In a single blind multicentre study, the efficacy and safety of ranitidine was compared with cimetidine in patients with gastric ulcer confirmed by endoscopy. Patients were randomly allocated to receive either 150 mg ranitidine twice daily, or 200 mg cimetidine three times a day and 400 mg at night for four weeks; patients with unhealed ulcers continued the same treatment for a further two weeks. Out of 260 patients, 197 were analysed. Of the ranitidine treated patients, 66% were healed after four weeks and 78% after six weeks and of the cimetidine treated patients 62% were healed after four weeks and 87% after six weeks. These differences are not significant. These results confirmed that ranitidine is as effective as cimetidine in the acute treatment of gastric ulcer.

A multiple linear regression analysis was carried out on 75 inpatients with gastric ulcer. In order to elucidate the effects of various factors - endoscopic and roentgenological findings, age, sex, medical history, and drugs such as antacids, anticholinergics or both - on the healing rate, these factors were compared between those with ulcer which healed within eight weeks after treatment and those which did not. In patients over 50 years of age, alcohol consumption of over 60 g per day until admission, duration of present ulcer pain for over three months, single ulcer, ulcer located in the lesser curvature and uneven elevation around the ulcer, there was significant delaying effect on ulcer healing. Drug ingestion, sex, smoking habits until admission, size, depth, and shape of ulcer, coexisting gastritis, and past and family history of ulcer disease had no significant effect on healing after eight weeks. The patients with less than two unfavourable factors (n = 46) had the best healing rate (100%) compared with those with three (n = 20) or four or more (n = 9) unfavourable factors. The healing rate of the latter two groups was 60% and 22%, respectively (p less than 0.001). A prognostic score based on these six factors represents the severity of gastric ulcer disease with regard to the healing rate in patients prescribed antacids, and/or anticholinergic drugs.

Forty patients with moderate degrees of dehydration and acidosis because of acute watery diarrhoea were successfully treated randomly with either WHO recommended oral rehydration solution containing 2.5 g sodium bicarbonate or an oral solution containing 2.94 g sodium citrate in place of sodium bicarbonate per litre of oral rehydration rehydration solution. Efficacies were compared by measuring oral fluid intake, stool and vomitus output, change in body weight, hydration status, and rate of correction of acidosis during a period of 48 hours. Seventy five per cent (21 cases) in the citrate group and 83% (19 cases) in the bicarbonate group were successfully rehydrated (p greater than 0.05). There were no significant differences in intake, output, gain in body weight, fall in haematocrit and plasma specific gravity, and correction of acidosis between the two groups of patients within 48 hours after initiation of therapy. The solution with sodium citrate base was as effective as WHO-oral rehydration solution for management of diarrhoea. This study shows the efficacy, safety, and acceptability of citrate containing oral rehydration solution for rehydration and correction of acidosis in diarrhoea.

Of 212 patients with duodenal ulcer treated with four weeks of one gram daily cimetidine, 25 had ulcers which underwent no reduction in size despite treatment. The effects of tripotassium dicitrato bismuthate (TDB) tablet four times a day or cimetidine 1.6 g daily on the healing of these cimetidine resistant ulcers were compared in a randomised crossover trial. Ten of 12 patients on tripotassium dicitrato bismuthate and five of 13 patients on high dose cimetidine had complete healing (p less than 0.02). On crossing over, seven of the eight ulcers not healed by high dose cimetidine completely healed with TDB in another four weeks, and one of the two ulcers not healed by TDB healed with high dose cimetidine. Overall, TDB healed 85% of cimetidine resistant ulcers, whereas high dose cimetidine healed 40% (p less than 0.006). Tripotassium dicitrato bismuthate is recommended for cimetidine resistant duodenal ulcers.

Of 663 patients treated with radical surgery for colorectal cancer, 52 showed a progressive rise in serum carcinoembryonic antigen (CEA) with no other evidence of recurrent disease and were randomised in a prospective study of chemotherapy. Twenty six patients in the treatment group received 5FU and methyl CCNU from the time of randomisation and the remaining 26 controls were given further therapy only if there were clinical indications. All patients were followed for five years or until their death and all but one (control) developed clinical evidence of recurrence. Overall there was no significant difference between the two groups with respect to disease free interval and survival. Whereas the rise in CEA in controls was generally progressive, marked inflections on the CEA curves were seen in the majority of patients receiving early treatment. Eight of 26 treated patients showed a fall in CEA of greater than 20% two months after starting therapy. These patients had a median disease free interval of 90 weeks and a median survival of 107 weeks, these figures being longer than those of treated patients who did not show a fall in CEA and control patients. The serum CEA therefore appeared to give important prognostic information in patients receiving cytotoxic treatment. Early therapy was generally well tolerated.

