diverticular disease of the sigmoid, brown in colour in nine of the severe selected for the operation after the failure patients but in none of the mild ones. P. C. HAWKER, A. I. MORRIS, AND L. A. of antispasmodics, high residue diet, and Concentrations of albumin, protein, TURNBERG (Department of Medicine, bran as medical therapy'. and transaminase in the return fluid pro- Hope Hospital (University of Manchester We recorded sigmoid intraluminal pres- vided a high degree of discrimination School ofMedicine), Salford) It has been sures and the manometric tracings were between the two grades of severity. There suggested that after colectomy the small correlated with the corresponding photo- were also differences between the two intestine 'adapts' by enhancing salt fluorograms before and after the operation groups with respect to amylase (p < 0-001), absorption and this may be reflected in a for a period of one year. Motor activity Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society oJ Gastroenterology A959 was recorded at 25, 20, and 15 cm from procedures. Significantly better results Clinical trial of cytotoxic perfusion for anal verge by open-ended perfused were achieved in the cases of upper rectal colorectal liver metastases catheters under basal condition, after a growths than in cases affecting the colon standard meal and after prostigmine (B, or lower rectum. The occurrence of post- I. TAYLOR (Department ofSurgery, Liver- M, P). Motility indices were computed operative sepsis had no effect on survival. pool) (introduced by Professor R. and the results shown in a Table. Suture-line and wound recurrence rates SHIELDS) Multiple liver metastases are A significant (t test) decrease under were high, suggesting that technical fac- frequently found at laparotomy for colo- stimulus was found in patients who under- tors influenced the results. However, the rectal cancer, often as an unexpected went TTM. small proportion of A and B lesions in the finding1. In these cases the primary lesion, These functional changes were accom- series indicates that delay in presentation if resectable, should probably be removed panied by a marked clinical recovery, and diagnosis is also involved. but whether any specific treatment should expressed in terms of lower abdominal be prescribed for the liver metastases is not References clear. pain and of weekly bowel movements 'Slaney, G. (1971). Results of treatment of carci- (WBM). noma of the colon and rectum. Modern Trends in A clinical trial to assess the value of dif- Considering functional and clinical dis- Surgery, Vol. 3, pp. 69-89. Edited by W. T. ferent perfusion techniques in the manage- advantages reported after colectomy and Irvine. Butterworths: London. ment of colorectal liver metastases is 2Peto, R., et al. (1977). Design and analysis of longitudinal myotomy (Reilly's opera- randomized clinical trials requiring prolonged presented. The perfusion with 5-fluoro- tion)1'2'3 and observing our results after observation of each patient. II Analysis and uracil was commenced at the time of TTM, even though they are short-term examples. British Journal of Cancer, 35, 1-39. resection of the primary tumour when results, we conclude that the later opera- palpable liver metastases were found. In tion is a simple, low risk, rational, and Results of local excision for 'early' terms of survival no benefit was found effective procedure for the treatment of colorectal cancer with hepatic artery ligation and perfusion diverticular disease with muscular hyper- (mean 3-0 4 2-0 months) and with portal trophy and high intracolonic pressure, not M. R. LOCK, JEAN K. RITCHIE, AND H. E. vein perfusion alone (mean 4-1 ± 3-8 responding to medical and dietetic LOCKHART-MUMMERY (St. Mark's Hospi- months) compared with the control group. regimen. tal, London) A retrospective analysis is However, the combination of the two presented of 140 patients with an 'early' improved the survival rate (mean 9-8 ± References single adenocarcinoma of the colon or 3-4 months) and had palliative value. rectum treated at St. Mark's Hospital by It would appear that little is gained by 'Hodgson, J. (1973). Transverse taeniamyotomy local excision between 1 January 1948 and treating colorectal liver secondaries at the for diverticular disease. Diseases of the Colon by either hepatic and Rectum, 16, 4, 283-289. 31 December 1972 and followed up until time of initial surgery 2Parks, T. G. (1970). Rectal and colonic studies 31 July 1976. Patients with ulcerative colitis artery ligation and perfusion or by portal after resection of the sigmoid for diverticular or adenomatous polyposis coli were vein perfusion alone. However, the disease. Gut, 11, 121. excluded. combination may confer some benefit in http://gut.bmj.com/ 3McGinn, F. P. (1976). Distal colomyotomy: fol- low-up of 37 cases. British Journal ofSurgery, 63, None of the 30 patients with pedun- prolonging symptom-free survival. 309-312. culated colonic tumours developed a recurrence. Reference Factors influencing survival of patients with Eight-eight patients with pedunculated 'Oxley, E. M., and Ellis, H. (1969). Prognosis of colorectal cancer in a regional hospital rectal tumours were treated; 68 required carcinoma of the large bowel in the presence of no further operation, although one died liver metastases. British Journal of Surgery, 56, P. G. GILL, P. J. MORRIS, AND M. G. with widespread metastases. Twenty 149-152. KETTLEWELL (Nuffield Department of patients underwent further operation; 16 on September 28, 2021 by guest. Protected copyright. Surgery, University of Oxford, Radcliffe for suspected residual tumour and four Perfusion of the rat small intestine Infirmary, Oxford) The survival of later for recurrent disease. patients with colorectal cancer treated out- Only 22 patients with non-pedunculated H. J. LEESE, J. R. BRONK, P. A. INGHAM, AND side specialised centres is thought to be rectal tumours were treated. These J. PRENDERGAST (introduced by G. poor'. We examined the records of 335 tumours were excised by peranal or trans- WATKINSON) (Department of Biology, patients who were treated at one regional sphincteric approaches utilising various University of York, York) Two prepara- hospital between 1966 and 1971. Actuarial techniques. Five patients underwent early tions for the perfusion of the rat jejunum survival curves were obtained and the reoperation for suspected incomplete will be presented. In the first, a stream of nfluence of clinical and pathological excision, although residual tumour was oxygenated Krebs Ringer bicarbonate factors on survival were analysed using the found only in two. Two other patients medium at 37°C is recirculated through log-rank test2. developed a recurrence. the lumen of an isolated loop, by gas-lift. One-hundred-and-ninety-two patients Although 15 % of all colorectal cancers The serosal surface is bathed in a similar had resection for cure with an adjusted resected at this hospital are Dukes A solution. The preparation to be demon- five-year survival of 53-8 %, while 37-2 % of cases, only about 4 % were treated by local strated incorporates an on-line Auto- patients survived overall. excision during these 25 years. Perhaps analyser system for the continuous Pathological stage was the most import- local excision should be considered more monitoring of glucose, or lactate in the ant determinant of prognosis, but a sig- frequently. Close consultation between perfusion media. A major disadvantage nificantly worse survival was associated clinician and pathologist is essential as with this type of preparation is that with emergency presentations, age less poorly-differentiated or incompletely ex- absorbed solutes are not readily cleared than 35 years, and with staged operative cised tumours need early major surgery. from the basal surfaces of the epithelial Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A960 The British Society of Gastroenterology cells as they would be in vivo but have to The mean pancreatic/parotid ratio for chondria (malate dehydrogenase, 1-18); traverse the submucosa, and cut mesenteric excretion of 75-selenomethionine was 2-8 endoplasmic reticulum (Tris-resistant a- and lymph vessels. (range 1-7-4-8) in chronic pancreatitis and glucosidase, 1-16); basal-lateral mem- This disadvantage is overcome in the 0-8 (range 0-2-1-6) in pancreatic carcinoma. branes (5'-nucleotidase, 1P12); cytosol second preparation in which the blood This combined pancreatic/parotid func- (lactate dehydrogenase). Homogenisation vessels serving the jejunum are cannulated tion test may help to differentiate chronic in digitonin (0-2 mg/ml) resulted in a clear and the vascular bed is perfused, in pancreatitis from pancreatic carcinoma. separation ofbrush borders and lysosomes. addition to the lumen'. The medium for Jejunal mucosa can now be simply vascular perfusion includes washed human References obtained from the dog and a complete erythrocytes and serum albumin. The pre- 'Karizaki, G., Noto, N., Saito, T., Fujiwara, Y., resolution of all the organelles of the paration is stable for at least 40 minutes Ohizumi, T., Soeno, T., and Ishidate, T. (1973). enterocyte achieved. Application of these during which time it is possible to monitor Laboratory diagnostic test for pancreatic dis- techniques will include a study of the orders by examination of parotid saliva. the vascular appearance of sugars or Tohoku Journal of Experimental Medicine, 109, comparative aspects of small intestinal amino acids added to the luminal fluid. 121-133. diseases and investigations of the physi- 2Pinheiro, C. E., Tarzia, O., and Taga, E. M. (1972). ology and biochemistry of enterocyte Reference The influence of endocrine and exocrine pan- creas on the carbonic anhydrase activity of the function. 'Hanson and Parsons. (1976). Journal ofPhysiology, rat salivary glands. Revista Brasileira de 255, 77. Pesquisas M6dica Biologia, 5, 1-5. References

