Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from
Gut, 1984, 25, A1129-A1193
The British Society of Gastroenterology
The 1984 Annual Meeting of the Society was held at the University of Liverpool under the presidency of Dr R B McConnell. One hundred and thirty four oral and 94 poster communications were presented in the scientific sessions; the abstracts of these are printed below.
reflecting differences in susceptibility of the diagnosis and monitoring the progression of LIVER protein moieties of the ligands to pro- disease or response to treatment. W1-14 teolysis. This model produced a good statis- tical and graphical fit to both sets of data without the need for exocytosis. The data W3 WI show that ligands entering the cell by a com- Intrahepatic shunting and its relationship to Metabolism of mannose-terminated glyco- mon receptor may subsequently be proces- portal pressure and blood flow proteins by hepatic sinusoidal cells sed differently. M MCLAREN, J FLEMING, S KARRAN, AND I J A SUMMERFIELD, M E TAYLOR, AND M S LEAN- TAYLOR (University Surgical Unit, South- ING (Departments of Medicine and Physics, W2 ampton) It has been suggested that in cir- Royal Free Hospital, London) Mannose Dynamic scintigraphy in cirrhosis rhosis intrahepatic shunting between all (Man-) terminated glycoproteins are these major blood vessels occurs. The rapidly cleared from the blood by receptors M MCLAREN. J FLEMING. S KARRAN, AND I relationship of the degree of shunting to the on hepatic sinusoidal cells. In earlier studies TAYLOR (University Surgical Unit, South- level of portal pressure is not known but if a using acid precipitation to estimate the ampton) Dynamic hepatic scintigraphy manipulation of shunting results in a fall in catabolism of the glycoproteins, measure- yields information related to portal pressure this could have therapeutic http://gut.bmj.com/ ment artifacts led to models requiring haemodynamic and reticuloendothelial implications. A study was undertaken to exocytosis of whole ligand. In these studies function in liver disease by measuring the assess the relationship of portal venous the fate of glycoprotein was assessed in rats mesenteric fraction of liver blood flow (M shunting to blood flow and portal pressure. by measuring radioactivity in blood, liver, F) and the liver:spleen activity ratio (L:S Cirrhosis, assessed by histological and bile and other tissues over 40 minutes after ratio). It has been used to study 45 patients biochemical criteria, was induced in 45 male an intravenous injection of 57 pmol with liver cirrhosis, 24 of whom had bled Wistar rats by intragastric administration of radioiodinated glycoprotein. Ligand from varices. Control data were provided either carbon tetrachloride (n=25) or catabolism was measured by gel filtration. by 30 subjects with normal liver function. dimethlynitrosamine (n=20). Effective on September 30, 2021 by guest. Protected copyright. With these data a new compartmental For the overall group of cirrhotic patients liver blood flow (ELBF) and its relative model was formulated. The metabolism of the median MF was 0-28 compared with a arterial/venous components were measured 125I-agalactoorosoinucoid (1251I-AGOR) control value of 0-56 (p<0-001) and the L:S using Tc99m sulphur colloid, portal pres- and ' I-mannose 36-bovine serum albumin ratio was 1-5 compared with 4-75 sure was recorded manometrically and the (125I-Man36BSA) was studied. Both ligands (p<0-001). The sensitivity in the diagnosis degree of shunting obtained by intraportal accumulated principally in liver but more of cirrhosis was 84% for the MF and 89% injection of Co57 microspheres. '25I-AGOR (-30%) than 125I-Man36BSA for the L:S ratio. This increases to >95% by Both portal hypertension (median con- (-10%) accumulated in other sites. Uptake calculating the geometric mean of MFxL:S trol 9cm saline, cirrhosis 16-5cm saline parameters indicated that Man36BSA (0-78 ratio. Within the group of patients with cir- p<0-001) and shunting (median control min) had a higher affinity for the cell recep- rhosis the median MF for patients who had 0 3%, cirrhosis 23-0% p<0-001) increased tor thanr AGOR (0-50 min). Iritracellular gastrointestinal bleeding was 0-22 com- significantly in cirrhosis. There was no sig- transport of ligand from the cell membrane pared with 0-33 for non-bleeders nificant correlation between shunting and to the lysosome was estimated by a trans- (p=0-035), and the L:S ratio was 0-95 com- either a decrease in ELBF (r=0.3) or a port parameter (Tau) in the model. This pared with 1-9 (p=0-003). decrease in its venous component (r=0-36). was much greater for Man36BSA (-3 min) These data indicate a significant reduc- There was, however, a significant corre- than for AGOR (-0 min). These data may tion in the venous flow to the liver and a sig- lation between the increase in shunting and indicate that the rate of receptor-ligand nificant increase in functional splenomegaly an increase in portal pressure, r=0-67 uncoupling of Man36BSA is slower than for not only in patients with cirrhosis when p<0.001. The results do not indicate any AGOR. Furthermore, the rate of compared with controls but also between direct relationship between the develop- catabolism of Man36BSA (0-27 min) was those who have or have not bled from var- ment of shunting and changes in measured twice that of AGOR (0-12 min) probably ices. The value of such information lies in flow but intrahepatic portal venous shunt- A1129 Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from
A1130 The British Society of Gastroenterology ing does increase with rising portal pres- in normal subjects, haemophiliac and von liver blood flow. The present study sure. Willebrand patients, mainly by raising the examines the simultaneous pharmacokine- concentration of all components of factor tics of two separate anions ICG and "4C- VIII complex. DDVAP, however, also glycocholate. Extraction ratios were esti- W4 shortens bleeding time in uraemics, and is mated by analysis of the biexponential Defective sulfoxidation combined with rapid used for prophylaxis and treatment of plasma disappearance curves and liver carbon oxidation in the liver may predispose bleeding, despite already raised factor VIII blood flow calculated. to chlorpromazine jaundice. concentrations. The latter is also seen in cir- Ten healthy volunteers fasted and rhotics, but the effects of DDVAP in such received a single oral dose of cimetidine 400 E ELIAS, R H WARING, AND S C MITCHELL patients is not well reported. We have mg, ranitidine 150 mg or placebo in random (Department of Medicine, QE Hospital studied the effect of a 15 minute intravenous order on three occasions one week apart. Medical School, Birmingham, Department infusion of 0*3,ug/kg DDVAP at one and Two hours later clearances measured for of Biochemistry, University, Birmingham, three hours post infusion as compared with ICG (ml/min/kg) were: cimetidine, 6 9+ and the Department of Pharmacology, St baseline values of prothrombin, partial 2-9; ranitidine, 7-9+3-1; placebo, 7-1±1-6; Mary's Hospital Medical School, London) thromboplastin (PTTK), thrombin and and for '4C-glycocholate: cimetidine, 8-4+ Chlorpromazine is a major tranquillising bleeding times factors VII, IX, X, XI, XII, 2.3; ranitidine, 8 1±2 2; and placebo, 8-6+ agent which is known to be metabolised in VIIIC, VIIIRAG, VIIIR-Cof, fibrinogen, 1-9. Similarly there was no difference in the man to give both hydroxylated and sul- fibrin monomers (FM) and degradation calculated extraction ratios or liver blood foxide metabolites. We proposed on the products (FDP), euglobulin lysis time and flow. basis of in vitro work that rapid conversion fibrin plate assay. Results to date are for six Using the same technique, it has recently of chlorpromazine (CPZ) to hydroxy- patients: five with parenchymal liver dis- been suggested that cimetidine but not metabolites and/or slow metabolism to the ease (prothrombin ratio of 1-3 or more) and ranitidine may reduce liver blood flow after relatively non-toxic sulphoxides might be one patient with non-malignant obstructive chronic administration secondary to inhibi- the underlying cause of CPZ hepatotoxic- jaundice. All were vit K replete. Abnormal tion of enzyme activity and reduction of ity. This hypothesis was investigated using and normal bleeding times were shortened intrinsic clearance. The lack of effect of a S-carboxymethyl-cysteine (SCMC) and by about 30% at both one and three hours. single dose of cimetidine on liver blood flow debrisoquine as probes for in vivo sulphur- At the same time PTTK was shortened to would be compatible with this hypothesis as and carbon oxidation-capacity respectively. within the normal range, and increases in this study neither H2 receptor antagonist Both these drugs are known to show a wide above baseline concentrations were seen for caused significant alteration of liver blood range of metabolism in normal populations. factors VIIIC by 26-106 lu/1, VIIIRAG by flow in normal subjects. Urinary metabolites and unchanged com- 50-95iu/1 and VIIIRiCof by 80-12Oiu/1. pound concentrations (0-8 h) were deter- There were also increases in factors XI and mined after oral SCMC (750 mg) and XII. There was no change in other factors, W7 http://gut.bmj.com/ debrisoquine sulphate (10 mg) in consecu- prothrombin time, fibrinogen, FM, or FDP. Hepatobiliary fibrocystic diseases tive days in three subjects who had fully No side effects were encountered. The recovered from prolonged jaundice after reduction in bleeding time is probably J A SUMMERFIELD, J CADAFALCH, AND S SHER- exposure to CPZ (twice in one subject). All because of increases in the components of LOCK (Academic Department ofMedicine, three subjects showed very low capacity for factor VIII complex. Equivalent increases Royal Free Hospital, Pond Street, London) sulfoxide formation (Sulfoxidation Index would only be seen following large volumes Cystic lesions of the liver and bile ducts are (SI) of 32, 35, and 80). These values are at (2-3 1) of fresh frozen plasma. Thus being increasingly recognised with DDVAP may be very useful as adjuvant the extreme end of the range found in a nor- improved diagnostic techniques. We have on September 30, 2021 by guest. Protected copyright. mal population. None of the patients pos- therapy in the prophylaxis and treatment of reviewed 49 patients diagnosed between sessed an impaired debrisoquine oxidation bleeding in cirrhosis. Clinical evaluation 1966-1984. They had congenital hepatic fib- capacity (debrisoquine Metabolic Ratio and further studies on haemostasis are rosis (CHF) 14, CHF and Caroli's disease (MR) 0.3, 3-6, and 0-6). All three CPZ- needed. (CD) 12, CD 8, polycystic liver (PC) 11, toxicity patients therefore had high SI/MR microhamartoma (MH) 10, and choledoc- values, and we suggest that the combination hal cyst (CC) 3. Three patients (27%) with of relatively defective sulfoxidation and W6 PC also had MH. Six patients (24%) with extensive carbon-oxidation capacity may Oral H2 - receptor antagonists do not acutely PC, MH or CC also had CHF or CD. The predispose to CPZ jaundice. alter liver blood flow presentation age of CHF (7±3 years: mean±SEM) was younger than CHF and J CRAMPTON, M STAPLETON, G DAVIES, AND I T CD (15±4 years) or CD (37±9 years). W5 GILMORE (Gastroenterology Unit, Broad- Polycystic liver (37±6 years) and MH (50+ Effects ofde-amino 8 D arginine vasopressin green Hospital, Liverpool) There have 6 years) presented later. Most CHF and CD (DDVAP) on haemostasis in patients with been conflicting reports of the effect of H2 (83%) and CD (75%) were male. Congeni- liver disease receptors on liver blood flow. The issue is of tal hepatic fibrosis presented with variceal some clinical importance because of poten- haemorrhage (4) and/or hepatospleno- A K BURROUGHS, K MATTHEWS, D KELLY, M tial effects on drug metabolism and portal megaly (13). Congenital hepatic fibrosis QADIRI, T TUDDENHAM, AND N McINTYRE pressure. Interpretation of previous studies and CD patients presented with variceal (Department ofMedicine and Haemophilia, has been difficult because only a single haemorrhage (3), hepatosplenomegaly (10) Royal Free Hospital School of Medicine, anion, indocyanine green (ICG), has been or cholangitis (2). Caroli's disease patients London) DDVAP shortens bleeding time used and its clearance often equated with presented with cholangitis (5) and/or Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from
The British Society of Gastroenterology A1131 hepatosplenomegaly (6). Variceal haemor- conversion is an important source of E2 and chronic toxicity profile remains to be rhage began earlier (14±3 years) than DHT in men, and the low levels of all three evaluated. cholangitis (36±5 years). Polycystic liver steroids measured in the current study in and MH presented with incidental liver dis- patients with HCC are consistent with ease or abdominal pain. Portal hyperten- reduced substrate (T) availability. Low W10 sion developed in most patients with CHF levels of T, a feature we have found in other Metabolic bone disease in PBC - high bone (12/14) and CHF and CD (7/10), but in no malignancies, may be due to impaired tes- turnover, not osteomalacia patient with CD. Cholangitis developed in ticular production and/or pituitary/ 8/10 with CHF and CD and 6/7 CD. Five hypothalmic dysfunction. H C MITCHISON, A J MALCOM, M F BASSENDINE, patients with CHF and CD first developed ANDOFWJAMES (DepartmentofMedicine, variceal haemorrhage and 10±3 years later Freeman Hospital, Newcastle upon Tyne began to have cholangitis. Polycystic kid- and Department of Pathology, Royal Vic- neys were most frequent in CHF (9/14) but W9 toria Infirmary, Newcastle upon Tyne) were also found in other groups. In conclu- Mitoxantrone as single agent therapy in The nature and incidence of metabolic bone sion (1) more than one fibrocystic disease primary hepatocellular carcinoma disease in PBC is still controversial. Bone and polycystic kidneys were usually found biopsy with tetracycline label is the best in a patient, (2) CHF and CD divided into method of assessment. A A DUNK, S C SCOlT, P J JOHNSON, I MURRAY- We examined 13 women with PBC who three groups: CHF and CD alone or CHF LYON, RWILLIAMS, AND H C THOMAS (Royal and CD. Most CD were male. Congenital Free Hospital, Cyanamid International had received no treatment likely to influ- hepatic fibrosis had variceal haemorrhage, Research Centre, Kings College Hospital, ence bone status. Five had cirrhosis, eight CD had cholangitis, CHF and CD had first Charing Cross Hospital, London) Forty had Stage III features on histology, three haemorrhage and later cholangitis. were premenopausal, 10 postmenopausal, patients with primary hepatocellular car- 12 were symptomatic of liver disease, none cinoma (PHC) were treated with Mitoxan- of bone disease, four had bilirubin >50 m/l trone, an anthracenedione structurally simi- for >6 months. Photon absorbtiometry of W8 lar to Adriamycin. Thirty five of these femur and forearm and right iliac crest bone Low serum androgens in primary hepatocel- patients had received no previous form of biopsy after double tetracycline label were lular carcinoma therapy. The drug was given intravenously carried out in each patient, together with a at a dose of 12 mg/M2 once every 21 days. C-14 triolene breath test to look for fat M JAWED IQBAL, T P CORBISHLEY, M L WILKIN- Dosage could be modified by 2 mg/mi2 incre- malabsorbtion. SON, J KEATING, AND ROGER WILLIAMS ments depending on toxicity and tolerance. The photon absorbtiometry showed a (Liver Unit, King's College Hospital and All patients were considered evaluable for wide scatter of values but not outside those School ofMedicine and Dentistry, Denmark toxicity/tolerance analysis and at the time of of an age-matched control population, Hill, London) The importance of andro- reporting, 22 patients were considered http://gut.bmj.com/ gens in hepatocellular carcinoma tHCC) evaluable for response analysis. Based on a results did not correlate with other vari- has been shown in previous studies from this modification of the UICC criteria, one ables. The bone biopsies showed no evi- unit in which achieved a remission of 13 dence of osteoporosis beyond that expected androgen receptors were patient complete for age and sex. The percentage of trabecu- detected in HCC tissue but not in normal or weeks duration. To date, five patients have lar bone with osteoid was within normal cirrhotic liver tissue and in a further study achieved partial remission, the longest limits but the osteoid seams were wide (os- showing an alteration in the characterisa- being of 21 weeks duration. The overall teoid volume 2-48%±+05, normal 1-9%+ tion of binding of circulating sex-steroid response rate is 27%. A further four 0-4). This hyperosteoidosis, however, was coincident with the development of HCC in patients remained in the UICC 'No change' associated with high normal appositional on September 30, 2021 by guest. Protected copyright. patients with primary biliary cirrhosis category, the longest for 42 weeks. rate of 1 mm/day average which is not com- (PBC). In the current study total serum The drug was well tolerated. Nausea patible with osteomalacia. Four patients testosterone (T), 5 -dihydrotestosterone occurred in 23% of cycles and vomiting had abnormal triolene breath tests but this (DHT) and oestradiol-17 (E2) lends occurred in only one patient. Alopecia did not correlate with clinical or histological (radioimmunoassay) and sex hormone occurred in one patient and other adverse status or bone results. binding globulin (SHBG) levels (two-tier effects were rare. Leucopenia was dose- In conclusion, we found neither column assay) were determined in 20 male limiting and a white cell count of < 1000/ osteoporosis or osteomalacia on biopsy. We patients with both cirrhosis and HCC and mm3 occurred on three occasions. Throm- suggest that previous reports of the results compared with those in age- bocytopenia occurred but was not a clinical osteomalacia in PBC have been because of matched groups with alcoholic cirrhosis problem. A platelet count of < 40 000/mm3 interpretation of wide osteoid seams in the (AC) and PCB and with normal controls. occurred twice. Haematological toxicity absence of information about the apposi- Serum T (2.6 + SD., 2-70 nmol/l), DHT was easily managed by dosage adjustment. tional rate (only obtainable after double (0.51±0-305 nmol/l) and E2 (83-1±99-80 Cardiac events'occurred in three patients oxytatracycline label). Our findings are pmol/A) levels were lower in the HCC (two cases of atrial arrythmias, one case of compatible with a high rate of bone tur- patients than in either cirrhotic group and asymptomatic diminution in cardiac func- nover; they raise no contraindications to a the levels of the two androgens were also tion revealed by radionuclide ventriculog- therapeutic trial of prednisolone in these lower than those in normals. Sex hormone raphy). Two of these patients had received patients. binding globulin (96±42.1 nmol DHT > 13 cycles of therapy. bound/l) levels were higher than in normal Mitoxantrone shows activity in PHC, controls but not significantly different from similar to that seen with Adriamycin, but Wil those in the two cirrhotic groups. Peripheral with significantly less acute toxicity. Its Familial IgM rise in PBC Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from
A1132 The British Society of Gastroenterology
D R TRIGER AND R J MUGGLETON (Depart- shunt was carried out because of continuing ml/min/100g) significantly (p<005; Stu- ment of Medicine, Royal Hallamshire Hos- haemorrhage despite resuscitation and dent's paired t test) without influencing pital, Sheffield) In a study to examine pos- sclerotherapy, in some cases. In group II heart rate or BP. An intraportal injection of sible genetic and environmental factors in (n=14), an elective shunt procedure was B2-blocker resulted in an immediate but primary biliary cirrhosis, we have studied carried out (12 distal splenorenal and two transient fall in PP (12-4±0-48 to 10-3±0*41 the clinical, biochemical, and serological mesocaval). In group III a modified Sugiura mmHg; p< 0-05). features in 200 relatives of 44 patients with operation was carried out electively in 22 These results suggest that (a) a selective this condition (spouses and their first degree and as an emergency in two. The age, sex, 62-blocker (ICI 118,551) can modify hepatic relatives 63, siblings 72, children 65). Posi- Child's grading and the pathological causes haemodynamics without a significant effect tive antimitochondrial antibody (titre equal of portal hypertension were comparable on the systemic circulation, and (b) an or greater than 1:20) was found in only three among the groups. All patients but one intraportal 82-blocker may be ofvalue in the cases (all female siblings) and clinical evi- were non-alcoholic. Patients were control of bleeding oesphageal varices. dence of PBC was present in only one. A evaluated at 4-55 months after treatment. significant rise in mean IgM levels was seen In the patients of group I, the operative in the female siblings (2-4 g/l vs 1*67 g/l mortality was 20%, recurrent haemorrhage W14 p>O-OS) as well as in the daughters (2.40 g/l 40%, shunt occlusion 20%, encephalopathy Effect of bile duct ligation on hepatic vs 1-88 g/l p>005) of PBC compared with 20%, late death 20% and patient survival glutathione S-transferase activity and bile age and sex matched controls. These differ- 60%. In group II, the operative mortality acid binding capacity ences were largely accounted for by cluster- was 14-3%, recurrent bleeding 14-3%, ing of high IgM levels in eight of these encephalopathy 7%, late death 7% and P R BAKER AND Y SIOW (University Depart- families. No difference was found in IgM patient survival 85 7%. In group III, opera- ment of Surgery, Ninewells Hospital and levels in male relatives compared with con- tive mortality was 5%, recurrent bleeding Medical School, Dundee) Glutathione S- trols. There was no difference in serum IgG, 5%, no encephalopathy, no late deaths and transferases (GST), a group of detoxifica- IgA or routine biochemical values between patient survival 95%. It is concluded that a tion enzymes, are also believed to play a any of the groups of relatives and controls. modified Sugiura non-shunt operation is an role in the intracellular binding and hepatic In conclusion elevated IgM in PBC appears effective procedure in arresting variceal transport of bile acids. As bile acids inhibit to occur independent of the clinical disor- haemorrhage, it has low operative mortal- these enzymes, however, other cytosolic der. The pattern of family clustering does ity, increased patient survival and no proteins may be involved, particularly in not correspond to any recognised mode of encephalopathy. large duct obstruction where bile acids inheritance but the data are consistent with accumulate in the liver. To investigate this, an environmental factor playing at least GST activity on 1-chloro-2,4 -dinitroben- some contributory role. This factor may be W13 zene and protein binding of 14C - bile acids relevant to the pathogenesis of PBC. Effect of a selective B2-blocker on hepatic (ultra filtration method) were studied in http://gut.bmj.com/ haemodynamics in the cirrhotic rat hepatic cytosol (100 000 g supernatant) pre- pared from rats one week after a sham(SH) W12 S A JENKINS, J JOHNSON, J N BAXTER, P DEVI'IT, procedure, and one (BDL1) and four Modified Sugiura procedure versus porto- AND R SHIELDS (Department of Surgery, (BDL4) weeks after ligation and division of systemic shunt operations for portal hyper University of Liverpool, Liverpool) the common bile duct (n=6 per group). tension and variceal bleeding - prospective Although propranolol may be effective in Glutathione S-transferases activity (mmol/ study reducing the rate of rebleeding from min/kg body weight) in cytosol diafiltered to
oesophageal varices, B1-blockade some- remove inhibitors such as bile acids was on September 30, 2021 by guest. Protected copyright. G M ABOUNA. A T MENKARIOUS, H BAISSONI. times makes resuscitation difficult should progressively and significantly (Student's t AND 0 F Y OMAR (Department of Organ the patient experience recurrent variceal test) decreased in BDL1 (2-5±0.3 (SD), Transplantation Surgery, Faculty ofMedical haemorrhage. This study was therefore car- p<0005) and BDL4 (1.7±0.5 p<0.001) and Mubarak Al-Kabeer Hospital, Kuwait ried out to investigate the effects ofsystemic rats compared with SH rats (3.5±0-4). Bile University, Kuwait) The surgical treat- and intraportal administration of a selective acid binding capacities of hepatic cytosolic ment of bleeding oesophageal varices 62-blocker (ICI 118,551) on hepatic proteins (,umol/kg body weight) remained remains controversial. A prospective study haemodynamics in the cirrhotic rat. at control levels in BDL1 rats. In BDL4 involving 48 patients with variceal bleeding Rats made cirrhotic with dimethynitro- rats, however, although there was little was carried out in order to compare the samine received systemic infusions of 0, 2, change in glycocholic acid and cholic acid results of a modified Sugiura operation with 4, or 8 mg 62-blocker/kg body wt/min. Por- binding, significant increases in the binding those of shunting procedure. In this modifi- tal pressure (PP), portal venous flow capacities compared with BDL1 animals cation a transabdominal, one-stage opera- (PVF), arterial blood pressure (BP) and was observed for chenodeoxycholic acid tion, a highly selective vagotomy without liver blood flow (LBF) were measured (19-8±6-5 (SD), and 28-6±6-7, p<0.05) pyloroplasty is performed and a stapling before and after the infusion of the B2- and lithocholic acid (65-8±16-5 and 119-5+ machine used for oesophageal transaction. blocker. Similar measurements were made 22-5, p<0-001). After fractionation of After the source of bleeding is determined before and after intraportal bolus injection pooled cytosol on an affinity chromatog- by endoscopy, patient resuscitation is con- of the B2-blocker. raphy gel, proteins eluted with 10 mM tinued with blood transfusions, Pitressin The systemic infusion of 10 ug/kg body taurochenodeoxycholic acid or 3M sodium and oesophageal tamponade. The study wt/min 62-blocker reduced PP (15-4±1-0 to thiocyanate exhibited the highest bile acid comprised three groups of patients: In 13-0±0-9 mmHg), PVF (17.2±2-2 to 10-6± binding but negligible GST levels. This group I (n=10) an emergency mesocaval 1 ml/min) and LBF (25.2±2-0 to 19-3±1-6 study has shown that large duct obstruction Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from
The British Society ofGastroenterology A1133 causes depletion of important detoxifica- T2 conventional and dynamic liver function tion enzymes. The enhanced cytosolic pro- Albendazole treatment of hydatid disease in tests (LFT's) the pathophysiological defects tein binding capacities for the more toxic an animal model in 47 PBC patients and in a subgroup dying bile acids, however, may represent a com- within 18 months. pensatory protective mechanism which is D L MORRIS, M F STALLBAUMER, M J Serum bilirubin, albumin, prothrombin induced by prolonged cholestasis. CLARKSON, J PRITCHARD, AND J CHINNERY index (PI), galactose elimination capacity (Department of Surgery, University Hospi- (GEC) (hepatic functional cell mass) and tal, Nottingham, Department of Veterinary BSP-k2 (hepatic excretory capacity) were Preventative Medicine, University of Liver- measured. Analysis was by Fisher's exact pool, Liverpool) Despite encouraging test. Group A consisted of 29 patients sur- clinical and radiographic results of alben- viving longer than 18 months and group B of LIVER dazole treatment of human hydatid disease 18 patients surviving less than 18 months. T1-12 neither constitute absolute proof of an The results show that serum bilirubin was therapeutic action. abnormal in 31% of group A and in 83.3% Tl Seventeen sheep with active naturally of group B (p=0.00055). Serum albumin Monocyte suppression in cirrhosis occurring pulmonary hydatid disease were was abnormal in 10.3% of group A and in identified radiographically. Six were 61.1% of group B (p=0.00036). Prothrom- UNA McKEEVER, N P KENNEDY, D G WEIR, AND treated with albendazole (three at 10 mg/kg bin index was abnormal in 11.5% of group C FEIGHERY (Department of Immunology and three at 20 mg/kg) for six weeks before A and in 35-7% of group B (p=0.082). and Clinical Medicine, Trinity College and necropsy examination. Viability of protos- Galactose elimination capacity was abnor- St. James' Hospital, Dublin, Eire) We colices was assessed by needle puncture, mal in 65-2% of group A and in 93-8% of recently described the presence of vital staining and warm microscopy. The group B (p=0041). BSP-k2 was abnormal monocytosis in patients with severe remaining sheep underwent thoracotomy in 58.3% of group A and in 100% of group alcoholic liver disease (ALD). In the pre- and needle puncture so that viability could B (p=0-00231). sent study, the functional significance ofthis be confirmed before therapy. There was We conclude that in the group as a whole, one postoperative death, one hydatid the conventional LFT's were abnormal in monocyte excess was investigated. proved to be non-viable, of the remainder 57.4%, while dynamic LFT's were abnor- Nineteen patients were studied: twelve seven were treated at 10 mg/kg and two at 20 mal in 92.3%. BSP-k2 was the earliest and with severe ALD; five with chronic active in PBC. hepatitis (CAH); two with primary biliary mg/kg for six weeks. Several sheep most consistent defect Dynamic developed leucopaenia which led to sep- LFT's are therefore the preferred method cirrhosis (PBC). Twelve patients had an established cirrhosis: ALD (seven), CAH ticaemia and death in two animals. At post- of monitoring response to drug treatment in (three) and PBC (two). Nineteen healthy mortem examination all cysts were flaccid, early disease. In most patients serum albu-
and contained little fluid which was straw min and bilirubin became abnormal only in http://gut.bmj.com/ served as age-matched subjects controls. coloured instead of clear. The laminated the late stages and 17% of our patients had Monocytes in the peripheral blood mono- and germinal membranes had often fallen a normal bilirubin within 18 months of nuclear cell (PBMC) population were enum- erated away from the ectocyst. Viability testing death. All tests combined gave a predictive using the monoclonal antibody MO-2. showed that all protoscolices were dead. In index for death within 18 months of 78%. Monocyte mediated suppression of PHA addition electron microscopy showed the Prediction of death was improved signifi- induced PBMC proliferation was assessed germinal membrane to be completely dis- cantly by determination of GEC and BSP-k2 by incorporating indomethiacin (a prosta- organised and degenerate. In order to con- and these tests should be performed in all glandin synthetase inhibitor) into the cul- whom be firm that thoracotomy alone has no detri- patients in liver transplant might on September 30, 2021 by guest. Protected copyright. ture system. mental effect on one sheep under- considered. The Wilcoxson's rank sum test and the v4ibility went thoractomy, conformation of viability Student's t test were used in statistical and at necropsy six weeks later the parasite analysis. The results (mean ± SD) showed was still alive. We conclude that six weeks that patients with ALD had a significantly T4 higher percent monocyte count (28.3±8.9, treatment with albendazole 10 mg/kg kills Use of a prognostic index in assessment of within viable in p<0.01) than controls (18.1±6.7) con- protoscolices hydatid cysts outcome of liver transplantation in patients sheep, but significant leucopaenia has been firming our earlier findings. Although with primary biliary cirrhosis seen. monocyte mediated per cent suppression in the ALD group was greater (20-1±28-0) J NEUBERGER, E CHRISTENSEN, D G ALTMAN, than the controls (3.9±16.7), this difference N TYGSTRUP, AND ROGER WILLIAMS (The was not statistically significant. When T3 Liver Unit, King's College Hospital and patients with cirrhosis were studied as a New biochemical criteria for hepatic trans- School of Medicine & Dentistry SE5 and group a significant monocytosis (28-7± plantation versus drug therapy in primary Department of Hepatology, Hvidovre Hos- 8-1%, p A1134 The British Society of Gastroenterology a transplant is offered when disability is 132±148 (35-448) days. 9/16 in Group A T7 severe and when the anticipated survival and B are well after 15.8±6.4 (6-25) Controlled trial of acyclovir in chronic time is less than one year. The present study months. Analysis of entry parameters in- HBsAg, HBeAg positive carriers was based on a prognostic index to compare dicate a marginal Group P disadvantage, the observed survival after grafting with preventing trial discontinuation. In biopsies G J M ALEXANDER, J E HEGARTY, E FAGAN, P estimated survival. The index was derived of survivors after six months, orcein staining GUARASCIO, A L W F EDDLESTON, AND ROGER from analysis of216 patients participating in was scanty or absent; three showed inactive WILLIAMS (The Liver Unit, King's College an international therapeutic trial in PBC, micronodular cirrhosis, and two were nor- Hospital and School of Medicine and using the Cox regression model for cen- mal. Dentistry Denmark Hill, London) Clini- sored survival. Factors of prognostic signifi- cal and histological improvement usually cance included age, serum bilirubin and follow spontaneous loss of ciral replication albumin, histological finding of cirrhosis in chronic HBsAg carriers - the basis of and central cholestasis. The index was T6 antiviral therapy. To date, no anti-viral transformed to give a median survival time. D-penicillamine in primary biliary cirrhosis agent has unequivocally been shown to Retrospective analysis using the model (PBC) - an untested (and untestable?) treat- increase the natural rate of seroconversion. showed the estimated median survival time ment To assess its antiviral properties, a ran- of the grafted patients was four months and domised controlled trial of acyclovir, 45 mg/ in only four was greater than one year O EPSTEIN, D G COOK, S JAIN, AND SHEILA kg by continuous infusion for 28 days, ver- although less than 21 months in all. After SHERLOCK (Academic Department ofMed- sus no treatment, has been performed in 30 grafting, five lived with survival periods of icine, Royal Free Hospital School of patients positive for HBsAg and HBeAg for 18 to 84 months and three are alive and well Medicine, London) Since 1973, 98 PBC a minimum of six months. Patients were over three years later. By life table analysis, patients have been enrolled into a ran- stratified for sex, histology (minimal liver the observed survival was significantly domised controlled trial of penicillamine. damage, chronic persistent hepatitis or greater than the estimated time (p<0.01). On entry to the study, the prognostic pro- chronic active hepatitis) and homosexual Perioperative mortality, however, was files of the penicillamine and placebo activity. high, with 13 patients dying within six weeks treated groups were similar. Because of At the end of the treatment period, serum because of surgical, infective, and graft expected drug side effects, the randomisa- DNAp activity, initially positive in 13 of the problems. This model may be of value in tion was weighted to allow a 3:2 ratio of 15 patients, had fallen in nine, inhibition selecting the optimal timing of transplanta- penicillamine to placebo treated patients. exceeding 50% in two patients. Side effects tion and further prospective evaluation is Over a mean follow-up of 66 months death were minimal (transient haematuria one, required to identify those factors determin- occurred in 16 of 37 placebo treated patients dry skin 14). No adverse effect on renal ing a satisfactory outcome of liver trans- (43%) and 18 of 61 penicillamine treated function was observed. plantation. patients (30%). This difference in After 12 months' follow up, four of 14 of http://gut.bmj.com/ survival, although favouring the peni- the treated group and two of 13 of the cillamine group does not achieve statis- untreated group had seroconverted to anti- tical significance when analysed by the log HBe; one of those treated had also T5 rank test (p=0.08). This result differs from developed anti-HBs. One further patient in Interim results show major improvement in a previous published analysis of 87 patients each group had become DNAp negative, survival in pre-icteric Indian childhood followed for a mean of 45 months, which but remained HBeAg positive. Seroconver- cirrhosis (ICC) treated with D-penicillamine indicated significantly improved survival in sion was unrelated to histology, duration of (DMC). penicillamine treated patients (p<0.01). To disease or homosexuality. on September 30, 2021 by guest. Protected copyright. determine whether the changing signifi- The results of this study indicated that M S TANNER, D G SIDHAYE, S A BHAVE AND A M cance level reflects inadequate sample size, acyclovir partially inhibits viral replication PRADHAN (Department Child Health, Uni- we calculated the size of penicillamine trial in HBsAg positive patients but that this versity of Leicester, Leicester, UK, and necessary to detect a real reduction i-n five effect is not accompanied by a significantly Department Pediatrics, KEM Hospital, year mortality from 40% to 30%, with 80% increased rate of seroconversion. Poona, India) Untreated, 43 of 58 chil- certainty, at the 5% significance level. To dren with ICC died within eight weeks achieve this goal, 710 patients would be (1980). d-Penicillamine in advanced cases required to participate in the study. Neither insignificantly improved survival (1980-81). this study, nor any other published penicil- T8 d-Penicillamine 20 mg/kg/day (Group A), lamine trial has been designed to accommo- Effect of propranolol treatment on salt and DMC + prednisolone 2 mg/kg/day for four date the possibility of type II error. Future water homeostasis weeks then 5 mg/kg/day (Group B), or design of clinical trials in PBC must placebo tablets (Group P), was given to 24 appreciate the scale of trial required to test P C HAYES, M K FENWICK. AND I A D earlier cases of ICC without ascites or jaun- the treatment effect. BOUCHIER (University Department of dice. Thirteen were allocated to treatment Despite 10 years of clinical evaluation, Medicine, Ninewells Hospital and Medical groups in rotation (1982). Eleven entered a the effect of penicillamine on survival School, Dundee, Scotland) The effect of double blind study with code breaking after remains uncertain. The trend in our trial chronic administration of long acting pro- three months (1982). remains encouraging, but unless long-term pranolol on body weight, skinfold thick- Results to February 1984: show 8/8 in collaborative multicentre trials are ness, and urinary sodium excretion was Group P died after 41±31 (12-109) days. 4/8 mounted, this, and any other treatment, measured at 0, six and 12 months in 15 in Group A and 3/8 in Group B died after will remain untested. patients with chronic liver disease in double Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society ofGastroenterology A1135 blind, placebo controlled fashion. Total (range 14) were required to again achieve The results of this study indicates that body exchangeable sodium and total body obliteration. In 20 patients a second recur- propranolol is ineffective in reducing the water (TBW) was also measured using rence of varices occurred with bleeding in frequency of recurrent variceal haemor- [24NA] sodium and tritiated water. eight cases but no associated deaths. There rhage in the pre-obliteration phase of injec- Patients taking propranolol showed a was no correlation between the aetiology of tion sclerotherapy. weight gain of 6*65±4.74 kg at 12 months cirrhosis or the severity of the underlying which was significantly greater than in con- liver disease and the development of 'new' trols 1-04±3*2 kg (p<0-05), largely because varices. The high rate of recurrence of var- T1l of an increase in body fat, as determined by ices applied equally to those with a portal Non-invasive endoscopic measurement of skinfold thickness which increased by 17-6± vein thrombosis. oesophageal variceal pressure: effect of 13*6 mm compared with a fall of 0*5±6*7 The results indicate that recurrence of somatostatin mm control subjects (p<005). Body fat varices can be expected in the majority of (% of body weight) in patients increased by patients after initial obliteration by D CLEMENTS, J M RHODES, AND E ELIAS 3-6% vs -0.02% in controls (p<0-05). sclerotherapy. The frequency of bleeding, (Department of Medicine, Queen Elizabeth Urinary sodium excretion increased by however, may be minimised by regular fol- Hospital, Birmingham) The efficacy of 49±52 mmol/l after one year compared with low up endoscopy, and injection of 'new' somatostatin in the treatment of a decrease of 7±37 mmol/l in controls varices, particularly during the first 12 oesophageal variceal haemorrhage and its (p<0.05). Total body water in patients tak- month period. effect on portal pressure are currently ing propranolol fell from 39.6±4-7 to 35 0+ unclear, some authors reporting favourable 4.9 L (p<0.01) at six months compared with responses and others not. There have been control values (35.4±10.2 to 33*9±10-1 L) T1O no studies on the effect of somatostatin on (p A1136 The British Society of Gastroenterology P DYKES, G V H BRADBY, P HILLENBRAND AND H J HAGEL, M MELCHNER, G KACHEL, H RUP- relevance to gastric pathology. To investi- E ELIAS (Departments of Medicine, Queen PIN, W DOMSCHKE, AND D N CROFT (Univer- gate this further, antral biopsies were Elizabeth, Selly Oak and General Hospitals, sity of Erlangen-Nuremberg, Federal obtained from 108 unselected patients Birmingham, Sandwell Hospital and Good Republic of West Germany and St. Thomas' attending for endoscopy and submitted for Hope Hospital, Sutton Coldfield) A trial Hospital, London) The mechanism histology and culture under micro- was conducted to determine whether use of whereby aspirin and alcohol damage gastric aerophilic conditions. Spiral-shaped gram- the Williams overtube followed by Seng- mucosa is controversial, one possibility negative organisms were cultured in 43 staken balloon compression of oesophgal being an acute toxic effect on gastric surface (40%). Patients with positive cultures were varices increases the likelihood of variceal epithelial cells leading to their exfoliation. more likely to have either a history of ulcer obliteration after sclerotherapy. Forty Instillation of soluble aspirin into the disease (53% vs 9% p<0*0001) or active patients bleeding from previously untreated human stomach has been shown to cause ulceration (46% vs 9% p<0.0001). Only 10 oesophageal varices were randomised to exfoliation of surface epithelial cells which patients of 43 with ulcer disease were nega- have their first sclerotherapy by one of two has been quantitated by measuring DNA tive in culture. Positive culture was also techniques; in 19 patients fibreoscopic (or cell) loss from the gastric mucosa. In associated with histological evidence of gas- injection of the varices was performed order to further investigate the acute effect tritis (88% vs 15% p<0.0001) and H2 under general anaesthetic using a Williams of chemical insults to the human stomach antagonist use (39% vs 15% p<0-004), but overtube and a Sengstaken balloon was the gastric DNA loss technique has been not with sex, endoscopic evidence of gas- then inserted and the oesophageal balloon used on seven healthy volunteers to test two tritis(19% vsll%)orerosions(7% vs 3%). inflated to 40 mmHg overnight; in 21 strengths of soluble aspirin, a microencap- Only 10 of 55 patients with histological gas- patients varices were injected under iv seda- sulated aspirin, a bicarbonate-ascorbic acid tritis were negative in culture. tion using a 'free' technique without the formation of aspirin and three strengths of Preliminary microbiological studies overtube -or Sengstaken tamponade. Sub- alcohol. In each study three instillations of suggest that these organisms are all similar sequent scleroses in all patients were per- one of the seven preparations was followed or closely related strains (Campylobacter- formed at three to four week intervals using by two saline washings after each instilla- like). the 'free' technique. Five per cent tion. All seven preparations were studied at The relevance ofthese organisms remains ethanolamine oleate was used as sclerosant weekly intervals ip the seven volunteers. obscure, but this comfirmation of their with intention to inject intravariceally. In Instillations of0 5 g and 1-0 g soluble aspirin association with ulcer disease and gastritis is none of 19 Sengstaken-treated patients and caused significant (p<0- 10) increases of interesting and deserves further study. only one of 21 'free' injected patients were greater than 150% above basal gastric DNA the varices eradicated by the first treatment. loss rates and the loss was dose dependent. In a median follow up of 12 months five of Microencapsulated aspirin caused insig- T15 19 (26%) Sengstaken treated patients died nificant increase of 50% and 75% after the 'Campylobacter pyloridis' in peptic ulcer and five had non-fatal bleeds while six of 21 first two instillations but after the third disease: pathogen or opportunist? http://gut.bmj.com/ (29%) 'free' treated patients died and six instillation it rose significantly to 150%. had non-fatal bleeds. Varices have so far After the ascorbic acid-bicorbonate prep- A SMITH, A B PRICE, J DOLBY. AND J LEVI. been completely obliterated in five of 19 aration values of <150% were obtained (Northwick Park Hospital and CRC, Har- Sengstaken treated patients (median after all three instillations; particularly high row Middlesex) 'Campylobacter pyloridis', number of scleroses required = five) and in levels occurred after the first instillation only recently identified, may have a role in six of 21 'free' treated patients (median perhaps due to lower Ph caused by the peptic ulcer disease. Therefore a complete number of scleroses = four). Two of the ascorbic acid. Increased DNA loss occurred microbiological and histological analysis Sengstaken treated patients died as a direct after alcohol 10% (strong German beer), (including scanning electron microscopy) on September 30, 2021 by guest. Protected copyright. consequence of the sclerotherapy, one from 20% (Campari) and 40% (whisky) which was performed prospectively on 54 sets of oesophageal perforation and one from in- was significant after Campari and whisky, endoscopic antral biopsies from 50 patients halational pneumonia. the responses being again dose dependent. with varied upper gastrointestinal com- Compression of varices by Sengstaken We conclude that the gastric DNA (cell) plaints. The organism was cultured in 16 of tamponade after injection of sclerosant loss technique can be used satisfactorily to the 20 (80%) antral biopsies from patients does not increase the likelihood of variceal quantify gastric epithelial damage caused by with an acute duodenal ulcer, four of seven obliteration and may be associated with an local chemical insults which in the case of (57%) with a chronic gastric ulcer, five of increased risk of complication. aspirin and alcohol appear to be dose nine (56%) with a healed gastric or dependent. duodenal ulcer, one of two with gastritis only and was absent from two patients with pernicious anaemia. It was present in five of T14 fourteen (36%) 'controls', patients with Clinical correlates of spiral shaped dyspepsia but normal endoscopy. Signifi- GASTRODUODENAL organisms from antral biopsies cantly these five had abnormal microscopy. T13-26 Histological correlation was within a clas- A IRELAND, G HOLDSTOCK, L BOOTH, P HAW- sification chronic superficial and chronic TIN, J BAMFORTH, AND A PEARSON (South- atrophic gastritis, active or quiescent. 