To compare the efficacy of two oesophageal tamponade tubes, 28 patients with endoscopically proven actively bleeding varices were randomly allocated to be intubated with either a newly available 4-lumen tube incorporating an extra lumen for oesophageal suction, or the modified 3-lumen Sengstaken tube. The patients and the nursing staff preferred using the 4-lumen tube and both aspiration pneumonias and balloon dysfunction occurred less frequently. Variceal haemorrhage was successfully controlled for the first 12 hours in most patients in the two treatment groups, although the incidence of re-bleeding at 48 hours after the tube had been deflated was high.

In a study of 28 outpatients with endoscopically proven duodenal ulcers, 14 patients (with a total of 15 ulcers) were treated with bismuth tablets (colloidal bismuth subcitrate, De-Nol, Gist-Brocades NV) and 14 patients (14 ulcers) were treated with cimetidine (Smith, Kline, and French). Clinical and endoscopic assessments were made after four and six weeks' therapy. After four weeks, 10 of the bismuth treated ulcers (67%) and eight of the cimetidine treated ulcers (57%) were completely healed. After six weeks of therapy, complete healing was seen in 86% of both the bismuth treated and the cimetidine treated ulcers. Twenty of the 24 completely healed ulcer patients (10 of each group) cooperated in a three month follow-up study. Pain recurred in three patients of the bismuth group and four of the cimetidine group and they were examined endoscopically. A recurrent ulcer was found in one of the bismuth treated patients and in three of the cimetidine treated patients. These observations indicate that colloidal bismuth subcitrate was at least as effective as cimetidine in the healing of duodenal ulcer.

In a double-blind, randomised trial, neither aprotinin nor glucagon given in relatively high doses for five days influenced the rate of recovery or incidence of complications in 257 patients with acute pancreatitis.

Sulphasalazine is widely used in the maintenance treatment of ulcerative colitis but the optimum dose is not known. In the present study, 170 patients were allotted at random to three treatment groups, in which the daily dose was 1, 2 and 4 g respectively, and the trial period of treatment lasted for six months. A daily dose of 2 g was found to be much more efficacious than 1 g. A daily dose of 4 g was more efficacious than 2 g but at the price of fairly frequent symptomatic side-effects. Haematological abnormalities were observed at all dosage levels, but they occurred chiefly among the patients on 4 g daily. Both symptomatic and the haematological side-effects were usually associated with high concentrations of serum sulphapyridine and these high levels occurred chiefly among the slow acetylators. It is concluded that, for general use, a daily dose of 2 g sulphasalazine is satisfactory for the maintenance treatment of ulcerative colitis. If a patient does not do well on 2 g daily, it is worth trying a larger dose but in this case the patient's condition should be monitored by blood film, haemoglobin, MCV, and reticulocyte count.

Fourteen patients with liver cirrhosis received oral prednisone or prednisolone (0.3 mg per kg) randomised on two consecutive days. Serum prednisone and prednisolone were measured over the following four hours. Mean serum prednisolone concentration after oral prednisone decreased with impaired liver function estimated by galactose elimination capacity (r = 0.64, P less than 0.03). Mean serum prednisolone concentration after oral prednisone in the seven patients with severely impaired liver function was only 53% (P less than 0.05) of that observed in the seven patients with slightly impaired liver function. Conversely, mean serum prednisone concentration after oral prednisone in the patients with severely impaired liver function was 74% higher (P = 0.05) than in patients with slightly impaired liver function. Mean serum prednisolone after oral prednisolone was independent of liver function. As only prednisolone exerts glucocorticoid activity, our results indicate that prednisolone should be preferred to prednisone in the treatment of patients with impaired liver function.

A long-term follow-up of at least 10 years or until death of 44 patients taking part in a controlled prospective trial of prednisolone therapy in hepatitis B antigen negative chronic active hepatitis (lupoid hepatitis) has been performed at the Royal Free Hospital, London. Patients presenting between 1963 and 1967 were randomly allocated into control and treatment groups. Ten year life table survival curves showed a significantly improved survival in the treatment group where 63% of patients were alive at 10 years compared with only 27% in the control group (log rank test, P = 0.03). The median survival in the treatment group was 12.2 years compared with 3.3 years in the control group. The mean duration of treatment was 4.5 years. Age, presence of antinuclear factor, cirrhosis, or level of serum transaminases at presentation did not appear to affect survival. Male patients if untreated had a poorer prognosis than females (P = 0.02). The natural history of chronic active hepatitis appeared from clinical, biochemical, and histological findings to be from an active hepatitis or cirrhosis to inactive macronodular cirrhosis. Prednisolone therapy significantly improved survival by reducing mortality in the early active phase of the disease.