PLENARY SESSION 'Hill, F. W. G. (1972). Journal of Small Animal Separation and characterisation of the Practice, 13, 575-594. organelles in peroral jejunal biopsies from 'Peters, T. J. (1976). Clinical Science and Molecular Parotid gland function in patients with the dog Medicine, 51, 557-574. pancreatic disease R. M. BATT, B. M. BUSH, AND T. J. PETERS Subcellular distribution of di-, tri-, tetra- K. E. L. MCCOLL, M. J. BRODIE, R. WHITE- (Department of Medicine, Royal Post- and penta-peptidase in human jejunum SMITH, AND T. J. THOMSON (Department of graduate Medical School and Royal Gastroenterology, Stobhill Hospital, Glas- Veterinary College, London) Naturally J. A. NICHOLSON AND T. J. PETERS (Depart- gow) A close functional relationship occurring malabsorptive syndromes have ment of Medicine, Royal Postgraduate exists between the exocrine pancreas and been described in the dog including Medical School, London) Dipeptide the parotid glands"2. We report our degenerative atrophy of the pancreas and hydrolase activity has been recently results of parotid gland function in various small intestinal disorders', some shown to be almost entirely located in the patients with pancreatic disease. of which resemble coeliac disease. In order cytosol of the enterocytel. As larger pep- Parotid salivary gland function was to examine the small intestine in these tides are also found in the intestinal lumen assessed in 12 patients with pancreatic cases a technique has been developed for after a protein meal2, the subcellular http://gut.bmj.com/ exocrine insufficiency due to chronic peroral jejunal biopsy. This has been used distribution of hydrolases acting upon pancreatitis and in 12 control subjects in conjunction with an analytical sub- peptides of two to five amino acid residues matched for age, sex, and alcohol con- cellular fractionation procedure and has been investigated. sumption. Pure parotid juice was col- enzymic analysis to characterise the Jejunal biopsies from control subjects lected for five minutes during lingual various organelles in normal and diseased were homogenised and subjected to stimulation using 10 ml 10% citric acid. mucosa. sucrose density gradient centrifugation3. The volume of juice produced and its A Watson paediatric capsule was passed The distributions of mitochondrial, concentration of amylase and various to the stomach with an outer flexible endoplasmic reticulum, lysosomal, on September 28, 2021 by guest. Protected copyright. electrolytes were measured. The concen- sheath protecting the tubing. The sedated peroxisomal, brush border, basal-lateral trations of sodium and bicarbonate were dog was then placed in right lateral membranes and cytosolic marker en- significantly reduced in the patients with recumbency and the capsule positioned at zymes were determined and compared chronic pancreatitis (31 ± 20 and 26 i 13 the pylorus with fluoroscopic screening. with those of the peptidases. mmol/l) compared with the controls (70 ± Using a guide wire and assisted by peri- Peptidase activities, assayed at pH 8-0- 9 and 46 + 9 mmol/l) (p = < 0 001). stalsis, the capsule was passed into the 8 5, were found in the cytosol and in the Parotid and pancreatic function was duodenum and on to the proximal brush border fraction but in no other simultaneously assessed by measuring jejunum. organelle. There were striking differences their excretion of injected 75-seleno- The biopsies were fractionated by iso- in the distribution of peptidase between methionine after a Lundh test meal in pycnic centrifugation on a continuous the two fractions depending on the chain- eight patients with chronic pancreatitis, sucrose density gradient2. In control tissue length of the substrate. Almost all eight with pancreatic carcinoma, and 12 the following organelles were charac- activity (96-98%/) against dipeptides was control subjects. In the patients with terised, with marker enzymes and modal found in the cytosol. However, for tri-leu chronic pancreatitis both the pancreatic densities between parentheses: peroxi- and tri-phe, hydrolase activity was divided and parotid excretion was impaired to a somes (catalase, 1-21); brush borders nearly equally between the two fractions. similar extent. In the patients with pan- (alkaline phosphatase, leucyl-2-naphthyl- Rather less tri-gly hydrolase activity (20%) creatic carcinoma there was only minimal amidase, Zn-resistant a-glucosidase, y- was associated with the brush border. For impairment of parotid excretion with glutamyl transferase, 1 19); lysosomes tetra-phe and tetra-gly most of the marked impairment of pancreatic excre- (N-acetyl-,B-glucosaminidase, a-mannosi- peptidase was in the brush border (73% tion. dase, acid phosphatase, 1 19); mito- and 88 % respectively). Penta-gly hydrol y- Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A961 sis was exclusively localised to the brush under physiological conditions and to (Department of Medicine, Royal Post- border but approximately 50%. of the detect alterations in intestinal disease. graduate Medical School, London) It has activity against penta-phe was found in been suggested that the mitochondria of the cytosol. Reference the enterocyte play a role in the regulation These data are in agreement with 'Peters, T. J. (1976). Clinical Science and Molecular of intestinal iron absorption'. The sub- concepts of peptide transport which sug- Medicine, 51, 557-574. cellular distribution of labelled and of gest brush border hydrolysis of tetra and In vitro uptake of iron by human duodenal total iron has been determined with longer peptides and intracellular hydro- biopsies analytical centrifugation techniques in lysis of dipeptides and triglycine. guinea-pig enterocytes during the absorp- T. M. COX AND T. J. PETERS (Department of tion of 59ferric chloride. References Medicine, Royal Postgraduate Medical An injection of 90 nmol 59FeC13 in 0 15 School, London) The duodenal entero- M NaCl-5 mM HCI was made into 15 'Nicholson, J. A., and Peters, T. J. (1977). Clinical cyte is the primary regulatory site for iron cm closed jejunal loops of anaesthetised Science and Molecular Medicine, 52, 16P. 'Matthews, D. M., and Adibi, S. A. (1976). absorption. The absorption process invol- guinea-pigs. After periods from 10 to 180 Gastroenterology, 71, 151-161. ves several steps including uptake by the minutes the contents of the loops were 3Peters, T. J. (1976). Clinical Science and Molecular brush border, transfer to intracellular removed and the enterocytes isolated. The Medicine, 51, 557-574. binding proteins and organelles, and enterocytes were homogenised and the sub- transport across the basal-lateral cell cellular organelles separated by either Isolation and characterisation ofpolypeptide membranes to the portal plasma. The isopycnic or rate zonal centrifugation on hormone storage granules from human controlling steps and, in particular, the sucrose density gradients2. There was jejunum process whereby iron deficiency leads to rapid binding of labelled iron to the brush enhanced iron absorption, are unknown. borders and uptake into the soluble M. G. BRYANT, S. R. BLOOM, P. E. JONES, AND In order to investigate these mechanisms fraction of the cell. Approximately 30% of T. J. PETERS (Department of Medicine, in man a technique has been developed to the radioactivity was localised to the Royal Postgraduate Medical School, Lon- study in vitro the uptake and intracellular mitochondria. Addition of 59FeC13 directly don) It is now apparent that abnormali- processing of iron compounds by human to the enterocyte homogenate was not ties of gut hormone release are an duodenal mucosa. associated with uptake of the label by important aspect of human intestinal Portions of mucosal biopsies were mitochondria. Subfractionation of the disease. Little work has been undertaken incubated in oxygenated buffered balanced mitochondria by either sonication or on the synthesis, storage and release salt solution containing 57Co-labelled digitonin treatment showed that most of mechanisms for these hormones. Analyti- cyanocobalamin as a non-absorbed marker the iron was associated with the mito- cal subcellular fractionation1 of jejunal for extracellular fluid. Iron complexes chondrial matrix or inner membranes biopsy specimens in conjunction with 159Fe3+] were prepared with a molar indicating active uptake of the metal ion specific radioimmunoassays have been excess of nitrilotriacetatic acid and were by this organelle3. Chromatographic http://gut.bmj.com/ used to isolate and characterise the hor- added to the medium to final concentra- analysis4 of the mitochondrial fractions mone-containing granules from normal tions of 18-450 ieM. After incubation at showed that the labelled iron was mainly human jejunum. 37°C the tissue was removed, rinsed, blot- (85 Y.) associated with a transferrin Crosby capsule specimens of jejunum ted, weighed and the uptake of 59Fe fraction with little binding to ferritin, were homogenised in 0 3 M sucrose determined. haemprotein or haemosiderin fractions. containing 1 mM Na2 EDTA and 20 mM Iron uptake was linear in the above These experiments demonstrate that iron is ethanol and after low speed centrifugation concentration range for up to 20 minutes; rapidly localised to the interior of intesti- the 8000 g-min post-nuclear supernatants the extracellular fluid marker equilibrated nal mitochondria during its absorption on September 28, 2021 by guest. Protected copyright. were fractionated by sucrose density within five minutes. Uptake of 18 uM Fe3+ supporting the proposed role of this gradient centrifugation. Aliquots of the was inhibited by 48% when 0 l mM organelle in the regulation of iron gradient fractions were assayed for dinitrophenol and 10 mM sodium absorption. organelle marker enzymes and immuno- fluoride were added to the medium. Up- reactive hormone content. Gastrin and take of iron over the range 17°-37° was References with shown to be highly dependent on the GIP showed similar distributions 'Worwood, M., and Jacobs, A. (1972). British distinct particulate components at a modal temperature (Qlo = 2 8) indicating that Journal of Haematology, 22, 265-272. density (MD) of 1-22. Granules containing iron uptake by the human duodenum is at 2Peters, T. J., and Shio, H. (1976). Clinical Science VIP (MD = 1 17), motilin (MD = 1-20), least partially an energy requiring process. and Molecular Medicine, 50, 355-366. 'Romslo, I., and Flatmark, T. (1974). Biochimica and secretin (MD = 1-24) were clearly Studies on duodenal biopsies from Biophysica Acta, 347, 160-167. separated. VIP immunoreactivity was also patients with iron deficiency demonstrated "Drysdale, J. W., and Ramsay, W. N. M. (1965). found in the low speed pellet probably a striking increase in the rate of iron up- Biochemical Journal, 95, 282-287. reflecting its partial localisation to take indicating that at least part of the neuronal elements. controlling process for iron absorption is Immunity and the hyposplenism of coeliac These experiments demonstrate the at the entry step. disease (CD) presence of at least four distinct popula- tions of gut hormone-containing granules Role of mitochondria in iron transport by A. W. BULLEN, R. HALL, E. M. COOKE, AND in human jejunum. This combination of guinea-pig small intestine M. S. LOSOWSKY (Department ofMedicine, techniques will make it possible to study University of Leeds, St. James's Hospital, the dynamic changes in granule density J. HOPKINS, T. M. COX, AND T. J. PETERS Leeds) Evidence for the immunological Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A962 The British Society of Gastroenterology importance of splenic atrophy in CD is thrombocytosis, and hyposplenism also mmol/24 h. Seventy-six patients with confined to the demonstration of the occurs in CD2. We have compared platelet diarrhoea, known GI disease, or suspected association between hyposplenism and counts in treated and untreated CD and steatorrhoea underwent the test concur- impaired antibody production to an measured splenic function to assess the rently with routine three day gravimetric experimentally administered coliphage relationship between the bowel lesion, faecal fat estimation. These patients were antigen'. We have assessed humoral and hyposplenism, and thrombocytosis. divided into three groups on the results cell mediated immunity to naturally Platelet counts were significantly higher of the tests: (1) 26 patients had abnormal -occurring, frequently encountered antigens in 26 untreated coeliacs than in 32 treated absorption (less than 95 %, range 001- in normal subjects and treated coeliac coeliacs (p < 0-001). Ten of 26 untreated 93 7%) and faecal fat excretion greater -patients with hyposplenism or normal patients (38 %) and four of 32 treated than 21 mmol/24 h (range 26-556); this :splenic function. patients (13 %) had platelet counts greater group included one patient with pancrea- Splenic function was assessed by Tc99 than 350000/mm3 (range 360000-780000). tectomy (0-01 % absorption), five with Dabelled heat damaged red cell clearance in 10 of these 14 patients had blood film pancreatic insufficiency, 11 coeliacs, and 28 patients; 13 showed hyposplenism. evidence ofhyposplenism on careful study. four with Crohn's disease; (2) 26 patients Serum antibodies to 11 types of E. coli Splenic function was assessed by Tc99 had no abnormality of fat absorption or were measured2 and recall skin tests with labelled heat damaged red cell clearance in faecal fat excretion; (3) 20 patients were PPD, candida, and streptokinase-strepto- 30 patients. In untreated CD, platelet found to have steatorrhoea (range 22-164 ,dornase were performed. counts were significantly higher (p < 0-05) mmol/24 h) but normal absorption. Ten of In coeliac patients with normal splenic in nine hyposplenic patients than in 10 these patients had blind loop syndrome or function, the number of E. coli anti- patients with normal splenic function; jejunal overgrowth and five had coeliac bodies was significantly higher than in 42 counts fell after treatment in 16 out of the disease. :healthy controls (P < 005). In coeliacs 19 patients. In treated patients the platelet This test is of value in the investigation *with hyposplenism the number (p < 0 02) count correlated with heat damaged red of fat malabsorption and has distinguished .and maximum titre (p < 0 05) of E. coli cell clearance times (p < 0 01). No cor- two types ofsteatorrhoea, one ofthese due .antibodies was significantly lower than in relation with serum iron, B12 or folate to malabsorption of triglyceride. The ;those with normal splenic function. levels was found. excess faecal lipid in the second type may Both groups ofcoeliacs had significantly These results suggest that both hypo- originate from cell-exfoliation, bacteria or -fewer positive skin tests than controls; splenism and activity of the bowel lesion sterols of unknown origin. -there was no significant difference between contribute to the thrombocytosis of CD -the two groups. and that the platelet count may be a guide Reference The results suggest that humoral to splenic function. immunity is impaired in patients with CD 'Gerskovitch, V. P., and Russell, R. I. (1974). and hyposplenism. The increase in E. coli References Tritiated glycerol triether as an oil marker in in with man. Journal of Lipid Research, 15, 432-435. http://gut.bmj.com/ antibodies coeliacs normal 'Nel3on, E. W., Ertan, A., Brooks, F. P., and ;splenic function may reflect the impaired Cerda, J. J. (1976). Thrombocytosis in patients mucosal resistance in CD. The general with celiac sprue. Gastroenterology, 70, 1042- Third division of the autonomic nervous decrease in skin reactivity may reflect 1044. system. An important element in gut 'McCarthy, C. F., Fraser, I. D., Evans, K. T., and control impaired cell mediated immunity during Read, A. E. (1966). Lymphoreticular dys- antigen exposure, but seems unrelated to function in idiopathic steatorrhoea. Gut, 7, 140- hyposplenism. 148. A. C. BISHOP, J. M. POLAK, A. M. J. BUCHAN, S. R. BLOOM, AND A. G. E. PEARSE (Depart- References Dual isotope method of clinical measure- ment of Histochemistry and Medicine, on September 28, 2021 by guest. Protected copyright. ment of fat absorption using tritiated Royal Postgraduate Medical School, Lon- 'Baker, P. G., Jones, J. V., Peacock, D. B., and glycerol triether-results in 101 subjects don) The autonomic nervous system was, Read, A. E. (1975). The immune response to X 174 in man. III Evidence for an association be- classically, considered to consist of two tween hyposplenism and immunodeficiency in J. F. MACKENZIE, L. M. NELSON, E. divisions, cholinergic and adrenergic. patients with coeliac disease. Gut, 16, 538-542. ROBERTSON, AND R. I. RUSSELL (Gastro- However, in the gut wall, for example, -Webster, A. D. B., Efter, T., and Asherson, G. L. enterology Unit, Royal Infirmary, electron microscopy shows three distinct (1974). Escherichia coli antibody: a screening Glasgow) test for immunodeficiency. British Medical Tritiated glycerol triether has been groups of nerve types: (1) the adrenergic Journal, 2, 16-18. validated as a non-absorbable oil-phase nerves, containing small vesicles (300-500 marker in man'. Oral administration of A); (2) the cholinergic nerves, mainly 'Mechanisms of thrombocytosis in coeliac 14C labelled triolein, a typical dietary tri- agranular; (3) nerves with large granules disease (CD) glyceride, together with the 3H labelled (800-2000 A). marker enables the percentage absorption This third group has been termed .A. W. BULLEN, R. HALL, R. C. BROWN, AND of triolein to be calculated from the ratio purinergic by Burnstock'. The increasing M. S. LOSOWSKY (Department ofMedicine, of the isotopes in an aliquot of faeces. number of peptides common to brain and University of Leeds, St. James's Hospital, This technique has been applied gut has led to discovery of a dual localisa- Leeds) Thrombocytosis is well docu- clinically in 101 subjects to assess its role tion of peptides in both the endocrine cells mented in untreated CD and is usually in the diagnosis of fat malabsorption. and peripheral nerves of the gut. attributed to a non-specific reaction to the Twenty-five normal subjects had greater Immunocytochemical light and EM -bowel lesion, or to iron deficiency'. How- than 95% absorption (range 964-100%) studies carried out on 10 surgical biopsies .ever, hyposplenism may also cause and a faecal fat excretion of less than 21 of human gut and pancreas have localised Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A963 vasoactive intestinal peptide (VIP) both in pulse rate from 86 to 125/min was seen. Reference sparse endocrine cells and in numerous After the second ischaemic period portal 'Bryant, M. G., Bloom, S. R., Polak, J. M., intramural nerves. VIP rose from 18 ± 6 to 100 ± 12 and a Albuquerque, R. H., Modlin, I., and Pearse, VIP appears to be present in the nerve greater fall of blood pressure was seen. A. G. E. (1976). Lancet, 1, 991-993. fibres and terminals. The granules are Explanation of the profound circulatory large (700-1600 A) and electron dense and changes of gut ischaemia is complex and Release of VIP by duodenal acidification in appear to correspond to the 'purinergic' uncertain. Since VIP is a potent vasodilator man nerves. Other peptides, including sub- which is found throughout the gastro- stance P, somatostatin, and the newly dis- intestinal tract, its apparently specific S. R. BLOOM, S. J. MITCHELL, G. R. covered bombesin, have also shown dual release by intestinal ischaemia may be a GREENBERG, N. CHRISTOFIDES, W. localisation. The granules appear to fall factor in the serious haemodynamic altera- DOMSCHKE, S. DOMSCHKE, P. MITZNEGG, AND with the 'purinergic' grouping but are dis- tions after gut infarction. L. DEMLING (Department of Medicine, tinguishable from each other. Royal Postgraduate Medical School, The study of gut hormones and their Hammersmith Hospital, London and actions has, thus, led to a new concept of a VIP infusion in man Department of Medicine, University of three-part autonomic control system con- Erlangen, Nuremburg, Erlangen, Germany) sisting of adrenergic, cholinergic, and Vasoactive intestinal peptide (VIP) is peptidergic nerves. The recognition of this S. R. BLOOM, S. J. MITCHELL, S. DOMSCHKE, known to be a potent stimulator of pan- new system may be helpful in the under- W. DOMSCHKE, P. MITZNEGG, G. LUX, U. creatic bicarbonate juice production and standing of some puzzling aspects of gut STRUNZ, AND L. DEMLING (Department of is present in high concentration in the duo- pathology. Medicine, Royal Postgraduate Medical denal mucosa, greatly exceeding that of School, Hammersmith Hospital, London, secretin. We have, therefore, investigated Reference and Department ofMedicine, University of its release after duodenal acidification. 'Burnstock, G. (1972). Purinergic nerves. Pharma- Erlangen, Nuremburg, Erlangen, Germany) Ten volunteers were studied during a cology Review, 24, 509. The physiological role of the powerful new basal period and after introduction via a hormonal peptide, VIP, is still undecided. duodenal tube of 50 ml 01 normal HCl VIP release in intestinal ischaemia We have therefore tested the effects of over three minutes. Plasma was assayed exogenous administration in man. for VIP, secretin, and motilin by highly I. M. MODLIN, S. R. BLOOM, AND S. J. Four healthy male volunteers received sensitive radioimmunoassays showing no MITCHELL (Departments of Surgery and separate 30 minute porcine VIP infusions hormonal cross-reaction. Basal VIP was Medicine, Royal Postgraduate Medical of 4, 8, and 16 pmol/kg/min. Plasma VIP 0-46 4+ 0-38 (SEM) pmol/l and rose at four School, Hammersmith Hospital, London rose from mean basal values of 4 pmol/l to minutes by 0-8 ± 0 3, at 10 minutes by with the low ± 1 6d1 i 1-2 at 30 minutes. WJ2, UK) Vasoactive intestinal peptide between 20 and 100 pmol/l 8-0 0, and by http://gut.bmj.com/ (VIP) has been isolated in large quantities dose, to 154 ± 22 (SEM) with the medium In contrast, the rise of plasma secretin from the gastrointestinal tract of all dose and to 351 ± 12 with the high dose. was much more rapid and short lived, mammalian species. It has a wide range of After discontinuing the infusion plasma basal 1b7 ± 0-6, four minute increment potent pharmacological actions including VIP fell precipitously with a half-life of 7-4 +t 1 1, 10 minute increment 0 3 ± 0-8, tachycardia and a powerful hypotensive 1-22 minutes from the medium dose and and 30 minute increment 07 ± 0-6. effect. We have therefore investigated its 1V03 minutes from the high dose infusion. Motilin showed an intermediate pattern possible role in the haemodynamic The calculated metabolic clearance rate with a basal concentration of 32 ± 9, four was 53 + 8 ml/kg and 46 ± 2 ml/kg minute increment of 17 ± 3, 10 minute sequelae of gut ischaemia. on September 28, 2021 by guest. Protected copyright. In six anaesthetised pigs small intestinal respectively. The medium VIP dose increment of 6 i 1, and a 30 minute ischaemia was produced by isolating the resulted in marked cutaneous flushing increment of 6 + 4. superior mesenteric axis and applying a which was even more intense with the 16 Thus, VIP does not appear to be an clamp. Portal, peripheral and arterial can- pmol/kg/min dose. Pulse rate rose by 35 important circulating hormone controlling nulae were inserted for plasma sampling. beats per minute and dyastolic blood pres- the pancreas, as its potency in man is much Constant recording of vital signs was per- sure fell 15 mm of mercury with the high less than that of secretin. VIP is a potent formed by an arterial pressure trans- dose infusion. There was also a small rise stimulant of small intestinal juice pro- ducer, CVP and ECG monitor. Two in plasma glucose and calcium concentra- duction. The rise of circulating VIP may fifteen-minute episodes ofintestinal ischae- tions. be an 'over-flow' phenomenon and may mia were produced with a 30-minute rest Animal experiments suggest that similar thus be an indication of the important interval. After the first ischaemic period amounts of VIP are required to produce local role of VIP in the intestinal response portal venous VIP rose from a mean basal the gastric inhibitory and pancreatic to acid. of 15 ± 5 (SEM) to a mean peak of45 ± 9 stimulatory effects of VIP. As no release of pmol/l. Plasma motilin concentrations VIP is seen in man after a meal and levels Altered intestinal sensitivity to bile acids remained unchanged and enteroglucagon above 20 pmol/l are rarely observed, it and small intestinal secretion in irritable levels did not change significantly. The seems unlikely, therefore, that VIP would bowel syndrome associated with diarrhoea arterial blood VIP concentrations reflected play a significant role as a circulating the portal levels, though the rise was less hormone. Its very rapid half-life is more in J. RASK-MADSEN, E. ODDSSON, AND E. KRAG marked. Concomitant with the release of favour ofthe previously suggested role as a (Department of Medicine C, Gastro- VIP a rapid fall in blood pressure from local hormone or neurotransmitter enterological Division, Herlev Hospital, 110/70 to 90/60 mm mercury, and a rise in substance'. University of Copenhagen, Denmark) An Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A964 The British Society of Gastroenterology abnormal intestinal motility cannot ac- 192 of the 232 babies so far delivered. within the follow-up period. However, count for the great loss offluid observed in Eighty-seven (45-3 %) were positive for local tumour invasion and distant metas- irritable bowel syndrome associated with HbsAg by radioimmunoassay. The antigen tases were major prognostic factors. We diarrhoea (IBSD). Since the colonic is usually present in very low titre and by propose a new staging classification based absorptive capacity has proved normal in six weeks it is present in a smaller propor- on these factors. this condition1 we found it pertinent to tion of infants at a still lower titre. focus on the small intestine. In order to However, irrespective of the results of Peptic ulcer in renal failure elucidate whether other secretory stimu- tests at birth or even at six weeks, some lants than those of the cAMP-system may infants develop very high titres of HbsAg C. C. DOHERTY, F. A. O'CONNOR, K. D. be involved in the mechanism ofdiarrhoea at 3 to 4 months of age. Of 112 infants BUCHANAN, J. M. SLOAN, J. E. S. ARDILL, AND in IBSD intestinal secretion was produced between 3 months and 2j years of age MARY G. MCGEOWN (Renal Unit, Belfast by glycochenodeoxycholic acid (GCDC). (mean 10 7 months), 16 (14-2Y) have very City Hospital and Department ofMedicine, We studied net movements of water and high titres. There is a marked ethnic dif- Royal Victoria Hospital) Attitudes differ electrolytes and the bi-directional fluxes of ference in these 'carrier' infants: most of regarding management of peptic ulcer in Na, Cl, and K by perfusing 25 cm of the the antigen positive mothers are Asians the patient with renal failure. We there- terminal ileum of 10 healthy volunteers from Pakistan, India, and Bangladesh fore studied the pathophysiology of ulcer and six patients with IBSD. Perfusates (56%); the Chinese and Afro-Caribbean disease in uraemic patients, in order to were isosmotic saline solutions containing mothers make up 11% each, and the evolve a logical approach to treatment. glucose, 22-Na, 42-K, and 36-Cl. Dilution Europeans 24%; but nine of the infants Fifteen of 31 haemodialysis patients had marker was 51-Cr-EDTA. 0-2 5 mM with high HbsAg titre are Chinese (56Y), pyloroduodenal ulceration (48 %) and GCDC was added. In normal subjects 1 four Afro-Caribbeans (25 %), only three gastric acidity (basal and peak) in mM stimulated absorption, while 1-5-2-5 are Asians (19%), and there are no 'car- haemodialysed patients was significantly mM decreased absorption and evoked rier' Europeans. All these infants are higher than in patients with untreated secretion of water and electrolytes. In clinically healthy, but the mean trans- chronic renal failure. The distribution pat- IBSD secretion occurred spontaneously. aminase levels in the antigen positive tern of peak acid output in uraemic GCDC 0-25 mM facilitated the absorptive group are two to three times that of the patients was found to be abnormal, with processes, while 1-02-5 mM caused pro- antigen negative and a normal control an increased proportion of acid hypo- fuse secretion. Changes in plasma to group of infants. secretors (22%) as well as hypersecretors lumen fluxes were responsible for spon- Vertical transmission appears to be an (28 %). Three patients with previous duo- taneous secretion in IBSD, while GCDC important factor in the maintenance of denal ulceration had atrophic gastritis reduced the opposite fluxes equally in both hepatitis B virus in the Chinese and Afro- with hypo or achlorhydria. groups. In conclusion, the ileal epithelium Caribbean population but not in the The upper limit for fasting plasma in IBSD shows increased sensitivity to Caucasians. gastrin in this laboratory is 125 pg/ml. http://gut.bmj.com/ GCDC and seems to be prestimulated by Thirty-one of 41 uraemic patients had some as yet unidentified agent which is not Tumour staging in colorectal cancer values above this level, and eight were a stimulant of cAMP and influences the greater than 500 pg/ml. Six of these eight fluxes in the same way as prostaglandin C. B. WOOD, C. R. GILLIS, AND L. H. had atrophic gastritis with hypochlor- E12. BLUMGART (University Department of hydria but the remaining two had acid References Surgery, Royal Infirmary, Glasgow) Stag- hypersecretion and severe ulcer disease. ing classifications for colorectal cancer in Peptic ulceration is therefore unusually 'Rask-Madsen, J. (1977). Unpublished data. current use are based on transmural frequent in uraemic patients and differs in on September 28, 2021 by guest. Protected copyright. 'Matuchansky, C., and Bernier, J. J. (1973). Effect spread of tumour and lymphatic involve- of prostaglandin El on glucose, water, and some aspects from conventional ulcer electrolyte absorption in the human jejunum. ment. However, they often do not take disease. It is predominantely duodenal, Gastroenterology, 64, 1111-1118. account of local tumour invasion of and gastric hyperacidity and fasting hyper- adjacent structures or even distant gastrinaemia occur more commonly (47 % Mother-to-infant transmission of hepatitis metastases. and 73% respectively) than in ordinary B virus We have prospectively studied 386 duodenal ulcer (DU). The finding of patients with large bowel cancer followed atrophic gastritis in association with pre- M. J. TARLOW, A. DERSO, E. H. BOXALL, AND for up to 3j years. Two hundred and eleven vious DU has important implications. T. H. FLEWETT (Paediatric Teaching Unit patients had Dukes B or Cl tumours. Many dialysis centres advise prophylactic and Regional Virus Laboratory, East Those patients with mobile primary acid-lowering surgery when there is a Birmingham Hospital, Bordesley Green tumours and no distant metastases definite history or radiological evidence of East, Birmingham) This study was de- showed no significant difference in survival DU1l2, and this would obviously be totally signed to determine the importance of despite the presence of lymph node illogical in those with atrophic gastritis. vertical (mother-to-infant) transmission of metastases. Where local invasion had hepatitis B virus surface antigen (HbsAg) occurred, survival time was decreased but References in the population. was not related to lymph node status. 'Hadjiyannakis, E. J., Evans, D. B., Smellie, In the West Midlands (birth rate 80 000 Similarly, patients with distant metastases W. A. B., and Calne, R. Y. (1971). Gastro- a year) 297 symptomless Hb8Ag carrier had a poor prognosis but survival was not intestinal complications after renal transplanta- mothers were detected between April 1974 altered by involvement. tion. Lancet, 2, 781. lymphatic sSpanos, P. K., Simmons, R. L., Ratazzi, L. C., and May 1977 by routine screening at ante- Thus, lymph node spread has not been Kjellstrand, C. M., Buselmeier, T. J., and natal clinics. Cord blood was received from an important determinant of survival Najarian, J. S. (1974). Peptic ulcer disease in the Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A965 transplant recipient. Archives of Surgery, 109, Massachusetts 02114, USA) Both exci- transplantation (three weeks after four 193. sion and exclusion of the jejunum expose renal subcapsular autotransplants/rat), Evidence for a mycobacterial aetiology of the distal bowel mucosa to higher luminal their corresponding controls: (3) six Crohn's disease concentrations offood and gastroduodenal solvent-injected, pair-fed rats; (4) adipose secretions'. Other possible factors involved tissue transplantation (n = 6), and com- W. R. BURNHAM, J. L. STANFORD, AND J. E. in the control of intestinal adaptation pared the results in (5) six normal, weight- LENNARD-JONES (St. Mark's Hospital, were tested in rats (N = 114) submitted to matched controls, and (6) five lactating City Road, London and The School oj 50% proximal small bowel resection or rats (14th day). Pathology, Middlesex Hospital, London) bypass. The results showed jejunal villus height Mesenteric lymph nodes taken at laparo- Within 48 hours, both operations to be increased from 344 ± SEM 36 ,um in tomy from 27 patients with Crohn's increased RNA and DNA contents in controls to 568 ± 29 during lactation, disease, 13 with ulcerative colitis, and 11 ileal mucosa by 20-52% over values in crypt depth from 144 ± 9 to 160 ± 14, controls have been cultured on control animals undergoing jejunal tran- mucosal wet weight from 30 ± 2 mg/cm to Lowenstein-Jensen and hypertonic Sauton section (differences, P = 0 05 to 0-001). At 63 ± 2, and protein from 4-15 ± 0-36mg/ media. After eight months, one culture of one week, persistent rises in nucleic acids cm to 6-93 :1 0-2 with comparable (17 to Crohn's disease tissue grew a mycobac- (35-90%: p < 0-005) were accompanied by 96%) increases in the ileum. However, in terium, subsequently indentified as a strain taller villi and deeper crypts (26-58%: spite of radioimmunoassay confirmed ofM. kansasii (1129). Tuberculin-type skin p < 0-01). In every variable at both times, hyperprolactinaemia in the perphenazine tests, using a reagent prepared from this increases were generally greater after treated and pituitary transplanted rats organism and another prepared from M. resection than after bypass (p = 0-05 to (169 ± 20 ng/ml) compared with 49 ± 8 tuberculosis, have been performed. Eight- 0-001). DNA specific acitivity after 3HTdR in controls) there were no intestinal een of 40 patients but only 10 of 50 con- remained raised by 43 % (p < 0 005) one adaptive changes and the indices of trols were positive to 1129 (p < 0-05). week after resection, despite the substantial mucosal mass actually fell slightly from 3 Conversely, 40 of 56 controls but only 22 increase (73%) in total DNA, indicating to 32 % in jejunum and 0 to 22 % in ileum. of 54 Crohn's disease patients were posi- progressive hyperplasia. By one month, We conclude that prolactin is not tive to M. tuberculosis (p < 0 05). Among however, values after resection were trophic to the intestine and that hyper- tuberculin positive subjects, 12 of 16 equalled by those after bypass. Modest prolactinaemia cannot explain the intesti- with Crohn's disease colonic hyperplasia occurred after proxi- nal adaptation of lactation. patients and nine of mal enterectomy alone. 36 control subjects, gave a positive re- References action to 1129 (p < 0-005). The provision of a richer chyme to the Twenty-two of the 27 Crohn's disease ileum by proximal enteric bypass did not 'Craft, J. L. (1970). The influence of pregnancy and cultures, seven of 13 colitis cultures but reproduce the early proliferative response lactation on the morphology and absorptive of the mucosa to proximal enterectomy. capacity of the rat small intestine. Clinical only one of 11 control cultures grew Science and Molecular Medicine, 38, 287-295. http://gut.bmj.com/ organisms during six months' incubation; Humoral factors2 may also contribute to 2Sar, M., and Meites, J. (1969). Effects of suckling these may be cell wall deficient myco- the rapidity and intensity ofcompensatory on pituitary release of prolactin, GH and TSH intestinal hyperplasia. in postpartum lactating rats. Neuroendocrinology, bacteria. 4, 25-31. These results suggest a mycobacterial References 3Elias, E., and Dowling, R. H. (1976). The mecha- aetiology of Crohn's disease which would nism for small bowel adaptation in lactating rats. be compatible with the published data on 'Dowling, R. H., and Gleeson, M. H. (1973). Cell Clinical Science and Molecular Medicine, 51, turnover following small bowel resection and 427-433. the transmissibility of inflammatory bowel bypass. Digestion, 8, 176-190. disease1'2'3. 2Williamson, R. C. N., Buchholtz, T. W., and Malt, Structure and function of the mouse small on September 28, 2021 by guest. Protected copyright. R. A. (1977). Adaptation of the shortened gut: References transfer ofa humoral agent by cross-circulation. intestine after infection with Schistosoma Gut, 18, 413. Mansoni 'Mitchell, D. N., and Rees, R. J. W. (1970). Agent transmissible from Crohn's disease tissue. Lancet, 2, 168-171. Is prolactin trophic to the intestine? P. B. VENGESA AND H. J. LEESE (introduced 'Cave, D. R., Mitchell, D. N., and Brooke, B. N. by G. WATKINSON) (Department of (1976). Evidence of an agent transmissible from E. MULLER, T. BATES, D. SAMPSON, AND R. Biology, University of York, York) It is ulcerative colitis tissue. Lancet, 1, 1311-1315. DOWLING and estimated that 200 "Cave, D. R., Mitchell, D. N., and Brooke, B. N. HERMON (Guy's Hospital million people suffer (1975). Experimental animal studies of the Medical School, London) The intestinal from bilharzia, also known as schistoso- etiology and pathogenesis of Crohn's disease. mucosal hyperplasia and enhanced absorp- miasis, which is caused by parasites of the Gastroenterology, 69, 618-624. tion of lactation' could, theoretically, be schistosome species. Although diarrhoea due to an enterotrophic effect of pro- is a symptom of this condition, very little SMALL BOWEL lactin2, as the adaptive changes develop is known of the structure and function of Adaptation of the shortened gut: greater equally in isolated Thiry-Vella loops as the infected small intestine. We have, initial response to resection than to bypass intact intestines. We therefore studied therefore, studied the effects of acute jejunal and ileal histomorphometry, Schistosoma mansoni infection on the R. C. N. WILLIAMSON, F. L. R. BAUER, AND mucosal wet weight, protein, and DNA in absorptive capacity of the small intestine R. A. MALT (introduced by Professor D. two groups of hyperprolactinaemic rats: of white mice, and also examined the JOHNSTON) (Surgical Services, Massachu- (1) perphenazine treated (five virgin structure of the gut under the light and setts General Hospital and Department of females given 5 mg.kg BW-1.day-') sub- electron microscope. Most of the work on Surgery, Harvard Medical School, Boston, cutaneously for seven weeks; (2) pituitary absorption was carried out using an in Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A966 The British Society of Gastroenterology vitro luminal perfusion apparatus. The Digestive myoelectric response to food ments of spike activity have been used to results indicated a striking impairment in study the effects of gastrin and CCK on the transport of D-glucose, 3-0-methyl D.WINGATE, HILARY THOMPSON, E. PEARCE, duodenal, jejunal, and ileal myoelectric glucose, sorbitol, and fluid, in mice seven AND ANNE DAND (Gastroenterology and activity in conscious fasted dogs. Each of weeks post-infection. Kinetic analysis of Endocrinology Units, and Departments of four dogs received six infusions of the glucose transport data suggested a Physiology and Experimental Surgery, pentagastrin (0 125-4 ,ug/kg/h intra- reduction in the number, rather than the London Hospital Medical College, London) venously) and five infusions of chole- affinity of the sugar absorptive sites. These Duodenal, jejunal and ileal electrical cystokinin (Karolinska) (0 125-2 U/kg/h findings correlated with the appearance of activity was recorded for two hours befoi e intravenously); each two hour infusion the villi which, in the infected animals, and four hours after a mixed meal in was preceded and followed by a two hour were swollen, eroded, and exhibited seven studies on dogs with implanted saline infusion. Both peptides abolished lesions and disruptions around their serosal electrodes. Recorded spike activity duodenal and jejunal migrating com- apices. The villous surface was also was analysed and measured during high- plexes (MMC), substituting irregular indented with deep sulci and covered with speed tape replay'. Serial measurements of spiking activity, but had little effect on pronounced strands of mucous. plasma insulin and gastrin were under- ileal MMCs. This was a threshold effect taken in four out of seven studies. rather than linearly dose-related. Chole- Elemental diet enhances the enteropathy of Irregular spike activity replaced fasting cystokinin-but not pentagastrin-sig- parasite infection in mice patterns at all three sites within minutes of nificantly (p < 0001) increased jejunal feeding. Feeding induced a significant spike activity; but, apart from this, the ANNE FERGUSON, GILLIAN PAUL, T. T. (p < 0 01) increase in overall spike main effect of the peptides was on the MACDONALD, AND R. F. A. LOGAN (Gastro- activity injejunum and ileum, but not duo- disorganisation of fasting activity in the intestinal Unit, Western General Hospital, denum. Except in the duodenum, post- duodenum and jejunum. There was a Edinburgh) We have reported that mice prandial peaks in spike activity were not dose-related acceleration of the gastric reared on the elemental diet Vivonex synchronous with plasma hormone peaks. pacemaker (p < 0 001) and the duodenal (Eaton Labs) will survive for months but There was a consistent and sustained fall pacemaker (p < 0 01) in response to are lighter than mice reared on a normal (p < 0 01) in the gastric basic electrical pentagastrin; cholecystokinin was without diet, have impaired antibody-forming rhythm after food, but the duodenum was effect. We conclude that cholecystokinin capacity, and have fatty livers" 2. The not affected. Comparison of these results has myoelectric effects which are similar effects of this elemental diet (ED) on with 44 studies of CCK and pentagastrin to3, but not identical with its structural intestinal histology of mice have now been infusion, suggests that neither peptide analogue; the failure of both peptides to examined; normal diet (ND) and ED accounts for the response to food in the abolish distal fasting (peristaltic) patterns mice have similar villus-crypt architecture, mid and distal small intestine2. It seems suggests a possible explanation for transit and intra- lamina propria cellularity, that the canine motor response to food is disturbances after denervating surgical http://gut.bmj.com/ epithelial lymphocyte counts. In ND mice, either mediated by other humoral agents procedures. infection with either Giardia muris or -our studies do not support insulin3 as a Nippostrongylus brasiliensis caused crypt candidate-or under neural control, or References hyperplasia and changes in intestinal both. 'Wingate, D. L., Barnett, T. G., Green, W. E. R., lymphoid cells; in ED mice, significantly and Armstrong-James, M. A. (1977). Automated greater crypt hyperplasia, and villus References high-speed analysis of the gastrointestinal myo- electric activity. American Journal of Digestive atrophy, were produced by these parasite 'Wingate, D. L., Barnett, T. G., Green, W. E. R., Diseases, 22, 243-251. and Armstrong-James, M. A. (1977). Auto- infections. 2Barnett, T. G., and Wingate, D. L. (1977). The on September 28, 2021 by guest. Protected copyright. Three possible explanations for the mated high-speed analysis of gastrointestinal logical analysis of the canine electroenterogram. of in myoelxctric activity. American Journal of Journal ofPhysiology, 268, 14-15p. enhanced enteropathy parasites Digestive Diseases, 22, 243-251. 3Weisbrodt, N. W., Copeland, E. M., Kearley, animals eating Vivonex will be discussed: 2Weisbrodt, N. W., Copeland, E. M., Kearley, R. W., Moore, E. P., and Johnson, L. R. (1974). the aberrant immune capacity of such R. W., Moore, E. P., and Johnson, L. R. (1974). Effects of pentagastrin on electrical activity of animals; sluggish intestinal motility; or Effects of pentagastrin on electrical activity of small intestine in the dog. American Journal of small intestine in the dog. American Journal of Physiology, 227, 425-429. improved nutrition of the parasites Physiology, 227, 425. themselves. 3Bueno, L., and Ruckebusch, Y. (1976). Insulin and Glucagon stimulates intestinal motor Elemental diets should be used with electrical activity in dogs and sheep. American activity caution in patients likely to have intestinal Journal ofPhysiology, 230, 1538-1544. parasite infections-for example, children Similar-but different: the myoelectric D. WINGATE, D. MORRIS, AND P. THOMAS with marasmus. response to cholecystokinin and penta- (Gastroenterology andEndocrinology Units, gastrin in the conscious dog and Departments ofExperimental Surgery References and Physiology, London Hospital Medical D. WINGATE, HILARY THOMPSON, ELIZABETH College, London) We studied the effect of 'Ferguson, A. (1976). Elemental diet: effects on PEARCE, AND ANNE DAND (Gastroenter- exogenous glucagon on myoelectric immune status and on hypersensitivity reactions in the gut. In The Role of Elemental Nutrition. ology Unit, and Departments of Experi- activity in the canine small intestine, both pp. 14-18. Edited by I. D. A. Johnston. MCS mental Surgery and Physiology, London in the isolated vascular-perfused organ, consultants: Tunbridge Wells. Hospital Medical College, London) New and in the conscious fasted dog with 'Ferguson, A., Paul, G., and MacDonald, T. T. methods" 2 of recording and analysing implanted serosal electrodes. Duodenal- (1977). Immunodeficiency and fatty liver in mice reared on an elemental diet. (Submitted for digestive myoelectric activity that permit, but not jejunal or ileal-inhibition was publication). for the first time, quantitative measure- seen with I mg rapid intravenous doses, Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A967 supporting the accepted view of glucagon rats a large dose (1840 mg/kg) of hy- vitro incorporation of 14C tyrosine into as an inhibitor'. By contrast, slow infusion droxyurea, an agent which kills proliferat- cell protein3 showed that enterocytes from (0 25-1 0 mg/2 h) stimulated all levels of ing cells in DNA synthesis. The recovery the steroid-treated animals synthesised the small bowel, abolishing fasting com- sequences in the crypt were initiated by protein at an enhanced rate compared to plexes and inducing irregular spiking. The increased cell production rates in basal the control. increase in jejunal spike activity was crypt cells produced by a decrease in their These studies suggest that the beneficial greater than we have encountered with any cell cycle time, which led to repopulation effects of prednisolone on the small other agent tested. Serial assays of plasma of the depleted crypt. intestinal mucosa are due to an enhanced insulin during the infusions did not sup- Using metaphase arrest methods with rate of synthesis of specific proteins, port the hypothesis that insulin is the vincristine, we have shown that long particularly those associated with the active agent2; moreover, insulin had no cycling basal crypt cells also occur in man. brush border, probably mediated at the effect on the isolated tissue, whereas We propose that slowly proliferating basal levels ofboth transcription and translation. glucagon (50-100 fig) induced a brisk crypt cells are important candidates for the motor response, implying a direct action of role of stem cells in human and rodent References the peptide on the smooth muscle. We intestinal mucosa. conclude that current views on the intesti- 'Batt, R. M., and Peters, T. J. (1976). Clinical nal role of glucagon are based on pharma- Mechanism of action of prednisolone on the Science and Molecular Medicine, 50, 511-523. cological rather than physiological studies. absorptive-digestive functions of the rat 'Batt, R. M., and Peters, T. J. (1977). (Awaiting The widespread distribution of entero- small intestine publication). glucagon, and the resemblance between 'Fulks, R. M., and Goldberg, A. L. (1973). Journal of Biological Chemistry, 248, 7272-7275. the response to slow glucagon infusion and J. SCOTT, R. M. BAIT, AND T. J. PETERS the response to food", suggest the pos- (Department of Medicine, Royal Post- sibility of a major role for glucagon in the graduate Medical School, London) Corti- Action of prednisolone on the small bowel regulation of digestive motor activity. costeroids have been used successfully to mucosa treat patients with chronic intestinal References disease. Previous studies' have shown that H. AL-DEWACHI, N. A. WRIGHT, D. R. 'Chernish, S. M., Miller, R. E., Rosenak, B. D. in the rat oral administration of pharma- APPLETON, AND A. J. WATSON (Depart- Scholz, N. E. (1972). Hypotonic duodenography cological doses of prednisolone-21-phos- ments ofPathology and Medical Statistics, with the use of glucagon. Gastroenterology, 63, phate, 0 75 mg/kg body weight daily for University of Newcastle upon Tyne) 392-398. 2Bueno, L., and Ruckebusch, Y. (1976). Insulin and seven days, produces an approximately Adrenocortical steroids have found use in jejunal electrical activity in dogs and sheep. 50% increase in the absorptive and the treatment of coeliac disease and American Journal ofPhysiology, 230, 1538-1544. digestive capacities of the jejunal entero- earlier work' has suggested that these 3Wingate, D. L., Thompson, H. H., Pearce, E. A., cytes. These effects occurred without any drugs can decrease crypt cell populations; http://gut.bmj.com/ and Dand, A. (1977). Quantitative analysis of the effect of feeding on canine intestinal myo- alteration in the size of the cell population thus an inhibitory action on the hyper- electric activity. Gastroenterology, 72, 1151. or the cell kinetics and it is postulated that proliferative coeliac mucosa appears the corticosteroid directly affects the probable. However, recent studies2 have Identification of stem cells in the rat and mature enterocyte. failed to show such an action in the rat, human intestinal mucosa Analytical subcellular fractionation and Tutton3 has claimed that prednisolone studies2 have demonstrated enhanced stimulates crypt cell proliferation. N. A. WRIGHT, H. AL-DEWACHI, D. R. enzyme activities associated with the The effect of single and multiple doses

