Antacids can reduce gastroduodenal acidity for long periods if taken in substantial quantities after food. Their healing effect on gastric ulcer is minimal, if present at all, and easily overwhelmed by the benefit obtained from admission to hospital. Intensive antacid therapy appears effective in healing duodenal ulcer and preventing haemorrhage from stress ulcer, and is comparable in these respects with cimetidine but with a higher incidence of side-effects. Clinical impression strongly suggests that antacids relieve pain in peptic ulcer but objective confirmation is lacking.

We have undertaken a double-blind controlled trial of the use of transfer factor in Crohn's disease. Thirty-three patients with known Crohn's disease completed the trial in which half the patients had three injections of transfer factor and the other half were given saline. After six months there was no significant difference in the clinical condition of either of the two groups compared with before receiving treatment. There was also no difference in their in vitro lymphocyte function, although a number of patients exhibited altered responsiveness to skin testing with tuberculin or streptokinase/streptodornase. A signficant fall on Crohn's disease activity index score occurred over the initial 'acclimatising period' before the trial was started, probably related to overcoming initial introspection and the placebo effect of being part of a trial.

In a randomised double-blind trial over one year oral BCG has been compared with a control preparation in the treatment of chronic Crohn's disease. Overall assessment scores deteriorated in nine of 22 patients taking BCG, and 11 of 26 in the control group (P = 0.25); this deterioration was great enough to be regarded as a clinical relapse in three patients taking BCG and in seven taking the control preparation (P greater than 0.1). No significant benefit from oral BCG treatment has been demonstrated.

Patients suffering from chronic duodenal ulceration were allocated at random to treatment with either cimetidine (400 mg twice daily) or matching placebo for six months. Before entry to the trial all patients were shown to have healed ulcers on endoscopy. Most of the patients had participated in a one-month trial of cimetidine during which their ulcers healed. The trial showed that four of 29 patients relapsed on maintenance treatment with cimetidine, which therefore did not confer complete immunity from relapse. However, cimetidine treatment was very much better than placebo treatment, on which 18 of 31 patients relapsed. Of the 22 patients who relapsed clinically, 20 were submitted to endoscopy and 19 of these were shown to have ulcerated again. Endoscopy at the end of the trial showed that ulcers had also redeveloped in five of 28 asymptomatic patients. Length of previous dyspeptic history had no bearing on the results of the trial but there was evidence that relapse on placebo was less likely if the ulcer had originally healed on a high dose of cimetidine. Clinical relapse was associated with worsening duodenitis. Symptoms, clinical observation, and laboratory tests showed no important abnormalities in the patients.

Endoscopy, clinical assessment, and laboratory studies were used to compare, in a double-blind multicentre trial, the effects on patients with duodenal ulceration of treatment for four weeks by either placebo or 1 g/day cimetidine, or 2 g/day cimetidine. Ulcer healing occurred in 28% of patients on placebo, 61% of patients on 1 g cimetidine daily, and 70% of patients on 2 g cimetidine daily. Thus cimetidine conferred an advantage over placebo, but the effects of the two doses of cimetidine were not shown to be different. Symptomatic improvement in patients given cimetidine was usually marked and occurred early. Patients were required to report all symptoms, but the only symptom which might have been caused by cimetidine was headache in 5% of patients. Biochemical studies showed significant (though slight) rises in serum uric acid, and serum creatinine but no significant changes occurred in the serum levels of liver enzymes. This study confirms that 1 g is a suitable daily dose of cimetidine for the treatment of duodenal ulceration.

The effect of diazepam on the lower oesophageal sphincter (LOS) pressure is controversial. Therefore, a double-blind crossover study was performed on 18 healthy volunteers to determine the sphincter response to intravenous diazepam--70, 140, 280 microgram/kg, which correspond to a total dose of 5, 10, and 20 mg. respectively. After the 5 and 10 mg dose no signficant effect on LOS pressure could be observed when compared with placebo. After the 20 mg dose a significant rise in pressures (deltaPLOS) was recorded for 40 minutes with a maximum deltaPLOS of + 16.2 +/- 6.6 (mean +/- SEM) mmHg after 50 minutes (P less than 0.01) (46 +/- 1.3% increase above the basal pressure). It is concluded that diazepam does not affect lower oesophageal sphincter competence and therefore does not increase the risk of regurgitation and pulmonary aspiration in premedicated patients.