The effects of ceruletide on jejunal motility and experimentally induced pain were studied in 16 healthy men, who participated each in four experiments and received in random double blind fashion 5, 10, or 20 micrograms ceruletide intramuscularly or placebo. Jejunal pressures were recorded by three perfused catheters with orifices between 10 and 20 cm aboral of the ligament of Treitz. Ceruletide dose dependently diminished phase I and increased phase II type activity and tended to reduce the number, but not the duration, of activity fronts. The number and amplitude of contractions as well as the area under the curve increased significantly and dose dependently as did threshold and tolerance to electrically and threshold to thermally induced pain. Only mild sedative and other side effects occurred.

Cyclotropium bromide, a new antimuscarinic agent, inhibits gastrointestinal motility in animals at lower doses than those required to inhibit gastric acid secretion and salivation. In man, cyclotropium bromide suppresses fasting and meal stimulated colonic motility. This study investigated the effects of single oral doses of 60 mg cyclotropium bromide, 60 mg hyoscine N-butylbromide and placebo on gastric emptying and on antral motor activity. Twenty four healthy men (mean age 25 years) participated in three experiments one week apart. The drugs were administered, in random double blind fashion, 30 minutes before the ingestion of a semisolid test meal labelled with 74 MBq (2 mCi) 99mTc sulphur colloid. A gamma camera coupled to a computer monitored gastric emptying together with amplitude, frequency, and propagation velocity of antral contractions. Cyclotropium bromide and, to a lesser degree, hyoscine N-butylbromide delayed gastric emptying and reduced contraction amplitude, but did not affect frequency and propagation velocity of antral contractions. Cyclotropium bromide was significantly more active than hyoscine N-butylbromide; the effects of hyoscine N-butylbromide differed significantly from placebo. Antral contractile activity was present all the time. After cyclotropium bromide, there was a significant correlation between antral contraction amplitude and gastric emptying. No adverse side effects occurred with any one treatment. In conclusion, cyclotropium bromide markedly inhibits gastric emptying and reduces antral contraction amplitude.

Forty five patients with acute ulcerative colitis were randomly allocated to receive (a) sulphasalazine, (b) levamisole, or (c) a combination of sulphasalazine and levamisole. Each group contained 15 patients. The ulcerative colitis activity index (UCAI), the remission and relapse rates were compared at three monthly intervals for one year. The UCAI fell in each group. Detailed analysis of all clinical and biochemical parameters used for estimation of UCAI showed that the only difference was in patients receiving combined therapy who continued to have a raised ESR and platelet count. Fewer patients, however, went into remission on levamisole therapy (46.6%) compared with the other two groups (66.6%). The cumulative relapse rate was 20% for those receiving levamisole compared with 6.6% in the other groups. Side effects were observed in 20% of patients receiving levamisole, 26% receiving sulphasalazine, and 40% in those having combined therapy. The results indicate that levamisole is unlikely to have a major role in the management of patients with ulcerative colitis.

A randomised controlled trial of thymic hormone extracts (Thymostimulin) (1 mg/kg/day for seven days; 1 mg/kg/weekly thereafter) was undertaken in 30 patients (21 women, nine men) with treated, apparently inactive 'autoimmune' chronic active hepatitis during withdrawal of maintenance corticosteroid and azathioprine therapy. Reactivation of disease occurred in 26 patients (86%) during or after treatment withdrawal and was as frequent in the Thymostimulin treated (11 of 13; 84%) and untreated (15 of 17; 88%; p greater than 0.05) groups. Reactivation of disease was accompanied by a severe defect in concanavalin A induced suppressor cell activity, the magnitude of which was similar in the Thymostimulin treated and untreated groups (mean % suppression = 16.4 and 3.2 respectively; p greater than 0.05 vs 84.4 in control subjects). Further studies assessing the optimal dose, duration of treatment, and mode of administration are required to establish a therapeutic role for thymic hormone extracts in 'autoimmune' chronic active hepatitis.

To elucidate the mechanisms by which beta receptor blockade leads to a reduction of portal pressure, 18 patients with cirrhosis and portal hypertension were given comparable doses of propranolol or metoprolol. The fall in portal pressure was more marked with propranolol together with a significant reduction in hepatic blood flow, which was not seen with metoprolol. No correlation between the reduction in cardiac output and the decrease in portal pressure or changes in hepatic blood flow could be elicited in each group, but there was a direct relationship between the decrease in hepatic blood flow and fall in portal pressure in the propranolol treated patients. The difference observed may be related to blockade of beta 2 vasodilator receptors in the splanchnic circulation which will occur only with propranolol and lead to a greater fall in splanchnic blood flow than will be produced by a reduction in cardiac output alone. Metoprolol, by maintaining effective hepatic blood flow, may be preferable to propranolol in patients with severely impaired liver function.