APPLETON, AND A. J. WATSON (Depart- brush border and an increase in the modal of prednisolone on the rat jejunal crypt on September 28, 2021 by guest. Protected copyright. ments ofPathology and Medical Statistics, density of this organelle in the steroid- was studied, using autoradiographic and University of Newcastle upon Tyne) treated cells. This is consistent with an stathmokinetic techniques. Single injec- During treatment with abdominal radio- increase in the content of both enzyme and tions of prednisolone (2-5 mg/kg) depres- therapy and systemic cytotoxic chemo- carrier protein in the brush border mem- sed both flash thymidine labelling and therapy, intestinal side-effects can be a brane and suggests a selective effect of mitotic indices, shown to be due to a limiting factor in treatment; consequently, corticosteroid on this organelle. decreased cell production rate; seven days it becomes important to identify those The total RNA content of the after prednisolone a compensatory hyper- cells responsible for repopulating the prednisolone-treated enterocytes was plastic response, with a raised cell pro- intestinal crypts after death ofproliferating approximately twice that of the control duction rate, was demonstrated. cells, to design treatment regimes with cells. Subcellular fractionation has demon- Multiple daily injections ofprednisolone maximal bowel sparing action. strated that a large proportion of this (1 mg/kg) produced a sustained decrease in Detailed analysis of proliferation rates increase is associated with a distinct labelling and mitotic indices, lasting as in the rat jejunal crypt showed that a small particulate component not present in the long as injections were continued (seven subpopulation of basally situated cells control cells. Measurements of free and days). Crypt cell production rates were have long cell cycle times, between 20 and membrane-bound polysomes have shown also decreased overthis period. 30 h, compared with 11 h in the remainder this to be due to a proliferation of the We conclude that prednisolone depres- of the crypt. These cells would be expected rough endoplasmic reticulum. This indi- ses cell proliferative rates in rat jejunal to survive phase specific insult such as cates a specific effect of prednisolone on mucosa. Consequently, in addition to its irradiation, and be available for crypt the protein synthetic process for mem- anti-inflammatory role in coeliac disease, repopulation. brane components of the cell such as the the drug may also act by inhibition of cell This hypothesis was tested by giving brush border. Direct measurements of in division. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A968 The British Society of Gastroenterology References months but died after a prolonged 3-1 ± 0 3, female 3-8 ± 06, p < 0 05). 'Wall, A. J., anid Peters, T. J. (1971). Gut, 12, 445. neuropathy despite adequate chelation. Fibrosis, regeneration, portal inflamma- 2Batt, R. M., and Peters, T. J. (1976). Clinical The remaining four patients were less tion, fatty change, hepatocellular necrosis, Science and Mlolecular Medicine, 50, 511. severely ill and blood tests done several and piecemeal necrosis were graded in one sTutton, P. J. M. (1973). Virchows Archiv fur weeks after ingestion of the pills pathologische Anatomie und Physiologie und fur showed centre on a scale between 0 and 4, and Klinische Medizin, B. 13, 327. raised alkaline phosphatase and aspartate from these features an overall 'Pathscore' transaminase. Necropsy or biopsy speci- was developed. The Pathscore was also CLINICAL MEDICAL mens were obtained from all cases and higher among the Americans (male 14-1 ± showed acute hepatitis in the first fatal 0 9, female 15 ± 1-2) than the Irish (male Hepatitis B: absence of transmission by case and resolving hepatitis in the remain- 54 ± 0-6, female 8-5 ± 1-4, P < 005). gastrointestinal endoscopy ing five. Liver lead levels were grossly Significant correlations between alcohol raised in every case. consumption and pathological damage D. B. L. MCCLELLAND, C. J. BURRELL, R. W. Chronic lead poisoning in the indus- were more prominent in the Irish patients. TONKIN, AND R. C. HEADING (Depart- trially exposed or in children with pica The Cincinnati study group consumed less ments of Therapeutics and Bacteriology, does not usually affect liver function. food than their controls and correlations University of Edinburgh) After upper Goyer and Rhyme1 reported impaired between dietary factors and pathological gastrointestinal endoscopy with biopsy of respiratory and phospharylative function features were more significant in this a patient who was later discoverd to be a in the livers of lead intoxicated animals. It group. Milk, animal fat, and protein were carrier of both hepatitis B surface antigen seems likely that the livers of patients with associated with less fibrosis, regeneration, (HBsAg) and HBeAg, 38 patients were chronic lead poisoning are able to with- and fatty change. In summary, the greater examined with the same endoscope over a stand this insult, whereas in the cases severity of liver disease in the USA cannot period of 15 days. Nineteen of these described here the overwhelming dose of be explained in terms of alcohol con- patients were subjected to biopsy. Patients lead was sufficient to cause hepatic sumption only and dietary factors appear were followed up and two blood samples failure. to be important. obtained at approximately four-month intervals. There was no evidence of Reference Can we believe the figures? Deaths from hepatitis in any patient, no patient 'Goyer, R. A., and Rhyme, B. C. (1973). Patho- cirrhosis and hospital prevalence developed HBs antigenaemia, and no logical changes in lead poisoning. International patient acquired antibody to the HBsAg Review of Experimental Pathology, 12, 1. A. N. HAMLYN AND 0. JAMES (Department after examination. of Medicine, Royal Victoria Infirmary, In vitro experiments were then con- Comparison of features of alcoholic liver Newcastle upon Tyne) Suggestions' that ducted in which an endoscope and biopsy disease the incidence of alcoholic cirrhosis has forceps were deliberately contaminated been hitherto underestimated have http://gut.bmj.com/ with gastric juice containing inactivated A. M. CONNELL, D. WEIR, 0. FITZGERALD, prompted a survey of mortality for the 1251 HBsAg to evaluate the instrument W. MCDONALD, M. WHELTON, C. MCCARTHY, latest available year, 1975. cleaning procedures in routine use. More J. KENNEDY, M. FAIRMAN, AND C. BALL The number ofdeath entries for England than 200 ul of contaminated gastric juice (Departments of Medicine, University and Wales was 1835 (0 3°% of total was recovered from the instruments after Hospitals, Cincinnati, Ohio and Ireland) mortality). The proportion of all alcoholic routine cleaning, indicating that the pro- The severity and prevalence of alcoholic cirrhotic deaths was 22% compared with cedures are not effective. liver disease seems to be greater in the US 11 % in 1971. Estimated proportion of

Although the risks of transmission of than in Great Britain and Ireland. This is deaths attributable to various causes was on September 28, 2021 by guest. Protected copyright. hepatitis B infection during endoscopy usually attributed to greater alcohol con- as follows: alcoholic cirrhosis-males (M) appear to be smaller than expected, our sumption in the US, although the role of 30-3 %, females (F) 12-5 %; primary instrument cleaning procedures have been dietary deficiency has long been debated. biliary cirrhosis-M 0-8 %, F 8-6%; modified and will be described. A cross-sectional prospective study of cryptogenic cirrhosis-M 8-3 %, F 11-3 %; patients with alcoholic liver disease was active chronic hepatitis-M 5-8 %, F Acute lead poisoning-an unusual cause of undertaken simultaneously in Cincinnati 7-7%; secondary biliary cirrhosis-M hepatitis and Dublin, Cork, and Galway, Ireland. 2-9%, F 2-3 %; miscellaneous causes-M Dieticians and residents carefully assessed 5 7%, F 7-8%. The largest category was A. D. BEATTIE, P. MULLIN, R. BAXTER, AND clinical data, alcohol consumption, and cirrhosis, cause unspecified-males 46-2 %, M. R. MOORE (Southern General Hospital, diet. One - hundred - and - seventy - four females 49-8 %. In a 1:4 unstratified Victoria Infirmary, and University Depart- patients ('Study Group') (Cincinnati: male random sample of the non-alcoholic ment ofMateria Medica, Stobhill Hospital, (67), female (30), Ireland: male (55), female deaths 2-9 % of men and 4 5 % of women Glasgow) Six patients, aged 17 to 25 (22)) all of whom had a liver biopsy, were had been in 'alcoholic' occupations. The years, obtained lead and opium pills compared with a control group of 819 estimated post mortem rate was 59-2 % for which had been stolen from retail pharma- patients (Cincinnati, 216, Ireland, 603). males and 54-4 % for females. Comparison cists in 1973 and 1977. They crushed them, Laboratory and clinical data were con- with a local series of cirrhotic patients and suspended them in water and injected densed into a single index of clinical sever- published experience 2,3 from elsewhere them intravenously. Two of the patients ity termed 'Clinical Score'. The Clinical leads to the conclusions that (1) specified developed malaise and jaundice within Score (mean + SE) in the Cincinnati study forms of cirrhosis, such as PBC, were three days and one died of acute hepatic group was much higher (male 6-6 ± 0 4, certified more frequently than before, (2) failure. The other survived for two female 5 7 ± 0-7) than in the Irish (male alcoholic cirrhosis deaths were certified Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A969 twice as frequently asin 1971, (3) there was (Magnesium Carbonate Mixture BP). For an anatomically normal small intestine a disparity between diagnostic and death commercial antacids, neutralising capacity may be a common cause of malabsorption certifying habits over the period studied, of a 10 ml dose at 2 h, 37°C, varied from and malnutrition in elderly patients, par- (4) a large porportion of unspecified 314 ml 0-1N HCl (Asilone suspension) to ticularly in association with achlorhydria. cirrhosis deaths together with occupa- only 54 ml 0-1N HCI (Gaviscon liquid). It is notable that diarrhoea was not tional clues suggests significant under- For tablet antacids, sodium content prominant in these patients. Antibiotic representation in official figures of varied from 32 mg/tablet (Gaviscon) to treatment brought marked symptomatic alcoholic liver disease. < 1 mg/tablet (Prodexin, Maalox, Titralac) and nutritional improvement. giving a daily sodium consumption of < 8 References to 256 mg/day. Neutralising capacity of References the tablet antacids varied from 15 to 165 'Price, H. L., Gazzard, B. G., and Dawson, A. M. 'Hodgson, H. J. F., and Thompson, R. P. H. (1976). ml 0-1N HCI per tablet. (1977). Steatorrhoea in the elderly. British Cirrhosis in South London. Lancet, 2, 118-121. Conclusion The sodium content and Medical Journal, 1, 1582. 2Jain, S., Paton, A., and Wansborough-Jones. 2Donaldson, S. F. (1973). Blind loop syndrome. In (1973). Cirrhosis in Birmingham. Midland neutralising capacity of some commonly Gastrointestinal Disorders, p. 927. Edited by Medical Review, 9, 13-16. used antacid preparations have been M. H. Sl:isenger and J. S. Fortran. Saunders: 3Hamlyn, A. N., Brown, A. J., Sherlock, S., and measured. The information obtained London. Baron, D. N. (1975). Casual blood ethanol estimations in patients with chronic liver disease. allows ready identification of those pre- Lancet, 2, 345-348. parations which would seriously affect the Influence of metronidazole and neomycin on treatment of patients requiring sodium colonic microflora in healthy volunteers Estimation of the sodium content and restriction. neutralising capacity of some commonly Y. ARABI, F. DIMOCK, D. W. BURDON, J. used antacids Reference ALEXANDER-WILLIAMS, AND M. R. B. KEIGHLEY (The General Hospital, Bir- 'Fordtran, J. S., Morawski, S. G., and Richardson, has been R. E. BARRY AND J. FORD (Department of C. T. (1973). New England Journal of Medicine, mingham) Metronidazole (M) Medicine, University of Bristol, Bristol 288, 923-928. reported to reduce the anaerobic flora of Royal Infirmary) Patients suffering from the small bowel' but a reduction in colonic hepatic failure, renal failure, and heart Bacterial overgrowth without 'blind loop' a bacteria has been reported only when M failure commonly require treatment cause for malnutrition in the elderly has been used with either neomycin (N) regimes involving strict sodium restriction. or kanamycin2 3. The incidence of dyspeptic symptoms in S. H. ROBERTS, E. H. JARVIS, AND 0. JAMES The aim of this study has been to deter- these conditions is high, so that they are (Department of Medicine (Geriatrics) mine the influence of M and N on colonic frequently treated concommitantly with Newcastle General Hospital) Malnutri- microflora in volunteers taking a normal viable counts of fresh stool antacids. Several authors have warned tion is frequent in the elderly and is often diet. Daily http://gut.bmj.com/ that some antacids contain quite large ascribed to 'poor diet'. Recently interest were measured before, during and one quantities of sodium sufficient to compli- has increased in possible causes for mal- week after a five day course of antibiotic. cate seriously any therapeutic regime absorption in old people'. Bacterial over- Subjects received the following antibiotics: requiring salt restriction. growth is a recognised cause in those with group 1: N + M, (n = 9); group 2: M Information on the theoretical sodium jejunal diverticulosis2. We report five alone (n = 4); group 3: N alone (n = 4). content of BP and BNF preparations is elderly patients without anatomical ab- The dose of N was 1 g eight hourly and of readily available but only one commercial normalities of the small intestine in whom M, 200 mg eight hourly. In group I three days after treatment there was a mean antacid preparation available in the UK bacterial overgrowth was demonstrated by on September 28, 2021 by guest. Protected copyright. (June 1977) states the sodium content on abnormal 14C glycocholate breath tests. reduction of total aerobes from 105 to the statutory Product Data Sheet. In order All subjects presented with weight loss <101 orgs/ml and counts of anaerobes to make this information freely available, and debility. All had biochemical evidence were reduced from 107 to 101 orgs/ml. In we have measured the sodium content of of osteomalacia. Other abnormalities most cases the flora was still reduced three 13 liquid and 12 tablet antacids which are were steatorrhoea (two), abnormal Dico- days after finishing the antibiotics. In in common use in our health district. The pac (four), macrocytic anaemia (four), group 2 there was no influence on the neutralising capacity of each antacid was low B12 (two), low folate (one). total number of aerobes or anaerobes. In also measured by a method based on that Normal jejunal biopsies and 75Se group three there was only a moderate ofFordtran et al.1 so that a comparison of selenomethionine pancreatic scans made reduction of aerobes and no influence on in vitro neutralising capacity and sodium other causes of malabsorption less likely. anaerobes. content can be made. Despite hospital treatment no patient These results indicate that M alone has For liquid antacids, sodium content improved until broad spectrum antibiotics no influence on colonic microflora but varied from 225 mg to < 1 mg per 10 ml were given. This led to weight gain, that the addition of N is responsible for a dose. Based on manufacturer's maximum dramatic improvement in general health, profound reduction of both aerobic and recommended dose, daily sodium con- and maintenance of normal haemato- anaerobic organisms. These findings could sumption from commercial antacids may logical and biochemical indices. Associa- explain the disappointing results of treat- vary from 5 mg/day (Asilone suspension) ted factors contributing to bacterial ment with M in the management of blind to 1030 mg/day (Gaviscon liquid), whereas contamination were achlorhydria (three) loop syndromes and Crohn's colitis. consumption from BP preparations may and a grossly delayed small bowel vary from 2 mg/day (Magnesium Hydrox- transit of barium (one). References ide Mixture, BP) to > 1300 mg/day Conclusion Bacterial contamination of 'Barry, R. E., Chow, A. W., and Billesdon, J. (1977), Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A970 The British Society of Gastroenterology Role of intestinal microflora in colonic pseudo- AND J. A. BRADLEY (University Depart- weeks old developed villous atrophy after obstruction complicating jejunoileal bypass. Gut, 16, 356-359. ment of Surgery, The General Infirmary, seven days (villus/crypt ratio 1-05 ± 2Goldring, J., Scott, A., McNaught, W., and Leeds) Malnutrition, hypoproteinaemia, 0 26). Mucosal regeneration started by 14 Gillespie, G. (1975). Prophylactic oral anti- and in particular hypoalbuminaemia are days (V/C 164 + 0 24) as worms were microbial agents in elective colonic surgery. well-recognised problems in ulcerative x Lancet, 2, 997-999. eliminated, egg counts decreased (65 5 3Arabi, Y., Dimock, F., Burdon, D. W., and colitis and Crohn's disease. However, no 103 -* 5-5 x 103/g faeces) and Keighley, M. R. B. (1977). Influence of bowel survey exists to show the incidence of pro- mucosal mast cells increased (118 ± 3 0 preparation on colonic microflora. British tein malnutrition in inflammatory bowel 333 ± 39 3 cells/10 V/C units). Journal of Surgery. (In press.) disease (IBD). Growth was unimpaired. Seventy-four unselected patients were A diet marginally deficient in protein Serial light and electron microscopy of studied and allocated to one of six (NDp:E, 0 068) produced normal growth intestinal mucosa in Whipple's disease categories: ileostomy (16), remission (15), in uninfected young rats but a colony fed elective surgery (12), acute attack (12), over 12 generations produced low birth P. MILLS, I. MORE, A. DICK, R. HOLDEN, AND urgent surgery (10), and post-surgical weight offspring' (group II). Worm G. WATKINSON (Departments ofMedicine complications (nine). clearance in these after Nb at 3 weeks was and Pathology, Western Infirmary and To assess protein nutrition, per cent less efficient than in group I (364 ± 49 v. Southern General Hospital, Glasgow) A weight loss, arm muscle circumference, 212 ± 22 remaining at 15 days). Neither 39 year old man developed gross mal- haemoglobin, plasma albumin, plasma did egg excretion decrease; mucosal mast absorption associated with rectal bleeding, transferrin, and plasma pre-albumin were purpura, pyrexia, finger clubbing, and skin cells failed to increase. Villous atrophy at confirmed measured. Comparison was then made seven days was less severe than in group I pigmentation. Jejunal biopsy with the values obtained for 15 healthy (V/C 1-8 ± 0-41 v. 1-05 ± 0 26) but the diagnosis of Whipple's disease with controls. infected animals weighed 31% less than villous stunting, infiltration of the lamina In the whole group (excluding ileostomy uninfected controls suggesting that mar- propria with macrophages containing patients who were not significantly dif- ginal protein deficiency limits both PAS +ve staining granules and free rod- ferent from the controls) there was a expulsion mechanisms and mucosal shaped bacteria seen at electron micro- significant lowering of haemoglobin damage induced by Nb but changes are scopy. (14-7 ± 1-4 g/dl cf. 11-9 i 19 g/dl, sufficient to precipitate malnutrition. He was treated with parenteral penicillin p < 0-001); albumin (43-2 + 2-2 g/l cf. and streptomycin for three weeks, followed 40-5 ± 5-7 g/l, p < 0-05); transferrin Reference by oral deoxycycline 100 mg once daily (283 ± 25 mg/100 ml cf 230 89 mg/100 he is still taking. He has made a ± 'Stewart, R. J. C., Preece, R. F., and Sheppard, which ml, P < 0 025) and pre-albumin (29-5 i H. G. (1975). Twelve generations of marginal rapid and full clinical recovery. 4-2 mg/100 ml cf. 237 ± 12-0 mg/100 ml, protein deficiency. British Journal of Nutrition, Jejunal biopsies were carried out at six 33, 233-253.

p < 0-05) and there was an overall fall of http://gut.bmj.com/ weeks, then at three monthly intervals; 10 0 + 9-6% in body weight. seven months after starting therapy the This lowering was least in the patients INFLAMMATORY BOWEL biopsy appears little changed by light in remission (10-20%) and greatest in the microscopy. urgent surgery group (50-60%) and those Spectrum of hepatic dysfunction in inflam- Electron microscopy initially showed with post-surgical complications ( > 70 %). matory bowel disease many free bacteria and bacteria within foamy macrophages in varying stages of Of the nine patients in this group seven digestion in phagocytic vacuoles. Six required intravenous feeding and two died. M. J. DEW AND R. N. ALLAN (The Nutri-