'C T13 ampton General Hospital, Southampton) pyloridis' was cultured from 75% with Gastric mucosa cell damage caused by four There has been considerable controversy chronic superficial gastritis and 61% with acetylsaliclic acid preparations and three recently regarding the findings of spiral like chronic atrophic gastritis. Inflammatory strengths of alcohol organisms in the stomach and their possible activity (polymorphs infiltrating mucosal Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society ofGastroenterology A1137 epithelial cells) was of no influence. presence of CLO correlates closely with S L GRAINGER, JUDITH I GAUNT, D N CROFr Organisms were isolated in only one. of the gastritis we have been unable to AND R P. H THOMPSON (Gastrointestinal 12 (8%) patients with normal antral demonstrate any positive correlation with Laboratory, Rayne Institute, St Thomas' mucosa. Scanning microscopy identified peptic ulceration. Hospital, London) The irritable bowel organisms in two culture negative cases of syndrome accounts for up to 50% of refer- duodenalulcer raising this group's yield to rals to gastroenterological clinics. In one- 90%. T17 fifth abdominal pain occurs without altered Clearly 'C pyloridis' is strongly associated Gastric emptying in patients with flatulent bowel habit and conventional investigations with peptic ulcer disease, particularly dyspepsia, with and without gall bladder are normal. Associated symptoms in these duodenal ulceration. It rarely colonises nor- disease patients often suggest disturbed gastric mal antral mucosa. Whether pathogen or motility and we have previously observed opportunist will partly depend on the care- P WATSON AND A H G LOVE (Department of delayed initial gastric emptying of a solid in ful follow-up of the 36% of colonised 'con- Medicine, The Queen's University of Bel- such patients. trols'. Will they develop ulcers? fast, Belfast) A disturbance of antral motil- Twenty three patients with functional ity has been implicated in causing symptoms abdominal pain and normal bowel habit, of flatulent dyspepsia associated with gall and with normal upper GI endoscopy and T16 stones. Antral activity is an important gall bladder ultrasound were studied. After Campylobacter-like organisms in mucosa of determinant of the rate of gastric emptying an overnight fast, gastric emptying of 99m patients undergoing routine upper gastro- of a solid and so it is of note that similar Tc-labelled poached egg white was mea- intestinal endoscopy symptoms have been attributed to delayed sured with a gamma camera/computer sys- gastric emptying in a wide range of disor- tem. Gastric emptying measurements were J A H FORREST, C R FRICKER, R W A GIRDWOOD, ders. The aim of the present study was to repeated 30 minutes after one month's R A BURNETF, AND J B MACDONALD (Depart- determine if gastric emptying is abnormal in double blind treatment with either meto- ments of Bacteriology, Pathology and Gas- patients with dyspepsia, with or without gall clorramide 10 mg tds (n=8), domperidone troenterology Unit, Stobhill General Hos- bladder disease. Gastric emptying of a 20 mg tds (n=8) or placebo (n=7). pital, Glasgow) Ninety five consecutive scrambled egg meal was measured in 74 sub- Pre-treatment gastric emptying con- patients undergoing routine upper gastro- jects for 90 minutes by a fixed scintillation firmed the prolonged lag time before the intestinal endoscopy were investigated for counter method using 99Tc. The subjects start of emptying. Neither domperidone nor the presence of 'campylobacter-like' were divided into five groups: 24 normal placebo had any influence on the lag time or organisms (CLO) in the stomach and controls in whom gall stones were excluded gastric emptying rate. Metoclopramide, duodenal cap mucosa. Two biopsies were by ultrasonography; gall stones and flatu- however, shortened the lag time (before taken from three sites (antrum and body of no 22-5 min, after 14-5 min, SE of difference lent dyspepsia (n=13); gall stones, dys- http://gut.bmj.com/ stomach and duodenal cap) from each pepsia (n=12); postcholecystectomy dys- 2-6, p=0-016) and normalised the pattern of patient. One set was examined histologi- pepsia (n= 13); radiography/endoscopy gastric emptying. cally to determine the degree of gastritis and negative dyspepsia (n=12). Gastric empty- Domperidone is a dopamine antagonist, the presence of CLO; the other set being ing was significantly slower in the 25 but metoclopramide is also cholinomimetic. assessed and micro-biologically by stained patients with gall bladder disease compared The former inhibits adaptive relaxation of smear and culture for CLO. with controls after 45 minutes (p>0-02) and the gastric fundus, the latter also enhances 'Campylobacter-like organisms' were for the remainder of the test (p range 0-01- antral motor activity. The differential effect seen in antrum and body of stomach in 56 0-03). There was no difference between the of the drugs on gastric emptying in our cases (59%). When present CLO were seen two groups with gall bladder disease with or patients suggests the prolonged lag time is on September 30, 2021 by guest. Protected copyright. in both antrum and body; this not being so without dyspepsia and both were signifi- due to a defect of cholinergic activity or of in only two cases. There was an excellent cantly slower than controls (p>0-05). contractility in the antral 'pump'. correlation between the demonstration of Patients with postcholecystectomy dyspep- CLO by histology and culture; disagree- sia showed delayed emptying after 65 ment being noted in only five biopsies. Of minutes (p range 0.03-0-01). There was no T19 70 patients in whom gastritis was diagnosed delay compared with controls in patients Stress-induced suppression of antral motil- histologically CLO were detected in the with radiograph/endoscopy negative dys- ity in functional dyspepsia stomach by at least one method in 50 (71%) pepsia. For the three groups with a history whereas in the 25 patients with histologi- of dyspepsia, 22 patients experienced typi- M CAMILLERI, J R MALAGELADA (INTRO- cally normal stomachs only six (24%) were cal symptoms during the test but gastric DUCED BY S F PHILLIPS) (Gastroenterology positive for CLO (p<0-01). There was no emptying was not different from controls. It Unit, Mayo Clinic, Rochester, Minnesota, significant difference between the incidence is concluded that gall bladder disease, even USA) In healthy individuals, acute stress of CLO in mild (13 of 15 cases) or in severe after cholecystectomy, is associated with inhibits the antral pressure response to a gastritis (37 of 55) (p>0-05). CLO were delayed gastric flatulent dyspepsia are not meal, and delays its emptying from the only seen in duodenal cap mucosa in two usually associated with delayed emptying. stomach. It is not known whether patients cases. Twenty four patients with and two with functional dyspepsia (FD) respond to patients without histological evidence of stress in a similar manner. We studied 12 gastritis had endoscopically diagnosed pep- patients (age range 20-51, mean 35-8; five tic ulceration. Of these 26 patients, 14 had T18 men, seven women) afflicted with nausea, demonstrable CLO (54%). Antral motor disturbance in functional vomiting, epigastric discomfort or bloating Although this study has shown that the abdominal pain by means of a pneumohydraulic multilumen Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1138 The British Society ofGastroenterology perfusion system, with or without stressful provocation. Seventeen of the 55 patients centrations greater than 5 0 umol/l were stimulation to the hand by a transcutaneous with cholelithiasis have been studied pros- recorded in only one patient but there were electrical nerve stimulator (TENS). The pectively after cholecystectomy as well. The two others with peak hourly bile acid con- control group was composed of 12 healthy subjects were scanned in the erect position centrations greater than 0-5 umol/l. There volunteers, six of whom underwent the and control films obtained after injection of was marked fluctuation in bile acid concen- study with active TENS, and six with sham the HIDA. They were then scanned for one trations over the 24 hours of the study and TENS. Transcutaneous electrical nerve hour after ingesting 300 ml milk, and counts reflux would not have been identified from stimulator was applied for one hour starting in the gastric field were expressed as a per- a standard fasting two hour aspirate in two 10 minutes after the end of the solid-liquid centage of the total at five minute intervals. of the three patients with high bile acid con- meal, at an intensity that was just bearable The gall bladder was assessed during the centrations. These results indicate that bile in each individual. Sequential 20 minute test and identified as functioning, poorly reflux may occur despite a 50 cm Roux and antral motility indices (MI = loge [sum of functioning, or non-functioning depending was excessive in at least one of the six sub- amplitude X number of waves + 1]) were on the degree of count density in the gall jects studied. calculated from the antral phasic pressure bladder field and its emptying curve in activity in each study, and the slopes of response to milk by on-line computer cumulative 20 minute MI before and during analysis. Results were compared by both T22 one hour TENS were determined. the x2 and Mann-Whitney U-tests. Reflux Acid perfusion ofduodenal ulcer craters and Without TENS, seven FD patients was shown in eight of the 43 volunteers, but ulcer pain - a controlled double blind study (group I) had normal antral motility (0-554 was greater than 3% in only three which ±0-009 vs controls with sham TENS 0-574 constituted a positive test. In the J Y KANG, AND IVY YAP (Medical Unit 11, ±0-005) and five (group II) had decreased cholelithiasis group, the gall bladder func- National University ofSingapore, Singapore motility (0-477+0-011, all slopes being tion was normal in 34, impaired in 11, and General Hospital, Outram Road, Singa- below 5th percentile for controls: range absent in 20. In those without function there pore) Early uncontrolled observations 0.543-0-597). With TENS, antral motility was a significantly higher incidence showed a close relationship between peptic was suppressed in group I (0-518±0-009, (p<0-05) and amount (p<0.01) of ulcer pain and intragastric acidity. More p<0-05) but remained unchanged in group duodenogastric reflux. In all patients who equivocal results were, however, reported II (0.502±0.005). The degree of suppres- underwent cholecystectomy (n=34), there by subsequent workers and a recent control- sion of antral MI slopes during TENS was was also significantly more reflux (p<0-001) led study of gastroduodenal acidification similar in group I patients and healthy indi- than that seen in the volunteers. In the 17 and ulcer pain suggested that 'duodenal viduals. patients studied prospectively, 12 had no ulcer pain is largely and possibly totally We recognise two groups of patients with reflux before or after, two had reflux before unrelated to duodenal acidification'. FD: (I) those with normal postcibal antral which did not change after cholecystec- Patients who satisfied the following motility which is normally inhibited by tomy, and three developed reflux after criteria were included in the present study: http://gut.bmj.com/ acute stress; and (II) those with decreased cholecystectomy. (1) Each patient must have a history of motility unaffected by stress. Such a distinc- These results indicate that patients with upper abdominal pains related to food and tion may reflect differences in the gastric cholelithiasis and a non-functioning gall relieved by antacids. (2) The last episode of response to stress or its perception, and may bladder or those who have undergone pain must have occurred within 24 hours of influence the choice of therapy. cholecystectomy are more prone to the time of study. (3) An active duodenal deuodenogastric bile reflux. ulcer must be demonstrable at endoscopy. Nineteen patients were studied. There T20 were 18 men and one woman and their ages on September 30, 2021 by guest. Protected copyright. Effect of gall bladder function on T21 ranged from 19 to 71 years. Informed con- duodenogastric reflux How effective is the 50 cm Roux in prevent- sent was given. Endoscopy was performed ing reflux of bile acids into the gastric under local anaesthesia using the Olympus W G CHEADLE, V PATHI, C R MACKIE, AND A remnant: a 24 hour study? GIFQ or Q1O gastroscope. No premedica- CUSCHIERI (University Department of tion or sedation was given. Using a washing Surgery, Ninewells Hospital and Medical V POXON, B HOGG, AND M R B KEIGHLEY tube 100 ml normal saline and 100 ml School, Dundee, Scotland) Symptomatic (Department ofSurgery, General Hospital Bir- O.IN hydrochloric acid were infused sequen- enterogastric reflux after gastrectomy is well mingham) It has always been assumed from tially onto the duodenal ulcer crater over recognised, but controversy exists about isotope scans and measurement of bile acid five minute periods. The order of infusion primary duodenogastric reflux as a clinical concentrations in gastric juice that a long was randomised and double blind. If the entity. The occurrence of previous Roux Y loop prevents bile reflux. patient reported pain on one solution infu- cholecystectomy has been frequent in those We have collected gastric juice by hourly sion of that solution was terminated. patients with epigastric symptoms and aspiration over 24 hours from six healthy Eight out of 19 patients reported pain endoscopic bile gastritis, and cholecystec- subjects two years after Roux Y bile diver- when acid was being perfused. One patient tomy has been incriminated as a causitive sion when a loop of at least 50 cm in length reported pain when saline was being given factor of bile reflux. Seventy two patients, was used. Aspirates were analysed for pH, (p<0025). Seven out of the eight patients of whom 55 had cholelithiasis and 17 had bacterial counts and bile acid concentra- developing pain on acid reported that the undergone a previous cholecystectomy, and tions. The pH was invariably greater than pain was similar to their usual ulcer pains. If 43 asymptomatic volunteers were studied 4-0 and there was persistent bacterial over- the patient with atypical pain was excluded for the presence of duodenogastric reflux growth with between 10-18 different species the difference between acid and saline using intravenous 99m Tc-HIDA with milk in each patient. Peak hourly bile acid con- remained significant (p<0-05). In six Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1139 patients who developed pain on acid the infu- is itself pathological and causes inappro- intra-gastric pH in eight asymptomatic sate was changed to saline until the pain has priately high acid secretion as a conse- volunteers with a past history of duodenal subsided. Acid was then reinfused. In five quence. ulceration. Each subject received placebo, C instances the pain was reproducec. 400 mg bd, P 50 mg bd, C 400 mg with P 50 Acid therefore appears to have a role in mg bd, or C 200 mg with P 25 mg bd on five the production of duodenal ulcer pain T24 separate occasions. The data were analysed although other factors are likely to be Comparison of tripotassium dicitrato bis- as hydrogen ion activity using Wilcoxon's important also. muthate (TDB) tablets and cimetidine in the rank sum test. healing and long term relapse of duodenal Mean hourly hydrogen ion activity during ulcer. the total 24 hours was significantly lower T23 with the lower dose combination (6-45±1-5 Duodenal loop alkalinisation in DU: I HAMILTON, H J O'CONNOR, N C WOOD, AND SEM) than with P (16-9±4-1, p<0.05) or C stimulus or response? AT R AXON (Gastroenterology Unit, General (11 -9±2-8, p<0-05) alone. The higher dose Infirmary at Leeds, Leeds) In a double blind combination produced similar inhibition J M RAWLINGS, B J Z DANESH, D FARAH, A N H endoscopically controlled trial, TDB tablets (7.09±1.5) but this did not reach statistical MAIN, R J MORGAN, W MURRAY, M L LUCAS, (1 qds) were compared with cimetidine (1 g significance. At night both combination AND R I RUSSELL (Institute of Physiology, daily) in the treatment of duodenal ulcer treatments (high dose 1-75±0-7, low dose Glasgow University, Gastroenterology (DU). Eighty patients (58 men, 22 women, 2.91±1 1) were significantly better than P Department, The Royal Infirmary, The mean age 45 years, range 22-72 years) with (13.9±4.5, p<0-05) but not better than C Department of Surgery, The Western Infir- DU were randomly allocated to treatment (3.5±0.09) alone. mary, Glasgow) Mucosal and intraluminal with either TDB (41 patients) or cimetidine We conclude that a low dose combination pH measurements have been made in the (39 patients) for six weeks. Patients kept a of C 200 mg and P 25 mg is significantly bet- stomach and duodenum of 64 patients daily record of symptoms on a diary card ter in inhibiting intragastric acidity over a 24 undergoing upper gastrointestinal endos- and ulcer healing was determined by endos- hour period than either drug given alone at copy, with or without anti-cholinergic pre- copy during the final week of treatment. In twice the dosage: this is suggestive of a medication. A catheter pH electrode those who had healed, a further endoscopy synergistic effect between the drugs in com- inserted down the biopsy channel allowed in was done at one year, or earlier if symptoms bination. situ pH readings at standardised sites. recurred. The groups were similar with Patients were divided into two groups, respect to age, sex, smoking and duration of those with no endoscopic abnormality ulcer symptoms. Healing occurred in 33 T26 (n=43, 17 from an ERCP study); those with (80%) treated with TDB and 29 (74%) Intravenous omeprazole rapidly raises duodenitis or an active duodenal ulcer treated with cimetidine (x2, p>0-05). Relief intragastric pH (n=21). of symptoms was similar with both drugs. http://gut.bmj.com/ Without anticholinergic premedication, No significant difference was seen in the R P WALT, J R REYNOLDS, M J S LANGMAN, H L control patients had an acid gastric fundal early relapse rate (up to nine months follow SMART, K W SOMERVILLE, G KITCHINGMAN, lumen and a neutral duodenal loop mucosal up) after healing with either drug. Late AND C J HAWKEY (Departments Therapeutics surface, pH of 7-02±0-12(7); 6-87± relapse (>9 months follow up) was signifi- and Surgery, University Hospital, Not- 0-10(17) at ERCP. Patients with duodenitis cantly more common in patients whose tingham) Intravenous antisecretory drugs or active DU also had acid gastric fundus ulcers had initially been healed wyith are often used to treat upper GI bleeding lumen values with a strikingly alkaline cimetidine. At 16 months, 13 of 30 (43%) and to prevent stress ulceration. Their duodenal surface of pH 7-74±0.04(7). given TDB, compared with 18 of 23 (78%) effects on 24h intragastric acidity, however, on September 30, 2021 by guest. Protected copyright. When anti-cholinergic premedication given cimetidine, had relapsed (x2, have been poorly studied. Omeprazole, an was used, luminal pH in the fundus was p<002). Eighty seven per cent of relapses H+K+ ATPase inhibitor, is the most potent reduced in both groups as expected but the were symptomatic. Our results suggest that oral antisecretory agent used in man. We DU group fundal pH remained lower TDB tablets are as effective as cimetidine in have studied the effect on 24h intragastric than normal. Duodenal mucosal surface pH the short-term treatment of DU and, acidity of intravenous omeprazole in five did not change in the controls but there was moreover, appear to be superior in the long duodenal ulcer patients. Two dosage regi- a highly significant reduction (p<0-001) in term prevention of ulcer recurrence. mens (80 mg at 0900h with 40 mg at 1700h the DU group to 6-99±0-17(14). [A], and 80 mg at 0900h with 80 mg at 1700h Two notable features therefore occur in [B]) were compared double blind with the DU group. Firstly, lower than normal T25 placebo given at the same times in random gastric fundal pH persists, despite choliner- Are pirenzepine and cimetidine additive or order. In a fourth study three patients gic and H-2 receptor blockade: secondly, synergistic in combination? received three doses of omeprazole (80 mg duodenal alkaline secretion, as mucosal sur- at 0900h, 40 mg at 1700h and 40 mg at 0100h face pH is significantly. above assumed M DEAKIN, J K RAMAGE AND J G WILLIAMS [C]). The drugs or placebo were infused plasma values. This is predicted by the (RN Hospital, Haslar, Gosport, Hampshire, over 12 minutes by mechanical pump. Acid- cytoprotection hypothesis and may be a UK) The effect of cimetidine (C) and piren- ity was measured on hourly aspirates of gas- response to increased duodenal acid loads zepine (P) has been shown to be greater in tric contents with a glass electrode. Meals in DU. Loop pH fell, however, while fundal combination than when the individual were identical in all studies. Mean (± SEM) pH rose after atropinisation, while normal drugs are given alone, but it is not clear intragastric acidity (1000-0800h) fell from loop pH did not change. An alternative whether this is a simple additive or a syner- 34-3±4-3 mmol/l on placebo to 2-1±0+9 hypothesis is that high duodenal pH in DU gistic effect. We have monitored 24 hour mmol/l [A], (- 94% p<0.001 anov) and to Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1140 The British Society of Gastroenterology 0-7±0-2 mmol/l [B], (- 98%). The intragas- Ceruletide in all these cases. The mean two of 15 without air in the billiary tree. tric pH remained <4 0 for 95% of record- residual pressure in the cholecystitis/biliary There is a tendency for surgical sphinc- ings on placebo and for 20% of recordings colic group was 3-57±0-78 mmHg com- terotomies to heal with time back to a near after either [A] or [B]. pH values were <4-0 pared with 0*83±0*40 in the pancreatitis normal state and providing that gall stones for only 10% of recordings and mean group (p<0-05). Ceruletide did not lower have been completely removed, this may intragastric acidity decreased by 99% to the postinfusion or residual pressure in the not be disadvantageous. 0 5±0 4 mmol/l with regimen [C]. Gastric pancreatitis group. pH rose to >4-0 in all patients one hour This study has shown that Ceruletide has after the first infusion of omeprazole. Ph a marked relaxant effect on the human T29 remained at about this level for the majority choledochal sphincter. Previous pan- Long term patency of sphincteroplasty: a of the next 23 hours. Unexpectedly large creatitis is associated with an atonic, func- radiolological review doses of intravenous omeprazole were tionally unreponsive sphincter. needed to achieve this compared with ear- C F HARVEY, C J H LOGAND, AND K WILSON, lier studies using oral omeprazole. (INTRODUCED BY T G PARKS) (The Ulster Intravenous omeprazole may be of use T28 Hospital, Dundonald, Belfast.) Sphinc- when rapid and prolonged neutralisation of Patency of the biliary sphincter after trans- teroplasty, first described by Jones (1952) in gastric acid is required. duodenal sphincterotomy. A review of 25 combination with transduodenal explora- years surgical experience tion of the common bile duct may offer cer- tain advantages. Jones (1973) emphasised A R W HATFIELD, C PANAHY, AND H D RITCHIE that sphincteroplasty is only considered PANCREATICOBILIARY (Academic Department ofGastroenterology adequate when the complete sphincter is T27-40 and Surgical Unit, The London Hospital, divided surgically and that the demonstra- Whitechapel, London) Of 191 patients tion of free biliary reflux on barium meal is who underweynt transduodenal sphinc- essential to show continued patency of the T27 terotomy and exploration of the bile duct at sphincteroplasty. Continued patency Effect of Ceruletide on the human choledoc- The London Hospital between three and 24 should prevent ascending cholangitis and hal sphincter in patients undergoing years ago (mean 9-5), 34 volunteered for re- allow the passage of retained stones. cholecystectomy examination by ERCP. In nine patients Over a five year period 27 patients under- (26%) the sphincterotomy site was wide went sphincteroplasty. The mean age was A CUSCHIERI, J G R CUMMING, R A B WOOD, open and in 25 (74%) it had partially or 60 years and M:F ratio was 11:16. Fourteen AND P R BAKER (University Department of completely returned to a normal appear- patients were jaundiced at the time of Surgery, Ninewells Hospital & Medical ance. Of these 25 patients, 14 had a small slit surgery and the mean pre-operative biliru- School, Dundee, Scotland) The effect of like orifice on the papilla, seven had a com- bin in these patients was 176 mm/I. http://gut.bmj.com/ the synthetic peptide Ceruletide on the pletely normal looking papilla and in four In 20 patients reviewed there were no human choledochal sphincter complex has there was a small hole above an intact clinical episodes of jaundice or cholangitis been investigated in 20 consecutive patients papilla. Healing of the sphincterotomy did and liver function tests were normal. undergoing cholecystectomy either for pre- not correate with the period of time after Barium meal examination was performed in vious acute cholecystitis/biliary colic (group surgery. In no patient were gall stones 14 patients at a mean follow-up time of 32 I, n=14) or gall stone associated pan- demonstrated. months (range 11-68 months). creatitis group II (n=6) using a standardised A balloon catheter was used to assess Patency of the sphincteroplasty as shown technique of pump driven isotonic saline sphincterotomy size and the pressure gra- by entero-biliary reflux was present in seven on September 30, 2021 by guest. Protected copyright. perfusion manometry. Each patient had dient from bile duct to duodenum measured cases and asymptomatic retained stones two pressure profile studies with Ceruletide with a side hole perfused catheter. The nine were demonstrated in one of these. (1-0 ,tg iv) being administered before the gaping orifices usually took a 10 mm bal- It appears that many sphincteroplasties second run. All patients included in this loon and had little or no pressure gradient may not remain adequate as defined by the study had a normal intra-operative cholan- (mean-1-5 cm H20). Although those with demonstation of free biliary reflux and even giogram. Statistical analysis was by a non- slit like orifices and normal papillae usually where free reflux is demonstrated residual parametric test for paired and unpaired data took a 5 mm balloon and had higher pres- calculi may be present. (Wilcoxon's signed-ranks and Mann-Whit- sure gradients (mean-30cm H20), there ney U tests). There was no difference in the were four patients with endoscopically basal pressure between the two groups. The intact papillae through which a 5 mm bal- T30 postinfusion pressure in group I (x10.0± loon could not be pulled and pressure gra- Prospective randomised trial of early versus 1-03 mmHg) was significantly higher than dients that did not change after TT gluca- delayed surgery for actute biliary tract dis- the basal pressure (x6 57±0 68 p<002). gon. These four patients probably had some ease. The postinfusion pressure in group II x 7-5 degree of sphincterotomy stenosis. They 2-26 as opposed to a basal pressure of 6-66 were all, however, asymptomatic. B W A WILLIAMSON, C J SIMPSON, G McLATCHIE, + 2-16 (NS). Bile was aspirated from the bile duct for G GILLESPIE, AND C S McARDLE (Depart- Before injection of Ceruletide a signifi- culture in 32 patients and found to be posi- ments of Surgery, Royal and Victoria Infir- cant residual pressure (postinfusion minus tive in 17 and negative in 15. Although none maries and Southern General Hospital, basal >2mmHg) was encountered in 7/14 in of the patients had clinical cholangitis, of Glasgow) Prospective randomised studies the cholecystitis/biliary colic group. The those with air-reflux into the biliary tree, from specialised centres in Scandinavia and residual pressure was abolished by nine of 16 had infected bile compared with the UK have shown that early surgery in Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1 141 acute cholecystitis is not associated with they did not exist and stones were over- and that this route of excretion accounts for increased morbidity and mortality. The looked in only one patient (0.4% false nega- only a small proportion of administered value of this policy in routine surgical prac- tive). Thus the pocket computer had a sen- Temocillin, but that this drug is highly con- tice has not been assessed. sitivity of 99-6% and a specificity of 93% in centrated in the normal GB. Fifty patients with proven acute biliary the detection of choledocholithiasis. tract disease presenting to three hospitals Using this system of multivariate analysis were randomised to early (n=26) or and using a pocket 'mini-computer' (Sharp) T34 delayed (n=24) surgery. Groups were simi- very few bile duct stones will be overlooked Measurement ofbiliary lipid mass within the lar with respect to age, sex, mode of presen- and the incidence of negative exploration of gall bladder in health and in ileal Crohn's tation and clinical findings. the common bile duct will be low. We disease There was one postoperative death from believe that this technique is a useful pulmonary embolism in the early group and method for the operative determination of R P JAZRAWI, C BROWN, AND T C NORTHFIELD one from postoperative sepsis in the choledocholithiasis. (Department ofMedicine, St. George's Hos- delayed group. Five patients allocated to pital Medical School, London) Identifica- delayed surgery failed to settle on conserva- tion of supersaturated gall bladder bile gives tive management and require emergency T32 no indication of whether the underlying cholecystectomy. A further three patients, ABSTRACT WITHDRAWN cause is a deficit of bile acid and/or phos- died, two of gall bladder sepsis, before re- pholipid or an excess of cholestrol. In order admission for surgery. Postoperative mor- to make this distinction, we have developed bidity in the 16 patients undergoing delayed a method of measuring biliary lipid mass surgery were similar to that in the early T33 within the gall bladder following iv injection group; overall hospital stay was longer. All Quantification of biliary excretion and gall of 99"Tc HIDA. Activity over the gall blad- but one death occurred in patients older bladder bile concentration of temocillin in der is measured by camera, and a sample of that 80 years. man gall bladder bile then obtained for isotopic These results emphasise the aggressive and chemical determination, and biliary nature of acute biliary tract disease particu- D P MAUDGAL. A LANZINI. AND T C NORTH- lipid mass is derived from the following for- larly in the elderly and confirm the value of FIELD (Departments of Medicine, St. mula: early surgery. George's Hospital Medical School, Lon- mass in sample mass in GB don) Pharmacokinetics is concerned with TcHIDA in sample TcHIDA in GB measuring serum and urinary concentra- T31 tions of drugs, while biliary excretion is a We have applied this technique to nine Prospective study of the use of a pocket com- neglected area. We have therefore applied patients with ileal Crohn's disease and to 12 puter in the prediction of common bile duct techniques developed for measurement of healthy controls. In three patients we have http://gut.bmj.com/ stones biliary lipid secretion and biliary lipid mass validated this indirect measurement by in the gall bladder (GB) to biliary excretion comparing it with direct measurement of C P ARMSTRONG, T V TAYLOR, S LUCAS, AND of an antibiotic (Temocillin - a new synthe- mass for all three biliary lipids after surgical J JEACOCKS (Departments ofSurgical Gas- tic, long-acting parenteral 1-lactum said to removal of the gall bladder (r= troenterology and Computation, Manches- be of particular value in biliary tract infec- 0-99, p=O-OOOl). The ileal Crohn's group te.r Royal Infirmary, Oxford Road, Man- tions). We have carried out eight studies in had a significantly higher saturation index, chester) Many surgeons do not routinely six subjects with normal hepatobiliary and and this was because of a reduction in bile use operative cholangiography at the time renal function. In each study, duodenal per- acid and phospholipid mass (mM) without on September 30, 2021 by guest. Protected copyright. of cholecystectomy. An alternative method fusion was carried out with polyethylene any for predicting the presence of common bile glycol, and IV injection of Temocillin (0.5 g Group n SI BA PL XOL duct stones using a pocket computer has in three and 1 g in five studies) was given Ileal been prospectively evaluated. Thirty six after a 60 minute equilibration period. mTc Crohn's 9 1 36±0-11 2-4±0 5 0-8±0 2 0-31±0-06 was iv as a GB bile Healthy variables were assessed on each of a con- HIDA (lmci) given controls 12 0 93±-07 4-9±0-3 1-6±0-3 0-47±0-09 secutive series of 424 patients undergoing marker. Serum, intestinal aspirate and <0-005 <0-005 =0-05 NS cholecystectomy and used as a data base. urine were collected over six hours, and significant alteration in cholestrol mass. Using multivariate analysis, six variables then a GB ultrasound was carried out to We conclude that our method of measur- were selected to predict the presence of bile determine GB volume and a scintiscan to ing biliary lipid mass is valid, and that it pro- duct stones; bile duct diameter, patient's could 99mTc HIDA activity over the GB. vides a rapid new method of determining sex, history of jaundice, or pancreatitis, a Gall bladder bile was collected for Temocil- the underlying cause of supersaturated gall presentation of biliary colic and the number lin and Tc HIDA activity following bladder bile. of stones in the gall bladder. cholecystokinin infusion. Plasma half life A prospective study was then carried out was 210 minutes at both doses and mean uri- of a second group of 242 patients also under- nary excretion accounted for 35% and 38% T35 going cholecystectomy. Using the initial respectively. Mean biliary excretion of Intestinal transit rate, deoxycholic acid and data base 93% of this prospective group Temocilin was 2.2% of the a'dministered the cholesterol saturation of bile were correctly classified, when compared dose, and mean hepatic bile concentrations with the corresponding operative cholan- was 10 ug/ml, while GB bile concentration S N MARCUS AND K W HEATON (University giography. Bile duct stones were predicted was 474 ug/ml. We conclude that biliary Department of Medicine, Bristol Royal in 17 (7% false positive) patients in whom drug excretion can be studed quantitatively; Infirmary, Bristol) There is considerable Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1142 The British Society ofGastroenterology evidence that the level of deoxycholic acid gated with taurine. n-CDC induced an compound and between each parameter for (DCA) in the bile influences biliary choles- enormous canalicular choleresis of 231 ul/ the two drugs. The CL of each drug was sig- terol saturation. Deoxycholic acid is formed umol secreted BA; nCDC-taurine (9.5) nificantly faster in patients with all forms of in the colon and absorbed slowly. Hence, and chenodeocycholate (21) were much less pancreatic disease compared with controls. changes in colonic transit rate might influ- choleretic. Alcohol was the obvious inducer in 10 ence biliary DCA and the cholesterol sat- In the taurine replete rat, nCDC was patients (27%): in the remainder dietary, uration of bile. principally secreted as nCDC-taurine and social, occupational, domestic or iatrogenic When 10 constipated subjects took stan- was moderately choleretic (18); taurine exposure to xenobiotics may be the cause of dardised senna tablets for six weeks in a depletion decreased BA output, and both the induction of cytochrome P450, and dose sufficient to reduce mean whole gut choleresis was greatly enhanced (55). In of pancreatic disease. It is conceivable that transit time from 137 to 48h, DCA as a both animals nCDC increased bicarbonate the pancreas has a latent cytochrome P450 proportion of biliary bile acids fell from output. complex - as does the intestine, kidney and 24.6±3.2 to 15.6±6.9% (p=0004) and We suggest that the intrinsic choleretic lung - and that pancreatic disease is a con- DCA pool measured by isotope dilution fell effect of nCDC ions is amplified by passive sequence of local detoxification reactions. from 0-61±0-13 to 0-41±0.11g (p=0-006). ductular reabsorption of the protonated Alternatively the abnormal bile in our In those subjects (n=5) whose bile was ini- unconjugated BA which is then returned to patients may be the link between hepatic tially supersaturated with cholesterol and the hepatocyte by the peribiliary plexus and induction and pancreatic disease. whose transit time fell by >24h, the satura- resecreted into the canaliculus. The proton tion index fell from 1-5+0-1 to 1-2±0-1 is derived from carbonic acid, so that BA (p=0-03). anions are replaced by bicarbonate ions. T38 Conversely, when eight normal volun- Conjugated nCDC is less choleretic because Accuracy of preoperative arterlography in teers took loperamide capsules sufficient to its strong acid group prevents ductular reab- the assessment of resectability in pancreatic prolong mean transit time from 48 to 113h, sorption. carcinoma the DCA pool increased from 0-37±0-09 to This cholehepatic shunt pathway may 0-54±0-08g (p=0-001). Mean biliary DCA explain the greater choleretic effect of A R W HATFIELD, JANET B MURFIT., R W increased to a lesser extent, from 17-1 to unconjugated BA compared with their con- MOTSON, A D W MACLEAN, AND J E LENNARD- 20-9% (p=04065), because the estimated jugates, may also explain the choleretic JONES. (Academic Department of Gas- total bile acid pool expanded (from 2-10+ properties of many weak acids, and pro- troenterology, Department of Radiology 0-17 to 2-64±0-25g; p=0-04), presumably vides insight into the functional importance and Department of Surgery, The London due to loperamide slowing down small of BA conjugation. Hospital, Whitechapel, London) Few bowel transit. Despite this expansion of the pancreatic carcinomas are found to be suita- bile acid pool, loperamide increased the ble for radical resection at laparotomy. cholesterol saturation index from 1.1±0.1 T37 With the advent of the non-operative man- http://gut.bmj.com/ to 1-3±0-1 (p=0-02). Induction of cytochrome P450: unifying fac- angement of malignant obstructive jaundice Thus, manipulating colonic transit rate tor in pancreatic disease with endoprosthesis insertion, however, it is alters the size of the DCA pool and bile important not to deny the younger, fit cholesterol saturation. These findings D W K ACHESON, P N SHAW, J B HOUSTON, AND patient the chance of resection, should this suggest that slow colonic transit might J M BRAGANZA (University Department of be possible. increase the risk of supersaturated bile and Gastroenterology, Manchester Royal Infir- This present study assessed the accuracy hence of gall stones. mary and Pharmacy Department, Manches- of arteriography, over the last two years, in ter University) The hepatic cytochrome determining resectability in 17 consecutive on September 30, 2021 by guest. Protected copyright. P450 complex metabolises a wide range of patients with pancreatic - carcinoma, T36 substrates - both endogenous and exogen- demonstrated by ERCP and without liver Cholehepatic shunt pathway: new concept in ous - and is 'induced' by many of the secondaries on ultrasound scanning, in hepatic transport lipophilic drugs and xenobiotics that it pro- whom the age and general condition would cesses. Biotransformation usually results in permit an attempt at radical resection. K R PALMER, A F HOFFMANN, E B LJUNGWE, detoxification but, on occasion, highly reac- Coeliac and superior mesenteric arteriog- AND D GURANTZ (University of California, tive metabolites are generated which can raphy with delayed views of the portal ven- San Diego, CA, USA) Bile acid depen- cause hepatic necrosis and derange the sec- ous circulation were performed preopera- dent flow (BADF) is attributed to the osmo- retory pathways of exportable proteins. tively in all 17 patients. Involvement of the tic properties of secreted BA. Using the Pharmacokinetic studies using antipyrine superior mesenteric artery or vein or of the unnatural C-23 BA nor-chenodeoxycholate and theophylline assess overall cytochrome portal vein were considered to imply that (nCDC) as a probe, we examined the P450 and cytochrome P448 activity respec- the tumour would not be technically resect- hypothesis that BADF is influenced by duc- tively, and we have applied these methods able. tular events. to 35 consecutive patients with acute pan- In 10 patients the arteriogram showed no C'4-nCDC was intravenously infused into creatitis, chronic pancreatitis or pancreatic signs of major arterial or venous involve- hamsters and rats with biliary fistulae. In cancer. The drugs were given orally on ment but at laparotomy only five were hamsters biliary recovery of C'4-nCDC was separate days, under standardised condi- resectable and in five the tumour was incomplete. The nuclear moiety of the BA tions, and their concentrations in serial involving the superior mesenteric and/or was partially oxidised and hydroxylated. blood samples were measured by HPLC. portal vein, thus precluding resection. In Forty one per cent was secreted in unconju- There was good correlation between the seven patients the arteriogram showed non- gated form while the remainder was conju- half life (Ti½) and clearance (CL) of each resectability and this was confirmed at Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society ofGastroenterology A1143 laparotomy in all seven. of Surgery, Medical Physics and Haemotol- night one lg enema and 13 patients (three A normal arteriogram does not imply that ogy, Freeman Hospital, Newcastle upon taking SASP) to receive 2g. Among the a tumour is resectable but an abnormal Tyne) Overwhelming infection, the most patients receiving Ig enemas, three were in arteriogram appears to accurately predict feared post splenectomy complication has remission at day 14 and eight at day 28 (non- non-resectability. Patients with tumours been prevented in animal studies by splenic friable mucosa at sigmoidoscopy, no judged non-resectable on arteriographic autotransplants. malaise, two bowel actions or less in previ- evidence can therefore be managed, ifjaun- A study was undertaken to determine ous 24 hours, no rectal bleeding, normal diced, by a non-operative endoprosthesis whether, after removal of the normal stool consistency) while among those technique without the fear of denying a spleen, it was possible to preserve splenic receiving 2g enemas, two were in remission younger patient the chance of surgery and a function by seeding autoplastic splenic frag- at day 14 and four at day 28. Separate radical resection. ments into the peritoneal cavity. assessment by clinical sigmoidoscopy and Five patients (aged 24-59 years) required histological grades showed no trend toward splenectomy for access during distal pan- an advantage for 2g enemas. The combined T39 createctomy for chronic pancreatitis. At the response rate (overall improvement by day Bacteraemia in the closed duodenal loop bile end of the procedure approximately 30-S50g 28) was 62%. Our study shows no sign that infusion model of acute pancreatitis of the spleen was diced and the fragments 2g enemas are superior to Ig enemas and wrapped in a pocket of greater omentum. because Ig enemas are pharmaceutically I A GOULBOURNE AND G C DAVIES (INTRO- The survival and function of the splenic simpler to keep stable and 2g enemas rather DUCED BY R C HEADING) (University tissue was assessed 5-23 months post more prone to cause side effects we suggest Department ofClinical Surgery, Royal Infir- implantation. Although postsplenectomy that lg is the dose of choice in active distal mary, Edinburgh) The animal model RBC morphology persisted, in no patient colitis. described by Chetty consistently produces was thrombocytosis observed, and splenic Distension of haemorrhagic pancreatitis. phagocytic function was demonstrated in the loop with infected bile might produce three of the five patients using "Tcm-label- T42 bacteraemia which could account for pul- led heat-damaged autoplastic erythrocyte Place of the gastrointestinal surgeon in an monary previously abnormalities scintigraphy. In one patient a second infectious disease hospital We have studied this described. model, laparotomy provided a neo-splenunculus using specific pathogen free rats. Two for histological examination. R M SMITH, J STEWART AND T G BRENNAN (IN- groups (n=46 and 4) had pancreatitis. A This pilot study has shown that this simple TRODUCED BY PROF. G R GILES) (Seacroft group bile third (n=44) had infected technique merits consideration whenever a Hospital, Leeds) Between 1977 and 1983, injected into a closed small bowel loop (in- normal spleen is removed. 15 000 patients presented to a sub-regionaI testinal continuity maintained with a plastic infectious diseases unit, of these 186 tube). A fourth group (sham gastrotomy) (1-25%) did not have a specific infectious http://gut.bmj.com/ acted as controls. Animals were killed at six disease but were shown to have an underly- hours, except group 1 (18 h) Pancreatitis INFLAMMATORY BOWEL DISEASE ing condition needing surgery, often as an was confirmed by raised amylase concentra- T41-54 emergency. On the basis of the presenting tions in groups 1 and 2. Heart and inferior symptoms and signs three diagnostic groups vena caval blood from groups 1, 2 and 3 were identified. grew mixed aerobic and anaerobic T41 Group 1: gastroenteristis, 142 patients, organisms. Group 4 cultures were sterile. Controlled comparison of enemas contain- 19 infants had pyloric stenosis and 11 an Lungs were inflation preserved for scanning ing lg and 2g 5 aminosalicylic acid in intussusception, 11 children had appen- on September 30, 2021 by guest. Protected copyright. electron microscopy (SEM). Scanning elec- patients with ulcerative proctosigmoiditis. dicitis and 38 adults had inflammatory tron microcopy sections at 300x and 1000x bowel disease, 12 colonic neoplasia and from group 3 were identical to controls. J POWELL-TUCK AND R A PARKINS (Depart- others a wide variety of other problems. of Pancreatitis caused marked derangement ment of Gastroenterology, Charing Cross The children with appendicitis all had com- lung architecture with incompletely Hospital, London) We report a double plictions at surgery and 65% of the adults expanded alveoli, which had oedematous blind trial of enemas containing lg and 26 5 with colitis required urgent colectomy distorted walls. Lining cells were disrupted, amino-salicylic acid (5ASA) in 25 patients despite the use of an intensive steroid regi- cracked and covered in debris. The Chetty with ulcerative colitis diagnosed clinically, men after diagnosis. In four patients with model of pancreatitis produces bac- sigmoidoscopically, and histologically and inflammatory bowel disease and three with teraemia. Pancreatitis is necessary for lung shown on barium enema to be confined to colonic neoplasia the diagnosis was abnormalities to develop, however, as ani- the rectosigmoid. Patients were included if obscured and delayed by the positive cul- mals bacteraemic from a small bowel loop they had active disease and were taking no ture of a common infecting organisum. 