Antisecretory effect of single oral therapeutic doses of pirenzepine (25 mg and 50 mg) and cimetidine (200 mg and 400 mg) was studied in 12 patients with duodenal ulcer. Gastric secretion was studied in basal condition and after stimulation with pentagastrin. Basal, maximum and peak acid output, basal and maximum acidity, and basal and maximum volume were calculated after computerised correction for pyloric loss and duodenal reflux. Both drugs showed dose-related inhibition of all facets of gastric secretion. Cimetidine (200 mg) had a greater inhibitory effect on gastric basal secretion, but a similar effect on pentagastrin stimulated secretion as with pirenzepine (50 mg). Cimetidine (400 mg) showed about twice the inhibitory activity of pirenzepine (50 mg) both on basal and stimulated secretion.

The purpose of this single blind controlled multicentre trial was to compare the relative effectiveness of pirenzepine and cimetidine in healing endoscopically proven duodenal ulcers. One hundred and twenty six patients with duodenal ulcer were treated with a daily dose of 100 mg pirenzepine (50 mg each before breakfast and before the evening meal), and 128 patients were treated with 1000 mg cimetidine (200 mg with breakfast, lunch, and evening meal and 400 mg at bedtime). Endoscopy was repeated after four weeks by an endoscopist who had not been informed about the treatment. Pirenzepine showed a healing rate of 64.3%, cimetidine one of 73.4%. This difference is not statistically significant (one-sided test: chi 1(2) = 2.48). After four weeks a higher proportion of first ulcers than of recurrent lesions was healed. Pain relief was rapidly achieved with both drugs. A significant trend in favour of cimetidine may, however, not be clinically relevant considering the small difference in the absolute numbers of pain free days and nights. Adverse effects were rare and reversible. We conclude that the efficacy of pirenzepine is similar to that of cimetidine in healing duodenal ulcers.

We pursued the possibility that Mycobacterium kansasii might be an aetiological agent in Crohn's disease by carrying out a trial of treatment with antimycobacterial drugs. Twenty seven patients with Crohn's disease took part in a two year randomised double blind, crossover, controlled trial of rifampicin plus ethambutol against placebo. Fourteen patients completed the trial; four required an operation; five were withdrawn as poor compliers, and four because of adverse effects. There was no significant difference in response to the active drugs compared with placebo when expressed in terms of a Crohn's disease activity index or any clinical indicator of disease activity. There was no suggestion that any subgroup of patients - for example, different regions of bowel affected or previous operation - were favourably affected by the drugs. There was no consistent pattern of change in prednisolone requirements although eight patients on long term sulphasalazine had a significant reduction in their plasma sulphapyridine concentrations during the active treatment period. A significant reduction in total white blood count and an increase in plasma ALT were seen during active therapy. The results of the study do not suggest that rifampicin and ethambutol have a role to play in the treatment of Crohn's disease.

A prospective randomised study to compare the efficacy and complications of injection sclerotherapy carried out at intervals of one week and three weeks up to the time obliteration of varices was achieved, was undertaken in 55 patients (48 cirrhosis, six portal vein thrombosis, one nodular regenerative hyperplasia). The number of courses of injection required for obliteration of the varices was not different in the two groups and despite a shorter time scale for obliteration in the weekly treated patients the frequency with which further episodes of bleeding occurred before that was not significantly less. Mucosal ulceration during the period required for obliteration was observed at endoscopy more frequently in the weekly treated patients but was not associated with a greater frequency of postinjection pain, dysphagia or of long term stricture formation.

The effect of open treatment with coarse wheat bran was compared with response to placebo, given in the form of a double blind, cross over drug trial, in patients with irritable bowel syndrome. Both bran and placebo significantly reduced the severity of most of the symptoms. Constipation was the only symptom that improved significantly with bran, but not with placebo, and was the only symptom that predicted a successful outcome with bran. Diarrhoea did not improve with bran. In fact, stools became less formed in patients presenting with this symptom. The incidence of pain and urgency was significantly more frequent on bran compared with placebo. Compared with a baseline period, bran treatment resulted in an acceleration of whole gut transit time (p less than 0.05) increases in daily stool weight (p less than 0.01) and the proportion of unformed stools (p less than 0.01) but no change in stool frequency. Coarse wheat bran was no better than placebo for most symptoms in irritable bowel syndrome, although its efficacy in constipation was confirmed.