There was no significant difference tional and Intestinal Unit, The General on September 28, 2021 by guest. Protected copyright. weeks later fewer bacteria were present between the patients with Crohn's disease Hospital, Birmingham) The aims of this and most were in a state of degeneration. and those with ulcerative colitis. study are to categorise the types of hepatic At four months there were no free bacilli It is concluded that patients undergoing dysfunction in inflammatory bowel disease, and the still abundant macrophages urgent surgery for IBD require nutritional to define the risk factors and thus provide contained phagocytic vacuoles in a late support and that these findings may help a rational basis for clinical management. stage of digestion. to explain some of the severe post- From among 520 patients with Crohn's We would suggest that electron micro- operative complications encountered. disease, and 720 with ulcerative colitis scopy is important in diagnosing and follow-up 13-0 years including assessing response to treatment in cases of (mean Whipple's disease. Light microscopy of Effects of marginal protein malnutrition on sequential clinical and biochemical review) jejunal biopsies may remain unchanged parasitic infection of the intestine patients with serial alkaline phosphatase for long periods after treatment'. levels above 20 KA units of proven A. M. TOMKINS, K. MADI, AND B. M. OGILVIE hepatic origin have been studied. This (Clinical Nutrition and Metabolism Unit, level is most closely related to significant Reference Department of Human Nutrition, London liver disease'. 'Trier, J. S., et al. (1965). Gastroenterology, 48, 684. School of Hygiene and Tropical Medicine, Fifty-seven patients with Crohn's disease London and National Institute for Medical and 44 with ulcerative colitis were studied Survey of protein nutrition in inflammatory Research, London) Hooded rats fed an and divided into subgroups which included bowel disease-a rational basis for nutri- adequate diet (protein energy: total transient perioperative changes, peri- tional therapy metabolisable energy (NDp:E) 0 1) (group cholangitis, cirrhosis, stenosing cholangi- I) infected with Nippostrongylus brasiliensis tis, and bile duct carcinoma. Liver biopsy I. PICKFORD, G. L. HILL, R. L. BLACKETT, (Nb) (500 larvae subcutaneously) when 3 was performed in more than 60 %. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A971 Transient perioperative rise was common The losses ranged from 0 1 to 26-2 g in 24 required to lyse allogeneic colonic epithelia cells. Gastroenterology, 70, 171-176. in Crohn's disease (44% vs 10%). This hours. The protein loss correlated well 2Strickland, R. G., Husby, G., Black, W. C., and was often related to sepsis but not disease with the clinical severity of the attack and Williams, R. C. (1975). Peripheral blood and extent, duration, or type of resection. In a favourable response to treatment was intestinal lymphocyte sub-populations in Crohn's contrast cirrhosis is much commoner in disease. Gut, 16, 847-853. associated with a reduction in the faecal 3Jewell, D. P., and MacLennan, I. C. M. (1973). ulcerative colitis (22% vs 5%) and occurs protein loss. A significant inverse correla- Circulating immune complexes in inflammatory only with total colitis. Stenosing cholan- tion between the faecal protein loss and bowel disease. Clinical and Experimental gitis and bile duct carcinoma occurred the serum albumin concentration was Immunology, 14. 219-226. almost exclusively in ulcerative colitis demonstrated (r = -054, p < 001). (27 % vs 2%) and is associated with long- Experiment to determine the active standing total disease. Drug therapy did Reference therapeutic moiety of sulphasalazine not seem to induce hepatic dysfunction. 'Pesce, M. A., and Strande, C. S. (1973). A new The effect of defining these subgroups on micromethod for determination of protein in A. K. AZAD KHAN, J. PIRIS, AND S. C. clinical management will be discussed. cerebrospinal fluid and urine. Clinical Chemistry, TRUELOVE (Nuffield Department of Clini- 19, 1265-1267. cal Medicine and Department of Morbid Reference Anatomy, Radcliffe Infirmary, Oxford) Killer cell activity and numbers in inflam- Sulphasalazine (SASP) is of proven value 5Eade, M. N. (1970). Liver disease in ulcerative matory bowel disease colitis. Annals ofInternal Medicine, 72, 4/5-487. in the treatment of ulcerative colitis but its mode ofaction is unknown. When taken Direct method of measuring faecal protein M. W. DRONFIELD AND M. J. S. LANGMAN by mouth, nearly all the dose reaches the loss in patients with ulcerative colitis (Department ofTherapeutics, City Hospital, colon intact and there it is split by the Nottingham) The results of colon cell colonic bacteria into sulphapyridine (SP) cytotoxicity' and other studies2 in inflam- The N. A. BUCKELL, S. R. GOULD, M. A. matory bowel disease (IBD) suggest that a and 5-aminosalicylic acid (5-ASA). HERNANDEZ, J. KOHN, J. E. LENNARD- present experiment was devised in order to killer (K) cell is involved in pathogenesis. the JONES, J. POWELL-TUCK, P. G. RICHES, AND K determine whether therapeutic pro- S. G. WELCH (St Mark's Hospital, We have, therefore, measured cell perty of SASP is a function of the parent London and The London Hospital, White- activity by the lytic effect of peripheral molecule or of one of these two principal chapel, London, Supraregional Protein blood lymphocytes on chromium 51-label- metabolites. Retention enemata were pre- Reference Unit, Putney Hospital, London) led chick RBC's when incubated together pared of SASP, SP, and 5-ASA and were Isotopic techniques ofmeasuring intestinal with anti-chick RBC antibody in 35 administered to volunteer patients with protein loss assume that the labelled pro- patients with IBD and 11 controls. sigmoidoscopic evidence of active ulcera- tein is metabolised in the same way as When a fixed number of lymphocytes tive colitis. The experiment was conducted and that the label were added to the chick RBCs the per- as a blind controlled therapeutic trial, each endogenous protein http://gut.bmj.com/ remains bound to the protein. A simple centage of RBC lysis, which expresses K patient using one of the test enemas daily direct method for measuring protein loss cell activity, was only 42-7 ± 5-7 (mean ± for a period of two weeks. Pronounced from the colon has been developed using a SEM) in 12 patients with severe sympto- histological improvement was shown in modification of the Ponceau-S dye matic IBD, compared with 59 5 ± 5*0 in approximately 30% of the patients receiv- technique'. Weighed aliquots are taken 10 patients with mild symptoms, 68-6 ± ing SASP or 5-ASA, whereas only 5% of from 24 hour faecal collections, the pro- 2-9 in 13 asymptomatic patients and the patients receiving SP showed such a tein is extracted in saline and the faecal 72-4 ± 2-1 in 11 healthy controls. change. It is concluded that the active debris is separated by centrifugation at Lymphocytes with temperature depen- therapeutic moiety of SASP is 5-ASA and 16000 r.p.m. An aliquot of the super- dent binding of fluorescein labelled that the SP functions as a carrier ensuring on September 28, 2021 by guest. Protected copyright. natant is added to a standard solution of immunoglobulin may well be K cells. and that the 5-ASA is liberated within the Ponceau-S dye in 3 % trichloracetic acid. this is supported by our finding that the colon. The resulting suspension is thoroughly proportion of such cells in the peripheral mixed, centrifuged, and the supernatant blood of normal people correlates well Levamisole in Crohn's disease-a double- with K cell activity. By contrast, in blind controlled trial removed, thereby eliminating any dis- symptomatic IBD more lymphocytes colouration caused by soluble faecal binding immunoglobulin in this way are material. The dye-stained protein is detectable than would be expected from E. WESDORP, P. T. A. SCHELLEKENS, R. redissolved in 0-8 % sodium hydroxide and WEENING, S. G. M. MEUWISSEN, AND G. N. J. the amount of protein determined the K cell activity. We therefore conclude TYTGAT (Department of Medicine, Divi- colorimetrically. that symptomatic IBD patients have sion of Gastroenterology, Wilhelmina The method is highly reproducible and reduced K cell activity but that the num- Gasthuis, University of Amsterdam, and the recovery of known amounts of added bers of circulating K cells are normal, Laboratory for Experimental and Clinical albumin was 99-5 ± 12-6% (SD). The their function perhaps being impaired by Immunology, Amsterdam, The Nether- method has been compared with the the action of circulating immune com- lands) We tested the hypothesis that Kjeldahl technique and a highly significant plexes3. levamisole, a non-specific immunostimu- correlation (r = 0-96, P < 0 001) found References lant, is beneficial to patients with Crohn's between the two methods. disease, who suffer from an impaired 24 5Stobo, J. D., Tomasi, T. B., Huizenga, K. A., anamnestic cellular immune response'. Serial hour faecal protein losses have Spencer, R. J., and Shorters, R. G. (1976). In been measured in 24 patients undergoing vitro studies of inflammatory bowel disease. Therefore 21 consecutive patients (six treatment for attacks of ulcerative colitis. Surface receptors of the mononuclear cell males and 15 females between 21-62 Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A972 The British Society of Gastroenterology years) with active Crohn's disease entered Edinburgh) The value of salicylazo- steroids and 26 placebo therapy for a double-blind placebo-controlled study. sulphapyridine (SASP) in the treatment of between six months to three years; 30 None of the patients received immuno- ulcerative colitis is well established'. patients have been in the trial for three suppressive therapy. They were randomly Successful treatment of ulcerative colitis years. A clinical relapse was defined at the allocated to either levamisole (11 patients) coincides with a total serum concentration onset of the trial and occurred when or placebo (10 patients) given in a dose of of sulphapyridine (SP) greater than 20 additional steroids had to be given (four 2-5 mg/kg body weight on two successive ug/m12. patients), or if surgery were necessary (10 days each week for three months. All We have studied more patients with patients); patients who required steroids patients were seen at the start and six and ulcerative colitis with continuing disease for more than six weeks were withdrawn 12 weeks later, for physical examination, activity in whom the concentration of SP from the trial. Eight of the 14 patients laboratory analysis (ESR, peripheral exceeds 20 ug/ml. withdrawn were on active therapy and six blood count, thrombocytes, serum albu- There were 64 out patients with ulcera- on placebo. The overall relapse rate at min, immunoglobulin, lysozyme, C3 and tive colitis receiving maintenance therapy three years was 30%. C4 levels, and fecal fat and fecal Cr51Cl3 with SASP and disease activity related to Prednisone, 7 5 mg daily, does not protein loss) and for immunological serum concentration of SP. Of 43 patients appear to reduce the risk of recurrent investigation (cutaneous reactivity to in remission, 32 had serum SP concentra- disease or clinical relapse in patients with PPD, varidase, trichophyton, candida tions over 20 ug/ml. Of 21 patients with Crohn's disease who at the onset of the and mumps; in vitro lymphocyte stimula- active disease 10 were for various reasons trial did not require steroids. tion with phytohemagglutinin, a cocktail taking inadequate dosage of SASP, as of the above skin antigens, and allogenic indicated by low serum SP levels. Eleven National Cooperative Crohn's Disease cells; determination of % T lymphocytes patients with active disease and serum Study (NCCDS): a controlled prospective with the E rosette technique, granulocyte concentrations are over 20 ug/ml. Nine trial of three drugs vs placebo chemotaxis and phagocytosis). The had faecal stasis proximal to active colitis Crohn's disease activity index2 was used which went into remission with hydro- R. W. SUMMERS (University Hospitals, for clinical scoring. philic colloid therapy and unchanged Iowa City, Iowa, introduced by D. L. The overall results of this study did not SASP therapy. In the group in remission WINGATE) and J. W. SINGLETON (Coordinat- show any obvious improvement neither in (43), 23% had faecal stasis. ing Center: GI Division, University of clinical, nor in biochemical parameters. This suggests that SASP or its meta- Colorado Medical Center, Denver) The The pre- and post-activity index was bolites SP or 5 amino-salicylic acid act NCCDS randomised 584 patients at 14 141-5 i 75 9 versus 131-8 ± 71-3 in the topically in the colon and that serum SP centres in a double-blind comparison of placebo group and 83-1 + 59-6 versus concentrations are secondary correlations. prednisone-P, sulfasalazine-S, azathio- 79.9 ± 63-8 in the levamisole group. Only prine-A, with a placebo control-C. two placebo and one levamisole patients References Response was analysed using the Wilcoxon http://gut.bmj.com/ improved clinically and biochemically Rank Sum method and a Crohn's Disease 'Truelove, S. C., and Watkinson, G. (1962). during the observation period. Neither Comparison of corticosteroid and sulpha- Activity Index (CDAI), an eight-item was there a change in the extensively salazine therapy in ulcerative colitis. British numerical clinical index of degree of ill- studied various immunological para- MedicalJournal, 2, 1708-1711. ness'. In Part I, phase 1, 300 patients with meters. In particular the depressed skin 'Das, K. M., Eastwood, M. A., McManus, J. P. A., disease (CDAI 150) and Sircus, W. (1973). The metabolism of active symptomatic reactivity was not influenced by levamisole. salicylazosulphapyridine in ulcerative colitis. were followed for 17 weeks. Response to This study therefore shows that levami- Gut, 14, 631-641. P or S was better than to C (p = 0 001, sole, under the conditions ofthis protocol, p = 0-017). Response to A did not differ on September 28, 2021 by guest. Protected copyright. was ineffective in ameliorating clinical, Effect of low dose steroids on clinical from C (p = 0-32). In patients on steroids biochemical, and immunological para- relapse in Crohn's disease at randomisation (n = 51), substitution of meters in patients suffering from Crohn's S was no better than substitution of C disease. J. RHODES, R. M. SMITH, L. E. HUGHES, D. L. (p = 0-94); however, continuation of CROSBY, B. REES, H. JONES, R. V. HEATLEY, steroids on P was superior to C (p = 0 025). References K. T. EVANS, AND B. W. LAWRIE (Univer- Separate comparison of coded initial and 5Meuwissen, S. G. M., Schellekens, P. T. A., sity Hospital of Wales, Heath Park, final barium x-rays showed improvement Huismans, L., and Tytgat, G. N. (1975). The effect of low dose steroids with A, or C. In Part I, Impaired anamnestic cellular immune response Cardiff) with P, but not S, in patients with Crohn's disease. Gut, 16, 854- (7 5 mg prednisone daily in adults and on phase 2 the 95 patients responding 860. alternate days in patients less than 14 favourably to phase 1 therapy (CDAI 150 2Best, W. R., Becktel, J. M., Singleton, J. W., and years old) has been examined in a double- at week 17) were followed to see whether Kern, F. (1976). Development of a Crohn's disease activity index. Gastroenterology, 70. 439 blind controlled trial in 64 patients who continued drug therapy at reduced dose 444. did not appear to need steroids. Twenty- would maintain remission. Response to six (group I) had recently had all apparent any drug was no different from that to Further studies of salicylazosulphapyridine disease removed by surgery; 11 (group II) C at either one or two years. In Part II, metabolism in the treatment of ulcerative were known to have residual disease after a prophylactic effect of low dose therapy colitis surgical resection, and 22 (group III) had against flare-up or recurrence was sought not undergone surgical resection. Five in 284 patients who had either quiescent G. 0. COWAN, K. M. DAS, AND M. A. patients were withdrawn within six months disease (CDAI 150), or who had surgical EASTWOOD (Wolfson Laboratory, Gastro- for reasons other than clinical relapse. resection of all involved bowel within a intestinal Unit, Western General Hospital, Thirty-three of the patients received year before entry. Response to any drug Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A973 was no different from that to C at either taneous electrolyte investigations in man using Liverpool) It is commonly held that one or two years. Clinical or x-ray deteri- "Br, 43K and 24Na. International Journal of gastro-oesophageal reflux occurs more oration had occurred in 32% at one year Applied Radiation and Isotopes, 21, 183-191. frequently during sleep' 2. At this time its and 69% in two years. Controlled comparison of sodium cromo- effects are said to be more dangerous, as the influence of gravity is reduced and Reference glycate and sulphasalazine in the mainten- ance of remission in ulcerative colitis swallowing is less frequent. We cannot 'Best, W. R., Becktel, J. M, Singleton, J. W., Kern, confirm this pattern of prolonged noctur- F., Jr. (1976). Developrrent of a Crohn's Disease M. W. DRONFIELD AND M. J. S. LANGMAN nal reflux and, in addition, have noticed Activity Index. Gastroenterology, 70, 439-444. (Department ofTherapeutics, City Hospital, that, ifreflux occurs during sleep, swallow- ing occurs normally. Electrolyte depletion in patients with Nottingham) The results of preliminary trials have suggested that sodium cromo- Continuous overnight pH measure- ileostomies: a failure of normal homeo- ments have been recorded from a position stasis? glycate (SCG) may be effective in the treatment of active ulcerative procto- 5 cm above the gastro-oesophageal A. I. MORRIS, P. C. HAWKER, AND L. A. colitis1'2, and bearing in mind the pro- sphincter in 24 patients and seven controls. TURNBERG (Department of Medicine, phylactic role of SCG in bronchial The patients had symptomatic oesoph- Hope Hospital (University of Manchester asthma, we are comparing it with agitis confirmed by endoscopy or radi- School ofMedicine), Salford. Horth, C. E. sulphasalazine (SSZ) in patients with ology. None had oesophageal stricture or Biochemical Pharmacology Department, G. ulcerative colitis in remission. gastro-duodenal ulceration. Reflux was D. Searle and Co. Ltd., High Wycombe) Twenty-four patients have so far been judged to have occurred when the pH fell Clarke and his colleagues' have suggested randomly allocated to SSZ treatment 2 below 4. that patients with established ileostomies g/day, 17 to high dose SCG (2 g/day) and In the control group the mean duration are chronically dehydrated and salt 12 to low dose SCG (160 mg/day). The of reflux between 6.00 pm and 12.00 pm depleted. We have investigated the extent cumulative proportion of patients free of was 56 4 minutes + SEM 17-4 and of electrolyte depletion, assessed possible relapse after six months of treatment is between 12.00 pm and 6.00 am 11 -4 mechanisms for it and searched for 0 71 in the SSZ treated group, 0 58 in the minutes ± 8-2 (p = < 005). In the adaptive hormonal responses in 14 high dose SCG group, and 0-29 in the low patients, the duration of reflux was 71-5 ileostomists. dose SCG group. One patient could not minutes ± 14-5 and 24 3 minutes ± 9-2 Using an isotope dilution technique tolerate high dose SCG because it pro- respectively (p = < 0 01). There was, (Skrabal et al.2) nine women and one of duced intolerable urgency of defaecation, however, no significant difference between five men with established ileostomies were but no other withdrawals because of side- the two groups themselves. shown to have a significantly reduced total effects have been necessary, and no Further analysis shows that reflux exchangeable sodium. All the women and haematological or biochemical abnor- activity reflects the patients' activity, in that it falls as the patients go to sleep and

three men were strikingly potassium malities have been found. http://gut.bmj.com/ depleted, a finding not previously demon- These preliminary results show that low rises again after 6.00 am. This was also the strated. No patient had significantly dose SCG is relatively ineffective, but that pattern in the control subjects. reduced total body water or ECF volumes. results withhigh dose SCG are inter- In view of these findings we feel that There was no evidence ofrenal retention mediate between those with the low dose nocturnal supine reflux may not be very of sodium or potassium in the face of and SSZ. If current trends are maintained important in patients with oesophagitis. depletion and there was no correlation SCG in a dose of 2 g/day could prove a References between total exchangeable sodium or useful second drug for maintaining remis- potassium and daily urinary or ileostomy sion in ulcerative colitis. 'Spencer, J. (1969). Prolonged pH recording in the study of gastro-oesophageal reflux. British on September 28, 2021 by guest. Protected copyright. losses of sodium, potassium or water. Journal of Surgery, 56, 12, 912. Plasma aldosterone concentrations were References 'Lichter, I. (1974). The measurement of gastro- normal in all but one patient, as were oesophageal acid reflux: its significance in 'Heatley, R. V., Calcraft, B. J., Rhodes J., Owen, hiatus hernia. British Journal of Surgery, 61, 4, plasma renin and prolactin concentrations. E., and Evans, B. K. (1975). Disodium cromo- 253. We conclude that apparently glycate in the treatment of chronic proctitis. healthy Gut, 16, 559-563. ileostomists are usually significantly potas- 'Mani, V., Lloyd, G., Green, F. H. Y., Fox, H., and Transmucosal potential difference; diagnos- sium depleted, commonly sodium depleted, Turnberg, L. A. (1976). Treatment of ulcerative tic value in gastro-oesophageal reflux but not dehydrated. They appear to have colitis with oral disodium cromoglycate. Lancet, adjusted to a new state of stable but 1, 439. B. KHAMIS, C. KENNEDY, J. FINUCANE, AND depleted electrolyte balance without a J. STEPHEN DOYLE (Department ofGastro- maintained change in plasma salt retaining OESOPHAGUS enterology, St. Laurence's Hospital, Dublin) hormone concentrations and without It has been suggested that transmucosal evidence of renal or intestinal sodium and Pattern of nocturnal gastro-oesophageal potential difference (PD) reflects the potassium conservation. reflux mucosal integrity' and that any disruption of the mucosa causes a fall in PD. References R. J. R. GOODALL, D. J. HAY, D. W. WARD, In this study we have measured PD in 19 'Clarke, A. M., Chirnside, A., Hill, G. L., Pope, G., AND J. G. TEMPLE (Introduced by M. H. patients in the lower oesophagus. The and Stewart M. K. (1967). Chronic dehydration IRVING) (Department of Surgery, Hope exploring electrode was firmly placed and sodium depletion in patients with estab- Hospital (University of Manchester School against the mucosa, 5 cm above the lished ileostomies. Lancet 2, 740-743. 'Skrabal F., Arnot, R. N., Helus, F., Glass, H. 1., of Medicine), Salford, Lancs., and Gastro- gastro-oesophageal mucosal junction and Joplin, G. F. (1970). A method for simul- enterology Unit, Broadgreen Hospital, under direct vision via an endoscope and Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A974 The British Society of Gastroenterology biopsy specimens were subsequently pression was similar before and after Conclusion (1) No significant changes obtained from the same site. surgery. The incidence of reflux symptoms of the GOSP were recorded after extrinsic The histological criteria for diagnosis of were similar to nonoperated duodenal denervation of the lower end of the gastro-oesophageal reflux were those laid ulcer patients in patients submitted to PCV oesophagus. (2) No manometric features down by Ismail-Beigi and his colleagues2. or SGV + D, but higher in patients after of achalasia were seen in any case, in spite In 10 patients with normal biopsy SGV + A. Gastro-oesophageal reflux of the presence of dysphagia in three specimens, the mucosal surface was measured by oesophageal pH was present cases. (3) Postoperative transient dys- always electro-negative with respect to the in similar proportion of patients after phagia is mainly due to mechanical body surface (mean - 14-4 mV ± 0 4 mV surgery. factors and not to denervation of the SEM). In nine patients with histological Conclusion (1) Reflux oesophagitis lower oesophagus and 'transient achalasia. changes ofgastro-oesophageal reflux mean symptoms and gastro-oesophageal reflux value was +9-4 mV (+30 mV SEM) a are present in an important percentage of Cricopharyngeal myopathy and fibrosis reversal of polarity in all but one case. nonoperated duodenal ulcer patients. (2) Excellent correlation was also found The severity of reflux symptoms in P. CRUSE, D. A. W. EDWARDS, J. F. SMITH, betwecn histological findings, PD, and patients with PCV or SGV + D were AND J. H. WYLLIE (Departments of Path- symptoms of lower oesophageal disease similar to nonoperated cases. In patients ology and Surgery, University College such as heartburn, lower retrosternal pain, with an associated antrectomy, symp- Hospital Medical School, London) Crico- and dysphagia. Visual appearance was a toms and gastro-oesophageal reflux were pharyngeal 'achalasia' causing dysphagia less reliable predictor of reflux changes. more pronounced. is usually attributed to neuromuscular Measurement of PD provides a simple, incoordination and a specific histological rapid and reliable index of lower oeso- Effect of extrinsic denervation of the lower change in the muscle has not been clearly phageal mucosal integrity and may prove end of the oesophagus on resting and described. useful in diagnosis and assessment of cholinergic-stimulated gastro-oesophageal Cricopharyngeus muscle from 20 nec- therapy. sphincter pressure ropsies on patients without dysphagia; References biopsies from seven patients with crico- A. CSENDES, M. 0STER, J. M0LLER, 0. pharyngeal 'achalasia', from three patients 'Geall, M. G., Phillips, S. F., and Summerskill, W. BRANDSBORG, M. BRANDSBORG, AND E. with pharyngeal pouch, and from one H. J. (1970). Profile of gastric potential differ- ence in man; effects of aspirin, alcohol, bile and AMDRUP (Surgical Gastroenterological patient with motor neurone disease were endogenous acid. Gastroenterology, 58, 437-443. Department L, Kommunehospitalet, Uni- examined by light microscopy. 2[smail-Beigi, F., Horten, P. F., and Pope, C. E. versity of Arhus, Denmark) Twelve Tissue from patients with crico- (1970). Histological consequences of gastro- patients with duodenal ulcer were studied pharyngeal 'achalasia' showed damage to oesophageal reflux in man. Gastroenterology, 58, 163-174. one week before and one week and 12 muscle fibres (shrinkage, internal nuclei,