30 preparation are free from SEM abnor- treatment patients annually with a specific gastro- malities. medication for its except sul- phazalazine (SASP) which was continued in enteritis also develop the signs of unaltered dose. The trial lasted 28 days with peritonitis, these patients tend to settle and T40 assessment at entry and days 14 and 28 by laparotomy can often be avoided. clinical of bowel fre- Group 2: infectious hepatitis, 33 patients: Born again spleen - but is there life after grading malaise, death? quency, stool consistency, rectal bleeding, the jaundice was due to pancreatic car- sigmoidoscopy and rectal biopsy and possi- cinoma in 63% and choledocholithiasis in S NICHOLSON, G H HUTCHINSON, T HAWKINS. ble side effects. Twelve patients (six taking 33%. Six patients had 20 hepatic carcinoma. B PAUL, AND C W VENABLES (Departments SASP) were randomised to receive each Group 3: pyrexia of unknown origin, 11 Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1144 The British Society ofGastroenterology patients: this group included cases of occult treatment for CC provided the rectum is ence in the West Midlands suggests other- abdominal absesses, cholangitis, chronic minimally involved. wise. This study reports data on cases of UC pancreatitis and gonnococcal peritonitis. and CD in immigrants from throughout the We conclude that patients thought to region collected by the Midland Gastroen- have an infectious disease often have surgi- T44 terologial Society. cal problems and that specific gastroen- Are there ethnic differences in inflammatory Eleven hospitals have contributed 126 teritis may mimick the surgical acute abdo- bowel disease in England? patients to this study. One hundred and two men but that in these cases laparotomy can were diagnosed as having UC, 24 as CD. Of often be avoided. A KESHAVARZIAN. S GUPTA. S H the UC patients, 88 were Asian, 10 were SAVERYMU1TU, AND H J F HODGSON (Royal West Indian and four were from other coun- Postgraduate Medical School, Ham- tries. The average number of years resident T43 mersmith Hospital, London) Environ- in the UK by.first generation immigrants Ileorectal anastomosis in the treatment of mental, racial and familial facters are all before developing symptoms was 11 (range inflammatory bowel disease (IBD) relevant to the epidemiology of inflam- 1-41). Of the CD patients, 19 were Asian, matory bowel disease (IBD). Inflammatory four West Indian and one was from another J C COOPER AND N S WILLIAMS (Ulniversity bowel disease has been increasingly recog- country. The average number of years spent Department of Surgery, The General Infir- nised in immigrants, however the mag- in the UK by first generation immigrants mary, Leeds) The place of colectomy and nitude of the problem, and relative propor- before developing symptoms was 11 years ileorectal anastomosis (C+IRA) in the sur- tion of immigrant patients residing in the (range 2-21). gical management of IBD remains controv- UK having ulcerative colitis (UC) and In one centre, 150 new patients with UC ersial. In Crohn's colitis (CC) there appears Crohn's disease (CD) has not been studied. and 66 with CD have been entered into a to be a greater risk of recurrence whereas in In this survey, we have determined the long term prospective study over a seven ulcerative colitis (UC) there is the risk of types of idiopathic inflammatory bowel dis- year period; of these 29 patients (13%), malignant change. ease present in patients of two immigrant were of Indian or West Indian origin, 24 The outcome of 59 patients who under- groups of different racial background and (16%) had UC, five (8%) had CD. The went C+IRA (10 anastomosis n=40; 2° compared them with Europids. Of the 250 Indian and West Indian population is 15% anastomosis n=19) between 1955 and 1982 patients attending a single IBD clinic 10-8% of the total population. Furthermore, from were reviewed. In all cases the macroscopic were Indian (from the subcontinent or East estimated current prevalence rates of 80 per appearance of the rectum at the time of Africa) and 3-6% Caribbean. The propor- 105 population for UC and 30 per 105 for surgery was either normal or showed mild tion of immigrants in IBD clinic was similar CD, 31 immigrants would be expected to inflammation. Thirty seven operations to the chest and antenatal clinics in the same have had UC and 12 CD; the observed were performed for CC (mean age 35+ hospital. Among the Indians 78% had figures were 38 and six respectively. SEM 2 years; M:F 8:29) and 22 for UC (39+ UC, 22% had CD. Among the West Indians This study suggests that the prevalence http://gut.bmj.com/ 3 years; M:F 8:14). Operative mortality was 22% had UC, 78% had CD. Among and incidence of inflammatory bowel dis- 8% for CC and 0% for UC. Seven patients Europids 42% had UC, 58% had CD. ease in the Indian and West Indian popula- (18.9%) with CC suffered a clinical anas- Ulcerative colitis was significantly more tion is similar to-the native population. tomotic leak compared with three patients common amongst the Indian patients with (13-6%) with UC. Nine of these ten patients IBD than the Europids (X2= 12-31, had undergone a 1° anastomosis. p<0-001) or the West Indians (X2=9 03, T46 Overall follow up was 7-2±1 years, and at p<0-01). In both immigrant groups similar Abnormal pulmonary function in ulcerative the time of review 11/30 patients (37%) with high proportions (over 78%) of patients colitis on September 30, 2021 by guest. Protected copyright. CC, and 6/19 patients with UC (32%) had were non-smokers. The data indicate that undergone re-operation for recurrent dis- IBD occurs in immigrant racial groups and I M CHESNER, A WILLIAMS, J OSMAN, D E STAB- ease. Cumulative re-operation rates at 10 the pattern differs between Indians and LEFORTH, AND P ASQUITH (The Alastair years however were 76% and 73% respec- West Indians. Whether this reflects genetic, Frazer and John Squire Metabolic and Clin- tively. No case of carcinoma of the rectum or environmental factors remains uncer- ical Investigation Unit, East Birmingham has occurred and the patients in both groups tain. Hospital, Birmingham) The association with an intact IRA enjoy good health with a between non-smoking and ulcerative colitis stool frequency of 4-6/day. (UC) remains unexplained but recently it The results suggest that the outcome of T45 has been suggested that UC is characterised C+IRA in terms of recurrence is similar for Non-specific inflammatory bowel disease in by a change in smoking habit and that smok- UC and CC. Anastomotic leakage can be immigrants: incidence and prevalence in the ing may confer some protection against reduced by delayed anastomosis. Although Midlands UC. The effect of pulmonary pathology in the re-operation rate was high in both association with UC has never received con- groups, many young patients avoided an E T SWARBRICK, R D MONTGOMERY, P W sideration. We have therefore studied the ileostomy and pelvic nerve damage and DYKES. R H GRACE. J A LLOYD. AND R N pulmonary function and smoking habit of52 remained in good health for several years. ALLAN (New Cross and Royal Hospitals, unselected patients with UC compared with As mucosal proctectomy with an ileal Wolverhampton, and The East Birmingham 57 age and sex matched controls with non- reservoir, the alternative sphincter saving and General Hospital, Birmingham) While inflammatory bowel disease. Eight of 52 procedure for the treatment of UC, is ulcerative colitis (UC) and Crohn's Disease (15%) of UC patients were current smokers contra-indicated in Crohn's disease, we (CD), are often thought to be uncommon in compared with 29/57 (51%) of controls recommend C+IRA as first line surgical Asian and West Indian immigrants, experi- (p<0.01). However, 24/52 (46%) were ex- Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society ofGastroenterology A1145 smokers compared with 5/57 (9%) of con- which respiratory tract viruses account for H McKENZIE, J MAIN, D PARRATr, AND C R trols (p<0-01) demonstrating that UC is the major proportion (40.8%). PENNINGTON (Department of Bacteriology, associated with a change to non-smoking Ninewells Hospital, Dundee and Depart- rather than life long non-smoking. There ment of Medicine King's Cross Hospital, was no difference in the mean number of Dundee) IgA containing immune com- cigarettes smoked expressed as pack years, T48 plexes have been shown in the sera of UC 22-8, controls 25.5. Airway obstruction Specificity of "'In-granulocyte scanning and patients with inflammatory bowel disease (FEVI/FVC<65%) was found more fre- faecal excretion measurement - an (IBD) by means of a conglutinin binding quently in UC's 7/52 (13%) compared with autoradiographic study ELISA assay. In 13 patients with Crohn's, 1/57 (1-7%) in controls (p<0-05). Disease disease, the mean levels of IgG and IgA activity did not correlate either with airways A KESHAVARZIAN, Y E PRICE, A M PETERS, J P complexes respectively were 39 .tg aggre- obstruction or with current smoking habit. LAVENDER, N WRIGHT AND H J F HODGSON gated IgG equivalent/ml, range 13-105, and In conclusion, this new finding of signifi- (Royal Postgraduate Medical School, Ham- 76 arbitrary units IgA/ml, range 14-178. cant airways obstruction in association with mersmith Hospital, London) "'In-WBC These were significantly higher than the UC may be an important factor in influenc- scanning is now a well-established corresponding values in seven control sub- ing the change in smoking habit of these technique for diagnosis and assessment jects of 16 ,ug aggregated IgG equivalent/ patients. of inflammatory bowel disease (IBM). ml, range 7-33, and 26 arbitrary units IgA/ "'-Indium is used to label granulocytes in ml, range 944 (p<0-01, Mann-Whitney vitro, and then cells are subsequently test). In seven patients with ulcerative col- T47 injected intravenously. The isotope itis, mean levels of immune complexes were Role of intercurrent infections in acute localises in inflamed bowel and sub- 23 ,tg of aggregated IgG equivalent/ml, exacerbation ofchronic inflammatory bowel sequently can be counted in faeces. The val- range 10-65, and 57 arbitrary units IgAJml, disease idity of the test in distinguishing cell loss range 10-180. Gel filtration of selected from protein losing enteropathy critically Crohn's disease sera has shown that depends on stability of granulocyte label- HO KANGRO, SK FCHONG, RB HEATH, ANDJ A immune complexes measured by the con- WALKER-SMITH (Department of Virology ling. We have therefore investigated this, glutinin binding assay are heterogeneous in and Child Health, St Bartholomew's Hospi- using an autoradiographic technique, in size, but that in general the IgA complexes tal, West Smithfield, London) Between nine patients in whom"' In granulocyte scan are significantly larger than IgG complexes. October 1981 and June 1983, 85 children and colonoscopy were carried out simul- There have been many reports of raised with chronic inflammatory bowel disease taneously. "'In autologous granulocytes levels of immune complexes in IBD, but (CIBD) were investigated serologically to were injected three to four hours before col- there is little information available on their determine the role of intercurrent virus onoscopy, and intraluminal fluid, mucosal composition. Detailed analysis is essential infections as a cause of acute exacerbations. brushings, and colonic biopsies were col- to ensure that in vitro immunoglobulin http://gut.bmj.com/ Altogether 151 episodes of acute onset lected during the colonoscopic procedure. aggregates do not produce false positive gastrointestinal symptoms were recorded. In two patients with no histological evi- results. Our findings provide the first direct There was no definite seasonal pattern, dence of inflammatory bowel disease, and evidence of IgA involvement in immune although peaks of incidence occurred dur- three with clinically and histologically inac- complex formation in IBD, and it should be ing the winter months and in April/May tive disease, no "l'In was detected in fluid, possible to establish whether the IgA is sys- brushings or biopsies. In patients with in each year, coincidentally with peaks of " temic or secretory origin. respiratory tract infection (RTI). active disease, 88% of the '1Indium activity There was no difference in the prevalence in colonic fluid was precipitated by low on September 30, 2021 by guest. Protected copyright. of antibody to 11 viruses, Mycoplasma speed centrifugation. Autoradiography T50 and confirmed that the label remained attached pneumoniae, Chlamydia psittaci to whole in colonic fluid and Histopathological features of focal lesions in Coxiella burnetti between children with granulocytes the jejunal mucosa in Crohn's disease are children of similar mucosal brushings. Studies on biopsies, at CIBD and 79 control half hours follow- consistent with a cell-mediated immune age. intervals up to four and a response Follow up serum specimens were ing labelled granulocyte injection, showed labelled neutrophils on the inflamed epithe- obtained from 72 of the children with CIBD J H ENTRICAN, A BUSUTTIL, AND ANNE and in these, 49 intercurrent infections were lial surface, with occasional neutrophils in FERGUSON (Gastrointestinal Unit and diagnosed during the study period. Twenty crypt abscess by three hours. We conclude Department of Pathology, Western General seven (55%) of these infections were caused that the technique of '1In-granulocyte scan- Hospital, Edinburgh) Cell mediated by the respiratory viruses: influenza, ning and faecal counting in patients with immune responses in the small intestine are parainfluenza and respiratory syncytial IBD are specifically measuring cell loss; characterised by an increase in intra-epithe- virus, and 22 were systemic infections. labelled neutrophils are capable of migrat- lial lymphocyte numbers and in crypt Altogether 20 (40.8%) infections - 10 ing through the gastrointestinal mucosa, in length, with or without a reduction in villous respiratory and 10 systemic - were accom- active disease, within three hours of length. With the introduction of peroral panied by acute gastrointestinal symptoms. administration. jejunal biopsy, minor non-specific abnor- Our study shows that the frequency of malities of jejunal mucosal architecture intercurrent virus infections is not increased have been observed in Crohn's disease, in children with CIBD. Such infections, T49 however no formal measurements of crypt however, are frequently associated with Circulating IgA immune complexes in and villous length have been carried out. episodes of acute exacerbation of CIBD of inflammatory bowel disease The intra-epithelial lymphocyte (IEL) Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1146 The British Society ofGastroenterology count in jejunal biopsies from patients with was no significant rise in transformation in UC: 1-12+0-19, n=9, p<0.001). Crohn's Crohn's disease has been reported to be controls by comparison (24842±13938 to disease and UC PBL responses were normal. 24570± 13577). The mean percentage reduced in AB plasma, but this was only sig- A study of jejunal biopsies from 33 monocyte induced suppression calculated nificant for UC cells at a suboptimal dose of patients with Crohn's disease, in whom the from these results are 42-6±20 for CIBD as Con A (0-625 ,ugm/well), p<0-05. Crohn's sites of macroscopic disease were known, against -7-62±36-7 for controls, a differ- disease cells required a higher concentra- has revealed the presence of focal lesions in ence which is highly significant. Percentage tion of Con A for peak response than CO 10 biopsies. These focal abnormalities con- monocyte count was also significantly ele- (X 2=10-2, p<0-01). In autologous plasma, sisted of ulcers, fissures and granulomas, vated in patients (22±10%) versus controls peak responses of CD cells to both mitogens and their occurrence was independent of 6+1.3%). There was a good correlation was reduced compared with AB plasma the presence of macroscopic jejunal dis- between percentage monocyte count (PHA, p<0-01; Con A, p<0.02). ease. Comparison of the IEL counts and and percentage monocyte suppression Cell mediated immunity is abnormal in crypt and villous length measurements in (r=0-81). IBD. In UC this appears to be due to an Crohn's biopsies with and without a focal In summary, the reduction in lymphocyte abnormal PBL OKT4: OKT8 ratio. In con- abnormality with biopsies from normal con- transformation seen in inflammatory bowel trast, in CD there is a qualitative cell defect trols has been made. A highly significant disease appears to be mediated by the rela- and abnormal factors in plasma. increase in IEL count was found in those tive monocytosis seen in this condition. biopsies with a focal abnormality (x=67.2 Pure lymphocyte transformation is in fact SEM=9 5 per 100 epithelial cells) com- enhanced. The exacerbations of inflam- T53 pared to those without a focal abnormality matory bowel disease seen following Possible role for anti-idiotypic antibodies in (x=32 SEM=1-7). Likewise a highly sig- therapy with anti-prostaglandin agents, Crohn's disease nificant increase in crypt length occurred in such as indomethacin, may result from the those biopsies with a focal abnormality lifting of monocyte induced suppression. C O'MORAIN, R JAEGER, AND K M DAS (x=387 Am SEM=54-9) compared to those (Albert Einstein College of Medicine, biopsies without a focal abnormality Bronx, NY, USA, and the Adelaide and (x=122 gm SEM=9-2). These findings are T52 Meath Hospitals, Dublin, Ireland) consistent with a local cell-mediated Abnormal cell mediated immunity in inflam- Immunological mechanisms have been immune response at focal lesions in the matory bowel disease implicated in the aetiology and jejunal mucosa in Crohn's disease. pathogenesis of Crohn's disease (CD). C C AINLEY, J CASON, R A WOLSTENCROFT, P W Idiotypic and anti-idiotypic antibodies (Id- N KEELING, AND R P H THOMPSON (The anti-Id) have a role in autoimmune diseases T51 Gastrointestinal Laboratory, Department of characterised by remissions and exacerba- Lymphocyte transformation in inflammat- Immunology, St Thomas' Hospital, Lon- tions. The aim of this study was to see if Id- http://gut.bmj.com/ ory bowel disease - effect of the monocyte don) Abnormal cell mediated immunity anti-Id occurred in Crohn's disease. IgG suppressor cell (CMI) in inflammatory bowel disease was purified from sera of healthy volunteers (IBD) is controversial because limited indi- (n=12), Crohn's disease (n=15) and D KELLEHER, A MURPHY, C FEIGHERY, C A vidual studies use differing methods and patients with ulcerative colitis (n= 10). WHELAN, P W N KEELING, AND D G WEIR patient groups. Cell mediated immunity Antisera was raised in Balb/c mice against (Departments of Clinical Medicine and was studied in detail in 27 patients with IgG from normal volunteers and Crohn's Immunology, Trinity College and St. Jame's Crohn's disease (CD), 13 with ulcerative disease and ulcerative colitis patients. A Hospital, Dublin, Eire) Previous studies proctocolitis (UC) and 25 controls (CO). radioimmunoassay was developed and stan- on September 30, 2021 by guest. Protected copyright. have shown impairment ofthe cell mediated Delayed hypersensitivity skin testing to dardised using IgG as the solid phase anti- immune response in inflammatory bowel four recall antigens was assessed as the sum gen antisera to IgG as the antibody and 35S- disease. Experiments using mixed popula- of diameters of reactions. Peripheral blood labelled monoclonal mouse anti K chain as tions of mononuclear cells have suggested lymphocytes (PBL) were counted and T cell the second antibody. IgG from the three reduced lymphocyte transformation. populations estimated using OKT mono- groups were coincubated with the antisera To investigate the effects of the monocyte clonal antibodies. Peripheral blood lym- in a competitive binding assay. The control suppressor cell on lymphocyte transforma- phocytes transformation responses to IgG inhibited bind by 42+7%, ulcerative tion, we performed lymphocyte transforma- graded doses of phytohaemagglutinin colitis IgG by 38+8% and 11 of 15 patients tion studies in the presence and absence of (PHA) and concanavalin A (Con A) were with Crohn's disease IgG by 52+10%. Four indomethacin. The monocyte can suppress measured by tritiated thymidine incorpora- of patients with Crohn's disease did not lymphocyte transformation by prostaglan- tion in 72 hr cultures containing either 10% inhibit the binding at all and rather din production, and the alteration in trans- autologous or pooled AB plasma. enhanced the binding by 10%. This was formation induced by indomethacin allows Skin reactions were reduced in CD and observed when the assay conditions were calculation of the percentage monocyte UC (CO: 48-5 mm±7-1, n=11, v CD: Crohn's disease IgG as the solid phase and induced suppression. The percentage 20-5+4-3, n=21, p<0-001, and UC 25-4± antisera to that IgG as the antibody. These monocyte count was also assessed using the 4-0, n=11, p<0-005; mean±SEM). In CD four patients had systemic manifestations of MO2 monoclonal antibody. In 21 patients and UC there was a small reduction in PBL arthritis. All four sera were negative on with inflammatory bowel disease mean counts. The percentage OKT3+ cells, and latex agglutination and two were positive by transformation with 5 ,ug/ml of Con A rose the OKT4+ ('helper'): OKT8+ ('suppres- C Iqbinding assay. The explanation of these from 22641±10287 to 38807±12859 on sor') ratio were normal in CD, but in UC the results could be that patients with extrain- addition of indomethacin (p<.01). There ratio was reduced (CO 1-93±0-07, n=14, v testinal manifestations of arthritis have cir- Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society ofGastroenterology A1 147 culating anti-idiotypic antibodies in the IgG and there was no relation between zinc (Department of Gastroenterology, Llan- fraction that cross-react with the IgG to levels and CMI. dough Hospital, Penarth, S Glamorgan) enhance binding. Characterisation of the Malnutrition, but not zinc deficiency, Although functional bowel disorders are antibody would be important in the causes impaired CMI in CD. known to be common, associated and treat- pathogenesis of Crohn's disease. able depressive illness is often overlooked. To determine the value of screening and the incidence of depression as indicated by the PLENARY SESSION self-administered Beck depression inven- T54 T55-59 tory (BDI), 110 consecutive referrals to a Malnutrition, but not zinc deficiency, causes gastro-intestinal/general medical clinic depressed cell mediated immunity in completed the inventory - 100 satisfactor- Crohn's disease T55 ily. Alternate BDIs were retained unseen as A new gastroenterologist in a district general controls. From a maximum score of 39, nine C C AINLEY, J CASON, B M SLAVIN, R A hospital and is there a need for more of patients scored more than 16 (severe depre- WOLSTENCROFT, P W N KEELING, AND R P H them? ssion), 20 from eight to 15 (moderate), 21 THOMPSON (The Gastrointestinal Labora- from five to seven (mild) and 50 less than tory, Department of Chemical Pathology, W R BURHAM (Department of Gastroen- five (normal). The highest score was 30. Department of Immunology, St Thomas' terology, Oldchurch Hospital, Romford, Appropriate investigation failed to reveal Hospital, London) Malnutrition, in par- Essex) Thirty two senior registrars were organic disease in 33 of the 50 depressives ticular zinc deficiency, may be important in appointed as consultant gastroenterologists (66%), two thirds of whom presented with the depressed cell mediated immunity between 1980 and 1982, often replacing a abdominal pain or symptoms of irritable (CMI) of Crohn's disease (CD). Cell general physician. Analysis of discharge bowel syndrome. The BDI diagnosis of mediated immunity was studied in detail in summaries and other records indicate the depression was disregarded in 13 patients, 27 patients with CD and related to their nut- workload of one of these. The numbers of nine of whom were only mildly depressed rition and zinc status. in-patients on the firm were similar before and eight of whom had associated organic Delayed hypersensitivity skin testing to and after the appointment (1980; 802 admis- disease. Sixty six per cent of the severe four recall antigens was assessed as the sum sions; 1982; 868 admissions), but the prop- depressives were, however, correctly diag- of diameters of reactions. Peripheral blood ortion with gastrointestinal conditions nosed and appropriately treated, 55% of lymphocyte (PBL) populations were esti- increased from 11% to 19%. This was the moderate and 29% of the mild. No nor- mated using OKT monoclonal antibodies. because of an increase in referrals from all mal patient was given anti-depressants. Peripheral blood lymphocyte transforma- sources and some diagnostic transfer. For Knowledge of the BDI score increased the tion responses to graded doses of diagnosis from 8/22 (36%) to 16/28 (57%). example, more patients were diagnosed as http://gut.bmj.com/ phytohaemagglutinin (PHA) and con- having pain of oesophageal rather than The BDI showed that half of new outpa- canavalin A (Con A) were measured by uncertain cause; when these two diagnostic tients were depressed and the majority of tritiated thymidine incorporation in 72 h groups were combined, a significant reduc- these had no other organic disease. cultures containing either 10% autologous tion was found in the number staying more or pooled AB plasma. Nutrition was asses- than seven days (1980; 13 of 54: 1982; three sed from anthropometric measurements, of 48: X2=4*83, p<005); this was perhaps T57 plasma albumin and retinol binding pre- related to the increased availability of Cholecystectomy rates in the United States albumin (RBPA). The zinc contents of and the United Kingdom compared: does the endoscopy. on September 30, 2021 by guest. Protected copyright. plasma and separated peripheral blood New outpatient attendances per month difference matter? polymorphonuclear and mononuclear increased from 50 to 84 in two years; 96% leucocyte subpopulations were measured were for gastrointestinal problems. Endos- T BATE, P J GODFREY, M HARRISON, B WALSH, by atomic absorption spectrophotometry. copies performed increased by 14 times in AND D H LEVIEN (William Harvey Hospital, Fifteen patients were normal (N) and 12 three years to 1473 in 1983; 75% of these Ashford, Kent. New Rochelle Hospital Med- malnourished (MAL), being <90% of ideal were abnormal. In 100 cases, the endos- ical Centre, New York, USA) Chole- body weight. Albumin but not RBPA was copic and clinical diagnosis differed in 38% cystectomy rates are higher in N America reduced in MAL compared with N, p<0-01. but only in 15% might this have resulted in than the UK and this may be partly due to The two groups were well matched for age, serious problems. Limited facilities have an increased prevalence of gall stones. If, sex, drug treatment, and duration, activity impaired patient care. The gastroen- however, there is a real difference in surgi- and site of disease. Skin reactions were terologist's work load was much greater cal practice, what is the consequence? reduced in MAL 15-0±5-9, n=11, v N than that stated in a recent report. This We have compared two necropsy series, 26-5±6-6, p<005. Peripheral blood lym- suggests that there may be an urgent need one from a US suburban hospital and the phocyte counts and T cell populations were for more consultant gastroenterologists in other from a partly rural UK health district similar in N and MAL. In AB plasma, MAL the UK. in which the biliary tract was specifically peak responses to PHA (p<0.01) and Con examined in each case for gall stones (A) or A (p<0.01) were reduced compared with a cholecystectomy scar (B). In the US series N. In both groups, peak PBL responses T56 of 1000 subjects, gall stone disease (A+B) were reduced in autologous plasma com- Beck depression inventory screening of was found in 33% of women and in the UK pared with AB plasma. While plasma and Gastro-intestinal outpatients series of 1701, 24%. The male prevalence of polymorphonuclear zinc was reduced in gall stones was 20% in the US series and MAL, mononuclear levels were normal, J D R ROSE, A H TROUGHTON, AND P M SMITH 12% in the UK series. The cholecystectomy Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1 148 The British Society ofGastroenterology rates for those with gall stone disease patients could be expected to have been gastrointestinal continuity should be consi- (B/A+B) for women were, however, US, detected at an earlier stage of disease by dered in all elective operations. 39% versus UK, 15% and for men, US, more prompt diagnosis. 35% versus UK 5%. The overall cholecys- Delay in diagnosis does not appear to be tectomy rate was 51/2 times greater in the US a major contributing factor to the all too fre- series and, even allowing for the higher pre- quent late presentation ofcolorectal cancer. valence of gall stones, was still 31/2 times the It would seem the key to diagnosis at an rate in the UK series. There were 11 gall earlier stage of the disease must rest with COLORECTAL stone related deaths in US series (1.1%) of presymptomatic detection. F1-8 which six were postoperative, compared with 10 such deaths in the UK series (0.6%) Fl of which four were postoperative. The T59 Early detection of carcinoma in sigmoid operative mortality for cholecystectomy in Changes in the surgical management of diverticular disease the US hospital was 2-2% and in the UK dis- ulcerative colitis trict was 1-1%. A COWIN, D G KARAMANOLIS, P B BOULOS, P R Neither the hospitals nor the populations D G NASMYTH, D JOHNSTON, AND N S WIL- SALMON, AND C G CLARK (Department of served are strictly comparable. We found LIAMS, (University Department of Surgery, Surgery, Faculty of Clinical Sciences, Uni- no evidence, however, to support the idea The General Infirmary, Leeds) Mucosal versity College London, and The Rayne that a higher cholecystectomy rate leads to a proctectomy (MP) or intersphincteric dis- Institute, London) The sigmoid colon is a lower, operative mortality and therefore a section (ISD) permit the eradication of rec- common site for diverticular disease and lower overall death-rate from gall stone dis- tal disease in ulcerative colitis (UC) without neoplasia but the frequency of their coexis- ease. It is concluded that there is no demon- the risk of damage to pelvic nerves. After tance is not clear. With increasing fre- strable advantage to be gained from increas- mucosal proctectomy, gastrointestinal con- quency of colonic cancer, precision in diag- ing the present cholecystectomy rate in the tinuity may be restored by ileo:anal anas- nosis is necessary but radiological diagnosis United Kingdom. tomosis (IAA) with or without a pelvic has its limitations because of the difficulty in reservoir (RES). The impact of these proce- outlining the mucosa in the presence of dures on surgery for UC is presented in a diverticulae. This study therefore investi- T58 consecutive series of 80 patients who under- gates this clinical problem. Symptom duration and pathologic staging of went their first operation for UC between In 105 symptomatic patients reported to colorectal cancer 1977 and 1984. have sigmoid diverticulae on barium Thirty three (41%) cases were emergen- enema, colonoscopy was performed. There R S STUBBS AND M G LONG (introduced by PRO- cies and the rectum was conserved in 29 were 42 men and 64 women whose age FESSOR L H BLUMGART) (Hillingdon and (88%), 22 (67%) underwent subsequent medians and ranges were 72 (47-85) and http://gut.bmj.com/ West Middlesex University Hospitals, elective surgery. Of the 80 patients, 25 68-5 (45-89) years respectively. In 31 Middlesex) Delays in diagnosis are often felt (31%) underwent MP+IAA+RES, 6 (8%) patients (group A) the barium enema to be responsible for the late presentation MP+IAA, 5 (6%) MP+caeco-anal anas- showed polyps in 29 and carcinoma in two and hence poor prognosis seen in so many tomosis, 19 (24%) MP/ISD+ileostomy, 5 but colonoscopy confirmed polyps in 11 and patients with large bowel cancer. The pre- (6%) panproctocolectomy, 10 (12.5%) ileo- excluded the others. In 74 patients (group sent prospective study examines the dura- rectal anastomosis, and in 10 (12.5%) the B) the barium enema showed diverticular tion of symptoms and stage of disease in 211 rectum was defunctioned. disease alone but colonoscopy revealed consecutive patients with colorectal cancer. The results of IAA+RES are good in 19 polyps in 22 and carcinoma in three. The on September 30, 2021 by guest. Protected copyright. Patients were allocated to one of four (86%) after restoration of gastrointestinal polyps were adenomas and in two patients groups according to the duration of continuity. The mean frequency of defaeca- in each group were malignant graded symptoms; 0-3 months, 3-6 months, 6-12 tion is 5-8/24 hours. All patients evacuate Duke's A. The carcinomas were Duke's B months, and over 12 months. Tumours were spontaneously without intubation and 75% in two and Duke's C in one. staged according the Dukes classification can defer defaecation for over 30 minutes. Therefore 36 (34%) patients had coexis- with the addition of stage D to include those Overall the functional results of IAA were tant neoplasia, benign in 29 (27.6%) and patients with distant metastases. Four better with a reservoir. malignant in seven (6-6%). The peak age patients could not be staged. The mean + The operative mortality was 0% in elec- incidence was 60-80 years with a 3:1 female SE duration of symptoms for Dukes A tive and 6% (n=2) in emergency cases. to male distribution; five carcinomas were patients was 11-2±2-6 months; for Dukes B Twenty four per cent (n=6) of IAA+RES in women and two men. Similar number of patients 4.9+0.6 months; for Dukes C, underwent re-operation for early complica- patients had abdominal pain or change in patients 5-3±0-7 months; Dukes C2 patients tions, and 16% (n=4) for late complica- bowel habit as in the remaining 69 patients 3-9±1-9 months, and for Stage D patients it tions, compared with 23% (n=8) and 15% without neoplasms but 22 with and 26 was 3-8±0-6 months. In summary there was (n=5) where gastrointestinal continuity was without neoplams had rectal bleeding no tendency for a longer symptomatic not restored. No bladder or sexual dysfunc- (p<0-025). period in patients with late stage disease. tion has been reported. Hence both This study shows that patients' symptoms Indeed the reverse was the case. Dukes A mucosal proctectomy and intersphincteric are not diagnostic and as the barium enema patients had a significantly longer duration dissection are safe and preferable to pan- was inaccurate in 45 (43%) examinations, of symptoms than Stage D patients proctocolectomy in the surgical treatment routine colonoscopy or flexible sigmoidos- (p<0-01). In the light of current knowledge of UC. Preservation of the rectum is recom- copy is desirable but such a policy is concerning tumour growth relatively few mended in emergencies, and restoration of demanding. The results suggest that it is Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology Al 149 probably essential in patients more than 60 stimulation of the dorsal nerve of the penis ous and 13 metachronous). There were 53 years especially women and definitely all or clitoris and recording reflex contraction strictures, 14 fistulae, nine perforations and those with rectal bleeding. of the external anal sphincter. We have eight bleeds. The period between RT and utilised the presence and latency of the SER clinical manifestation of the lesion was as an index of SSC function in 14 patients approximately two years and was longer for F2 with chronic idiopatic constipation and strictures than for the other lesions. The Sigmoidoscopy/proctoscopy service with compared the data with 22 asymptomatic majority of the lesions were in the rectosig- open-access to general practitioners age-matched control subjects. All the con- moid (39) or mid and distal small bowel stipated patients had investigations to (34). Forty nine patients required one or I P DONALD, J S FITZGERALD FRAZER, AND S P exclude organic or systemic disease and more operations and review of the opera- WILKINSON (Gloucestershire Royal Hospital, none had previous abdominal surgery. Anal tive results up to 1977 showed a high inci- Great Western Road, Gloucester) Many sphincter manometry was also performed to dence of anastomotic leak and death after hospitals now offer barium enema examina- measure functional sphincter length, resting resection and primary anastomosis. We tions to general practitioners (GPs) on an and squeeze pressures and the' rectos- noticed, however, that the ascending, trans- open-access basis thus bypassing the tradi- phincteric reflex. The dorsal nerve of the verse and descending colons were relatively tional sequence of first carrying out a sig- penis and clitoris was stimulated electrically free of radiation-induced disease. Since moidoscopy. An open-access sigmoidos- using a surface electrode (duration 0.1 then we have used a non-irradiated part of copy service was therefore opened with msec, frequency 2Hz, voltage 3 to 4 times the colon for one end of the anastomosis. requests for a barium enema not being sensation threshold). Over 100 anal sphinc- Thus terminal ileal resection has been fol- accepted without prior sigmoidoscopy. ter responses were detected by a bipolar lowed by an ileo-transverse anastomosis During the first three and a half years surface platinum anal plug electrode and and rectosigmoid resection by mobilisation 1458 patients referred directly from their gp the digitally averaged response recorded. of the splenic flexure to bring the descend- were examined using a rigid sigmoidoscope. The procedure was repeated for each sub- ing colon down for anastomosis. Using The patient was also examined with a proc- ject. Reproducible responses were con- these techniques there has been one leak in toscope if thought appropriate. After the firmed in all cases. The control group had a 12 anastomoses and none of the 11 patients first year of the service a subsequent exami- latency range of 27*2-47.6 msec (mean have died. These results are significantly nation with a fibreoptic sigmoidoscope was 37-3±1-4 SEM). In contrast two patients in better (p<0-05) than our previous figures also carried out if the presenting symptom the constipation group had an absent SER, when 12 of 24 amastomoses leaked with 10 was bleeding and no cause for this found the remainder having a latency range of deaths. with the rigid instruments. 39 6-65-2 msec (mean 51-2±2-2 SEM). The We conclude that use of non-irradiated Five hundred and sixteen abnormalities prolongation of the SER latency in the con- bowel for one end of an anastomosis sig- were found to account for the patient's stipation group is significant (p<0-01; Wil- nificantly improves the results of resection symptoms in 506 patients, giving a diagnos- coxon's rank sum test). Sensation threshold of irradiated bowel. http://gut.bmj.com/ tic rate of 35%. The most common was piles and anal sphincter manometry did not show (307 cases). Other relatively common any significant differences between the two pathologies included inflammatory bowel groups. F5 disease (107), benign tumours (44) and These abnormalities of the SER in the Is the balloon expulsion test a valid measure malignant tumours (38). Of 41 patients sub- presence of normal peripheral sensation of the pelvic floor abnormality in slow transit sequently undergoing fibreoptic sigmoid- and anal sphincter function suggest an constipation? oscopy a cause for the bleeding was found in occult neurogenic dysfunction of the SSC in 32 the most common being a malignant some cases of chronic idiopathic constipa- A M ROE. D C C BARTOLO, J VIRJEE. AND N J on September 30, 2021 by guest. Protected copyright. tumour (16). tion. McC MORTENSEN (Departments of Surgery Most gps in the district have used the ser- and Radiodiagnosis, Bristol Royal Infir- vice and a questionnaire survey indicated mary, Bristol) Some patients with slow the majority to have fallen by almost two- F4 transit constipation (STC) have a pelvic thirds with the waiting time falling from up Development ofa rational surgical policy for floor abnormality. It has been suggested to nine months to only two weeks. the management of radiation-induced gas- that a ballon expulsion test is a useful mea- tro-intestinal lesions sure of this disorder. We have studied 12 patients (IIF, IM) F3 R B GALLAND AND J SPENCER (Department with STC (defined radiologically) and 16 Abnormal sacral spinal cord function in of Surgery, Royal Postgraduate Medical controls. After anorectal manometry, chronic idiopathic constipation School, Hammersmith Hospital, Ducane changes in the anorectal angle and perineal Road, London) Sixty patients (13M, 47F) descent on straining were measured on J S VARMA AND A N SMITH (University presented with radiation-injured gut be- proctograms and compared with the Department of SurgerylUrology, Gastro- tween 1958 and 1984. The median age at patient's ability to expel a 50 ml water-filled Intestinal Wolfson Laboratory, Western receiving radiotherapy (RT) was 54 years. balloon from the rectum. There were eight General Hospital, Edinburgh) The func- Radiotherapy was performed mainly for patients who could not (group A) and 4 who tion of neurones within the sacral spinal gynaecological (43) or urological (14) could (group B) expel the balloon. All con- cord (SSC) is essential for the normal malignancy. External RT was used in all trols tested could expel the balloon. mechanisms of defaecation. This site also cases, combined with internal treatment for There was no significant difference in mediates a polysynaptic sacral evoked cervical cancer. Eighty four gastrointestinal resting anal pressure between controls and response (SER) which can be elicited by lessions were produced (11 being synchron- group A or B. Medians and ranges were Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1150 The British Society of Gastroenterology controls 80 (60-105) cmH2O, group A 113 biopsy was a false negative for cytology, associated with reduced survival compared (60-145), group B 100 (85-120). Anorectal malignant tissue being seen histologically. with non-mucinous carcinoma. Over a angle significantly increased on straining in Intraoperative cytology can accurately seven year period there were 669 new controls but did not in group A or B. Mean assess lateral spread of rectal cancer and patients with colorectal cancer of known measurements in degrees at rest and on also determine lymph node status. histological type; 93 (14%) had mucinous straining were controls (n=11) 91-4±6.7 tumours. The pathological features and out- and 108-1±13-7 (p<0005); group A come of mucinous and non-mucinous car- 100-3±11-6 and 96-1±13*6 (p=NS); group F7 cinomas were compared. A higher propor- B 93-3±17-3 and 90-8±18-6 (p=NS). There A clearance technique for the detection of tion of patients with mucinous compared was no significant difference in perineal de- lymph nodes in colorectal cancer with non-mucinous tumours were <40 years scent on straining between controls and old (5% vs 2%:NS). The proportion of group A. Perineal descent, however, was S J CAWTHORN, N M GIBBS, AND C G MARKS mucinous tumours occurring in the right significantly greater in group B than con- (The Royal Surrey County Hospital, colon was greater than non-mucinous trols and group A. Medians and ranges in Guildford, Surrey) Lymph node met- tumours (27% vs 14% p<0.01), whereas cm below the pubococcygeal line were con- astases are the most important determinant the opposite held in the rectum (31% vs trols 1-7 (0.9-4.3), group A 1-5 (0.4-2-1) of prognosis after surgery for rectal cancer. 46%: p<0.01). More mucinous than non- and group B 3-2 (2.8-3.7) (p<0-02 com- A minimum number of lymph nodes must mucinous tumours were incurable at pre- pared with controls and p=0002 compared be identified in each specimen for accurate sentation (41% vs 28%: p<0-02). Polypoid with group A). Proctogram showed small staging of the tumour. In Guildford, a zylol/ adenomas were more often associated with rectocoeles in three of the four group B alcohol clearance technique is used to iden- mucinous than non-mucinous tumours patients. tify lymph nodes. We report a comparison (32% vs 22% :NS). Six per cent of mucinous We conclude that inability to expel a bal- between the numbers of lymph nodes carcinomas were multiple compared with loon from the rectum is a reflection of a pel- obtained from the mesorectum of patients 3% of non-mucinous cancers. Tumour vic floor disorder in which STC patients fail undergoing a randomised trial of pre-opera- resection rates were lower for mucinous to increase the anorectal angle on straining. tive radiotherapy at Guildford (n=51), St. than non-mucinous carcinomas, both over- When there is significant perineal descent, Mark's (n=50) and eight other centres all (83% vs 92%: p<0-02) and 'curative' however, the test may be misleading. Proc- (n=221). The total number of lymph nodes (61% vs 72%: p<0.05). Five year survival tograms give a more accurate indication of found in the Guildford series (mean rates, however, were similar both overall the dynamics of the pelvic floor disorder. =23-1±1-18 SEM) was significantly higher (29 and 37%) and after 'curative' resection than St.Mark's (m=10-9±0-86) and the (53% and 57%). Mucinous tumours of the other eight centres combined (m=11-65± right colon had better five year survival F6 0-4) (p<0-001). The total number of lymph rates, than at any other site (42% vs 17- Intraoperative staging of rectal cancer by node metastases was also significantly 30%). In Dukes' C tumours treated 'cura- http://gut.bmj.com/ imprint cytology higher in the Guildford patients (m=3-21 + tively' five year survival rates were better 0.58) when compared with the combined for mucinous that non-mucinous tumours S H SILVERMAN, JANET MOORE, H THOMPSON, eight centres (m=2-09±0-2) (p<0.05). The (37% vs 28% NS). AND M R B KEIGHLEY (Departments of distribution of lymph nodes was examined The outcome of mucinous colorectal car- Surgery and Pathology, General Hospital, by dividing the mesorectum into four zones, cinomas is similar to 'ordinary, carcinomas. Birmingham) Restorative anterior resec- and a significantly higher number of lymph The high proportion of advanced cases at tion for locally advanced tumours may be nodes were found in each zone of the presentation seems to be balanced by the followed by recurrence around the anas- Guildford patients. When the number of tendency for lymph node metastases to on September 30, 2021 by guest. Protected copyright. tomosis necessitating later A-P resection lymph nodes involved by tumour were com- remain localised for a longer time. or defunctioning colostomy. Subjective pared, these were significantly raised in the assessment of invasion of glands or perirec- lowest (supra-levator) zone (m=1-2±0-4) tal tissue by the surgeon can be misleading. compared with St. Mark's (m= 0.13±0-1) Intra-operative pathological examination of and the eight centres combined (m=0-4± the tumour bed and local lymph nodes 0-1). Using this clearance technique, we OESOPHAGEAUJGASTRIC would allow a more rational decision on the have detected increased numbers of lymph F9-18 type of resection to be performed. nodes finding more involved by tumour in After tumour mobilisation, biopsies from the supra-levator region ofthe mesorectum, the pelvic side walls, C1 and C2 lymph nodes a feature know to correlate with poor prog- Is a columnar-lined (Barrett's) oesophagus were examined by imprint cytology and sub- nosis. reversible with medical treatment? sequently by paraffin section histology. The result of cytological examination was availa- C J STODDARD, JANE E PATTERSON, AND D ble within 15 minutes. Fifty two biopsies (23 F8 FLOOK (Department of Surgery, Univer- nodes and 29 pelvic side wall tissues) were Clinical importance of mucinous carcinoma sity of Liverpool, Liverpool) A columnar examined. Cytology and histology concur- of the large bowel lined oesophagus (CLO) develops as a con- red in 48. In three (one node, two pelvic side sequence of gastro-oesophageal reflux wall tissue) malignant cells were seen H C UMPLEBY AND R C N WILLIAMSON (Uni- (GOR) and predisposes to the development cytologically but histology was negative. versity Department ofSurgery, Bristol Royal of an oesophageal adenocarcinoma. The From previous experience we feel these are Infirmary, Bristol) Mucinous carcinoma role of medical treatment in reversing this true positives for cytology. One further of the large bowel is reported to be epithelial change is unclear. Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society ofGastroenterology A1151 Twenty patients (16 men, four women) the solid portion of the meal and Indium- oesophagitis (16/23 and 14/23 respectively) with a diagnosis of CLO, based on endo- 113m DTPA to label the liquid portion. compared with minimal upright exposure scopic and histological examination, were Gastric emptying was measured for 90 (8/23) and total exposure (10/23). When treated with routine anti-reflux measures, minutes by a fixed scintillation detector and marked reflux in each period (exposure ranitidine 150 mg bd, metoclopramide 10 blood samples for hormone analysis were times >20%) was seen, the three hour post- mg tds and Gaviscon 10 ml qds for 12 taken basally and at 15, 30, 60 and 90 prandial recordings predicted more patients months. Oesophageal manometry and 24 minutes after meal ingestion. Emptying with oesophagitis (17/29) than the supine hour pH studies were performed before the index values for solid and for liquid compo- (8/29) or upright measurements (10/29). start of treatment. Patients were seen at nents of the meal were significantly smaller The results indicate that upright reflux three monthly intervals for symptomatic in patients than in control subjects, indicat- correlates at least as well as supine reflux review and repeat endoscopy and ing a delay in gastric emptying in the patient witb total acid exposure. A short period of oesophageal biopsy. At each endoscopy the group (p <0-01) (Wilcoxon's signed rank pH monitoring after a meal may be an distance of the squamocolumnar junction test). An analysis of variance, however, adequate predictor of the degree of acid from the incisor teeth, presence of detected no evidence of abnormal release of reflux demonstrable in a 24 hour monitoring oesophageal ulcers and strictures and posi- glucose, insulin, gastrin, neurotensin, GIP period. tion of the gastro-oesophageal junction or PP in the patient group. We conclude were carefully determined. that gastric emptying of solid and liquid Initially, all patients had GOR components of a meal is delayed in patients F12 symptoms, 19 had a hiatus hernia, 10 an with erosive oesophagitis but we have found Normal gastro-oesophageal reflux patterns oesophageal ulcer and six an oesophageal no evidence for a hormonal or vagal in young and middle-aged control subjects stricture. Gastro-oesphageal reflux symp- mediated mechanism for the motility distur- toms and dysphagia improved in 19 bance. B J COLLINS, R A J SPENCE, T G PARKS AND patients. Oesophageal ulcers healed com- A H G LOVE (Departments ofMedicine and pletely in seven patients and only two Surgery, The Queen's University of Belfast, needed a stricture dilating more than once. Fl1 Belfast) Abnormal gastro-oesophageal There was no evidence of significant Importance of upright and postprandial reflux is best detected by prolonged intra- mucosal regression in any patient. Thus this reflux in gastro-oesophageal reflux disease oesophageal pH monitoring. Published treatment regimen gives symptomatic control data with this technique are limited, improvement but does not lead to mucosal J S DE CAESTECKER, J N BLACKWELL, JOAN however, and no studies have assessed the regression. There is no evidence that medi- BROWN, AND R C HEADING (Department of influence of age on normal reflux patterns. cal treatment causes mucosal regression in Therapeutics and Clinical Pharmacology, We have monitored oesophageal pH for at patients with a CLO. Royal Infirmary, Edinburgh) Fifty two least 16 hours in 13 young asymptomatic patients underwent 23 hour ambulatory subjects, mean age 22 years, age range 19- http://gut.bmj.com/ intraoesophageal pH monitoring using a 30 years, and in 14 middle-aged FIO naso-oesophageal probe with its tip sited asymptomatic subjects, mean age 49 years, Gastrointestinal hormone release and gas- 5cm above the distal end of the lower age range 39-61 years. A pH sensitive tric emptying in reflux oesophagitis oesophageal sphincter. Recordings were radiotelemetry capsule and a portable made on a modified Holter portable recor- receiving system were used for ambulatory B J COLLINS, R J MCFARLAND, K D BUCHANAN, der. Twenty nine patients were being inves- monitoring, but all studies were conducted AND A H G LOVE (Department ofMedicine, tigated for suspected gastro-oesophageal during an overnight hospital stay so that The Queen's University ofBelfast and Royal reflux and 23 for recurrent chest pain. All activity of the volunteers could be stan- on September 30, 2021 by guest. Protected copyright. Victoria Hospital, Belfast) Delayed gas- patients were endoscoped and oesophagitis dardised. Data were analysed for frequency tric emptying has been recognised recently was detected in 29. and duration of daytime (erect) and noctur- in patients with reflux oesophagitis but its The acid exposure time was calculated as nal (supine) reflux episodes. When reflux mechanism has not been studied. Several the proportion of time with pH<4. Total was defined as a fall in pH to <4 pH units gastrointestinal hormones including gas- exposure time correlated well with upright young subjects experienced 0-235 (0-08- trin, neurotensin, and gastric inhibitory (daytime) and supine (night-time) exposure 0-58), median (range), daytime episodes/h, polypeptide (GIP), have been shown to (r=0-88 and 0-76 respectively), though and 0-1 (0-0-92) nocturnal episodes/h. influence gastric motility when infused there was a poor correlation between the Cumulative duration of the daytime intravenously. Vagal action is an important latter two (r=0-48). Exposure during the episodes was 1-3 (0-3-3-8) min/h and the regulator of gastric emptying and pancreatic three hour period after the evening meal nocturnal episodes, 0-15 (0-1-9) min/h. polypeptide (PP) blood concentrations pro- was calculated for each patient, and corre- Middle-aged subjects experienced 0.305 vide a crude index of vagal activity. Thus, lated well with the total exposure time (0-07-0.71) daytime reflux episodes/h and we have observed the release of glucose, (r=0-76). Although longer acid exposures 0-115 (0-0-26) nocturnal episodes/h. Dura- insulin, gastrin, neurotensin, GIP and PP were broadly associated with the presence tion of their daytime episodes was 1-98 after a test meal of beefsteak pieces, potato, of oesophagitis, 11/29 .patients with (0-42-3-21) min/h and the nocturnal and orange juice during gastric emptying oesophagitis had minimal supine reflux (ex- episodes, 0-19 (0-4-43) min/h. No statisti- studies in patients with erosive reflux posure time <5%) compared with 3/29 in cally significant difference was detected be- oesophagitis. Fifteen patients and 15 age both the upright and three hour post pran- tween young and middle-aged subjects for and sex-matched control subjects were dial studies. Minimal supine and post pran- either frequency or duration of daytime or studied. Technetium-99m sulphur colloid dial reflux (<5% exposure time) predicted nocturnal reflux episodes (Mann Whitney labelled chicken liver (8 g) was used to label the greatest number of patients without U test). Definition of a reflux episode as a Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1152 The British Society ofGastroenterology fall to pH <5 or pH <3 units, or as a drop in oesophageal high pressure zone. Oeso- hour pH monitoring using a radiotelemetry pH >2 pH units, did not alter the results of phageal pH was recorded in the memory of capsule (RTC) with standard nasogastric the comparison between the groups. We a portable microprocessor. Computer prog- aspiration over 24h. Eight studies were per- conclude that young and middle-aged con- rammes for interpretation of the formed on four male duodenal ulcer trol subjects have similar erect and supine oesophageal pH record allowed rapid com- patients in remission receiving either reflux patterns and it is acceptable to use parison of each patient with the cohort of placebo or an antisecretory agent. At 0800h young volunteers to establish normal values volunteers. Two analyses were used in both a 1OFG Salem sump nasogastric tube was in reflux studies of young and middle-aged the erect and supine position. The reflux passed and the RTC was swallowed and patients. event analysis calculated number and dura- fixed at 52 cm from the teeth. Gastric aspi- tion of reflux events, and the total time rates were taken half-hourly for the first five pH <4, and the cumulative acid exposure hours and then hourly until 0800h the next F13 analysis calculated percentage of all data day. The pH of aspirated samples was mea- Gastro-oesophageal reflux (GOR) in points below pH 3,4, and 5. sured immediately using a glass electrode. patients with chronic duodenal ulcer (DU) Patients were divided into three groups Continuous RTC pH was stored using a for the purpose of comparison with endo- Medilog recorder. The pH measurements D FLOOK AND C J STODDARD (Department scopic findings. Group 1 (n=69) consisted of gastric contents were compared with the of Surgery, University of Liverpool, Liver- of patients with classic reflux symptoms, RTC recordings at the same times. One pool) Gastro-oesophageal reflux (GOR) group 2 (n= 16) those with predominant hundred and eighty seven paired pH record- symptoms have been reported in 40% and abdominal pain and mild reflux symptoms, ings were analysed. A significant correla- oesophagitis in 26-68% of pre-operative and group 3 (n=26) those with previous gas- tion was found between RTC and aspirate duodenal Uilcer (DU) patients, yet DU tric operations. Endoscopy was done in all pH measurements (Spearman correlation patients are rarely investigated or treated patients and classified as normal, oeso- coefficient =0-9, p <0-01). No significant for coexistent GOR. After vagotomy, phagitis, or presence of stricture. The difference was found between median symptoms of GOR are less common but the Mann-Whitney U test was used to compare aspirate pH and median RTC pH for each prevalence of oesophagitis and the extent of groups of patients and volunteers. There individual (Mann-Whitney U test). Radio- GOR have not been quantified. was a stepwise increase in all parameters of telemetry measurements clearly showed the Fifty patients with DU were admitted for reflux using both analyses which were all onset of action of the antisecretory drug detailed symptomatic enquiry, endoscopy significantly greater than the volunteer val- (median 18, range 17-19min) and the buf- with oesophageal biopsy, oesophageal man- ues (p<0-05), and this corresponded to the fering effect of meals. This cannot other- ometry and 24 hour pH study before elec- endoscopic severity of inflammation. A wise be shown without very frequent aspira- tive surgery. The tests were repeated three positive pH monitoring test was defined as tion. Radiotelemetry pH monitoring is as months postoperatively and the results one in which any reflux parameter fell out- good as gastric sampling in the measure- compared. side the mean plus 3SD of the 35 volunteers. ment of 24h intragastric acidity. It allows http://gut.bmj.com/ Before and after vagotomy, respectively, Seventy three per cent of patients in group 1 continuous measurement of pH during nor- 50% and 12% of patients had symptoms of had positive tests, and 87% were identified mal acitivity without the supervision GOR, 30% and 32% had evidence of as acid refluxers using both endoscopy and required when using repeated aspiration. oesophagitis, 18% and 14% had a low value pH monitoring. Sixteen patients in groups 2 This technique accurately assesses the effect for lower oesophageal sphincter pressure and 3 had normal endoscopic findings, yet of drugs on gastric acidity. and 58% and 48% had an abnormal pH were identified as acid refluxers on pH study. monitoring. This study has shown the com- We conclude that GOR and oesophagitis plimentary nature of these tests, and that F16 on September 30, 2021 by guest. Protected copyright. are common in patients with chronic DU, pH monitoring especially identifies those Modified sham feeding: a measuring jug and that although symptoms of GOR are patients with early or quiescent gastro- ward test for completeness of vagotomy lessened by vagotomy, there is no evidence oesophageal reflux disease not seen on of a reduction in levels of GOR or in the endoscopy. A C ATHOW, A T SEWERNIAK, T P BARTON, M R prevalence of oesophagitis. LEWIN, AND C G CLARK (Department of Surgery, University College London, The F15 Rayne Institute, London) Sham feeding F14 Comparison of radiotelemetry with gastric has been advocated as an alternative to the Ambulatory oesophageal pH monitoring: aspiration in the measurement of 24 hour insulin test, as a check of completeness of correlation of computerised interpretation intragastric acidity vagotomy because of its safety and speed. of acid reflux with endoscopy In studies on 22 normal subjects and of 33 J R REYNOLDS, J P WALT, J D HARDCASTLE, A G preoperative patients with duodenal ulcer, W G CHEADLE, G C VITALE, S A SADEK, AND A CLARK, H L SMART, AND M J S LANGMAN volume responses to modified sham feeding CUSCHIERI (University Department of (Departments of Surgery and Therapeutics, for 15 minutes were equivalent to those of Surgery, Ninewells Hospital and Medical University Hospital, Nottingham) Hourly insulin (0-2 IU/kg bw) despite the fact that School, Dundee, Scotland) A com- gastric aspiration has commonly been used insulin at this dosage was a more powerful puterised system for ambulatory to assess the efficacy of antisecretory com- stimulant of acidity. Similarly,. when 28 oesophageal pH monitoring was used in the pounds. Intragastric electrodes have not postoperative patients were studied volume evaluation of 111 patients and 35 volun- generally been used because of fears regard- responses were found to be as great to MSF teers. A pH-sensitive radiotelemetry pill or ing accuracy in the presence of food. We as to insulin, although the mean PAO,h was probe was positioned 5cm above the lower have compared continuous ambulatory 24 significantly lower than PAO,. Thus peak Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1153 Vobs and peak VG to sham were found to be Storage at 4°C showed no loss of activity significantly correlated with hypochlorhyd- as discriminatory in the diagnosis of RU as for up to three days, but longer storage ria (pH>4), chronic atrophic gastritis or PAO, and peak VG to insulin. In six patients caused significant loss of activity when the intestinal metaplasia or with bacterial over- results of MSF and insulin testing gave pH was below 1-2. The percentage of peptic growth and the presence of nitrate-reducing opposite verdicts, in three MSF indicated activity remaining after 28 days of storage at bacteria in the stomach. Our data suggest incompleteness and three insulin tests indi- 4°C was 99±35 at ambient pH, 75±13 at pH that there is widespread human intragastric cate likewise. 