This study examines which methods are most appropriate for preparation of the large bowel for double contrast barium enema. Two proprietary laxatives, X-Prep and Picolax, mechanical colonic lavage, and dietary restriction were evaluated in a randomised study of 160 patients. Four alternative preparations were compared with or without dietary restriction. The four preparations were X-Prep alone, X-Prep plus lavage, Picolax alone, and Picolax plus lavage. Scoring of the radiographs was carried out on a double blind basis. Picolax proved superior to X-Prep overall (p less than 0.01) but this was almost entirely because of its greater effect in the right colon and transverse colon. Cleansing in the left colon and rectosigmoid was similar with both laxatives. Restriction of solid food improved bowel cleansing and gave better results than mechanical lavage. The addition of a colonic lavage in starved patients did not significantly improve the quality of bowel preparation with either laxative.

The effects of different types of adrenoreceptor blocking agents on portal venous pressure were studied in patients with cirrhosis and portal hypertension. Oral atenolol (selective beta 1 blocker), propranolol (non-selective beta 1 and beta 2 blocker), and prazosin (alpha blocker) were compared in three groups of eight patients. Haemodynamic measurements were made before and after two or three and eight weeks of therapy. The dose of beta blockers was sufficient to reduce the exercise heart rate by more than 25%. Propranolol and prazosin produced a sustained reduction in the mean portohepatic venous pressure gradient of the order of 25% and 18% respectively. The cardiac index was significantly reduced by propranolol but not altered by prazosin. Atenolol produced an early reduction in portohepatic venous pressure which, although not sustained, showed a good correlation with reduction in cardiac index. No such relationship was found with propranolol. All three drugs were well tolerated by these patients with advanced cirrhosis. Therefore propranolol and prazosin have proved to be effective agents for the reduction of portal venous pressure.

Forty patients with duodenal ulcer were randomly allocated to treatment with either tripotassium dicitrato bismuthate tablets or cimetidine for six weeks. Endoscopically confirmed healing of the ulcer occurred in 80% treated with tripotassium dicitrato bismuthate tablets and in 85% treated with cimetidine. Symptomatic improvement was also similar in the two groups. Treatment with cimetidine was associated with an increase in pH of gastric aspirate during treatment and increased numbers of bacteria were isolated from the gastric aspirate during treatment, while the pH and bacterial flora of gastric aspirate did not change during tripotassium dicitrato bismuthate treatment. Serum and urinary bismuth levels rose during treatment with tripotassium dicitrato bismuthate and urinary excretion remained raised two weeks after cessation of treatment. Tripotassium dicitrato bismuthate tablets appear to be as effective as cimetidine in the treatment of duodenal ulcer without the potentially undesirable effects of a reduction in gastric acid secretion.

Twenty-eight patients with radiolucent biliary duct stones without cholangitis and jaundice were randomly allocated into two treatment groups receiving ursodeoxycholic acid 12 mg/kg (group A) or placebo (group B) in three daily doses for 24 months. In group A stones disappeared completely in seven patients and partially in one; placebo administration had no effect on stone size and three patients of group B (only one of group A) went to surgery for complications. Ursodeoxycholic acid treatment did not adversely affect liver function tests, and alkaline phosphatase decreased. Abdominal and biliary colics also became less frequent in the first six months of therapy in group A, but not in the placebo group. The bile was supersaturated with cholesterol in both groups, but decreased significantly only in patients receiving ursodeoxycholic acid even though the lithogenic index remained high. Cholesterol saturation of bile does not seem to be the only factor determining the dissolution of biliary duct stones which sometimes contain cholesterol as the main component.

To study the effects of stressful stimulus (cold pain) upon postprandial gastric, duodenal, and pancreatic function, nine healthy adult volunteers were intubated and then given two identical liquid meals, (199 cal (789 KJ) 240 ml), each being ingested during a period of irregular fasting gastroduodenal motility. Ten minutes after each meal the subjects received, in randomised order, either a test or control stimulus. The test stimulus consisted of repeated one minute immersions of a hand into ice water, with 15 seconds recovery between immersions, for a total of 20 minutes, while for the control, water at 37 degrees C was used. Serial samples of gastric and duodenal contents allowed estimation of changes in gastric emptying and acid secretion, together with pancreatic trypsin output, by a double marker perfusion technique. Measurements of blood pressure, pulse, and finger temperature acted as extra-intestinal indices of autonomic response to the stimuli. Cold pain significantly delayed gastric emptying and produced a biphasic alteration in both gastric secretion and pancreatic trypsin output, with an initial reduction during the response to the stress followed by an increase during the post-stress period. Our findings show that the normal postprandial function of the upper gut can be measurably disturbed by a stressful stimulus. The coincidence of these disturbances with other extra-intestinal autonomic changes suggests that they are a further manifestation of the somatic response to a stress.