weeks after randomised surgery. Seven nuclear condensation, phagocytosis) and http://gut.bmj.com/ Gastro-oesophageal reflux in duodenal patients were submitted to parietal cell increased intermuscular stroma which ulcer and after parietal cell vagotomy vagotomy (PCV) and five patients to looked like fibrous tissue and stained like (PCV), selective gastric vagotomy plus selective gastric vagotomy (SGV + D). collagen. Nerves seen were normal. drainage (SGV + D) and selective gastric Resting gastro-oesophageal sphincter pres- Fibrosis was not noted in controls, patients vagotomy plus antrectomy (SGV + A) sure (GOSP) and serum gastrin concen- with pouch, or motor neurone disease, nor trations were measured. The response of in adjacent muscles from two patients the GOS to 2 or 4 jug/kg body weight of with fibrosis, nor in any of the 14 pharyn- M. 0STER, A. CSENDES, 0. BRANDSBORG, M. was 10 and examined carbacholine measured every geal laryngeal muscles post on September 28, 2021 by guest. Protected copyright. BRANDSBORG, AND E. AMDRUP (Surgical minutes for 90 minutes after the sub- mortem from another patient with crico- Gastroenterological Department L, cutaneous injection. pharyngeal fibrosis. Kommunehospitalet, University of Arhus, There was no significant change in rest- It seems likely that the histological Denmark) Gastro-oesophageal reflux ing GOSP after PCV or SGV + D. features of cricopharyngeal 'achalasia' are was determined by intraoesophageal pH The response of GOSP to the cholinergic specific, the disorder is localised to the measurement in 20 patients with duodenal drug was dose dependent before and after cricopharyngeus and the dysphagia is ulcer, 15 patients after PCV, 15 patients surgery. In all patients a depressed caused by the resistance to stretch of the after SGV + D, and 12 patients after response to carbacholine was observed fibrous tissue rather than by a disorder of SGV + A. The average time between the one week after surgery, which was timing ofcontraction and relaxation of the operation and this study was 30 months restored to normal preoperative values 12 muscle. Myotomy can produce dramatic (range 12 to 50). Gastro-oesophageal weeks after surgery. Three patients had a relief of dysphagia. sphincter pressure (GOSP) and the transient low dysphagia starting one week response of GOS to graduated increase in after surgery and disappearing in two Dysphagia in Parkinson's disease-a study intra-abdominal pressure were deter- months. Sphincter relaxation reached of oesophageal motility and vagal function mined in each case. Duodenal ulcer fundic pressure in all patients. Resting patients had reflux symptoms in 45% of intraoesophageal pressure was always M. G. BRAMBLE, J. CUNLIFFE, AND A. W. the cases and the majority of these had a negative and no change in the amplitude DELLIPIANI (North Tees General Hospital, positive acid reflux test. No correlation of the peristaltic waves of the distal Hardwick, Stockton) To investigate a between serum gastrin concentrations and oseophagus was recorded. Basal serum possible disease specific disturbance of resting GOSP was found. The increase in gastrin concentrations were higher after oesophageal motility as a cause of sphincter pressure with abdominal com- surgery in every case. dysphagia in Parkinson's disease (PD) Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A975 oesophageal manometry was performed in ideal opportunity to study the effects of ject. The standard meal alone dropped 20 affected patients and 20 controls, gastrin under physiological conditions. LOSP significantly from a basal value matched for age and sex. The recording Two groups of eight patients were (mean ± SEM) of 12-64 ± 1-24 cm ofH2O system incorporated a triple lumen tube studied after PPG and HSV to determine to 10 63 ± 1-57 cm of H20 (t = 2-437, perfused at 0-6 ml/min, Statham trans- the effects on LOSP of (1) physiological p < 0 05). Coffee with milk after the ducers, and a Devices recorder. Vagal variations of endogenous gastrin, and (2) meal also dropped LOSP from 13-83 ± function was assessed by measuring rest- two types of pylorus preserving operation. 2-08 cm of H20 to 12-03 ± 1-79 cm of ing R-R interval on an ECG and beat to LOSP was measured and blood taken H20 (t = 2-375, p < 0 05). Black coffee beat variation of the same on deep for gastrin assay-fasting and at one and after the meal produced no significant breathing'. two hours after a standard protein meal. change in LOSP. A significant acid Recordings were repeated after bethane- Pressures were recorded on a Mingograph reflux was found in two non-fasting sub- chol (17 patients) and atropine (15 multiple channel recorder via side hole jects after coffee. patients). constantly perfused cannulas. These results suggest that black coffee No differences emerged between the Results showed that gastrin levels were might prevent the postprandial drop in two groups in respect of all the parameters significantly higher after HSV (p < 0-01; LOSP. measured on the basal recordings. After one tailed t tests); there was no significant bethanechol, aperistalsis significantly in- difference between LOSPs in the two References creased in the PD group (P=0-02), though groups (p > 0-1; one tailed t tests); there comparison with controls failed to achieve was no significant correlation between 'Cohen, S., and Booth, G. H. (1975). Gastric acid significance. Atropine increased the per- gastrin levels and LOSP (Pearson's r < secretion and intraoesophageal-sphincter pres- sure in response to coffee and caffeine. New centage of aperistaltic swallows in both 0-2; p > 0 2). England Journal of Medicine, 293, 897-899. groups (P=0001), though this was signifi- Conclusions LOSP in man is not signifi- 2Dennish, G. H., and Castell, D. 0. (1972). Caffeine cantly greater in the PD group (p=0-05). cantly affected by physiological variations and the lower oesophageal sphincter. Americanr A relationship between dysphagia, in gastrin concentration; HSV or Journal of Digestive Diseases, 17, 993-996. PPG 3Wadleck, F. (1972). A new procedure for func- severity of disease, and evidence of an does not affect the LOSP mechanism. tional analysis of the lower oesophageai autonomic neuropathy was explained by sphincter (LES). Pflugers Archiv fur die gesamte age alone. Beat to beat variation diminish- References Physiologie, 335, 74-84. ed with increasing age in the PD group (r = -0-580, P=0-01) and controls 'Grossman, M. I. (1973). What is physiological? Significance of measurements of lower Gastroenterology, 65, 994. (r- -0-468, P=0-05). 2Hennessy, T. (1973). Serum gastrin levels following oesophageal sphincter pressure in patients Increased sensitivity to atropine may be pylorus preserving gastrectomy. British Journal with symptomatic gastro-oesophageal reflux due to a disease specific change in neuro- of Surgery, 60, 909. transmitter in the dorsal vagal nucleus2, 3Korman, M. G., Hansky, J., Coupland, G. A. E., M. G. GREANEY. D. K. CHATTOPADHYAY, AND and Cumberland, V. H. (1973). Gastrin studies http://gut.bmj.com/ but does this produce intermittent after parietal cell vagotomy: is drainage neces- T. T. IRVIN (University Surgical Unit, dysphagia ? sary? Digestion, 8, 1-7. Royal Infirmary, Sheffield) It is alleged that weakness of the lower oesophageal References Effect of coffee on human lower oeso- sphincter is a significant factor in the pathogenesis of gastro-oesophageal 'Lloyd-Mostyn, R. H., and Watkins, P. J. (1975). phageal function Defective innervation of the heart in diabetic refluxl, but manometric studies of lower autonomic neuropathy. British Medical Journal, S. S. FEDAIL, P. R. SALMON, H. P. WURZNER, oesophageal sphincter pressure (LOSP) 3, 15-18. R. F. HARVEY, AND A. E. READ (University have failed to demonstrate any consistent 2Spehlman, R., and Stahl, S. M. (1976). Dopamine on September 28, 2021 by guest. Protected copyright. acetylcholine imbalance in Parkinson's disease. Department of Medicine, Bristol Royal abnormality in symptomatic patients. Lancet, 1, 724-726. Infirmary, Bristol) The physiological ef- These findings may be due to the variables fect of coffee and caffeine on the oeso- which affect the fidelity of LOSP measure- Effects of two types of pylorus preserving phagus has been the subject of a number ments, and it has been suggested that more operations on lower oesophageal sphincter of studiesl12; the results, however, have accurate measurements of LOSP are pressure (LOSP) and the correlation with been conflicting. Lower oesophageal achieved with a new rapid pull-through endogenous gastrin levels sphincter pressure (LOSP) using the rapid (RPT) technique of manometry2. pull-through technique3, and intraoeso- LOSP measurements were made in 30 P. V. DELANEY, P. J. BYRNE, AND T. P. J. phageal pH using an indwelling micro- asymptomatic volunteers (group 1) and in HENNESSY (Trinity College, Department of electrode were measured in healthy volun- 27 patients with symptomatic gastro- Surgery, Sir Patrick Dun's Hospital, teers under different conditions. oesophageal reflux (group 2) using the Dublin) There are conflicting reports on Each subject was studied five times both RPT method of manometry. Basal LOSP the influence of gastrin on the lower fasting and after a standard meal. The measurements were made and the effects oesophageal sphincter in man. The rele- effect of standardised coffee, black and of abdominal compression and intra- vance of these reports is doubtful because with milk, was assessed by sequential venous metoclopramide (10 mg) on LOSP the gastrin levels achieved are mostly LOSP measurements. Intraoesophageal were determined. There was no significant pharmacological'. Pylorus preserving gas- pH was continuously monitored basally difference in basal LOSP measurements in trectomy (PPG) causes a significant and in response to standard acid reflux the two groups, and intravenous metoclo- reduction in gastrin levels2, whereas highly tests. pramide was followed by a similar selective vagotomy (HSV) produces the Coffee with or without milk has no sig- increase in LOSP in both groups (25-4 ± reverse effect3. These patients provide an nificant effect on LOSP in the fasting sub- 7'0%y in group 1, and 23-2 ± 7-6% in Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A976 The British Society of Gastroenterology group 2). Abdominal compression caused Reference Medical School, London) Efficacy Of a rather greater increase in LOSP in group 'Dodd, W. J., Stef, J. J., and Hogan, W. J. (1976). 135 gallstone patients accepted 2 (50-5 ± 15-8%) compared with group 1 Factors determining pressure measurement for treatment 116 have radiolucent (27-1 i 11-9%) but the difference is not accuracy by intra luminal oesophageal mano- stones and a functioning gallbladder, in statistically significant. metry. Gastroenterology, 70, 117-123. those 40 with stones < 15 mm diameter The results suggest that RPIT measure- treated for one year with 3 13 mg kgBw-' ments of LOSP do not distinguish between LIVER AND BILIARY II day-' and who achieved unsaturated bile, normal subjects and patients with sympto- efficacy reached 65 % (complete gallstone matic reflux. Clinical pharmacology of oral chenode- dissolution) or 93 % (partial + complete). oxycholic acid (CDCA) Withdrawal Of 44 patients stopping References M. PONZ DE LEON AND R. HERMON DOWLING CDCA (27 surgery) nine defaulted < one 'Cohen, S., and Harris, L. D. (1971). Does hiatus (Guy's Hospital and Medical School, month, 14 stopped 15 mm phageal sphincter? New England Journal of London) For many drugs, efficacy relates (unrelated causes), Medicine, 284, 1053-1056. to peripheral blood concentration and bio- stones, seven took < 13 mg kgBw-' day-', 2Dodds, W. J., Hogan, W. J., Stef, J. J., Miller, W. availability to areas under 'tolerance' three had noncholesterol stones or debris, N., Lydon, S. B., and Arndorfer, R. C. (1975). A (concentration-time)curves-AUCs. How- one took clofibrate (which causes super- rapid pull-through technique for measuring lower esophageal sphincter pressure. Gastro- ever, CDCA's effect in dissolving gall- saturated bile'), six developed non- enterology, 68, 437-443. stones is within the liver and peripheral opacifying gallbladders, and four biliary levels represent only hepatic 'spillover'. colic ± pancreatitis. Thus few patients Variation in resting lower oesophageal To study CDCA bioavailability, therefore, stopped treatment because of CDCA sphincter tone: a neglected factor affecting in nine control subjects we measured failure per se. recording accuracy? (1) solubility of 500 mg oral CDCA Resistance Failure to achieve unsatura- (gelatin-coated capsules) in aspirated ted bile despite 13-15 mg kgBw-' day-' D. J. HAY, R. J. R. GOODALL, AND J. G. intestinal contents, (2) CDCA absorption occurred in 19 patients, including eight TEMPLE (introduced by M. H. IRVING) from aqueous intraduodenal solutions obese patients who ultimately achieved (Department of Surgery, Hope Hospital (250, 500, and 750 mg) of 3H-CDCA con- unsaturated bile with increased dosage (University of Manchester School of taining nonabsorbable marker 14C-PEG, (18-6 ± 1[4 mg CDCA/kg)2. Two obese Medicine), Salford) Using a multi-lumen (3) resultant four hour serum CDCA and four non-obese patients had super- catheter assembly for the measurement of tolerance curves, and (4) corresponding saturated bile despite 19-22 mg CDCA/kg lower oesophageal sphincter pressure AUCs after 250, 500, and 750 mg CDCA and >70% CDCA in biliary bile acids (LOSP) by the station pullthrough tech- in capsules given (a) during fasting, (b) (suggesting compliance). The mechanism nique (SPT), spurious between channel with food. of CDCA 'resistance' in these patients is pressure variation is common. Radial Results showed that (1) the distribution unknown but results on one patient sug- http://gut.bmj.com/ pressure asymmetry is said to be respon- ratio (aqueous phase: precipitate) of gest excess hepatic cholesterogenesis sible for this'. ingested CDCA in ultracentrifuged intes- (HMGCoA reductase activity 143 pmol SPT was performed twice upon the same tinal contents ranged from 1:49 at pH 2-9 microsomal protein mg-' min-; un- day on 10 normal subjects, each test after a (stomach) to 9:1 at pH 6-7-5 (jejunum); treated gallstone patients 65-76). fast of at least four hours. In one test, a however, CDCA 'solubility' seemed inde- Summary Despite the high withdrawal water perfused tube with three radially pendent of endogenous conjugated bile rate, in selected patients CDCA is effective orientated orifices situated 5 cm from the salts at concentrations > 2-3 mM; (2) and treatment failure infrequent. A new tip (tube I) was used, and in the other test CDCA 'absorption', as judged by 3H:14C syndrome of resistance to CDCA has been on September 28, 2021 by guest. Protected copyright. the orifices were similarly arranged, but at ratios, was 96-100% complete after 0-5-1 identified. 15 cm (tube II). The tests were carried out h, 120 cm distal to duodenal infusion site; in random order. (3) absolute AUCs increased with increase References Resting LOSP was calculated as the in capsule and infusion CDCA dose but 'Pertsemlidis, D., Panveliwalla, D., and Arhens, E. mean of the three pressure channel record- percent of dose spilling into peripheral H. (1974). Effects of clofibrate and of an oestrogen progestin combination on fasting ings. Using tube I the mean LOSP was blood diminished with increasing numbers biliary lipids and cholic acid kinetics in man. 9-88 mm Hg ± SD 3-81, whereas with tube of capsules; (4) comparing AUCs and Gastroenterology, 66, 565-573. II it was 14-1 mm Hg ± SD 5-03, this dif- using duodenal infusion for reference, 'Iser, J. H., Murphy, G. M., and Dowling, R. H. ference being significant (p < 0-001). The CDCA absorption (250 and 500 mg in (1976). Chenodeoxycholic acid (CDCA) treat- ment of gallstones: a follow up at five years. highest and lowest pressure channel capsules) was 100% complete. Gut, 17, 822. recordings in each test were also compared Summary Ingested CDCA is solubilised and showed a significant variation (p < with increasing intestinal pH, appears well Dissolution ofradiolucent gallstones using a 0-001). absorbed, and seems to be highly 'bio- fixed dose of chenodeoxycholic acid These results confirm that radial pres- available'. sure asymmetry is a cause of variation in M. C. BATESON, P. E. ROSS, J. MURISON, AND resting lower oesophageal sphincter pres- Efficacy of withdrawal from and resistance I. A. D. BOUCHIER (Department of Medi- sure measurement, but equally important to chenodeoxycholic acid treatment in cine, Ninewells Hospital and Medical in recording accuracy appears to be the patients with gallstones School, Dundee) The ideal dose of length of catheter assembly which projects chenodeoxycholic acid in the treatment of into the gastric lumen below the recording P. N. MATON, J. H. ISER, G. M. MURPHY, AND radiolucent gallstones has yet to be orifices. R. HERMON DOWLING (Guy's Hospital and established and there is much disagreement Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A977 in the literature. We report our experience for 72 hours was less than that of 10 con- fluids remains to be determined, and its with 750 mg/day chenodeoxycholic acid in trol patients, and as a result the CSI was current place in therapy is under review. 48 patients with gallbladder stones, of again significantly (p < 0-01) lowered by whom 38 have been followed for six to 36 the drug. months. Complete dissolution was Conclusion R may prove an effective Epidemiological study of neonatal hepatitis achieved in six and partial dissolution in alternative to chenodeoxycholic acid in the syndrome in infancy: incidence and early five patients. In contrast with previous treatment of patients with cholesterol course reports, response did not depend upon gallstones. dosage/unit body weight nor on gallstone A. P. MOWAT, H. PSACHAROPOULOS, AND R. size. The composition of fasting bile References WILLIAMS (King's College Hospital Medi- showed a drop in the percent of choles- cal School, London) From January 1971 'Braun, H. (1965). The modern therapy of choleli- terol and a rise in bile acids but values did thiasis and other biliary diseases, with particular to December 1973, all infants developing not become normal even in patients with reference to Rowachol. Zeitschrift Fur Therapie, the hepatitis syndrome within a circum- successful dissolution. Biliary symptoms 5, 279-288. scribed area (population 3 5 million) were improved even in the absence of dissolu- 2Hordinsky, B. Z. (1971). Terpenes in the treatment to determine of gallstones. Minnesota Medicine, 54, 649-652. prospectively investigated tion. No important changes were observed 3Thomas, P. J., and Hofmann, A. F. (1973). A the incidence of known causes and are in serum biochemistry or the histology of simple calculation of the lithogenic index of bile: regularly reviewed to assess factors of stomach, jejunum, and liver. After dis- expressing biliary lipid composition on rectangu- prognostic significance. Fifty-four cases solution patients were maintained on 500 lar co-ordinates. Gastroenterology, 65, 698-700. were identified from 137 000 live births. mg/day and stones recurred in two of four *Rowa Ltd., Bantree, Co. Cork, Eire. Eleven had extrahepatic biliary atresia, patients reviewed at 12 months. The use of seven dying in the first year of life, two in 1000 mg/day in 22 patients failing to Local infusion therapy for radiolucent the second. The two current survivors have respond to 750 mg daily was accompanied retained common duct stones using sodium cirrhosis, are frequently jaundiced and by unacceptable diarrhoea in eight. One of cholate, heparinised saline, and physio- have bled from varices. Four of seven nine patients with common bile duct logical saline infants with the genetic deficiency of stones achieved dissolution on 750 mg/ alpha-1-antitrypsin died with cirrhosis by day and there was a high proportion of M. C. BATESON AND I. A. D. BOUCHIER 3 years of age. Two survivors are unacceptable side effects. We make (Department of Medicine, Ninewells Hos- clinically well but have raised serum recommendations for the use of cheno- pital and Medical School, Dundee) transaminases; the third has cirrhosis. All deoxycholic acid based on this experience. Twenty patients have been referred over 2J three infants with confirmed congenital years for non-operative treatment of infection and one infant with trisomy 18 Rowachol-a possible treatment for chol- retained radiolucent gallstones. died in the first year of life with severe esterol gallstones? One had a hepatic duct stone which dis- cardiac and central nervous system appeared on removal of the T-tube. All abnormalities. http://gut.bmj.com/ J. DORAN, M. R. B. KEIGHLEY, AND G. D. others started on a regime of infusion Twenty-nine infants had cryptogenic BELL (University Department of Thera- therapy with sodium cholate, or hepa- hepatitis. Two died at eight and 12 weeks peutics, City Hospital, Nottingham and rinised saline or physiological saline. after laparotomy. Jaundice cleared in the General Hospital, Birmingham) The pro- Twelve patients received sodium cholate remainder in two to 36 weeks. At 1 year prietary terpene preparation Rowachol 100 mM initially. There were five success- of age, 11 had raised transaminases, one (R)* has been marketed extensively on the ful treatments, three after five and two having hepatosplenomegaly, and three Continent as a choleretic for over 25 years. after 10 days. In five patients toxicity splenomegaly. A further two children had In the rat it significantly reduces biliary limited therapy, and in three of those hepatomegaly. At recent follow-up (mean on September 28, 2021 by guest. Protected copyright. cholesterol secretion'. In man, there have reviewed at five days stones persisted. age 4 9 years), only four children had any been a number of case reports of gall- Five patients received heparinised evidence of liver disease, one having cir- stones dissolving during R treatment2. The physiological saline (100 000 units/l) for 10 rhosis and three mild persistent hepatitis. present study examines the effect of R on days. There were two successes and three Cryptogenic hepatitis is thus approxi- biliary lipid composition. failures. The failures proceeded to sodium mately three times as common as biliary Gall bladder bile was obtained at cholate infusion for 10 days without atresia or hepatitis with alpha-l-anti- cholecystectomy from 30 patients with success. trypsin deficiency and has a much better gallstones and functioning gall bladders. Of two patients treated with physio- prognosis than suggested by previous Eighteen patients received R preoperat- logical saline alone, one showed resolution reports"2'3. ively at a dose of either 1 or 2 capsules tds of stones at 10 days. for 48 hours, while the remaining 12 acted Therefore altogether 15 patients re- References as controls. The cholesterol saturation ceived sodium cholate with five successes, 'Danks, D. M., Campbell, P. E., Smith. A. L., and index3 (CSI ± SD) in the control subjects and seven patients received heparinised or Rogers, J. (1977). Prognosis of babies with neo- 0 was similar to that of the physiological saline with three successes natal hepatitis. Archives of Diseases in Childhood, (1-46 ± 40) 52, 368-372. patients given the smaller R dose (1-38 i without serious side-effects. 2Shirati, K., Okamoto, Y., and Takatso, T. 1966). 0-09). However, at the higher dose R sig- All saline infusions used removed com- A follow-up study of prolonged obstructive nificantly (p < 0-001) lowered the CSI mon bile duct stones, but sodium cholate jaundice in infancy. Paediatri Universitas severe side- Tohuku, 12, 41-45. (0-88 ± 0-15). The biliary cholesterol is associated with frequent "Thaler, M. M., and Gellis, S. (1968). Studies in neo- secretion in eight patients with a T-tube in effects. Whether sodium cholate resolves natal hepatitis and biliary atresia. American situ given R in a dose of three capsules tds stones resistant to infusion of other Journal of Diseases in Children, 116 257-279. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A978 The British Society of Gastroenterology Prognosis in childhood of liver disease achieve plasma levels comparable with histological activity and unsuitable para- associated with alpha-l-antitrypsin de- those observed post-prandially. In separate meters for determining changes in ficiency, type PiZ (Alpha-l-antitrypsin experiments (N = 8) the effect of BPP on immunosuppressive drug doses. Although deficiency) stimulated gastric secretion was assessed thecytotoxicity assay is too cumbersome by infusing pentagastrin at 0-7 iLg/kg-h to for routine use, the results indicate the A. P. MOWAT, H., PSACHAROPOULOS, R. achieve 50% MAO. potential importance of tests of specific WILLIAMS, B. PORTMAN, AND R. A. J. TAIT Mean basal and stimulated gastric acid immunological reactivity in the manage- (King's College Hospital Medical School, outputs of 3-5 ± 0-8 (mmol/h) and 25 0 + ment of chronic active hepatitis. London) Prospectively recorded data in 4-5 (mmol/h) respectively were unaffected 33 children with alpha-l-antitrypsin de- by BPP infusion as was pepsin secretion. Radioimmunoassay for antibodies to human ficiency in liver disease were analysed to However, under basal conditions BPP liver-specific membrane lipoprotein (LSP) determine the course and features of decreased mean net intraduodenal fluid in chronic active hepatitis and chronic prognostic importance. In 32 acute accumulation by 76 ± SEM 4-7%. This persistent hepatitis hepatitis developed in the first four months was associated with a highly significant of life. Serum bilirubin fell to normal in reduction (>90%) in bilirubin output D. JENSEN, I. G. MCFARLANE, A. L. W. F. four to 48 weeks, but serum trans- with a variable period of recovery in the EDDLESTON, AND ROGER WILLIAMS (Liver aminase and alkaline phosphatase re- post-infusion hour. Unit, King's College Hospital and Medical mained abnormal, except in seven children We conclude that BPP infusions in man School, London) Indirect evidence sug- (group 1) who are now well aged 2-9 which achieve physiological plasma con- gests that antibody to a liver membrane years (mean 51). Eighteen survive with centrations (1) have no effect on basal or lipoprotein (LSP) in co-operation with K- persistently abnormal liver function tests, pentagastrin-stimulated acid or pepsin cells plays a pathogenetic role in the con- eight having cirrhosis (group 2, age 1-10 secretion; (2) reduce bilirubin output sug- tinuing hepatocellular necrosis in chronic years, mean 5 0), eight died of cirrhosis gesting a possible role in the regulation of active hepatitis (CAH). Using highly (group 3, age 1-8 years, mean 5 3). gallbladder storage. purified LSP labelled with 1251, we have The prognosis in these groups was developed a solid phase radioimmunoassay related to the severity of the acute Relative value of lymphocyte cytotoxicity for detection of anti-LSP antibodies in hepatitis, jaundice lasting 11, 14, and 20 for hepatocytes and conventional blood serum. The specificity of the assay has weeks and the mean maximum AST con- tests in assessment of histological activity been demonstrated by blocking experi- centration 88, 173, and 295 IU/litre in in chronic active hepatitis ments with LSP, other liver proteins, F- groups 1, 2, and 3 respectively. Semi- actin, and plasma proteins. quantitative assessment of liver biopsies in A. M. G. COCHRANE, B. PORTMANN, A. L. W. Circulating anti-LSP was found in all of the first six months of life showed in group F. EDDLESTON, AND ROGER WILLIAMS nine patients with HBsAg-negative CAH