Oral disodium cromoglycate (200 mg qds) has been tested in 26 patients with ulcerative colitis that was resistant to medical treatment. In a double-blind crossover trial disodium cromoglycate and placebo were added to conventional treatment in random order, each for four weeks. There was no significant difference in therapeutic effect between disodium cromoglycate and placebo.

Patients with ulcerative colitis in remission were randomly allocated to treatment with sulphasalazine (2 g/day) or oral sodium cromoglycate (160 mg/day or 2 g/day), and the relapse rates in these treatment groups were compared during continued treatment for one year. The percentage cumulative relapse rate after 12 months' treatment was 30% in the 33 patients treated with sulphasalazine compared with 71% in the 25 treated with high dose sodium cromoglycate, a highly significant difference (P less than 0.01). Patients allocated low dose sodium cromoglycate were only treated for a maximum of six months, and the relapse rate in these 12 patients was similar to that in patients on the high dose. These results suggest that oral sodium cromoglycate is considerably less effective than sulphasalazine in maintaining remission, and by analogy with results in other trials may be no more effective than placebo tablets.

Ninety-six patients with gastric ulcer were randomly allocated to treatment either with deglycyrrhizinised liquorice or placebo. After four weeks no differences were found between the treatment groups in the proportions with complete healing, whether assessed by gastroscopy or radiology, or in the percentage reduction in ulcer area, or in clinical improvement.

The long-term effect of prednisone in Crohn's disease has been examined in a double-blind controlled trial. Clinical relapse, recurrence, and extension of the disease were examined in 64 patients followed-up for up to three years. Fourteen patients were withdrawn because of severe symptoms (eight on prednisone and six controls); the withdrawal rate in both groups was 30% at three years. Nine other patients had radiological recurrence or extension of disease (five prednisone and four controls). Prednisone did not improve the relapse rate, nor did it affect recurrence or extension of disease.

Two modifications of the standard method of treatment of ascites in chronic liver disease were investigated in three separate randomised trials involving a total of 201 patients. These modifications were (1) an unrestricted sodium intake and (2) limitation of diuresis to partial removal of ascites, to the point of relief of abdominal tension. Mean serum sodium fell significantly in all patient groups receiving the low sodium diet and did not fall in the groups given an unrestricted diet. Mean serum urea nitrogen rose significantly in the patient groups undergoing complete diuresis and did not change in the groups undergoing partial diuresis. Mean serum uric acid rose only in the groups undergoing complete diuresis. We concluded that the advantages of these two modifications of therapy of ascites were increased dietary palatability and decreased likelihood of hyponatraemia and of rise in serum urea nitrogen and uric acid. Disadvantages included dissatisfaction of patients over incomplete clearing of ascites, occasional difficulty in performing diagnostic studies because of prolonged ascites, and unsuitability of a high sodium intake in patients whose ascites is highly refractory to treatment.

A sample of 16 patients had pentagastrin stimulation studies performed before starting a 12 week course of cimetidine, and again 12 hours after completing the course. Basal and pentagastrin stimulated intrinsic factor secretion was assayed in 13 patients. There was no significant difference in the pattern of secretion after 12 weeks' treatment with cimetidine. The basal and peak acid outputs of all 16 patients were measured. No significant difference was found in the pattern of acid secretion after treatment. It appears that parietal cell secretory function is restored to normal within 12 hours of discontinuing a prolonged course of cimetidine.

In order to establish whether alcohol in amounts in amounts customarily imbibed during social drinking causes gastro-oesophageal reflux, 12 healthy young individuals, without symptoms of gastro-oesophageal reflux, were studied twice. Each time, distal oesophageal pH was monitored continuously for three hours after a standard meal which included either 180 ml 100 proof vodka or 180 ml water. The order of studies with and without alcohol was random. Peak blood alcohol concentrations ranged between 0.63 and 1.29 g/l. Eleven of the 12 subjects refluxed more after alcohol; and the difference in mean reflux scores for studies with and without alcohol was highly significant. We conclude that relatively modest quanttities of alcohol induce gastro-oesophageal reflux in healthy people.