1, 124+24 at pH 4, and 105±37 at pH 6. exposure to potentially genotoxic sub- These results suggest that MSF is as effi- Preliminary studies show that addition of stances and identification of their nature cient as the insulin test. In addition to its glycerol to a final concentration of 11.5% and source(s) has important implications in other advantages, volume measurements preserves peptic activity for at least 60 days the prevention of gastric cancer. alone are all that is required, making this a when gastric juice is stored at -70°C. simple ward test. We conclude that pepsin is unstable to usual methods of storage, the rate of decay being inversely correlated with the pH of the sample, and accelerated with freezing. NUTRITION F17 It is possible that reports of changes in pep- Instability of pepsin in stored gastric juice - sin secretion induced by secretagogues may a cause for concern? be artefactual because of the altered pH. F19 Patterns of villus cell migration in the small D W BURGET, C J DE GARA. AND R H HUNT intestine (Intestinal Disease Research Unit, McMaster University, Hamilton, Ontario, Canada) F18 G WILSON. B PONDER. AND N A WRIGHT Reported variations in studies of pepsin sec- Mutagenic activity of gastric juice - further (Department Histopathology, Royal Post- retion may be because of the use of different clues to the aetiology of gastric cancer graduate Medical School, London and Insti- assay methods or their application. Of espe- tute of Cancer Research, Sutton, Surrey) cial concern are differing reports on the H J O'CONNOR, SE RILEY. AT R AXON. AND R C The pathway of epithelial cell migration effects of storage conditions on pepsin mea- GARNER (Gastroenterology Unit, General along the villus has for many years been a surement. We present the results of our Infirmary, Leeds, Microtest Research Ltd., topic of conjecture. We describe a model experiments which aim to clarify the effects Heslington, York, Cancer Research Unit, for which the first time clearly demonstrates of time, temperature, and pH on pepsin sta- University of York, York) Mutation tests the pathway taken. The mouse aggregation bility. using modified strains of Styphimurium chimera between a RIII/ro and a C57BL/6 Gastric juice specimens (n=36) were col- measure the ability of physical or chemical mouse displays a genotypic carbohydrate lected from normal volunteers during a agents to damage DNA and are used to polymorphism, distinguished by the ability http://gut.bmj.com/ basal period, and' after pentagastrin screen substances for potential mutagenic- of a cell to bind the plant lectin Dolichos administration. Each sample was divided ity/carcinogenicity to human beings. Biflorus Agglutinin. In the intestine of such into four portions which were left at the Intragastric carcinogens may be important an animal, the crypts will either stain posi- ambient pH of collection or adjuted to pH in the aetiology of gastric cancer but the tive or negative to the lectin, the villus stain- values of 1.0, 4.0, 6.0. Samples were then extent of human exposure and their nature ing pattern depending upon the genotype of stored at either 4°C or -70°C and the result- remain controversial. To gain further the crypts feeding it. Using serial tangential ing 1440 aliquots removed at intervals for insight in this important clinical area, we sections and plotting the distribution of the pepsin assay by the bromophenol blue- have prospectively assessed the mutagenic labelled/unlabelled cells with a drawing on September 30, 2021 by guest. Protected copyright. albumin kinetic method. activity of fasting gastric juice using two tube and the use of a computer graphics 3D A dramatic loss of peptic activity was strains of Styphimurium, TA98 and TA100, reconstruction.facility the pathway has been observed in samples stored frozen at low in a sensitive fluctuation assay. Gastric juice shown to be in tight cohorts of similar cell pH, irrespective of whether the low pH was was aspirated at endoscopy from adult type, upwards in straight lines; there is little ambient or adjusted to pH 1 following col- patients with normal endoscopic findings cell mixing. Also shown is that the villus cell lection. After one day of storage at -70'C, (17), peptic ulcer (62),gastric carcinoma loss may not be confined to villus tips but percentage of peptic activity remaining was (seven), pernicious anaemia (12), and after could also take place from the villus side; 27 ±38 in samples frozen at ambient pH, surgery for peptic ulcer (22). Ninety three of the ability of a single crypt to feed cells to 0.2±0.7 at pH 1, 99±16 at pH 4, and 97+13 121 samples (77%) were found to be more than one villus is also proven. The at pH 6. Similar results were obtained on mutagenic and 70 of these (58%) were model allows the migration of cells, as they assay after storage at -70°C for 2, 3, or 7 designated as highly mutagenic. Apart from emerge from the crypt orifices, transverse days. There was complete loss of activity in a significant difference in the proportion of the vestibule and move onto the villus, to be ambient samples frozen at pH less than 1.4, highly mutagenic samples detected from determined in precise detail, as the crypts and negligible loss in samples frozen at pH patients with gastric ulcer (22/27) compared supplying the cells can be individually iden- above 2-2. At intermediate pH, partial loss to normals (8/17) (x2, p<0-05), the propor- tified. This type of model has undoubted of activity on freezing correlated with pH. tion of mutagenic samples detected was application to other problems in gastro- After 28 days of storage at -70° loss of similar from each of the patient groups intestinal cell migration. activity was seen at pH 4-0. Percentage of studied. A significant increase in mutagenic peptic activity remaining was 15+35, 0+0, activity was not detected following therapy 65+43, and 101±16 at ambient pH, pH 1, with cimetidine or ranitidine in 12 patients. F20 pH 4, and pH 6 respectively. The presence of mutagenic activity was not Effect of carbohydrate, fat and protein on Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1154 The British Society ofGastroenterology superior mesenteric artery blood flow in EGF) in the salivary glands and the Brun- Ethanol- Control man ner's glands suggests that Uro-EGF may fed rats rats Jejunum have a role in the maintenance of gastroin- CCPR/h 199±1 1 256±11 p<()()I M I QAMAR, A E READ, R MOUNTFORD, R SKID- testinal homeostasis. Four experiments Crypt/villus ratio 184±07 21 4±1 8 NS MORE, AND P N T WELLS (University were performed in which rats were main- Net villus influx/h 365±25 548±52 p<0(05 Department of Medicine, Bristol Royal tained by total parental nutrition (TPN) in Ileum CCPR/h 14 2±0 9 21 8±1 0 p<()()l Infirmary and Department of Medical order to reduce intestinal epithelial cell pro- Crypt/villus ration 12 8±0+9 13-0±019 NS Physics, Bristol General Hospital, Bris- liferation to a basal level and to lessen the Net villus influx/h 181±17 283±23 p<()0()1 tol) We have previously shown that effects of luminal nutrition and endogenous superior mesenteric artery blood flow secretions. Chronic ethanol ingestion reduces (SMABF) measured by transcutaneous Ten days of TPN caused a consistent and enterocyte turnover in the small intestine. Doppler ultrasound technique is increased highly reproducible reduction (p<0-01) in This effect is probably systemic rather than differentially in response to meals of various intestinal weights and in the rate of accumu- local, because the changes in the jejunum caloric content and physical state (liquid or lation of vincristine arrested metaphases and ileum were similar. soild). The mechanism of postprandial (Crypt Cell Production Rate) (p<0001). SMABF increase is still unclear. The pre- Fifteen ,ug per rat per day of urogastone sent study was designed to investigate sepa- administered intravenously with an F23 rately the SMABF responses to carbohy- isocaloric amount of the TPN diet signific- Confirmation of human jejunal Na+/H+ drate, fat and protein meals. antly increased (p<0.01 - 0-001) both the exchange and the first demonstration of a A set of three experiments was per- weights of the various sections of the intes- congenital defect, using brush border mem- formed in each of 12 healthy volunteers and tine and the CCPR of five sites in the intes- brane vesicles (BBMV) fromjejunal biopsies SMABF was measured before and serially tine (p <0.05 - 0.001). The equivalent daily over a period of one hour after three liquid dose of Uro-EGF administered via an I W BOOTH, P J MILLA, G STRANGE. AND H isocaloric meals (each made up to 400 ml intragastric cannulae thrice daily had no sig- MURER (Institute ofChild Health, London and containing 400 Kcal. Meals consisted of nificant effect on intestinal weight or and Physiologisches Institut der Universitat- carbohydrate (105g caloreen), fat (90 ml CCPR, neither did the luminal administra- Zurich, Switzerland) Although jejunal prosparol), and protein (11Og Maxipro). tion of higher doses of Uro-EGF (150 and Na+/H+ exchange has been directly shown The SMABF increased within five minutes 300 fig/rat/day) have any significant effect in the experimental animal using BBMV, of the end of each meal (carbohydrate 45% on intestinal weight or 2 hour metaphase the evidence for this important homeostatic (p<0.01), fat 24% (p<0-1), and protein collection. It is proposed that one of the in mechanism in man is indirect. We have 16% (p<0-05). The maximal responses vivo actions of Uro-EGF is in the mainte- therefore miniaturised the Mg-EGTA pre- were of similar magnitude but reached at nance of gastrointestinal growth and that cipitation method of isolating jejunal different times from the end of the meals: this occurs primarly via a systemic BBMV, using 20-50mg jejunal biopsies http://gut.bmj.com/ carbohydrate 63% (p <0-01) at 15 min., fat mechanism. obtained from infants and children. A 9x 63% (p<0-01) at 30 min, and protein 52% enrichment of alkaline phosphatase occur- (p<0-01) at 45 min. red during membrane preparation. An Na+/ An hour after the end of ingestion, H+ exchange mechanism was shown in SMABF was still increased: carbohydrate F22 BBMV, using a rapid filitration technique, 45% (p<0-01), fat 47% (p<0-01), and pro- Effect ofchronic ethanol ingestion on entero- by observing a 7x enhancement of sodium tein 46% (p<0-01). cyte turnover in the small intestine uptake at 15 sec, by a pH gradient, (in- These results show that the chemical travesicular pH 6-0; extravesicular pH 7-4) on September 30, 2021 by guest. Protected copyright. nature of the meal is a significant factor R MAZZANTI AND W J JENKINS (Department compared with no pH gradient (p<0.002). determining postprandial SMABE. The of Medicine, Royal Free Hospital School An inward Na+ gradient (100mM) resulted mechanism is uncertain but may reflect the of Medicine, London) Whether chronic in a 5x enhancement of D-glucose uptake differential time course of digestion for the ethanol ingestion significantly damages the compared with no gradient (p <0-05). various substrates. small intestine remains controversial. To Similar studies were performed in jejunal elucidate this we have analysed the mor- mucosa from a 3 year old child with secret- phology of the small intestinal epithelium ory diarrhoea which began in utero. Steady and quantified its renewal in chronically stat jejunal perfusion studies have shown F21 ethanol-fed rats. defective Na+/H+ exchange only (1). Effects of systemic and luminal adminstra- Twenty adult male rats were pair-fed for Studies in BBMV confirmed such a defect, tion of urogastrone on intestinal epithelial 28 days a liquid diet containing either with markedly impaired Na+ uptake at 15 cell proliferation in parenterally fed rats ethanol at 36% of total calories or an sec in the presence of an outward H+ gra- isocaloric diet in which fat substituted for dient (p<0-05) when compared with con- R A GOODLAD, T J G WILSON, W LENTON, H GRE- ethanol. Crypt cell production rate (CCPR) trols. Na+ uptake in the absence of an H+ GORY. K G MCCULLAGH, AND N A WRIGHT was determined in the jejunum and ileum gradient, and D-glucose uptake were not (Department of Histopathology, Ham- by the metaphase arrrest method. significantly different from controls. mersmith Hospital, London, ICI Alderley Weight gain and intestinal morphology These data not only provide direct confir- Park, Macclesfield, G D Searle, High were similar in ethanol-fed and control rats, mation of the presence of Na+/H+ exchange Wycombe, Bucks) The location of the but enterocyte turnover was significantly in the human jejunum but also in conjunc- main sites of production of the polypeptide reduced in the jejunum and ileium of the tion with our previous in vivo studies urogastone-epidermal growth factor (Uro ethanol-fed rats: describe for the first time, a congenital Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1155 defect in this mechanism. M E PENNY, D LLOYD, AND A S MCNEISH (In- glucose and fructose in the jejunum of five stitute of Child Health, University of children (age 1-14 years) with GGM and F24 Birmingham and East Birmingham Hos- controls. In eight control subjects glucose Relationship between intestinal crypt cell pital, Birmingham) Enteric pathogens absorption obeyed saturation kinetics production rate and water absorption mea- infect different and specific parts of the gut (appKm 76mmol/l Vmax 25-6,umol/min/ sured in vitro in the perfused rat small intes- - for example, rotavirus (RV) and cm). In GGM two groups of patients were tine enteropathogenic E coli (EPEC) colonise discernible, GpA(n= 2) with negligible glu- the proximal small intestine; salmonella and cose absorption and GpB (n=3) with R A GOODLAD. J A PLUMB. AND N A WRIGHT shigella infect the distal bowel. There is a marked depression of glucose absorption (Department of Histopathology, Royal need to devise clinical tests that can follow but still by a saturable process (appKm 70 Postgraduate Medical School, Ham- the course of the intestinal lesion induced by Vmax 3.7). Both groups were significantly mersmith Hospital, London, and Depart- different pathogens. different from controls (p<0001) and from ment of Biochemistry, University of Glas- We have measured the one hour blood each other (p<0-001). One patient from gow, Glasgow) The measure of the rate of xylose (a test of proximal small intestinal GpB over a four year period developed accumulation of vincristine arrested mucosal funtion) after intraduodenal in- some clinical glucose tolerance. No change metaphases in microdissected intestinal fusion of 05g/kg D-xylose in a 10% solution was found in affinity for glucose by the crypts (crypt cell production rate, CCPR) is in 29 infants with acute diarrhoea aged transport process, appKm 75 and 80mmol/ the most efficient method of estimating 0-56 weeks. Longitudinal data were 1; but maximal velocity (Vmax) increased intestinal epithelial cell proliferation which obtained in 15. from 4-2 to 10-2 umol/min/cm. is robust enough to withstand scrutiny. Infants with pathogens that damage the These data suggest that at least two Studies in the field of intestinal adaption, proximal intestine had initial blood xylose molecular variants of GGM exist; one however, could be much more informative levels below the lower limit of normal (1-25 where there are no functional transport sites if a valid measure of the functional compart- mmol/1); RV (n=13) mean xylose 0-97 and one where there are decreased numbers ment, such as the in vitro water absorption mmol/1 (range 0- 17-2- 17); adenovirus of normally functioning transport sites. In capacity could be included. The intra- (AV, n=2) 0-71, 0-83 mmol/1; EPEC (n=4) this latter group clinical remission may be peritoneal injection of lmg/kg of vincris- 0-53 mmol/1 (0-31-0-71); enterotoxigenic E because of increasing numbers of transport tine, sulphate 30-180 minutes before perfu- coli (ETEC, n=1) 0-26 mmol/1. All infants sites. sion, had no significant effect on the water with shigella (n=2), salmonella (n=3), no absorption capacity of the small intestine pathogen isolated (n=8), had results within (from the ligament of Treitz to 5 cm before the normal range. F27 the ileo-caecal valve) as measured by the Longitudinal data showed persisting Two new selective inhibitors of intestinal segmented flow single pass perfusion xylose malabsorption during the first week carbohydrate absorption method. (Control 138-4±4-6, vincristine in seven infants with RV, with recovery in http://gut.bmj.com/ 144-7±7-8,ul/cm/h). the second week (n=4) reflecting clinical R H TAYLOR. HELEN M BARKER, ELIZABETH A The CCPR of the jejunum and water improvement. Xylose malabsorption per- BOWEY, AND JEAN E CANFIELD (Depart- absorption of the intestine were then both sisted in 1 RV infant with cow's milk intoler- ment of Gastroenterology and Nutrition, measured in 25 groups of hypo and hyper- ance. Three infants with EPEC (two with Central Middlesex Hospital, London) All proliferative rats which should have been cow's milk intolerance) had low xylose dietary carbohydrate except lactose is in a 'steady state'. The minimum values levels for seven, 24 and 56 days. digested by intestinal a-glycosidases; starch were obtained after hypophysectomy This test of xylose absorption discrim- by luminal a-amylase, its products and the (CCPR=6-73±2-87 cells/crypt/h Absorp- inated between infants with pathogens disaccharides by brush border a- on September 30, 2021 by guest. Protected copyright. tion=68-0±6-67 p1u/cm/h) and the damaging different parts of the gut. The test glycosidases, before absorption as mono- maximum values were observed in lactation can be used to follow the time course of pro- saccharides. Two new a-glycosidase (CCPR=126- 1±20 12 cells/crypt/h Absorp- ximal mucosal damage in gastroenteritis. inhibitors (BAY mlO99 & o1248) have been tion=225-0±16-9 ,1/cm/h) The CCPR and derived from deoxynojirimycin. Their absorption were highly significantly corre- effects on absorption of six dietary car- lated (p<0.001) when all the data or par- F26 bohydrates have been compared with those ticular subsets of data were considered, Glucose absorption in congenital glucose- of acarbose using a steady state of perfusion except when a non-steady state model (the galactose malabsorption: a kinetic basis for technique. intestine of starved rats after refeeding) was clinical remission Young adult female anaesthetised investigated. The combined study of CCPR Sprague-Dawley rats had isolated 20cm seg- and water absorption is a practical and con- P J MILLA, E WOZNIAK. AND T R FENTON ments of proximal jejunum perfused in vivo venient approach to the study of iltestinal (Institute ofChild Health, London and Hos- at 0-2ml/min for 210 min. Solutions con- cell proliferation and intestinal adaptation, pital for Sick Children, Great Ormond tained 23-4mmol/l of sucrose (n=40), mal- and shows that in 'steady state' models of Street, London) Glucose-galactose mal- tose (40), lactose (20), glucose (19) or fruc- hypo and hyperplasia cell, production is absorption (GGM) is an inherited disorder tose(15) or 15g 1-l starch (36); 3g/1 PEG closely linked to functional capacity. of carrier-mediated intestinal glucose trans- 4000 labelled with I, Ci 14C and NaCl to 290 port. Previous studies have shown failure of mosmol. From 60 to 90 min test solutions microvillous membrane binding but also contained m1O99 6-5mg 1, o1248 4-5mg F25 paradoxically clinical amelioration may I or acarbose 30mg 1 or the control solution D-xylose absorption in acute gastroenteritis occur with increasing age. continued. Each animal had one substrate of known aetiology We have studied the in vivo absorption of ± one drug. Sugars were measured by Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from Al 156 The British Society of Gastroenterology HPLC, PEG by scintillation counting and stomach, small bowel, colon and pancreas Radcliffe Hospital, Oxford, and Depart- disappearance rates calculated in the usual compared with the control group and no sig- ment of Medicine, University of way. nificant changes in CCPR in any region of Washington, Seattle, WA, USA) Dioctyl Luminal disappearance rates compared the gut. sodium sulphosuccinate (DSS) is an anionic with control fell as follows: sucrose, 51±6% This study shows that PYY is greatly detergent which is used widely as a laxative with mIO99, 57±7% with o1248 and 68+ raised after intestinal resection in the rat and promoted as a stool softener. Although 7% with acarbose (all p (Royal Postgraduate Medical School, Ham- prednisone (20 mg) (35 patients) or SCG sodium sulphosuccinate had no effect on http://gut.bmj.com/ mersmith Hospital, London) Peptide YY (600 mg) (35 patients) enema groups; the stool weight, stool frequency, stool water or (PYY) is a circulating gastrointestinal hor- enemas were used twice daily for 4 weeks mean transit time. mone localised to the endocrine cells of the and then once daily. Patients were assessed We conclude that 300 mg daily of DSS ileum and colon. The physiological role of at presentation, and at four and eight does not increase ileal or colonic output of PYY is still being defined but it has inhibit- weeks. Data relates to symptoms, to solids or water in human subjects and may ory gastrointestinal secretory and motor appearances on sigmoidoscopy, and to his- increase cholesterol absorption. The wide- effects. We have intestigated PYY in the tology. spread use of DSS deserves reevaluation. adaptive response following intestinal Each group showed a significant on September 30, 2021 by guest. Protected copyright. resection. improvement in relation to stool frequency Fourteen groups of eight rats underwent and rectal bleeding both at four and eight F31 either jejunal transection or varying weeks, though the Predsol group was more A modified 'gut-sterilisation' regime, com- degrees of small bowel resection. Adimals effective at four weeks in relation to rectal pared with oral prednisolone, in a ran- were killed at intervals up to 48 days and bleeding (p<0.05). There was, however, no domised trial for the treatment of Crohn's plasma PYY estimated by radioimmuno- difference in relation to the appearances on disease assay. Two further groups were given PYY sigmoidoscopy and to histology, with both or saline via an implanted osmotic pump. groups again showing significant improve- S H SAVERYMUTTU, H J F HODGSON, AND V S Animals were killed at 12 days and plasma ment at four and eight weeks. CHADWICK (Department of Medicine, PYY, intestinal weight and crypt cell pro- It is suggested that there is a place for Royal Postgraduate Medical School, Ham- duction rate (CCPR) estimated. SCG retention enemas in the management mersmith Hospital, London) A random- Seventy five per cent intestinal resection of ulcerative colitis. ised clinical trial has been performed, com- caused a rise in plasma PYY from a transec- paring two regimes for the inpatient treat- tion value of 28±3 to 85±12 pmol/1 ment of active Crohn's disease affecting (p The British Society of Gastroenterology A1157 conventional diet. Patients were assessed Seventy two patients entered the study: (-5-8±3.0 to +3-0±2 5 ml.cm-2h, p F32 or chronically, stimulate net sodium (Na) mal in patients with histologically proven http://gut.bmj.com/ Trials of antimicrobial therapy for relapsing and water (HOH) absorption and potas- large and/or small bowel CD compared with Crohn's disease sium (K) secretion in mammalian colon, that found in control subjects (CS). and may therefore reduce stool volumes in The results show that PBMC from N S AMBROSE, D YOUNGS, D W BURDON, R N colitic patients, at least in part, by exerting patients with CD produce greater amounts ALLEN, M R B KEIGHLEY, P BARNES, AND J E specific effects on colonic transport. To of PGE2 compared with that found in CS LENNARD JONES (General Hospital, Bir- investigate this, a rectal dialysis technique (n=8, 123±278 vs n=8, 45±5 ng/106 mono- mingham, and St. Mark's Hospital, Lon- was used to measure transmural potential cytes, -±SE, p<0.001, CD vs CS) when don) Infection is responsible for many of difference (pd., lumen negative), and neV stimulated with opsonised zymosan (Zy). In on September 30, 2021 by guest. Protected copyright. the complications of Crohn's disease. Fur- Na, HOH and K movements (+ =absorp- the presence of 10 nMoles AA + Zy, the thermore, extra intestinal sites are col- tion; -= secretion) in control subjects and PBMC from patients with CD produced onised by pathogenic bacteria in over 50% patients with untreated (active) ulcerative greater amounts of PGE2 compared with of patients requiring resection for uncom- colitis, before and five hours after the that found in CS (n=6, 1021±286 vs n=6, plicated disease. We decided therefore to intravenous administration of glucocor- 351±95 ng/106 monocytes, p<0-001). undertake a trial of one month's antimicro- ticoid. In controls (n=9), 100 mg of hyd- Furthermore, the uptake of 10 nmol H3 AA bial therapy for patients with symptomatic rocortisone (HC) increased pd (-36-8±4.9 and conversion to H3 PGE2 was of a similar relapse of Crohn's disease. to -54-1±7.5 mV, p<0-025), and stimu- magnitude, in=9, 1061±242 vs n=12, Criteria for entry included: two major lated Na absorption (+3.1±0.6 to 353±47 ng/10 monocytes, p<0-001). symptoms: fever, abdominal pain, diar- +5-4±0-7 mmol.cm-2h, p<0.005). HOH The essential fatty acid AA content of rhoea, weight loss, abdominal mass or com- absorption (-3-7±2.9 to +8-8±2-7 PBMC was significantly higher in patients plications (excluding perianal disease) and ml.cm-2h, p<0-02), and K secretion with CD compared with that found in CS, two haematological abnormalities: (-2.0±0.3 to -3 2± 0-6 mmol.cm-2h, (n=16, 96±18 vs n=12, 48±9 ug/mg DNA, haemoglobin, ESR, CRP, albumen, iron, p<005). Similar changes occurred in con- p<0.02). In addition, serum levels showed a TIBC. Patients were monitored for the trols (n=8) after 40 mg of methylpred- similar increase in CD (n=8, 163±25 vs above clinical and haematological paramet- nisolone. Although pd and transport rates n=28, 82±4,g/ml, p<0.001). ers over six weeks and for changes in faecal were abnormal in colitic patients (n=6), 100 The results of this study show that there is flora. Randomisation was to four groups: mg of HC increased pd (-12-0±2.8 to a larger serum and cellular pool of AA in Metronidazole alone (M), Cotrimoxazole -291±7-8 mV, p<0.05), and stimulated patients with CD. Also, these patients pro- alone (C), Metronidazole and Cot- Na absorption (+0.4±0.4 to +2-4±0-9 duce significantly greater amounts of PGE2 rimoxazole (C+M) or double placebo (P). mmol.cm-2h, p<0-025), HOH absorption when stimulated with opsonised Zy. Our Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1 158 The British Society of Gastroenterology results would support the concept that HOMME (Research Group on Digestive and ML of the small bowel is a significant PBMC from patients with CD have an Immunopathology, University Hospital, association, which may affect caucasians enhanced capacity to produce greater Poitiers, France, University Hospital, Cler- born and living in western countries. amounts of the immunomodulator PGE2 mont Ferrand, France) In Mediterranean which might be a consequence of increased areas, diffuse small intestinal nodular lym- availability of precursor AA. phoid hyperplasia (NLH) may be a his- F37 topathologic variant of immunoprolifera- Comparative effects ofenteral liquid diets on tive small intestinal disease, which is fre- growth; nitrogen (N) balance, whole body N, F35 quently associated with overt malignant N. Wastage and faecal residue in rats. Changes in whole body protein synthesis and lymphoma (ML). In western areas, benign breakdown in acute malnourished Crohn's extensive NLH is a well-known entity A N H MAIN, L M NELSON, W EAST, T PRESTON, G disease patients before and after nutritional occurring mainly in immunodeficient sub- MITCHELL, J CUMMINGS, AND R I RUSSELL restoration jects. Though very rare, its association with (Gastroenterology Unit, Royal Infirmary, ML is considered to be non-fortuitous; Glasgow, Scottish Universities Reactor T W O'CALLAGHAN. R DOCKRELL, J R LENNON, nevertheless, this is based upon only a very Research Centre, East Kilbride and MRC M A MORGAN, AND J P CROWE (Mater Mis- limited number of isolated cases observed Dunn Nutrition Unit, Cambridge) In a ericordiae Hospital Dublin and Department principally in non-immunodeficient controlled study, five commonly used com- of Biochemistry and Soil Science, University patients. We report the occurrence of small plete enteral liquid diets differing in nitro- College Dublin, Eire) Metabolic changes intestinal ML in three out of five consecu- gen, carbohydrate and fat composition: were studied in seven consecutive mal- tive NLH patients without overt immu- Vivonex (V), Vivonex HN (VHN), Flexical nourished patients with an acute exacerba- nodeficiency, observed over seven (F), Ensure (E), Clinifeed ISO (C), and a tion of Crohn's disease at the beginning and years. Typical benign NLH extending to the control rat chow (Oxoid 41B) were fed to 36 end of nutrional restoration with a whole whole length of jejunum, ileum and/or rats (six rats each diet) for 28 days in protein diet. The nutritional supply pro- duodenum was diagnosed, on operative isocaloric amounts (70.3 Kcal (290KJ) per vided 2-5 g. of protein and 60 kcal energy/ specimens, in four men and one woman, rat per d.). Mean weight gain (% of starting kg/day. Rates of flux, protein synthesis and aged 16 to 32, who presented with long- weight) varied from 35(V) to 58(C), similar breakdown were calculated from the standing abdominal pain without evidence to controls (64%), N Balance.(mean ±SEM enrichment of urinary urea and ammonia of malabsorption (four cases), or with inter- mmol/24h) varied from 7-6±0.5 (V) to with '5N glycine. mittent diarrhoea of two year duration (one 10-7±1-7 (VHN) but no significant differ- Significant nutritional restoration was case). All patients was caucasians: three ences were observed. Whole body N (neut- achieved with mean body weight increasing were born and had lived since birth in cent- ron activation analysis) (g) after 28d feeding by 14% from 84% to 96% of ideal, and ral France. Two were born in Portugal and was less with V (8-58±0- 16) than F (9.56± mean serum albumin by 23% from 35 to 43 Algeria, respectively, but had lived in 1. 15) (p<0-05) or C (9.39±0.27) (p<0.05). http://gut.bmj.com/ g/l (p<0.02). Mean rates of whole body pro- France since the age of 2 and 10, respec- Mean N wastage (N excretion as % of tein synthesis and breakdown in the mal- tively. Their socio-economic status was intake) was least for F (47) and greatest for nourished state were 6-8±1-1 and 5-3±1 4 excellent (two cases) or good (three cases). E (70), controls excreting 75%. Faecal g/kg/day, respectively. After nutritional Immunoglobulin levels, systemic antibody residue (daily dry weight) was less with V restoration these values fell significantly to response, and delayed hypersensitivity tests and VHN (230±9 and 180±20mg/d respec- 4-5±0-8 and 3 3±0-8 g. protein/kg/day were normal. Normal density and distribu- tively) than F (420±30) (p<0-01), E (390+ (p<0.02). These markedly increased rates tion of IgA, IgM and IgG-producing plasma 30) (p<0-01) and C (570±50) (p<0-01). All of synthesis and breakdown show that cells were found, in each case, in the lamina were <8% of the high residue control diet. on September 30, 2021 by guest. Protected copyright. although whole body protein breakdown is propria both of the small intestine at a dis- Bacterial content of faeces was least for con- increased in an acute exacerbation of tance from the hyperplastic lymphoid trols (26%) and varied from 46% (VHN) to Crohn's disease, this 'catabolic' state is nodules, and of the colon and rectum. In the 65% (C) in the test diets. These differences paralled by an equal or greater increase in one case studied, the almost exclusive T-cell may reflect the differing digestibility of fibre protein synthesis when the nitrogen and subset in the germinal centers of the in the diets. energy supply is adequate. This emphasises hyperplastic nodules was T8. Intestinal giar- In conclusion, V produced least growth the importance of an adequate nutritional diasis was found in two cases. A large ulcer- (N accretion) of the test diets but it and supply in the treatment of acute Crohn's dis- ated tumour of the jejunum (two cases) and VHN had significantly lower faecal residue ease which in the majority of such patients proximal ileum (one case) was found at than the other test diets. The methods used should be enteral feeding with a whole pro- laparotomy in three patients (two French are applicable to human subjects and the tein diet. and the Portugese), simultaneously to or diets will be tested in patients with impaired two years after diagnosis of diffuse NLH. small bowel function or bowel stricutures in The tumours were B-cell malignant lym- whom low nitrogen wastage and low faecal F36 phoma of centrocytic-centroblastic type residue are considered desirable. Diffuse nodular lymphoid hyperplasia and (two patients), and T-cell lymphoblastic western type malignant lymphoma of the lymphoma (1 patient). Tumour resection small bowel, without overt immunodefi- and combination chemotherapy resulted for ciency: a signficant association two patients in prolonged complete remis- F38 sion. Intestinal NLH persisted unchanged Physiological starch malabsorption: direct C MATUCHANSKY, G TOUCHARD, P BABIN, F in each case. quantitation in ileostomates and effect of DEMEOCO. Y FONCK. M MEYER, AND J L PREUD' We thereby suggest that extensive NLH small bowel transit time. Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1 159 R W CHAPMAN, J SILLERY AND D R SAUN- inhibition of polyamine synthesis, ment of Bi-organic Chemistry, Shizouka, DERS (Dept of Gastroenterology, John therefore, may reduce these processes. Japan, and the Karolinska Institute, Radcliffe Hospital Oxford and Dept, of Ornithine decarboxylase (ODC) the rate Sweden) Regional specific antibodies and Medicine, University of Washington, Seat- limiting enzyme in polyamine synthesis chromatography were used to analyse the tle, WA, USA) Recent studies using indi- which converts ornithine to putrescine, is distribution and molecular forms of PHI rect breath hydrogen and intubation specifically and irreversibly inhibited by and VIP in the porcine intestine. Concen- techniques have indicated that in excess of DFMO. Thus DFMO in tissue culture trations of PHI immunoreactivity (PHI- 10% of starch in normal foods may be reduces cell division and when given orally IR), measured with three different malabsorbed in the small intestine and enter inhibits adaptive growth in intestine and antisera, and VIP immunoreactivity (VIP- the colon. The explanation for this pancreas - for example, it depresses IR), were approximately equal in all parts phenomenon is unclear. caerulin induced pancreatic hyperplasia in of the gastrointestinal tract apart from the First, we measured in six healthy ileosto- the rat. To see if DFMO also modifies the stomach. In the stomach the concentration mates on a fixed starch intake, 150 g daily pancreatic hyperplasia induced by PBD of PHI-IR, measured with the N-terminally for four days, daily unabsorbed dietary (interposition of 50 cm of jejunum between directed antibody (R8403) although equal starch by chemical analysis of ileostomy stomach and duodenum) eight pairs of rats to the corresponding VIP-IR concen- effluent. Daily unabsorbed starch ranged were given either 2% DFMO in water or tration, was three-four times higher than from 1.3% to 5-0%, mean 2-4%, of total drinking water alone beginning two days the PHI-IR concentrations detected with 2 ingested starch. before PBD. C-terminally directed PHI antisera (T33 Second, we measured in six ileostomates Both food intake and bw decreased and T41). Gel permeation of gastric unabsorbed dietary starch from a significantly in the DFMO treated rats so extracts revealed one VIP-IR peak which radiolabelled solid meal containing 50 g that 14 days after PBD, mean bw in the co-eluted with the porcine standard at a potato starch, under control conditions DFMO group (197±SEM 6 g) was less Kav of 0-5. Only one PHI-IR peak was also after altering transit time with either (p<0.001) than that in the controls detected with T33 and T41. This PHI-IR loperamide (8 mg) or magnesium citrate (250±6). As expected, PBD increased was eluted in a similar position to the (0.1 g/kg body weight). Loperamide sig- pancreatic wet weight by approx 70% in porcine PHI standard (Kav=0.5). With nificantly prolonged the time taken for the the controls but surprisingly, mean R8403 two PHI-IR peaks were detected, meal to empty from the ileum and signific- pancreatic weight, corrected/100 g bw, was however, the minor form co-eluted with antly decreased the amount of unabsorbed significantly greater in the DFMO group the porcine PHI standard whereas the starch in all six ileostomates (p<0-05). Mag- (847±59 mg) than in the controls (634±26; predominant form eluted earlier nesium citrate significantly reduced the p<0-01). Similarly, mean pancreatic (Kav=0-37). The earlier eluting PHI-IR time taken for the test meal to empty from protein (mg 100 g/bw) was also 33% peak was present in the rest of the intestine the ileum and significantly increased starch greater after DFMO (138±12) than in the in only minute amounts. As VIP and PHI malabsorption in all six subjects (p<0-05). rats given water (103±4; p<0-02). are believed to be derived from a common http://gut.bmj.com/ Mean unabsorbed starch (±SD) was 0-8 g± Pancreatic DNA (mg 100 g/bw), although precursor, it is suggested that in the 0-4 after control meal alone; 0-4±0-2 after greater after DFMO (5.0±0-4) than in stomach the post-translational enzymic loperamide and 1-6 g±0-8 after magnesium controls (4.2±0.3), was not significantly processing of the precursor protein is citrate. different. Difluoromethylornithine also different from other parts of the intestine, We conclude that the degree of starch increased mean testicular weight/100 g bw yielding a big PHI-like peptide'. As the malabsorption by the small intestine may be by 23% (p<0.001); it did not significantly gastric PHI receptor is known to differ less than previously estimated by less direct affect the weights of heart, kidney, liver, or from other tissues, big PHI may have a methods, and is dependent upon small spleen, when related to bw. Wheln different biological role. Isolation and on September 30, 2021 by guest. Protected copyright. intestinal transit time. pancreatic and testicular weights were pharmacological characterisation of this uncorrected for bw, however, there was no newly described peptide will undoubtably difference between the two groups. soon provide an answer. These results show that the pancreatic POSTERS hyperplasia induced by PBD is not F39-F133 inhibited by DFMO. This finding F41 challenges the concept that inhibition of Localisation and biochemical character- ODC reduces adaptive growth in the isation of CGRP in brain and gut Regulatory peptides pancreas. F39 M A GHATEI, P K MULDERRY, A E BISHOP, M G Polyamine synthesis inhibitor, difluoro- ROSENFELD, J M POLAK, AND S R BLOOM methylornithine (DFMO) does not prevent F40 (Departments of Medicine and Immuno- the pancreatic hyperplasia induced by Non-equimolor levels of PHI and VIP in the cytochemistry, Royal Postgraduate Medical pancreatico-biliary diversion (PBD) in the stomach explained by the presence of a big School, London) As a result of alter- rat PHI-like molecule native RNA processing during calcitonin gene expression an entirely different N H STACE, M HOSOMI, S VAJA, G M MURPHY, Y YIANGOU, N D CHRISTOFIDES, M A BLANK, N peptide with 37 amino acid residues called AND R H DOWLING (Gastroenterology Unit, YANAIHARA, A BISHOP, K TATEMOTO, J M calcitonin gene-related peptide (CGRP) is Guy's Hospital and Medical School, POLAK, AND S R BLOOM (Departments of generated in the rat hypothalamus. As London) Polyamines are thought to Medicine and Histochemistry, Royal Post- many of the neuropeptides so far described regulate cell division and growth: graduate Medical School, London. Depart- are also located in peripheral tissues, the Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1160 The British Society of Gastroenterology distribution of CGRP in the rat gastro- were compared in healthy controls and 1246) p=0-001; AV, 440 (158-672) intestinal tract, pancreas, and regions of several groups of patients with gastro- p=0.005. the brain was studied by radioimmuno- intestinal disease. Basal PYY concen- The effects of atropine and TV confirm assay and immunocytochemistry. The trations in healthy subjects were 8-5±0-8 previous findings. Coeliac ganglionectomy highest concentrations of CGRP (pmol/g) pmol/l and showed a small but significant slightly reduced PP response, consistent were found in the stomach 7 0±1 3, postprandial rise (3.7±0.9, p 0.005). with known distribution of some vagal pancreas 5-6±0 8, duodenum 4 4±0-8 and Peptide YY levels were grossly risen in fibres via the coeliac plexus. During AV. colon 5-0±+10 with lower concentrations in patients with small intestinal mucosal vagal fibres distal to the pylorus were the jejunum and ileum. In the brain there inflammation (sprue, n=9, 79-5±18-0 carefully preserved, but AV abolished PP was considerably more CGRP in the brain pmol/l). High basal PYY concentrations response. Two possible explanations exist. stem (37.0±4-8) compared with the other were seen in patients with inflammatory (1) All efferent fibres to the pancreas might regions. Permeation chromatography of bowel disease (Crohn's, n= 14, 22-6±3-9, p be cut by AV. This seems unlikely on gut extracts revealed three immunoreactive 0(())5; ulcerative colitis. n=24, 13-4+ 15. p anatomical grounds, *and in view of the peaks, the major peak co-eluted with 0.01) and in patients with acute infective observed effect of CG. (2) The release of synthetic CGRP and two other peaks diarrhoea (n=12, 22-0±4-8, p 0-01); post- PP after food might be dependent on emerged later. HPLC analysis further prandial responses were enhanced in these antro-pancreatic reflexes. Section of the resolved one of these into two distinct conditions. In patients with steatorrhoea afferent fibres by AV would then abolish peaks although most of the CGRP-like due to chronic pancreatitis, basal PYY the response. The effects of CG suggest immunoreactivity still co-eluted with the levels were markedly risen (n=12, that some of the efferents pass through the synthetic peptide. Immunocytochemistry 49-5±6-3, p 0-001), whereas pancreatic coeliac ganglion and plexus. revealed CGRP-immunoreactivity in an patients without malabsorption had only extensive network of nerve fibres in the moderately raised levels (n=21, 15-8±1-5, pancreas and gut. In the pancreas, the p 0.001). Peptide YY levels were normal in F44 fibres were scattered in the exocrine peptic ulcer and diverticular disease. The Occurrence and distribution of a novel parenchyma and connective tissue and rise of plasma PYY levels after food would regulatory peptide, galanin, in the mam- showed a particular association with blood suggest that this peptide may play an malian gastrointestinal tract vessels and the islets of langerhans. important role as a gastrointestinal Calcitonin gene-related peptide fibres were hormone. Investigation of the abnormal A E BISHOP, ND CHRISTOFIDES, J CH'NG, S R found at the periphery of the islets and also PYY release seen in gastrointestinal BLOOM, AND J M POLAK (Departments of in the midst of the endocrine cells. A disease may shed light on the role of this Histochemistry and Medicine, RPMS, proportion of the islet cells were immuno- interesting hormonal peptide and into the London) The system of mammalian stained by the CGRP antibodies. Scattered pathophysiology of these common gastro- regulatory peptides continues to expand CGRP-nerves could be seen in the gut. The intestinal disorders. with the discovery of new active molecules. http://gut.bmj.com/ finding of high concentrations of this novel One of the latest peptides to be isolated neuropeptide within the brain and and characterised consists of 29 amino alimentary tract establishes CGRP as F43 acids and has been termed galanin, a name another gut-brain peptide and suggests that Neural pathways mediating pancreatic derived from the fact that its N- and it may be important in the control of polypeptide response to food C-terminal residues are glycine and alanine gastrointestinal function. Galanin has pharmacological effects on the C D JOHNSON, J A CHAYVIALLE, M-A DEVAUX, gut. including contraction of smooth AND H SARLES (INSERM U31, Marseille, muscle. In this study, immunocyto- on September 30, 2021 by guest. Protected copyright. F42 France) Pancreatic polypeptide (PP) chemistry and radioimmunoassay showed PYY, a new colonic hormone: changes in release is mediated by the vagus and is that galanin is present in significant gastrointestinal diseases abolished by pyloric transection. We have quantities in the gut of mammals, including measured PP release for 45 minutes after man. The concentrations of galanin ranged 1 E ADRIAN, A P SAVAGE, A J BACARESE- food in normal, conscious dogs, with or from 2 6 to 77 pmol/g wet weight of tissue HAMILTON, K D WOLFE, H S BESTERMAN, AND without atropine 20 ,Ag/kg/h (n=6) and and were generally higher in the large S R BLOOM (Department of Medicine, after truncal vagotomy (TV, n=6), coeliac bowel. The peptide-immunoreactivity was Royal Postgraduate Medical School, ganglionectomy (CG, n=4) or section of localised exclusively to a ramifying ,Hammersmith Hospital, London) Peptide the vagal fibres to the gastric antrum network of nerve fibres which infiltrated YY (PYY) is a hormonal peptide, recently (antral vagotomy, AV, n=4). All each layer of the bowel wall There was isolated from porcine intestine, which has operations were performed under general some evidence for a differential distribu- been localised to endocrine cells of the ileal anaesthesia. tion of galanin-containing nerves in the and colonic mucosa. Peptide YY potently Basal PP in controls was 89 pg (eq various areas of gut. For example, these inhibits gastric secretion in man and also BPP)/ml (SD:61) and was reduced after nerves were numerous in the mucosa of reduces gut motility. Although the AV and TV. The mean PP response (sum each level of the tract except the stomach, abundance of the peptide suggests an of six measurements in each dog) was 3126 where they were found only infrequently. important physiological role for PYY in the (range 1565-4181) in normals. In all other Neuronal cell bodies containing galanin circulation, its secretion in gastrointestinal groups the response was reduced (analysis immunoreactivity were restricted to the diseases has not previously been investi- of