1 much more prominent hepatocellular (Liver Unit, King's College Hospital and and in eight of nine with HBsAg-positive http://gut.bmj.com/ infiltration, and much less portal tract Medical School, London) Management of CAH. Titres ranged from 1:200 to 1:2400 fibrosis and bile duct proliferation than in immunosuppressive therapy in patients (log mean 1:550) and were similar in both groups 2 and 3. Four already had cirrhosis, with chronic active hepatitis, in the absence groups. Eight of 13 patients with chronic including one who had a clinically mild of repeated liver biopsies, is dependent on persistent hepatitis (CPH) also had anti- hepatitis. changes in standard liver function tests. LSP, but at significantly lower titres (P < Combined clinical, biochemical, and We have assessed the value ofthese tests in 0-01) ranging from 1:50 to 1:400 (log histological assessment is necessary to predicting histological activity, and have mean 1:120), with no significant difference assess prognosis ofliver disease in alpha-1- compared them with the results ofa test of between HBsAg-positive and negative on September 28, 2021 by guest. Protected copyright. antitrypsin deficiency. specific autoimmune reactivity, lympho- cases. Anti-LSP was not found in the sera cyte cytotoxicity for isolated hepatocytes. of a control group of nine patients with Effect of bovine pancreatic polypeptide Histological activity was determined sub- idiopathic haemochromatosis. (BPP) infusions on gastric and biliary jectively, and individual features scored to This sensitive and reproducible radio- function in man give a quantitative index. Patients with an immunoassay provides direct evidence of active biopsy had significantly higher the presence of antibody to LSP in chronic G. R. GREENBERG, R. F. MCCLOY, V. S. levels of aspartate aminotransferase, active hepatitis. The finding of lower titres CHADWICK, T. E. ADRIAN, J. H. BARON, AND bilirubin, alkaline phosphatase, IgG, and in chronic persistent hepatitis suggests S. R. BLOOM (Royal Postgraduate Medical cytotoxicity, than those with an inactive that levels of the antibody may be related School, Hammersmith Hospital, Ducane biopsy. There was also a significant to severity of liver damage. Road, London) The role of pancreatic quantitative relationship between these polypeptide in human physiology is same indices and the biopsy score. DNA binding antibodies in HBsAg positive unknown yet plasma concentrations rise However, when the chi-squared test was and negative acute and chronic liver disease rapidly after a meal. Because powerful used to assess the value of a normal or biological effects in gastric and biliary abnormal test result in predicting disease J. G. C. KINGHAM, N. K. GANGULY, S. T. function are reported for the dog, we activity, only two of the tests led to sig- HOLGATE, D. R. TRIGER, M. MCGUIRE, B. investigated these parameters in man. nificant differentiation-total globulin. COHEN, S. RASSAM, AND RALPH WRIGHT Using simultaneous gastric and duodenal (p < 0-05) and lymphocyte cytotoxicity (Professorial Medical Unit, Southampton perfusion techniques to measure basal for isolated hepatocytes (p < 0-0005). General Hospital, Southampton) High gastric and biliary outputs, six healthy These results suggest that conventional double-stranded DNA binding antibodies subjects received IV infusions of BPP to blood tests are unreliable in assaying were initially thought to be specific for Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A979 systemic lupus erythematosus but subse- phagocytose sheep erythrocytes, Latex, Reference quently were reported in chronic active and Staph. albus by visual assessment, and 'Potter, et al. (1976). Journal of Laboratory and hepatitis" 2. The findings in other forms of uptake and cytotoxicity of 61Cr labelled Clinical Medicine, 88, 427-439. liver disease have been conflicting, with sheep erythrocytes. considerable overlap with the normal Macrophages from patients with quies- Levamisole in the treatment of HBs antigen range'w. cent chronic liver disease showed signifi- positive chronic active liver disease Using a modified Farr technique, we cantly poorer phagocytic ability than did have found high DNA binding in a wide those in control subjects, but function was R. G. CHADWICK, S. JAIN, H. C. THOMAS, AND range of acute and chronic liver diseases not impaired in cirrhosis with evidence of S. SHERLOCK (Department of Medicine, in United Kingdom patients with acute inflammatory activity (either hepatic or Royal Free Hospital, London) Patients hepatitis (21), HBsAg negative chronic extra hepatic). It is suggested that peri- with HBs +ve CALD have decreased T active hepatitis (38), primary biliary cir- pheral macrophage function in patients cell and increased null cell concentrations. rhosis (18), cirrhosis (17), and alcoholic with chronic liver disease is depressed, but In vitro exposure to levamisole partially liver disease (15) with little overlap with these macrophages remain capable of corrects this defect'. In this study we have healthy controls. Forty-sev_sn patients with responding to external stimuli. investigated the in vivo effect of levamisole HBsAg positive liver disease from Iraq on T cell function and liver function in had significantly higher DNA binding seven patients with HBs +ve CALD. levels (21-8 ± 3-7 %) than 46 who had no Clq binding activity and complement (Clq, Each patient was subjected to serial hepatitis B markers (13-3 + 2-9%). Six C3) catabolism in primary biliary cirrhosis observations at weekly intervals over six HBsAg-negative but HB core antibody and chronic active liver disease months in an on/off/on/off designed trial. positive patients formed an intermediate In all patients there was a significant group. Hepatitis B associated groups were H. C. THOMAS, B. J. POTTER, E. ELIAS, D. DE increase in T cell concentrations during well above 48 controls (7 5 ± 1-7 %). VILLIERS, AND S. SHERLOCK (Department levamisole treatment. In three patients High DNA binding antibodies in liver of Medicine, Royal Free Hospital, Hamp- after two to six weeks of treatment there disease may be due to release of hepatic stead, London) Sera from patients with were significant increases in transaminases nuclear DNA, macrophage sequestered chronic active hepatitis (CALD) and and in HBs antigen titres. These rises exogenous DNA or specific viral DNA. primary biliary cirrhosis (PBC) were lasted for four to six weeks and returned examined for immune complexes by the to control values when the drug was stop- References Clq binding assay. C3 and Clq catabolism ped. Four weeks later, on recommencing 'Davis, P., and Read, A. E. (1975). Gut, 16, 413- were studied using purified trace labelled treatment the same changes occurred. 415. proteins. During the period ofraised transaminases, 'Jain, S., Markham, R., Thomas, H. C., and Increased Clq binding was detected in Sherlock, S. (1976). Clinical and Experimental T cell concentrations (measured by E Immunology, 26, 35-41. all patient groups (control group (mean ± rosetting) increased and, after this, anti- SEM) 12-9 + 0-6; PBC 28-6 + 4-1; CALD core titres increased. http://gut.bmj.com/ Peripheral macrophage function in patients (HBs +ve) 34-4 ± 5-l; CALD (HBs -ve) In four patients, although T cell con- with chronic liver disease 35-1 i 3 3). In sucrose gradient studies centration increased, there was no change the Clq binding material was found in in transaminase or HBs antigen titres. D. R. TRIGER, J. G. C. KINGHAM, R. S. 7-lOS and > 20S fractions. These patients were anergic to a group of LLOYD, AND RALPH WRIGHT (Department In PBC the fractional catabolic rate skin test antigens. of Medicine, Southampton University, (FCR) of C3 has been shown to be Conclusion Levamisole resulted in in- Southampton) One of the mechanisms increased' and in this study the FCR of creased T cell concentrations in all seven postulated to account for the hyper- Clq is also significantly raised (range 3-4 to patients. In three patients who responded on September 28, 2021 by guest. Protected copyright. globulinaemia in chronic liver disease is an 6-2% of plasma pool/h; normal range 1 9 normally to skin test antigens, this was inability of the liver to sequester antigens to 2-9%/h). In HBs +ve CALD the FCR accompanied by increased transaminases, because of a defect in liver macrophage of C3 ranged from 2-0 to 3-5 %/h (normal and increased HBs antigen titres, probably function. Because of the difficulty in range 13 to 2-4%/h) and the FCR of Clq representing increased lysis of infected isolating Kupffer cells, an attempt to was also significantly increased (range 3-4 cells. In four patients who were anergic on assess macrophage function in man has to 7-5 %/h). However, in HBs -ve CALD skin testing, there was no response. been made by isolating macrophages from the FCR of C3 and Clq were within the Lavamisole may therefore by its immuno- the peripheral circulation and examining normal range. stimulant properties accelerate lysis of their functional properties. Twenty-seven Conclusion Increased concentrations of infected hepatocytes. patients with chronic liver disease (12 Clq binding material were found in PBC alcoholic and 15 non-alcoholic) were and in HBs +ve and -ve CALD. This Reference studied and the results compared with probably indicates the presence of immune 'Thomas, et al. (1976). Clinical Experimental those obtained from simultaneously complexes. The increased catabolism of Immunology. 26, 222-227. studied age/sex matched healthy controls. C3 and Clq in PBC and HBs +ve CALD Macrophage preparations were obtained indicates activation of the classical path- PANCREAS by differential centrifugation of hep- way of complement. The finding of arinised blood on Ficoll-Hypaque gradient increased Clq binding with normal cata- Diagnostic value of the oral pancreatic followed by separation of macrophages bolism of Clq and C3 in HBs -ve CALD function test (PFT) from lymphocytes by glass adherence. suggests failure of activation of this path- Function was assessed by ability to way. C. J. MITCHELL, C. S. HUMPHREY, A. W. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A980 The British Society of Gastroenterology

BULLEN, AND J. KELLEHER (Departments usually preceded pancreatography and level in control subjects was 65 ng/ml, of Medicine and Surgery, University of the two hour mean tryptic activity (MTA) range 30-308 ng/ml; in patients with Leeds, St. James's Hospital, Leeds) An was measured'. Pancreatogram changes chronic pancreatitis 2350 ng/ml, range oral PFT using the synthetic peptide N- were assessed retrospectively by two 870-11400 ng/ml; and in patients with benzoyl-L-tryrosyl-P-aminobenzoic acid independent observers and classified into pancreatic cancer 40 ng/ml, range 10-387 (Bz-Ty-PABA) can differentiate normal normal, minimal change and gross change ng/ml. In a single patient with both cancer subjects from patients with pancreatic using a modification of the criteria of and pre-existing chronic pancreatitis the disease1'2. The ingested peptide is specifi- Kasugai et al.2. A third opinion was used lactoferrin level was high-l 300 ng/ml. cally hydrolysed by chymotrypsin to to arbitrate in five pancreatograms on These results suggest that the measure- liberate P-aminobenzoic acid (PABA) which there was disagreement. ment of lactoferrin levels in pure pancrea- which is absorbed, conjugated, and Of the 19 patients with normal pan- tic juice may be a useful diagnostic test for excreted in the urine to provide an creatograms, all but four had a MTA pancreatic diseases. indirect index of exocrine pancreatic greater than 11 IU (mean 15-4 ± 4 0 SD). function. The diagnostic value of the test Ten patients with minimal changes of the Paired pancreatic function studies using will depend upon ability to distinguish pancreatogram had moderate but signifi- pure pancreatic juice and duodenal juice pancreatitis from intestinal disease. cant depression of the MTAs (mean 9 0 ± We have studied urinary eight hour 2-8 SD) (p < 0 01), although there was M. E. DENYER, P. B. COTTON, M. KYNE, AND PABA excretion in 26 subjects after an some overlap into the normal range. A. MILLER (Gastrointestinal Unit and oral dose of 2g Bz-Ty-PABA. In eight Eleven patients with gross pancreatogram Courtauld Institute of Biochemistry, The control subjects, mean PABA excretion changes had gross depression of the Middlesex Hospital and Medical School, was 74-2 ± 10-25 (SD)% of ingested dose MTAs (mean 3 0 ± 1-4 SD) (p < 0 01). London) Thirteen patients (eight con- -similar to previous reports. In 10 In conclusion, there is seen to be a good trols, five pancreatitis) underwent paired patients with pancreatic disease (eight correlation between the Lundh test and studies using two methods: pure pancreatic chronic pancreatitis, two acute relapsing pancreatography but both tests are juice (PPJ) collection after duodenoscopic pancreatitis), excretion was lower than required to establish minimal change duct cannulation, and duodenal juice controls at 44-8 i 10-2% (p = <0 001) pancreatitis as the exocrine function test (DJ) using a four-lumen tube with gastric with no overlap between the two groups. may be equivocal in this condition. and duodenal markers. After a bolus However, in eight patients with gastro- injection of GI H secretin (1 CU/kg) in intestinal disease (six extensive small References seven subjects, or an infusion of secretin bowel disease, two post-gastrectomy), all 1Mottaleb, A., et al. (1973). The Lundh test in the and pancreozymin (1 CU/kg/h) in six sub- with normal Lundh tests and six with diagnosis of pancreatic disease: A review of five jects, 10 minute collections were made for steatorrhoea, urinary PABA excretion years' experience. Gut, 14, 835-841. up to 50 minutes, and analysed for et al. was also impaired (mean 42 25 with 'Kasugai, T., (1974). Manumetric endoscopic and Mean http://gut.bmj.com/ ± %) retrograde pancreatocholangiography: Tech- volume bicarbonate amylase. only three values within the control range. nique, significance and evaluation. American volume recovery in DJ studies was 69% The Lundh test correlated with PABA Journal of Digestive Diseases, 19, 6, 485-502. (range 12-5-100%). Corrected mean DJ excretion in controls and pancreatic volumes exceeded PPJ volumes by a ratio disease (r = 094) but not in the gastro- Lactoferrin radioimmunoassay: levels in of 2-3:1 (range in normal subjects 045- intestinal disease group. pure pancreatic juice 9-6:1; in pancreatitis 1-22:1). Despite We conclude that the test cannot dif- mean bicarbonate concentration being 34 ferentiate between pancreatic and gastro- S. S. FEDAIL, R. F. HARVEY, P. R. SALMON, mmol/l higher in PPJ than DJ (range 0-100 intestinal disease, which is often the AND A. E. READ (University Department of mmol/l), the overall bicarbonate output in on September 28, 2021 by guest. Protected copyright. clinical problem. Medicine, Bristol Royal Infirmary, Bristol) DJ studies was greater (mean ratio 1-5:1; References We have developed a radioimmunoassay range 0-26-13-5:1). This excess includes for lactoferrin and used it to study the biliary bicarbonate, but also reflects in- 'Gyr$ K., et al. (1976). Oral administration of a levels in pure pancreatic juice obtained PPJ mean chymotrypsin-labile peptide-a new test of complete collection; amylase exocrine pancreatic function in man. Gut, 17, endoscopically. An antiserum of high concentration and output were also 27-32. affinity and specificity was obtained by slightly greater in DJ. Duodenal juice is 'Arvanitakis, A., and Greenberger, N. J. (1976). immunisation of sheep with purified contaminated and its analysis provides a Diagnosis of pancreatic disease by a synthetic peptide. Lancet, 1, 663-666. lactoferrin isolated from human milk. crude assessment of pancreatic function. When the antiserum is incubated at a final Pure pancreatic juice studies are difficult The Lundh meal and ERCP in pancreatic dilution of 1 in 2-25 x 106 with 125I1 to perform, often incomplete, and cannot disease lactQferrin and a double-antibody techni- yet claim a diagnostic role. que used to separate free from antibody- M. G. ASHTON, A. T. R. AXON, AND D. J. bound lactoferrin, the assay has a sensi- Pancreatic juice analysis, carcinoembryonic LINTOTT (University Department ofMedi- tivity of 1 ng/ml. antigen (CEA) and endoscopic retrograde cine, The Gastroenterology Unit and the We have studied 16 patients with cholangiopancreatography (ERCP) in the Department of Diagnostic Radiology, chronic pancreatitis, nine patients with diagnosis of pancreatic disease Leeds General Infirmary, Leeds) Forty carcinoma of the pancreas, and nine patients underwent both a Lundh test and control subjects being investigated for sus- D. L. CARR-LOCKE (Department of Medi- endoscopic retrograde cholangiopan- pected pancreatic disease and later found cine, University of Leicester) To define creatography (ERCP) for suspected or to be normal. the place of pancreatic juice analysis in the known pancreatic disease. The Lundh test The median pancreatic juice lactoferrin diagnosis and differentiation of pancreatic Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A981 disease, ERCP has been performed and Although there was a significant rise in tion with Mycoplasma pneumoniae may be pancreatic juice cytology, volume, bicar- fourth hour breath "4CO2 after oral 14C- causally related. bonate, protein, and CEA and serum glycocholate, only one patient had a value CEA measured in 121 patients. Of 50 above the normal range during cimetidine Reference patients with pancreatic disease 24 had therapy. Thin layer chromatography for 'Leinikki, P., Pantzar, P., and Tykka, H. (1973). pancreatic cancer, 17 chronic pancreatitis, deconjugated bile acids in postprandial Antibody response in patients with acute pan- and nine acute relapsing pancreatitis, jejunal contents was negative in all creatitis to Mycoplasma pneumoniae. Scandi- while 71 without pancreatic disease patients. All other measurements re- navian Journal of Gastroenterology, 8, 631-635. included 31 with benign obstructive mained within the normal range in all jaundice, 12 with malignant disease out- individuals during the study. Rise of secretin after oral feeding side the pancreas and 28 without relevant We conclude that oral cimetidine treat- concomitant disease. Pancreatic juice flow ment increases bacterial deconjugation of G. R. GREENBERG, W. HACKI, W. DOMSCHKE, was stimulated by a bolus injection of 50 bile acids in the small intestine, but this S. DOMSCHKE, P. MITZNEGG, L. DEMLING, units Boots secretin and collections made effect is too small to be clinically import- AND S. R. BLOOM (Department of over five minutes in one minute samples. ant; and that it has no significant effect on Medicine, Royal Postgraduate Medical Pancreatic juice volume, maximum and pancreatic or gallbladder function in School, Hammersmith Hospital, London, mean bicarbonate concentrations, and response to food. and Medizinische Klinik mit Poliklinik, bicarbonate output were all significantly Erlangen, West Germany) Secretin, the lower in pancreatic cancer and chronic Reference first hormone described, has been said not juice pro- pancreatitis, whereas pancreatic 1Thjodleifsson, B., and Wormsley, K. G. (1975). to have a physiological role in man. How- teins concentrations did not differ sig- Effect of metiamide on the response to secretin ever, clarification of its importance has nificantly between groups. Raised serum and cholecystokinin in man. Gut, 16, 33-35. been hampered by the failure to demon- CEA correlated with the presence of strate a rise after food. We therefore obstructivejaundice rather than pancreatic Mycoplasma pneumoniae-an aetiologi- investigated first whether any detectable disease but pancreatic juice CEA was cal factor in acute pancreatitis? release of secretin occurs with endogenous found to be less than 110 tg/l in all acid stimulation, by assessing secretin patients with a normal pancreas. Cytology R. FREEMAN AND M. J. MCMAHON (Public levels after pentagastrin (6 pg/kg/h) with- gave less than 50% correct diagnoses of Health Laboratory, Chapel Allerton Hos- out gastric aspiration. Secretin levels were pancreatic cancer, whereas ERCP pro- pital, Leeds and University Department of also measured after a standard breakfast duced an overall accuracy of 95 %. Surgery, The General Infirmary, Leeds) (CHO 66 g, fat 22 g, protein 18 g) and Of the diagnostic criteria formulated, a Twenty-seven cases of acute pancreatitis after 250 ml of an oral lemon drink (pH maximum pancreatic juice bicarbonate of presenting to a surgical service were 27). studied for serological evidence of infec- less than 32 mmol/l indicated pancreatic After pentagastrin (n = 6) secretin http://gut.bmj.com/ disease but a mean juice bicarbonate tion with common viruses and related levels increased from basal values of 2-2 i greater than 90 mmol/l and a five minute agents. Serum specimens were obtained on 0-63 (mean ± SEM) pmol/l to a peak of volume greater than 10 ml made pancreatic presentation and during early convalesc- 7-0 ± 1-81 (P < 0-005). No change occur- disease unlikely. ERCP and juice analysis ence and tested against complement fixing red after control experiments with together have allowed correct diagnosis in antigens prepared from influenza viruses pentagastrin and gastric aspiration or with all but one patient in this study. A and B, mumps virus, adenovirus, 0'9% saline. Chlamydia psittaci, Coxiella burneti, and After ingestion of the breakfast (n = 9) Effect of cimetidine on biliary and pancrea- Mycoplasma pneumoniae. In addition, a peak increase to 5*1 ± 0-67 pmol/l from on September 28, 2021 by guest. Protected copyright. tic function in man antibody to mumps virus was assayed by basal levels of 2 5 ± 0 34 occurred at 45 haemagglutination-inhibition, and neu- minutes (P < 0005). By contrast, after D. P. MAUDGAL, D. LAWRENCE, R. BIRD, tralising antibodies to coxsackie viruses drinking lemonade a more substantial P. SANDERSON, AND T. C. NORTHFIELD types Bl to B6 were measured. mean incremental rise of 10-8 pmol/l (Norman Tanner Gastroenterology Unit, St. Thirty-three per cent of the patients had (P < 0 005) at four minutes was observed. James' Hospital and Department of Medi- a significant and reproducible rise in anti- These data demonstrate that endo- cine, St. George's Hospital Medical body to Mycoplasma pneumoniae over the genous acid production releases secretin. School, London) Intravenous metiamide course of their illness. No evidence of The rise of secretin seen after food or reduced trypsin output in response to infection with any of the other agents lemonade was proportional to the duo- intravenous cholecystokinin infusion in tested was found with the exception of two denal acid load and adequate to stimulate man'. We have studied the effect of oral patients in whom there was a rise in anti- pancreatic bicarbonate output'. Thus, cimetidine therapy on jejunal tryptic body to coxsackie virus. secretin is indeed a hormone with a activity and bile acid concentration, and A high incidence of serological evidence physiological role in man. on gallbladder emptying, in response to a ofinfections with Mycoplasmapneumoniae standard Lundh meal. We have also has been previously reported in acute checked whether cimetidine, by blocking pancreatitis1, although it was felt possible Reference gastric acid secretion, causes increased that the antibody was autoimmune in bacterial deconjugation of bile acids. origin. Preliminary biochemical and epi- 'Hacki, W. H., Bloom, S. R., Mitznegg, P., Domschke, W., Domschke, S., Belohlavek, D., Eight patients with peptic ulcer were demiological studies in the Leeds area, Demling, L., and Wunsch, E. (1977). Plasma studied before and during cimetidine though not conclusive, suggest the pos- secretin and pancreatic bicarbonate response to treatment. sibility that acute pancreatitis and infec- exogenous secretin in man. Gut, 18, 191-195. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A982 The British Society of Gastroenterology Half-life, clearance, and endogenous secre- the Boots preparation appeared to be the creatitis and coeliac disease. tion rates of cholecystokinin-pancreozymin more potent. We have therefore studied A standard test breakfast was ingested in man the hormone content of these two CCK by 16 healthy controls and 21 patients preparations in more detail. with chronic pancreatitis, nine having R. F. HARVEY, JANE, M. OLIVER, A. E. READ, Bioassay, using isolated strips of rabbit severe chronic steatorrhoea and 12 having A. EDERLE, I. VANTINI, L. A. SCURO, J. F. gall-bladder, showed Boots Pancreozymin x-ray calcification or ERCP abnormalities GROARKE, AND 0. FITZGERALD (Depart- to be approximately eight times more but no overt exocrine deficiency. Plasma ment of Medicine and Gastroenterology potent than expected. PP in controls rose from 28 ± 7 pmol/l to Unit, Frenchay Hospital, Bristol; Depart- Radioimmunoassay revealed an even a 30 minute peak of 166 ± 25 and in the ment ofMedicine, Bristol Royal Infirmary; larger difference between the immuno- patients with pancreatic disease without III Clinica Medica Generale dell'Universita reactive content of these two hormone steatorrhoea from 38 ± 10 pmol/l to di Padova, Verona; and Department of preparations-Boots Pancreozymin being 156 ± 32. In the nine subjects with Medicine and Therapeutics, University approximately 18 times more immuno- exocrine deficiency PP release was grossly College, Dublin) Serum cholecystokinin- reactive than GIH CCK. impaired (18 ± 5 pmol/l rising to 44 ± 12 pancreozymin (CCK) levels were mea- Because of these unexpectedly large at 30 min, P < 0 001). Injection of Boots sured by radioimmunoassay in 10 normal discrepancies, samples of Boots Pancreo- Secretin, a previously described intra- subjects after a mixed meal and after zymin (batch nos. 6295, 6139, and 5833) venous stimulus to PP release', gave an infusion of cholecystokinin at two differ- and GIH CCK (nos. 273121, 27582, and exactly parallel reduction in response in ent rates. The mean serum increment 27633) were chromatographed on columns the pancreatic exocrine deficiency patients. during infusion of exogenous hormone of sephadex G50 (Pharmacia) and the In contrast, in 10 untreated coeliac was linearly related to the dose infused. hormone content of each eluted fraction patients with severe steatorrhoea PP After stopping the infusion, serum CCK measured by radioimmunoassay. release was quite normal. levels fell rapidly with a half-life of 2-46 The patterns of eluted CCK-like Thus, measurement of PP after a test minutes and a calculated clearance rate of immunoreactivity were quite different meal or intravenous Boots Secretin may 913 ml/kg-min. For the first 30 minutes with the two preparations. The Karolinska form a new and convenient test in the after the meal, serum levels were similar to Institute preparations consisted mainly of initial assessment of steatorrhoea. those produced by infusion of exogenous peptides eluting in the positions corre- porcine CCK at 2 Ivy dog units per kg-h, sponding to CCK-33 and CCK-39. In Reference falling gradually thereafter. contrast, theBoots preparations weremade Rapid injection of porcine CCK into up of fractions which eluted immediately 'Adrian, T. E., Bloom, S. R., Besterman, H. S., normal subjects and patients with Barnes, A. J., Cooke, T. J. C., Russell, R. C. G., pan- before and after the salt peak. and Faber, R. G. (1977). Mechanism of pan- creatic diseases showed that the halflife of Conclusions (1) One nominal Crick creatic polypeptide release in man. Lancet, 1,