One hundred and one patients were studied in a double-blind controlled trial to assess the role of oral cimetidine in preventing the continuation or recurrence of acute upper gastrointestinal haemorrhage from various sources, chiefly peptic ulcer. The dose of cimetidine was 800 mg on entering the study followed by 400 mg six hourly. The source of bleeding was identified endoscopically in 96% of patients, peptic ulcer comprising 70%. Bleeding continued or recurred in 11 of 51 (21.5%) of patients on cimetidine and in 12 of 50 (24%) of patients on placebo. Analysis of the effect of cimetidine according to age or severity of bleeding showed no significant advantage for the drug.

Seventy-six patients with advanced gastric adenocarcinoma were studied in a prospecitive, randmoised, controlled trial using vincristine, methotrexate, cyclophosphamide, and 5-fluorouracil in an initiation course and mitomycin-C with 5-fluorouracil as maintenance therapy. Thirty-seven patients were inoperable and 39 had the primary tumour resected with histological evidence of residual disease. Survival in the inoperable group was short and showed no significant difference between treated and control patients. The median survival times for treated and control groups were 9.5 and 9.0 weeks respectively. In the resected patients there was no difference in ultimate overall survival between the groups but up to 20 weeks there was a suggestion that the probability of survival in treated patients was higher (P = 0.06). The patients were well-matched and it is concluded that chemotherapy has had an early effect but that a further trial with more detailed stratification, particularly of staging and histological grade, is needed. No patient received treatment for longer than two years and unacceptable toxicity occurred in only two patients. Nausea occurred more frequently in the treated group but was short-lived and clinically manageable.

Sixty patients with gastric ulcers were treated for four weeks with either 1 g cimetidine per day or with identical tablets containing lactose. The healing rate, assessed by endoscopy, was 23 out of 35 (66%) in the patients given cimetidine and 13 out of 25 (52%) in those given placebo. The difference between the groups is not significant. During each of the four weeks of the study the cimetidine group experienced significantly fewer attacks of pain and consumed less antacids than the placebo treated patients.

In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer.

A randomised, un-blinded clinical trial of hydrocortisate treatment in acute liver failure was carried out by 17 European centres. During a four year period 40 patients entered the study, 26 in the steroid group and 14 in the control group. The groups were found to be comparable, and the survival was 12 and 14%, respectively. A number of clinical and laboratory data, particularly HBsAg-positivity, appeared to carry some prognostic information, irrespective of treatment, but statistical significance was not achieved. Pooling of the present results with those from relevant published reports indicates a significant negative effect of steroid treatment in acute liver failure (P less than 0.2).

Forty-two patients with endoscopically diagnosed duodenal ulcer were studied in a double-blind trial after their ulcers had been healed with cimetidine. Cimetidine was effective in preventing relapse, only five of the 20 patients allocated to cimetidine 400 mg twice daily relapsing during the six months' treatment, compared with 16 of the 22 on placebo treatment (P less than 0.01). Cimetidine was safe in the dosage and duration used, no symptomatic, haematological, or biochemical abnormalities occurring during the trial. Subsequent follow-up at the end of the trial when treatment had been stopped showed that relapse was frequent, particularly in the cimetidine group, making the cumulative relapse rate eight months after completion of the trial similar in the two groups (75% in the cimetidine group, 86% in the placebo group). It seems likely that maintenance cimetidine treatment has to be continued indefinitely in patients with duodenal ulcer, and, until such treatment is shown to be safe and effective, surgical treatment remains a logical option for many patients.

Previous experimental studies suggest that bile salt-induced colonic fluid secretion is mediated by adenosine 3':5'-phosphate (cyclic AMP). Two biopsy specimens of colonic mucosa were obtained endoscopically before and after different periods of therapy (five, 10, or 15 days), from each of 21 patients receiving chenodeoxycholic acid. A rise of cyclic AMP intracellular levels was found, but only after five and 10 days of treatment was the increase statistically significant when compared with basal levels. Similar changes were observed for guanosine 3':5'-phosphate (cyclic GMP), but percentage increases were higher than for cyclic AMP. Initial diarrhoea disappeared spontaneously, and at 15 days the levels of both cyclic nucleotides were not significantly different from basal levels. Our findings suggest that colonic adaptation to increase in luminal bile salt levels is related to changes in intracellular levels of cyclic nucleotides and support the hypothesis that not only cyclic AMP, but also cyclic GMP may play an important role in producing bile salt-induced diarrhoea in man.

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.

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.