variance, p<0.001): CG, 2291 (1906- submucous plexus mainly of the upper gated. Plasma PYY levels, measured 2928), U=4, p=0-057; atropine 1743 small intestine. Thus, a newly recognised basally and after a standard breakfast, (1073-2614) U=3, p=0-015; TV, 489 (130- type of peptide-containing nerve has been Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1 161 discovered in the mammalian gut. The functional status of the enteric nervous traditional lengthy and unpleasant known pharmacological effects of galanin system laboratory procedure of homogenisation suggest that it is a potential controlling and heat drying of fresh three day faecal factor but the full extent of its physiological A E BISHOP, F CARLEI. P J MARANGOS, J Q collection for fat analysis, a technique for actions and involvement in gut pathology TROJANOWSKI, D DAHL, AND J M POLAK collection, freeze drying and homogen- remain to be elucidated. (Department of Histochemistry, RPMS, isation of the total faecal collection in a London, Department of Pathology, single container is described. University of Pennsylvania, Clinical Freeze drying was performed in a SBFD F45 Psychobiology Branch, NIMH, Maryland freeze drying cabinet for 24 hours at 40°C Monoclonal antibodies to chromogranin A and Spinal Cord Injury Research, Boston, with subsequent homogenisation of the in the demonstration of all currently identi- Mass, USA) Neurofilaments and neurone total dry collection in an Atomix fiable endocrine cells of the human gut specific enolase (NSE) are both known to homogeniser (MSE) for 15 minutes. be present in the nervous system. Neuro- Comparison of results from 25 patients A E BISHOP, P FACER, R V LLOYD, B S WILSON, filaments are intermediate-sized proteins of whose faecal fat values range from low AND J M POLAK (Departmeni of Histo- the cytoskeleton whilst NSE is an isomer of normal to grossly abnormal showed highly chemistry, RPMS, London, and Depart- a major enzyme of glycolysis. In this study, significant correlation between heat and ment of Pathology, University of Michigan, immunocytochemistry was used to assess freeze drying methods (r=99, p<0-0l). USA) A long standing impediment to the and compare the suitability of the two Recovery studies using both methods on visualisation of entire endocrine cell substances as neuronal markers in the known fat concentrations (range 0-5 g to 70 populations has been the lack of reliable, enteric nervous system. Fresh specimens of g) showed significantly greater accuracy for easily reproducible techniques. Previous human, porcine, and rodent gut (stomach, the freeze drying procedure (p<0-01). methods have not always been totally small and large intestine) were fixed in Reproducibility was tested by multiple successful. For example, not all endocrine formalin or benzoquinone solution and analyses (10) at each of seven different cells are argyrophil and the level of the serial 4 gm sections were cut in a cryostat. known fat concentrations. The coefficient enzymatic marker neurone specific enolase The first section of each pair was picked up of variance using freeze dry technique was can vary with cell function, particularly in directly from the knife but the second was significantly less than for the heat dry the lower bowel. Chromogranin A is a inverted and picked up. In this way, the technique (p<0-02). protein which has been found in the same cut face was uppermost in both Freeze dried faecal analysis has wide catecholamine storage granules of adrenal sections. One section of each pair was applications, and this new technique of dry medulla cells. In this study, immunocyto- immunostained for neurofilaments and the homogenisation eliminates any need for chemistry, using monoclonal antibodies to other for NSE, so that a direct comparison handling of the fresh faecal collection chromogranin A, was applied to test could be made of the occurrence of the two making it a more acceptable procedure for whether the protein can be used as a proteins in the same neuronal cell bodies. laboratory personnel. The technique is http://gut.bmj.com/ general marker for all currently identifiable Both proteins could be identified in an significantly more accurate and precise endocrine cells of the gut. Fresh surgical extensive network of nerve fibres infil- than conventional heat drying methods. samples of each area of human gut were trating all regions of the gut wall, as well as fixed in formalin and serial sectiqns were in the ganglion cells of both plexuses. cut. The first of each pair of sections was Neurofilament-immunoreactivity was F48 immunostained for chromogranin A and observed in all cell bodies but some of Do fibre containing enteral diets have the second for a peptide. In all regions, these were found, in serial sections, to advantages over existing low residue diets? chromogranin A-immunoreactive cells contain no or equivocal NSE-immuno- on September 30, 2021 by guest. Protected copyright. were more numerous than those showing reactivity. This apparent lack of NSE may D H PATIL, G K GRIMBLE, P KEOHANE. H peptide immunoreactivity. In serial relate to its level of activity and production AlTRILL, M LOVE, P G FROST, AND D B A SILK sections, it was possible to see that all types in individual cells. Our findings show that (Department of Gastroenterology and of peptide-immunoreactive cells also immunostaining of neurofilaments allows Nutrition, Central Middlesex Hospital, contained chromogranin A. The protein visualisation of the complete enteric London) Fibre modifies the pattern of was also found in cells which showed no nervous system, irrespective of its func- absorption of the products of luminal peptide immunoreactivity, suggesting the tional state, whilst that of NSE may starch digestion. The aims of the present existence of other endocrine cell types yet provide information on the dynamic status study were to determine whether fibre to be identified. The density of chromo- of the nerves. influences the pattern of absorption of granin A immunostaining did not vary in protein and carbohydrate after administra- the different regions of gut nor in the tion of a polymeric enteral diet and to different cell types. Immunostaining of Small bowel document what effects fibre has on bowel chromogranin A thus provides a means for action, stool weight, and gastrointestinal the demonstration and rapid assessment of F47 side effects during enteral nutrition. entire populations of gut endocrine cells. Freeze drying technique for faecal fat Six fasted normal volunteers drank on analysis alternate days 750 ml of fibre free polymeric diet (Sokaham; 9gN 1200 Kcal) F46 T W O CALLAGHAN, J MCCANN, E WRIGHT, A and the identical diet with 9 g added fibre. Immunostaining of neurofilaments and MORGAN, AND J CROWE (Mater Miseri- The postprandial rises in blood glucose and neurone specific enolase: a possible means cordiae Hospital, Dublin, University levels of 17 individual amino acids for assessment of the morphological and College Dublin, Eire) To eliminate the measured at half hourly intervals for three Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1162 The British Society of Gastroenterology hours were similar on both occasions. The We have assessed our technique in 58 of some agents in under 24 hours. addition of fibre was without effect on patients. Although adequate double postprandial breath hydrogen excretion. contrast views of the small bowel were In a prospective r.andomised crossover considered to have been achieved in only F51 clinical trial, five patients with normal 25 patients (43%), adequate lumenal Immunoassay of giardia antigen for gastrointestinal function requiring distension was achieved in 56 (96%) and diagnosis of giardiasis nutritional support were randomised after adequate separation of small bowel loops a five day equilibration period of enteral in 49 (84%). The examination was A K J GOKA, P M G INGE, AND M J G FARTHING feeding to receive two five day periods of completed in under one hour in 25 patients (Department of Gastroenterology, St continuous 24 hour nasogastric infusion of (43%) between one and two hours in 24 Bartholomew's Hospital, London) the same polymeric diet (2L; 22 gN, 3200 (41%) and in over two hours in nine Diagnosis of giardiasis relies on the Kcal) with or without 25 g of fibre. There (16%). Each examination took, on detection of Giardia forms in stool (lacks was no significant difference in daily stool average, 25 minutes of the radiologist's precision) or intestinal aspirate (invasive). wet weights during infusion of the fibre time. We have therefore evaluated the suitability containing (58±20 g/24h; mean±SEM) or These results suggest that the main of four immunologic techniques, immuno- fibre free diet (52±16 g/24h). Bowel criticisms of the small bowel barium follow diffusion (ID), immunoelectrophoresis frequency (0-8±SE 0-4 vs 0-6±0 2 motions through have been largely overcome by the (IE), countercurrent immunoelectro- per day) was similar during feeding with gas enhanced technique. phoresis (CIE), and indirect enzyme- the fibre containing and fibre free diet and linked immunosorbent assay (ELISA) for the two diets were tolerated equally well. detecting Giardia antigen under experi- These findings lend no support to recent F50 mental conditions in stool and intestinal suggestions that there could be advantages Radiometric assay for antigiardial drugs aspirate, Axenic G lamblia was used as in using fibre containing diets in enteral experimental trophozoite antigen and for nutrition. Low residue diets are less viscous P M G INGE, A K J GOKA, AND M J G FARTHING antiserum production in rabbits. Cysts and easier to administer and still appear to (Department of Gastroenterology, St were concentrated from stool by a modified be the diets of choice. Bartholomew's Hospital, London) Anti- Ficoll-Urografin technique. Immuno- giardial drug sensitivity testing is not diffusion, IE, and CIE were performed in generally available despite evidence of 1% agarose in barbitone/barbital buffer, F49 variable parasite susceptibility to standard pH 8-6. ELISA was optimised using anti- The gas enhanced small bowel barium giardiacidal agents. We describe a 3H- rabbit Ig linked horse-radish peroxidase as follow through thymidine radiometric method for anti- second antibody and tetramethyl benzidine giardial drug assay and relate this to as substrate. Immunodiffusion, IE, and G M FRASER AND P G PRESTON (Department parasite growth during 24 hour culture, and CIE detected experimental Giardia http://gut.bmj.com/ of Radiology, Western General Hospital, to motility (by phase microscopy) and trophozoite antigen but were relatively Edinburgh) In the radiology of the small viability (trypan blue exclusion) both insensitive requiring a minimum of bowel the three main criticisms of the assessed in a four hour microassay. We 8-5x10 trophozoites for the formation of barium follow through are (1) that it fails to have investigated antigiardial effects of precipitin lines. These methods failed to adequately distend the small bowel lumen metronidazole (M) (0-05-400 ,uM), reproducibly detect cyst antigen at the and may consequently fail to demonstrate mepacrine (Mep) (0-05-400 ,uM) and the concentration tested (2.3x106/ml). diseased segments. (2) overlapping loops bile saltlike antibiotic, sodium fusidate (F) Enzyme-linked immunosorbent assay, of small bowel may obscure disease and (3) (0-01-1-0 mM) in which we have demon- however, detected as -few as three on September 30, 2021 by guest. Protected copyright. the examination is time consuming. strated antigiardial activity. Parasite trophozoites and 15 cysts and successfully In order to try to overcome these uptake of 3H-thymidine was closely detected Giardia antigen in 12 cyst-positive criticisms each patient is given orally 300 correlated with growth in drug-free control stools and was negative in 38 of 40 cyst- ml of Baritop diluted to 50% WIV and lies cultures (r=0.91, p<0.001). Minimal negative stools. Although preliminary, on his right side outside the barium room. inhibitory concentrations (MIC) for M, these studies indicate that stool ELISA for After approximately half and hour most of Mep, and F were 50 Am, 50 ,mm and 300 Giardia antigen is a simple and sensitive the barium will have entered the small ,um respectively at 24 hours for both approach to the diagnosis of giardiasis. bowel. At this stage 100 Baritop effer- radiometric assay and growth. At four vescent tablets are given in divided doses hours, radiometric assay detected anti- liberating approximately one litre of gas giardial activity of F (3H-thymidine uptake F52 into the stomach which rapidly passes into -60% control) but not of M (--100% Intestinal permeability changes in asympto- the small bowel. Multiple spot films of the control). Trophozoite motility at four matic travellers to South India small bowel are taken, if necessary with hours was a less sensitive indicator being compression. By this method we can reduced to only 50% by drug concen- C NOONE, I S MENZIES, AND V I MATHAN (St significantly increase the amount of trations in excess of MIC's (M, Mep, and Thomas' Hospital, London, and Christian contrast medium (barium + air) in the F; >0-2, >0-35 and >0-6 mM respectively) Medical College, Vellore, India) The small bowel and at the same time reduce its and viability at these concentrations was urinary excretion ratio of lactulose and density thus achieving the twin objectives reduced by only -20%. Thus the radio- L-rhamnose-molecular radii 0-5 and 0-4 of distending the small bowel lumen whilst metric assay represents a sensitive and mm, may be used to assess intestinal reducing the number of overlapping objective assessment of antigiardial drug mucosal permeability, both sugars being barium filled small bowel loops. activity and may indicate inhibitory effects quantitatively excreted in the urine follow- Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1163 ing their unmediated intestinal absorption. maximal water absorption occurred with 80 n=8). Na+ absorption correlated signifi- Increases in intestinal permeability have and 100 mmol/l acetate with mean values of cantly with luminal [Na'] (r=0-75±0-04, previously been shown to be a useful index +18-80±3-59 and +25-25±2-78 ,ul/min/g p<0000l n=112) and perfusate [Na'] of mucosal damage. respectively. Water absorption also (r=0(62±0.06, p<().()()l n=112). but was Eleven visiting medical students who occurred from 30, 50, and 80 mmol/l independent of variations in glucose or denied any gastrointestinal disturbance bicarbonate solutions with mean values of water absorption. By extrapolation Na+ were studied one month after their arrival + 10-17±2-11, + 15-15±3-16 and secretion would occur if luminal [Na+] fell in South India, as were 10 healthy + 13-54±2-45 ,lI/min/g respectively when below 74-5 mmol/l or perfusate [Na+] was indigenous students in London and South compared with isotonic saline (+0.88±1-35 <48 mmol/l. India. Following an overnight fast all ,u/min/g, p<0.01). Sodium movement The sodium content of oral sugar- subjects ingested an isotonic load paralleled water movement. Surprisingly, electrolyte solutions or liquid enteral feeds containing lactulose 5 g, L-rhamnose 1 g, after induction of intestinal secretion by may therefore, be critical for sodium and collected urine for five hours. Quanti- cholera toxin, acetate (30 and 100 mmol/l) balance in the short gut. tative sugar analysis was carried out by and bicarbonate (30 mmol/l) both resulted paper and thin layer chromatography. in marked enhancement of the secretory The visiting students showed an state with mean values of -30 24±4-00, increased lactulose/L-rhamnose excretion -35-66±5 70 and -28-51±5-90 /.Ll/min/g F55 ratio (mean 0-12; range 0.01-0-40) respectively, compared to isotonic saline Effects of bacteroides melaninogenicus compared with both their Indian (0-04; (-12.95±2.49 pJI/min/g, p<0-001). How- toxin and bile salts on fat and calcium 0.01-0.06) and UK (0.03; 0.01-0.04) non- ever, 56 mmol/l glucose-saline completely absorption travelling colleagues. The changes in the reversed the secretory state to absorption. excretion ratio were due mainly to In the light of these findings, as well as K WALSHE, A B J SPEEKENBRINK, C T KEANE, D increases in lactulose excretion, mean 0-64, the results of clinical trials, one must G WEIR, AND R R O'MOORE (Departments of 0-24, 0-21% oral load excreted respec- question the use of acetate and bicarbonate Biochemistry, Microbiology and Clinical tively. Two students had sequential studies in oral rehydration solutions. Medicine, Trinity College and St James' showing a normal ratio in the UK, Hospital, Dublin, Eire) The mechanism increasing (0-1 and 0-3) soon after arrival for fat malabsorption in the contaminated in India, and returning to normal (0-02 and small bowel syndrome (CSBS) remains 0.02) later during their stay. Although F54 controversial. Most authorities' consider symptom-free, increases in permeability Jejunal Na+ absorption is concentration inadequate micelle formation to be the were associated with a decrease in whole dependent major factor. Recent studies, however, gut transit time. B J M JONES, B E HIGGINS, AND D B A SILK have suggested a possible role for bacterial Permeability changes of similar magni- (The Department of Gastroenterology and toxins in the pathogenesis of CSBS. We http://gut.bmj.com/ tude have been described in acute gastro- Nutrition, The Central Middlesex Hospital, have investigated the effects of bile salts enteritis and during the asymptomatic London) Sodium balance may be difficult and a specific toxin isolated from temporary passage of stool pathogens in to attain in patients with short bowel Bacteroides melaninogenicus, a common infants. The changes described in this study syndrome fed enterally and in whom net CSBS isolate, on the functional and imply asymptomatic mucosal damage, Na+ loss occurs with Na+ free drinks. The structural properties of the isolated loop which may be associated with changes in aim of the present study was to determine from rat small intestine. gut flora. the critical luminal [Na'] required for net After exposure of the intestine to the Na+ absorption over a short jejunal toxin, fat absorption, assessed in vivo, was on September 30, 2021 by guest. Protected copyright. segment. Thirty three normal subjects decreased from 604±13 nmol per 10 F53 underwent steady state perfusion of the minutes to 489±23 nmol per 10 minutes Acetate and bicarbonate enhance cholera proximal 25 cm jejunum with a double (p<0 (05). Toxin also reduced calcium toxin induced secretion in the rat proximal lumen-proximal occlusive balloon uptake from 0 907±0+03 nmol/mgl10 small intestine technique. Twelve different mono-, di-, or minutes to 0-776±0t)023 nmol/mg/10 polysaccharide substrates of varying minutes (p<0 005) as determined using as D D K ROLSTON, M J KELLY, M M BORODO, M J osmotic effect but equivalent to 140 mM in vitro tissue slice uptake technique. G FARTHING, M L CLARK, AND A M DAWSON glucose on complete hydrolysis were Deoxycholate (0( 25nM) decreased calcium (Department of Gastroenterology, St perfused at 20 ml/min. Isotonicity was uptake from 0-907±0+032 nmol/mg/l() Bartholomew's Hospital, West Smithfield, achieved by addition of NaCl (70-152 minutes to 0(761±0+027 nmol/mg/l0 London) Controversy exists as to the mmol/l). Na+ absorption (mmol/h/25 minutes (p<0-0(5) but had no effect on fat ideal composition of oral rehydration cm±SEM) from 140 mM monosaccharide absorption. Mucosal disaccharidase solutions. Acetate has been suggested as an solutions (5.3±6-2, n=33) was significantly activity was significantly depressed by toxin alternative to the conventionally used less than from maltose (28.3±2-4, n=6 and deoxycholate. Electron microscopic bicarbonate anion in oral rehydration p<0-001) sucrose (25.7±4-2, p<0-01 n=6) findings showed damaged microvilli and solutions. To study the effect of acetate maltotriose (35.9±3-7, p<0-001 n=8), mitochondria and swelling of the endo- (5-150 mmol/l) and bicarbonate (30, 50, glucose oligomers (38-7±3.1 p<0-001 plasmic reticulum. These results suggest and 80 mmol/l) on water and sodium n= 10) a complete amylolysate of starch that the malabsorption which occurs in transport in the secreting gut we performed (30(6±414. p<0.00l n=6). Caloreen CSBS is related to mucosal damage and steady state perfusions in the rat proximal (41.3±5.5, p<0-001 n=9) and a poly- that bacterial toxins are a possible small intestine. In the normal intestine, saccharide mixture (28.3±4.8, p<0001 contributory factor in its causation. Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1164 The British Society of Gastroenterology F56 excitation above and inhibition below a was made with DR3 and DR7. MB2-DC3, Fasting small intestinal motor activity in zone of distension, and this reflex has been an allelic specificity of the MB-DC locus chronic idiopathic intestinal pseudo- tested in man. Local responses to upper which is linked to DR, has recently been obstruction (CIIP) small intestinal distension were recorded in shown to have an even stronger eight healthy, fasted volunteers using a association. Thirty per cent of the general E R WOZNIAK, T R FENTON, AND P J MILLA standard perfused tube system. A 5 cm population possess this antigen. (Institute of Child Health, London, and diameter balloon separated three proximal The opportunity was taken to look for Hospital for Sick Children, Great Ormond and three distal recording channels. MB2-DC3, in children in whom the Street, London) Chronic idiopathic Studies comprised two consecutive three diagnosis of gluten intolerance was intestinal pseudoobstruction usually hour randomly ordered periods, during considered. Three groups of children were presents in childhood and may be due to one the balloon was inflated to produce studied. Group 1 (n=22) consisted of 15 disease of smooth muscle, enteric nerves or transient discomfort, during the control with proven coeliac disease (ESPGAN alterations of their neuroendocrine period the balloon was deflated. Imme- criteria); all were positive for MB2-DC3: environment. We have studied the diately after inflation a marked reduction and seven children provisionally diagnosed functional effects of these disease processes in total distal motility occurred; over at as coeliac disease by flat mucosal biopsy using constantly perfused nasojejunal least 15 cm, which persisted thoughout the and response to gluten free diet; all were catheters and simultaneously recording study period (mean reduction in con- MB2-DC3 positive. Group 2 (n=4) motility and myoelectric activity in nine tractions = 8-7±0-79 SEM/10 minutes, consisted of children with presumed children. In four neonates with a p=O-001)*. Total proximal motor activity transient gluten intolerance - that is, who myopathy, migrating motor complex showed a small increase (mean increase in are currently gluten tolerant; two were (MMC) like activity was present but both contractions = 8.3±3-9 SEM/10 minutes, MB2 - DC3 negative. In group 3 (n=5) the pressure (27-5±8.5 cm H20 controls p=0-1).* Normal phase 3 migration, over diagnosis of coeliac disease was excluded; 63±19-2 p The British Society of Gastroenterology A1165 decrease in xylose absorption occurred. No treatment with a gluten free diet. In IgA F62 histopathological abnormalities were seen deficient patients the mucosa produces Action of cytochalasin B and colchicine on in any of the jejunal biopsy specimens at very little IgA; IgG and IgM increase by the cytoskeleton of foetal human intestinal the end of the challenge. The present study way of compensation. The results are epithelium; an in vitro model for congenital does not support the concept that gluten compatible with the suggestion that the microvillus atrophy alone is toxic in susceptible individuals who pathogenesis of the coeliac lesion could be do not have overt coeliac disease. It due to antigliadin antibody. R R DOURMASHKIN, L CARRUTHERS, R J suggests further that factors other than DR SAPSFORD, AND J A WALKER-SMITH antigens and gluten are also important in (Laboratory for Paediatric Gastro- disease expression. enterology, St Bartholomew's Hospital, London) In congenital microvillus F61 atrophy (CMA), there is uptake of brush Small bowel mucosal conjugation and border material including microvilli into F60 pharmacokinetics of ethinyloestradiol in cytoplasmic vacuoles of the gut epithelium. Immunoglobulin production during in vitro patients with coeliac disease In our laboratory, SDS gel analysis of culture of biopsies from coeliac and IgA brush border preparations from a biopsy of deficient patients S F M GRIMMER, D J BACK, ANN COWIE, A this disease showed that myosin, normally ELLIS, I GILMORE, R B MCCONNELL, M L'E present in control biopsies, was greatly G M WOOD, P D HOWDLE, AND M S LOSOWSKY ORME, AND J TJIA (Department of Pharma- diminished. It was suggested that in this (Department of Medicine, St James's cology and Therapeutics, University of condition there is a defect in the actin- Hospital, Leeds) Attempts to study the Liverpool, and Departments of Gastro- myosin function of the cytoskeletal system production of immunoglobulins by the enterology, Royal Liverpool and Broad- of the enterocytes that leads to intractable small bowel mucosa have mostly been green Hospitals, Liverpool) In female secretory diarrhoea. In this study, we have indirect, with collection of secretions from patients with coeliac disease there is only examined the effect of cytochalasin B the small bowel. This method ha§ a number minimal impairment of fertility, and the (CB), which disrupts microfilaments, and of disadvantages such as contamination by usual method of contraception is the colchicine, which depolymerises secretions from the biliary system or combined oral contraceptive steroid microtubules, on enterocytes of human stomach and degradation of immuno- preparation (OCS). The usual oestrogenic foetal gut epithelium cultured in vitro. In globulins by digestive enzymes. Such work component of the OCS is ethinyloestradiol this way, we aimed to provide an in vitro has indicated that the secretions from which is extensively conjugated in the small model for CMA. Electron microscopy of untreated coeliac patients have raised bowel mucosa by conjugation with cultures treated with CB showed a biphasic levels of IgA and IgM. There is one sulphate. The bioavailability of ethinyl- effect. After 40 min treatment, cytoplasmic previous report which describes increased oestradiol in normal women is 41-8±9-5% belbs containing 7 nm filaments (micro- http://gut.bmj.com/ IgA concentration in the culture medium (mean±SE) but this figure might be filaments) formed at the cell membranes following organ culture of a small bowel increased, with toxicological implications, and notably, at the tight junctions of the biopsy from a single untreated coeliac if small bowel disease impaired sulphate enterocytes; also, the microfilaments that patient. conjugation. This study links in vitro form the rootlets of the microvilli were We have cultured small bowel biopsies metabolism data with the pharmaco- either very short or absent. After 24 h from treated and untreated coeliac and IgA kinetics of ethinyloestradiol in the sathe treatment, large areas of the brush border deficient patients and from normal controls patients. Six patients (aged 22-37 years) were taken up into cytoplasmic vacuoles, and measured IgA, IgG, IgM and IgE with confirmed coeliac disease were and the microvilli within the vacuoles on September 30, 2021 by guest. Protected copyright. concentrations in the culture medium studied. At diagnostic biopsy, samples of showed various stages of degeneration. following 24 hours culture. jejunal mucosa were removed and SDS gel analysis of brush borders from this In 11 untreated coeliac patients, IgM and incubated with 3H-ethinyloestradiol. The preparation showed markedly diminished IgA concentrations were raised compared mean percentage conjugation of ethinyl- myosin, as was found in the case of CMA. with 11 normal control patients; IgG was oestradiol was only 5 9±+17% compared Colchicine treated cultures showed little not significantly raised. In 11 treated with 16-6±2-9% in eight control women uptake of brush border material into the coeliac patients only IgM remained raised who had histologically normal small bowel cells, and there was no effect on myosin when compared with control patients. mucosa (p>0-02). Each patient then binding in SDS gel analysis. Control There was no additional effect when received 50 ,ug ethinyloestradiol by the iv cultures showed neither phenomena. It was Frazer's gluten fraction III (1 mg/ml) was and oral routes on separate occasions and concluded that the integrity of the micro- present in the medium during culture. IgE blood samples were collected over a 24 filament structure of the cytoskeleton is was less than 5 IU/ml in the culture hour period. The bioavailability of ethinyl- necessary for the maintenance of the brush medium from all patients. Three IgA oestradiol was calculated by comparing the border and the actin-myosin system, and deficient patients had markedly decreased area under the plasma ethinyloestradiol that a defect in this system is present in concentrations of IgA in the medium and concentration versus time curve for the iv CMA. significantly raised IgG and IgM values and oral doses. The mean bioavailability of compared with controls. ethinyloestradiol was 6144±121% (n=5, These findings show that the untreated p>0-05) and there was no clear correlation coeliac mucosa itself is responsible for the between the in vitro gut wall metabolism of F63 production of increased amounts of IgM ethinyloestradiol and its in vivo bio- Non-invasive investigation of the gastro- and IgA and these changes are reversed by availability. intestinal tract in collagen-vascular disease Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1166 The British Society ofGastroenterology A KESHAVARZIAN, S H SAVERYMUTTU, V S and Crohn's disease. It has been suggested of Crohn's disease between 1964 and 1979, CHADWICK, J P LAVENDER, AND H J F that the serum concentration of the acute with a more marked rise in women in HODGSON (Royal Postgraduate Medical phase protein, C-reactive protein (CRP) recent years. The clinical study discloses School, Hammersmith, Hospital, London) may be higher in Crohn's disease compared that the incidence of toxic megacolon, liver Collagen-vascular diseases frequently with ulcerative colitis for the same degree disease arthropathy, and eye disease have affect the gastrointestinal tract, and such of inflammatory disease activity, but this shown no significant change with time involvement is a significant cause of conclusion was reached using clinical whereas a significant fall has occurred since mortality and morbidity. Investigation is assessments for judging disease activity. 1967 in the occirrence of enterocutaneous frequently difficult in severely ill patients, We have now used the technique of faecal and enterovesical fistulae. As regards and yield of conventional investigations "'Indium granulocyte excretion to macroscopic disease, the ileum has become such as intestinal biopsy is disappointingly quantify precisely acute inflammatory significantly less commonly involved, and low. We have investigated the use of activity and performed a prospective the left colon, rectum and perineum signi- 111-Indium leucocyte scanning, which correlative study with serum C-reactive ficantly more commonly so since 1967. would be expected to identify areas of protein in 38 patients with Crohn's disease These data support the view that a perivascular or generalised neutrophil and 30 patients with ulcerative colitis. change is occurring in the clinical pattern as infiltration, in patients with collagen- Patients were divided into groups matched well as the incidence of Crohn's disease vascular diseases suffering from either for disease activity according to faecal with time. gastrointestinal symptoms (diarrhoea or "'Indium granulocyte excretion. Serum abdominal pain, 15 patients) or from CRP concentration ranged between <2 otherwise unexplained fever (six patients). mg/l - 196 mg/l in Crohn's disease and <2 F66 Among patients with gastrointestinal mg/l - 54 mg/l in ulcerative colitis.. For all Intestinal permeability in inflammatory symptoms, seven out of 15 had positive groups of disease activity serum CRP diseases scans suggesting large or small bowel concentration was significantly higher for involvement: three out of three patients Crohn's disease compared with ulcerative R T JENKINS, R L GOODACRE, P R ROONEY, R H with Behcet's syndrome, four out of five colitis (p<0.01). No significant difference HUNT, AND J BIENENSTOCK (Intestinal with vasculitis, but none out of six with was found in ESR. These findings show Disease Research Unit, McMaster Univer- systemic lupus erythematosus. Among that the acute phase response differs sity, Hamilton, Ontario, Canada) Abnor- patients without gastrointestinal symp- significantly between Crohn's disease and malities in intestinal permeability in toms, only one patient (with polyarteritis ulcerative colitis. This may reflect a signifi- inflammatory disease have been recently nodosa) had a positive scan showing both cant difference either in the pathological documented by measuring the urinary large and small intestinal involvement. processes, or in the aetiopathogenesis of excretion of various molecular probes after White cell scanning offers a non- these diseases. oral ingestion. The purpose of this study invasive, readily tolerated technique for was to elucidate alterations in bowel http://gut.bmj.com/ identifying inflammatory involvement of permeability in patients with Crohn's the intestine in patients with collagen- F65 disease, ulcerative colitis, or rheumatoid vascular disorders. Involvement of the Changing scene in Crohn's disease in south- arthritis by using an oral dose (caSOuCi) of gastrointestinal tract is rare in the absence east Scotland 5iCr-EDTA, a hydrophilic molecule with a of symptoms. Among symptomatic molecular weight of 341-2 dalton. Perme- patients, inflammatory involvement of the J H ENTRICAN AND W SIRCUS (Gastro- ability was assumed to be directly related to gut is more likely to be found among intestinal Unit, Western General Hospital, urinary excretion of 5'Cr-EDTA. A control patients with vasculitis or Behcet's. Edinburgh) A study of Crohn's disease in group of 38 hospital personnel (21 men; 17 on September 30, 2021 by guest. Protected copyright. south-east Scotland has been carried out, women) between the ages of 22 and 56 the aim being to determine what changes if years and with no overt signs of either F64 any have occurred in the incidence and inflammatory bowel or joint disease was Differing acute phase response in Crohn's clinical pattern of Crohn's disease over assembled. A dose of 5'Cr-EDTA was disease and ulcerative colitis time. The study is in two parts. An administered orally, after an overnight epidemiological study was based on data fast, and urine was collected for 24 hours. S H SAVERYMU1TU, M B PEPYS, V S CHADWICK, collected from hospital records of all The normal control group had urinary AND H J F HODGSON (Gastroenterology Unit inpatients treated during the last 20 years excretions of the probe molecule from 0-61 and MRC Acute Phase Protein Research in Lothian Region (comprising the City of to 2-82%/d (mean 1*35%/d; SD, 0-61%/d; Group, Immunological Medicine Unit. Edinburgh, Mid-East and West Lothian). median, 1-16%/d; 95% confidence RPMS, Hammersmith Hospital, London) The clinical study involved detailed interval, 0-65-2*59%/d). Of the normal Crohn's disease and ulcerative colitis are analysis of the case notes of 300 patients controls, no difference could be accounted inflammatory conditions of unknown with Crohn's disease treated at the Gastro- for upon the basis of age or sex. Nine of 14 aetiology and unpredictable natural intestinal Unit of the Western General patients with active Crohn's disease history, but there are no haematological or Hospital between 1950 and 1981. The exhibited increased urinary excretion serological abnormalities which affect their clinical pattern of the disease was (range 2-95-7-20%/d) of the probe while clinical and pathological differences. The compared between two groups divided all patients in remission had excretion most widely used non-specific index of arbitrarily by year of onset of disease into within the 95% confidence interval. Seven inflammatory activity is the erythrocyte the two eras 1950-67 and 1968-81. of eight patients with active ulcerative sedimentation rate (ESR) which is raised The results show that overall there has colitis had raised excretion (range 4-09- to a similar extent in both ulcerative colitis been a three-fold increase in the incidence 11-23%/d), and seven of eight patients in Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1167 remission had normal levels of excretion. by measuring plasma sulphapyridine plasma zinc in ji mol/l. Crohn's disease no Thirteen of 16 patients with active concentrations in the same patients given steroids 2-4 and 10-3; CD on steroids 3-8 rheumatoid arthritis showed raised metronidazole 400 mg b d and sulpha- and 11 1; non-inflammatory non-steroid excretion (range 2-67-10-2%/d). The salazine g b d simultaneously for 10 days. controls 3-3 and 11-4. It is clear that both differences between the normal control Plasma sulphapyridine concentrations plasma zinc and ileal MT are decreased in group and the groups with inflammatory tended to fall in the CD group (day 1, Crohn's disease. Steroid administration diseases were statistically significant 22-1±2-0,g/ml; day 10, 15-95±4-5 ug/ml) results in an increase in both indices to the (Crohn's disease, p<0-001, ulcerative while it tended to rise in the colitis group levels observed in the control group which colitis, p<0-01; rheumatoid arthritis, (day 1, 26-0±6 ,ug/ml; day 10, 36-4±8-5 may reflect its therapeutic effect. We p<0.001). One patient with acquired ,ug/ml). These changes were not statis- conclude that the immunohistological immune deficiency syndrome and histo- tically different. demonstration of ileal mucosal MT logically documented severe atrophy of the Our results suggest that patients with provides a new and useful marker of body intestinal brush border showed a markedly Crohn's disease handle metronidazole in a zinc status in health and disease. raised urinary excretion (6-38%/d) of 5'Cr- similar manner to patients with UC and to EDTA after an oral dose. These findings normal subjects. Metronidazole, unlike confirm the work of other groups and other antibiotics, does not appear to provide further evidence that there are interfere with diazo-link splitting of F69 disturbances of intestinal permeability sulphasalazine. Renal proximal tubular dysfunction in associated with inflammatory diseases. The Crohn's disease observation that there is increased bowel permeability in patients with rheumatoid P A WINSTANLEY, J B YOUNG, A M arthritis raises the question of a possible BROWNJOHN, E H COOPER, AND A T R AXON intestinal defect that has hitherto not been F68 (Renal and Gastroenterology Units, studied. It seems clear, therefore, that Effect of steroid therapy on ileal zinc General Infirmary, Leeds, and Unit for there are increases in gut permeability metallothionein in Crohn's disease Cancer Research, University of Leeds, during episodes of inflammatory diseases, Leeds) Alpha-1-microglobulin (oi1M) is a although the mechanism involved in these MARGARET E ELMES, JOHANNA P CLARKSON, B circulating glycoprotein probably synthe- increases remains unknown. JASANI, AND M WEBB (Department of sised in the liver. It has a low molecular Pathology, Welsh National School of weight (26 000 daltons) and it is therefore Medicine, Cardiff, and MRC Toxicology filtered by the glomerulus followed by Unit, Carshalton, Surrey) Decreased zinc reabsorption and catabolism by the renal F67 absorption and low plasma zinc are found proximal tubular cells. Alpha-I- Can metronidazole and sulphasalazine be in poorly nourished patients with Crohn's microglobulin is not an acute phase http://gut.bmj.com/ used together to treat inflammatory bowel Disease (CD). Two patients on steroid reactant protein and the serum concen- disease? therapy for CD had an unexpectedly high tration undergoes little change in inflam- mucosal zinc measured by radiographic matory and neoplastic disease. Increased J L SHAFFER, A KERSHAW, J B HOUSTON, AND micro-analysis in the ileum. This may be urine concentration is therefore due to L A TURNBERG (Department of Medicine, because of steroid induction of synthesis of increased renal proximal tubular cell Hope Hospital, University of Manchester the zinc binding protein metallothionein function and its measurement provides a School of Medicine, Salford, and Depart- (MT). We have recently shown ihmuno- sensitive index of the reaction of the kidney ment of Pharmacy, University of reactivity to MT in formalin fixed human to various toxic stimuli. on September 30, 2021 by guest. Protected copyright. Manchester, Manchester) The pharmaco- small intestine using antibody to rat liver We have studied the urinary concentra- kinetics of metronidazole were studied in zinc MT and a sensitive DNP hapten tions of ol M in 22 consecutive patients with seven patients with Crohn's disease (CD) sandwich based immunocytochemical Crohn's disease attending an outpatient and five patients with ulcerative colitis technique. Metallothionein appears to be clinic. The Crohn's disease had been (UC) matched for age, sex, and weight. present in both cytoplasm and nucleus of present for one month to 22 years (mean 6A Multiple plasma samples were assayed for villous enterocytes, adjacent basement years) and a Simple Disease Activity Index metronidazole after an intravenous dose membrane region and lamina propria but was 0-S15 (mean 9). A random urine sample (400 mg) administered over 20 min and on was not found in the crypts. was collected and urinary cxM concen- another occasion after a similar oral dose. Surgically resected ileal mucosa from tration measured by single radial immuno- Bio-availability was calculated from the five cases CD (no steroids); six cases CD diffusion with the results corrected for two types of concentration/time curves and (on steroids) and 12 cases of non-inflam- urinary creatinine concentration and was found to be 88±0-03% in CD and matory bowel disease not on steroids was expressed as mg/g creatinine. 92±0 06% in UC. Plasma clearance rates examined immunocytochemically for MT Urine ox,M concentration was increased were comparable at 3-24±0+2 I/h in CD and scored on a 1-3 subjective scale for in 10 patients (>10 mg/g creatinine) (mean and 4-12±)-49 I/h in UC. Elimination intensity and distribution of the resultant (SD) 37-6 (26) mg/g). These findings half-lives (TI) were also similar (CD staining in three sites; enterocyte indicate a previously unrecognised renal 7-8±0-35 h. UC 6-7±0+64 h). These cytoplasm; enterocyte nucleus; basement proximal tubular dysfunction in Crohn's results are similar to those reported in membrane region. Preoperative plasma disease. Its significance is unknown as the normal subjects. zinc was measured by atomic absorption patients with raised ot,M could not be The influence of metronidazole on spectrophotometry. Results are shown distinguished by duration or severity of sulphasalazine disposition was determined with the overall zinc MT score first and disease in this small sample. Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1 168 The British Society of Gastroenterology F70 (Department of Prostaglandin Research, Policlinico, Modena, Italy) Evidence has Evidence of lymphocyte alveolitis in Wellcome Research Laboratories, been accumulated, in the last two decades, Crohn's disease patients Beckenham, Kent) In inflamed colonic indicating a relation between diet, tissue from patients with ulcerative colitis, intestinal degradation of acidic and neutral A CORTOT, B WALLAERT, P BONNIERE, J F there is an increased synthesis of several sterols by colonic bacteria and the develop- COLOMBEL, A B TONNEL, C VOISIN, AND J C prostanoids and also metabolites of the ment of colorectal cancer. The issue, PARIS (Gastroenterology Unit, C. H. R., lipoxygenase pathway of arachidonic acid however, is still controversial; thus, for and Pneumology Department, Hospital A. (AA) metabolism, 12-HETE, 15-HETE instance,, the risk of colonic tumours has Calmette, Lille, France) Reduced lung and LTB4. These metabolites may have a been associated either to an increased or to transfer factor without pulmonary role in the pathogenesis of inflammatory a decreased degradation of cholesterol to symptoms in Crohn's disease (CD) bowel disease (IBD). We have now investi- coprostanol and coprostanone. In normal suggests a latent pulmonary involvement. gated the metabolism of AA by inflamed North Americans on a free diet it has been Bronchoalveolar lavage (BAL) is adequate colon from a guinea-pig model of colitis. suggested the existence of two distinct for detection of alveolar silent abnormal- Inflamed colonic tissue from guinea-pigs pattern of degradation, one characterised ities. Therefore we have assessed skin sensitised to dinitrochlorobenzene by extensive conversion of cholesterol, the pulmonary function tests (PFT) and the (DNCB, 50 ul, 2-5% in ethanol) and other by little or no conversion. The cellular characteristics of BAL in 17 challenged 10 days later with intrarectal purpose of this study, therefore, was to consecutive CD: nine women, eight men, DNCB (1 ml; 1% in Orabase) was evaluate the excretion and the degradation 30±7 years (mean±SD) 7 smokers (S), 10 homogenised and incubated (30 min, 37°C) of cholesterol in a large group of volunteers non-smokers (NS) and in 26 controls: nine either alone for studies using RIA for kept under metabolic control. women, 17 men, 33±7 years, 14 S and 12 measuring AA metabolites or in the Thirty eight volunteers (members of the NS. None had clinical pulmonary history presence of 14C-AA (1-3 qug, 250 nCi). staff or patients without gastrointestinal or and all had normal chest radiograph. The Samples for RIA were frozen directly after other major disorders) were put on a CD duration was 53±61 months (1 month to incubation. '4C-AA metabolites were standard solid diet containing a constant 22 years). The site of CD was small bowel extracted and separated with standards by amount of cholesterol. Cr2O0 (300 mg/day) alone (1), colon alone (5), and both (11). TLC. was given to correct for changes of faecal Mean CDAI was 196±84 (50 to 355). Small amounts of PGE2 6-keto-PGFI,, flow. All faeces were collected for four to Seven patients had systemic manifest- TXB2 and LTB4 were formed by guinea- six days and each sample separately ations: arthritis (four), spondylitis (two), pig colon from endogeneous AA, as analysed. Individual sterols were identified aphtosis (one). Three has sulphasalazine 2 measured by RIA. In inflamed tissue the and quantified by GLC using 5-cholestane g/day (3 to 36 months). (1) PFT were formation of the prostanoids was signifi- as internal standard. abnormal in 12 CD, reduced transfer factor cantly increased (p<0.05); PGE2 (6-8 x Daily faecal neutral sterol excretion was being the most frequent (7) (43%). (2) control formation), 6-keto-PGF1, (x2-7) 420-4±31-5 mg (mean±SE, range 300-60 http://gut.bmj.com/ Total BAL cell count and viability of and TXB2 (x3.8) whereas LTB4 was mg/day). In all the investigated subjects alveolar macrophages were identical in unchanged. coprostanol was the most abundant neutral both groups. (3) Alveolar lymphocytes The formation of the major '4C-AA sterol (77.4±2-2%), followed by percentages were higher in NS metabolites was also significantly increased cholesterol (13.9±1.7% p<0.001 versus CD:39±24% versus 11*5±6% in NS in inflamed tissue; PGE2 (10-2 x control), coprostanol) and by coprostanone controls (p<0.0005) and in S CD 15±14% PGD2 (x3-5), TXB2, PGF.,, and 6-keto- (8.9±1 2% p CD (59%) had more than 18% of alveolar 15-HETE (x2-6). stanol and cholestanone were detected on September 30, 2021 by guest. Protected copyright. lymphocytes (normal upper limit: NS and S As in human colon, there is an increase only in a few patients and in trace amounts. controls mean +2 SD). (4) There was no in both prostanoid and HETE formation in Percent of degradation (coprostanol + correlation between BAL abnormalities inflamed guinea-pig colon, although LTB4 coprostanone) ranged between 63 and and any of CD features or altered PFT. We formation was not increased. The DNCB 98%. conclude that lymphocyte alveolitis exists model of colitis offers an experimental This study suggests the existence of only in one of two of our CD patients and is not means of investigating the effect of drugs one major pattern of cholesterol related to any characteristic of CD and/or on AA metabolism and the involvement of conversion in the normal human intestine - pulmonary dysfunction. This suggests a these metabolites in inflammation. that is, cholesterol is largely degradated to latent pulmonary involvement in CD its metabolites by colonic bacteria. In our similar to that described in patients with opinion, previous reports of two extrathoracic sarcoidosis or collagen degradation patterns depended on external vascular disorders and with normal chest Colorectal influences (diets, alcohol and other roentgenogram. beverages) due to the lack of metabolic F72 control. Excretion and degradation of faecal neutral F71 sterols in human beings under metabolic Increased metabolism of arachidonic acid in control F73 inflamed guinea-pig colon from a model of Inhibitory effect of peppermint and colitis M PONZ DE LEON, P DI DONATO, L RONCUCCI, menthol on human isolated coli P REBECCHI, AND N CARULLI (Clinica N K BOUGHTON-SMITH AND B J R WHITTLE Medica I, University of Modena, B A TAYLOR, D K LUSCOMBE, AND H L DUTHIE Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1169 (Department of Surgery, Welsh National tone in patients with the irritable bowel Velocimeter. (3) Xe '33 clearance with School. of Medicine, Cardiff, and Division syndrome (IBS) leading to spasm and scintillation counter. (4) Clark-type oxygen of Pharmacology, Welsh School of oversensitivity to distension. We have electrode and a picoammeter. Twenty Pharmacy, Cardiff) Peppermint oil (PO), measured rectal sensation, volume and segments of rabbit intestine were variably which improves some symptoms of irritable distensibility in IBS patients with constipa- devascularised from terminal mesenteric bowel syndrome, exerts its inhibitory effect tion and compared it with an age and vessels to main mesenteric artery, with on guinea-pig ileum via a mechanism sex-matched asymptomatic control group later revascularisation. Doppler ultrasound involving calcium antagonism. We have of subjects (n= 10). A proctometrogram measured velocity in the mesenteric vessel, now investigated the effects of PO and of was obtained by inflating a highly but not tissue flow. Laser Doppler was menthol, the major component of PO, on compliant rectal balloon at a constant rate sensitive to movement and the readings human isolated taenia coli. A total of 50 (67 ml H20/min) and monitoring intra- were not reproducible. The oxygen strips of taenia, approximately 30x3 mm, luminal pressure by a microtransducer. electrode has proved easy to use, and was were dissected from 20 resections for Volumes (V ml H20) were recorded at reproducible. The electrode was calibrated carcinoma. Tissues were either used imme- threshold and constant sensation and in air and 02 depleted solutions, the diately, or stored overnight at 4°C in maximal tolerance (MTV). Pressures (Pcm temperature coefficient was 4% per 'C. Kreb's solution (mM: NaCl 118-0; KCI 4-7; H20) were recorded simultaneously and The relation between 02 tension and Xe'33 CaC12 2.5; MgCl2 1-2; NaHCO3 25 0; rectal compliance (RC, (AV/AP) ml/cm clearance has shown that the intestine is NaH2PO4 1-4; glucose 11-5). Unless H20) was calculated on the linear portion able to adapt to reduced blood flow until a otherwise stated, experiments were carried of the graph. Seven out of 10 patients in the critical level of 30% is reached (Xe'33 out after 30 minutes equilibration at 37°C IBS group complained of extreme 'pain' clearance ti 280 (s). The use of vasodilators in Kreb's solution bubbled with 5% CO2 in and urgency compared with 'discomfort' in was then assessed using isoprenaline, nafti- 02. No gross differences were observed in the control group at the MTV. The induced drofuryl, isoxsurpine, and a thromboxane stimulated responses or in spontaneous pain was of the same quality and site as synthetase inhibitor. The first three vaso- activity in tissue taken from different their presenting complaint. here is a dilators reduced blood flow and oxygen regions of the colon. Peppermint oil and significant reduction in volumes at the tension to the colon as perfusion pressure menthol produced both inhibition of spon- constant sensation and MTV in the IBS was reduced to lowering of systemic blood taneous activity and decrease in basal tone group compared with controls (volume at pressure. The thromboxane synthetase in all tissues in a dose-dependent manner. constant sensation, mean 154±26 SEM v/s inhibitor did not effect blood pressure and Under isotonic conditions (tension 2 g), 290±23, p<0*01; MTV 294±32 v/s increased oxygen tension. It is concluded ID,,, values (concentration of antagonist 505±25. p<001) but not in volume at that the use of the 02 electrode in assessing producing 50% reduction in response to threshold sensation (mean 122±17 SEM intestinal viability shoud be studied. The carbachol, 10-6M) were calculated for v/s 210±30, p>0-05; Wilcoxon's signed effect of the thromboxane synthetase menthol (0-29±0-11 mM; n=5) and for PO rank sum test). Rectal compliance was also inhibitor on intestinal ischaemia and http://gut.bmj.com/ (0-41 ±0-06 mM; n=5: estimated MW 160). significantly reduced (IBS mean 3-8±0-5 anastomoses warrants further investi- Under isometric conditions, dose-response SEM v/s controls 8-5±0-5, p<0-01). A gation. curves to carbachol (10-7-10-4M) and to correlation exists between MTV and RC potassium (5-150 mM) demonstrated non- (r=0-9, p<001). Comparable pressure competitive inhibition by both PO and measurements showed no significant F76 menthol, this effect being rapidly differences. Granulocyte migration to uncomplicated reversible on wash-out. In calcium-free, This study indicates increase of rectal intestinal anastomoses in man depolarising Kreb's solution (mM: NaCl tone in the constipated IBS group which on September 30, 2021 by guest. Protected copyright. 