CCK in the circulation of such patients is Harper Raper unit ofBoots Pancreozymin 161-163. http://gut.bmj.com/ not significantly different from normal. is biologically approximately twice as Conclusions (1) Cholecystokinin-pancreo- potent as one nominal Ivy dog unit of Characterisation of secretin-like peptides zymin is cleared very rapidly from the Karolinska Institute Cholecystokinin; (2) from tissue and plasma extracts using circulation in man; (2) the raised serum the biological activity of Boots Pancreozy- immunoaffinity chromatography CCK levels in patients with pancreatic min is due largely to its content of small disease are not due to decreased clearance molecular forms of the hormone; (3) J. C. MASON, R. F. MURPHY, AND K. D. of the hormone; (3) a 'physiological' Boots Pancreozymin also contains im- BUCHANAN (Departments ofBiochemistry

infusion rate for CCK is approximately 2 munoreactive forms of CCK-PZ which and Medicine, Queen's University, Belfast) on September 28, 2021 by guest. Protected copyright. Ivy dog units/kg-h. lack biological activity. Antibodies to secretin raised in sheep and specific for a region of the hormone con- Hormonal content of commercial prepara- PP in the assessment ofpancreatic exocrine taining residues 14 to 27 were immobilised tions of cholecystokinin-pancreozymin function on CNBr-activated Sepharose 4B. Human plasma and preparations obtained by JANE M. OLIVER AND R. F. HARVEY (Depart- T. E. ADRIAN, H. S. BESTERMAN, C. N. extracting porcine duodenum and ment ofMedicine, Bristol Royal Infirmary MALLINSON, AND S. R. BLOOM (Royal jejunum with acidified ethanol were and Frenchay Hospital, Bristol) There Postgraduate Medical School, Hammer- applied to the immunoaffinity columns. are two widely available commercial pre- smith Hospital, and Greenwich District Non-biospecifically bound materials were parations of cholecystokinin-pancreozy- Hospital, London) The cells producing eluted1 with 0-15M Na Cl adjusted to pH min (CCK), one produced by the Boots pancreatic polypeptide (PP), the newest 11. Materials which bind antibodies to Company Ltd., Nottingham (Boots Pan- circulating hormone, are confined in man secretin in radioimmunoassay were re- creozymin) and one by the GIH Research almost entirely to the pancreas. Its tained on the columns and were subse- Laboratory, Karolinska Institute, Stock- measurement in plasma by radioimmuno- quently eluted with 4M guanidinium holm (GIH cholecystokinin). Although assay is straightforward and demonstrates chloride. The secretin-like fractions were each ampoule of GIH cholecystokinin a rapid and very substantial rise after a further characterised by gel-filtration on nominally contains 75 Ivy dog units of meal. As PP release appears to be con- Sephadex G50. At least four molecular CCK and each ampoule of Boots Pan- trolled by exactly the same mechanisms species of secretin-like peptides were creozymin about 100 Crick Harper Raper that control pancreatic enzymes', we have detected in the intestinal preparations. units (theoretically equivalent to 25 Ivy investigated its release in patients with Polypeptide material with molecular dog units), we observed in clinical use that two causes of steatorrhoea, chronic pan- weight 6000 was the predominant form Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A983 and was accompanied by peptides with Ultrastructural studies showed smaller CLINICAL DIAGNOSTIC molecular weight about 11 000, 3500, and and more numerous secretory granules in < 2000. Most of the secretin-like immuno- these patients, suggesting rapid synthesis Assessment of nutrition in surgical patients reactivity from plasma, however, was and release. -a comparison of simple anthropometry detected in fractions with molecular The present results indicate that GIP with measurement of total body nitrogen weight <3000 though a significant pro- cells in chronic pancreatitis are not hyper- from neutron activation analysis portion (10 to 20%) of the immuno- plastic but may be hypersecretory and thus reactivity had an apparent molecular empty of hormone. J. P. COLLINS, G. L. HILL, J. A. BRADLEY, weight about 12 000. The multiplicity of I. MCCARTHY, C. B. OXBY, AND L. BURKIN- secretin-like peptides in the intestine and Reference SHAW (University Departments ofSurgery plasma is analogous to that observed for and Medical Physics, The General Infir- glucagon-like immunoreactivity2 and may 'Creutzfeldt, W., Ebert, R., Arnold, R., Frerichs, mary, Leeds) There is increasing interest H., and Brown, J. C. (1976). Gastric inhibitory be due to the presence of precursors and polypeptide (GIP), gastrin and insulin. Response in the use of arm circumference triceps degradative products of secretin. to test meal in coeliac disease and after duodeno- skinfold, and derivatives of these for References pancreatectomy. Diabetologia, 12, 279-286. nutritional assessment of muscle and fat reserves in surgical patients. In order to 'Murphy, R. F., Conlon, J. M., Imam, A., and study the relationships of these measure- Kelly, G. C. (1977). Journal of Chromatography, New view of pancreatic endocrine tumours 135, 427. ments to body cell mass we measured body 2Conlon, J. M., Flanagan, R. W. J., Buchanan, weight, skinfold thickness (mid-biceps, K. D., and Murphy, R. F. (1976). Excerpta S. R. BLOOM, A. M. WEST, J. M. POLAK, AND mid-triceps, subscapular, suprailiac) arm Medica, 400, 50. T. E. ADRIAN (RoyalPostgraduate Medical circumference and total body nitrogen GIP cells in chronic pancreatitis School, Hammersmith Hospital, London) (TBN) by in vivo neutron activation Four clinically important types of pan- analysis on nine controls, 12 surgical A. M. J. BUCHAN, J. M. POLAK, S. R. BLOOM, creatic endocrine tumour have been des- patients with minimal weight loss (34%) H. BESTERMAN, M. SOUTH, R. MCCLOY, J. H. cribed-secreting glucagon, insulin, gas- and 12 patients with major weight loss (17- BARON, AND A. G. E. PEARSE (Departments trin, and VIP. The concept of pancreatic 31 %). Values for fat free mass, arm of Histochemistry, Medicine and Surgery, apudomas secreting more than one type of muscle circumference, and arm muscle Royal Postgraduate Medical School, Lon- peptide hormone has been raised, how- area were calculated from these values and don) Gastrin inhibitory polypeptide ever, and we have investigated this by compared with those of TBN. (GIP) is a 43 aminoacid polypeptide radioimmunoassay and immunocyto- TBN correlated well with all the originally extracted from the small intes- chemistry of two near pancreatic hor- anthropometric values except triceps skin- tine. Although first described by its effect mones, somatostatin and PP. fold. The correlation coefficients were for on gastric acid secretion, the main action Significant quantities of somatostatin fat free mass (r = 090), for body weight of GIP appears to be in the stimulation of were found in 19 pancreatic tumours (r = 0 83), for arm muscle circumference http://gut.bmj.com/ insulin release. The hormone has there- available for investigation. The highest (r = 0 78), for arm muscle area (r = 0 77), fore been renamed Glucose dependent concentration was present in the gastrino- and for arm circumference (r = 0-71). Insulin releasing Peptide. mas (2-2 ± 0 7 nmol/g, n = 5), less in two It is concluded that fat free mass, body Combined immunocytochemical and glucagonomas (mean 0-2 nmol/g) and two weight, arm muscle circumference, and radioimmunoassay studies have shown insulinomas (mean 0-1 nmol/g) and only arm circumference are reasonable indica- that GIP is predominantly localised in the small amounts in VIPomas (0 004 i 0 002 tors of body cell mass. Although anthro- small intestine (71 ± 8 pmol/g-12 5 cells/ nmol/g, n = 10). In many of these pometry lacks the precision to be clinically mm2). Electron-immunocytochemical tumours immunofluorescent D cells were useful for individual patients, these on September 28, 2021 by guest. Protected copyright. studies have now shown that the GIP cells seen. measurements are of value when groups of correspond to the previously described K In 27 out of 69 pancreatic tumours, patients are being compared. cell of the electronmicroscopic classifica- extracts showed a very high concentration tion. Knowledge of the cell of origin of of PP. On immunocytochemistry nume- Use of the creatinine-height index in under- GIP and the appearance of its secretory rous PP cells were found in these tumours. weight patients granules could be important in GIP In 60 patients fasting plasma PP concen- pathology. There is an abnormally high trations were measured and were grossly A. J. RICH, D. TREGONING, T. HAWKINS, AND GIP response to an oral glucose load in raised in 26. P. D. WRIGHT (Professor I. D. A. JOHNSTON) patients with chronic pancreatitis1. We Thus, in a pancreatic tumour thought (Departments of Surgery and Medical therefore carried out quantitative immuno- to be producing one type of hormone, it is Physics, University of Newcastle upon cytochemical and ultrastructural studies of common to find considerable quantities of Tyne) The creatinine-height index (CHI) duodenal GIP cells in biopsies from fast- other pancreatic hormones present. The has been proposed by several authors",2 as ing patients with the disease, in order to concept of endocrine tumours being com- an indicator of changes in lean body mass ascertain if the high circulating GIP levels posed of a single cell type appears no in normal individuals and during nutri- were due to a hyperplasia of normally longer valid. The chance predomination of tional support. However, creatinine me- secreting GIP cells or hypersecretion by a one cell type is responsible for the clinical tabolism in illness is not fully understood normal or decreased number of GIP cells. syndrome but all pancreatic endocrine and even in normal individuals Greenblatt Results showed a non-significant (11-52 %) tumours should now perhaps be classified et al.3 recorded considerable individual decrease in the number of detectable GIP under the more general heading of 'islet daily variation in urinary creatinine cells. cell tumours'. excretion. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A984 The British Society of Gastroenterology Two groups of patients were studied. syndrome of histological changes was IG molecules from their binding sites on Group I were 15 % or more below their then identified in aspiration biopsy albumin and, as a result, their renal excre- ideal weight. Group II were patients with specimens and termed 'biopsy evidence of tion is increased in the presence of jaun- colorectal cancer and were within 15 % of hyperplasia of Brunner's glands' HBg. dice; (2) IT should prove superior to IG as their ideal weight. Anthropometric mea- Among 260 unselected gastrointestinal a cholangiographic agent. surements were used to calculate the arm patients HBg was established in 10. muscle circumference for each patient. Statistically significant correlation was *Schering Chemicals, Ltd. SH H 273 AB Total body potassium was measured using found between HBg and polypoid x-ray a whole body counter and urinary crea- pattern as well as nodular appearance Urinary urobilinogen-should we bB mea- tinine used to calculate the CHI. The upon duodenoscopy. However, these suring it? results were compared with values for appearances were absent in hypotonic normal individuals described elsewhere'. duodenography and surgical exploration I. T. GILMORE, A. C. PEATFIELD, AND R. P. H. Analysis of the results showed that a in most cases. It is concluded that poly- THOMPSON (G.L Laboratory, Rayne Insti- better estimate of lean body mass as mea- poid x-ray and endoscopic pattern is tute, St. Thomas' Hospital, London) The sured by total body potassium was rarely caused by hyperplastic glands semiquantitative measurement of the con- obtained using arm muscle circumference themselves; more often it is caused by centration of urobilinogen in urine with than by the CHI. Urinary creatinine mucosal folds caused by irregular con- dipsticks is said to be a sensitive test of excretion showed marked variation on a traction of the muscularis mucosae dis- liver function and is probably the most day-to-day basis and more consistently rupted by protruding glands. Most widely used. We are reassessing its practi- underestimated lean body mass in group I patients with HBg and polypoid pattern cal value, and have compared Ehrlich's than in group II. had mild histological duodenitis and some aldehyde reagent (EAR) with a new, more It is suggested that the CHI as calculated sort of epigastric distress. specific chromogen, p-methoxybenzene- is diazonium-fluoboratel (p-MDFB), avail- from a single 24-hour urinary collection able also in dipstick form as 'B.M. test unlikely to reflect accurately the lean body Plasma binding, renal and biliary excretion urobilinogen'. mass in an underweight patient. As a of two intravenous cholangiographic agents Nine patients with active chronic single, simple measurement the arm in normal and jaundiced subjects hepatitis (ACH) in and out of control muscle circumference is more likely to be were studied fortnightly for one year with accurate, provided clinical oedema is J. DORAN, W. VENNART, AND G. D. BELL absent. (University Department of Therapeutics urinary urobilinogens and conventional and Department of Medical Physics, City liver function tests (LFT). There was a References poor correlation between biochemical Hospital, Nottingham) A new intra- relapses and urobilinogen, but the latter 'Butterworth, C. E., and Blackburn, G. L. (1975). venous cholangiographic agent, iotrox- were was sometimes raised when LFT http://gut.bmj.com/ Hospital malnutrition. Nutrition Today, 10, 8- amide (IT)* has recently been produced. It was also variable in 18. is claimed that IT gives better opacification normal. Urobilinogen "Gross, E., Holbrook, I., and Irving, M. H. (1976). of the bile duct, is less protein bound, and patients with viral hepatitis, but tended to The creatinine height index-a guide to nutri- be increased early and late in the illness. tional status. Gut, 17, 818. produces less side-effects than either Results with EAR and p-MDFB methods "Greenblatt, D. J., Ransil, B. J., Harmatz, J. S., ioglycamide (IG) or iodipamide. Smith, T. W., Duhme, D. W., and Koch-Weser, Biliary iodine concentration achieved were similar, but B.M. test urobilinogen J. (1976). Variability of 24-hour urinary crea- sticks and Urobilistix correlated poorly tinine excretion by normal subjects. Journal of during T-tube drainage after cholecystec- with either. Clinical Pharmacology, 16, 321-328. tomy was compared in eight patients (mean that with We conclude (1) testing dip- on September 28, 2021 by guest. Protected copyright. bilirubin 54-3 zmol/l, range 7-142). Each sticks should be abandoned; (2) urinary Biopsy evidence of hyperplasia of Brunner's patient received both agents, the infusions urobilinogen levels may be raised in ACH glands being given on the ninth and 11th post- operative days and the order of infusion when other liver function tests are normal the but i. probably not a useful routine test; Z. MA.ATKA, J. KOCIANOVA, P. JIRKO, AND being randomly allocated. In all (3) p-MDFB test for urobilinogen com- J. KUDRMANN (Hospital Bulovka, Prague, patients studied the maximum biliary with Ehrlich's Czechoslovakia) Hyperplasia of Brunner's iodine concentration was greater using pares favourably reagent. glands (HBg-diffuse or nodular) means iotroxamide than with ioglycamide, the Reference of their in average difference being 28% (paired increased thickness layer 'Kutter, D., and Humbel, R. (1973). Quantitative duodenal submucosa. A reliable diagnosis Student's t test, P < 0 01). assay of urinary urobilinogen with p-meth- can be made only by measuring in We have also studied the plasma binding oxybenzene-diazonium-fluoborate. Clinica postmortem or surgical specimens of and renal excretion of radio-labelled IT in Chimica Acta, 45, 61. the entire wall. In a postmortem study six normal and six jaundiced subjects and of 100 unselected specimens the average compared the results with those obtained Grey scale ultrasonography in diagnosing thickness in descending duodenum was in a similar number of patients given IG. gall stones 0O42 mm; thickness over 0-6 HBg No significant difference was observed was found in 16%. Simultaneously between IT and IG. However, with both A. J. MCKAY, J. G. DUNCAN, S. N. JOFFE, C. other changes were noted: marked compounds the plasma binding was W. IMRIE, AND L. H. BLUMGART (Univer- lobularity and septalisation, penetrating reduced (p < 0-05) and the renal excretion sity Department of Surgery and Depart- into the mucosa, fenestration and frag- increased (p < 0 01) in the presence of ment of Radiology, Royal Infirmary, mentation of muscularis mucosae, dis- jaundice. Glasgow) Grey scale ultrasonography placment of Lieberkiihn's glands. This Conclusion (I) Bilirubin displaces IT and (GSU) has been assessed prospectively in Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A985 100 patients in three clinical situations unsatisfactory in 21 %. B scanning was rise in UBI2BC. The range found was 009 where diagnosis by conventional contrast correct in 82%, incorrect in 9%, and to 6-1 ,ug/l, and only four values were radiology often fails'. The diagnosis of unsatisfactory in 9%. Cholescintography above the normal range. gall stones in each patient was subse- gave the correct diagnosis in eight Assay of UB12BC thus provides a simple quently confirmed by cholangiography patients investigated. method of monitoring treatment in and/or surgery. GSU was performed with- The results indicate that scanning patients with hepatocellular carcinoma in in 48 hours of admission in 30 patients (which is considerably more comfortable whom alpha fetoprotein levels are normal. with suspected acute cholecystitis. The gall for the patient), is comparable with oral It is unlikely to prove useful in adult bladder was outlined in 87% and stones cholecystography in the diagnosis of acute patients as plasma levels are not signifi- shown in 18 patients. In 30 outpatients cholecystitis. Our preliminary findings cantly raised. investigated for recurrent biliary colic, the also indicate that cholescintography is a gall bladder was demonstrated in 83%, rapid procedure acceptable to patients References and gall stones reported in 15, with only which may be very useful in diagnosis. one false positive. 'Burger, R. L., Waxman, S., Gilbert, H. S., References Mehlman, C. S., and Allen, R. H. (1975). In 40 patients with acute pancreatitis, Isolation and characterisation of a novel GSU was carried out within one week of 'McArthur, P., Cuschieri, A., Sells, R. A., and vitamin B,, binding protein associated with admission and outlined the gall bladder in Shields, R. (1975). Controlled clinical trial hepatocellular carcinoma. Journal of Clinical In 13 patients gall stones were comparing early with interval cholecystectomy Investigation, 56, 1262-1269. 72-5%. for acute cholecystitis. British Journal of 2Gottlieb, C., Lau, K. S., Wasserman, L. R., and accurately diagnosed with two false Surgery, 62, 850-852. Herbert, V. (1965). Rapid charcoal assay for positive results. Patients required no pre- 'Baker, R. J., Bellen, J. C., Ronai, P. M. (1974). intrinsic factor (IF), gastric juice unsaturated paration for the investigation and the '9Tc pyridoxylideneglutamate: A new rapid B,, binding capacity, antibody to IF, and serum cholescintographic agent. Journal of Nuclear unsaturated B,, binding capacity. Blood, 25, presence of gas obscuring the ultrasound 875-884. image was the main cause of technical Medicine, 15, 476. failure. Vitamin B12 binding protein in hepatocel- Breath hydrogen after lactulose as a The early and accurate diagnosis of gall lular carcinoma: value in monitoring diagnostic test for bacterial overgrowth stones in acute cholecystitis, biliary colic therapy and acute pancreatitis will lead to an J. M. RHODES, D. P. JEWELL, AND P. improved selection ofpatients for definitive S. P. KANE, J. KOHN, P. JOHNSON, R. MIDDLETON (Department of Medicine, surgery. WILLIAMS, AND I. M. MURRAY-LYON Royal Free Hospital, London) The lactu- Reference (Department of Gastroenterology, Charing lose breath test' has been compared with the C14 in the 1Raine, P. A. M., and Gunn, A. A. (1975). Acute Cross Hospital; Department of Chemical glycocholate breath test2 cholecystitis. British Journal of Surgery, 62, 697- Pathology, Queen Mary's Hospital; Liver assessment of suspected bacterial over- 700. Unit, King's College Hospital) Previous growth of the small intestine. Seventeen workers' have demonstrated high serum patients have been studied: nine with http://gut.bmj.com/ Ultrasound and cholescintography in the and tumour levels of an abnormal vitamin small bowel diverticula or fistulae, five diagnosis of acute cholecystitis B,2 binding glycoprotein in three adoles- with Crohn's disease of the small bowel, cents with malignant hepatoma. one with small bowel lymphoma, and one J. G. MOSLEY, C. METROVELI, AND A. We have used the serum unsaturated with partial ileal resection. GREGORY (introduced by J. SPENCER) vitmain B,2 binding capacity (UB12BC) Twenty millitres of lactulose syrup were (Departments of Surgery and Radiology, measured by radio-assay2 as an index of given to fasting patients. End-expiratory Royal Postgraduate Medical School, Lon- circulating vitamin B12 binding protein breath samples were analysed for hydro- don) Acute cholecystitis is one of the levels. This assay was employed to moni- gen using gas chromatography. The C14 on September 28, 2021 by guest. Protected copyright. major causes of emergency surgical tor the progress of two juveniles with high glycocholate breath test was that reviewed admission, and there is evidence that plasma levels during intermittent chemo- by James et al.2. Samples for bacteriology cholecystectomy within three or four days therapy with adriamycin. Both patients were obtained by using sterile anaerobic of admission reduces the duration of stay had a biopsy-proven hepatocellular carci- techniques and cultured for aerobes and in hospital without increasing morbidity'. noma and sera were negative for HBsAg anaerobes. Unfortunately, accurate diagnosis in the and alpha fetoprotein. The 15 year old Ten patients were normal on both tests. acute situation is often difficult. girl's UB,2BC at the onset of treatment After lactulose four patients showed early We report a consecutive series of 34 was 414 ug/l (normal range-0-83-17 ,ug/l) hydrogen excretion appearing before the emergency admission with a clinical diag- and it rose during three months to 828 main peak corresponding to the passage of nosis of acute cholecystitis. They were in- ,ug/ml in parallel with a deterioration in lactulose into the colon. All four had vestigated within 48 hours of admission by her clinical state and biochemical indices. abnormal C,, glycocholate tests. Three oral cholecystography, B mode scanning The 16 year old boy's initial UB,2BC was patients with abnormal C14 glycocholate equipped with grey scaling and more 132 sg/l, falling to 79 jug/l after three tests had no early hydrogen excretion and recently also cholescintography using courses of chemotherapy which resulted in were all known to have ileal disease likely intravenous 99mTc pyridoxylidene gluta- some decrease in hepatomegaly. UB12BC to cause bile-salt malabsorption. The6 mate2. The findings were subsequently levels rose again to 138 Itg/l as his disease absence of overgrowth was confirmed verified by further radiography or progressed. bacteriologically in these cases. laparotomy. We have screened the sera of 39 adult The lactulose breath test, therefore, is Oral cholecystography gave the correct patients aged 19-71 years with hepato- successful in diagnosing small bowel over- diagnosis in 79 % of cases and was cellular carcinoma for evidence of a gross growth and in distinguishing this from Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A986 The British Society of Gastroenterology ileal disease; this gives it a useful advan- in the rectal mucosa of patients with changes, crypt abscesses were seen with tage over the C14 glycocholate breath test. 'proctitis' suggesting that a local allergic focal mucus depletion. These appearances response may be important in the patho- are seen in other types of infective colitis References genesis of this disorder. In order to including shigella dysentery, gonococcal 'Bond, J. H., and Levitt, M. D. (1975). Investiga- investigate if a similar mechanism might proctitis, and amoebic colitis. tions of small bowel transit using pulmonary H, be involved in Crohn's disease (CD) and The pattern of inflammation in infective measurements. Journal of Laboratory and Clinical Medicine, 854, 546-555. ulcerative colitis and to see if the presence colitis is sufficiently distinctive for the sJames, 0. F. W., Agnew, J. E., and Bouchier, I. A. of rectal IgE-cells would help differentiate histopathologist to be able to differentiate D. (1973). Assessment of the C,, glycocholic these two conditions, we have studied the it from the appearances seen in rectal acid breath test. British Medical Journal, 3, 191- immunoglobulin-containing cells in rectal biopsies from patients with idiopathic 195. mucosa in patients with non-specific inflammatory bowel disease. In the seven antibody studies in giardiasis inflammatory bowel disease. Immuno- patients with coincidental salmonella Fluorescent fluorescent techniques were employed. infection, four have ulcerative colitis, two Rectal biopsies were obtained from 15 have Crohn's disease, and in one the S. G. WRIGHT, A. H. MOODY, A. M. TOMKINS, patients with Crohn's disease who had diagnosis remains equivocal. In general, D. S. RIDLEY (Hospital for Tropical rectal involvement, 12 with UC and the histology in these cases was of the Diseases, London, Department of Human these were compared with 15 control idiopathic inflammatory bowel disease. Nutrition, London School of Hygiene and subjects. No difference was found for Tropical Medicine, London) Giardiasis is IgA, IgM, or IgG cells in either disease Reference a protozoan infection of the gastro- group as with intestinal tract that usually produces no compared controls. The 'Mandal, B. K., and Mani, V. (1976). Colonic symptoms but in a proportion of patients few patients who had reduced IgA or involvement in salmonellosis. Lancet, 1, 887- IgM cell counts had greatly increased 888. is associated with malabsorption that extracellular staining implying secretion of resolves after appropriate treatment1. immunoglobulin rather than a true Sensitivy of gastric and colorectal cancers Parasitologicaldiagnosisisusuallystraight- to cytotoxic drugs in culture forward but in some patients with marked deficiency. IgE cells were rarely seen in symptoms and considerably disorderd control subjects but were present in large numbers in nine of 12 UC patients and I. L. ROSENBERG, T. W. HANNAM, AND G. R. absorption the parasite can be elusive. The seven of 15 with CD. These counts did not GILES (University Department ofSurgery, fluorescent antibody test for giardiasis2 correlate with extent, duration, or treat- St. James's University Hospital, Leeds) using Giardia lamblia cysts as antigen was ment of the disease nor was there any Cytotoxic chemotherapy for gastrointesti- evaluated in sera from patients with a difference within disease groups. nal cancer is usually prescribed on an empi- variety of intestinal disorders. rical basis. Improved selection of The test was positive in 18 out of 19 These findings suggest that an allergic drugs may mechanism may be important in both CD follow the use of chemosensitivity tests on http://gut.bmj.com/ cases of giardiasis with malabsorption in and UC. in vitro cultures of tumour cells. Twenty- reciprocal titres ranging from 20 to 320. five short-term monolayer cultures were Negative results were obtained in control Reference subjects (20), gluten enteropathy (eight successfully established from eight of 15 bowel diseases 'Heatley, R. V., Calcraft, B. J., Fifield, R., Rhodes, gastric cancers (53%) and 17 of 59 colo- cases), inflammatory (12 J., Whitehead, R. H., and Newcombe, R. G. rectal cancers (29 %). Failure to culture cases), and in 10 of 11 eleven patients with (1975). Immunoglobulin E in rectal mucosa of resulted from bacterial or fibroblast over- acute tropical sprue. This test appears patients with proctitis. Lancet, 2, 1010-1012. useful in the investigation of patients with growth. Successful cultures were innocula- Biopsy diagnosis of infective colitis ted into microtitre plates and exposed to on September 28, 2021 by guest. Protected copyright. malabsorption. 5-fluorouracil, I-phenylalanine mustard, References D. W. DAY, B. K. MANDAL, AND B. C. methotrexate, thiotepa, cyclophospha- MORSON (St. Mark's Hospital, London, mide, vincristine, and doxorubicin in 'Wright, S. G., Tomkins, A. M., Ridley, D. S. andMonsallHospital, Manchester) Infec- appropriate concentrations. a (1977). Giardiasis. Clinical and therapeutic Defining aspects. Gut, 18, 343-350. tion by salmonella organisms of food- response as a 50% inhibition of tritiated "Ridley, M. J., and Ridley, D. S. (1976). Serum poisoning type not uncommonly give rise leucin incorporation, doxorubicin appear- antibodies and jejunal histology in giardiasis to a dysenteric type of illness, with bloody ed most active (12/25) compared with associated with malabsorption. Journal of diarrhoea, tenesmus, and tenderness over 5-FU (8/25) and vincristine (7/25), with Clinical Pathology, 29, 30-34. the sigmoid colon'. Rectal biopsies were no activity demonstrated by cyclophos- Rectal IgE cells in inflammatory bowel studied from 29 patients with salmonella phamide. Only two cultures were sensitive disease colitis, seven of whom were subsequently to four or more drugs; 12 were sensitive to found to have idiopathic inflammatory one or two different drugs and six were D. P. O'DONOGHUE AND PARVEEN J. bowel disease. The biopsies from patients insensitive to any. KUMAR (Department ofGastroenterology, with salmonella infection alone showed With the exception of doxorubicin St. Bartholomew's Hospital, London) The changes of varying severity with mucosal sensitivity, the degree of drug activity in differentiation between Crohn's colitis and oedema, polymorphs in the lamina culture was similar to that seen in clinical ulcerative colitis (UC) is often difficult and propria, and infiltrating crypt epithelium, practice. Since most cultures respond to immunological studies have to date been but, in the majority, no increase in only one or two drugs, a degree of unhelpful in separating the two conditions. chronic inflammatory cells and preserva- selectivity in the tests is apparent. The Recently Heatley and colleagues1 have tion of crypt architecture and mucus study suggests that a clinical application shown an increase in IgE-containing cells content. In those with the most severe of this approach may be justifiable. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A987 Cell kinetic and cyclic amp studies in colo- Middlesex Hospital, London, and Depart- The average duration of stay in hospital rectal carcinoma-a guide to earlier ment of Surgery, University College fell slightly from a mean of 14 8 days to diagnosis? Hospital, London) Replies from 154 13-0 days. Blood transfusion requirements centres, representing 262 named BSG were not significantly affected (2 5 v 2-7 D. TREGONING, G. TURNER, A. J. WATSON, members, revealed considerable variations units), but in 87% a bleeding site was D. C. BRITTON, G. BONE, AND A. L. LATNER in opinions and practice. Only 29% of identified, as opposed to only 55% in the (Departments of Surgery, Clinical Bio- respondents controlled management of earlier group. The diagnosis was also made chemistry and Clinical Pathology, Univer- more than 80% of all bleeders admitted. more quickly (2-0 v 4-1 days) and surgery sity of Newcastle upon Tyne) The Physicians constituted 96% of admitting was performed earlier and more fre- Medical Research Council has indicated teams; 40% of centres never used inten- quently (32% v 9%). Despite this, the that colonoscopy and biological tumour sive therapy areas. Investigation within 24 overall mortality was not improved. It is markers are areas of the highest priority hours was usual (severe bleeders 98 %, concluded that endoscopy has had no in the study of colorectal cancer'. moderate 80%, minor 47%). Endoscopy effect on the prognosis of upper gastro- Colonoscopic mucosal biopsies were was the most accessible investigation, and intestinal bleeding, although the diagnostic obtained from patients with adenocarci- was used first in 82% of centres. Double yield is higher. nomas of the colon, and cell kinetics and contrast bariums and urgent angiograms cyclic nucleotide estimations were under- were rarely available. Serous complica- References taken in order to investigate the natural tions were experienced by 14% of endo- 'Hellers, G., and Ihre, T. (1975). Lancet, 2, 1250. history of colonic cancer and thus hope- scopists. Twenty-seven per cent of 'Hoare, A. M. (1975). British Medical Journal, 2, fully facilitate earlier diagnosis of this respondents (34% of physicians, 8% of 27. common condition. surgeons) did not know if a precise diag- Early endoscopy in the prediction of further The mean mitotic index of the caecal nosis helped, and 28% would withhold haemorrhage from peptic ulcers mucosa of six normal patients was 5-9% endoscopy for a controlled trial. Direct (SD ± 0-56). This was significantly higher non-surgical treatment was rarely used D. N. FOSTER, K. J. A. MILOSZEWSKI, AND than that of the rest of the colon-mean (angiographic 15 %, endoscopic 7 %). M. S. LOSOWSKY (Department ofMedicine, 3-6% (SD ± 0 1) (p = 0 03 Mann Most respondents believed that ulcer re- University of Leeds, St. James's Hospital, Whitney u-test). bleeding was commoner in men and the Leeds) Despite the recent explosion in The mean mitotic index of 19 rectal elderly, and were considerably influenced the use of endoscopy in upper gastro- tumours was I 1% (SD ± 0 35) and this towards surgery by increasing age and a intestinal haemorrhage (UGIH) there is a was lower than that of normal rectal previous bleed, less by ulcer size or pre- dearth of documentation of the detailed mucosa-mean 3-2% (SD ± 0 78) (Mann vious dyspepsia. Questions concerning findings unique to endoscopy. In most Whitney u-test P = 0 001). Intrinsic indications for surgery and its type in studies the lesion seen is accepted un- mucosal differences therefore exist in dif- hypothetical patients bleeding from critically as the source of bleeding and ferent parts of the normal colon and these chronic ulcers and acute erosions revealed few record the proportion of lesions bear- http://gut.bmj.com/ may be a factor in the anatomical distribu- many major disagreements. This lack of ing the stigmata of recent haemorrhage tion of colonic cancer. consensus suggests a need for specific (SRH), the potential value of which in Cyclic amp is an important determinant treatment trials. predicting the clinical course has thus been of cell growth and differentiation and ignored. hence may be a biological marker of Impact of endoscopy on the outcome and Early endoscopy in 245 of 277 consecu- colonic cancer. The mean cyclic amp management of upper gastrointestinal tive episodes of suspected UGIH managed concentration in 11 patients with rectal bleeding by our unit revealed duodenal ulcers (DU) carcinoma was found to be 1 1 pmol per alone in 48 and gastric ulcers (GU) alone on September 28, 2021 by guest. Protected copyright. mg (SD ± 0 2) for the malignant tissue G. B. LEE, P. M. SMITH, AND D. J. T. WEBSTER in 41, of which 27 (56%) and 33 (80%) and 0-78 pmol per mg (SD ± 0 2) for the (Departments of Medicine and Surgery, respectively bore SRH. In the absence of adjacent normal mucosa (Wilcoxon mat- Llandough Hospital, Nr. Penarth, S. SRH, only one patient with DU and none ched pairs and signed ranks test, P = 0 03). Glamorgan) It is generally assumed' 2 with GU had further haemorrhage (FH) Exploitation of these different levels of that endoscopy, by providing a quicker or emergency surgery (ES). In contrast, cyclic amp in normal and malignant tis- and more accurate diagnosis, will improve where SRH were present 16 of 27 DU sue may lead to the discovery of a reliable the prognosis ofpatients with upper gastro- patients (59%) and 15 of 33 GU patients biological marker. intestinal bleeding. We have examined (45 %) required ES. this assumption by comparing patients of The presence (or absence) or SRH is Reference comparable age admitted to Llandough superior to and enhances the value of any 'MRC Joint Statement of Policy for Biomedical Hospital over two consecutive three-year other factor commonly used to predict the Research. December 1976. periods, 1970-73, and 1973-76. An likelihood of FH from peptic ulcers and emergency endoscopy service came into the need for ES. Early endoscopy may CLINICAL MEDICAL It being at the start of the second three-year thus have prognostic as well as diagnostic period. functions in UGIH. Questionnaire on management of acute Ninety-eight patients were admitted bleeding with a diagnosis of upper gastrointestinal Cimetidine-an advance in gastric ulcer bleeding from 1970-73, and 151 patients treatment? G. E. THOMAS, P. B. COTTON, AND C. G. from 1973-76. One hundred and eight of CLARK (Gastrointestinal Unit, The the latter group underwent endoscopy. W. A. F. MCADAM, A. G. M9RGAN, C. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A988 The British Society of Gastroenterology PACSOO, B. E. WALKER, AND A. V. SIMMONS The proportion of deoxycholic acid in especially the Reitan trail test, just before (Airedale GeneralHospital, Steeton; Chapel bile and faeces was significantly reduced in diazepam administration, was of value in Allerton Hospital, Leeds) The use of oral AC compared with controls (p < 0.01 for predicting the degree of deterioration cimetidine (1 g/day) has been compared bile and faeces) but there was no signifi- (r = 0-82 for trail test). This was the case with carbenoxolone (100 mg tds for one cant difference between AC and CAH regardless of previous episodes of week, and then 50 mg tds) for patients groups. The proportion of chenodeoxy- encephalopathy. under 60 years of age, and Caved-S (two cholic acid in bile and faeces was signifi- It is concluded that susceptibility to tablets tds) for those over 60 years with cantly greater in AC than in controls diazepam in chronic liver disease is gastric ulceration. (p < 0-05 in both cases) and again the AC increased only when cerebral function is Initially, all patients were endoscoped, and CAH groups were not significantly already impaired, and the results indicate and the ulcer healing assessed either endo- different. Values for these two bile acids in a role for increased CNS sensitivity rather scopically or radiologically at monthly the ANC group were similar to those found than impaired drug metabolism. A Reitan intervals (x 3). Healing was always in the control group but significantly dif- trail test performed just before admini- confirmed endoscopically. ferent from patients with AC (deoxycholic stration of diazepam is a useful and Forty-nine patients entered the study, p < 001, p < 0-02 chenodeoxycholic; simple test for predicting response. 42 have completed, and a further three p < 0-01 for bile and faeces). The propor- withdrawn (one cimetidine rash; two tions of cholic acid and lithocholic acid Social toll of Crohn's disease treatment failures). did not differ significantly between the Under 60's Five patients received cimeti- controls and the other groups. B. G. GAZZARD, H. L. PRICE, AND A. M dine, two healed by one month, and all by We conclude that within the groups DAWSON (Department of Gastro- two months. studied the presence of cirrhosis is of enterology, St. Bartholomew's Hospital, Seven patients received carbenoxolone, greater importance than the alcohol London) Eighty-five patients with long but two were withdrawn for uncontrolled aetiology in the development ofdi-hydroxy standing Crohn's disease were inter- dyspepsia (at two and seven weeks), three bile acid disturbances. viewed concerning their knowledge of healed by one month, four by two months Crohn's disease, their aspirations, and and one remained unhealed at three References various aspects of their social life. These months. factors were correlated with the activity 'Vlahcevic, Z. R., Juttijudata, P., Bell, C. C., and Over 60's Sixteen patients received cime- Swell, L. (1972). Bile acid metabolism in of the disease, and the psychological tidine, eight healed by one month, 14 by patients with cirrhosis. Gastroenterology, 62, makeup of the patient assessed by the two months and all by three months. 1174-1181. Eysenck personality questionnaire and the 'Mehta, S. J., Struthers, J. E., Kaye, M. D., and morbid index. Fourteen patients received Caved-S, Naylor, J. L. (1974). Biliary deoxycholate in anxiety seven healed by one month, 11 by two patients with alcoholic cirrhosis. Gastro- The men, unlike the women, were more