Serum gastrin concentrations were measured in patients with duodenal ulcer and controls before, during, and after one-hour intravenous infusion of various doses of adrenaline (0.12 microgram to 6 microgram/min). Gastrin concentrations in the basal state were significantly increased in duodenal ulcer patients compared to controls. The maximal rise in serum gastrin concentrations was obtained at a dose of 4 microgram/min adrenaline in both groups of subjects, and the increase was significantly higher in duodenal ulcer patients than in controls. Adrenaline increased predominantly the gastrin III component (gastrin-17 like) in both duodenal ulcer patients and controls. The threshold level of adrenaline-induced gastrin release was significantly lower in duodenal ulcer patients: intravenous infusion of adrenaline in a dose of 0.12 microgram and 0.25 microgram/min increased serum gastrin concentrations 23 and 43%, respectively, but had no effect in controls. Rises in plasma adrenaline concentrations were similar in both groups of subjects in response to the various doses of adrenaline employed. Only the smallest dose of adrenaline (0.12 microgram/min) resulted in clearly physiological variations in plasma adrenaline concentrations. The results indicate that endogenous adrenaline may stimulate the secretion of gastrin during physiological conditions in patients with duodenal ulcer.

The results of a double-blind trial of glucagon in 69 patients with acute pancreatitis are reported. In a subgroup of 59 patients statistical analysis showed no significant differences between the glucagon-treated (n = 29; 2 X 5 mg protamine-zinc glucagon intramuscularly per day) and the placebo-treated (n = 30) subjects for the following data: duration of pain left spontaneously and induced by palpation, amounts of analgesics and antispasmodics required by the patients, duration of hospital stay, amylase activities in serum and 24 hour urine collections. Mortality rates did not differ significantly between the glucagon-treated and the placebo-treated subjects in the total group of 69 patients and in the two subgroups of patients who were treated conservatively (n = 59) and those who underwent laparotomy because of severe peritonitis (n = 10). From the results of this study it is concluded that favourable effects of glucagon upon the course of acute pancreatitis--if they do exist--are not significant.

In a double blind trial, 23 patients with endoscopically confirmed duodenal ulceration received cimetidine (300 mg four times daily in six patients, or 400 mg four times daily in 10 patients) or placebo (seven patients) for six weeks. Before entry into the trial, pentagastrin (6 microgram.kg-1.h-1)--stimulated gastric acid secretion after a single oral dose of 300 or 400 mg cimetidine was lowered by 82.1% and 81.0%, respectively, while no significant inhibition was recorded in the patients receiving placebo (8.8%). The same test repeated after six weeks of continuous treatment showed that the effect of the drug was maintained, the percentage inhibition of acid secretion being of the same order as in the first test.

Twenty-two patients with symptomatic diverticular disease of the colon were randomly allocated to control and high-fibre groups so that the long-term effect (up to 12 months) of bran on serum, faecal and biliary lipids could be studied. Even in cases of high initial values, faecal mass was increased by bran and the change was positively correlated with the change in dietary fibre. Faecal fat and dry weight were also increased. Faecal bile acids were initially slightly raised and were positively correlated with wet weight both off and on bran. The latter significantly decreased the excretion and concentration of bile acids, in particular the high initial values. The change in bile acids was not correlated with the change in dietary fibre or faecal wet weight. Sterol balance values indicated that the bran-induced decrease in faecal bile acids was associated with a lower cholesterol synthesis. Serum cholesterol decreased significantly in two hypercholesterolaemic individuals only. Correlations between different parameters revealed that the higher the initial level or the greater the drop in cholesterol synthesis, the greater the decrease in serum cholesterol. Bran had no effect on the biliary saturation of cholesterol. The percentage of biliary deoxycholate was negatively correlated with faecal mass (less so with faecal bile acid output) both before and during bran and was significantly decreased by bran. The percentage of cholic acid increased correspondingly and that of chenodeoxycholate remained unchanged. Faecal bile acids also indicated that the synthesis of the two primary bile acids was lowered by bran to the same degree.

In a double-blind controlled trial amylopectin sulphate (Depepsen) had no significant advantage over placebo in the symptomatic treatment of duodenal ulcer.

Eighty-six patients with duodenal ulcer were treated in a multicentre controlled trial with carbenoxolone capsules (Duogastrone, 50 mg four times a day for six weeks) or a placebo. Sixty-nine patients accepted endoscopy at the beginning and end of the treatment. Symptomatic responses and endoscopic improvement were significantly greater in those receiving the active preparation than in those receiving the control capsules, complete, endoscopically assessed, healing being achieved in 65% and 20%, respectively, of individuals having accepted endoscopy, after six weeks' treatment. Side-effects of salt and water retention or hypokalaemia were noted in over a quarter of those receiving the carbenoxolone capsules, but none of the adverse effects was severe enough to necessitate withdrawal of treatment.

Twenty-two patients with chronic proctitis were treated with metronidazole for 28 days in a double-blind controlled trial, but they did not appear to benefit from the drug.