82-7; KCI 40 0; NaHCO3 25-0; NaH2PO4 may be responsible for the reduced volume A KESHAVARZIAN, R GIBSON, J SPENCER, J P 1-4; glucose 11 5), dose-response curves to tolerance and oversensitivity to distension. LAVENDER, AND H J F HODGSON (Royal calcium (0-1-20 mM) showed a specific Postgraduate Medical School, Hammer- calcium antagonist effect of menthol, smith Hospital, London) Experimental which was dose-related and rapidly F75 work shows that neutrophil leucocytes are reversible. These results indicate that the Tissue oxygen tension and Xe'33 clearance not necessary for process of wound repair inhibitory effect of PO on human taenia in the assessment of intestinal perfusion and in skin in animals, although they accumu- appears also to involve calcium the effect of vasodilators late in aspetic wound within the first two antagonism, and that menthol is mainly days. The histological sequence of events responsible for this effect. A SHANDALL, R LOWNDES, H L YOUNG, E 0 in intestinal anastomoses is the same as CRAWLEY, AND K G LEACH (INTRODUCED BY those seen in wound healing elsewhere in J V PSAILA) (Departments of Surgery and the body, but, owing to presence of F74 Medical Physics & Bioengineering, bacterial flora, the magnitude, duration Abnormalities of rectal distensibility in the University Hospital of Wales, Cardiff) No and implications of neutrophil migration irritable bowel syndrome reliable methods of assessment of intestinal might be different. We therefore investi- tissue perfusion are available. We have gated this, using 111-Indium granulocyte J S VARMA AND A N SMITH (University studied Doppler ultrasound, laser Doppler scanning in patients with uncomplicated Department of Surgery/Urology, Gastro- and oxygen tension compared with Xe'3 intestinal anastomoses. Eight patients Intestinal Wolfson Laboratory, Western clearance in devascularised intestine. The underwent resection and anastomosis General Hospital, Edinburgh) There is methods used were: (1) 10 MHZ Doppler (right hemicolectomy five, sigmoid indirect evidence of increased intestinal and spectral analyser. (2) Laser Doppler colectomy two, ileal resection one). All Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from Al 170 The British Society of Gastroenterology patients had an uneventful postoperative (mean 37-7±1-4 SEM). All incontinent an earlier stage. Elderly patients with course, with no evidence of any leakage or patients showed abnormalities; four had diverticular disease may first need a barium infection. 111-Indium granulocyte scan and absent responses and 10 showed prolonged enema, but FS may save unnecessary abdominal ultrasound were performed 7- latencies (range 49-66-4 msec; mean examinations in others. Flexible sigmoid- 20 days (12±4.7, +±SD) following surgery. 56-4±1-8 SEM). This prolongation is oscopy has a place in the prompt investi- "'In scan showed the presence of labelled significant when compared with the control gation of lower gastrointestinal symptoms. granulocytes at the site of anastomosis in group (p<0-01, Wilcoxon's rank sum test) all patients. In three out of eight, cells and is not age-dependent. subsequently passed into the lumen of the This study indicates that the latency of bowel. In contrast, granulocytes were not the F79 sacral evoked response is a useful index factor in normal visualised along the abdominal incision. In of neuropathy. The abnormal responses Epidermal growth binding all cases, abdominal ultrasound was normal demonstrated in idiopathic faecal inconti- and cancerous human gut epithelia with no evidence of abscess or collection. nence in this disorder suggest a neurogenic Thus, in contrast to skin wounds, granulo- aetiology. Electrophysiological recording ALLISON F WREN, S R CROSBY, AND J B ELDER cytes continue migrating into the intestinal of the evoked response by the techrtique is (Department of Surgery, Manchester wall in areas of anastomoses for University Medical School, Manchester) up to 20 a convenient and reliable method of assess- Virus-transformed days. The role of granulocytes in intestinal ing the innvervation of the pelvic floor. cells and certain human repair may therefore be different from tumour cells produce transforming growth elsewhere in the body. Moreover, this factors (TGF's). Transforming growth factor-I is structurally related to EGF and phenomenon has an important clinical F78 implication, as "'In granulocyte scanning competes with it for the EGF receptor on Open access flexible sigmoidoscopy - a cell membranes. We have measured the is now being used following intestinal useful contribution to the management of surgery for detection of infection and binding of '25I-EGF to the cell membranes patients with lower gastrointestinal of human gastric and colonic adenocarcino- inflammation. The normal appearances symptoms? seen in uncomplicated intestinal anasto- mata, to non-cancerous but adjacent 'normal' epithelia and to the cell moses should not be confused with abscess A M ROE, K D VELLACOTr, AND N or diffuse mucosal inflammation. J MCC membranes of one truly normal colon. MORTENSEN (University Department of Aliquots of the crude membrane fractions Surgery, Bristol Royal Infirmary, Bristol) containing 100 ,ug protein were incubated As up to 25% of patients with colorectal with varying concentrations of '25I-EGF. F77 cancer are still admitted as emergencies we Bound and free peptide were separated by Sacral evoked response - a useful index of have investigated the place of an open filtration. From Scatchard analysis of the neuropathy in faecal incontinence access flexible sigmoidoscopy service (FS) binding data we have shown that in the management and early diagnosis of carcinomas of the ascending colon bound http://gut.bmj.com/ J S VARMA AND A N SMITH (University patients with rectal bleeding or symptoms 0-017 pM EGF/mg protein, significantly Department of SurgerylUrology, Gastro- suggesting colorectal disease. less (p<0-05) than adjacent 'normal' Intestinal Wolfson Laboratory, Western Of the first 150 consecutive patients, 89 membranes (n=4, 0-03 pM/mg protein). General Hospital, Edinburgh) Stimlu- presented with rectal bleeding, 59 with Similarly, carcinomatous tissue of the lation of the dorsal nerve of the penis or change in bowel habit and 24 with sigmoid bound less EGF (0-11 pM/mg clitoris evokes a response at the bulbo- abdominal pain. Thirty one per cent (46) protein) than normal membranes (0-29 cavenous and external anal sphincter had a normal examination, but 13% (20) pM/mg protein). This spectrum of EGF muscles which is dependent on an intact had a colorectal neoplasm, 16% (24) binding - lower in ascending and transverse on September 30, 2021 by guest. Protected copyright. reflex arc mediated via the sacral spinal diverticular disease, 9% (13) proctitis or colon than in sigmoid - was also apparent cord. To assess its usefulness in the colitis and 24% (36) had haemorrhoids. in the truly normal colonic membranes. detection of neuropathy we have measured A full examination was achieved in 76% Antral carcinoma bound less EGF than the latency of the anal sphincter response and only 5% had insufficient bowel their adjoining 'normal' mucosa, though in 14 women patients with idiopathic faecal preparation. Of those with diverticular this difference was not significant. These incontinence and 22 asymptomatic control disease (DD), 83% had a limited examina- results are consistent with the proposal that subjects using an averaging electrophysio- tion to <50 cm (p<0.001 compared with gut carcinomas produce a species of TGF-I logical technique. non-DD), as a result of narrowing (13), which can utilise the normal EGF receptor Submaximal train stimuli (duration 0-1 pain (five) or failed preparation (two). to mediate its role in the growth of msec, frequency 2 Hz, voltage approxi- Twelve adenomatous polyps were found neoplastic cells, thereby reducing the mately three to four times sensation in 11 patients. Carcinoma was found in amount of exogenous EGF that can be threshold) were applied by a surface nine (five rectal, four sigmoid): two Dukes' bound to the membranes. electrode. One hundred to 200 anal B and six Dukes' C. A barium enema was sphincter responses were detected by a arranged in 17 patients (11%), significantly surface bipolar platinum anal plug more in those with DD than normals F80 electrode and the digitally average (p<0-05). One polyp missed by FS was Faecal carcinoembryonic antigen (CEA) in response recorded (sweep 100 msec). The discovered by subsequent barium enema. patients with colorectal cancer procedure was repeated for each subject. These results suggest open access FS will Stable and constant responses were yield a reasonable proportion of positive R S STUBBS, BAIRD I MCLEAN, AND J E SHIVELY obtained in all cases. The control group findings including neoplasms, but there was (Hillingdon and West Middlesex Hospitals, showed a latency range of 27-2-47-6 msec no evidence that carcinoma was found at Middlesex, and City of Hope National Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1171 Medical Center, Duarte, California, USA) Eighty six subjects with gastrointestinal screening compared to those detected by The early promise of serum CEA measure- cancer, 168 subjects with proven benign GI clinical symptoms and also a lower propor- ment for detecting colorectal cancer has disease and 750 individuals attending their tion of positive screened patients with both regrettably not been fulfilled because of practitioners with non-gastrointestinal Haemoccult methods. Patients with inadequate sensitivity and specificity. complaints were assessed. Each person colorectal polyps had 141/432 (32 6%), Immunofluorescent techniques have completed a 41 item questionnaire and 100/402 (24'9%) and 44/402 (10 9%) localised CEA primarily to the cell gave a blood sample for the estimation of positive samples with the three methods. membrane of tumour cells. It may CEA, C-reactive protein, alpha-l-acid Patients with polyps diagnosed through therefore be that colorectal cancers shed glycoprotein and gamma glutamyl trans- screening had a higher proportion of CEA into the bowel lumen. This is indeed peptidase. samples and patients positive with each the case. We measured faecal CEA in 21 To establish a series of probability coeffi- method compared to those diagnosed as colon cancer patients and 24 controls by a cients an initial logistic regression analysis part of a routine follow up study. radioimmunoassay technique utilising a was applied to 54 cancer patients, 80 We conclude (1) bleeding from conventional polyclonal antibody. As benign cases, and 200 GP subjects, and colorectal carcinomas and polyps is measured by this system CEA was present using these coefficients, the remaining detected more frequently by an immuno- in large amounts in all subjects. Paradox- cases were assessed. In the initial analyses, diffusion technique than by using ically, the concentrations were somewhat permitting only a 5% false positive rate, Haemoccult II kits, whether rehydration is higher in the controls than in the cancer the questionnaire identified 60% cancers, used or not. (2) The data suggest that patients (mean±SE 44 6±14 3 ,ug/g vs the tumour markers 67% cancers, and the 100% of colorectal carcinomas have 18 7±4 9 ,ug/g; p=NS). In a subsequent combination 92% cancers (X2 p<0.05). detectable bleeding using the immuno- study faecal CEA was measured in seven Applying the probability coefficients diffusion technique with six samples. (3) colon cancer patients and seven controls prospectively to the remaining cases, 88% The frequency of positive samples and utilising a monoclonal antibody in an cancers were detected with a false positive patients will be influenced by the way in enzyme linked immunoassay. Carcino- rate of 11%. which patients have been selected, as well embryonic antigen values in the controls Although a scoring index for symptoms as the technique used. ranged from 0 to 1 7 g.tg/g and those in the is simple to use, on its own there is a cancer patients from 0 4 to 27-0 ,g/g, with considerable risk of missing significant only one patient having a concentration of disease. The addition of the tumour F83 less than 2 0 gg/g. Mean±SE for the two markers to the system however does Faecal occult blood screening in sympto- groups were 0 74±0+22 and 10 76±3 65 indicate a reasonable number of subjects at matic patients in general practice ,ug/g respectively (p<0.05). 'risk' of bearing a cancer. Further work may show faecal CEA to N C ARMITAGE, P A FARRANDS, K D be a valuable diagnostic and perhaps VELLACOTT, AND J D HARDCASTLE (Depart- http://gut.bmj.com/ screening test for colorectal cancer. In this F82 ment of Surgery, University Hospital, context an assay using a monoclonal Immunological and haemoccult detection of Nottingham) Colorectal cancers tend to antibody appears to offer greater specificity faecal occult blood in patients with present late, with many months delay than one utilising a conventional polyclonal colorectal carcinomas and polyps between the onset of symptoms and antibody. diagnosis. A controlled trial of faecal D J FROMMER AND A KAPPARIS (INTRODUCED occult blood testing in patients attending BY S SHERLOCK) (Departments of Medicine their family doctor with gastrointestinal F81 and Gastroenterology, St Vincent's symptoms was instituted to attempt to on September 30, 2021 by guest. Protected copyright. Use of a questionnaire and four tumour Hospital, Sidney, NSW, Australia) reduce the time from consultation to markers to identify cancer risk in a sympto- Immunological methods of detecting faecal diagnosis. Patients over 45 with abdominal matic population occult blood have a higher specificity and symptoms were designated to test or sensitivity than chemical ones. This study control group. The former were given E M CHISHOLM, R MARSHALL, D BROWN, E H investigated the ability of Haemoccult II three-day faecal occult blood testing and COOPER, AND G R GILES (Universitv Depart- kits (with faecal samples tested with and the latter were identified and managed in ment of Surgery, St James's Hospital, without preliminary rehydration) to detect the conventional way. Those test subjects Leeds, and Unit for Cancer Research, bleeding from colorectal carcinomas and with positive tests were investigated by University of Leeds, Leeds) There is polyps, compared with a radial immuno- flexible sigmoidoscopy and double contrast currently much debate as to the role of diffusion method with a detection limit of 2 barium enema. multivariate analysis and scoring systems, mg haemoglobin/100 g faeces. Testing six Two hundred and ninety nine patients applied to symptoms, to identify high risk faecal samples from patients with (181 test, 118 control) were entered into individuals for significant gastrointestinal carcinoma with the immunological the study. In the test group 180 (99%) disease. A similar approach to predict the method, Haemoccult II, with and without completed the tests and there were 33 probability of GI cancer, using a panel of rehydration, gave 180/234 (76.9%), 153/ (18%) with positive tests. Five colorectal tumour markers, has successfully identified 234 (65-4%) and 120/228 (52-6%) positive cancers and one oesophageal cancer (mean 81% cancers, with a false positive rate of samples representing 39/39 (100%), 34/39 delay before seeking medical advice 16%. We have combined these two (87 2%) and 28/38 (73.7%) patients with at 8-7±8-6 weeks) have been diagnosed with approaches to determine whether the least one sample positive. Each method a mean time to diagnosis from consultation addition of tumour markers to symptom gave an appreciably lower proportion of of 16 5±9-6 days. Six colonic adenomas analysis has any merit. positive samples from patients detected by have been diagnosed with a mean time to Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from Al 172 The British Society of Gastroenterology diagnosis of 22-6±10 2 days. In the control cases) and pulmonary oedema (one case) properties at only one fourth substitution group five patients with colorectal cancer were rare. of the BA pool and raises the possibility of and one patient with carcinomatosis Mono-octonoin therapy is moderately its use in gall stone dissolution therapy. (primary unknown) have presented (mean effective though side effects are common. delay 12-6±14-0 weeks) with a mean time to diagnosis of 105±114 days. Two patients F86 have presented with adenomas with a mean F85 Deoxycholic acid (DCA) feeding induces time to diagnosis of 62-5 days. Ursocholic acid (UCA): a new potential signficant changes of biliary lipid compo- The time to diagnosis for cancers and agent for dissolving cholesterol gall stones sition in cirrhotic patients adenomas is significantly shorter in the test group (overall U = 4 5, p<0-001, cancers P LORIA, G MEDICI, R IORI, AND N CARULLI F CARUBBI, M PONZ DE LEON, P DI DONATO, U = 5, p<0-002). Faecal occult blood (INTRODUCED BY M PONZ DE LEON) Istituto AND N CARULLI (Istituto di Clinica Medica testing of patients attending their family di Clinica Medica I, Universita di Modena, I, Universiti di Modena, Modena, Italy) doctor with abdominal symptoms is well Modena, Italy) We have recently reported Feeding of bile acids such as chenodeoxy- accepted and significantly reduces the time that lipid secretion into bile is inversely cholic acid or ursodeoxycholic acid to to diagnosis of colorectal tumours. related to the hydrophilicity of the bile acid humans is associated with a selective (BA) pool. Ursocholic acid the expansion of the fed bile acid pool and a 7p1-hydroxyepimer of cholic acid (CA) is sharp decrease of biliary cholesterol satura- more hydrophilic than ursodeoxvcholic tion. It has also been shown, by some acid (UDCA). Its effect on biliary lipid authors, that DCA feeding increases bile Biliary secretion has not yet been reported in man. cholesterol saturation, especially in small The aim of the present study was to doses close to the daily intestinal DCA F84 evaluate the effect of acute intraduodenal production. As DCA is the most detergent Mono-octonoin therapy - combined exper- infusion and short term oral administration among the physiological bile acids it has ience in 343 cases of retained biliary calculi of UCA on biliary lipid secretion and BA been suggested that the capacity of composition. different bile acids to stimulate cholesterol K R PALMER AND A F HOFMANN (University Acute infusion: three T-tube patients secretion into bile could be relevant to of California, San Diego, CA, USA) The were infused with UCA in conditions of biliary lipid secretion and saturation. To gall stone dissolution agent mono-octonoin interrupted enterohepatic circulation. The test this hypothesis we investigated the (MO) has only been available from a single infusions were performed at a rate of 1 g/h effect of small doses of DCA feeding on centre on a named patient basis. Between for five hours, after five hours depletion of bile lipid composition in cirrhotic patients. January 1980 and September 1983, the endogenous BA pool. The same characterised by a very small DCA pool. complete records of MO therapy were procedure was employed for five infusions Eleven patients with advanced liver available on 343 gall stone patients, (this with UDCA. Oral administration: 10 gall cirrhosis were hospitalised and put on a http://gut.bmj.com/ includes several who have been the subject stone patients were administered UCA at a standard diet providing 400 mg cholesterol/ of smaller reports). dose of approximately 15 mg/g/die for 2 day. Fasting duodenal bile samples were Age ranged from 17-93, mean 65-5 weeks. Bile acid composition and biliary obtained by intubation after cerulein years. Two hundred and twenty six patients lipids were evaluated on bile samples induced gall bladder contraction; bile were women. Two hundred and fifty before and after acute infusion and oral samples were collected the first time one presented with biliary calculi more than six administration. week after beginning diet, the second time months after biliary tract surgery, 55 had The results show that after acute infusion after three weeks on DCA (3 mg/kg/day retained calculi after recent surgery, 38 had UCA reached by 2h 85-95% of the BA per os) and the third upon discontinuing on September 30, 2021 by guest. Protected copyright. a gall bladder in situ. Two to ten millilitres pool and it induced a significantly lower DCA ingestion, four weeks later. Bile an hour (mean 5-9) of MO was constantly cholesterol (CH) and phospholipid (PL) lipids were measured with standard tech- infused via T tube (230 cases), nasobiliary secretion than UDCA. Slope values of the niques and biliary bile acids by gas liquid catheter (82), PTC (23) or cholecystostomy regression lines for CH/BA secretion wore chromatography. (eight). In 88 patients (26%) calculi dis- 0-03 for UDCA and 0 01 for UCA, those Biliary bile acids pool composition appeared. In 70 (21%) stones became for PL/BA were respectively 0-12 and 0(04. changed significantly during DCA feeding: smaller but remained. In 29 (9%) it was Oral administration: after treatment UCA the fraction of DCA in bile rose sharply thought that MO contributed to successful constituted 20-5+8-68% of the BA pool, from a mean pretreatment value of endoscopic therapy. One hundred and deoxycholic increased from 30-35±19 7 to 5-36±4-9% to a post-treatment value of twenty four patients (33%) failed to 42-55± 18 33 (p<0.01) while chenodeoxy- 439±12% (p<0001, Student's paired t respond and side effects curtailed treat- cholic and CA decreased. Mean saturation test) and returned to basal values after ment in 32 (9%) patients. Mean dissolution index (SI) fell from 1-22±0 22 to discontinuing treatment (5-9±4 7%). As time was 10 days (SD 3), and successful 0-99±0 17 (p<0.05) but in four patients in expected, the increase of DCA was asso- therapy was unrelated to stone size or whom basal SI was less than 1 there was no ciated with a marked reduction of the number. Side effects occurred in 67% of significant variation respect to pretreat- fraction of the other bile acids. Bile choles- cases; the commonest were abdominal pain ment value. terol saturation index (calculated according (36%), nausea (28%), cholangitis (8%) We conclude that after acute replace- Carey's critical tables) rose from mean and diarrhoea (15%). Life threatening ment UCA, which is more hydrophilic than values of 092-±0t26 before DCA feeding complications including septicaemia (four UDCA, induced a lower lipid secretion. to 1-34±0-47 after DCA ingestion cases), gastrointestinal haemorrhage (three This effect may explain its desaturation (p<0.005) and returned to 0-91±0-44 after Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1 173 discontinuing DCA feeding. No hepatic the solubility of cholesterol in biliary lipid bile flow is richer in calcium than the alterations or other side effects were systems by at least two different mecha- BA-independent component. observed during DCA treatment. nisms; (a) nucleation onto the seed We conclude that in a selected group of crystals; (b) alteration of the equilibrium with small DCA, solubility of cholesterol. The relative patients very biliary F89 treatment with low doses of this bile acid importance of these effects depends on the Short-term biliary stenting in the manage- to marked of bile acid pool nature of the seed crystal and on led changes chemical ment of sclerosing cholangitis composition in the sense that when DCA the time available for growth to occur. pool expansion was obtained by DCA feeding, bile cholesterol saturttion signifi- I HAMILTON, J S SOUTAR, A CUSCHIERI, AND cantly increased. These findings lend I A D BOUCHIER (Departments of Medicine, F88 Surgery and Radiology, Ninewells Hospital further support to the hypothesis that and Medical School, Dundee, Scotland) modifications of the detergent power of Biliary calcium secretion in man has bile biliary bile acids pool induced by DCA acid-dependent and acid-independent The value of dilatation of the biliary tract components with long term biliary stenting in the feeding influence bile cholesterol secretion management of sclerosing cholangitis has and saturation. been shown. We describe three patients in D GLEESON, N SCRIVENS, G M MURPIIY. AND) whom a short period of biliary stenting R H DOWLING (Gastroenterology Un1it, produced effective relief of extrahepatic Guy's Hospital and Medical School, stricture with no effect on intrahepatic F87 London) Although 1(0-30% of gall stones disease. Gall stone pathogenesis: evidence of in developed societies contain calcium and All had inflammatory bowel disease with separate nucleation and equilibrium solu- are radio-opaque, little is know about sclerosing cholangitis diagnosed by bility effects after addition of calcium salts factors influencing biliary calcium secretion cholangiography and liver biopsy pre- to biliary lipid systems in man. Therefore, in five T-tube patients operatively. Colectomy and exploration of studied seven to 10 days postcholecystec- the biliary tract were performed and a B W A WILLIAMSON, M TRAINER, AND I W tomy, we examined the relationships silastic stent with multiple side holes passed PERCY-ROBB (University Departments of between bile flow, bile acid (BA) and through the liver and into the duodenum. Surgery, Royal Infirmary and Pathological biliary calcium concentrations. first with an Stents remained in situ for 3-11 months. Biochemistry, Western Infirmary, Glasgow) intact entero-hepatic circulation (after All patients have undergone ERCP after The rate of growth of crystalline clamping the T-tube for 48-6) h) and then removal of the stents. In each case, radio- cholesterol in purified bile-salt-lecithin- in 30 min collections of T-tube bile for five logical, and biochemical criteria suggest cholesterol-water systems was studied over to eight hours. as bile flow and BA considerable improvement in extrahepatic 60 minutes in the presence of crystals of concentrations fell during depletion of the disease occurs shortly after insertion whilst http://gut.bmj.com/ calcium carbonate in three size ranges: BA pool by washout. intrahepatic disease may improve only 5-10 ,um, 100-300 gm, and >300 gm. As planned, the BA concentrations in after longer periods of stenting. Overall growth was inversely proportional the T-tube bile fell progressively with time We believe short term biliary stenting to the calcium crystal size: 1-45, 0 70, and from maxima of 9-56 mM to 2-7 mM may be valuable in the management of 0 46 mg/ml/min respectively reflecting the during the washout. There was a corre- extrahepatic sclerosing cholangitis but a different total surface areas of the three sponding fall in bile flow and in all five prolonged period may be necessary to crystal groups. The cholesterol growth rate patients, we confirmed significant linear' effect intrahepatic disease. per unit area was, however, higher for the correlations between bile volume and BA on September 30, 2021 by guest. Protected copyright. larger crystals than for the smaller crystals output (r=0-60-0-96; p<0-05-0001) (0-340 and 0-035 mg/ml/min/cm2 respec- thereby validating the model. In four of the tively). Similar experiments were five patients, biliary calcium concentrations Pancreas performed with calcium carbonate, [CA' '] also fell during BA pool depletion hydroxyapatite, calcium bilirubinate, and by 50-60Uo from maxima of 1-803-25 mM F90 cholesterol microcrystals. In these experi- and there were positive correlations Effects of somatostatin on experimentally ments also, cholesterol growth occurred between biliary [CA++] and BA concen- induced pancreatitis in the rat within the first 60 minutes. These studies trations, which were highly significant in were extended for 21 days. Cholesterol three (r=0-80, 0-84, and 0-96; p<0-005). J N BAXTER, S A JENKINS, C R MACKIE, N growth continued in the presence of By extrapolation, there were positive ROBERTS, D W DAY, W H TAYLOR, AND R hydroxyapatite or cholesterol crystals intercepts with the ordinate so that at zero SHIELDS (Departments of Surgery, Path- down to saturation indices (CSI's) of 0-60- BA concentration, the BA independent ology and Chemical Pathology, Royal 0-70. By contrast in the presence of calcium fraction of bile flow still contained 083-1 1 Liverpool Hospital, Liverpool) Although carbonate and calcium bilirubinate, growth mM calcium. it has been suggested that somatostatin ceased at CSI's >0-90. Scanning electron We conclude that: (i) in man, as in (SRIF) may be of value in the treatment of microscopy at the end of all these experi- animals, biliary calcium secretion seems acute pancreatitis, there is little evidence to ments showed cholesterol crystals both linearly related to BA output. (ii) As for support this claim. Therefore, we studied directly attached to the seed crystal and bile volume, there are BA-dependent and the effects of SRIF on experimentally also free in the suspension. These data lead BA-independent components of biliary induced pancreatitis in the rat. to the conclusion that crystals of com- calcium secretion, and (iii) in most Pancreatitis was induced in 20 male pounds that occur in gall stones influence patients, the BA-dependent component of Wistar rats by ligating the common bile Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from Al 174 The British Society of Gastroenterology duct at its point of entry into the concentrations of amylase in the pancrea- Lecithin in the bile may be an important duodenum. Twelve hours later, 10 rats titis group. moderator of pancreatic duct damage received a bolus dose of 4 ug SRIF Platelet entrapment was significantly induced by the natural detergents, bile salt followed by a constant infusion of 4 ,g/kg higher in pancreatitis animals (pk0-001). and lysolecithin. A reduced biliary concen- body wt/h for 24 hours. The remaining rats These significance values held true when tration of lecithin renders the bile more received a bolus dose and an infusion of the the percentage radioisotope uptake was noxious same volume of saline. All rats were bled corrected for body mass. before and after the induction of pancrea- Increased platelet deposition has been titis and again 12 hours after the start of the confirmed in lungs of animals with acute SRIF or saline infusion. pancreatitis and may contribute by way of F93 After the induction of pancreatitis there the platelet release reaction to the Low circulating androgens and high were increases in serum amylase and serum pulmonary complications of this disease in oestrogens in pancreatic adenocarcinoma: lipase, (p<0.01, Students t test) in all rats. man. evidence for a possible hypothal- Twelve hours after the start of SRIF amo-pituitary defect infusion, nine of the 10 rats were alive and the serum amylase (4538±225 to T P CORBISHLEY, J J KEATING, M J IQBAL, M L 1619±72.3 U/L) and serum lipase WILKINSON, P J JOHNSON, AND ROGER (3-06±0-46 to 11+±0 1 U/L) were signifi- F92 WILLIAMS (The Liver Unit, King's College cantly reduced. In the group of rats Lecithin is important in maintaining Hospital and School of Medicine & receivingsaline only five rats were surviv- pancreatic duct integrity Dentistry, London) The previous obser- ing after 12 hours of infusion and the serum vation that pancreatic tumour tissue amylase and serum lipase had significantly C P ARMSTRONG, T V TAYLOR, ANp H B contained oestrogen and progesterone increased. Only two rats receiving SRIF TORRANCE (Department of Surgical receptors and increased aromatase and died in the 24 hour period after the Gastroenterology, Manchester Royal 5cx-reductase activity has led us to investi- induction of pancreatitis whereas all rats Infirmary, Manchester) The pancreatic gate the pattern of total and free plasma receiving saline died. duct possesses a barrier (PMB) to free back sex steroid hormone concentrations and These results suggest that SRIF may be diffusion which is damaged by the natural the integrity of the hypothalamo-pituitary of value in the treatment of acute detergents, bile salt and lysolecithin. axis in patients with pancreatic carcinoma. pancreatitis. Although lecithin may have a physiological The total and free plasma concentrations of role in the protection of biliary and testosterone (T), 5o-dihydrotestosterone intestinal epithelium, its effects on the (DHT), 17 oestradiol (E2) were measured F91 pancreatic duct is unknown. in 47 pancreatic tumour patients (28 men), Pulmonary sequestration of radiolabelled The bile-pancreatic duct of rats was 45 tumour control patients (27 men), and http://gut.bmj.com/ autologous platelets in acute pancreatitis in perfused at low pressure at 100 ,ul/h with a 40 age and sex matched healthy controls. the rat standard solution (SPS) [Na' 150, HCO3 The free plasma E2 concentrations were 120, Cl- 30 mmol/l1 - period I, with the test significantly raised in male pancreatic I A GOULBOURNE, H WATSON, AND G C DAVIES solution - period II and with SPS again - carcinoma patients (median 35 pmol/l (INTRODUCED BY R C HEADING) (Depart- period III. The difference in ionic flux (range 10-86)) compared with the tumour ments of Clinical Surgery and Haema- (,mol/cm/h) of CI- (AJCI) and HCO3 controls (median 7 pmol/l (range 3-31)) tology, Royal Infirmary of Edinburgh, (AJHCO3) and transductal potential differ- and healthy controls (median 19 pmol/l Edinburgh) The pathogenesis of the ence (ApD, mV) between periods III and I (range 10.7-30)) (p<0-001). The free on September 30, 2021 by guest. Protected copyright. severe respiratory complications of acute was calculated. Damage to the PMB was plasma T was significantly lower in men pancreatitis remains unclear, but probably indicated by a change in the pD with with pancreatic carcinoma (median free T involves leukocytes, fibrinogen/fibrin electron microscopic (EM) confirmation. 46 pmol/l (range 6-1447)), and tumour conversion and complement activation. We The test solutions were (A) SPS (control), controls (median free T 29 pmol/l (range have reported increased intrapulmonary (B) 10 mM glycodeoxycholate (GDC), (C) 4-1089)), than healthy controls (median fibrin deposition in pancreatitis and GDC + 50 mM lecithin, (D) lysolecithin, free T 826 pmol/l (range 290-1600)), correlated this with increased lung wet (E) lysolecithin + 50mM lecithin (n= 10 for (p<0-001) but no difference existed weight and decreased compliance. In the each). SPS alone (A) did not affect duct between the tumour groups. Basal plasma present series of experiments, 2 ml of integrity. Both bile salt (B) and lysolecithin LH and FSH concentrations, measured in blood were withdrawn from specific (D) produced significant changes in ion flux 19 patients with pancreatic tumours were pathogen free adult male Sprague Dawley and pD and EM showed epithelial within the low normal range. LHRH rats for labelling with Indium 111 oxine. disruption. The addition of lecithin (C,E) stimulation showed a normal FSH response The rats were partially rehydrated and significantly reduced the increased permea- but a reduced LH response however. The pancreatitis induced. Rats received the bility produced by both detergents. (Glyco- high plasma E2 concentrations seen in labelled platelets (100 kBeq) and one 125 deoxycholate; reduction in AJCI, patients with pancreatic carcinoma are fibrinogen (20 kBeq) intravenously at the AJHCO3, and ApD; each p<0-01, Mann- consistent with increased aromatisation of end of the operation. The rats were killed Whitney U test; lysolecithin also reduction androgens by tumour tissue. The results at 18 hours, the lungs were removed and in AJCI, AJHCO3 and ApD; each p,O01). also indicate that the reduced concen- scinticounted for fibrin and platelet Ultrastructural examination revealed that tration of plasma androgens may result deposition. lecithin had prevented any epithelial from a defect in the hypothalamo-pituitary Pancreatitis was confirmed by raised damage. axis. Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1175 F94 London) Haemochromatosis is caused by sible for these changes have not been well Liver histology in non-jaundice patients a defect in the control of iron absorption defined. with pancreatitis: a clue to aetiology? from birth. In this study we have investi- The aim of this study was to investigate gated the possibility that haemochroma- the first committed and rate-limiting step of H H ALI, N Y HABOUBI, AND J M BRAGANZA tosis is caused by persistence of the bile acid synthesis, that is the 7ci-hydroxy- (Pathology Departments of Withington neonatal mode of iron absorption. As it is lation of cholesterol, in patients with Hospital and the Medical School, not possible to study the ontogeny of iron cirrhosis. Manchester, and University Department of absorption in the human, we have studied Subjects investigated included five Gastroenterology, Manchester Royal the developing guinea pig. normal controls and seven patients with Infirmary, Manchester) Thirty three Whole body iron absorption in develop- different degrees of severity of liver consecutive non-jaundiced patients had a ing guinea pigs ranging in age from <24 disease. The severity of the disease was liver biopsy between 10 days and 6 months hours to adulthood was measured by graded by means of a scoring systems. after an attack or relapse of pancreatitis administering an oral dose of "9Fe. Mean Each subject received about 200 ,uCi of (acute eight, chronic 25): five additional serum iron in the neonatal and adult guinea 7cX-3H cholesterol dissolved in 20 ml of patients had painless chronic pancreatitis. pig was 74 AM (70-84) and 49 AM (32-70) plasma. Blood samples were taken at fixed Possible aetological factors were alcohol respectively. Iron absorption at birth intervals for four to five days, for the assay (eight), a drug (five), type IV hyperlipid- ranged between 40-60% of the dose. By 10 of specific activity of plasma free and aemia (two), and gall stones (two): days iron absorption decreased to the adult esterified cholesterol. Samples of blood pancreatitis was 'idiopathic' in the range (<10%). This development process cells were lyophilised to obtain the remainder (55%). was further investigated by studying sublimate for radioactivity assay of body Altered hepatocytes, occupying 10- mucosal uptake and total iron absorption, water. Volume of body water was esti- 100% of the parenchyma, were detected in using isolated duodenal loops perfused in mated by dilution of a small amount of 23 of the 38 cases (60%). Their appear- situ with varying concentrations of iron (10 tritiated water given 15 days after the study ances varied from large pale cells with ,u M-2000,M) complexed with nitrilo- was completed. From the specific activity- 'clear' cytoplasm to typical ground-glass triacetic acid and labelled with 59Fe. time curves of both plasma cholesterol and hepatocytes: toluidine blue staining of Chromium (5"Cr) EDTA was used as an body water the amount of cholesterol ultra-thin sections revealed extensive unabsorbable marker to correct for non- undergoing 7o-hydroxylation at any given microvesicular fat in three biopsies. Some specific uptake. At all concentrations time interval could be calculated from the biopsies showed excess lipofuscin or studied, both duodenal mucosal iron equation: increase of specific activity of steatosis. The portal tracts were altered in uptake and total absorption was signifi- body water/specific activity of cholesterol. 28 cases (74%): the changes included cantly increased in the neonate compared The results show that 7(x-hydroxylation diffuse lymphocytic infiltration, focal bile with the adult (p<0-002). The increase in of cholesterol was significantly (p<0.01) duct proliferation, focal ductopenia and mucosal iron uptake in the neonate and the decreased in patients with cirrhosis features suggestive of primary biliary rapid change to the adult mode in the (116±82 mg/24 h) compared with normal http://gut.bmj.com/ cirrhosis or sclerosing cholangitis. The postnatal period indicates a fundamental controls (314± 108 mg/24 h). The values of spectrum of hepatocytic and/or portal tract alteration in the physiology of iron absorp- 7(x-hydroxylation were inversely correlated abnormalities was similar in patients with tion. Inappropriate iron absorption in the (r=-0.94; p<0-001) with the severity of acute pancreatitis and chronic pancreatitis. neonatal guinea pig is similar to the the disease. Ground-glass hepatocytes are associated abnormalities in haemochromatosis. Our data show that patients with liver with microsomal 'induction' by drugs; Persistence of the neonatal mode might cirrhosis have an impairment of cholesterol microvesicular fat with damage by reactive underlie the increased iron absorpFion 7(x-hydroxylation, which seems to parallel intermediates, and lipofuscin with lipid occurring from birth in haemochromatosis. the extent of liver involvement. These on September 30, 2021 by guest. Protected copyright. peroxidation within tissues. Our findings Study of factors controlling neonatal iron findings suggest that the factor responsible thus collectively suggest that the hepato- absorption might provide new insight into for the decreased bile acid synthesis is the biliary changes that accompany pancrea- the pathogenesis of haemochromatosis. reduction of liver cell mass. titis may represent hepatic induction by xenobiotics, and the consequence of 'oxidative detoxification'. F96 F97 "In vivo" evaluation of cholesterol Plasmapheresis in fulminant hepatitis Liver 7cx-hydroxylation in liver cirrhosis J G FREEMAN, K MATTHEWSON, AND C 0 F95 M BERTOLOTTI, D MENOZZI, F ZIRONI, AND N RECORD (Department of Gastroenterology, Ontogeny of iron absorption and its possible CARULLI (INTRODUCED BY M PONZ DE LEON) Royal Victoria Infirmary, Newcastle upon relationship to pathogenesis of haemo- (Istituto di Clinical Medica I, Universitd di Tyne) Fulminant hepatitis (FH) carries a chromatosis Modena, Italy) It has been shown that high mortality regardless of its cause. qualitative and quantitative alterations of Recent research has been directed towards S K S SRAI, E S DEBNAM, M BOSS, AND 0 sterol metabolism are associated with liver charcoal haemoperfusion, which is only ESPTEIN (Department of Medicine, Royal cirrhosis. Particularly, a reduction of bile effective in 20% of cases when treatment is Free Hospital School ofMedicine, London, acid pool size has been described, mainly started after the patients has been and Department ofPhysiology, Department because of the elective reduction of cholic unresponsive to commands (Grade 4 of Medical Physics, Royal Free Hospital, acid synthesis. The mechanisms respon- coma). Plasmapheresis is a simpler Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1 176 The British Society of Gastroenterology technique with few side effects, allowing to changes in membrane fluidity (corre- vesicle-membrane recognition which may removal of 'hepatic toxins', and providing lation = 0.98). determine the normal direction of traffic essential plasma nutrients to support the These studies show that ethanol through the cell. patient during hepatic regeneration. Our produces a dose-related effect on liver experience of plasmapheresis in cases of plasma membrane fluidity and simul- FH is reported. taneously inhibits taurocholate transport. F100 Patients were eligible for the study if These findings suggest that the fluidity of of plasma Validation of a new chromogenic assay for they had FH and were in grade 4 hepatic the hydrophobic region endotoxaemia in liver disease coma. Nine patients with FH underwent a membrane lipids is a regulator of 3 litre exchange using a Haematech membrane transport. plasmapheresis machine, the discarded E M ALSTEAD, F J KHAN, A I MORRIS, I T GILMORE, AND J WARE (Department of plasma being replaced by equal quantities Medicine, University of Liverpool, Liver- of fresh frozen plasma, and plasma protein pool) The measurement of endotoxaemia fraction. No significant side effects were F99 in liver disease has been difficult, un- encountered. The mean number of plasma- Microtubules and the control of vesicle reliable and, at best, only semiquantitative. phereses performed on each subject was traffic in hepatocytes With the development of a kit using a new three. chromogenic substrate and limulus lysate Five of the nine patients made a full R COLEMAN, S G BARNWELL, AND P J LOWE (Byk Mallinckrodt), we have validated its recovery, four died as a and the remaining (INTRODUCED BY E ELIAS) (Department of use in patients with liver disease. Standard direct consequence of hepatic failure. In Biochemistry, University of Birmingham, curves using crystalloids appeared linear, the preceding three years and during the Birmingham) Protein secretion from study period, 1I patients with FH and with a mean gradient of 088±0-083 SD. hepatocytes occurs both from the Using normal plasma to which known 4 coma did not grade undergo plasma- sinusoidal pole of the cell (plasma proteins amounts of endotoxin were added, similar pheresis, and only two patients survived. carried in secretory vesicles originating linear results were obtained, with a mean Thus, the survival rate in our plasma- from the endoplasmic reticulum-golgi) and gradient of 0-60±0-062, a value signifi- pheresed series was 55% compared with a from the canalicular pole (secretory IgA, cantly different from the gradient for survival of 18% in the non-plasmapheresed and secretory component, carried in crystalloids; p Yale University School of Medicine, New the perfusion fluid of a liver perfused with plasma and crystalloids (p<0-01 in both on September 30, 2021 by guest. Protected copyright. Haven, USA) The fluidity of plasma rat plasma protein-free medium it cases). Thus, although bilirubin affects the membrane lipids may influence membrane promotes the secretion of rat plasma sensitivity of the assay, endotoxin concen- protein-related functions such as transport. albumin into bile. trations may be measured in jaundiced In this study we examined the effect of This phenomenon is not restricted to plasma provided appropriate standards are ethanol on this relationship. Basolateral albumin, however, as bile from colchicine- used. Studies in patients with diverse liver plasma membrane vesicles (right-side-out) treated livers also contains fibrinogen, disease show this assay to be simple, were prepared from rat liver. Membrane transferrin etc; these proteins cannot be repeatable and sensitive (lower limit of fluidity (anisotropy, r) was measured by detected in untreated livers. Colchicine detection = 0-1 Eu/ml). fluorescence polarisation using diphenyl- treatment does not, however, result in hexatriene as a lipid probe. Uptake of gross cell damage under these conditions, 3H-taurocholate was measured by a rapid because there is no loss of cytosol proteins. Millipore filtration technique. By electron microscopy the livers of F1IO Baseline anisotropy of basolateral colchicine treated animals contain an Prophylaxis of perinatal HBV transmission vesicles was 0-2262±0-0040 (mean±SEM, abundance of small vesicles, many of which and its relationship with HBe antibody n=8). Ethanol produced an instant are located close to the bile canaliculus. It status and HBV-DNA concentration-dependent fluidising effect is therefore suggested that: (i) vesicles (p<0-01) from 50 mM (Ar=-12-6 normally destined for secretory processes D A KELLY, D RUITER, C GREENFIELD, P +3x10-4) to 500 mM (Ar=-103-6± at the sinusoidal pole of the cell can KARAYIANNIS, J MONJARDINO, M FOWLER, 11x10-4). Taurocholate uptake into baso- discharge their contents into bile when the AND H C THOMAS (Department of Medicine lateral vesicles (a Na-coupled carrier- microtubular system is disrupted, (ii) it is and Paediatrics, Royal Free Hospital, mediated process) was inhibited in parallel the microtubular system rather than London) The risk of perinatal trans- Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1177 mission of hepatitis B virus' (HBV) is in 56 patients and correlated the results Intravenous administration resulted in related to the HBe antigen/antibody status with recognised biochemical and histo- similar urinary excretion in both groups, of the carrier mother. We have investi- logical parameters of disease progression. suggesting that impaired absorption occurs gated the relationship between the HBe Liver biopsies were graded for overall in alcoholics. The effects of alcohol antigen/antibody state, the presence of Ludwig stage (I-IV). The presence and administration on urinary vitamin C HBV-DNA and the risk of perinatal trans- extent of regeneration nodules and central excretion was investigated in nine healthy, mission in 90 pregnant Kenyan women (45 hepatic vein damage were assessed semi- non-alcoholic subjects who each drank nil, HBsAg+ve; 45 HBsAg-ve). In a pilot quantitatively, as was pericellular fibrosis water, lager, and whisky in random order. study, we also evaluated the efficacy of in Rappaport zone 1 (0 to +3). Non- The volume of water and lager adminis- combined active and passive immunisation parametric statistical methods were used. tered was 1 litre/70 kg body weight, in preventing perinatal transmission in A raised serum bilirubin (>22 mol/l) was resulting in the quantity of alcohol being three HBsAg carrier mothers. found in 46% of our PBC patients while 0-58/kg body weight. A similar quantity of In the Kenyan study, two of the Kenyan the corrected WHVP was significantly alcohol as whisky was used. The 28% HBsAg+ve mothers were HBeAg+ve and raised (p<0.001) in 86% (median 13 reduction in vitamin C excretion with HBV-DNA+ve; 11 women had no 'e' mmHg, control median 2 mmHg). WHVP fasting (p<001) was completely abolished markers, two were DNA+ve and nine showed a significant correlation with by drinking water. Alcohol in either form were DNA-ve; 31 mothers were anti- Ludwig stage (p<0-01) and also with the produced a 47% increase in urinary e+ve, nine were DNA+ve and 22 degree of pericellular fibrosis (p<0.005). vitamin C excretion (p<0025). Vitamin C DNA-ve. Three babies (7%) were No significant correlation existed between deficiency in alcoholics may thus be infected in the perinatal period, all mothers pericellular fibrosis and Ludwig stage. compounded by impaired absorption and were anti-HBe positive, one was HBV- Portal hypertension and oesophageal an ascorbiruesis. DNA positive and two were negative. varices are normally regarded as a late Three babies, including one from the feature of PBC but in the majority of our control group became infected at nine patients WHVP was significantly raised, months, presumably from horizontal trans- even in those who would be classified as F104 mission. early by conventional criteria (serum bili- Prognostic factors in alcoholic cirrhosis In the pilot study, the babies of an rubin and Ludwig stage). In 40% of our HBeAg+ve, HBV-DNA+ve mother and patients the WHVP was raised in the R BRADBEAR, W J JENKINS, D ASHBY, AND two anti-HBe negative (DNA+ve (1), presence of a normal serum bilirubin. SHEILA SHERLOCK (Departments of HBV-DNA-ve (1)) mothers were Thus, portal hypertension may occur with a Medicine and Epidemiology, Royal Free immunised with the combination of normal serum bilirubin, in early disease Hospital School of Medicine, London) To hepatitis B vaccine (Hep-Vax 0-5 ml) and (Ludwig stage I and II) and in the absence identify factors which influence the life hepatitis B immune globulin (HBIG-200 of regeneration nodules and central hepatic expectancy of patients with alcoholic http://gut.bmj.com/ mg) at birth and one month and with vein damage. The overall histological cirrhosis we analysed survival data from Hep-Vax only at six months. All babies assessment suggests that portal hyper- 138 consecutive patients admitted to t;lis were HBsAg-ve at birth and produced a tension in PBC originates at a sinusoidal hospital in 1980 and 1981. All patients were satisfactory rise in anti-HBs at one and six rather than a post-sinusoidal level. followed until death or until the end of the months. It is concluded that (i) perinatal study in February 1984. Clinical, transmission in African women is less likely laboratory and histological variables which than horizontal transmission; (ii) that anti- F103 are routinely recorded were screened and HBe may have a virus-neutralising effect as Inadequate diet is not the only cause for the relative risk associated with each the majority of these mothers who were vitamin C deficiency in alcoholics variable was calculated. on September 30, 2021 by guest. Protected copyright. also HBV-DNA+ve did not infect their At the end of the study 67 patients were babies and (iii) that the combination of R FAIZALLAH, A I MORRIS, N KRASNER, AND R J alive and 71 dead. Only 17 deaths could not active and passive immunisation was both WALKER (Gastrointestinal Unit, Walton definitely be accounted for by complica- safe and effective in these high risk babies. Hospital, Liverpool) The majority of tions of cirrhosis. The following abnormal- alcoholics are vitamin C deficient. ities were found to be statistically asso- Although traditionally ascribed to in- ciated with a higher risk of death; low F102 adequate dietary intake we have investi- serum albumin; high serum bilirubin; Portal hypertension in primary biliary gated the theoretical possibility that prolonged prothrombin time; high serum cirrhosis (PBC) - an early assault on the impaired absorption and/or increased creatinine; ascites, gastrointestinal sinusoids? urinary loss may be additional mecha- haemorrhage and encephalopathy on nisms. 