months and all by three months. enterology, 67, 674-679. introverted and neurotic than a control http://gut.bmj.com/ After healing, all patients were reasses- group. Twenty-eight patients with the sed at three monthly intervals, and to date Diazepam kinetics and sedation in chronic highest score for neuroticism were being eight have recurred. liver disease treated for depression. Neuroticism rather These results suggest that, in gastric than activity of the disease was found to ulceration, cimetidine has equivalent heal- J. B. MCCONNELL, M. DAVIS, S. CURRY, AND correlate with subjective feelings of illness, ing properties to both carbenoxolone and ROGER WILLLAMS (Liver Unit, King's time off work, worries about health, and Caved-S. A high recurrence rate in all College Hospita! and Medical School, doubts about the future.

treatment groups is noted. London, Department of Clinical Pharma- Despite periods of up to two years' sick on September 28, 2021 by guest. Protected copyright. cology, London Hospital, London) Diaze- leave, only five patients had retired Biliary and faecal bile acid composition in pam is the sedative of choice for endo- through ill health and required social liver diwase scopy and other investigative procedures, assistance. Of the 70 married patients 19 but patients with liver disease may be felt their relationship had grown closer N. KRASNER, S. T. ATHERTON, L. M. NELSON, unduly susceptible to its effects. In the through illness and only nine said it had H. FLEMING, AND R. I. RUSSELL (Gastro- present study we have investigated possible become worse, despite the diminution in enterology Unit, RoyalInfirmary, Glasgow) factors governing clinical response to an frequency of sexual intercourse in most Disturbances of bile acid metabolism and intravenous bolus dose of diazepam (0-25 couples and its cessation in 12. Extro- particularly of deoxycholate metabolism mg/kg) in 12 patients with chronic liver version rather than disease activity have been documented in patients with disease and age/sex matched controls. appeared to be the main determinant for a alcoholic cirrhosisl12. However, little In patients metabolic clearance rate successful marriage. attention has been directed to the role of (MCR) for diazepam was impaired (range The main conclusion was that patients alcohol in the development of bile acid 0-76-4-27 1/h, controls 1-07-6-12). How- adapted remarkably well to this life-long abnormalities in cirrhosis of differing ever, overall there was no difference from disease, despite being aware of the aetiology. Biliary and faecal bile acid paired controls in the degree and duration probability of relapse. This success was composition was determined in eight of sedation, assessed by psychometric dependent on their personality rather than patients with non-cirrhotic alcoholic liver tests including Reitan trail, digit symbol the extent and activity of the disease. disease (ANC), 23 with alcoholic cirrhosis substitution, card sorting, and short-term (AC), seven with cirrhosis with chronic memory tests. Sedation did not correlate Clinical studies on abetalipoproteinaemia active hepatitis (CAH) and in six healthy with diazepam MCR or serum albumin, control volunteers. but performance in psychometric tests, P. MILLS, F. BALLANTYNE, A. FLECK, R. J. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

The British Society of Gastroenterology A989

HOLDEN, W. FOULDS, AND G. WATKIN- six year period, 60 patients in whom a acid-ethanol extracts (IRI, GLI, and IRS) SON (Western and Royal Infirmaries, cholecystectomy was performed were of the tumours. In most instances, the Glasgow) Two new cases of this rare compared with two groups of 60 age- and tumours were also prepared for specific inherited metabolic disorder are pre- sex-matched controls who had undergone immunoperoxidase histochemistry. Of the sented'. They are both female aged 36 and vagotomy and pyloroplasty alone or 35 tumours investigated 20 were lung 46 years, demonstrating all five features of cholecystectomy alone. Post-vagotomy carcinomas and 15 from various sites in thesyndrome-namely, absent low-density diarrhoea (PVD) was present at two to the GI tract. Attempts were made to con- lipoproteins, steatorrhoea, acanthocytosis three months in 48-3 % after the combined trol the study, using tissue taken adjacent of red cells, spinocerebellar ataxia, and operations and in 11 6% after vagotomy to the tumours and from biopsies and tis- retinitis pigmentosa. and pyloroplasty alone (p = 0-00013). sues from other operations in patients The basic biochemical defect of lipo- The incidence in the combined group without cancer. Six of the lung tumours, a protein metabolism remains unresolved. fell to 16% at two years which was com- rectal carcinoma, and an oesophageal Serum is clear, containing very low levels parable with the rate of resolution of carcinoma showed significant levels of of cholesterol and triglyceride. At lipo- PVD after vagotomy and pyloroplasty IRGa, but none of the other hormones protein electrophoresis there is absence of alone. Different time relations between the was raised. Immunohistochemical studies all low-density lipoprotein including P, operations in the combined group had no confirmed the RIA data. pre-P lipoproteins, and chylomicrons. significant effect on the incidence of PVD. Therefore, IRGa production in cancers Only a lipoprotein (HDL) is present in Cholestyramine (4g tds) was more is not uncommon, although in this pre- significant amounts. We have demon- effective in treating PVD in 16 patients liminary survey other GI hormones were strated abnormality in apolipoproteins by after the combined operations than in 15 not involved. In most, but possibly not in polyacrylamide gel electrophoresis of patients after vagotomy and pyloroplasty all cases, the production of IRGa is insuf- tetramethylurea soluble apolipoproteins2. alone (p = 0-044), but diarrhoea returned ficient to produce clinical features but the There is markedly decreased apo-CIII, in on withdrawal of this treatment. Chole- importance of such hormone production HDL and abnormal apolipoproteins in the styramine was more effective in the treat- in the aetiology, progression, and diagnos- little remaining low-density lipoprotein. ment of PVD in these patients than tic spectrum of cancer remains to be Abnormal fat transport would be ex- aluminium hydroxide" or Lomotil. Pro- elucidated. pected from these lipoprotein abnormali- pranalol which has been reported to ties. Triglyceride accumulates in intestinal inhibit the stimulatory effect of bile acid Lethal familial protracted diarrhoea of mucosal cells failing to be incorporated on colonic mucosa2 was of no value in the undetermined cause: a report of 22 cases into chylomicrons and transported into treatment of PVD. lymph vessels3. This results in malabsorp- D. C. A. CANDY, V. LARCHER, D. J. S. tion of long-chain fatty acids and fat- References CAMERON, A. P. NORMAN, AND J. T. vitamins. Both were HARRIES (The Hospital for Sick Children, soluble patients and C. 'Sali, A., Watkinson, G., MacKay, (1977). http://gut.bmj.com/ deficient in Vitamins A and E and essential Management of bile salt diarrhoea with alu- Great Ormond Street, and Institute of fatty acids. minium hydroxide. Gut, 18, A419. Child Health, Guilford Street, London) The clinical illness may be due to mal- 2Coyne, M. J., Bonorris, G. G., Chung, A., We present 22 cases (10 girls; 12 boys) of Conley, D. R., Croke, J., and Schoenfield, L. J. severe protracted diarrhoea in absorption of these essential fats. We (1976). Inhibition of bile acid stimulation of whom, demonstrated an improvement in retinal rabbit colonic adenylate cyclase in vitro. despite intensive investigation, a definitive responses within 24 hours of a Vitamin A Gastroenterology, 71, 68-71. diagnosis could not be established. injection, but prolonged vitamin deficiency Eighteen patients (82 %), including all four had led to irreversible damage. We hope Gastrointestinal (GI) hormones in non- children of a consanguineous marriage, to prevent further deterioration by using endocrine cancers died. No such series has been previously on September 28, 2021 by guest. Protected copyright. vitamin and fatty acid supplements. reported. JOY ARDILL, MAIREAD O'HARE, J. The patients had a number offeatures in References MCFARLAND, OLIVE HARVEY, J. SLOAN, P. common: (1) Familial pattern: there was a 'Kornzweig, A. L. (1976). Metabolic Ophthalmology TITTINGERTON, R. F. MURPHY, AND K. D. high familial incidence of affected cases; 1, 51-53. BUCHANAN (Departments of Medicine, there were normal siblings in three 2Kane, J. P., et al. (1975). Journal of Clinical Pathology and Biochemistry, Queen's families, and normal offspring from three Investigation, 56, 1622-34. 'Ways, P. O., e! al. (1967). Journal of Clinical University of Belfast) Ectopic hormone parents' previous marriages; there were Investigation, 46, 35-46. production in tumours of non-endocrine two sibships from first cousin marriages. origin producing clinical syndromes is Associated extraintestinal congenital mal- Factors affecting the incidence and treat- well recognised but less known is the formations were not uncommon. (2) ment of post-vagotomy diarrhoea incidence of ectopic hormone production Course of illness: onset within first few in subclinical amounts. This is a pre- weeks of life with relentless deterioration T. V. TAYLOR, M. E. LAMBERT, AND B. liminary report of a survey of unselected and death after several months. (3) Stool TORRANCE (Manchester Royal Infirmary) malignant cancers of their content of GI volume: 'cholera-like' (up to 2 litres per 24 Although duodenal ulceration and gall hormones. hours). (4) Pathology: small intestinal stones are common conditions, there is no Immunoreactive insulin (IRI), glucagon- biopsy showed partial or subtotal villous reference to the clinical results of vago- like immunoreactivity (GLI), immuno- atrophy; rectal biopsy showed non-specific tomy, pyloroplasty, and cholecystectomy reactive gastrin (IRGa), and secretin (IRS) inflammatory changes. (5) Response to performed in the same patient. From a were measured by radioimmunoassay dietary manipulation and various phar- total of 589 vagotomies performed over a (RIA) in aqueous extracts (IRGa) and macological agents: nil or temporary. Gut: first published as 10.1136/gut.18.11.A940 on 1 November 1977. Downloaded from

A990 The British Society of Gastroenterology Details of individual patients, the mode children. Archives of Disease in Childhood 35. Similarity of bowel distension characteris- of inheritance, and pathophysiology will 484-486. tics in the irritable colon syndrome and be discussed. diverticulosis Long-term prospective follow-up ofchildren Is there a myoelectrical abnormality in the with a hiatal hernia (partial thoracic irritable colon syndrome? stomach) J. RITCHIE (From the Nuffield Department of Clinical Medicine, Radcliffe Infirmary, I. J. CARRE, R. ASTLEY, AND RHODA I. TAYLOR, C. DARBY, P. HAMMOND, AND Oxford) The uncertain relationship of LANGMEAD-SMITH (Department of Child P. BASU (introduced by Professor R. diverticulosis to the irritable colon syn- Health, The Queen's University ofBelfast, SHIELDS) (Departments of Surgery and drome (ICS) requires further investigation. and The Children's Hospital, Birmingham) Bioengineering, Liverpool) It has been Colonic motility studies have been under- It is known that the great majority of suggested that in the distal colon of taken as previously described' on 182 infants with vomiting due to a small hiatal patients with the irritable colon syndrome patients (mean age 43 years) with symp- hernia (partial thoracic stomach) lose (ICS) an abnormality of the 3 c/m slow toms resembling ICS. In 46 (25%) of their symptoms spontaneously', a process wave electrical rhythm exists' 2. However, these, diverticula were protruded during accelerated by postural treatment, par- it is not clear if this is related to altered the study. Other organic disease was ticularly when applied in early infancy2. bowel habit itself or whether it is a excluded. These patients were compared However, despite an absence of symptoms characteristic feature of the syndrome. We with 22 asymptomatic subjects (mean age the hiatal hernia can still be identified have therefore studied 10 patients referred 51) of whom seven (32%Y.) were found to radiologically in many of these children3. with ICS and 10 patients suffering from have diverticulosis. The predicted propor- The subsequent progress ofthese asympto- disorders with similar symptoms-for tion for this age was 30%. matic children into adult life is as yet example, chronic pancreatitis, diverticular ICS patients and those with diverticulo- unknown. The present study was under- disease, ulcerative colitis, etc. sis were each divided into three groups on taken to obtain further information on this Transit times, stool weights, percentage their response to balloon distension. particular aspect of the disorder. motility, and slow wave electrical activity Patients in group 1 could not tolerate Eighty-six children with a hiatal hernia were measured in each patient. The two inflation beyond 60 ml. Group 2 felt pain (uncomplicated by an oesophageal stric- groups were well matched for age and sex at 60 ml but could be further inflated, and ture) who were originally studied by two of and patients with similar symptoms in the group 3 had no pain under 100 ml. For the authors (I.J.C. and R.A.) at the two groups had similar values for transit both clinical divisions ofeach group mean Children's Hospital, Birmingham, between time and percentage motility. values were obtained of the minimum 1950-55 have been reviewed by the same In the ICS group 48 % of the balloon volume causing pain and of the 3 c/m slow wave were accompanied by two observers. These patients had either corresponding gut wall diameter and ten- http://gut.bmj.com/ received no specific treatment or had been 3/m motor waves. This did not occur sion. Values for the three parameters dif- managed conservatively by postural in the control group. fered significantly between groups but not, therapy; none had been treated surgically. Thus, in the irritable colon syndrome a within each group, between ICS and All were over 20 years old at review. high incidence of 3 c/m slow wave activity diverticulosis. The values for asympto- Although over 90% were symptom-free on is recognised in the distal colon. This matic subjects were not significantly dif- reassessment, approximately half still had appears to be specific to this condition, ferent from those of the equivalent group a hiatal hernia demonstrable on fluoro- but may well be due to its higher amplitude 3. making recognition easier. scopic examination. None had developed a These observations reinforce the hypo- on September 28, 2021 by guest. Protected copyright. stricture. thesis that diverticulosis is a common References asymptomatic condition and that patients References with symptoms of pain and dysfunction 'Snape, W. J., Carlson, G. M., et al. (1977). have ICS in addition. 'Carr6, I. J. (1959). The natural history ofthe partial Evidence that abnormal myoclectrical activity thoracic stomach (hiatus hernia) in children. produces colonic motor dysfunction in the Archives of Disease in Childhood, 34, 344-354. irritable colon syndrome. Gastroenterology, 72, Reference 'CarrC, I. J. (1960). Postural treatment of children 383-387. with a partial thoracic stomach (hiatus hernia). 'Taylor, I., Duthie, H. L., and Smallwood, R. Archives of Disease in Childhood, 35, 569-580. (1974). The effect of stimulation on the myo- 'Ritchie, J. (1973). Pain from distension of the 3Carr6, I. J., and Astley, R. (1960). The fate of the electrical activity of the rectosigmoid in man. pelvic colon by inflating a balloon in the irritable partial thoracic stomach (hiatus hernia) in Gut, 15, 599-601. colon syndrome. Gut, 14, 125-132.