14C ascorbic acid was administered admission and during follow-up. Neither T W WARNES, A SMITH, N Y HABOUBI, H AL14 V orally or intravenously to 12 non-cirrhotic age nor sex significantly influenced COPE, AND P VALES (Liver Section, Univer- alcoholic patients and 11 matched controls. survival, and continued alcohol abuse had sity Department of Gastroenterology, Total urinary recovery was measured over little effect, though this may be because Manchester Royal Infirmary, Manchester) a six day period, after administration of most patients drank little alcohol. Inflam- While it is recognised that patients with large flushing doses of 'cold' vitamin C. matory activity in liver biopsy, liver size PBC may present with bleeding oeso- There was significantly less "4C ascorbic and spleen size did not affect prognosis. phageal varices, the mechanism of portal acid excreted by the alcoholics after oral A multivariate analysis of the variables hypertension is poorly understood. We administration compared with controls screened improved discrimination of a have performed 83 WHVP determinations (p A1178 The British Society of Gastroenterology better prognostic index than a simple patients with acute and six with chronic (48-3±8-0 and 1.83±0-33), while total bile Child's grading. HBV infection were incubated with auto- acid concentration (91.2±20.7 .mol/ml/ logous liver cells with and without IFN-cx at kg) was significantly higher (p<0-05) in a concentration of 103 U/mI of culture EE-treated rats than in controls F105 medium in an 18 hour-cytotoxicity assay. (66-4± 10-1). Compared with rats given PG Endotoxin in portal blood - is it normal? Interferon-ct produced a significant alone, EE-treated rats secreted higher pro- increase in non-T cell cytotoxicity in portions of tauromuricholate (26.5+3.1% S BREARLEY, R I HARRIS, P STONE, AND M R B patients with acute and chronic hepatitis B and 46-2+3 4%; p<0.001) and glycomuri- KEIGHLEY (General Hospital and Queen (from 34-3±19-6% to 60 0±11 2%, cholate (6.8±1.8% and 18-3±8-8%; Elizabeth Hospital, Birmingham) Evalua- p<0-03, and from 41-2±17 2% to p<002), and lower percentages of tauro- tion of the role of bacterial endotoxin in 65 5±9-8%, p<0 01, respectively). In cholate (36.1±3.3% and 11 9±5*6%; disease has been hampered by the contrast, no significant effect was observed p<0OOl), glycocholate (7.8±3.5% and susceptibility to contamination and relative on T-cell-mediated cytotoxicity in either 2-8±1-3%; p<0.01) and taurodeoxy- insensitivity of most plasma endotoxin group of patients (from 39 5±11 1% to cholate (6.3±3.6% and 0-9±1+0%; assays, and previous studies of the occur- 44-2±12-9%, and from 32 3±15 1% to p<0005, rank sum test). Medroxy- rance of portal venous endotoxaemia in 33 0±16 9%, respectively). The in vitro progesterone acetate treatment produced a health have given conflicting results. We effect of IFN-ot was also evaluated in three less pronounced but similar pattern of have developed a chromogenic substrate patients who developed chronic NANB changes compared with control rats, with assay sensitive to < 10 pg/ml of E coli hepatitis after blood transfusion but no significant differences in tauromuricholate endotoxin in plasma in which the problem significant stimulatory effect was observed (34.5±61%;p<002) and taurocholate of contamination has been overcome. on either T- or non-T cell cytotoxicity (26.4±6.2%; p<0.01), apart from Using this assay 116 of 119 uninfected (from 47 7±11-9% to 48-7+10-7%, and tauroursodeoxycholate where concentra- individuals (98%) had systemic venous from 20-3+21-6% to 27-0±22-7% tions were significantly different in the two endotoxin values less than 015 optical respectively). Similarly, no significant steroid-treated groups (2-3±0.6% [EE] density (OD) units (trace amounts). increase in cytotoxicity was noted in three and 3 6±0-7% [MPA]; p<001: Portal and systemic blood samples were control subjects. The significant enhance- PG=2.8±1-3%. Steroid treated rats obtained from 17 patients undergoing ment of non-T cell cytotoxicity, but not of secreted, on average, approximately 10% elective upper abdominal surgery (chole- T-cell cytotoxicity, for autologous hepato- of the bile acids as taurohyodeoxycholate cystectomy 1, vagotomy three, gastrec- cytes in HBV infection suggests that IFN-ct which was higher than in controls. While tomy three). All samples were sterile on produce a selective stimulatory effect on the changes in individual bile acids culture except one (diptheroid isolated). NK/K cells. The absence of a similar effect observed in EE-treated rats could be Sixteen out of 19 patients samples showed in patients with chronic NANB hepatitis secondary to the induced cholestasis, the and control suggests altered zero endotoxin activity; no sample showed subjects that HBV bile acid pattern in the MPA group http://gut.bmj.com/ activity >0-045 OD units. infection alters the susceptibility of hepato- suggests that these clinically important We conclude that in the absence of cytes to interferon-stimulated NK/K cell steroids may have direct effects on bile acid intestinal disease or sepsis, only trace damage. synthesis and/or secretion. amounts of endotoxin are present in portal venous blood, and that concentrations in portal and systemic blood are similar. F107 F108 Ethinyl estradiol and medroxyprogesterone Prospective randomised controlled trial acetate induced changes in bile acid comparing somatostatin and vasopressin in on September 30, 2021 by guest. Protected copyright. F106 composition of rat bile the control of acute variceal haemorrhage Interferon-cr enhances non-specific cyto- toxicity for autologous hepatocytes in acute P R BAKER, G C VITALE, Y SIOW, AND A D REID J N BAXTER, S A JENKINS, W A CORBE1-T, P and chronic hepatitis B virus (HBV) (University Department of Surgery, DEVITT, J WARE, AND R SHIELDS infection Ninewells Hospital & Medical School, (Department of Surgery, University of Dundee) Contraceptive oestrogens, such Liverpool, Liverpool) Recent studies M MONDELLI, A ALBERTI, G REALDI, R as 17(x ethinyl estradiol (EE), and cancer have suggested that somatostatin (SRIF) WILLIAMS, AND A L W F EDDLESTON (The chemotherapeutic progestogens, such as lowers wedged hepatic venous pressure in Liver Unit, King's College Hospital and medroxyprogesterone acetate (MPA), cirrhotics and may be of value in the acute School of Miedicine & Dentistry, and influence certain enzyme activities of control of bleeding oesophageal varices. Istituto di Medicina Clinica, Padua, Italy) hepatic steroid metabolism which may This study was therefore carried out to Controlled clinical trials are currently effect the biliary output of individual bile compare the efficacy of SRIF and vaso- under way to assess the efficacy of acids, EE or MPA (5 mg/kg bw) in pressin (AVP) in the control of acute interferon (IFN) in a variety of viral propylene glycol (PG), or PG alone were variceal haemorrhage. infections, including hepatitis B. Although given subcutaneously for seven days to Twenty two consecutive patients IFN has been shown to enhance natural groups of six male Wistar rats. Rats given admitted with endoscopically proven, cytotoxicity for NK-sensitive cell lines in EE had significantly lower values for bile actively bleeding oesophageal varices were HBV infection, little is known of its effects flow (24-0±2-8 (SD) ,lI/min/kg; p<0.001) randomised to receive intravenously either when autologous hepatocytes are used as and bile acid output (1.07±0-31 ,mol/min/ AVP (0.4 U/min) or SRIF (bolus dose of target cells. In this study, T-enriched and kg; p<002) than rats given PG alone 250 ,ug followed by a constant infusion of non-T-enriched lymphocytes from six (49.3±4.3 and 1.65±0-38) or MPA 250 ug/h). The aetiology of the portal Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society ofGastroenterology A1179 hypertension was similar in the two groups direct vs i/p external (X2=0-02, p>O I 16-7 sec ± 2-2 (ns). Mean clearance times as was the distribution of the patients (life-table analysis to 800 days), survival to were prolonged from 42'4 sec ± 4-7 to among the categories of Child's classifi- discharge 73% vs 76%), alcoholics (40) vs greater than 60 sec in all but one subject. cation. non-alcoholics (103) (X2=0-004, p>0.1), Beyond one minute accurate quantitation Twelve patients received AVP and 10 bleeding source oesophageal varices (94) vs of clearance time was impossible as SRIF. The initial variceal haemorrhage other sources and undefined (49) (X2=0-42, computer acquisition ceased at this time. was successfully controlled in all 10 p>O- 1), i/p external group with and Post-treatment transit times were un- patients receiving SRIF. Moreover, no without previous bleed (X2=2-48, p>0- 1). related to symptoms or to the presence or complications were observed in any of the Marked differences between groups absence of stricture on endoscopy or 10 patients during SRIF infusion. Acute included direct vs internal referrals barium swallow. variceal haemorrhage was successfully (X2= 10-52, p<0 005, survival to discharge We conclude that oesophageal transit is controlled by AVP in four of the 12 73% vs 50% and to 600 days 60% vs 30%). impaired in the presence of varices and patients. AVP was unsuccessful in eight Early deaths were uncommon - 8% within further delay results from endoscopic patients and balloon tamponade of the eight days for the direct + i/p external sclerotherapy. oesophagus was required. group. Forty four per cent of inpatient The results suggest that SRIF is more deaths were for reasons other than effective than AVP in controlling AVH bleeding. (p=0003 Fisher's exact test). Further- In this centre i/p external and direct Fl11 more, SRIF infusion, unlike AVP admin- referrals are similar clinically and prog- Prospective study of a management istration was not associated with any nostically with admission survivals of protocol with early intervention for variceal compliations. around 75% (A=93%, B=84%, C=50%). bleeding in cirrhotics: possible prediction Internal referrals would in many cases for need of sclerosis or surgery probably benefit from transfer to allow a more centralised management policy. A K BURROUGHS, M R QADIRI, G HAMILTON, Oesophageal C KIBBLER, G JEFFREY, K HOBBS, AND N MCINTYRE (Depts of Medicine and F109 Fl 10 Surgery, Royal Free Hospital School of Outcome of gastrointestinal bleeding in Does sclerotherapy for oesophageal varices Medicine, London) Long term survival subjects with varices related to source of affect oesophageal function? after variceal bleeding is critically referal determined by outcome of the acute bleed. J G WILLIAMS, J R TURNER, AND D BECKLY Accepted management of variceal bleeding D W BULLIMORE (INTRODUCED BY M S (RN and General Hospitals, Plymouth, follows a sequential scheme from less to LOSOWSKY) (St James's Hospital, Leeds) Devon) The effect of endoscopic sclero- more invasive therapy. Variceal bleeding, http://gut.bmj.com/ Studies on subjects with oesophageal therapy for bleeding oesophageal varices however, is characterised by early repeated varices and gastrointestinal bleeding on post-treatment oesophageal function bleeding during the same admission. The derived from referral centres are has been assessed by measuring the effect of this rebleeding and timing of frequently believed to be biased by the oesophageal transit of a bolus of 99mTc intervention (sclerosis or surgery) has been inclusion of a 'better prognosis group' - sulphur colloid. Subjects were studied little studied. Prediction of rebleeding those subjects who have survived the initial supine and counts were recorded using a might allow earlier intervention and bleed sufficiently well to be stabilised and large field of view gamma camera lirked to possibly improve prognosis. Fifty four transferred from an outside hospital to the a computer. Time activity curves were then cirrhotics (27 alcoholic) during 71 on September 30, 2021 by guest. Protected copyright. referral centre. The outcome of gastro- generated from regions of interest drawn consecutive admission for variceal bleeding intestinal bleeding in a group of 143 over the oesophagus and stomach. were studied within an ongoing protocol subjects with oesophageal varices was For patients with no clinical abnormality with strict end points for intervention assessed to determine the degree of this of the oesophagus the mouth to stomach (following transfusion and/or glypressin bias if present. All patients with varices transit time for a single swallow was 7-15 and always after tamponade). Pugh's diagnosed in the endoscopy unit and sec ± 0-62 SEM (n=9). For nine patients classification on first hospital admission presenting with their first bleed (at this with oesophageal varices the mean transit was used, 41 grade 'AB', 30 'C'. 48% 'AB' hospital) from 1973-1982 were eligible. time was 12-44 sec ± 1-8 (p<005). The and 33% 'C' were haemodynamically Patient analysis included classification by transit time was taken as the first stable on admission, and of these over 70% original source of referral:- direct, internal appearance of activity in the stomach and it had not rebled at 24 hours. The remainder (from other physicians), in-patient (i/p) was notable that in most patients with received glypressin, with 44% having external (from surrounding hospitals, 2 to varices much activity was retained in the stopped bleeding by 24 hours. Intervention 80 miles) and outpatient external. mid and lower oesophagus. Time to clear within 48 hours was required in three 'AB' Comparisons were by life-table analysis 90% of this activity from the oesophagus (7%) and 10 'C' (33%), (p<0-01) and and Fisher's test. Prognostic factors, was 41-5 sec ± 7 for patients with varices subsequently in 10 'AB' and eight 'C'. including Child's grade, were comparable (n=9) compared with 9-8 sec ± 0-7 for Mean transfusion 7-1 units (0-20) 'AB'; in these groups apart from more subjects normals. Six patients with varices were 14-4 units (0-49) 'C' (p<0.01). Deaths ii with a past history of bleeding in the i/p studied before and after complet'e obliter- hospital (or within 30 days) 2 'AB' (5%) external group (48%) compared with direct ation of their varices by repeated endo- and 10 'C' (33%) (p<0-2). + internal group (27%), p<0-02. Survival scopic sclerotherapy. Mean arrival transit This mortality rate is the lowest per of the following groups was comparable: time was prolonged from 13-3 sec ± 2-8 to admission and per patient to date. The Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1180 The British Society of Gastroenterology behaviour of 'C' patients suggests a occurs in the absence of oesophagitis. For a Fl 14 sequential scheme of management may be full assessment of such patients, mano- Is dimethicone effective in the treatment of inappropriate. Earlier intervention as metry, radionuclide transit measurement reflux oesophagitis? means of improving prognosis requires and prolonged pH monitoring are all evaluation. Use of discriminant analysis necessary. A L OGILVIE AND MICHAEL ATKINSON based in part on Pugh's criteria allows (University Hospital, Nottingham) better prediction of continued or early Dimethicone (a silicone polymer) is added rebleeding, and may provide a basis for to several 'antacids but objective proof of more rational management of variceal its efficacy is lacking. Its effectiveness was bleeding. Fl 13 therefore assessed in a double blind Intragastric bile acid concentrations in controlled trial in 45 patients with endo- erosive oesophagitis scopically proven reflux oesophagitis. They were randomly allocated to receive either B J COLLINS, G CROTHERS, R J MCFARLAND, antacid-dimethicone gel (Gel AD) or an Fl 12 AND A H G LOVE (Department of Medicine, identically formulated gel containing Oesophageal disorders in patients with The Queen's University of Belfast and The antacid alone (Gel AA). Thirty eight recurrent chest pain of obscure origin Ulster Hospital, Dundonald, Belfast) patients completed the eight-week period Many patients with chronic reflux of the study. Symptoms of gastro- J S DE CAESTECKER, J N BLACKWELL, JOAN symptoms have no macroscopic oesopha- oesophageal reflux were graded for BROWN, AND R C HEADING (Department of gitis, whereas others develop oesophageal severity and frequency at weeks 0, 4, and 8, Therapeutics and Clinical Pharmacology, erosions and ulcerations. It has been while oesophagitis was assessed at weeks 0 Royal Infirmary, Edinburgh) Seventy one suggested that duodenogastric reflux of bile and 8 by endoscopy, oesophageal biopsy, patients with recurrent chest pain were acids increases the cytotoxic potential of oesophageal motility and acid perfusion referred for oesophageal motility studies. gastric juice and increases the likelihood of studies. Symptom scores were similar at 0, Thirty eight had anginal pain, exercise oesophageal damage occurring in patients 4, and 8 in both groups and no significant related in 26 but occurring at rest in 12. with gastro-oesophageal reflux. We have differences were detected. In the assess- Thirty three patients had non-anginal chest measured fasting and post-prandial total ment of oesophagitis there was a tendency pain, including six with known ischaemic bile acid concentrations after nasogastric for the Gel AD group to show greater heart disease. Coronary angiograms in 27 intubation, in 16 patients with chronic improvement in endoscopic and biopsy patients showed normal coronary arteries reflux symptoms and erosive oesophagitis. gradings and also in the results of (23), very mild disease (three) and We have also studied 16 age and sex oesophageal motility and acid perfusion coronary artery spasm (one). Chest pain in matched control subjects. No patient or studies. When a combined overall assess- the remainder was considered non-cardiac control subject had evidence of gall ment of the degree of change was calcu- http://gut.bmj.com/ in origin after clinical assessment and/or bladder disease. Gastric total bile acid lated, patients receiving Gel AD showed a investigations which included a normal concentrations and gastric juice pH were greater improvement (p<0-02) than the ECG with exercise. All patients underwent measured in fasting sample and at 20, 40, Gel AA group. barium radiology and/or endoscopy before and 60, minutes after a corn oil test meal. We conclude that in reflux oesophagitis oesophageal manometry and radionuclide At 60 minutes, gastric contents were the addition of dimethicone to antacids oesophageal transit study. Twenty seven completely aspirated. A wide inter- confers no symptomatic benefit, but causes patients underwent prolonged ambulatory individual range of bile acid concentrations improvements in the degree of oesopha- intraoesophageal pH monitoring. was detected in control subjects (0-1054 gitis as assessed by objective methods. on September 30, 2021 by guest. Protected copyright. Abnormality was detected in 44 of the 71 ,umol/l) and patients (0-2495 ,mol/l). No patients (63% of those with anginal pain, significant difference was detected, how- and 64% of those with atypical pain). The ever, between the two groups in either final diagnoses reached were: normal fasting or post-prandial bile acid concen- Fl 15 oesophagus (26), gastro-oesophageal reflux trations (Wilcoxon's signed rank test). Relationship between gastro-oesophageal (21), diffuse oesophageal spasm (16), non- Gastric juice pH values and gastric juice reflux (GOR), duodenal ulcer (DU) and specific oesophageal motility disorders volumes 60 minutes after the meal did not pyloric stenosis (PS) (15), hypertensive lower oesphageal differ between the two goups. Nine of the sphincter (four), nut-cracker oesophagus 16 patients had significant bile acid con- D FLOOK AND C J STODDARD (University (three), and vigorous achalasia (one). tamination of gastric juice (>100 ,mol/l) Department of Surgery, Liverpool) It has Fifteen of the 21 patients with reflux also and in seven of these the gastric juice pH been suggested that gastric outlet obstruc- had a motility disorder. In nine of these 21, was <3*5. Six of the control subjects had tion may be an important factor in the there was no endoscopic or histological bile acid concentrations >100 umol/l. pathogenesis of GOR. In one study 80% of evidence of oesophagitis. In six patients We conclude that patients with erosive patients with pyloric stenosis (PS) had with normal manometry, the radionuclide oesophagitis do not have abnormal duo- endoscopic evidence of oesophagitis com- transit pattern was typical of oesphageal denogastric reflux of bile acids. Contami- pared with 54% of patients with uncompli- spasm. nation of gastric juice with bile acids occurs cation duodenal ulcer (UD). The results confirm the high incidence of frequently in patients and in healthy We have studied 64 patients undergoing oesophageal motor disorders in this group volunteers, however, and it is likely that elective DU surgery, of whom 12 (19%) of patients and also show that unsuspected bile acids contribute to the toxic action of had PS. The diagnosis of PS was based on a gastro-oesophageal reflux disease often gastric juice on oesophageal epithelium. history of stasis vomiting and evidence of Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1181 gastric outlet obstruction on barium meal The mechanism of action cannot be a analysis of the pattern of changes in intra- and endoscopy. Preoperatively, all 64 direct effect of the prosthesis on the gastric pH and the study of dose related patients underwent upper GI endoscopy sphincter, or the angle of His, or by effects. with oesophageal biopsy, oesophageal compression or angulation of the gut tube manometry and 24 hour pH studies using by the prosthesis. The effect common to all standard techniques. patients was a reduction in hiatal flow. The Fl 18 Oesophagitis was present in three of the clinical results appear to be as good as Acid secretory capacity after treatment 12 patients with PS (25%) and in 14 of the those after conventional repair. with omeprazole 52 patients with an uncomplicated DU (27%). Abnormal gastro-oesophageal B K SHARMA, P LUNDBORG, R E POUNDER, M reflux (GOR) was demonstrated by pH Gastroduodenal AXELSON, M OHMAN, I A SANTANA, M TALBOT, monitoring in seven of the 12 patients with AND C CEDERBERG (Academic Department PS (58%) and in 32 (61%) of the Fl17 of Medicine, Royal Free Hospital, London, remainder. Pharmacological evaluation of an anti- and Research Labs, AB Hassle, Molndal, These results show that the incidence of secretory agent using continuous 24 hour Sweden) Omeprazole is a potent abnormal GOR and oesophagitis in PS is ambulatory gastric pH recording suppressor of gastric acid secretion: 30 mg no greater than in patients with an daily causes a 97% decrease of 24 hour uncomplicated DU. Gastric outlet obstruc- B KAPUR, JANE MILLS, SARAH DUNN, KATHIE intragastric acidity in duodenal ulcer tion, per se, does not appear to be of major WAREHAM, W L BURLAND, M J LUNT, AND K D patients. After 14 days of treatment with importance in the pathogenesis of GOR. BARDHAN (District General Hospital, omeprazole 30-60 mg/day there is a Rotherham and Smith, Kline & French progressive four-fold increase of fasting Research Ltd., Welwyn Garden City, plasma gastrin concentration, dropping to Fl 16 Herts) We have recently developed and a two-fold rise one week after stopping the Quantitative assessment of results with the validated a method for continuous 24 hour drug. The object of this study was to Angelchik prosthesis monitoring of intragastric pH, utilising a determine whether this rise of plasma microelectrode and computerised data gastrin has a trophic effect on the parietal J H WYLLIE AND D A W EDWARDS (Academic analysis. The potential of the technique in cell mass in man. Unit of Surgery, Whittington Hospital, studying the effect of gastric anti-secretory In a double-blind study, 16 healthy Highgate Hill, London) Our aim was to drugs was evaluated, using the H, receptor volunteers were studied twice before and 1, assess the usefulness and mode of action of antagonist, oxmetidine (Ox) as the 8, 15, 22, and 57 days after, 14 daily doses the Angelchik silicone antireflux prothesis example. Eight healthy subjects were of omeprazole 40 mg (n=8) or placebo in hiatal hernia and gastro-oesophageal studied up to four times each. They (n=8). Maximal acid secretion was stimu- reflux. Fifteen prostheses have been received either placebo, Ox 400 mg or 600 lated by intravenous pentagastrin (12 or inserted and assessed more than three mg at bedtime, or 400 mg after breakfast 2-0 ,ug/kg/h), with correction for pyloric http://gut.bmj.com/ months later; all patients (mean age 70 and bedtime. The treatment order was losses of acid using gastric phenol red- years) had severe intractable symptoms of randomised and the study conducted saline perfusion. Fasting plasma gastrin regurgitation and reflux - 12 with stricture. double-blind. concentration was measured in duplicate Hiatal flow, reflux, length and bore of The daytime (0850-2400 hours) samples taken before each pentagastrin strictures were quantified by standardised intragastric pH on placebo was <2-() for test. procedures including use of graded sizes of 72±5% (mean±SEM) of the time and Every subject showed a rise in fasting radio-opaque tablets. Position and orien- ¢4 () for only 4±1%. On Ox. the plasma gastrin concentration after two tation of the prosthesis, which part of the percentage of daytime below pH 2.0 fell to weeks of treatment with omeprazole 40 mg on September 30, 2021 by guest. Protected copyright. gut tube was encircled by it, the size and 65±7%, 57±8% and 35±5% for the three daily. After treatment with placebo there position of any intrathoracic stomach, and doses respectively and that above pH 4 0 was no change in either fasting plasma any evidence of angulation or compression rose to 9±3%, 11±5% and 19±6%. These gastrin concentration or mean peak acid of the gut tube were recorded on film and show a significant shift to higher pH with output. The only change in acid secretion videotape. Ox (p<0001) and the effect is dose related after treatment with omeprazole was a Preoperatively, all had hiatal flow of (p<0 05). 68% decrease of peak acid output one day barium and reflux flooding of the gullet. The nocturnal (2400-0650 hours) pH on after the last dose of the drug, with no Postoperatively, hiatal flow could not be placebo was <2-0 for 65±9% of the time evidence of a subsequent increase of acid provoked in nine and was only slight and and ¢4-0 for 24±9%. For the three doses output above the before treatment level. intermittent in six. Only in one could reflux of Ox, the percentage of night-time at pH In conclusion, this controlled study be provoked consistently. The mean <2-0 was 20±7%, 11±5% amd 20±7% shows that, despite omeprazole-induced preoperative length and bore of 12 and at pHI4-0 was 56±7%, 63±9% and rise of fasting plasma gastrin concen- strictures were 7-5±1-74 mm (SEM) and 56±8% respectively. These also show a tration, there is no evidence of parietal cell 7-95±0-73; the mean postoperative significant shift to higher pH with Ox hyperplasia. 3-5± 121 and 11-12±1-13 respectively; five (p<0-001) but no dose related effect. strictures disappeared. Eight prostheses In conclusion, the anti-secretory effect of were in the chest but this did not cause oxmetidine was confirmed and quantified. Fl19 symptoms or influence the results. The Compared with the traditional method Effect of morning or evening dosage with 10 sphincter was not encircled by the involving intermittent gastric aspiration, mg omeprazole on 24 hour gastric pH in prosthesis in any patient. the new technique allows more detailed duodenal ulcer patients in remission Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1 182 The British Society of Gastroenterology P J PRITCHARD, N D YEOMANS, D B JONES, W J dialysis day when placebo was given; day 2, in order to elucidate the mechanism of LOUIS, AND R A SMALLWOOD (INTRODUCED BY a non-dialysis day when 30 mg omeprazole their supposed cytoprotective activity. Five G D KERR) (Depts of Gastroenterology and was given; day 3, a dialysis day when 30 mg groups of rats (n= 10) were studied. Clinical Pharmacology, Austin Hospital, omeprazole was given and conventional Groups A, B, C, and D received ASA- Melbourne, Australia) Omeprazole, an haemodialysis was carried out over 5 HCI (25 mg/kg ip) daily and group E inhibitor of the parietal cell (H '/K ') ATP- hours. Basal and plateau acid output (to received placebo. In addition, group A ase, substantially raises gastric pH when 1 2 ,g/kg pentagastrin for one hour) received cimetidine (28 mg/kg day), group given once/day at doses of 3(0-40 mg (which (BAO, PAO) were measured on each B ranitidine (8 mg/kg day) and group C heal duodenal ulcers). Lower dosage (- 10 occasion. Basal acid output (Mean+sd) on pirenzepine (28 mg/kg day). After 21 days, mg) is being considered for maintenance day 1 was 2-5±3 0 mmol/h. On days 2 and PGE2 content was measured by RIA on therapy, but little is known about its 3, five out of six patients were achlorhydic. extracts from fundic mucosa, while influence on gastric pH. The aims of this Plateau acid output was 27-2±15 0 on day specimens from the gastric body and study were: (1) to examine the effect of 1, 6 3±8-0 on day 2 (-77U/C; p<(0(2) and antrum were stained for muco-substances 10 mg omeprazole daily on gastric pH in 2-8±6 2 on day 3 (-90%; p<0.02). There (PAS technique). Semiquan.itative duodenal ulcer patients in remission, (2) to was no significant difference between days analysis (% of PAS-positive foveolar cells) compare the efficacy of am and pm dosage. 2 and 3. was performed. Eight male patients aged 45-65 years The time to reach peak plasma concen- Results show: received 10 mg/d (EC granulate) either in trations (range 0-5 to 2.0 h) and the peak PGE2 '% PAS the am or pm (double-blind) for two concentrations obtained (range 154 to 1187 (pgll00 "itg) Poxitil( weeks, then crossed over to the alternative ,Ag/l) showed marked intersubject variation (GroupL nean + SELM foleoltar cell regimen. Gastric pH was measured hourly and were not influenced by dialysis. The A 1084±+ 148 83* _(2 for 24 hours on three occasions; baseline, area under the concentration/time curve B 1959+ 191 7(0-4 3-5 and on day 14 of each dosage period. (0-8 h) ranged from 138-3248,g/h/I on day C '2720+649 58.9* 4(1 There was no D 1(62h+ 148 84 * 2(0 Twenty four hour median pH's (inter- 2 and 99-2365 on day 3 (NS). 6617+546 1(0 55 quartile range) were 16 (14-2-1) for difference in omeprazole concentrations E baseline, 3 3 (1 7-5.9) for am dose and 2 9 from arterial and venous samples during * p ().()I (1-7-5-2) for pm dosage. Differences dialysis, and omeprazole was not detected We conclude that in rats chronic admini- between control and each omeprazole in dialysis fluid. stration of small doses ASA inhibit PGE2 study were significant (p<)-01 Wilcoxon's Omeprazole is a powerful inhibitor of generation without causing mucosal lesions paired ranks test). Despite these marked gastric acid secretion in patients with CRF, in the stomach. Ranitidine as well as rises during treatment in the group overall, and neither its antisecretory effect nor its pirenzepine significantly antagonise these a striking feature was the intersubject kinetic profile are influenced by haemo- effects while cimetidine does not. Similarly variation at this dose; in two subjects, dialysis. ranitidine and pirenzepine but not median pH did not alter during treatment, cimetidine also modify the reduction of http://gut.bmj.com/ while in another it rose to 6-2 on am mucosa production induced by chronic dosage, while for pm dosage pH was higher F121 administration of ASA. from 2100-0200 only. Comparison between the effects of H2- It is concluded that 10 mg omeprazole blockers and anti-muscarinic drugs on given either am or pm raises gastric pH prostaglandin generation and mucosal cell F122 through the 24 hour period. The failure of activity in the stomach of rats Adherent gastric mucus thickness in two of 8 subjects to respond to this dose patients with gastroduodenal disorders on September 30, 2021 by guest. Protected copyright. suggests that a higher maintenance dose D LOMANTO, E LEZOCHE, M D D'ALESSANDRO, may be required in some ulcer patients. F CARLEI, AND P MARIANI SPERANZA W J CUNLIFFE, A ALLEN, D A HUTTON, J P (VI Clinica Chirurgica, Universita Degli PEARSON, AND C W VENABLES (Departments Studi La Sapienzd, Rome, Italy) Cyto- of Physiological Sciences and Surgery, F120 protection is defined as the property of University, Newcastle upon Tyne) The Influence of haemodialysis on the antisecre- different substances of protecting the gastric mucosa is covered by a layer of tory effect and oral pharmacokinetics of gastric mucosa against various noxious adherent mucus gel. This adherent mucus omeprazole in chronic renal failure agents unrelated to the inhibition of gastric protects underlying epithelial cells from acid secretion. acid, by facilitating mucosal surface C W HOWDEN, C D PAYTON, P A MEREDITH, A I Previous studies have shown that anti- neutralisation (mucus bicarbonate barrier), MACDOUGALL, J L REID, AND J A H FORREST muscarinic drugs may have cytoprotective from digestion by luminal pepsin and from (University Department of Materia,Medica, activity and also H2-blockers have been shear forces during digestion. Previous Renal Unit and Gastroenterology Unit, indicated as cytoprotective agents structural studies have shown a decrease in Stobhill General Hospital, Glasgow) The although, these results are still disputed. the proportion of gel-forming polymeric effects of single 30 mg oral doses of As prostaglandin generation is considered glycoprotein in adherent mucus from omeprazole on gastric acid secretion were an important factor in gastric cytoprotec- patients with peptic ulcer disease compared assessed in six patients with chronic renal tion. We have compared the effects of with that from histologically normal failure (CRF) receiving regular haemo- cimetidine, ranitidine and pirenzepine on stomachs. There is, however, no informa- dialysis. Patients (age range 19-51; mean the inhibition of prostaglandin generation tion concerning the continuity and depth of 31 years) were studied on three occasions induced by administration of non- this mucus layer in these patients. A one week apart - namely, day 1, a non- ulcerogenic doses of aspirin (ASA) in rats technique developed for measuring gastric Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1183 mucus thickness in laboratory animals has incubation with arachidonic acid: 375 (40- F125 been adapted to measure adherent antral 2262) pg/mg (n=33, uninflamed) and 460 Levels of n-nitroso compounds, bile acids mucus thickness on mucosa in patients who (173-1898 pg/mg (n=17, inflamed and bacteria do not predict histological have undergone gastrectomy. A minimum p=0)038). Catabolism of PGF2d measured change in the operated stomach of 25 readings, at 500 ,um intervals along by quantitative thin layer chromatography three sections, were taken per patient. The was 42% (16-66%) (n=38, uninflamed) S BREARLEY, H R THOMPSON, V POXON, D adherent mucus gel in all cases was seen as and 30% (8-63%/c) (n=21, inflamed YOUNG, AND M R B KEIGHLEY (Department a continuous opalescent layer adhering to p=0)036). There was no significant of Surgery and Department of Histopath- the mucosa. Values for median thickness differences in these values for patients with ology, General Hospital, Birmingham) (n = number of patients) were as follows: gastric ulcers compared with controls with N-nitroso compounds and free bile acids duodenal ulcer, 100 ,um (n=4); gastric similar levels of gastritis. may be carcinogens in the operated ulcer, 250 gm (n=3); gastric cancer, 240 Thus, both enhanced PG synthesis and stomach. To test this hypothesis, gastric ,tm (n =6); non-diseased stomachs depressed PG catabolism may contribute aspirates were collected over a 24 hour (Whipple's resection, Roux-en-Y for reflux to increased gastric PG concentrations in period from 12 patients who had had ulcer oesophagitis) l)m180 (n=4). The distri- gastritis. No additional abnormalities of curing operations (PVG 5, TV+P 5, bution of mucus thickness measurements in PG synthesis or of PG metabolism were TV+A 2) between one and nine years duodenal ulcer patients was significantly found in gastric ulcer patients. (mean four) previously and from eight lower compared with that in the other healthy volunteers. Total and stable n- groups. The distribution of median nitroso compounds, nitrite, total and thickness measurements for a group of nitrite reducing bacteria and total and free patients with pre-pyloric ulcer (n=5) F124 bile acids (six patients) were measured. ranged in values between those obtained Gastric juice bile acids and scintigraphy in The patients subsequently had a gastro- for duodenal ulcer and gastric ulcer the assessment of duodenogastric reflux scopy and eight biopsies were taken in a patients. The thickness of mucus layer is a standard manner from each. dynamic balance between secretion and P W J iHOUGHTI)N, N J McC Mt)RITENSEN, W F G There was no significant difference erosion by pepsin and with respect to the THOMAS, M J COOPER, A P MORGAN, AND F R between patients and controls with regard thinner layer of adherent gastric mucus in DAVIES (Departments of Surgery and to any variable. Values varied widely duodenal ulcer patients it is- relevant that Radiodiagnosis, Bristol Royal Infirmary, between individual patients. All patients pepsin concentrations are raised in this Bristol) Duodenogastric reflux has been showed mild to moderate gastritis but the disease. implicated in the pathogenesis of several severity of the changes did not correlate upper gastrointestinal disorders. Scinti- with any variable. One patient (PVG) had graphy is increasingly being used as an a focus of intestinal metaplasia in one F123 assessment of reflux and although the biopsy and three patients showed mild http://gut.bmj.com/ Prostaglandin synthesis and catabolism in grading of reflux correlates with histo- regenerative dysplasia. None of these had gastritis and gastric ulcer logical abnormalities, intragastric pH and high concentrations of n-nitroso com- nitrite concentrations, its accuracy is not pounds, bile acids or bacteria. There was C J HAWKEY (Department of Therapeutics, fully established. no true dysplasia. University Hospital, Nottingham) To We have compared the grade of reflux This study has failed to find gastric assess the significance of endogenous assessed scintigraphically with the result of metaplasia or dysplasia within the first prostaglandins (PGs) in gastritis and gastric bile acid assay in gastric juice samples. In postoperative decade even in patients with ulcer PG synthesis and catabolism by non- 104 patients undergoing review or routint high concentrations of n-nitroso com- on September 30, 2021 by guest. Protected copyright. ulcerated human gastric mucosa was gastroscopy, gastric juice was aspirated and pounds, bile acids and bacteria. studied. total and free bile acids were measured. Endoscopic biopsy specimens from 59 Duodenogastric reflux was then deter- patients not taking anti-inflammatory drugs mined by milk CCK/BIDA scanning and F126 were homogenised on ice in Tris HCI 0 05 graded 0-4 by a radiologist. Gastric cancer developing after operations M pH 7-4. Aliquots (10 mg; 0-5 ml) were In patients with grade 0 and I reflux for benign peptic ulcer (a) extracted immediately; (b) incubated (n=40) median total bile acids were 45 with arachidonic acid 2 gg for 30 min at ,umol/l (range 0-13102) compared with G CORCORAN, J WARE, D DAY, AND J N BAXTER 37°C; or (c) incubated with (9 B H3) PGF'a grade 2 and 3 reflux patients (n=631), 2176 (Royal Liverpool Hospital, University 1 ,tg (0.1 uCi) and NAD 2 mM for five min ,umol/l (range 0-50368), p<0O001 (Mann Departments of Surgery and Pathology, at 37°C. Histological appearances in Whitney test). Free bile acids were also Liverpool) Hitherto no large retrospec- adjacent biopsy specimens were classified lower in patients with grade 0 and 1 reflux tive survey to identify the relative risk of (blind) as uninflamed (normal or mild (n=39) compared with those with grade 2 gastric cancer after operations for benign gastritis) or inflamed (moderate or severe and 3 reflux (n=61); 0 ,umol/l (range peptic ulcer disease has been reported from gastritis) by standard criteria. (-5818) versus 299 ,umol/l (range 0-19030), the UK (operated stomach cancer, OSC). Synthesis of PGE, (median and range) p<0-()l. The Mersey Regional Cancer Registry measured by radioimmunoassay was; (a) These results suggest that milk CCK/ contains the records obtained from a after homogenisation: 67 (16-465 pg/mg BIDA scintigraphy correlates with gastric population of 3 15x 10'. Clinical details wet weight (n=36. uninflamed) and 122 juice total bile acids and free bile acids and were available for 85% of the 4296 gastric (18-667) pg/mg (n= 18, inflamed p=0 036. is a useful clinical assessment of duodeo- cancer registrations between 197(}-1975 two tailed Mann Whitney U test); (b) after gastric reflux. inclusive. From the 3638 notes reviewed, Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1184 The British Society of Gastroenterology 62 OSC cases were identified (1.7%). episodic diarrhoea in five (3%) patients. pressure activity; however, N significantly Using regional Hospital Activity Analysis The poor results in the remaining patients reduced the magnitude of pyloric response data, 7304 benign peptic ulcer operations was because of delayed gastric emptying in to 1B-E in a dose-dependent fashion were observed to relate to the same popu- seven (5%) and recurrent ulceration in 34 (p<0-05). 1-E also induced episodes of lation and period of the survey. The annual (20%) patients. Of the seven patients who repetitive phasic and tonic pyloric con- incidence for OSC and gastric cancer de developed gastric stasis six to 24 months traction ('pylorospasm') which were not novo were 141 and 30 per 10' respectively. after PGV, a pyloroplasty was necessary in completely abolished by N. No changes Thus the relative risk of developing OSC six. Recurrent ulceration occurred within were observed in plasma catecholamines. after surgery was 4-7 (95% confidence two years in 11 (32%) patients, between We conclude that infusion of synthetic limits, 3.5-6-0). Although the mean ages of two and five years in 12 (35%) and in 11 human 13-E directly stimulates pyloric the diagnosis of OSC and gastric cancer de (32%) after five years. The recurrences activity in man; this 'pylorospasm' may be novo were similar. 66-7 years and 65-6 were duodenal in 25 and gastric in nine responsible for the delayed gastric years respectively, the sex ratio of M:F; 3:2 patients. emptying induced by certain opiates and by for gastric cancer de novo was more heavily These results confirm the safety of PGV experimental stress. weighted for men in OSC, M:F 4:1. The and its low rate morbitiy. Although the mean time interval between operation and recurrence rate is high in this series it is diagnosis of OSC was 21-8 years, and the within the range reported by others who F129 crude survival was 2-2 months. Contrary to followed their patients for a similar period. Influence of intraduodenal chenodeoxy- previous reports there was a duodenal cholic acid (CDC) on fasting secretory and ulcer predominance at the original opera- pressure activity in the stomach and tion (65% of those cases where details were duodenum of man certain, 40/62). F128 It is concluded: (1) there is a demon- 'Pylorospasm' induced by infusion of an I A EYRE-BROOK, N W READ, T BROWNSON, strably increased risk of developing OSC endogenous opiate in man AND A G JOHNSON (University Departments after benign peptic ulcer surgery, and (2) of Surgery and Physiology, Royal Hallam- contrary to previous reports, duodenal M CAMILLERI, V STANGHELLINI, A R shire Hospital, Sheffield) The influence of ulcer disease does not protect a patient ZINSMEISTER, P C KAO, C H Li, AND J R duodenal infusion of bile acid at a concen- from developing this lethal malignancy. MALAGELADA (INTRODUCED BY S F PHILLIPS) tration similar to that in the common bile (Gastroenterology Unit, Mayo Clinic, duct (50 mmol/l) upon fasting antro- Rochester, Minnesota, and Laboratory of duodenal motility, duodenogastric reflux F127 Molecular Endocrinology, University of and gastric and duodenal secretion was California, San Francisco, studied in 10 healthy volunteers. Intra- Proximal gastric vagotomy: 5-13 years California, http://gut.bmj.com/ follow up USA) Acute stress in man inhibits gastric luminal pressures were recorded in the emptying of a meal and increases plasma antrum and the first and second parts of the A FRESINI, P B BOULOS, AND C G CLARK P-endorphin (,6-E) concentrations. Stress- duodenum, and distal duodenal contents (Department ofSurgery, Faculty of Clinical induced gastric stasis could be because of were collected by continuous low pressure Sciences, University College London, The 'pylorospasm' via stimulation of opiate sump aspiration during infusion of either Rayne Institute, London) Proximal gastric receptors. To test the hypothesis that the saline or CDC into the second part of vagotomy (PGV) has become a standard human pyloric sphincter is sensitive to duodenum. Values for reflux and secretion procedure for chronic uncomplicated -circulating we studied, were calculated with reference to the P-endorphin (P-E), on September 30, 2021 by guest. Protected copyright. duodenal ulceration in specialised surgical in 45 healthy volunteers, the dose-related recovery of two non-absorbable markers departments. Although there is an agree- effects of iv infusion of synthetic human infused into the stomach and duodenum. ment on its fewer side effects, there is still a j-E (dose range 2-5-2500 ng/kg/min, with 1 Each volunteer received at least three hour wide discrepancy on the reported incidence log stepwise separation) and naloxone (N: of saline and two hours of C?C infusion. of recurrent ulceration probably because of range 114-1140 ng/kg/min, with 1 log During saline infusion, duodenogastric the inconsistency in which the results have separation) on pyloric pressure activity reflux varied with the MMC, being statis- been reported. In too few series, patients after a meal. We used a low-compliance tically greater at the end of duodenal phase were followed up for an adequate period to pneumohydraulic perfusion system with 10 III activity than at any other time draw out accurate conclusions. manometric sites 1 cm apart across the (p<0.05). Chenodeoxycholic acid From 1970 to 1981, 234 patients (176 antroduodenal region. Plasma P-E and abolished the MMC and inhibited antral men and 48 women with mean ages of 42 catecholamines were measured during the contractions (p<005), but the amount of and 43 years repsectively) underwent PGV study. The pylorus was identified by mano- reflux was not increased compared with the without drainage. There was one post- metric criteria. Statistical analysis was by saline period. Chenodeoxycholic acid also operative death (0.4%) and an overall an analysis of variance of surface responses produced an increase in secretion of trypsin morbidity of 20-5% owing to minor compli- programme written for the 4x5 factorial (p<0-001), bicarbonate (p<0 001), cations in 34 (14-5%) patients. The results design that was used in this study. phospholipase A2 (p<0.05) and endo- were analysed in only 168 patients who 1-E increased pyloric contractions genous total bile acid (p<0-05) into the were followed up for five to 13 years; an (p<0.01) in the linear dose-dependent duodenum though gastric acid secretion average of eight years. The functional fashion up to an infusion of 250 ng/kg/min was unaffected. These findings suggest that result in 126 (75%) patients was good, (corresponding to mean plasma concen- bile acid may play a key role in the control graded as Visick I or II. Mild dumping tration range of 300 to 17000 pg/ml). of gastroduodenal motor activity and occurred in three (1.8%) patients and mild Naloxone alone did not alter the pyloric pancreatico-biliary secretion. Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1185 F130 upper GI lesions. We have assessed its activity persisted even at maximum Disordered gastric motility in chronic renal value in a double blind controlled trial. concentration of the inhibitor. failure Fifty four patients with a history of upper The effect of aprotinin on gastric (n=5) GI haemorrhage and endoscopic evidence and duodenal (n=9) juice in vivo was B J COLLINS, P T McNAMEE, G W MOORE, C C of a solitary peptic ulcer with stigmata of studied in healthy volunteers. Samples DOHERTY, M G McGEOWN, AND A H G LOVE recent haemorrhage were studied. Eight were collected during a control period and (Renal Unit, Belfast City Hospital and were excluded for the following reasons: during intragastric infusion of aprotinin. In Department of Medicine, The Queen's poor access of the lesion in six (in four gastric juice trasylol reduced the mean University of Belfast, NI) Anorexia, physical access was restricted and in two diameter of the zone of fibrinolysis from nausea and vomiting almost invariably torrential bleeding obscured the lesion), 4 0±SD 1 3 cm to 0-5±SD 0-6 cm accompany advanced chronic renal failure anticoagulant therapy in one, pyloric (p<0.001) and rendered trypsin un- (CRF), yet the mechanisms responsible are stenosis in one. The remaining 46 were detectable. largely unknown. Disordered gastric randomly allocated to electrocoagulation In duodenal juice the zone of fibrinolysis motility may be associated with these or sham treatment. In all patients the ulcer was reduced from 3 8±0-8 to 2-3±0-4 cm symptoms, but there have been no base was washed and those in the treat- (p<0.OOl) and tryptic activity fell from previous studies of gastric emptying in ment group then had electrocoagulation 0 92±0-25 to 0 10±0 12 mmol/ml patients with CRF. We have measured performed. The 2 3 mm diameter probe (p<0-02). gastric emptying of a solid meal in 12 was used to deliver 2 second pulses of Intragastric infusion of aprotinin may patients (GFR <5 ml/min), all of whom coagulating current with a generator power prove useful in preventing rebleeding had normal barium meal appearances, and setting of 7. A mean number of 8-3 following upper gastrointestinal in 10 control subjects. The test meal applications was required to achieve haemorrhage. consisted of 30 g porridge, mixed with 150 charring of the ulcer base. There was no ml milk, and labelled with 300 gCi significant difference in the rate of Technetium-99m tin colloid. Gastric rebleeding: treatment 7/21 (33%); control F133 emptying was monitored over a 90 minute 5/25 (20%), rate of surgery: treatment 2/21 A trial design with dynamic treatment period using a gamma camera. The reten- (9.5%); control 2/25 (8%), mean trans- allocation for gastrointestinal bleeding tion of isotope in the stomach was signifi- fusion requirement: treatment 1-98 units; cantly greater at 30, 60, and 90 minutes in control 3 27 units or duration of hospital D R APPLETON, C W VENABLES, AND C 0 the 12 CRF patients compared with the 10 stay: treated 6 5 days; control 6-8 days. RECORD (Department of Medical Statistics control subjects (p<0.05) (Mann-Whitney- There were no deaths in either group. and Gastroenterology Unit, Royal Victoria U test). Emptying index values were Massive bleeding complicated electro- Infirmary and University ofNewcastle upon significantly smaller in the patient group coagulation of a visible vessel in one Tyne) Random allocation of patients to compared with the control subjects, again patient but perforation did not occur. different therapeutic modalities for life http://gut.bmj.com/ indicating that a slower pattern of In conclusion the ACMI Bicap system, threatening conditions can suffer from the emptying occurs in CRF patients (p<005). as used in this study, has not been found to disadvantage that patients allocated to one Three of the 12 CRF patients were on be effective in the treatment of bleeding group may fare particularly badly, so that regular dialysis treatment and their gastric peptic ulcers. the overall mortality during the trial is emptying rates were similar to those of the higher than would be expected after the control group. trial was finished. To overcome this We conclude that non-dialysed patients F132 problem in the case of gastrointestinal with chronic renal failure have impaired Inhibition of gastroduodenal fibrinolytic bleeding, where potentially beneficial new on September 30, 2021 by guest. Protected copyright. gastric emptying and it is possible that this activity - a suggested treatment for upper treatments have recently been suggested, disturbance improves with regular dialysis. gastrointestinal bleeding we have devised a dynamic allocation of Further assessment of this motility disorder peptic ulcer patients with an endoscopically is required as it may contribute to, or S BREARLEY, V POXON, D L MORRIS, P W visible vessel to three possible treatments - influence gastrointestinal symptoms, nutri- DYKES, AND M R B KEIGHLEY (Department namely, (i) surgery immediately after tional state and drug bioavailability in of Surgery and Department of Medicine, endoscopy, (ii) endoscopic bipolar electro- uraemic patients. General Hospital, Birmingham) Most coagulation, (iii) conservative treatment; if deaths from upper gastrointestinal treatment (ii) or (iii) is unsuccessful bleeding are associated with episodes of surgery is performed. F131 rebleeding. Prevention of rebleeding might The probability of being allocated to Controlled trial of endoscopic bipolar be achieved by inhibiting the lysis of clot each treatment depends on the success rate electrocoagulation in the treatment' of sealing the bleeding point. The ability of to date of each treatment, on an extension bleeding peptic ulcers the protease inhibitor aprotinin to inhibit of the principle that for two treatments tryptic activity (measured by a BANA with success rates PI and P2 the relative B M GOUDIE, K G MITCHELL, G G BIRNIE, AND chromogenic substrate assay) and fibrino- probability of a patient receiving treatment C MACKAY (Western Infirmary, Glasgow) lytic activity (measured by a fibrin plate 1 is P,/(1-P1):P./(l-P.). These probabil- The ACMI Bicap bipolar electrocoagu- method) in duodenal juice was studied in ities are calculated by computer from a lation system is a portable, relatively vitro. There was a good correlation continuously updated database. Simula- inexpensive device which can be used in between the two variables (r=0.8 p<0 05). tions have shown that with this method of conjunction with a standard endoscope to Trypsin becomes undetectable in the biassed random allocation the proportion of deliver coagulating current to bleeding presence of aprotinin but some fibrinolytic patients on a less successful treatment can Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1186 The British Society of Gastroenterology be considerably lower than if allocation F135 systems comparing their performance with were completely at random, while at the Sphincterotomy with gall bladder in situ; standard diameter electrodes. A large same time sufficient patients receive each one to eight year follow up diameter heater probe (3.2 mm), bipolar treatment for significant differences to be (Bicap) and monopolar electrodes were detected. This dynamic allocation T P YIN, J W C LEUNG, A G VALLON, AND P B compared with their small 295 mm procedure should be particularly valuable CO1fTON (Department of Gastroenterology, diameter counterparts in 60 standard in situations where treatment success rates The Middlesex Hospital, London) We bleeding ulcers and on 60 large bleeding are controversial or unknown. have followed a total of 159 patients with mesenteric vessels. The large bipolar and gall bladders, who underwent endoscopic heater probe but not the monopolar probe sphincterotomy for clearance of duct were significantly more effective (p<(X)l) stones between 1975 and June 1983. Most than their smaller counterparts in control- had had symptoms chronically, for up to 10 ling bleeding in these models and equally years, and 43% of the patients had acute safe. We have designed and built (a) the biliary symptoms (cholangitis, jaundice, first non-stick electrode using new UPPER GI ENDOSCOPY pancreatitis) at the time of referral. Twenty composite plastics specifically developed F134-39 eight per cent had other major medical by us for this purpose (b) an optional laser problems. Sphincterotomy succeeded in tip of non-stick material transparent to Nd F134 158, and the duct was clear at the end of YAG laser light designed to exert pressure Design, development and testing of an the procedure on 142. Fifteen patients on the bleeding point during photocoagu- endoscopic sewing machine underwent early surgery for retained lation and protect the fibre waveguide. In stones, without mortality. The remaining 40 standard canine experimental bleeding C P SWAIN, T N MILLS, S MARGARET ROE, two died, from biliary cirrhosis and hepatic ulcers, the non-stick monopolar electrode AND T C NORTHFIELD (The Department of abscesses present prior to endoscopic treat- was as highly effective as a standard mono- Medical Physics, University College ment. Of the 142 patients with clear ducts, polar electrode requiring 5-4±2 7 vs Hospital and Departments of Gastroenter- 22 underwent cholecystectomy during the 6 2±3-0 pulses to stop bleeding. Its low ology, St Georges Hospital, London and same admission; three for acute cholecyst- thermal dissipation significantly reduced Ashford Hospital, Middx) The availability itis, and 19 because of relative fitness (six the total energy required to stop bleeding of an endoscopically controlled sewing of the gall bladders contained no stones). (90 J±32 vs 132±48, p<0001), enhancing machine would enable endoscopists to Follow up has been possible in 109 of the safety and tissue adherence was markedly perform a wide range of surgical 121 patients who left hospital with their gall reduced. A coaptive Nd YAG laser tip was procedures. The problems involved in the bladders; their mean age was 74 years and designed to allow pressure to be exerted on design of such a machine are not trivial. they had been followed between one to a bleeding vessel during laser coagulation. Vision is limited by the optics of the eight years, or earlier death. Thirty In isolated arteries of 15-4 mm, this tip http://gut.bmj.com/ endoscope, only one side of the tissue can patients had died from unrelated cause, but significantly enhanced occlusion, welding be reached directly, the tissue is poorly none had died from biliary disease; nine 12/14 (mean bursting pressure 520 mm Hg) supported, power to and control of the required cholecystectomy for gall bladder vs 0/14 arteries with Nd YAG laser without sewing machine is via two small diameter symptoms (none urgently), and two coaptation. biopsy channels. This study reports the needed further endoscopic duct clearance. We conclude that better mechanical design and development of an endoscopic We confidently recommend endoscopic occlusion of the vessel at the bleeding point sewing machine and its testing in the management for patients acutely ill with by these simple means can markedly human cadaveric stomach and oesophagus. duct stones, and those who are old and frail improve the performance of probe type on September 30, 2021 by guest. Protected copyright. Preliminary studies established a'method with gall bladders. The risk of leaving the coagulators and the laser. of 'hand sewing' via an endoscope using a gall bladder in place appeared to be small. transparent overtube with a lateral orifice to allow suction of tissue into a conform- F137 ation that is easily transfixed by a threaded F136 Endoscopic biliary prostheses for large bile needle. Reliable methods of knotting are Development and testing of contact endo- duct stones essential for secure surgery. We have scopic thermal methods which are more developed a method of tying knots and a effective than conventional lasers and A FORBES, J W C LEUNG, AND P B COTIrON crimped collar method for securing thread diathermy electrodes in controlling bleeding (Department of Gastroenterology% The in the gastrointestinal tract via endoscopes. in the gastrointestinal tract Middlesex Hospital, London) Most fail- A prototype endoscopic sewing machine ures of endoscopic stone extraction are utilising two synchronously driven needles C P SWAIN, T N MILLS, K MATTHEWSON, T C treated surgically. We have used endo- to produce a running stitch has been built NORTHFIELD, AND P R SALMON (Depart- scopic prostheses in 22 patients with strong and successfully tested in the human ments of Gastroenterology and Medical contra-indications for surgery. Two young cadaveric stomach. This study has shown Physics, University College Hospital and patients had problematic portal hyper- that sewing tissue under endoscopic contol Norman Tanner Gastroenterology Unit, St tension. The mean age of the remainder is feasible and that the problems inherent James Hospital, London) The aim of this was 79 years. Ten patients had acute to such a procedure can be readily study was to evaluate and develop cholangitis. Access was limited by large overcome using either a range of new improved methods of endoscopic thermal diverticula in seven cases, and by Billroth simple endoscopic tools or an endoscopic haemostasis. We have tested three new II gastrectomy in four. Stones ranged in sewing machine. large diameter endoscopic electrode size from 15-28 mm. Nine patients had Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1187 intact gall bladders. Cholangitis recurred gastritis only showed 6/24 (25%) positives. after prosthesis insertion in four patients, No significant difference in the LDH OESOPHAGUS who were managed surgically (at two days isoenzyme ratio was found in any group. F 1 40-45 and one, two, and 52 weeks); three had Two adenoma cases were both negative major peri-operative complications. Two and a 'premalignant' group- for example. F140 other patients died after two months (from severe dysplasia and/or type 2B IM showed What is abnormal oesophageal manometry? cirrhosis and pulmonary embolism). Stone 4/4 ((1)0%) positives. J S and prosthesis passed spontaneously in one We feel that this technique may identify J N BLACKWELL, DE CAESTECKER, JOAN AND R C HEADING patient during the first month, and, in three patients either with early gastric cancer or BROWN, (Department of asymptomatic patients, the duct was those at high risk of developing cancer, and Therapeutics and Clinical Pharmacology, cleared at repeat ERCP after several now intend to undertake a large scale Royal Infirmary, Edinburgh) Oesopha- months. Twelve patients remained well prospective study to evaluate this further. geal manometry has gained an established with prostheses in situ after follow up of role in the investigation of oesophageal 5-26 months (mean 14). Most patients had disorders. Technical problems have largely been given urso-deoxycholic acid, but its F139 been overcome and the procedure is now contribution is difficult to assess. Biliary Laser therapy in the management of accurate and reproducible. Difficulties prostheses may be justified in selected very oesophagogastric tumours have arisen, however, in the interpretation high risk patients with difficult duct stones. of tracings as achalasia is the only disorder N KRASNER AND A I MORRIS (Gastrointes- with generally accepted manometric tinal Unit, Walton Hospital, Liverpool) criteria. Recognition and classification of F138 Where surgery is practicable, this must other motor disorders have been uncertain Estimation of lactic dehydrogenase and remain the treatment of choice in patients and subjective. In an attempt to clarify the beta-glucuronidase in gastric juice as a with tumours of the oesophagus and gastric manometric features and to establish manometric criteria for diagnosis of routine screening test for gastric cancer - a cardia. In many cases, however, patients preliminary communication present with advanced malignancy or are oesophageal motor abnormalities, we have too old or ill to undergo surgery. Laser reviewed the results of 150 patients P FINCH, F P RYAN, K ROGERS, AND S HOLT irradiation offers the prospect of restoring referred for manometry between 1981- (Dept of Gastroenterology, Northern luminal patency where obstruction by the 1984. General Hospital Sheffield) In a previous tumour may be complete. The tracings were analysed by compari- presentation to this society, Rogers et al Twenty five patients of mean age 76 son with the normal values from 50 control (1981) advanced the measurement of lactic years were treated with a Nd-Yag laser set subjects both in qualitative and quanti- dehydrogenase (LDH) and beta-glucuron- to deliver about 100 watts in pulses of 0(5 tative terms. From this comparison the to a abnormalities in the patients have been idase (bG) in gastric wash samples as a 1i) seconds via catheter fed through http://gut.bmj.com/ useful test in the diagnosis of gastric the biopsy channel of a standard forward grouped into manometric categories, which cancer. In a selected population they viewing panendoscope. Intravenous have previously been described but are accurately predicted 42 cancers from a diazepam was used for sedation. Histology incompletely defined and not universally group of 113 patients. We now present our showed 17 tumours to be adenocarcinoma. accepted. We identified the following - findings using the same technique in a Seven were squamous carcinoma and the manometric groups achalasia (eight), prospective group of all patients over 40 other a leimyosarcoma. Patients under- vigorous achalasia (two), diffuse oesopha- years of age undergoing routine upper GI went an average of three treatments with a geal spasm (18), hypertensive lower was on mean energy applied per session of about oesophageal sphincter (15), nutcracker endoscopy. Buffer sprayed the on September 30, 2021 by guest. Protected copyright. gastric mucosa, then retrieved for analysis 3000 joules. The mean survival time aftlr oesophagus (four), non-specific oesopha- of LDH, the m-isoenzyme and bG. the first application of the laser was 16 8 geal motor disorder (20), secondary Multiple biopsies were taken and histo- weeks (range 1 to 68 weeks). Five survived motility disorder (three), and we are able logical examination included typing of more than six months, seven for three to to suggest manometric criteria for these intestinal metaplasia (IM) using mucin six months and 13 survived less than three diagnoses. histochemistry. The sum of the cube roots months. Two died after oesophageal The results indicate that confusion in the of LDH and bG were derived and a level of perforation consequent upon the laser interpretation of oesophageal manometry 5 0 and over was taken as positive. Overall procedure. A further two succumbed as a can be resolved by using a standardised there was 52/149 (35%) positives. All six result of perforation of the oesophagus manometric technique coupled with know- cancers (including three early gastric following attempted intubation when it was ledge of the normal range of pressures and cancers, two malignant ulcers and one felt that laser therapy had no more to offer. awareness that aberrantly conducted advanced cancer) were positive and only In the majority. dysphagia was relieved swallows occur in normal subjects. Definite 1/20 (5%) of normal histology was positive. after the first or second laser session and manometric abnormalities may then be The remaining positives were found in dietary restriction thereafter was minimal. classified with clarity and objectivity. patients with chronic gastritis (CG) either Laser treatment of oesophagogastric alone, 10/39 (26%) or with IM 21/40 tumours is a palliative technique, but easily (53%). Chronic gastritis + IM with repeatable and readily tolerated by the dysplasia showed 4/10 (40%) positives and patient. Relief of dysphagia and improve- F141 CG with dysplasia showed 4/8 (50%) ment in quality of life, even for short Oesophageal bolus transit: effect of positives. A group with no biopsy and periods suggest that the technique is atropine and bethanecol on radionuclide endoscopically normal or with mild worthy of fuller consideration. transit (RT) Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from Al 188 The British Society of Gastroenterology C O H RUSSEIL AND D STROUD (INTRODUCED C 0 H RUSSELL, A DAVIDSON, AND G F143 BY R G FABER) (Departments of Surgery LITT1LEJOHN (INTRODUCED BY R G FABER) Dysphagia for solids after insertion of and Nuclear Medicine, Prince Henry's (Departments of Surgery and Medicine, Angelchik prosthesis Hospital, Melbourne, Victoria, A ustralia) Prince Henry's Hospital, Melbourne, Manometric studies indicate IV atropine Victoria, Australia) Oesophagitis and D L MORRIS, S AMAR, J A JONES, D F EVANS, J (12 /pg/kg) abolishes or decreases the peri- stricture secondary to gastro-oesophageal DORAN, AND J D HARDCASTLE (Departments staltic response to deglutition and reflux (GER) are troublesome complica- of Surgery and Radiology, University decreases peristaltic wave amplitude. Sub tions of connective tissue disorders (CTD) Hospital, Nottingham) Of a prospective cut bethanecol (5 mg) increases wave - especially scleroderma. The primary series of 15 patients who underwent amplitude but decreases velocity. The disease process destroys the normal mecha- insertion of Angelchik prostheses for effect of these drugs on transit of a fluid nisms that control GER- lower oesopha- gastro-oesophageal reflux, two developed bolus has not been studied. geal sphincter and oesophageal peristalsis - complete dysphagia. In the first of these The aim was to study the effect of and predisposes to these complications. the prosthesis had rotated and displaced, atropine and bethanecol on oesophageal Identification of oesophageal motor requiring removal. In the second the transit of a liquid radionuclide bolus. dysfunction in patients with CTD may dysphagia was because of an impacted food On four separate occasions 10 fasting predict those at risk for developing bolus. This prompted us to study the normal volunteers ingested 600 gCi Tc SC oesophagitis and stricture. swallowing of solids in our remaining in 10 ml water with a single swallow, while Our aim is to (a) assess the prevalence of patients. supine over a gamma camera linked to a oesophageal motor dysfunction in patients After a (liquid) barium swallow each minicomputer. Intravenous atropine (12 with CTD using radionuclide transit (RT). patient was asked to swallow a half marsh- Ag/kg), sub cut bethanecol (5 mg), iv or (b) To test the association between mallow washed down with a further aliquot sub cut saline (1 ml) preceded each study abnormal RT and macroscopic evidence of of barium. In a normal subject this by 15, 30, 15, and 30 mins respectively and oesophagitis. standard solid swallow can be expected to in random order. Radionuclide transit was Fifty four patients with CTD - 15 sclero- be delayed in the lower oesophagus for less recorded continuously for 30S. derma (SD), 18 CRST and 21 mixed CTD than 20 seconds. Eleven of our patients Radionuclide transit analysed by two - and 30 normal volunteers were prospec- consented to undergo the solid swallow. methods (a) region of interest (ROI) - this tively studied. RT - 2x 10 ml homogenous No patient had any significant abnorm- describes the 'pattern' of transit (normal boluses of water and 400 ACi TcSC were ality of liquid barium transit. The results of [ activity vs time) through each ROI. (b) posture. Transit was normal if >95% have classified patients into less than 20 http://gut.bmj.com/ Average velocity - distribution of radio- radioactivity cleared the oesophagus in seconds, 20 seconds to three minutes and activity within oesophagus calculated at <15S. Abnormal transit was graded as over three minutes. In eight of the 11 regular intervals and the average velocity of severe if transit time >15S in supine and patients solid transit was slowed to over the trailing edge of the bolus calculated and upright posture or moderate if >15S in three minutes. The delay always occurred expressed in mm/S (±SD). Velocities supine but <1SS in upright posture. 15/33 at the site of the Angelchik prothesis. compared with saline (control) values by SD/CRST group had endoscopy to assess While our clinical experience of the paired t. macroscopic evidence of oesophagitis using Angelchik prosthesis has been encourag- Saline (n= 19) normal RT pattern in standard criteria. Association between RT ing, six patients have complained of on September 30, 2021 by guest. Protected copyright. 19/19. Mean bolus velocity 27 mm/S (±4): abnormality and oesophagitis assessed by dysphagia (of solids), and the radiographic bethanecol (n= 10) normal RT pattern in Kappa statistic. evidence of dysphagia for solids should 6/10; prolonged RT in 4/10. Mean bolus Abnormal RT seen in 13/15 (87%) of perhaps limit the use of this procedure until velocity 20 mm/S (±6) p<0-01: atropine scleroderma group (five severe, eight long term results are known. (n= 10) normal RT pattern in 1/1); moderate); 13/18 (72%) of CRST group impaired clearance 6/10; adynamic 3/10 (four severe, nine moderate); and 7/21 Mean bolus velocity 27 mm/S (±7). (33%) of mixed CTD (two severe, five F144 We conclude that (1) RT studies can be moderate). Endoscopy of sclero- Lower oesophageal high pressure zone after used to calculate bolus velocity (2) atropine derma/CRST group revealed oesophagitis partial fundoplication and after (12 ,ug/kg) can either abolish transit or in 6/7 with severe, 3/5 with moderate and gastroplasty with partial fundoplication - a impair oesophageal clearance of the bolus 0/3 with no RT abnormality. There was a comparison without affecting the velocity of the positive association between the presence clearing wave (3) bethanecol (5 mg) does of oesophagitis and abnormal RT K JEYASINGHAM, L CHiOINIERE, AND tI R J not affect clearing efficiency of the wave (p=0(03). PAYNF (Department of Thoracic Surgery, but can decrease the velocity of that wave. We conclude that the preliminary results Frenchay Hospital, Bristol) The efficiency of this study would suggest an association of a high pressure zone (HPZ) created by between abnormal RT and oesophagitis surgical correction of gastro-oesophageal (p=-O.3) and suggest that SD/CRST reflux is dependent not only on its location F142 patients with abnormal RT should be and length, but also on its ability to relax Oesophageal dysfunction in connective considered for long term anti-reflux with oncoming peristalsis. tissue diseases measures. Seven patients who had undergone Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1189 partial fundoplication (group 1) in the patients with established GOR not KS of 5-8 (p=0(07). Six of eight requiring treatment of gastro-oesophageal reflux and responding to standard conservative CB, thought the diet 'easy', compared with seven others who had undergone a gastro- measures. There has been no mortality, 10/42 not requiring CB (p<0( (15). There plasty and partial fundoplication (group 2) minimal morbidity and no significant was no relationship between the need for in the treatment of an acquired short mechanical complications. CB and the number of parents at home or oesophagus were evaluated mano- The first 100 patients have been parental trust in the child's compliance. metrically. reviewed clinically after a mean follow up Knowledge score was positively correlated The length of the HPZ in group 1 ranged period of 3 4 years and graded sympto- with - social status score (p<0(0006), from 1-3 cm with a mean of 2 cm. In group matically using a modified Visick grading. dietary adherance (p<0(000l) and 2 the length varied between 2-4 cm with a Eighty five per cent of patients came into possession of a recent list of gluten free mean of 2-7 cm. In both groups the HPZ grade I and 97%7/ within grades I and II. products (p<0'028) and membership of the was located at the level of the diaphragm. More recently, the clinical studies have Coeliac Society (p<0'00)5). In neither group was it possible to distin- been complemented by pre and post- We conclude that 2/5 CD cases do not guish an HPZ from the diaphragm. In both operative measurements of lower oesopha- adhere to a GFD and in 16% there had groups the HPZ showed a large diaphrag- geal sphincter pressure and intra- previously been a serious problem with matic respiratory artifact at the onset of oesophageal pH, the preliminary results in compliance. Parents' perception of the diet swallow, followed by co-ordinated relax- 12 patients showing a mean percentage and the child's ability to comply may be at ation which was complete. The resting tone increase of 54% in lower oesophageal variance. More emphasis should be placed of the HPZ in both groups ranged between sphincter pressure, and on pH testing a upon regular dietetic advice. Membership 14-40 mms mercury with no significant change from a mean Tuttle score of 3 of the Coeliac Society should be difference between the two. pre-operatively to 0 58 postoperatively, encouraged. This study suggests that the HPZ created adding objective support to the clinical as a result of partial fundoplication, be it impression of the efficacy of the procedure. on its own or in conjunction with a gastro- F147 plasty, responds as a normal gastro- Non-invasive evaluation of intestinal per- oesophageal sphincter does. It was not meability in food allergy, coeliac disease possible to separate a pre-existing gastro- and inflammatory bowel diseases oesophageal sphincter within the HPZ in either group. COELIAC DISEASE C ANDRE, L COLIN, 1 DESCOS, AND S DANIERE F 146-51 (INTRODUCED BY R N ALLAN) (Groupe d'Immunopathologie Digestive INSERM, F145 F146 Centre Hospitalier LYON SUD, Pierre A clinical and pathophysiological study of a Parents' understanding of coeliac disease Benite, France) Gastrointestinal http://gut.bmj.com/ simple, safe and effective operation for the (CD) and its dietary management permeability was investigated by the correction of resistant gastro-oesophageal ingestion of 65 ml water containing 5 g reflux P T JACKSON, J F T GLASGOW, AND R THOM lactulose, as a marker of abnormal absorp- (Department of Child Health, The Queen's tion of large molecules, and 5 g mannitol, A WATSON (Department of Surgical Universiti of Belfast, Institute of Clinical as a marker of absorption of small Gastroenterology, Royal Lancaster Science, Belfast, N Ireland) For the past molecules. Complete five hour urine Infirmary, Lancaster) The ideal operation 12 years CD has been diagnosed on the ccllections were made, volumes recorded for resistant gastro-oesophageal reflux basis of a flat' jejunal biopsy and a good and aliquot of each preserved for sugar on September 30, 2021 by guest. Protected copyright. should be safe, effective, and free from clinical response to strict gluten withdrawal analysis using gas chromatography. In 90 complications. Objective studies have (GFD). During this period, dietary healthy fasted subjects (aged 6 months to shown the Nissen fundoplication to be adherance having been questioned, eight 70 years), mean mannitol excretion was perhaps the most effective operation of the 50 cases in this study had had an 14 11% (SD±3'56; normal lower limit currently available, but it involves distor- additional compliance biopsy (CB). In the >71%) and mean lactulose excretion was tion of the normal anatomy and conse- present study a standard questionnaire was 0(26% (SD+±016; normal upper limit quential mechanical complications are given to parents of 50 (the mother in 48) <0 60c%) The mean lactulose/mannitol frequently described. For these reasons, children with CD, current age 1.5-19.0 ratio was 0)020 with normal upper limit the use of the Angelchik sialastic prosthesis years, and responses scored to give quanti- 0(085. has been investigated, having been the tative data about understanding of CD, Twenty three patients with proved food subject of recent communications to this knowledge of and attitude to the GFD and allergy as diagnosed by history and society, but has been found also to be likely compliance. Twenty seven knew that laboratory tests (prick tests, specific IgE, associated with mechanical complications the GI tract is primarily involved, 30 that number of IgE intestinal plasma cells, and a high re-operation rate. CD is lifelong, 41 that gluten is to be provocation test), showed a slightly lower A more anatomical and physiologically avoided and >70% knew which of 14 recovery of mannitol (mean 11 62%; based procedure is described which is common foods contain gluten. Although SD±+377) and a slightly higher recovery of simply performed and corrects and accen- 113 considered it an 'easy' diet to maintain, lactulose (mean 0)39%; SD+±029) tuates those factors which have been shown in 40% adherance was less strict. Eight of resulting in an insignificant rise of the to influence lower oesophageal sphincter 33 parents with a knowledge score (KS) of lactulose/mannitol ratio (mean 0(0)40; competence. This procedure has been <4 had a child who previously had SD±0(030)). performed over the past nine years in 188 required CB, compared with 0/17 with a In seven allergic patients, intestinal Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1190 The British Society of Gastroenterology permeability was also studied immediately ((-733 2); coeliac patients on gluten free who had shown good response to a gluten after the ingestion of an offending food diet, casein IgG 2 8 (0-8(9), IgM 8 2 free diet. There was a significant dimin- allergen. This provocation test resulted in a (1 4-12-0), IgA 0 9 (0-3.6); gliadin IgG 6 6 ution in the immune response to soya 25% decrease of mannitol recovery, in a (13-23-3), IgM 20 2 (10-87 9), IgA 2 7 protein also. 75c/c increase of lactulose recovery, and in (06-6.0). Thus, a significant proportion of patients a 100%/)c rise in the lactulose/mannitol ratio. Untreated coeliac jejunal mucosa with coeliac disease who respond poorly to Oral cromoglycate (300 mg before provo- secreted more IgG (p<0.05), IgM a gluten free diet have concomitant cation test) proved in all to be completely (p<0'0l) and IgA (p<005) antigliadin immunological hypersensitivity to soya protective both as regards symptoms and antibodies than controls. Untreated coeliac protein causing their poor response to a permeability abnormalities. Eight patients mucosa secreted more IgG, IgM and IgA gluten free diet alone. with coeliac disease presented marked anticasein antibodies than controls but the changes: mean mannitol recovery 183°% results did not reach significance. Values and mean lactulose recovery 1 41%. Their for treated coeliac IgG and IgM antigliadin F15( lactulose/mannitol urine excretion ratio antibody secretion fell between controls Transient gluten intolerance (mean 0(610) fell to 0(110 after a three and untreated coeliac patients and were month gluten free diet resulting in partial not significantly different from either J A WALKER-SMITH, A D PHILLIPS, M ROSSITER, recovery. In patients with ulcerative colitis, group. Treated coeliac IgA antigliadin AND B A WHARTON (Queen Elizabeth disease activity was associated with an antibodies were similar to normals and Hospital for Children, London) By increased lactulose permeability and a significantly lower than untreated coeliac definition, coeliac disease is a state of normal mannitol absorption. In patients patients (p<0'05). Treated coeliac permanent intolerance to gluten. There is with Crohn's ileocolitis, activity was anticasein antibody concentrations were evidence that a state of transient gluten associated with reduced absorption of similar to normals. intolerance exists in infancy, presenting mannitol and increased permeability to We conclude that raised gliadin before the age of two years. In practice this lactulose. antibody secretion by jejunal mucosa may diagnosis is usually retrospective and Measurement of intestinal permeability be involved in the pathogenesis of coeliac presumptive - that is, a child previously is of great value for the investigation of disease. diagnosed as coeliac disease fails to relapse food allergy, for the management of clinically and histologically after two years coeliac disease and for the assessment of or more back on a gluten containing diet; activity in inflammatory bowel diseases. F149 McNeish et al have commented upon the Soya protein hypersensitivity in non- lack of evidence to endorse this two year responsive coeliac disease rule. The purpose of this paper is to F148 describe a group of 11 children diagnosed Gliadin antibody secretion by coeliac N MIKE AND P ASQUITH (Alastair Frazer and retrospectively as transient gluten http://gut.bmj.com/ jejunal mucosa John Squire Metabolic and Clinical Investi- intolerance, based upon the following gation Unit, East Birmingham Hospital, features: ( I ) initial illness associated with a P J CICLITIRA, H J ELLIS, G M WOOD, P D Birmingham) Ten to 15% of patients with small intestinal enteropathy. (2) Complete HOWDLE, AND M S LOSOWSKY (Gastrointes- adult coeliac disease show a suboptimal clinical remission on a gluten free diet. (3) tinal Unit, The Rayne Institute, St Thomas' response to a gluten free diet. We have Healing of the enteropathy on a gluten free Hospital and Department of Medicine, St previously shown evidence of humoral and diet. (4) Normal small intestinal mucosa James' Hospital, Leeds) Untreated cellular immunity to soya protein in these two years after return to a gluten coeliac patients have raised circulating patients. Twelve patients out of 84 with containing diet. These children have now on September 30, 2021 by guest. Protected copyright. antibody titres to wheat gliadin and other adult coeliac disease were identified who been followed for a period from eight to 10 food antigens. showed a poor response to gluten years. Four have had further biopsies; one Our aim is to investigate the secretion of withdrawal. These patients remained was abnormal. This was seven years after antibodies to gliadin and casein by coeliac highly symptomatic and had persisting return to gluten but this child clearly has jejunal mucosa. haematological and biochemical abnor- coeliac disease. This finding casts doubt Jejunal biopsies from normal controls malities and malabsorption after two years upon the validity of the 'two year rule' for (10), coeliac patients on a normal diet (10), or more on a strict gluten free diet. excluding coeliac disease postgluten and a gluten free diet (nine) were Morphometric analysis of their jejunal challenge. The remaining 10 children who maintained for 24 hours in organ culture. biopsies; while showing some improve- all presented before 1974, have remained The tissue culture media were assayed for ment; showed significantly less improve- clinically well. This experience highlights IgG, IgM, and IgA antibodies to gliadin ment than that seen in good responder the need to reassess the diagnosis of coeliac and casein by ELISA. coeliacs. disease made in early infancy, Nevertheless Mean values and range of antibody Ten of these 12 patients were placed on a the question must remain as to whether any secretion in ng per mg of tissue were: gluten and soya free diet. Reassessment of these children will eventually relapse at normal controls, casein IgG 2'6 (0-10(4), after six monthes showed clinical improve- a later date? There is clearly a variable IgM 1 8 (0-4.7), IgA 0 (0); gliadin IgG 3 4 ment, a return to normal of haematological response to gluten in some individuals. It is ((0-92), IgM 6 2 (2-9-20 5), IgA 4.6 ((}- and biochemical parameters, normal intes- known that most children with coeliac 29Q7); coeliac patients on normal diet, tinal absorption and statistically significant disease will relapse three months post- casein IgG 4 4 ((0-95), IgM 4.6 (0(7-12.2), morphometric improvement in jejunal gluten challenge. A few will take much IgA 1 1 (0-5.2); gliadin IgG 215'5 (5 5- histology in nine. Jejunal morphology was longer. Some appear to have had a state of 2000), IgM 84'6 (4 7-360), IgA 155 9 now indistinguishable from those coeliacs temporary intolerance. Only long term Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from The British Society of Gastroenterology A1191 follow up with careful monitoring will F152 formation on a potential GI tract determine the dietary requirements of the Recurrence after sphincter saving resection carcinogen individual patient who fails to relapse for low and mid rectal cancer histologically after three months of gluten J WARE AND B BEIJE (INTRODUCED BY R B challenge. P DURDEY, D JOHNSTON, AND N S WILLIAMS MCCONNELL) University Department of (University Department of Surgery, The Surgery, Liverpool, and Wallenberg General Infirmary, Leeds) The intro- Laboratory, Stockholm University, F151 duction of new techniques has enabled Sweden) Dietary selenium has been Asthma, eczema, seasonal rhinitis and skin more patients with low rectal carcinoma to shown to have an inverse relationship with atopy in adult coeliac disease undergo sphincter saving resection (SSR). the incidence of colon cancer. Moreover, This policy, however, has provoked experimental colon carcinogenesis can be A WILLIAMS, P ASQUITH, AND D STABLEFORTH controversy concerning the adequacy of inhibited with dietary excess of selenium. (The Alastair Frazer and John Squire excision and fear of increased rates of The mutagenic effects of - I dimethyl- Metabolic and Clinical Investigation Unit, recurrence compared with abdominal hydrazine (UDMH), a known experi- and the Department of Thoracic Medicine, perineal excision (APER). We have there- mental colon carcinogen, were studied in a East Birmingham Hospital, Birmingham) fore examined our results of SSR for low liver perfusion/cell culture system. Male Asthma, eczema and seasonal rhinitis are and mid rectal cancers from 1978 to mid Wistar rats, fed a selenium deficient diet reported to be more common in children 1982. supplemented with Se+) or without with coeliac disease but there are few One hundred and fifty nine patients selenium (Se-) in the drinking water were studies in adults. We have studied 76 presented with tumours less than 12 cm used as liver donors. The perfusate was patients (52 women) with treated adult from the anal verge; 153 (96%) underwent dosed to 5 mM UDMH and Chinese coeliac disease (ACD), mean age 41 years resection, of whom 46 (30%) had dissemi- hamster V79 cells were used as the genetic (range 16-75), by a detailed questionnaire nated disease. One hundred (68%) targets for both the perfusate and bile. enquiring into personal and family history underwent SSR, 47% of whom had a Whereas UDMH per se caused no of atopic disorders. Skin hypersensitivity stapled anastomosis, 33 (22%) had an mutagenic effect compared with controls, was determined to 21 common allergens, APER and 16 (10%) had a local the presence of livers from SE+ and Se- including 16 foods. Total serum IgE and procedure. Operative mortality was 4% rats increased the observed mutagenicity RAST specific IgE were measured. Results after APER and 7% after SSR. Of 74 by 135% and 236% respectively (p<0.005 have been compared with 81 age and sex patients undergoing radical SSR, 38 (52%) for both results). Bile alone and from Se+ matched controls with non-inflammatory had tumours below 9 cm. rat livers showed no mutagenicity, while a gastrointestinal disorders. Patients were followed for a mean of 4-6 highly significant increase was observed in A history of asthma was found in 15 years (range 2-6 years), only four (2.5%) the bile of Se- rat livers (<600%, (20%) ACD patients compared with four being lost to follow up. All gurviving p<0-0005). It is known that standard com- http://gut.bmj.com/ (5%) controls (p<0-01). Eczema and patients were examined for recurrence mercial pellet rodent diets vary consider- seasonal rhinitis were no more common in within the past six months. The incidence ably in selenium content, which can explain ACD patients themselves or their first of recurrence after radical SSR was variable results in studies of colon carcino- degree relatives compared with controls. compared with a historical control group genesis. More important, however, are the Positive prick skin tests to food and who underwent radical APER, matched implications of these in vivo findings with environmental allergens were more for age, sex, Dukes' stage and height of the both a suggested relationship between common in ACD patients compared with lesion (range 3-12 cm). The extent of higher faecal bile salt concentrations in controls (45% compared with 27%. histologically proven extra-rectal spread colon cancer patients and the incidence of on September 30, 2021 by guest. Protected copyright. p<0-05). Two thirds of ACD patients with was similar in both groups. After an colon cancer being related to areas of low asthma had positive skin tests. Positive skin equivalent follow up period, overall local sedlenium intake. tests to foods were invariably associated recurrence rates were 13-6% after SSR and with skin hypersensitivity to other environ- 18-8% after APER. For patients with mental allergens and rarely occurred in tumours below 9 cm the corresponding F154 isolation (4%of cases). Raised total IgE rates were 11-1% and 20-5%. After SSR Is a circulating factor responsible for the concentrations were found in similar only one recurrence was detected at the promotion of intestinal carcinogenesis after numbers of ACD patients and controls anastomotic line. Overall distant jejunal resection in the rat? (22%° 18% respectively) and rises of recurrence rates were 14-5% and 20% RAST specific IgE occurred only in those respectively. Ten patients (13.5%) died of A P SAVAGE, J L MATrHEWS, T COOKE, AND S R patients with positive skin tests. their disease within two years of radical BLOOM (Department of Surgery, Charing An increased prevalence of asthma and SSR, 15 (15%) after radical APER. Cross Hospital and Department of positive skin tests has not previously been Thus, SSR does not appear to carry an Medicine, Royal Postgraduate Medical reported in ACD. increased risk of recurrent disease School, London) Small bowel resection compared with APER after an equivalent promotes experimentally induced colonic follow up period. carcinogenesis in the rat possibly by inducing a trophic response in the colon. The relationship of these effects to circulat- COLORECTAL ing concentrations of trophic hormonal F152-57 F153 factors has not been assessed. Effect of selenium and hepatic biotrans- Eighty male Wistar rats were randomly Gut: first published as 10.1136/gut.25.10.A1129 on 1 October 1984. Downloaded from A1192 The British Society of Gastroenterology allocated to four groups undergoing either further information we studied the and Dept of Surgery, Lausanne, Switzer- jejunal transection or 20%, 50%, or 80% excretion and the degradation of neutral land) Nineteen patients with colorectal small bowel resection. One week after sterols in the following groups of subjects carcinoma were each injected with 1-5 mg operation each rat received the first of 12 at risk: (A) 14 members (three affected and of F(ab')2 (n = 13) or Fab fragments (n =6) weekly subcutaneous injections of azoxy- 11 first degree relatives) of four families of monoclonal anti-CEA antibody (No 35) methane 10 mg/kg. Plasma enteroglucagon with familial colonic polyposis; (B) nine labelled with '21 (3-4 mCi). Tomoscinti- was measured at two and 16 weeks and on subjects with solitary polyps of the colon; graphy was performed 6, 24 and 48 h death at 26 weeeks. The number and site of (C) 15 members (six affected and nine first postinjection with a dual head rotating tumours were recorded. degree relatives) of two families with a high camera. With F(ab')2 the following results There was a significant rise in colonic prevalence of multiple polyps. The results were obtained. All seven primary or tumours from 0-44±0-21/rat in the were compared with those of 38 controls. recurrent tumours were visualised. Two transection group to 1.24±0 24 (p<0*02) in The investigated subjects were kept on a small lung metastases in a patient under the 50% resection group but falling to standard solid diet containing a constant chemotherapy could not be demonstrated. 0-86±0 31 in the 80% resection group. amount of cholesterol per day. Cr2O3 (300 Of the eight patients with liver involvement There was a six-fold increase in duodenal mg/day) was also given as a marker of four showed clearly positive, two equivocal tumours from 0 89±0-02 in the control faecal flow. All faecal samples were and two negative ECT images. Image group to 6-0±1-27 (p The British Society of Gastroenterology Al 193 cells contain normal amounts of DNA underwent curative surgery (four Dukes' than those with diploid cancers (20) of (diploid) and those with abnormal DNA Stage A, 34 Stage B, three Stage C), 13 34 4±18 9 months. (U=101 5, p=0()01). (aneuploid). (72c/% ) of 18 with diploid cancers compared For each Dukes stage and histological The DNA content of 84 primary with only 9 (41°%) of 22 with aneuploid grade there was a survival advantage to colorectal cancers was measured from cancers surviving five years (X-=4 1- those patients with diploid cancers. patients with at least five years follow up. p=0.04). Nuclear DNA content is an important The mean overall survival time of patients Forty four patients underwent non- prognostic factor in colorectal cancer with aneuploid tumours (46) at 27±20 2 curative surgery (12 Stage B, 23 Stage C, giving a clear survival advantage to those months was significantly worse than those nine Stage D). The mean survival time of patients with diploid cancers which appears with diploid cancers (38) at 43 1±19 5 patients with aneuploid tumours (24) of independent of stage and histological months (U=490, p<0)01l). Forty patients 17-5±12-5 months was significantly shorter grade. http://gut.bmj.com/ on September 30, 2021 by guest. Protected copyright.